Wang DH

Background: Digestive system malignancies constitute 18% of all cancers in the US veteran population (VA Central Cancer Registry 2010 data). Managing these patients involves multiple treatment modalities. The Multidisciplinary Gastrointestinal Malignancy Clinic (MGMC) was established at the Dallas VAMC in 2016. Prior to the MGMC, patients presented to their primary care physicians, who once a malignancy was biopsy confirmed, consulted an oncologic specialist. Patients requiring multidisciplinary oncologic care had three or more appointments (medical, surgical, and radiation oncology) scheduled on separate days. However, since the MGMC was established, various oncologic specialists now evaluate the patients on a single clinic day and a definitive consensus therapy course is planned.

Methods: Patients seen in the MGMC were matched to patient controls (seen 2 years before the MGMC was established) by pathologic diagnosis and stage. The main endpoints were; time between initial oncologic consult and first definitive therapy; time from biopsy to completion of staging and first definitive therapy. The average times for each endpoint for these 2 groups was evaluated statistically using the student T test.

Results: 40 patient cases were selected from the group seen at the MGMC from July 2016 - June 2018 and matched with 40 controls. A statistically significant reduction in the average time between initial oncologic consult to the time of first definitive therapy was found in favor of patients seen in the MGMC (44.3 ±20.5 days vs 60.7 ±41.4 days). The average time from biopsy to first definitive therapy was not statistically significant different between patient groups. Average time from biopsy to completion of staging was significantly reduced in the MGMC group (31.4±33.1 days vs 53.2±40.5 days). Post-MGMC, fewer patients were referred to the CHOICE program and more patients completed treatment.

Conclusion: Establishment of the MGMC allowed cancer patients to meet with various oncology specialists in a single setting and for these providers to form an initial treatment plan, resulting in reduced time between initial consult and first definitive treatment. Staging was completed more efficiently. These results suggest that a multidisciplinary oncology clinic enhances delivery of care in patients with gastrointestinal malignancies.

Background: Digestive system malignancies constitute 18% of all cancers in the US veteran population (VA Central Cancer Registry 2010 data). Managing these patients involves multiple treatment modalities. The Multidisciplinary Gastrointestinal Malignancy Clinic (MGMC) was established at the Dallas VAMC in 2016. Prior to the MGMC, patients presented to their primary care physicians, who once a malignancy was biopsy confirmed, consulted an oncologic specialist. Patients requiring multidisciplinary oncologic care had three or more appointments (medical, surgical, and radiation oncology) scheduled on separate days. However, since the MGMC was established, various oncologic specialists now evaluate the patients on a single clinic day and a definitive consensus therapy course is planned.

Methods: Patients seen in the MGMC were matched to patient controls (seen 2 years before the MGMC was established) by pathologic diagnosis and stage. The main endpoints were; time between initial oncologic consult and first definitive therapy; time from biopsy to completion of staging and first definitive therapy. The average times for each endpoint for these 2 groups was evaluated statistically using the student T test.

Results: 40 patient cases were selected from the group seen at the MGMC from July 2016 - June 2018 and matched with 40 controls. A statistically significant reduction in the average time between initial oncologic consult to the time of first definitive therapy was found in favor of patients seen in the MGMC (44.3 ±20.5 days vs 60.7 ±41.4 days). The average time from biopsy to first definitive therapy was not statistically significant different between patient groups. Average time from biopsy to completion of staging was significantly reduced in the MGMC group (31.4±33.1 days vs 53.2±40.5 days). Post-MGMC, fewer patients were referred to the CHOICE program and more patients completed treatment.

Conclusion: Establishment of the MGMC allowed cancer patients to meet with various oncology specialists in a single setting and for these providers to form an initial treatment plan, resulting in reduced time between initial consult and first definitive treatment. Staging was completed more efficiently. These results suggest that a multidisciplinary oncology clinic enhances delivery of care in patients with gastrointestinal malignancies.

