E.L. Kwak

Yttrium-90 Radioembolization as Salvage Therapy for Liver Metastases From Colorectal Cancer.

Purpose: To report safety and survival outcomes of Yttrium-90 (Y-90) radioembolization when used as salvage therapy for chemotherapy-resistant liver metastases from colorectal cancer. Methods: In this IRB-approved retrospective study, 45 patients with hepatic metastases from colorectal cancer underwent Y-90 radioembolization after failure of systemic chemotherapy. Toxicities were assessed as per NCI-CTCAE and response based on RECIST and PET. Kaplan-Meier survival analysis was performed to calculate median survival, prognostic factors on univariate analysis, and Cox regression analysis for independent predictors of survival. Results: Y-90 radioembolization was technically successful in all (100%). Twenty-three patients (51%) had no toxicities, whereas 6 patients (13%) had grade 3 toxicities, and no patients had grade 4 toxicity. Two patients died within 30 days of treatment from renal failure unrelated to the procedure. Per RECIST, 1 patient (2%) had partial response, 34 (71%) had stable disease, and 6 (13%) had progressive disease. PET response was seen in 46% of patients with 2 patients (4%) demonstrating complete and 22 (42%) demonstrating partial metabolic response. The median survival was 186 days (95% CI, 149-277 d). Response on PET was the only independent predictor of superior overall survival. Patients who had response on PET following Y-90 therapy had a median overall survival of 317 days (10.6 mo) (95% CI, 193-564 d), whereas patients with no response on PET had a median overall survival of 163 days (5.4 mo) (95% CI, 64-283 d). Conclusions: Y-90 radioembolization as a salvage therapy for chemotherapy-resistant hepatic metastases from colon cancer was safe and resulted in disease stability. Response on PET was an independent predictor of superior overall survival.

Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer.

BACKGROUNDnTo determine the maximal tolerated dose of erlotinib when added to 5-fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of this combination in patients with locally advanced rectal cancer.nnnPATIENTS AND METHODSnPatients with Magnetic resonance imaging (MRI) or ultrasound defined T3 or T4 adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously, along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg orally daily and advanced by 50 mg increments in the subsequent cohort. Open total mesorectal excision was carried out 6-9 weeks following the completion of chemoradiation.nnnRESULTSnThirty-two patients received one of three dose levels of erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally tolerated dose. Thirty-one patients underwent resection of the primary tumor, one refused resection. Twenty-seven patients completed study therapy, all of whom underwent resection. At least one grade 3-4 toxicity occurred in 46.9% of patients. Grade 3-4 diarrhea occurred in 18.8%. The pathologic complete response (pCR) for all patients completing study therapy was 33%. With a median follow-up of 2.9 years, there are no documented local recurrences. Disease-free survival at 3 years is 75.5% (confidence interval: 55.1-87.6%).nnnCONCLUSIONSnErlotinib added to infusional 5-FU, bevacizumab and radiation in patients with locally advanced rectal cancer is relatively well tolerated and associated with an encouraging pCR.

Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer.

Purpose: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. Materials and Methods: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival. Results: All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS. Conclusions: We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.

A matter of timing: is there a role for radiation in locally advanced pancreatic cancer, and if so, when?

The role of radiation therapy in the management of locally advanced pancreatic cancer is controversial. Despite its localized presentation, locally advanced pancreatic cancer is characterized by high rates of metastases. Historic data have been mixed, and newer studies have called into question the use of radiation therapy. However, it appears that patients more likely to benefit from chemoradiation can be identified with an induction phase of chemotherapy. Data evaluating this approach suggest that approximately 30% of patients will develop metastatic disease within the first 3 to 4 months of chemotherapy. Patients without progression who receive chemoradiation therapy may experience improved survival. Future directions include the validation of this strategy and the integration of biologic agents.