Faculty Bibliography

Introduction: Oral mucositis (OM) is among the most common, painful and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Objectives: The aim of this study is to explore the changes in the microbiome associated with OM onset in head and neck cancer patients (oral cavity and oropharynx squamous cell carcinoma) undergoing radiotherapy alone (RT) or chemoradiotherapy (chemoRT) using molecular techniques. Methods: We recruited patients scheduled for receiving radiotherapy alone or chemoRT. Site-specific oral biofilms samples were collected using Isohelix swabs at two time points: before initiating RT/ChemoRT (pre-OM), and at the onset of OM (post-OM ie OM > 1, WHO scale). Changes in microbial abundance were detected using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) and metagenomic analyses. An integrative computational model estimated average changes of microbial abundance patterns of 768 species identified from pre-and-post OM onset. Results: Relative changes in abundance of 54 microbial biomarkers in 16 subjects were discriminative between pre and post OM onset. Discriminant species such as Gemella haemolysans, Granulicatella elegans, Haemophilus spp., Prevotellaoris, and Aggregatibacter sp. HOT512 were found to be significantly overabundant in post-OM onset samples as compared to pre-OM. (Table Presented) Conclusions: Our results suggest a dynamic shift in the oral microbiome during the onset of OM. These species may act as opportunistic pathogens in this population, and further investigation is warranted to explore if they facilitate further tissue damage and subsequent pain

BACKGROUND: HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. OBJECTIVE: Here, we report a large series in the highly active antiretroviral therapy era comparing outcomes between HIV-positive and HIV-negative patients with anal cancer. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at an outpatient oncology clinic at large academic center. PATIENTS: A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. MAIN OUTCOME MEASURES: Data on patient characteristics, treatment, toxicity, and outcomes were collected. Overall survival, colostomy-free survival, local recurrence-free survival, and distant metastasis-free survival were analyzed. RESULTS: Median follow-up was 15 months. HIV-positive patients were younger (median, 52 vs 64 years; p < 0.001) and predominantly men (82% men vs 49% men; p = 0.001). There were no significant differences in T, N, or stage groups. HIV-positive patients had a significantly longer duration from biopsy to start of chemoradiation (mean number of days, 82 vs 54; p = 0.042). There were no differences in rates of acute toxicities including diarrhea, fatigue, or dermatitis. HIV-positive patients had significantly higher rates of hospitalization (33% vs 15%; p = 0.024). The 3-year overall survival rate was 42% in HIV-positive and 76% in HIV-negative patients (p = 0.037; HR, 2.335 (95% CI, 1.032-5.283)). Three-year colostomy-free survival was 67% in HIV-positive and 88% in HIV-negative patients (p = 0.036; HR, 3.231 (95% CI, 1.014-10.299)). Differences in overall survival rates were not significant on multivariate analysis. LIMITATIONS: This study was limited by its retrospective design and small patient numbers. CONCLUSIONS: In this cohort, HIV-positive patients had significantly worse overall and colostomy-free survival rates than HIV-negative patients. However, differences in survival were not significant on multivariate analysis. Additional studies are necessary to establish the etiology of this difference.

OBJECTIVE: To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital. METHODS: We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks >/=10 days were compared using t-test and chi(2) test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed. RESULTS: The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks >/=10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis. CONCLUSIONS: Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.

There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.

Background: Combined chemoradiotherapy (CRT) has been successful in both tumor eradication and colostomy prevention in patients with squamous-cell carcinoma of the anal canal. Unfortunately, CRT can be toxic with high rates of acute gastrointestinal and skin toxicity. This can necessitate treatment interruptions, prolonging therapy, possibly leading to loss of local control. In RTOG 0529, intensity modulated radiation therapy (IMRT) decreased the rate of treatment interruption compared to historical controls. We aim to compare toxicity and outcomes in patients treated with CRT based on radiation technique. Methods: We retrospectively reviewed 107 consecutive patients, 39 HIV+, 68 HIV-, who underwent definitive CRT for anal cancer at a single institution between 2004 and 2013. Overall survival (OS), colostomy-free survival (CFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were analyzed. Chi-square test was used to compare frequencies and t-test was used to compare means. Kaplan-Meier survival was calculated and differences were evaluated by Log-rank statistic. Results: Median follow-up was 15 months. Radiation technique was IMRT in 60% of patients with the remainder treated with 3-dimensional conformal radiation therapy (3D). Dose to the draining lymph nodes was higher in patients treated with IMRT (mean dose 40 Gy vs. 32 Gy, p < 0.001). Fewer patients had a greater than 10 day treatment break in IMRT cohort than the 3D cohort (21% vs. 43%, p = 0.028). Three-year OS (91% vs. 47%, p < 0.001) and DMFS (88% vs 64%, p= 0.033) were improved in patients treated with IMRT. There was no significant difference in acute GI or skin toxicity. There was no difference in stage, number of chemotherapy cycles and dose reductions, growth factor support, transfusion necessity, hospital admission, LRFS, sphincter function preservation, or CFS. Conclusions: In this cohort, patients treated with IMRT had better OS and DMFS than patients treated with 3D. Higher radiation doses to the draining lymph nodes and fewer prolonged treatment breaks may contribute to improved outcomes in patients treated with IMRT. Further studies are necessary to establish the etiology of this difference in outcomes

OBJECTIVE: Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. METHODS: Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. RESULTS: Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) >/=5 mug/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size >/=3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge >/=3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery >/=8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CONCLUSION: CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.