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Purpose A multi-institutional phase II trial assessed the utility of dose-painted IMRT (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% as compared to the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials T2-4N0-3M0 anal cancer patients received 5FU and MMC days 1 and 29 of DP-IMRT, prescribed per stage - T2N0: 42Gy elective nodal and 50.4Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3: 45Gy elective nodal, 50.4Gy ≤ 3cm or 54Gy > 3cm metastatic nodal and 54Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results Of 63 accrued patients, 52 were evaluable. Tumor stage included: 54% II, 25% IIIA, 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=0.032), grade 3+ gastrointestinal, 21% (9811 36%, P=0.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<0.0001) with DP-IMRT. On initial pre-treatment review, 81% required DP-IMRT re-planning, while final review revealed only three cases with normal tissue major deviations. Conclusions Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic, and grade 3+ dermatologic and gastrointestinal toxicity. While DP-IMRT proved feasible, the high pre-treatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

Context Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m 2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m 2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m 2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (PϽ.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (Ͼ85%). Conclusions The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00003216

The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

PurposeWe assessed the safety and antitumor activity of avelumab, a fully human anti–programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma.MethodsIn this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells.ResultsForty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%).ConclusionAvelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

Lung RF ablation appears to be safe and linked with promising long-term survival and local tumor progression outcomes, especially given the patient population treated.

57 adiofrequency (RF) ablation is a minimally invasive technique that is used for the treatment of primary and secondary liver tumors [1]. Early results indicate that tumor reduction and eradication can be achieved with this percutaneous imagingguided procedure. For the most part, RF ablation can be performed under conscious sedation in the outpatient setting with a low incidence of side effects [1]. Malignant tumors in bone [2], head and neck [3], and bronchi [4] have also been treated with RF ablation with early results showing promise. A 30% 3-year survival has been shown in the RF ablation of colorectal hepatic metastases [5], but long-term results in extrahepatic malignancies are not available. The percutaneous technique has not been validated in the treatment of lung tumors. The technique has been applied to a lung tumor model in animals [6] but, to our knowledge, has not been reported in humans. This report describes the successful application of RF ablation in three patients with lung malignancies. Materials and MethodsThe first patient is a 45-year-old man who in 1996 was diagnosed with stage IV bronchogenic adenocarcinoma, with a left infrahilar mass, mediastinal lymphadenopathy, and a solitary T4 bone lesion. Aggressive treatment with paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) and external beam radiation effected a complete response of 2-years' duration. On follow-up chest CT, a new 2.5-cm mass was revealed within the radiation field in the left infrahilar region (Fig. 1). Analysis of the biopsy sample confirmed recurrent adenocarcinoma. Bone scan and MR imaging of the spine were normal. The patient was not considered a candidate for surgery because of the extent of disease at the time of diagnosis. Additional radiation therapy was contraindicated to some extent because of the location of the nodule within the prior radiation field. Therefore, percutaneous RF ablation was considered the best option for attempting local tumor eradication.The second patient is a 66-year-old woman who was examined for pain in the right wall of the chest. Her medical history included stroke, emphysema, and myocardial infarction. An initial chest radiograph revealed a mass in the right lower lobe, which was biopsied and proven to be adenocarcinoma. Staging was based on CT of the chest and abdomen and total-body bone scan. No evidence of regional or distant disease was found, and disease was staged at 1B. The lung mass measured 5.0 cm on the CT image. The patient refused surgery because of her comorbid conditions and was scheduled for external beam radiotherapy. Because the mass was so large, RF ablation was selected for initial cytoreduction.The third patient is a 58-year-old woman with a history of metastatic breast cancer that was treated with systemic chemotherapy and bone marrow transplantation. One lung metastasis had been treated with thoracotomy before the bone marrow transplantation.CT scans had recently shown a growing 2-cm pulmonary nodule adjacent to the left main pulmonary artery. Whole-body scannin...

Purpose CA 19-9 is an important tumor marker in patients with pancreatic adenocarcinoma. A secondary end point of Radiation Therapy Oncology Group trial 9704 was prospective evaluation of the ability of postresectional CA 19-9 to predict survival. Methods CA 19-9 expression was analyzed as a dichotomized variable (< 180 v ≥ 180) or (≤ 90 v > 90). Cox proportional hazards models were utilized to identify the impact of CA 19-9 expression on overall survival (OS). Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results Three hundred eighty-five patients patients had assessable CA 19-9 levels. The majority had a CA 19-9 level lower than 180 or ≤ 90 (n = 220 and 200, respectively), while 34% were Lewis Antigen negative and 33 (9%) and 53 (14%) patients had levels higher than 180 and higher than 90. When CA 19-9 was analyzed as a dichotomized variable, there was a significant survival difference favoring patients with CA 19-9 lower than 180 (hazard ratio [HR], 3.53; P < .0001). This corresponds to a 72% reduction in the risk of death for patients with a CA 19-9 lower than 180. This was also true for patients with CA 19-9 ≤ 90 (HR, 3.4; P < .0001). Multivariate analyses confirmed that CA 19-9, when analyzed as both a continuous and a dichotomized variable, is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusion To our knowledge, this is the first phase III trial to perform prospective analysis of CA 19-9 levels in patients treated with adjuvant chemoradiotherapy. It definitively confirms the prognostic importance of postresectional CA 19-9 levels after surgery with curative intent in patients with pancreatic cancer.