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Resources limit availability of bone marrow transplants
Peripheral blood is a major stem cell source for hematopoietic stem cell transplantation in many parts of the world – even though bone marrow is preferred – likely due to costs, the need for patient hospitalization, and a lack of trained physicians and necessary equipment for performing bone marrow transplant, Dr. Ayami Yoshimi, and colleagues reported for the Worldwide Network of Blood and Marrow Transplantation.
Peripheral blood stem cells are readily available at transplant centers, as they are collected routinely for other indications, and they offer short-term cost savings due to rapid engraftment, the network reported in a research letter (JAMA. 2016;315[2]:198-200. doi:10.1001/jama.2015.13706).
In patients with nonmalignant disorders, use of peripheral blood stem cells in HSCT has a higher rate of graft-vs.-host disease and lower survival rates.
In the network’s retrospective survey, which they estimate covered 90% of transplants performed in 2009 and 2010, 114,217 HSCTs were reported by 1,482 transplant teams and 3,282 allogeneic HSCTs were performed for bone marrow failure. Use of peripheral blood stem cells in HSCT varied from 80% in countries with low and middle incomes to 50% in those with high-middle incomes to 36% in those with high incomes (P less than .001). For the 3,282 allogeneic HSCTs performed for bone marrow failure worldwide, stem cell sources included bone marrow (1,766, 54%), peripheral blood stem cells (1,336, 41%), and cord blood (180, 5%).
Use of unrelated donors was highest in Europe (515/1107; 47%); use of matched sibling donors was highest in the Eastern Mediterranean region and Africa (249/274; 91%).
Bone marrow was used most commonly in the Americas (631/843; 75%) and in Europe (632/1057; 60%), but not in the Eastern Mediterranean region and Africa (123/266; 46%) and in the Asia Pacific region (380/936; 41%; excluding Japan, 19%).
“National and international transplant organizations and authorities should foster regional accredited bone marrow harvest centers for patients with nonmalignant disorders and provide resources to establish such infrastructures. Unrelated donor registries should provide information on the necessity of bone marrow donation for patients with bone marrow failure,” wrote Dr. Yoshimi of the University of Freiburg, Germany, and colleagues.
Funding for the study was indirectly provided by the Worldwide Network of Blood and Marrow Transplantation. Dr. Yoshimi reported having no disclosures.
Peripheral blood is a major stem cell source for hematopoietic stem cell transplantation in many parts of the world – even though bone marrow is preferred – likely due to costs, the need for patient hospitalization, and a lack of trained physicians and necessary equipment for performing bone marrow transplant, Dr. Ayami Yoshimi, and colleagues reported for the Worldwide Network of Blood and Marrow Transplantation.
Peripheral blood stem cells are readily available at transplant centers, as they are collected routinely for other indications, and they offer short-term cost savings due to rapid engraftment, the network reported in a research letter (JAMA. 2016;315[2]:198-200. doi:10.1001/jama.2015.13706).
In patients with nonmalignant disorders, use of peripheral blood stem cells in HSCT has a higher rate of graft-vs.-host disease and lower survival rates.
In the network’s retrospective survey, which they estimate covered 90% of transplants performed in 2009 and 2010, 114,217 HSCTs were reported by 1,482 transplant teams and 3,282 allogeneic HSCTs were performed for bone marrow failure. Use of peripheral blood stem cells in HSCT varied from 80% in countries with low and middle incomes to 50% in those with high-middle incomes to 36% in those with high incomes (P less than .001). For the 3,282 allogeneic HSCTs performed for bone marrow failure worldwide, stem cell sources included bone marrow (1,766, 54%), peripheral blood stem cells (1,336, 41%), and cord blood (180, 5%).
Use of unrelated donors was highest in Europe (515/1107; 47%); use of matched sibling donors was highest in the Eastern Mediterranean region and Africa (249/274; 91%).
Bone marrow was used most commonly in the Americas (631/843; 75%) and in Europe (632/1057; 60%), but not in the Eastern Mediterranean region and Africa (123/266; 46%) and in the Asia Pacific region (380/936; 41%; excluding Japan, 19%).
“National and international transplant organizations and authorities should foster regional accredited bone marrow harvest centers for patients with nonmalignant disorders and provide resources to establish such infrastructures. Unrelated donor registries should provide information on the necessity of bone marrow donation for patients with bone marrow failure,” wrote Dr. Yoshimi of the University of Freiburg, Germany, and colleagues.
Funding for the study was indirectly provided by the Worldwide Network of Blood and Marrow Transplantation. Dr. Yoshimi reported having no disclosures.
Peripheral blood is a major stem cell source for hematopoietic stem cell transplantation in many parts of the world – even though bone marrow is preferred – likely due to costs, the need for patient hospitalization, and a lack of trained physicians and necessary equipment for performing bone marrow transplant, Dr. Ayami Yoshimi, and colleagues reported for the Worldwide Network of Blood and Marrow Transplantation.
Peripheral blood stem cells are readily available at transplant centers, as they are collected routinely for other indications, and they offer short-term cost savings due to rapid engraftment, the network reported in a research letter (JAMA. 2016;315[2]:198-200. doi:10.1001/jama.2015.13706).
In patients with nonmalignant disorders, use of peripheral blood stem cells in HSCT has a higher rate of graft-vs.-host disease and lower survival rates.
In the network’s retrospective survey, which they estimate covered 90% of transplants performed in 2009 and 2010, 114,217 HSCTs were reported by 1,482 transplant teams and 3,282 allogeneic HSCTs were performed for bone marrow failure. Use of peripheral blood stem cells in HSCT varied from 80% in countries with low and middle incomes to 50% in those with high-middle incomes to 36% in those with high incomes (P less than .001). For the 3,282 allogeneic HSCTs performed for bone marrow failure worldwide, stem cell sources included bone marrow (1,766, 54%), peripheral blood stem cells (1,336, 41%), and cord blood (180, 5%).
Use of unrelated donors was highest in Europe (515/1107; 47%); use of matched sibling donors was highest in the Eastern Mediterranean region and Africa (249/274; 91%).
Bone marrow was used most commonly in the Americas (631/843; 75%) and in Europe (632/1057; 60%), but not in the Eastern Mediterranean region and Africa (123/266; 46%) and in the Asia Pacific region (380/936; 41%; excluding Japan, 19%).
“National and international transplant organizations and authorities should foster regional accredited bone marrow harvest centers for patients with nonmalignant disorders and provide resources to establish such infrastructures. Unrelated donor registries should provide information on the necessity of bone marrow donation for patients with bone marrow failure,” wrote Dr. Yoshimi of the University of Freiburg, Germany, and colleagues.
Funding for the study was indirectly provided by the Worldwide Network of Blood and Marrow Transplantation. Dr. Yoshimi reported having no disclosures.
FROM JAMA
Key clinical point: In regions with limited resources, peripheral blood stem cells were used more frequently than bone marrow in hematopoietic stem cell transplantation for bone marrow failure.
Major finding: For the 3,282 allogeneic HSCTs performed for bone marrow failure worldwide, stem cell sources included bone marrow (1,766, 54%), peripheral blood stem cells (1,336, 41%), and cord blood (180, 5%).
Data source: Data on 3,282 allogeneic HSCTs for bone marrow failure performed in 2009 and 2010 were collected by retrospective surveys by the Worldwide Network for Blood and Marrow Transplantation, and by direct contact with transplant centers in countries without registries.
Disclosures: Funding was indirectly provided by the Worldwide Network of Blood and Marrow Transplantation. Dr. Yoshimi reported having no disclosures.
High-dose interferon offered no survival benefit in patients with melanoma and a single tumor–positive sentinel lymph node
Patients with melanoma and a single tumor–positive sentinel lymph node (SLN) had no improvement in overall (OS) or disease-free survival (DFS) with adjuvant high-dose interferon alfa-2b (HDI), and patients with histologically negative, RT-PCR–positive SLNs had no improvement with completion lymph node dissection (CLND) or CLND plus interferon, according to researchers.
For patients with a single positive SLN who received HDI, compared with the observation-only group, 5-year OS was 71.4% and 74.8% and 5-year DFS was 70.9% and 67.1%, respectively. For patients with reverse transcription polymerase chain reaction (RT-PCR)–positive but histologically negative SLNs who received CLND plus interferon, or CLND only, compared with the observation-only group, 5-year OS was 86.9%, 85.9%, and 85.5%, and 5-year DFS was 83.9%, 84.0%, and 79.4%, respectively.
The finding that HDI offers no survival benefit contradicts an earlier study (ECOG E1694) that compared HDI with ganglioside vaccine treatment.
“The results of this study refute the conclusion that improved DFS and OS in ECOG E1694 was due to a beneficial effect of HDI because HDI treatment in ECOG E1694 was not compared with observation or placebo, but to a vaccine that is now known to be associated with a greater risk of recurrence and mortality,” wrote Dr. Kelly M. McMasters, surgical oncologist at the University of Louisville (Ky.) and his colleagues (J Clin Oncol. 2016 Feb 8. doi: 10.1200/JCO.205.63.3776).
The prospective, randomized Sunbelt Melanoma Trial included patients with melanoma of thickness 1 mm or greater without evidence of metastasis. Protocol A, with 218 patients with histologically positive SLNs, did not meet its accrual goal of 150 patients each for arms 1 and 2. Protocol B had 556 patients with RT-PCR–positive but histologically negative SLNs. The median follow-up was 71 months.
The trial found that HDI therapy after CLND did not improve DFS or OS for patients with minimal nodal tumor burden. For patients randomly assigned to HDI versus observation after CLND, hazard ratios for DFS and OS were 0.82 (95% confidence interval, 0.50-1.36; P = .45) and 1.10 (0.69-1.76; P = .68).
