Chemoradiation For Anal Cancer Research Articles

The Association of Chemoradiation Induced Lymphopenia with Racial Disparity and Its Prognostic Impact on Survival for Anal Cancer

While the association between chemoradiation induced lymphopenia (CIL) and poor overall survival (OS) is established in multiple solid malignancies, it has not been studied in anal cancer. Racial and socioeconomic disparities as potential predictors of lymphopenia have not been reported. We hypothesize that race and socioeconomic status is associated with increased incidence of severe CIL, which can predict worse overall survival for patients with anal cancer. A cohort of 75 patients treated with definitive chemoradiation (CRT) for squamous cell anal cancer from January 2014 to December 2020 was reviewed. Total lymphocyte counts (TLC) at baseline and TLC nadir at 1 month post-CRT were analyzed. Logistic regression was used to identify associations between race, gender, ethnicity, median household income by zip code, marital status, baseline hematopoietic cell counts, and post-CRT Grade 3+ lymphopenia (TLC <0.5k/μL). Kaplan-Meier method and Cox regression model were used to perform survival analysis. Of the 75 patients identified, mean age was 66.9 years and median follow-up time was 37.1 months. There were 63 females, 53 non-Hispanic whites, 22 minorities (12 Blacks, 9 Hispanics, 1 Asians) Radiation dose ranged from 41.4 Gray to 56 Gray. At 1 month post CRT, 85.3% developed lymphopenia (G1 9.3%, G2 26.7%, G3 37.3%, G4 12.0%). On multivariate logistic regression, non-white race demonstrated a trend to have more Grade 3+ lymphopenia (OR = 3.5, p = 0.07). On univariate Cox regression, poorer overall survival was associated with race (HR 3.7, p = 0.04), baseline white blood count (HR 1.3, p = 0.04), baseline hemoglobin (HR 0.6, p = 0.04), and post-CRT Grade 3+ lymphopenia (HR 5.8, p = 0.03). On multivariate Cox regression, only post-CRT Grade 3+ lymphopenia was associated with worse OS (HR 7.5, p = 0.049). 5-year OS significantly differed between patients with and without post-CRT Grade 3+ lymphopenia (62.3% vs 94.7%, P = 0.01). Lymphopenia is commonly observed after chemoradiation for anal cancer. Racial disparity is associated with severe lymphopenia induced by chemoradiation, which is a robust predictor of poor survival in anal cancer. More attention to lymphopenia induced by chemoradiation for anal cancer is needed, particularly in racial minorities.

Long-Term Patient-Reported Quality of Life of Anal Cancer Survivors Treated With Intensity Modulated Radiation Therapy and Concurrent Chemotherapy: Results From a Prospective Phase II Trial

Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P=.003), role functioning (19.3; P=.0017), emotional functioning (18.9; P=.008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P=.172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P=.001), mucous or blood discharge per rectum (-22.8; P=.005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P=.421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P=.014). Deterioration of dyspareunia was clinically significant (26.7; P=.099) at 60 months. Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.

Quality of life in patients treated with radiochemotherapy for primary diagnosis of anal cancer

Anal cancer and the related treatment are generally known to affect patients’ quality of life. The aim of this study was to assess self-reported quality of life (QoL) of anal cancer patients after combined radiation and chemotherapy, and to identify patient-, disease-, and therapy-related factors associated with QoL. A total of 94 patients treated with definitive chemoradiation for anal cancer at our institution in the period from 2004 to 2018 were identified from our database. QoL was assessed in the remaining 52 patients using the EORTC QLQ-C30 questionnaire (cancer-specific QoL) and the newly developed anal cancer module QLQ-ANL27 (site-specific QoL). Differences in QoL between anal cancer patients and a German age and sex adjusted reference population were examined. The median follow-up was 71 months (range, 7–176). In the cancer-specific QoL module, the anal cancer cohort presented with significantly lower scores in role (− 12.2 points), emotional (− 6.6 points), and social functioning (− 6.8 points), but higher scores in diarrhea (+ 36.3 points) and constipation (+ 13.3 points) than the German reference population. There were no significant differences in disease- or therapy-related factors, but age greater than 70 years and a follow-up time greater than 71 months had a negative impact on global QoL. As for the site-specific QoL, patients with a tumor relapse showed significantly higher symptom scores than patients with a complete clinical remission in all scales except of micturition frequency. Compared to 3D conformal radiotherapy, IMRT treatment seemed to improve non-stoma bowel function (+ 23.3 points), female sexual functioning (+ 24.2 points), and came along with less scores in the symptom scales pain (− 35.9 points), toilet proximity (− 28.6 points), and cleanliness (− 26.2 points). Most of the functional scores of anal cancer patients were lower compared to the general German population, but did not seem to affect the general QoL. Fatigue, physical, and role functioning had the strongest impact on global QoL causing psychological symptoms as important as physical.

