Interim FDG-PET 'Not Justified' in Diffuse Large B-Cell Lymphoma

LONDON – There is no benefit of performing ¹⁸fluorodeoxyglucose positron emission tomography after the first cycle of treatment in patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, the results of an Italian study suggest.

The imaging technique failed to pick up signs of disease in 10 of 85 (12%) of patients who later relapsed following treatment with R-CHOP (rituximab [Rituxan], cyclophosphamide [Cytoxan], hydroxydaunorubicin [doxorubicin, Adriamycin], Oncovin [vincristine], and prednisolone) in conjunction with radiotherapy.

Interim ¹⁸FDG-PET was associated with a positive predictive value (PPV) of just 58% and a negative predictive value (NPV) of 77%. By comparison, the PPV and NPV of ¹⁸FDG-PET performed after the last treatment cycle were higher, at 70% and 82%, respectively.

"The early identification of nonresponders might be a pivotal step for cure of diffuse large B-cell lymphoma (DLBCL), said study investigator Dr. M. Christina Cox, who presented the findings at the annual congress of the European Hematology Association.

Dr. Cox of the Azienda Ospedaliera Sant’ Andrea in Rome explained that the use of the imaging method early on in the treatment of Hodgkin’s lymphoma had been shown to be a strong predictor of outcome, allowing earlier adjustment of therapy.

"From 2005, several studies showed than in [DLBCL], interim PET might be predictive of event-free survival, progression-free survival, and overall survival," Dr. Cox said. However, "more recent studies have yielded heterogeneous results."

Aiming to clarify the issue, Dr. Cox and colleagues undertook a prospective study of treatment-naive patients with either DLBCL (72 patients) or primary mediastinal large B-cell lymphoma (PMLBCL, 13 patients) enrolled between April 2005 and April 2010. Patients were eligible for the study if they had already undergone a PET or contrast enhancement computed tomography (CECT) scan, had no CNS involvement, were HIV negative, and were not eligible for R-CHOP-like treatments.

After initial staging with ¹⁸FDG-PET and CECT, patients with stage II or higher DLCBL received six cycles of treatment with either R-CHOP-14 if they were younger than 70 years or R-CHOP-21 if they were aged 70 years or older. In both cases, the duration of treatment was reduced to three cycles for patients with stage I disease. Patients with PMLBCL were treated with R-MACOP-14 (rituximab, methotrexate, ara-C [cytarabine], cyclophosphamide, Oncovin [vincristine], and prednisone) for 12 weeks. All patients with PMLBCL and those with stage I DLCBL received radiotherapy.

Interim staging using PET and CECT was performed within 10-20 days of the first cycle of treatment, with the final scans using both imaging techniques taken 6-8 weeks after the last treatment. The recently validated Deauville 5-point scale was used to compare the differences between interim and final PET scans. This scale gauges the uptake of ¹⁸FDG within the tissues.

The minimum observation time was set at 2 years, unless a DLBCL event occurred earlier. Targeted biopsies were performed at the end of treatment if there was a mismatch between PET and CECT results, and at the interim stage if results were conflicting and the site in need of biopsy was easy to reach.

Almost two-thirds (62%) were biopsy negative. Dr. Cox noted that none of the interim PET, biopsy-negative patients relapsed.

At a median follow-up of almost 3 years, 70 (82.3%) patients were still alive, with 65 (76.4%) being disease free after first- or second-line therapy. One-fifth had been refractory to first-line treatment. Of these patients, 78% had a positive interim PET scan.

Looking at factors that might predict the achievement of a complete remission to first-line treatment, only the interim CECT results were statistically significant in a multivariate analysis (P less than .002).

In addition, only the final PET scan was predictive of both overall and progression-free survival, whereas interim and final CECT were both predictive.

"In this series, interim PET proved not to be a robust tool for the early shifting of patients to high-dose therapy," Dr. Cox reported. She added that compared with interim CECT and final PET, "interim PET was not really of adjunctive value." Indeed, most refractory patients (61%) were identified by interim CECT.

"We think that the use of this [interim PET] expensive, radioactive, and emotionally distressing tool is presently not justified outside of clinical trials."

Commenting on the findings in an interview, Dr. Andrew Pettitt, professor of hematological oncology at the University of Liverpool (England), said that although it was a good study, he was not convinced it was adequately powered to draw such a definitive conclusion. "I also have some reservations of the PET-CT reporting and quality control," Dr. Pettitt, who was not involved in the study. "It’s very provocative, but I don’t think it’s definitive."