In patients with stage I or II melanoma who have tumor-negative SLNs by hematoxylin and eosin histopathology and immunohistochemistry, but have molecular evidence of melanoma by RT-PCR analysis, no significant differences were observed among patients randomly assigned to CLND or CLND plus interferon treatment. Compared with observation, CLND alone showed a slight DFS improvement (hazard ratio, 0.58; 95% CI, 0.35-0.94; P = .0277), but no OS improvement (HR, 1.00; 95% CI, 0.634-1.59; P = .99). Patients who received CLND plus interferon had no significant improvement in DFS or OS, compared with observation.
Subgroup analysis showed that in patients with a single positive SLN, HDI was associated with improved DFS only in patients with ulceration (HR, 0.43; 95% CI, 0.21-0.87; P = .0183; n = 75) and with Breslow thickness more than 4 mm (HR, 0.35; 95% CI, 0.14-0.88; P = .0259; n = 42). No OS improvement was observed.
“Taken together, these data support the conclusion that the benefit of HDI is small, perhaps because only a fraction of the patient population responds to therapy,” the investigators wrote.
Patients with melanoma and a single tumor–positive sentinel lymph node (SLN) had no improvement in overall (OS) or disease-free survival (DFS) with adjuvant high-dose interferon alfa-2b (HDI), and patients with histologically negative, RT-PCR–positive SLNs had no improvement with completion lymph node dissection (CLND) or CLND plus interferon, according to researchers.
For patients with a single positive SLN who received HDI, compared with the observation-only group, 5-year OS was 71.4% and 74.8% and 5-year DFS was 70.9% and 67.1%, respectively. For patients with reverse transcription polymerase chain reaction (RT-PCR)–positive but histologically negative SLNs who received CLND plus interferon, or CLND only, compared with the observation-only group, 5-year OS was 86.9%, 85.9%, and 85.5%, and 5-year DFS was 83.9%, 84.0%, and 79.4%, respectively.
The finding that HDI offers no survival benefit contradicts an earlier study (ECOG E1694) that compared HDI with ganglioside vaccine treatment.
“The results of this study refute the conclusion that improved DFS and OS in ECOG E1694 was due to a beneficial effect of HDI because HDI treatment in ECOG E1694 was not compared with observation or placebo, but to a vaccine that is now known to be associated with a greater risk of recurrence and mortality,” wrote Dr. Kelly M. McMasters, surgical oncologist at the University of Louisville (Ky.) and his colleagues (J Clin Oncol. 2016 Feb 8. doi: 10.1200/JCO.205.63.3776).
The prospective, randomized Sunbelt Melanoma Trial included patients with melanoma of thickness 1 mm or greater without evidence of metastasis. Protocol A, with 218 patients with histologically positive SLNs, did not meet its accrual goal of 150 patients each for arms 1 and 2. Protocol B had 556 patients with RT-PCR–positive but histologically negative SLNs. The median follow-up was 71 months.
The trial found that HDI therapy after CLND did not improve DFS or OS for patients with minimal nodal tumor burden. For patients randomly assigned to HDI versus observation after CLND, hazard ratios for DFS and OS were 0.82 (95% confidence interval, 0.50-1.36; P = .45) and 1.10 (0.69-1.76; P = .68).
In patients with stage I or II melanoma who have tumor-negative SLNs by hematoxylin and eosin histopathology and immunohistochemistry, but have molecular evidence of melanoma by RT-PCR analysis, no significant differences were observed among patients randomly assigned to CLND or CLND plus interferon treatment. Compared with observation, CLND alone showed a slight DFS improvement (hazard ratio, 0.58; 95% CI, 0.35-0.94; P = .0277), but no OS improvement (HR, 1.00; 95% CI, 0.634-1.59; P = .99). Patients who received CLND plus interferon had no significant improvement in DFS or OS, compared with observation.
Subgroup analysis showed that in patients with a single positive SLN, HDI was associated with improved DFS only in patients with ulceration (HR, 0.43; 95% CI, 0.21-0.87; P = .0183; n = 75) and with Breslow thickness more than 4 mm (HR, 0.35; 95% CI, 0.14-0.88; P = .0259; n = 42). No OS improvement was observed.
“Taken together, these data support the conclusion that the benefit of HDI is small, perhaps because only a fraction of the patient population responds to therapy,” the investigators wrote.
Patients with melanoma and a single tumor–positive sentinel lymph node (SLN) had no improvement in overall (OS) or disease-free survival (DFS) with adjuvant high-dose interferon alfa-2b (HDI), and patients with histologically negative, RT-PCR–positive SLNs had no improvement with completion lymph node dissection (CLND) or CLND plus interferon, according to researchers.
For patients with a single positive SLN who received HDI, compared with the observation-only group, 5-year OS was 71.4% and 74.8% and 5-year DFS was 70.9% and 67.1%, respectively. For patients with reverse transcription polymerase chain reaction (RT-PCR)–positive but histologically negative SLNs who received CLND plus interferon, or CLND only, compared with the observation-only group, 5-year OS was 86.9%, 85.9%, and 85.5%, and 5-year DFS was 83.9%, 84.0%, and 79.4%, respectively.
The finding that HDI offers no survival benefit contradicts an earlier study (ECOG E1694) that compared HDI with ganglioside vaccine treatment.
“The results of this study refute the conclusion that improved DFS and OS in ECOG E1694 was due to a beneficial effect of HDI because HDI treatment in ECOG E1694 was not compared with observation or placebo, but to a vaccine that is now known to be associated with a greater risk of recurrence and mortality,” wrote Dr. Kelly M. McMasters, surgical oncologist at the University of Louisville (Ky.) and his colleagues (J Clin Oncol. 2016 Feb 8. doi: 10.1200/JCO.205.63.3776).
The prospective, randomized Sunbelt Melanoma Trial included patients with melanoma of thickness 1 mm or greater without evidence of metastasis. Protocol A, with 218 patients with histologically positive SLNs, did not meet its accrual goal of 150 patients each for arms 1 and 2. Protocol B had 556 patients with RT-PCR–positive but histologically negative SLNs. The median follow-up was 71 months.
The trial found that HDI therapy after CLND did not improve DFS or OS for patients with minimal nodal tumor burden. For patients randomly assigned to HDI versus observation after CLND, hazard ratios for DFS and OS were 0.82 (95% confidence interval, 0.50-1.36; P = .45) and 1.10 (0.69-1.76; P = .68).
In patients with stage I or II melanoma who have tumor-negative SLNs by hematoxylin and eosin histopathology and immunohistochemistry, but have molecular evidence of melanoma by RT-PCR analysis, no significant differences were observed among patients randomly assigned to CLND or CLND plus interferon treatment. Compared with observation, CLND alone showed a slight DFS improvement (hazard ratio, 0.58; 95% CI, 0.35-0.94; P = .0277), but no OS improvement (HR, 1.00; 95% CI, 0.634-1.59; P = .99). Patients who received CLND plus interferon had no significant improvement in DFS or OS, compared with observation.
Subgroup analysis showed that in patients with a single positive SLN, HDI was associated with improved DFS only in patients with ulceration (HR, 0.43; 95% CI, 0.21-0.87; P = .0183; n = 75) and with Breslow thickness more than 4 mm (HR, 0.35; 95% CI, 0.14-0.88; P = .0259; n = 42). No OS improvement was observed.
“Taken together, these data support the conclusion that the benefit of HDI is small, perhaps because only a fraction of the patient population responds to therapy,” the investigators wrote.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Adjuvant high-dose interferon (HDI) did not improve survival in patients with a single tumor–positive sentinel lymph node (SLN), and in patients with RT-PCR–positive but histologically negative SLNs, no survival benefit was observed with completion lymph node dissection (CLND) or adjuvant HDI.
Major finding: For patients with a single positive SLN who received HDI or observation, 5-year OS was 71.4% and 74.8% and 5-year DFS was 70.9% and 67.1%, respectively; for patients with RT-PCR–positive but histologically negative SLNs who received CLND plus interferon, CLND, or observation, 5-year OS was 86.9%, 85.9%, and 85.5%, and 5-year DFS was 83.9%, 84.0%, and 79.4%, respectively.
Data source: The prospective, randomized Sunbelt Melanoma Trial included patients with melanoma 1 mm or greater in thickness without evidence of metastasis. Protocol A had 218 patients with histologically positive SLNs and protocol B had 556 patients with RT-PCR–positive but histologically negative SLNs.
Disclosures: Dr. McMasters holds a leadership role with Provectus Biopharmaceuticals. Several of his coauthors reported ties to industry.
Early mortality predicted by age and poor performance status in patients with colon cancer
To better assess patients being considered for clinical trials, researchers determined that the risk of early mortality was low overall, but elderly patients and those with performance score (PS) of 2 or greater had particularly high risk. In addition, a large proportion of deaths within 6 months occurred in patients with early recurrence.
Mortality rates at 30, 60, and 90 days, and 6 months were 0.3%, 0.6%, 0.8%, and 1.4%, respectively, and age and PS were significantly associated with mortality at every time point (P less than .001 for all). The highest early mortality rates were observed in patients treated with surgery alone: from 0.6% at 30 days to 2.0% at 6 months. The lowest mortality rates occurred in patients treated with FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), ranging from 0.2% to 1.2% (J Clin Onc. 2016 Feb 7. doi: 10.1200/JCO.205.65.1158).
Patients who experienced early recurrence had an 82-fold increased risk of early death and accounted for 40% of all deaths prior to 6 months post–random assignment.