Prognostic impact of lymphopenia and neutrophil-lymphocyte ratio for patients with anal squamous cell carcinoma.

Outcomes after definitive chemoradiation for squamous cell carcinoma are generally favorable. However, biomarkers to further yield prognostic information are desired. Treatment-related lymphopenia as well as an elevated baseline neutrophil-lymphocyte ratio have been associated with worse survival in several cancer types. We evaluated absolute lymphocyte count and neutrophil-lymphocyte ratio at baseline and at treatment-related nadir in patients with anal cancer for associations with oncologic endpoints. We conducted a retrospective analysis of 428 consecutive patients with non-metastatic anal cancer treated with definitive, intensity-modulated radiation therapy-based chemoradiation. We analyzed absolute neutrophil and lymphocyte counts at several timepoints: pretreatment, weekly during treatment, and in the six weeks following treatment completion. Neutrophil-lymphocyte ratio was calculated at baseline and treatment-related nadir. We estimated oncologic endpoints using life tables and compared them using the log-rank test. We conducted univariate and multivariable time-to-event analyses using Cox proportional hazards. Median absolute lymphocyte count at baseline and nadir were 1.80 [interquartile range (IQR), 1.45-2.32] k/µL and 0.26 (IQR, 0.18-0.36) k/µL, respectively, and 31% developed treatment-related grade 4 lymphopenia. Median neutrophil-lymphocyte ratio at baseline and nadir were 2.34 (IQR, 1.68-3.30) and 8.80 (IQR, 5.86-12.68), respectively. Estimates of overall survival, local failure-free survival, distant metastasis-free survival (DMFS), and freedom from colostomy at 5 years were 87%, 86%, 82%, and 88%, respectively. Baseline and nadir absolute lymphocyte count were not associated with selected outcomes on univariate analysis. On multivariable analysis, factors independently associated with death included T3-T4 disease, HIV-positive status, treatment break, and baseline neutrophil-lymphocyte ratio >3. Baseline neutrophil-lymphocyte ratio showed a trend toward association with distant progression or death (P=0.07). The 5-year overall survival estimates for patients with baseline neutrophil-lymphocyte ratios ≤3 and >3 were 92.3% and 80.6%, respectively. Lymphopenia during and after chemoradiation for anal cancer is common but does not appear to be associated with worse survival, recurrence, or metastases. However, elevated baseline neutrophil-lymphocyte ratio was independently associated with overall survival, local recurrence-free survival, and DMFS. Further studies are needed to determine the clinical utility of baseline neutrophil-lymphocyte ratio to guide treatment and follow-up.

PO-1252 Chemoradiation for anal cancer: correlation of hematologic toxicity and dose to pelvic bone marrow.

PO-1252 Chemoradiation for anal cancer: correlation of hematologic toxicity and dose to pelvic bone marrow.

