Prevalence of patient-reported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

PURPOSE: Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. MATERIALS AND METHODS: Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45-56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS ≥ 3 and CTCAE ≥ 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen's kappa coefficient. RESULTS: Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of ≥3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score ≥3) improved during treatment (13.4% at week 5). "Poor" agreement was observed between patient- and clinician-reported proctitis (Cohen's k = 0.11; n = 58); however, there was "good" agreement for diarrhea (Cohen's k = 0.68; n = 58). CONCLUSIONS: Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4-5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments.

Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors.

Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell/progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2/M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.

Intensity-modulated radiotherapy vs. conventional radiotherapy in the treatment of anal squamous cell carcinoma: a propensity score analysis.

BACKGROUND AND PURPOSE: Definitive chemoradiation is the standard management for anal squamous cell carcinoma (ASCC); more conformal pelvic radiotherapy using intensity modulated radiotherapy (IMRT) minimizes toxicity but may increase locoregional recurrences (LRR). We compared IMRT and conventional radiotherapy (CRT) outcomes in ASCC patients. MATERIAL AND METHODS: We retrospectively reviewed records of 223 ASCC patients treated at Memorial Sloan-Kettering Cancer Center from 1991 to 2010. Forty-five patients received IMRT and 178 CRT. We determined locoregional recurrence-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) for each radiation modality. A propensity score analysis was performed using potentially confounding variables. Locoregional and distant patterns of failure for CRT and IMRT were compared. RESULTS: Patients treated with IMRT had significantly higher N stage (P<.01), and were less likely to be treated with induction chemotherapy (P=.01). The 2-year LRFS, DMFS, and OS were 87%, 86%, and 93%, respectively, for IMRT; and 82%, 88%, 90%, respectively, for CRT; with no significant difference in outcomes by univariate analysis or in a propensity score analysis adjusted for disparity between the groups. CONCLUSIONS: This large, single-institution experience of definitive chemoradiation for ASCC using CRT vs. IMRT demonstrates that outcomes are not compromised by more conformal radiotherapy. In the absence of prospective, multi-institutional, randomized trials of IMRT in ASCC, these retrospective data, using methods to minimize bias, can help to establish the role of IMRT in the definitive therapy of ASCC.