Background: Digestive system malignancies constitute 18% of all cancers in the US veteran population (VA Central Cancer Registry 2010 data). Managing these patients involves multiple treatment modalities. The Multidisciplinary Gastrointestinal Malignancy Clinic (MGMC) was established at the Dallas VAMC in 2016. Prior to the MGMC, patients presented to their primary care physicians, who once a malignancy was biopsy confirmed, consulted an oncologic specialist. Patients requiring multidisciplinary oncologic care had three or more appointments (medical, surgical, and radiation oncology) scheduled on separate days. However, since the MGMC was established, various oncologic specialists now evaluate the patients on a single clinic day and a definitive consensus therapy course is planned.

Methods: Patients seen in the MGMC were matched to patient controls (seen 2 years before the MGMC was established) by pathologic diagnosis and stage. The main endpoints were; time between initial oncologic consult and first definitive therapy; time from biopsy to completion of staging and first definitive therapy. The average times for each endpoint for these 2 groups was evaluated statistically using the student T test.

Results: 40 patient cases were selected from the group seen at the MGMC from July 2016 - June 2018 and matched with 40 controls. A statistically significant reduction in the average time between initial oncologic consult to the time of first definitive therapy was found in favor of patients seen in the MGMC (44.3 ±20.5 days vs 60.7 ±41.4 days). The average time from biopsy to first definitive therapy was not statistically significant different between patient groups. Average time from biopsy to completion of staging was significantly reduced in the MGMC group (31.4±33.1 days vs 53.2±40.5 days). Post-MGMC, fewer patients were referred to the CHOICE program and more patients completed treatment.

Conclusion: Establishment of the MGMC allowed cancer patients to meet with various oncology specialists in a single setting and for these providers to form an initial treatment plan, resulting in reduced time between initial consult and first definitive treatment. Staging was completed more efficiently. These results suggest that a multidisciplinary oncology clinic enhances delivery of care in patients with gastrointestinal malignancies.

Background: Esophageal cancer continues to affect US veterans as the risk factors for esophageal adenocarcinoma and squamous cell carcinoma are highly prevalent in this patient population. While localized esophageal cancer can be cured with a tri-modality approach that includes neoadjuvant chemoradiation followed by esophagectomy, only those patients who achieve a pathologic complete remission to neoadjuvant chemoradiation have a 50% five-year overall survival. Those who do not achieve a pathologic complete remission or those with metastatic disease have a worse prognosis. Thus, there is a need to develop novel molecularly targeted agents for the treatment of esophageal
cancer. We have found that the Hedgehog signaling pathway, required for normal esophageal embryogenesis but silenced in the adult esophagus, is reactivated in both histologic subtypes of esophageal cancer.

Results: Using immunohistochemistry for the pathway ligand Sonic hedgehog or in situ hybridization for either Sonic hedgehog or the pathway target gene Gli1 on esophageal cancer tissue microarrays, we found that 206/346 (60%) cases were Hedgehog pathway active while normal squamous esophagus was negative. The anti-fungal agent itraconazole has previously been shown to inhibit Hedgehog signaling, and we were able to inhibit cell proliferation (cell number), Hedgehog pathway activity (quantitative real-time PCR), and VEGFR2 phosphorylation (Western blot) in vitro in OE33 esophageal adenocarcinoma cells. In a novel intraperitoneal xenograft model of liver metastases, itraconazole significantly improved overall survival in mice injected intraperitoneally with OE33 cells.

Conclusions: Based on these results we are conducting a phase 0 clinical trial administering itraconazole 300 mg po bid for 14-17 days to patients with localized esophageal cancer before neoadjuvant chemoradiation. To date, we have treated 6 patients with itraconazole and demonstrated inhibition of Hedgehog signaling by quantitative real-time PCR. It is hoped that results from this early phase trial may lead to further study and development of itraconazole as a molecularly targeted agent for esophageal cancer.

