Miller, Robert C.

Rare tumor research presents many challenges. Large, randomized clinical trials are often impractical in this field and access to biospecimens may be problematic. These difficulties can best be addressed through multidisciplinary, national and international collaborative efforts among researchers, clinicians, governmental bodies, and patients. Numerous governmental and private organizations now exist to facilitate cooperation between researchers and institutions. Patient advocacy organizations now play an increasingly important role in partnering with traditional research groups to promote rare tumor research. Rare Tumors is now beginning an editorial series focusing on the problems of rare tumor research. We wish to invite all researchers and clinicians who are involved in rare tumor research and treatment to contribute their observations on the problems of working in this field, either as a letter to the editor, an editorial on a select issue, or as a review paper.

Purpose To assess the effectiveness of depot octreotide for the prevention of diarrhea during pelvic radiation therapy. Patients and Methods Patients receiving pelvic radiation therapy (planned minimum dose, 45 Gy; 1.7 to 2.1 Gy daily) were eligible for the study. From May 10, 2002, through October 14, 2005, 125 patients were randomly allocated in a double-blind fashion to receive octreotide (100 μg, administered subcutaneously on day 1, followed by depot octreotide, 20 mg, administered intramuscularly on days 2 and 29; n = 62) or to receive a placebo (n = 63). Results Grade 0, 1, 2, and 3 diarrhea were observed in 18%, 31%, 31%, and 21% of patients in the octreotide arm, respectively, and in 25%, 32%, 22%, and 21% of patients in the placebo arm, respectively (P = .64). Grade 0, 1, 2, and 3 abdominal cramps were observed in 32%, 45%, 21%, and 2% of patients receiving octreotide, respectively, and in 51%, 24%, 21%, and 5% of patients receiving the placebo, respectively (P = .053). Some patient-reported symptoms were worse in the octreotide group, including nocturnal bowel movements (70% v 45%; P = .004), clustering of bowel movements (90% v 69%; P = .004), and bleeding with bowel movements (57% v 35%; P = .01). Conclusion As administered in this study, octreotide did not decrease diarrhea during pelvic radiation therapy. Some gastrointestinal symptoms were worse in patients treated with octreotide. Octreotide is not indicated for prevention of diarrhea during pelvic radiation therapy.

Purpose To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Patients and Methods We performed a retrospective review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT. Results Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio [RR] = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001). Conclusion This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.

Purpose To report a multicenter experience treating anal canal cancer patients with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT). Patients and Methods From October 2000 to June 2006, 53 patients were treated with concurrent chemotherapy and IMRT for anal squamous cell carcinoma at three tertiary-care academic medical centers. Sixty-two percent were T1-2, and 67% were N0; eight patients were HIV positive. Forty-eight patients received fluorouracil (FU)/mitomycin, one received FU/cisplatin, and four received FU alone. All patients underwent computed tomography–based treatment planning with pelvic regions and inguinal nodes receiving a median of 45 Gy. Primary sites and involved nodes were boosted to a median dose of 51.5 Gy. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All late toxicity was scored using Radiation Therapy Oncology Group criteria. Results Median follow-up was 14.5 months (range, 5.2 to 102.8 months). Acute grade 3+ toxicity included 15.1% GI and 37.7% dermatologic toxicity; all acute grade 4 toxicities were hematologic; and acute grade 4 leukopenia and neutropenia occurred in 30.2% and 34.0% of patients, respectively. Treatment breaks occurred in 41.5% of patients, lasting a median of 4 days. Forty-nine patients (92.5%) had a complete response, one patient had a partial response, and three had stable disease. All HIV-positive patients achieved a complete response. Eighteen-month colostomy-free survival, overall survival, freedom from local failure, and freedom from distant failure were 83.7%, 93.4%, 83.9%, and 92.9%, respectively. Conclusion Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.