“Contrary to the general assumption that systemic therapy exerts its effect mainly by reducing late recurrences, this observation suggests that chemotherapy may also prevent early recurrences, even within the first six months of treatment. Our current finding that nearly one half of the observed early deaths were preceded by a documented recurrence supports this hypothesis,” wrote Dr. Winson Cheung of the division of medical oncology at the British Columbia Cancer Agency, Vancouver.
The analysis used the ACCENT (Adjuvant Colon Cancer Endpoints) database of 37,568 patients with colon cancer who had participated in 25 adjuvant phase III trials since 1977.
The association between advanced age and early mortality was nonlinear and increased sharply beyond 70 years. In addition to age and PS, other patient characteristics that influenced risk of early mortality were tumor grade, lymph node ratio, and tumor stage. Results of the multivariate analysis contributed to development of a nomogram for 6-month mortality. Using external validation data from 3,227 patients, the nomogram correctly predicted the 1.1% mortality rate observed at 6 months.
By quantifying risk of early death in potential clinical trial patients, the nomogram informs risk-to-benefit assessments and identifies individuals for whom increased vigilance may be necessary throughout a study.
To better assess patients being considered for clinical trials, researchers determined that the risk of early mortality was low overall, but elderly patients and those with performance score (PS) of 2 or greater had particularly high risk. In addition, a large proportion of deaths within 6 months occurred in patients with early recurrence.
Mortality rates at 30, 60, and 90 days, and 6 months were 0.3%, 0.6%, 0.8%, and 1.4%, respectively, and age and PS were significantly associated with mortality at every time point (P less than .001 for all). The highest early mortality rates were observed in patients treated with surgery alone: from 0.6% at 30 days to 2.0% at 6 months. The lowest mortality rates occurred in patients treated with FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), ranging from 0.2% to 1.2% (J Clin Onc. 2016 Feb 7. doi: 10.1200/JCO.205.65.1158).
Patients who experienced early recurrence had an 82-fold increased risk of early death and accounted for 40% of all deaths prior to 6 months post–random assignment.
“Contrary to the general assumption that systemic therapy exerts its effect mainly by reducing late recurrences, this observation suggests that chemotherapy may also prevent early recurrences, even within the first six months of treatment. Our current finding that nearly one half of the observed early deaths were preceded by a documented recurrence supports this hypothesis,” wrote Dr. Winson Cheung of the division of medical oncology at the British Columbia Cancer Agency, Vancouver.
The analysis used the ACCENT (Adjuvant Colon Cancer Endpoints) database of 37,568 patients with colon cancer who had participated in 25 adjuvant phase III trials since 1977.
The association between advanced age and early mortality was nonlinear and increased sharply beyond 70 years. In addition to age and PS, other patient characteristics that influenced risk of early mortality were tumor grade, lymph node ratio, and tumor stage. Results of the multivariate analysis contributed to development of a nomogram for 6-month mortality. Using external validation data from 3,227 patients, the nomogram correctly predicted the 1.1% mortality rate observed at 6 months.
By quantifying risk of early death in potential clinical trial patients, the nomogram informs risk-to-benefit assessments and identifies individuals for whom increased vigilance may be necessary throughout a study.
To better assess patients being considered for clinical trials, researchers determined that the risk of early mortality was low overall, but elderly patients and those with performance score (PS) of 2 or greater had particularly high risk. In addition, a large proportion of deaths within 6 months occurred in patients with early recurrence.
Mortality rates at 30, 60, and 90 days, and 6 months were 0.3%, 0.6%, 0.8%, and 1.4%, respectively, and age and PS were significantly associated with mortality at every time point (P less than .001 for all). The highest early mortality rates were observed in patients treated with surgery alone: from 0.6% at 30 days to 2.0% at 6 months. The lowest mortality rates occurred in patients treated with FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), ranging from 0.2% to 1.2% (J Clin Onc. 2016 Feb 7. doi: 10.1200/JCO.205.65.1158).
Patients who experienced early recurrence had an 82-fold increased risk of early death and accounted for 40% of all deaths prior to 6 months post–random assignment.
“Contrary to the general assumption that systemic therapy exerts its effect mainly by reducing late recurrences, this observation suggests that chemotherapy may also prevent early recurrences, even within the first six months of treatment. Our current finding that nearly one half of the observed early deaths were preceded by a documented recurrence supports this hypothesis,” wrote Dr. Winson Cheung of the division of medical oncology at the British Columbia Cancer Agency, Vancouver.
The analysis used the ACCENT (Adjuvant Colon Cancer Endpoints) database of 37,568 patients with colon cancer who had participated in 25 adjuvant phase III trials since 1977.
The association between advanced age and early mortality was nonlinear and increased sharply beyond 70 years. In addition to age and PS, other patient characteristics that influenced risk of early mortality were tumor grade, lymph node ratio, and tumor stage. Results of the multivariate analysis contributed to development of a nomogram for 6-month mortality. Using external validation data from 3,227 patients, the nomogram correctly predicted the 1.1% mortality rate observed at 6 months.
By quantifying risk of early death in potential clinical trial patients, the nomogram informs risk-to-benefit assessments and identifies individuals for whom increased vigilance may be necessary throughout a study.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Among patients with colon cancer enrolled in phase III trials for adjuvant therapy, mortality within 6 months of random assignment was low overall, but it was significantly higher among elderly or patients with poor performance status.
Major finding: Mortality rates at 30, 60, and 90 days, and 6 months were 0.3%, 0.6%, 0.8%, and 1.4%, respectively, and age and PS were significantly associated with morality at every time point (P less than .001 for all).
Data source: ACCENT database included information on more than 37,568 patients with colon cancer who participated in 25 adjuvant, phase III trials since 1977.
Disclosures: Dr. Cheung reported having no disclosures. Several of his coauthors reported ties to industry.
Cola enhances absorption of erlotinib in NSCLC
Drinking cola significantly improved bioavailability of the orally administered tyrosine kinase inhibitor (TKI) erlotinib in patients with lung cancer who were concomitantly taking the acid-reducing agent esomeprazole, investigators reported online in the Journal of Clinical Oncology.
Mean exposure of erlotinib was significantly higher after drinking cola, compared with water in patients treated concomitantly with esomeprazole (area under the plasma concentration curve, AUC0-12h was 39% higher; range, –12% to +136%; P = .004 and Cmax was 42% higher; range, –4% to +199%; P = .019), probably due to increased solubility and absorption. In patients treated with erlotinib only (without esomeprazole), exposure was moderately increased with cola intake (AUC0-12h was 9% higher; range, –10% to +30%; P = .03 and Cmax was comparable; range, –19% to +18%; P = .75).
Use of proton pump inhibitors (PPIs) is often indicated during erlotinib therapy for patients with gastroesophageal reflux disease, or for patients treated with corticosteroids and nonsteroidal anti-inflammatory drugs.
“When erlotinib and a PPI are given concomitantly, the AUC of erlotinib steeply decreases, which suggests that lower bioavailability due to PPI use (up to 46% for erlotinib) may deprive patients from optimal therapy. Thus, in the case that the combination of a PPI and erlotinib is inevitable, the pH-lowering effects of cola may help physicians to optimize erlotinib therapy,” wrote Dr. Roelof van Leeuwen of Erasmus MC Cancer Institute, Rotterdam, the Netherlands (J Clin Oncol. 2016 Feb 7. doi: 10.1200/JCO.205.65.1158).
The researchers noted that Coca-Cola Classic has a substantially lower pH (about 2.5) than other acidic drinks, such as orange juice (pH about 4), 7-Up (pH about 3.5), and diet colas (pH about 3-4), making it well suited for use with erlotinib, since drinks with higher pH may not enhance absorption as well. Patients had 250 mL of cola, a volume that was well tolerated.
Previous studies have shown that erlotinib has significant intrasubject and intersubject variability, and intragastric pH is an important determinant. The drug’s pKa, at 5.4, is near the stomach pH range of 1 to 4, and intragastric pH changes lead to shifts toward the nonionized (less soluble) form and subsequent lower bioavailability than TKIs with higher pKa values.
The results with erlotinib might extrapolate to other TKIs with pH-dependent solubility, such as dasatinib, gefitinib, nilotinib, the authors suggested, which should be tested in future studies.
Drinking cola significantly improved bioavailability of the orally administered tyrosine kinase inhibitor (TKI) erlotinib in patients with lung cancer who were concomitantly taking the acid-reducing agent esomeprazole, investigators reported online in the Journal of Clinical Oncology.
Mean exposure of erlotinib was significantly higher after drinking cola, compared with water in patients treated concomitantly with esomeprazole (area under the plasma concentration curve, AUC0-12h was 39% higher; range, –12% to +136%; P = .004 and Cmax was 42% higher; range, –4% to +199%; P = .019), probably due to increased solubility and absorption. In patients treated with erlotinib only (without esomeprazole), exposure was moderately increased with cola intake (AUC0-12h was 9% higher; range, –10% to +30%; P = .03 and Cmax was comparable; range, –19% to +18%; P = .75).
Use of proton pump inhibitors (PPIs) is often indicated during erlotinib therapy for patients with gastroesophageal reflux disease, or for patients treated with corticosteroids and nonsteroidal anti-inflammatory drugs.
“When erlotinib and a PPI are given concomitantly, the AUC of erlotinib steeply decreases, which suggests that lower bioavailability due to PPI use (up to 46% for erlotinib) may deprive patients from optimal therapy. Thus, in the case that the combination of a PPI and erlotinib is inevitable, the pH-lowering effects of cola may help physicians to optimize erlotinib therapy,” wrote Dr. Roelof van Leeuwen of Erasmus MC Cancer Institute, Rotterdam, the Netherlands (J Clin Oncol. 2016 Feb 7. doi: 10.1200/JCO.205.65.1158).