Background: Esophageal cancer continues to affect US veterans as the risk factors for esophageal adenocarcinoma and squamous cell carcinoma are highly prevalent in this patient population. While localized esophageal cancer can be cured with a tri-modality approach that includes neoadjuvant chemoradiation followed by esophagectomy, only those patients who achieve a pathologic complete remission to neoadjuvant chemoradiation have a 50% five-year overall survival. Those who do not achieve a pathologic complete remission or those with metastatic disease have a worse prognosis. Thus, there is a need to develop novel molecularly targeted agents for the treatment of esophageal
cancer. We have found that the Hedgehog signaling pathway, required for normal esophageal embryogenesis but silenced in the adult esophagus, is reactivated in both histologic subtypes of esophageal cancer.

Results: Using immunohistochemistry for the pathway ligand Sonic hedgehog or in situ hybridization for either Sonic hedgehog or the pathway target gene Gli1 on esophageal cancer tissue microarrays, we found that 206/346 (60%) cases were Hedgehog pathway active while normal squamous esophagus was negative. The anti-fungal agent itraconazole has previously been shown to inhibit Hedgehog signaling, and we were able to inhibit cell proliferation (cell number), Hedgehog pathway activity (quantitative real-time PCR), and VEGFR2 phosphorylation (Western blot) in vitro in OE33 esophageal adenocarcinoma cells. In a novel intraperitoneal xenograft model of liver metastases, itraconazole significantly improved overall survival in mice injected intraperitoneally with OE33 cells.

Conclusions: Based on these results we are conducting a phase 0 clinical trial administering itraconazole 300 mg po bid for 14-17 days to patients with localized esophageal cancer before neoadjuvant chemoradiation. To date, we have treated 6 patients with itraconazole and demonstrated inhibition of Hedgehog signaling by quantitative real-time PCR. It is hoped that results from this early phase trial may lead to further study and development of itraconazole as a molecularly targeted agent for esophageal cancer.

Background: Esophageal cancer continues to affect US veterans as the risk factors for esophageal adenocarcinoma and squamous cell carcinoma are highly prevalent in this patient population. While localized esophageal cancer can be cured with a tri-modality approach that includes neoadjuvant chemoradiation followed by esophagectomy, only those patients who achieve a pathologic complete remission to neoadjuvant chemoradiation have a 50% five-year overall survival. Those who do not achieve a pathologic complete remission or those with metastatic disease have a worse prognosis. Thus, there is a need to develop novel molecularly targeted agents for the treatment of esophageal
cancer. We have found that the Hedgehog signaling pathway, required for normal esophageal embryogenesis but silenced in the adult esophagus, is reactivated in both histologic subtypes of esophageal cancer.

Results: Using immunohistochemistry for the pathway ligand Sonic hedgehog or in situ hybridization for either Sonic hedgehog or the pathway target gene Gli1 on esophageal cancer tissue microarrays, we found that 206/346 (60%) cases were Hedgehog pathway active while normal squamous esophagus was negative. The anti-fungal agent itraconazole has previously been shown to inhibit Hedgehog signaling, and we were able to inhibit cell proliferation (cell number), Hedgehog pathway activity (quantitative real-time PCR), and VEGFR2 phosphorylation (Western blot) in vitro in OE33 esophageal adenocarcinoma cells. In a novel intraperitoneal xenograft model of liver metastases, itraconazole significantly improved overall survival in mice injected intraperitoneally with OE33 cells.

Conclusions: Based on these results we are conducting a phase 0 clinical trial administering itraconazole 300 mg po bid for 14-17 days to patients with localized esophageal cancer before neoadjuvant chemoradiation. To date, we have treated 6 patients with itraconazole and demonstrated inhibition of Hedgehog signaling by quantitative real-time PCR. It is hoped that results from this early phase trial may lead to further study and development of itraconazole as a molecularly targeted agent for esophageal cancer.