The Patient’s Perspective on Chemoradiation for Anal Cancer: Evaluation of Expectations and Stigma

While the efficacy and toxicity of chemoradiation (CRT) for anal cancer have been well studied, little is known about how actual patient experience compares with initial expectations. Although studies have suggested stigma associated with anal cancer screening, whether stigma impacts patients after treatment remains unclear. Consecutive patients with squamous cell carcinoma of the anus treated with definitive CRT from 2009-2018 who were without recurrence and with ≥6 months of follow-up were surveyed. The survey assessed patients’ baseline knowledge and fears regarding CRT and asked them to compare their short-term and long-term side effects with initial expectations. Levels of stigma were evaluated by asking patients the degree to which their diagnosis impacted personal relationships. Questions were adapted from validated scales including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Discrimination and Stigma Scale. We surveyed 46 patients, of which 33 responded (response rate 72%). The median age was 66 years (range 54-88); 61% were female and 12% were HIV positive. The stage distribution was 15% stage I, 33% stage II, and 52% stage III. All patients underwent intensity-modulated radiation therapy (median total dose 54 Gy, range 48.6-59.4 Gy) with the most common chemotherapy 5-fluorouracil/mitomycin C (94%). Median follow-up at survey was 30.0 months (range 6.2-116.5). Prior to treatment, 73% of patients indicated little to no knowledge of CRT, with most commonly top ranked fears including skin burns (12%), organ damage (11%), and need for a stoma (11%). Seventy percent reported overall short-term effects to be worse than expected, with changes to bowel habits (82%), energy (73%), and interest in sexual activity (64%) most commonly rated as worse than expected. Thirty-nine percent reported overall long-term effects to be worse than expected, with changes to bowel habits (73%), sexual function (67%), and interest in sexual activity (58%) most commonly rated as worse than expected. However, 94% agreed they were better off after treatment, and only 24% indicated CRT was scarier than expected. Regarding stigma, a subset reported hiding their diagnosis (12%, 24%) and side effects (24%, 30%) from friends/family or work colleagues, respectively, with 15% indicating they stopped themselves from having a close relationship due to concerns over how others might respond to their diagnosis. Although patients’ perceptions of the severity of short-term CRT side effects were inferior to expectations, the vast majority agreed they were better off after treatment. Targeted counseling on common concerns may improve the anal cancer treatment experience. A notable subset reported stigma associated with treatment, warranting further evaluation to understand the impact on the patient experience.

5-year survival following radiotherapy in anal cancer audit in a single center.

e15070 Background: Anal cancer accounts for 1% of new cancer diagnoses. Incidence rates are increasing and predicted to rise. Randomised controlled trials have demonstrated superior outcomes with chemoradiation, the standard of care. The recommended dose for two phases is 50.4Gray in 28 fractions, with 5- fluorouracil (5-FU) and mitomycin C as per the UKCCCR ACT I trial. The addition of chemotherapy has been shown to improve outcomes, however is contraindicated in certain cases. Retrospective audit is important to ensure effectiveness of chemoradiation for anal cancer. Methods: Patients were identified retrospectively in a single centre, who had undergone radiotherapy for anal cancer between 2008 and 2013. The only histological subtype included was squamous cell carcinoma. Patients were included who received radiotherapy alone and concomitant chemotherapy. All TNM stages were included and patients treated with palliative intent at the outset were included. Available imaging was reviewed and staging updated in line with TNM 8th edition. 5 year survival was primarily evaluated. The proportion of patients who had a defunctioning stoma and subsequent reversal was investigated. Results: 55 patients were included in the analysis. The overall 5 year survival was 75% and 5 year relapse free survival 87%. 45 patients received chemoradiotherapy and 38 (84%) of this group received mitomycin C and 5-FU regimen. 7 (13%) patients relapsed, 3 (43%) of which were local. All of these patients proceeded to an abdomino-perineal resection. The commonest fractionation schedule used was 50.4 Gray in 28 fractions. The median stage at presentation of this cohort was T2 N0 M0. The mean age at diagnosis 61.4 years. 1 patient died whilst receiving treatment. 13 (24%) patients had a defunctioning stoma prior to radiation treatment. 3 (23%) had a subsequent reversal of the stoma. Conclusions: Chemoradiotherapy is an effective treatment for squamous cell carcinomas of the anal canal, with good relapse free survival. When a defunctioning stoma is performed prior to chemoradiation there is a low rate of reversal.