The researchers noted that Coca-Cola Classic has a substantially lower pH (about 2.5) than other acidic drinks, such as orange juice (pH about 4), 7-Up (pH about 3.5), and diet colas (pH about 3-4), making it well suited for use with erlotinib, since drinks with higher pH may not enhance absorption as well. Patients had 250 mL of cola, a volume that was well tolerated.
Previous studies have shown that erlotinib has significant intrasubject and intersubject variability, and intragastric pH is an important determinant. The drug’s pKa, at 5.4, is near the stomach pH range of 1 to 4, and intragastric pH changes lead to shifts toward the nonionized (less soluble) form and subsequent lower bioavailability than TKIs with higher pKa values.
The results with erlotinib might extrapolate to other TKIs with pH-dependent solubility, such as dasatinib, gefitinib, nilotinib, the authors suggested, which should be tested in future studies.
Drinking cola significantly improved bioavailability of the orally administered tyrosine kinase inhibitor (TKI) erlotinib in patients with lung cancer who were concomitantly taking the acid-reducing agent esomeprazole, investigators reported online in the Journal of Clinical Oncology.
Mean exposure of erlotinib was significantly higher after drinking cola, compared with water in patients treated concomitantly with esomeprazole (area under the plasma concentration curve, AUC0-12h was 39% higher; range, –12% to +136%; P = .004 and Cmax was 42% higher; range, –4% to +199%; P = .019), probably due to increased solubility and absorption. In patients treated with erlotinib only (without esomeprazole), exposure was moderately increased with cola intake (AUC0-12h was 9% higher; range, –10% to +30%; P = .03 and Cmax was comparable; range, –19% to +18%; P = .75).
Use of proton pump inhibitors (PPIs) is often indicated during erlotinib therapy for patients with gastroesophageal reflux disease, or for patients treated with corticosteroids and nonsteroidal anti-inflammatory drugs.
“When erlotinib and a PPI are given concomitantly, the AUC of erlotinib steeply decreases, which suggests that lower bioavailability due to PPI use (up to 46% for erlotinib) may deprive patients from optimal therapy. Thus, in the case that the combination of a PPI and erlotinib is inevitable, the pH-lowering effects of cola may help physicians to optimize erlotinib therapy,” wrote Dr. Roelof van Leeuwen of Erasmus MC Cancer Institute, Rotterdam, the Netherlands (J Clin Oncol. 2016 Feb 7. doi: 10.1200/JCO.205.65.1158).
The researchers noted that Coca-Cola Classic has a substantially lower pH (about 2.5) than other acidic drinks, such as orange juice (pH about 4), 7-Up (pH about 3.5), and diet colas (pH about 3-4), making it well suited for use with erlotinib, since drinks with higher pH may not enhance absorption as well. Patients had 250 mL of cola, a volume that was well tolerated.
Previous studies have shown that erlotinib has significant intrasubject and intersubject variability, and intragastric pH is an important determinant. The drug’s pKa, at 5.4, is near the stomach pH range of 1 to 4, and intragastric pH changes lead to shifts toward the nonionized (less soluble) form and subsequent lower bioavailability than TKIs with higher pKa values.
The results with erlotinib might extrapolate to other TKIs with pH-dependent solubility, such as dasatinib, gefitinib, nilotinib, the authors suggested, which should be tested in future studies.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Taking oral erlotinib with cola significantly increased the drug’s bioavailability in patients concomitantly taking the acid-reducing agent esomeprazole.
Major finding: Patients treated with erlotinib and esomeprazole had significantly better absorption after drinking cola, compared with water (AUC0-12h was 39% higher; range, –12% to +136%; P = .004 and Cmax was 42% higher; range, –4% to +199%; P = .019).
Data source: 28 evaluable patients with lung cancer; 14 received erlotinib and esomeprazole and 14 received erlotinib only.
Disclosures: Research was supported by Stichting de Merel and Roche. Dr. van Leeuwen reported research funding from Roche. Several of his coauthors reported ties to industry.
Minimally invasive and abdominal hysterectomy yield similar results for endometrial cancer
Use of minimally invasive hysterectomy in patients with endometrial cancer, on the rise since 2007, has long-term survival rates comparable to those of abdominal hysterectomy, and a favorable morbidity profile.
Minimally invasive hysterectomy had similar overall mortality (hazard ratio[HR], 0.89; 95% CI, 0.75 to 1.04) and cancer-specific mortality (HR, 0.83; 95% CI, 0.59-1.16), compared with abdominal hysterectomy. Robot-assisted hysterectomy, compared with laparoscopic, had similar overall and cancer-specific mortality.
Adjuvant radiation was increased in women who underwent minimally invasive compared with abdominal hysterectomy (for pelvic radiation 34.3% vs. 31.3%; odds ratio[OR], 1.14; 95% CI, 1.04-1.26; for brachytherapy 33.6% vs. 31.0%; OR, 1.13; 95% CI, 1.03-1.24).
“The mechanism underlying the need for increased use of adjuvant therapy after minimally invasive hysterectomy remains unclear ... Particularly for women with large uteri, manipulation at the time of surgery or disruption or spillage of tumor from the uterine cavity may prompt use of radiation. This phenomenon warrants further investigation and careful monitoring,” wrote Dr. Jason Wright, chief of gynecologic oncology at Columbia University College of Physicians and Surgeons, New York, and colleagues (J Clin Oncol. 2016 Feb 1. doi: 10.1200/JCO.2015.65.3212).
The population-based analysis used SEER-Medicare data of 6,305 patients aged 65 years and greater with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. In total, 4,139 (65.7%) underwent abdominal hysterectomy and 2,165 (34.3%) underwent minimally invasive surgery.
Results showed that the use of minimally invasive hysterectomy has increased from 9.3% in 2006 to 61.7% in 2011, and over 60% of the minimally invasive surgeries were robot-assisted.
Minimally invasive hysterectomy had fewer complications than did abdominal hysterectomy (22.7% vs. 39.7%; OR, 0.46; 95% CI, 0.41-0.51), including lower rates of surgical site complications, medical complications, transfusions, and perioperative mortality.
Robot-assisted hysterectomy had a slightly higher complication rate than did laparoscopic hysterectomy (23.7% vs. 19.5%; OR 1.28; 95% CI, 1.03-1.59), due to postoperative medical complications. Respiratory and renal failure were higher after robot-assisted surgery, as was bacteremia. The complications may be a result of longer operative times, as reported in previous studies.
Use of minimally invasive hysterectomy in patients with endometrial cancer, on the rise since 2007, has long-term survival rates comparable to those of abdominal hysterectomy, and a favorable morbidity profile.
Minimally invasive hysterectomy had similar overall mortality (hazard ratio[HR], 0.89; 95% CI, 0.75 to 1.04) and cancer-specific mortality (HR, 0.83; 95% CI, 0.59-1.16), compared with abdominal hysterectomy. Robot-assisted hysterectomy, compared with laparoscopic, had similar overall and cancer-specific mortality.
Adjuvant radiation was increased in women who underwent minimally invasive compared with abdominal hysterectomy (for pelvic radiation 34.3% vs. 31.3%; odds ratio[OR], 1.14; 95% CI, 1.04-1.26; for brachytherapy 33.6% vs. 31.0%; OR, 1.13; 95% CI, 1.03-1.24).
“The mechanism underlying the need for increased use of adjuvant therapy after minimally invasive hysterectomy remains unclear ... Particularly for women with large uteri, manipulation at the time of surgery or disruption or spillage of tumor from the uterine cavity may prompt use of radiation. This phenomenon warrants further investigation and careful monitoring,” wrote Dr. Jason Wright, chief of gynecologic oncology at Columbia University College of Physicians and Surgeons, New York, and colleagues (J Clin Oncol. 2016 Feb 1. doi: 10.1200/JCO.2015.65.3212).
The population-based analysis used SEER-Medicare data of 6,305 patients aged 65 years and greater with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. In total, 4,139 (65.7%) underwent abdominal hysterectomy and 2,165 (34.3%) underwent minimally invasive surgery.
Results showed that the use of minimally invasive hysterectomy has increased from 9.3% in 2006 to 61.7% in 2011, and over 60% of the minimally invasive surgeries were robot-assisted.
Minimally invasive hysterectomy had fewer complications than did abdominal hysterectomy (22.7% vs. 39.7%; OR, 0.46; 95% CI, 0.41-0.51), including lower rates of surgical site complications, medical complications, transfusions, and perioperative mortality.
Robot-assisted hysterectomy had a slightly higher complication rate than did laparoscopic hysterectomy (23.7% vs. 19.5%; OR 1.28; 95% CI, 1.03-1.59), due to postoperative medical complications. Respiratory and renal failure were higher after robot-assisted surgery, as was bacteremia. The complications may be a result of longer operative times, as reported in previous studies.
Use of minimally invasive hysterectomy in patients with endometrial cancer, on the rise since 2007, has long-term survival rates comparable to those of abdominal hysterectomy, and a favorable morbidity profile.
Minimally invasive hysterectomy had similar overall mortality (hazard ratio[HR], 0.89; 95% CI, 0.75 to 1.04) and cancer-specific mortality (HR, 0.83; 95% CI, 0.59-1.16), compared with abdominal hysterectomy. Robot-assisted hysterectomy, compared with laparoscopic, had similar overall and cancer-specific mortality.