Dr. Cox and Dr. Pettitt stated that they had no relevant financial disclosures.

LONDON – There is no benefit of performing ¹⁸fluorodeoxyglucose positron emission tomography after the first cycle of treatment in patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, the results of an Italian study suggest.

The imaging technique failed to pick up signs of disease in 10 of 85 (12%) of patients who later relapsed following treatment with R-CHOP (rituximab [Rituxan], cyclophosphamide [Cytoxan], hydroxydaunorubicin [doxorubicin, Adriamycin], Oncovin [vincristine], and prednisolone) in conjunction with radiotherapy.

Interim ¹⁸FDG-PET was associated with a positive predictive value (PPV) of just 58% and a negative predictive value (NPV) of 77%. By comparison, the PPV and NPV of ¹⁸FDG-PET performed after the last treatment cycle were higher, at 70% and 82%, respectively.

"The early identification of nonresponders might be a pivotal step for cure of diffuse large B-cell lymphoma (DLBCL), said study investigator Dr. M. Christina Cox, who presented the findings at the annual congress of the European Hematology Association.

Dr. Cox of the Azienda Ospedaliera Sant’ Andrea in Rome explained that the use of the imaging method early on in the treatment of Hodgkin’s lymphoma had been shown to be a strong predictor of outcome, allowing earlier adjustment of therapy.

"From 2005, several studies showed than in [DLBCL], interim PET might be predictive of event-free survival, progression-free survival, and overall survival," Dr. Cox said. However, "more recent studies have yielded heterogeneous results."

Aiming to clarify the issue, Dr. Cox and colleagues undertook a prospective study of treatment-naive patients with either DLBCL (72 patients) or primary mediastinal large B-cell lymphoma (PMLBCL, 13 patients) enrolled between April 2005 and April 2010. Patients were eligible for the study if they had already undergone a PET or contrast enhancement computed tomography (CECT) scan, had no CNS involvement, were HIV negative, and were not eligible for R-CHOP-like treatments.

After initial staging with ¹⁸FDG-PET and CECT, patients with stage II or higher DLCBL received six cycles of treatment with either R-CHOP-14 if they were younger than 70 years or R-CHOP-21 if they were aged 70 years or older. In both cases, the duration of treatment was reduced to three cycles for patients with stage I disease. Patients with PMLBCL were treated with R-MACOP-14 (rituximab, methotrexate, ara-C [cytarabine], cyclophosphamide, Oncovin [vincristine], and prednisone) for 12 weeks. All patients with PMLBCL and those with stage I DLCBL received radiotherapy.

Interim staging using PET and CECT was performed within 10-20 days of the first cycle of treatment, with the final scans using both imaging techniques taken 6-8 weeks after the last treatment. The recently validated Deauville 5-point scale was used to compare the differences between interim and final PET scans. This scale gauges the uptake of ¹⁸FDG within the tissues.

The minimum observation time was set at 2 years, unless a DLBCL event occurred earlier. Targeted biopsies were performed at the end of treatment if there was a mismatch between PET and CECT results, and at the interim stage if results were conflicting and the site in need of biopsy was easy to reach.

Almost two-thirds (62%) were biopsy negative. Dr. Cox noted that none of the interim PET, biopsy-negative patients relapsed.

At a median follow-up of almost 3 years, 70 (82.3%) patients were still alive, with 65 (76.4%) being disease free after first- or second-line therapy. One-fifth had been refractory to first-line treatment. Of these patients, 78% had a positive interim PET scan.

Looking at factors that might predict the achievement of a complete remission to first-line treatment, only the interim CECT results were statistically significant in a multivariate analysis (P less than .002).

In addition, only the final PET scan was predictive of both overall and progression-free survival, whereas interim and final CECT were both predictive.

"In this series, interim PET proved not to be a robust tool for the early shifting of patients to high-dose therapy," Dr. Cox reported. She added that compared with interim CECT and final PET, "interim PET was not really of adjunctive value." Indeed, most refractory patients (61%) were identified by interim CECT.

"We think that the use of this [interim PET] expensive, radioactive, and emotionally distressing tool is presently not justified outside of clinical trials."

Commenting on the findings in an interview, Dr. Andrew Pettitt, professor of hematological oncology at the University of Liverpool (England), said that although it was a good study, he was not convinced it was adequately powered to draw such a definitive conclusion. "I also have some reservations of the PET-CT reporting and quality control," Dr. Pettitt, who was not involved in the study. "It’s very provocative, but I don’t think it’s definitive."

Dr. Cox and Dr. Pettitt stated that they had no relevant financial disclosures.

