NAL CANAL CARCINOMA IS AN uncommon malignancy in the United States. Among 1 437 180 new cancer diagnoses projected for the year 2008, approximately 5070 will be new cases of anal canal carcinoma. 1 Anal canal carcinoma has a unique clinical biology that can be distinguished from all other gastrointestinal cancers. It is mostly a local-regional cancer, with a metastatic potential in only 15% of patients, 2 and it is highly sensitive to concurrent chemoradiation, 3 resulting in a cure in 60% of cases. The size of the primary tumor has a direct bearing on the cure rates, 4-6 and the 5-year survival rates decrease precipitously for tumors larger than 5 cm in diameter. 7 Similarly, the presence of nodal metastases results in a reduction in the cure rate. 4,[8][9][10] In addition, with larger primary cancers, the likelihood of lymph node metastases increases. [11][12][13][14] Approximately 25% of newly diagnosed anal canal carcinomas are larger than 5 cm in diameter and clinically node-positive.It has been established that chemoradiationismoreeffectivetherapyforsmaller analcanalcarcinomasthanforlargerones. This suggests that a strategy that could reduce the burden of cancer in the primary See also Patient Page.

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

CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.

Liver transplantation with neoadjuvant chemoradiation achieved better survival with less recurrence than conventional resection and should be considered as an alternative to resection for patients with localized, node-negative hilar CCA.

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This study demonstrates that many patients with locally recurrent rectal cancer can be resected with negative margins. Long-term survival can be achieved, especially for patients with no symptoms and minimal fixation of the recurrence in the pelvis, provided no gross residual disease remains.

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n ‫؍‬ 6), subsequent development of malignant ascites (n ‫؍‬ 1), or death from intrahepatic biliary sepsis (n ‫؍‬ 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients G 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma. (Liver Transpl 2000;6:309-316.)