Adjuvant radiation was increased in women who underwent minimally invasive compared with abdominal hysterectomy (for pelvic radiation 34.3% vs. 31.3%; odds ratio[OR], 1.14; 95% CI, 1.04-1.26; for brachytherapy 33.6% vs. 31.0%; OR, 1.13; 95% CI, 1.03-1.24).
“The mechanism underlying the need for increased use of adjuvant therapy after minimally invasive hysterectomy remains unclear ... Particularly for women with large uteri, manipulation at the time of surgery or disruption or spillage of tumor from the uterine cavity may prompt use of radiation. This phenomenon warrants further investigation and careful monitoring,” wrote Dr. Jason Wright, chief of gynecologic oncology at Columbia University College of Physicians and Surgeons, New York, and colleagues (J Clin Oncol. 2016 Feb 1. doi: 10.1200/JCO.2015.65.3212).
The population-based analysis used SEER-Medicare data of 6,305 patients aged 65 years and greater with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. In total, 4,139 (65.7%) underwent abdominal hysterectomy and 2,165 (34.3%) underwent minimally invasive surgery.
Results showed that the use of minimally invasive hysterectomy has increased from 9.3% in 2006 to 61.7% in 2011, and over 60% of the minimally invasive surgeries were robot-assisted.
Minimally invasive hysterectomy had fewer complications than did abdominal hysterectomy (22.7% vs. 39.7%; OR, 0.46; 95% CI, 0.41-0.51), including lower rates of surgical site complications, medical complications, transfusions, and perioperative mortality.
Robot-assisted hysterectomy had a slightly higher complication rate than did laparoscopic hysterectomy (23.7% vs. 19.5%; OR 1.28; 95% CI, 1.03-1.59), due to postoperative medical complications. Respiratory and renal failure were higher after robot-assisted surgery, as was bacteremia. The complications may be a result of longer operative times, as reported in previous studies.
Key clinical point: Robot-assisted and laparoscopic hysterectomy had long-term survival comparable to that of abdominal hysterectomy in patients with uterine cancer.
Major finding: Minimally invasive hysterectomy had similar overall mortality (hazard ratio[HR], 0.89; 95% CI, 0.75-1.04) and cancer-specific mortality (HR, 0.83; 95% CI, 0.59-1.16), compared with abdominal hysterectomy.
Data source: Population-based analysis using SEER-Medicare data on 6,305 patients who underwent hysterectomy (4,139 abdominal and 2,165 minimally invasive) from 2006 to 2011.
Disclosures: Dr. Wright reported having no disclosures. Two of his coauthors reported ties to industry.
Intense tumor lymphocytic infiltration indicates favorable prognosis in NSCLC
Tumor lymphocytic infiltration (TLI), categorized as intense or nonintense, was an independent prognostic indicator for survival in non–small cell lung cancer (NSCLC).
Patients with intense TLI had significantly longer overall survival (OS) and disease-free survival (DFS), compared with patients who had nonintense TLI. In the validation data set, 5-year OS for patients with intense TLI was 85% (95% confidence interval, 70-92), compared with 58% (95% CI, 54-62) for patients with nonintense TLI (P = .002). Five-year DFS was 79% (95% CI, 65-88) for intense and 50% (95% CI, 47-54) for nonintense TLI (P = .001).
The retrospective study evaluated data from four randomized clinical trials, separated into a discovery set of 783 patient samples and a validation set of 763 patient samples. The LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) collaborative group trials examined the benefit of platinum-based adjuvant chemotherapy in NSCLC. The median follow-up for the discovery and validation sets were 4.8 and 6.0 years, respectively.
Differences in outcomes according to TLI were significant in both discovery and validation data sets. In the discovery set, hazard ratios for OS and DFS were 0.56 (95% CI, 0.39-0.81; P = .002) and 0.59 (95% CI, 0.42-0.83; P = .002), respectively. In the validation set, OS and DFS hazard ratios were 0.45 (95% CI, 0.23-0.85; P = .01) and 0.44 (95% CI, 0.24-0.78; P = .005), respectively. Differences in risk reductions between the two data sets may be a result of differences in trial populations.
“The results raise the question about whether lymphocytic infiltration should be considered a stratification factor in trials that test immunotherapy or immunomodulation. Therefore, as suggested recently for CD8 density level in NSCLC, which predicted survival independently of all other variables and within each pathologic stage, intense lymphocytic infiltration could be a good candidate marker for establishing a TNM immunoscore,” wrote Dr. Elisabeth Brambilla of Institut Albert Bonniot–Institut National de la Santé et de la Recherche Médicale, La Tronche, France, and her colleagues (J Clin Onc. 2016 Feb. 1. doi: 10.1200/JCO.2015.63.0970).
In contrast to results from breast cancer studies, TLI did not predict differential survival benefit from adjuvant chemotherapy in NSCLC.
The intensity of TLI on hematoxylin- and eosin-stained representative sections was first assigned into one of four categories (minimal, mild, moderate, and intense). The first three categories subsequently were collapsed into one to form a binary scoring system of intense and nonintense infiltration.
Tumor lymphocytic infiltration (TLI), categorized as intense or nonintense, was an independent prognostic indicator for survival in non–small cell lung cancer (NSCLC).
Patients with intense TLI had significantly longer overall survival (OS) and disease-free survival (DFS), compared with patients who had nonintense TLI. In the validation data set, 5-year OS for patients with intense TLI was 85% (95% confidence interval, 70-92), compared with 58% (95% CI, 54-62) for patients with nonintense TLI (P = .002). Five-year DFS was 79% (95% CI, 65-88) for intense and 50% (95% CI, 47-54) for nonintense TLI (P = .001).
The retrospective study evaluated data from four randomized clinical trials, separated into a discovery set of 783 patient samples and a validation set of 763 patient samples. The LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) collaborative group trials examined the benefit of platinum-based adjuvant chemotherapy in NSCLC. The median follow-up for the discovery and validation sets were 4.8 and 6.0 years, respectively.
Differences in outcomes according to TLI were significant in both discovery and validation data sets. In the discovery set, hazard ratios for OS and DFS were 0.56 (95% CI, 0.39-0.81; P = .002) and 0.59 (95% CI, 0.42-0.83; P = .002), respectively. In the validation set, OS and DFS hazard ratios were 0.45 (95% CI, 0.23-0.85; P = .01) and 0.44 (95% CI, 0.24-0.78; P = .005), respectively. Differences in risk reductions between the two data sets may be a result of differences in trial populations.
“The results raise the question about whether lymphocytic infiltration should be considered a stratification factor in trials that test immunotherapy or immunomodulation. Therefore, as suggested recently for CD8 density level in NSCLC, which predicted survival independently of all other variables and within each pathologic stage, intense lymphocytic infiltration could be a good candidate marker for establishing a TNM immunoscore,” wrote Dr. Elisabeth Brambilla of Institut Albert Bonniot–Institut National de la Santé et de la Recherche Médicale, La Tronche, France, and her colleagues (J Clin Onc. 2016 Feb. 1. doi: 10.1200/JCO.2015.63.0970).
In contrast to results from breast cancer studies, TLI did not predict differential survival benefit from adjuvant chemotherapy in NSCLC.
The intensity of TLI on hematoxylin- and eosin-stained representative sections was first assigned into one of four categories (minimal, mild, moderate, and intense). The first three categories subsequently were collapsed into one to form a binary scoring system of intense and nonintense infiltration.
Tumor lymphocytic infiltration (TLI), categorized as intense or nonintense, was an independent prognostic indicator for survival in non–small cell lung cancer (NSCLC).
Patients with intense TLI had significantly longer overall survival (OS) and disease-free survival (DFS), compared with patients who had nonintense TLI. In the validation data set, 5-year OS for patients with intense TLI was 85% (95% confidence interval, 70-92), compared with 58% (95% CI, 54-62) for patients with nonintense TLI (P = .002). Five-year DFS was 79% (95% CI, 65-88) for intense and 50% (95% CI, 47-54) for nonintense TLI (P = .001).
The retrospective study evaluated data from four randomized clinical trials, separated into a discovery set of 783 patient samples and a validation set of 763 patient samples. The LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) collaborative group trials examined the benefit of platinum-based adjuvant chemotherapy in NSCLC. The median follow-up for the discovery and validation sets were 4.8 and 6.0 years, respectively.
Differences in outcomes according to TLI were significant in both discovery and validation data sets. In the discovery set, hazard ratios for OS and DFS were 0.56 (95% CI, 0.39-0.81; P = .002) and 0.59 (95% CI, 0.42-0.83; P = .002), respectively. In the validation set, OS and DFS hazard ratios were 0.45 (95% CI, 0.23-0.85; P = .01) and 0.44 (95% CI, 0.24-0.78; P = .005), respectively. Differences in risk reductions between the two data sets may be a result of differences in trial populations.
“The results raise the question about whether lymphocytic infiltration should be considered a stratification factor in trials that test immunotherapy or immunomodulation. Therefore, as suggested recently for CD8 density level in NSCLC, which predicted survival independently of all other variables and within each pathologic stage, intense lymphocytic infiltration could be a good candidate marker for establishing a TNM immunoscore,” wrote Dr. Elisabeth Brambilla of Institut Albert Bonniot–Institut National de la Santé et de la Recherche Médicale, La Tronche, France, and her colleagues (J Clin Onc. 2016 Feb. 1. doi: 10.1200/JCO.2015.63.0970).
In contrast to results from breast cancer studies, TLI did not predict differential survival benefit from adjuvant chemotherapy in NSCLC.