LONDON – There is no benefit of performing ¹⁸fluorodeoxyglucose positron emission tomography after the first cycle of treatment in patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, the results of an Italian study suggest.

The imaging technique failed to pick up signs of disease in 10 of 85 (12%) of patients who later relapsed following treatment with R-CHOP (rituximab [Rituxan], cyclophosphamide [Cytoxan], hydroxydaunorubicin [doxorubicin, Adriamycin], Oncovin [vincristine], and prednisolone) in conjunction with radiotherapy.

Interim ¹⁸FDG-PET was associated with a positive predictive value (PPV) of just 58% and a negative predictive value (NPV) of 77%. By comparison, the PPV and NPV of ¹⁸FDG-PET performed after the last treatment cycle were higher, at 70% and 82%, respectively.

"The early identification of nonresponders might be a pivotal step for cure of diffuse large B-cell lymphoma (DLBCL), said study investigator Dr. M. Christina Cox, who presented the findings at the annual congress of the European Hematology Association.

Dr. Cox of the Azienda Ospedaliera Sant’ Andrea in Rome explained that the use of the imaging method early on in the treatment of Hodgkin’s lymphoma had been shown to be a strong predictor of outcome, allowing earlier adjustment of therapy.

"From 2005, several studies showed than in [DLBCL], interim PET might be predictive of event-free survival, progression-free survival, and overall survival," Dr. Cox said. However, "more recent studies have yielded heterogeneous results."

Aiming to clarify the issue, Dr. Cox and colleagues undertook a prospective study of treatment-naive patients with either DLBCL (72 patients) or primary mediastinal large B-cell lymphoma (PMLBCL, 13 patients) enrolled between April 2005 and April 2010. Patients were eligible for the study if they had already undergone a PET or contrast enhancement computed tomography (CECT) scan, had no CNS involvement, were HIV negative, and were not eligible for R-CHOP-like treatments.

After initial staging with ¹⁸FDG-PET and CECT, patients with stage II or higher DLCBL received six cycles of treatment with either R-CHOP-14 if they were younger than 70 years or R-CHOP-21 if they were aged 70 years or older. In both cases, the duration of treatment was reduced to three cycles for patients with stage I disease. Patients with PMLBCL were treated with R-MACOP-14 (rituximab, methotrexate, ara-C [cytarabine], cyclophosphamide, Oncovin [vincristine], and prednisone) for 12 weeks. All patients with PMLBCL and those with stage I DLCBL received radiotherapy.

Interim staging using PET and CECT was performed within 10-20 days of the first cycle of treatment, with the final scans using both imaging techniques taken 6-8 weeks after the last treatment. The recently validated Deauville 5-point scale was used to compare the differences between interim and final PET scans. This scale gauges the uptake of ¹⁸FDG within the tissues.

The minimum observation time was set at 2 years, unless a DLBCL event occurred earlier. Targeted biopsies were performed at the end of treatment if there was a mismatch between PET and CECT results, and at the interim stage if results were conflicting and the site in need of biopsy was easy to reach.

Almost two-thirds (62%) were biopsy negative. Dr. Cox noted that none of the interim PET, biopsy-negative patients relapsed.

At a median follow-up of almost 3 years, 70 (82.3%) patients were still alive, with 65 (76.4%) being disease free after first- or second-line therapy. One-fifth had been refractory to first-line treatment. Of these patients, 78% had a positive interim PET scan.

Looking at factors that might predict the achievement of a complete remission to first-line treatment, only the interim CECT results were statistically significant in a multivariate analysis (P less than .002).

In addition, only the final PET scan was predictive of both overall and progression-free survival, whereas interim and final CECT were both predictive.

"In this series, interim PET proved not to be a robust tool for the early shifting of patients to high-dose therapy," Dr. Cox reported. She added that compared with interim CECT and final PET, "interim PET was not really of adjunctive value." Indeed, most refractory patients (61%) were identified by interim CECT.

"We think that the use of this [interim PET] expensive, radioactive, and emotionally distressing tool is presently not justified outside of clinical trials."

Commenting on the findings in an interview, Dr. Andrew Pettitt, professor of hematological oncology at the University of Liverpool (England), said that although it was a good study, he was not convinced it was adequately powered to draw such a definitive conclusion. "I also have some reservations of the PET-CT reporting and quality control," Dr. Pettitt, who was not involved in the study. "It’s very provocative, but I don’t think it’s definitive."

Dr. Cox and Dr. Pettitt stated that they had no relevant financial disclosures.