The intensity of TLI on hematoxylin- and eosin-stained representative sections was first assigned into one of four categories (minimal, mild, moderate, and intense). The first three categories subsequently were collapsed into one to form a binary scoring system of intense and nonintense infiltration.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Intense tumor lymphocytic infiltration (TLI) predicted longer overall and disease-free survival in patients with non–small cell lung cancer.
Major finding: Five-year overall survival for patients with intense TLI was 85% (95% CI, 70-92), compared with 58% (95% CI, 54-62) for patients with nonintense TLI (P = .002).
Data source: Retrospective study using LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) collaborative group data from four randomized clinical trials of platinum-based adjuvant chemotherapy, with 783 patient samples in the discovery set and 763 patient samples in the validation set.
Disclosures: Dr. Brambilla reported having no disclosures. Several of her coauthors reported ties to industry.
Patient prognostic score may lessen DCIS overtreatment
A prognostic score based on tumor size, age, and nuclear grade indicated the magnitude of survival benefit from radiation therapy (RT) after breast-conserving surgery for ductal carcinoma in situ (DCIS).
For patients of younger age with larger tumors and higher nuclear grade, survival among those who received radiation therapy was significantly better than among those who did not. In the absence of these risk factors, survival was similar for the RT and non-RT groups. The magnitude of the survival improvement with RT was significantly correlated with the patient prognostic score: for score 0, hazard ratio (HR) was 1.2 (95% CI, 0.67 to 2.06); for score 5, HR was 0.29 (95% CI, 0.09 to 0.91).
“Overall [breast cancer mortality] was only approximately 1%, whereas mortality from other causes was approximately 10% in our study. These results, when taken together with our earlier findings on DCIS, suggest that further research investigating the overdiagnosis and overtreatment of breast cancer is warranted and that a less invasive and more individualized local treatment strategy on the basis of one’s probability of local recurrence should be considered,” wrote Dr. Yasuaki Sagara of Brigham and Women’s Hospital and Dana-Farber/Brigham and Women’s Cancer Center, Boston, and colleagues (J Clin Oncol. 2016 Feb 1. doi: 10.1200/JCO.2015.65.1869).
The retrospective longitudinal cohort study used SEER data of 32,144 patients with DCIS: 20,329 (63.2%) received radiation therapy and 11,815 (36.8%) did not. At a median 8-year follow up, there were 304 breast-cancer specific deaths (0.9%).
The patient prognostic score is based on three factors: age, tumor size, and histology, with a cumulative score ranging from 0 (lowest risk) to 6 (highest risk). Patient age categories are 61 years or greater (0 points), 40-60 years (1 point), and 40 years or less (2 points); size categories are less than 16 mm (0), 16 mm to 40 mm (1), and 41 mm or greater (2); histology categories are low grade (0), intermediate grade (1), and high grade (2).
Investigators cautioned that this retrospective study was unable to measure potential confounders, such as surgical margin status, endocrine therapy, patient comorbidities, and reasons for treatment selection, which are factors that can significantly impact overall survival outcome measures.
The researchers highlighted the utility of the prognostic score in predicting survival benefit of RT, which can guide individual treatment decisions.
“As an oncology community, we must be cognizant of overtreatment for this disease process that has low [breast cancer mortality],” they wrote.
A prognostic score based on tumor size, age, and nuclear grade indicated the magnitude of survival benefit from radiation therapy (RT) after breast-conserving surgery for ductal carcinoma in situ (DCIS).
For patients of younger age with larger tumors and higher nuclear grade, survival among those who received radiation therapy was significantly better than among those who did not. In the absence of these risk factors, survival was similar for the RT and non-RT groups. The magnitude of the survival improvement with RT was significantly correlated with the patient prognostic score: for score 0, hazard ratio (HR) was 1.2 (95% CI, 0.67 to 2.06); for score 5, HR was 0.29 (95% CI, 0.09 to 0.91).
“Overall [breast cancer mortality] was only approximately 1%, whereas mortality from other causes was approximately 10% in our study. These results, when taken together with our earlier findings on DCIS, suggest that further research investigating the overdiagnosis and overtreatment of breast cancer is warranted and that a less invasive and more individualized local treatment strategy on the basis of one’s probability of local recurrence should be considered,” wrote Dr. Yasuaki Sagara of Brigham and Women’s Hospital and Dana-Farber/Brigham and Women’s Cancer Center, Boston, and colleagues (J Clin Oncol. 2016 Feb 1. doi: 10.1200/JCO.2015.65.1869).
The retrospective longitudinal cohort study used SEER data of 32,144 patients with DCIS: 20,329 (63.2%) received radiation therapy and 11,815 (36.8%) did not. At a median 8-year follow up, there were 304 breast-cancer specific deaths (0.9%).
The patient prognostic score is based on three factors: age, tumor size, and histology, with a cumulative score ranging from 0 (lowest risk) to 6 (highest risk). Patient age categories are 61 years or greater (0 points), 40-60 years (1 point), and 40 years or less (2 points); size categories are less than 16 mm (0), 16 mm to 40 mm (1), and 41 mm or greater (2); histology categories are low grade (0), intermediate grade (1), and high grade (2).
Investigators cautioned that this retrospective study was unable to measure potential confounders, such as surgical margin status, endocrine therapy, patient comorbidities, and reasons for treatment selection, which are factors that can significantly impact overall survival outcome measures.
The researchers highlighted the utility of the prognostic score in predicting survival benefit of RT, which can guide individual treatment decisions.
“As an oncology community, we must be cognizant of overtreatment for this disease process that has low [breast cancer mortality],” they wrote.
A prognostic score based on tumor size, age, and nuclear grade indicated the magnitude of survival benefit from radiation therapy (RT) after breast-conserving surgery for ductal carcinoma in situ (DCIS).
For patients of younger age with larger tumors and higher nuclear grade, survival among those who received radiation therapy was significantly better than among those who did not. In the absence of these risk factors, survival was similar for the RT and non-RT groups. The magnitude of the survival improvement with RT was significantly correlated with the patient prognostic score: for score 0, hazard ratio (HR) was 1.2 (95% CI, 0.67 to 2.06); for score 5, HR was 0.29 (95% CI, 0.09 to 0.91).
“Overall [breast cancer mortality] was only approximately 1%, whereas mortality from other causes was approximately 10% in our study. These results, when taken together with our earlier findings on DCIS, suggest that further research investigating the overdiagnosis and overtreatment of breast cancer is warranted and that a less invasive and more individualized local treatment strategy on the basis of one’s probability of local recurrence should be considered,” wrote Dr. Yasuaki Sagara of Brigham and Women’s Hospital and Dana-Farber/Brigham and Women’s Cancer Center, Boston, and colleagues (J Clin Oncol. 2016 Feb 1. doi: 10.1200/JCO.2015.65.1869).
The retrospective longitudinal cohort study used SEER data of 32,144 patients with DCIS: 20,329 (63.2%) received radiation therapy and 11,815 (36.8%) did not. At a median 8-year follow up, there were 304 breast-cancer specific deaths (0.9%).
The patient prognostic score is based on three factors: age, tumor size, and histology, with a cumulative score ranging from 0 (lowest risk) to 6 (highest risk). Patient age categories are 61 years or greater (0 points), 40-60 years (1 point), and 40 years or less (2 points); size categories are less than 16 mm (0), 16 mm to 40 mm (1), and 41 mm or greater (2); histology categories are low grade (0), intermediate grade (1), and high grade (2).
Investigators cautioned that this retrospective study was unable to measure potential confounders, such as surgical margin status, endocrine therapy, patient comorbidities, and reasons for treatment selection, which are factors that can significantly impact overall survival outcome measures.
The researchers highlighted the utility of the prognostic score in predicting survival benefit of RT, which can guide individual treatment decisions.
“As an oncology community, we must be cognizant of overtreatment for this disease process that has low [breast cancer mortality],” they wrote.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: A recurrence risk score based on clinicopathologic features of ductal carcinoma in situ (DCIS) was associated with survival benefit of radiation therapy after breast-conserving surgery.
Major finding: For patients of younger age with larger tumors and higher nuclear grade, survival among those who received radiation therapy was significantly better than among those who did not; in the absence of the risk factors, survival was similar for the two groups.
Data source: Retrospective longitudinal cohort study using SEER data of 32,144 patients with DCIS: 20,329 received radiation therapy and 11,815 did not.
Disclosures: Dr. Sagara reported having no disclosures. Two of his coauthors reported ties to industry.
Proton radiotherapy effective for childhood medulloblastoma
Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.
At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).
For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).
“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.
“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.
Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.
The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.
There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.
The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.
The prospective study by Dr. Yock and colleagues sets a new benchmark for treatment of medulloblastoma in pediatric patients and alludes to the clinical benefits of advanced radiation treatment. It becomes increasingly important for radiation oncologists to incorporate new findings in genomics and molecular subtyping for diseases such as medulloblastoma in the design of prospective studies, and to implement strategies to prevent cognitive decline in pediatric patients. The investigators demonstrate benefits of low-dose sparing afforded by proton therapy, but further improvements are possible. With newer delivery techniques, such as spot scanning proton therapy for the craniospinal component of treatment, more improvements in hearing outcomes can be expected.
The rarity of the disease, combined with the compelling results of Dr. Yock and colleagues, make randomized trials of photons versus protons for medulloblastoma unlikely. Without randomized trial data, some states require that all pediatric patients be treated with photon therapy, a requirement that could result higher rates of cardiovascular disease and other adverse effects. Radiation oncologists understand the potential for severe adverse effects of treatment, and many embrace new technologies that mitigate effects of radiation therapy on patients’ quality of life, a consideration that is particularly important in treatment of pediatric cancers.
Dr. David Grosshans is at the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. These remarks were part of an editorial accompanying the report by Dr. Yock and colleagues (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00217-X. Dr. Grosshans reported having no disclosures.
The prospective study by Dr. Yock and colleagues sets a new benchmark for treatment of medulloblastoma in pediatric patients and alludes to the clinical benefits of advanced radiation treatment. It becomes increasingly important for radiation oncologists to incorporate new findings in genomics and molecular subtyping for diseases such as medulloblastoma in the design of prospective studies, and to implement strategies to prevent cognitive decline in pediatric patients. The investigators demonstrate benefits of low-dose sparing afforded by proton therapy, but further improvements are possible. With newer delivery techniques, such as spot scanning proton therapy for the craniospinal component of treatment, more improvements in hearing outcomes can be expected.
The rarity of the disease, combined with the compelling results of Dr. Yock and colleagues, make randomized trials of photons versus protons for medulloblastoma unlikely. Without randomized trial data, some states require that all pediatric patients be treated with photon therapy, a requirement that could result higher rates of cardiovascular disease and other adverse effects. Radiation oncologists understand the potential for severe adverse effects of treatment, and many embrace new technologies that mitigate effects of radiation therapy on patients’ quality of life, a consideration that is particularly important in treatment of pediatric cancers.
Dr. David Grosshans is at the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. These remarks were part of an editorial accompanying the report by Dr. Yock and colleagues (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00217-X. Dr. Grosshans reported having no disclosures.
The prospective study by Dr. Yock and colleagues sets a new benchmark for treatment of medulloblastoma in pediatric patients and alludes to the clinical benefits of advanced radiation treatment. It becomes increasingly important for radiation oncologists to incorporate new findings in genomics and molecular subtyping for diseases such as medulloblastoma in the design of prospective studies, and to implement strategies to prevent cognitive decline in pediatric patients. The investigators demonstrate benefits of low-dose sparing afforded by proton therapy, but further improvements are possible. With newer delivery techniques, such as spot scanning proton therapy for the craniospinal component of treatment, more improvements in hearing outcomes can be expected.
The rarity of the disease, combined with the compelling results of Dr. Yock and colleagues, make randomized trials of photons versus protons for medulloblastoma unlikely. Without randomized trial data, some states require that all pediatric patients be treated with photon therapy, a requirement that could result higher rates of cardiovascular disease and other adverse effects. Radiation oncologists understand the potential for severe adverse effects of treatment, and many embrace new technologies that mitigate effects of radiation therapy on patients’ quality of life, a consideration that is particularly important in treatment of pediatric cancers.
Dr. David Grosshans is at the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. These remarks were part of an editorial accompanying the report by Dr. Yock and colleagues (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00217-X. Dr. Grosshans reported having no disclosures.
Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.
At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).
For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).
“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.
“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.
Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.
The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.
There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.
The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.
Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.
At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).
For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).
“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.
“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.
Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.
The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.
There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.
The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.
FROM THE LANCET ONCOLOGY
Key clinical point: Proton radiotherapy for childhood medulloblastoma resulted in similar survival outcomes to those of photon-based therapy and had acceptable toxicity.
Major finding: At 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16%; 5-year progression-free and overall survival for patients with standard risk were 85% and 86%, respectively, and for those with high to intermediate risk, 70% and 75%, respectively.
Data source: A prospective, nonrandomized, phase II study with 59 patients aged 3-21 years who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk).
Disclosures: Dr. Yock and coauthors reported having no disclosures.
Peripheral T-cell lymphoma incidence and survival varies significantly by race
Peripheral T-cell lymphoma (PTCL) incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States, according to analysis of SEER cancer registries.
Compared with non-Hispanic whites, blacks had higher incidence rates overall of PTCL, due to higher rates of PTCL not otherwise specified (PTCL-NOS) (incidence rate ratio [IRR], 1.67; 95% CI, 1.53-1.82) and adult T-cell leukemia/lymphoma (ATLL) (IRR, 4.37; 3.42-5.56). By contrast, blacks had lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL) than non-Hispanic whites. Underlying causes for these differences are not understood.
“Our findings also highlight the need for stronger efforts to increase recruitment of blacks into clinical trials of PTCL therapies,” wrote Dr. Scott Adams of Fred Hutchinson Cancer Research Center, Seattle, and colleagues (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.635540).
Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL (IRR, 3.61; 2.93-4.42), and ENKCL comprised a larger proportion of PTCL (14%) in these populations than for non-Hispanic whites (3%), findings which reflect global variations. High rates of ENKCL may be influenced by both genetic and environmental factors, as 35% of this subpopulation was born outside the U.S., compared with 16% of all patients with PTCL. Epstein-Barre virus infection is associated with ENKCL.
Similar to global incidence patterns, Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL).
Higher incidence of ATLL among blacks and Asians/Pacific Islanders corresponded to a higher prevalence of human T-lymphotropic virus type 1 in these populations. Substantial differences in survival were also observed. Compared with non-Hispanic whites, survival with PTCL-NOS was shorter for every minority group, and blacks had worse prognoses for almost every histology. For patients with any PTCL, median survival time varied by race: 49 months for non-Hispanic whites, 24 for blacks, 22 for Asians/Pacific Islanders, 28 for Hispanic whites, and 36 for American Indians/Alaskan natives.
Reasons for survival disparities are not known, but contributing factors may include racial variations in pharmacokinetics or pharmacodynamics of therapeutic agents and genomic variations of the tumors, as well as healthcare disparities and socioeconomic factors.
The analysis used data from SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.
For non-Hispanic whites, the annual incidence rate of all PTCLs was 1.56 (95% CI; 1.52-1.59) per 100,000. Compared with non-Hispanic whites, incidence rate ratios were 1.32 (1.25-1.39; P less than .001) for blacks, 0.89 (0.83-0.95; P less than .001) for Asians/Pacific Islanders, 0.63 (0.49-0.79; P less than .001) for American Indians/Alaskan natives, and 0.96 (0.90-1.01; P = .13) for Hispanic whites.
Peripheral T-cell lymphoma (PTCL) incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States, according to analysis of SEER cancer registries.
Compared with non-Hispanic whites, blacks had higher incidence rates overall of PTCL, due to higher rates of PTCL not otherwise specified (PTCL-NOS) (incidence rate ratio [IRR], 1.67; 95% CI, 1.53-1.82) and adult T-cell leukemia/lymphoma (ATLL) (IRR, 4.37; 3.42-5.56). By contrast, blacks had lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL) than non-Hispanic whites. Underlying causes for these differences are not understood.
“Our findings also highlight the need for stronger efforts to increase recruitment of blacks into clinical trials of PTCL therapies,” wrote Dr. Scott Adams of Fred Hutchinson Cancer Research Center, Seattle, and colleagues (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.635540).
Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL (IRR, 3.61; 2.93-4.42), and ENKCL comprised a larger proportion of PTCL (14%) in these populations than for non-Hispanic whites (3%), findings which reflect global variations. High rates of ENKCL may be influenced by both genetic and environmental factors, as 35% of this subpopulation was born outside the U.S., compared with 16% of all patients with PTCL. Epstein-Barre virus infection is associated with ENKCL.
Similar to global incidence patterns, Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL).
Higher incidence of ATLL among blacks and Asians/Pacific Islanders corresponded to a higher prevalence of human T-lymphotropic virus type 1 in these populations. Substantial differences in survival were also observed. Compared with non-Hispanic whites, survival with PTCL-NOS was shorter for every minority group, and blacks had worse prognoses for almost every histology. For patients with any PTCL, median survival time varied by race: 49 months for non-Hispanic whites, 24 for blacks, 22 for Asians/Pacific Islanders, 28 for Hispanic whites, and 36 for American Indians/Alaskan natives.
Reasons for survival disparities are not known, but contributing factors may include racial variations in pharmacokinetics or pharmacodynamics of therapeutic agents and genomic variations of the tumors, as well as healthcare disparities and socioeconomic factors.
The analysis used data from SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.
For non-Hispanic whites, the annual incidence rate of all PTCLs was 1.56 (95% CI; 1.52-1.59) per 100,000. Compared with non-Hispanic whites, incidence rate ratios were 1.32 (1.25-1.39; P less than .001) for blacks, 0.89 (0.83-0.95; P less than .001) for Asians/Pacific Islanders, 0.63 (0.49-0.79; P less than .001) for American Indians/Alaskan natives, and 0.96 (0.90-1.01; P = .13) for Hispanic whites.
Peripheral T-cell lymphoma (PTCL) incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States, according to analysis of SEER cancer registries.
Compared with non-Hispanic whites, blacks had higher incidence rates overall of PTCL, due to higher rates of PTCL not otherwise specified (PTCL-NOS) (incidence rate ratio [IRR], 1.67; 95% CI, 1.53-1.82) and adult T-cell leukemia/lymphoma (ATLL) (IRR, 4.37; 3.42-5.56). By contrast, blacks had lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL) than non-Hispanic whites. Underlying causes for these differences are not understood.
“Our findings also highlight the need for stronger efforts to increase recruitment of blacks into clinical trials of PTCL therapies,” wrote Dr. Scott Adams of Fred Hutchinson Cancer Research Center, Seattle, and colleagues (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.635540).
Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL (IRR, 3.61; 2.93-4.42), and ENKCL comprised a larger proportion of PTCL (14%) in these populations than for non-Hispanic whites (3%), findings which reflect global variations. High rates of ENKCL may be influenced by both genetic and environmental factors, as 35% of this subpopulation was born outside the U.S., compared with 16% of all patients with PTCL. Epstein-Barre virus infection is associated with ENKCL.
Similar to global incidence patterns, Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL).
Higher incidence of ATLL among blacks and Asians/Pacific Islanders corresponded to a higher prevalence of human T-lymphotropic virus type 1 in these populations. Substantial differences in survival were also observed. Compared with non-Hispanic whites, survival with PTCL-NOS was shorter for every minority group, and blacks had worse prognoses for almost every histology. For patients with any PTCL, median survival time varied by race: 49 months for non-Hispanic whites, 24 for blacks, 22 for Asians/Pacific Islanders, 28 for Hispanic whites, and 36 for American Indians/Alaskan natives.
Reasons for survival disparities are not known, but contributing factors may include racial variations in pharmacokinetics or pharmacodynamics of therapeutic agents and genomic variations of the tumors, as well as healthcare disparities and socioeconomic factors.
The analysis used data from SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.
For non-Hispanic whites, the annual incidence rate of all PTCLs was 1.56 (95% CI; 1.52-1.59) per 100,000. Compared with non-Hispanic whites, incidence rate ratios were 1.32 (1.25-1.39; P less than .001) for blacks, 0.89 (0.83-0.95; P less than .001) for Asians/Pacific Islanders, 0.63 (0.49-0.79; P less than .001) for American Indians/Alaskan natives, and 0.96 (0.90-1.01; P = .13) for Hispanic whites.
Key clinical point: Peripheral T-cell lymphoma incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States.
Major finding: Compared with non-Hispanic whites, blacks had higher incidence rates of PTCL not otherwise specified (PTCL-NOS) and adult T-cell leukemia/lymphoma (ATLL), and lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL); Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL; Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL); survival with PTCL-NOS was shorter for every minority group compared with non-Hispanic whites.
Data source: SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.
Disclosures: Dr. Adams reported having no disclosures. Dr. Shustov, a coauthor, reported financial ties to Celgene, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Millennium, Gilead Sciences, Seattle Genetics, and Pfizer.
CAR T-cells induce remissions, avoid GVHD in relapsed B-cell malignancies
In patients with B-cell malignancies who did not obtain remissions after allogeneic hematopoietic stem-cell transplantation (alloHSCT), infusion of anti-CD19 chimeric antigen receptor (CAR19) T-cells induced remissions without causing graft-versus-host disease (GVHD).
Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions, while none of the patients experienced new-onset acute GVHD.
“The increased antimalignancy potency of CAR19 T-cells allowed small doses of T-cells to eradicate malignancy without causing GVHD; therefore, this work demonstrates a solution to the central problem of alloHSCT, the separation of [graft-versus-malignancy] from GVHD,” wrote Dr. Jennifer Brudno of the National Cancer Institute, Bethesda, Md., and colleagues (J Clin Onc. 2016 Jan. 25. doi: 10.1200/JCO.2015.64.5929).
In general, CAR19 T-cells did not persist longer than 4 weeks, the median time it takes for GVHD to develop after donor lymphocyte infusion, which may be a factor in avoiding GVHD. Smaller doses may be another contributing factor: CAR19 T-cell doses administered in the trial ranged from 106/kg to 107/kg, which is 10-fold smaller than typical donor lymphocyte infusions.
In contrast to previous CAR T-cell studies, patients did not receive chemotherapy before CAR19 T-cell infusion, so endogenous T-cells and natural killer cells were not depleted. Evidence indicates that lymphocyte depletion enhances antitumor activity of adoptively transferred T-cells, but the current results indicate that prior lymphocyte depletion is not an absolute requirement.
The CAR19 T-cell infusion was especially effective in acute lymphoblastic leukemia (ALL), with four of the five ALL patients obtaining complete remission. Patients with chronic lymphocyte leukemia and lymphoma also obtained remissions.
Toxicities observed were consistent with previous CAR T-cell studies and included fever, tachycardia, and hypotension, indicative of cytokine release syndrome.
Peak levels of CAR19 T-cells were significantly higher in patients with complete or partial responses, and patients who did not obtain a complete or partial response were more likely to have undetectable or very low levels. Increasing peak blood levels of CAR19 T-cells in vivo is an important goal for future research, according to investigators. Since endogenous CD19+ cells may promote proliferation of CAR19 T- cells, CD19+ cellular vaccines might enhance CAR19 T-cell proliferation in patients with low levels, they suggested.
Administration of programmed cell death protein-1 (PD-1) antagonists may also offer improvements. High levels of PD-1 expression on CAR19 T-cells were observed at the time of peak blood CAR19 T-cell levels.
Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.
In patients with B-cell malignancies who did not obtain remissions after allogeneic hematopoietic stem-cell transplantation (alloHSCT), infusion of anti-CD19 chimeric antigen receptor (CAR19) T-cells induced remissions without causing graft-versus-host disease (GVHD).
Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions, while none of the patients experienced new-onset acute GVHD.
“The increased antimalignancy potency of CAR19 T-cells allowed small doses of T-cells to eradicate malignancy without causing GVHD; therefore, this work demonstrates a solution to the central problem of alloHSCT, the separation of [graft-versus-malignancy] from GVHD,” wrote Dr. Jennifer Brudno of the National Cancer Institute, Bethesda, Md., and colleagues (J Clin Onc. 2016 Jan. 25. doi: 10.1200/JCO.2015.64.5929).
In general, CAR19 T-cells did not persist longer than 4 weeks, the median time it takes for GVHD to develop after donor lymphocyte infusion, which may be a factor in avoiding GVHD. Smaller doses may be another contributing factor: CAR19 T-cell doses administered in the trial ranged from 106/kg to 107/kg, which is 10-fold smaller than typical donor lymphocyte infusions.
In contrast to previous CAR T-cell studies, patients did not receive chemotherapy before CAR19 T-cell infusion, so endogenous T-cells and natural killer cells were not depleted. Evidence indicates that lymphocyte depletion enhances antitumor activity of adoptively transferred T-cells, but the current results indicate that prior lymphocyte depletion is not an absolute requirement.
The CAR19 T-cell infusion was especially effective in acute lymphoblastic leukemia (ALL), with four of the five ALL patients obtaining complete remission. Patients with chronic lymphocyte leukemia and lymphoma also obtained remissions.
Toxicities observed were consistent with previous CAR T-cell studies and included fever, tachycardia, and hypotension, indicative of cytokine release syndrome.
Peak levels of CAR19 T-cells were significantly higher in patients with complete or partial responses, and patients who did not obtain a complete or partial response were more likely to have undetectable or very low levels. Increasing peak blood levels of CAR19 T-cells in vivo is an important goal for future research, according to investigators. Since endogenous CD19+ cells may promote proliferation of CAR19 T- cells, CD19+ cellular vaccines might enhance CAR19 T-cell proliferation in patients with low levels, they suggested.
Administration of programmed cell death protein-1 (PD-1) antagonists may also offer improvements. High levels of PD-1 expression on CAR19 T-cells were observed at the time of peak blood CAR19 T-cell levels.
Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.
In patients with B-cell malignancies who did not obtain remissions after allogeneic hematopoietic stem-cell transplantation (alloHSCT), infusion of anti-CD19 chimeric antigen receptor (CAR19) T-cells induced remissions without causing graft-versus-host disease (GVHD).
Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions, while none of the patients experienced new-onset acute GVHD.
“The increased antimalignancy potency of CAR19 T-cells allowed small doses of T-cells to eradicate malignancy without causing GVHD; therefore, this work demonstrates a solution to the central problem of alloHSCT, the separation of [graft-versus-malignancy] from GVHD,” wrote Dr. Jennifer Brudno of the National Cancer Institute, Bethesda, Md., and colleagues (J Clin Onc. 2016 Jan. 25. doi: 10.1200/JCO.2015.64.5929).
In general, CAR19 T-cells did not persist longer than 4 weeks, the median time it takes for GVHD to develop after donor lymphocyte infusion, which may be a factor in avoiding GVHD. Smaller doses may be another contributing factor: CAR19 T-cell doses administered in the trial ranged from 106/kg to 107/kg, which is 10-fold smaller than typical donor lymphocyte infusions.
In contrast to previous CAR T-cell studies, patients did not receive chemotherapy before CAR19 T-cell infusion, so endogenous T-cells and natural killer cells were not depleted. Evidence indicates that lymphocyte depletion enhances antitumor activity of adoptively transferred T-cells, but the current results indicate that prior lymphocyte depletion is not an absolute requirement.
The CAR19 T-cell infusion was especially effective in acute lymphoblastic leukemia (ALL), with four of the five ALL patients obtaining complete remission. Patients with chronic lymphocyte leukemia and lymphoma also obtained remissions.
Toxicities observed were consistent with previous CAR T-cell studies and included fever, tachycardia, and hypotension, indicative of cytokine release syndrome.
Peak levels of CAR19 T-cells were significantly higher in patients with complete or partial responses, and patients who did not obtain a complete or partial response were more likely to have undetectable or very low levels. Increasing peak blood levels of CAR19 T-cells in vivo is an important goal for future research, according to investigators. Since endogenous CD19+ cells may promote proliferation of CAR19 T- cells, CD19+ cellular vaccines might enhance CAR19 T-cell proliferation in patients with low levels, they suggested.
Administration of programmed cell death protein-1 (PD-1) antagonists may also offer improvements. High levels of PD-1 expression on CAR19 T-cells were observed at the time of peak blood CAR19 T-cell levels.
Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: In patients who relapsed after allogeneic hematopoietic stem-cell transplantation, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy induced remissions without causing graft-versus-host disease (GVHD).
Major finding: Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions; none experienced new-onset acute GVHD.
Data source: Patients with B-cell malignancies who had progressed after allogeneic hematopoietic stem-cell transplantation.
Disclosures: Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.