EP-1475: Brachytherapy boost after chemoradiation in anal cancer: a systematic review

EP-1475: Brachytherapy boost after chemoradiation in anal cancer: a systematic review

EP-1487: The prognostic role of haemoglobin in patients undergoing concurrent chemo-radiation for anal cancer

EP-1487: The prognostic role of haemoglobin in patients undergoing concurrent chemo-radiation for anal cancer

Anal sphincter dysfunction in patients treated with primary radiotherapy for anal cancer: a study with the functional lumen imaging probe

Background: Sphincter-sparing radiotherapy or chemoradiation are standard treatments for patients with anal cancer. The ultimate treatment goal is full recovery from anal cancer with preserved anorectal function. Unfortunately, long-term survivors often suffer from severe anorectal symptoms. The aim of the present study was to characterize changes in anorectal physiology after radiotherapy for anal cancer.Method: We included 13 patients (10 women, age 63.4 ± 1.9) treated with radiotherapy or chemoradiation for anal cancer and 14 healthy volunteers (9 women, age 61.4 ± 1.5). Symptoms were assessed with scores for fecal incontinence and low anterior resection syndrome. Anorectal physiology was examined with anorectal manometry and the Functional Lumen Imaging Probe.Results: Patients had a median Wexner fecal incontinence score of 5 (0–13) and a median LARS score of 29 (0–39). Compared to healthy volunteers, patients had lower mean (±SE) anal -resting (38 ± 5 vs. 71 ± 6, p < .001) and -squeeze pressures (76 ± 11 vs. 165 ± 15, p < .001). Patients also had lower anal yield pressure (15.5 ± 1.3 mmHg vs. 28.0 ± 2.0 mmHg, p < .001), higher distensibility, and lower resistance to flow (reduced resistance ratio of the anal canal during distension, q = 5.09, p < .001). No differences were found in median (range) rectal volumes at first sensation (70.5 (15–131) vs. 57 (18–132) ml, p > .4), urge (103 (54-176) vs. 90 (32-212), p > .6) or maximum tolerable volume (173 (86–413) vs. 119.5 (54–269) ml, p > .10).Conclusion: Patients treated with radiotherapy or chemoradiation for anal cancer have low anal resting and squeeze pressures as well as reduced resistance to distension and flow.

Brachytherapy boost after chemoradiation in anal cancer: a systematic review.

Radio-chemotherapy (RCT) is the primary treatment of anal cancer (AC). However, the role and the optimal total dose of a radiation boost is still unclear. No randomized controlled trials nor systematic reviews have been performed to analyze the efficacy of brachytherapy (BRT) as boost in AC. Therefore, we performed this systematic review based on PRISMA methodology to establish the role of BRT boost in AC.A systematic search of the bibliographic databases: PubMed, Scopus, and Cochrane library from the earliest possible date through January 31, 2018 was performed. At least one of the following outcomes: local control (LC), loco-regional control (LRC), overall survival (OS), disease-free survival (DFS), or colostomy-free survival (CFS) had to be present for inclusion in this systematic review in patients receiving a BRT boost. Data about toxicity and sphincter function were also included.Ten articles fulfilled the inclusion criteria. All the studies had retrospective study design. All studies were classified to provide a level of evidence graded as 3 according to SIGN classification. Median 5-year LC/LRC, CFS, DFS, and OS were: 78.6% (range, 70.7-92.0%), 76.1% (range, 61.4-86.4%), 75.8% (range, 65.9-85.7%), and 69.4% (63.4-82.0%), respectively. The reported toxicities were acceptable.RCT is the treatment cornerstone in AC. High-level evidences from studies on BRT boost in AC are lacking. Further studies should investigate: efficacy of BRT boost in comparison to no boost and to external beam boost, patients who can benefit from this treatment intensification, and optimal radiation dose.

FDG-PET Correlation With Active Bone Marrow and Leukopenia during Chemoradiation for Anal Cancer

FDG-PET Correlation With Active Bone Marrow and Leukopenia during Chemoradiation for Anal Cancer

Influence of radiation treatment technique on outcome and toxicity in anal cancer

ObjectiveIntensity-modulated radiation therapy (IMRT) has largely supplanted three-dimensional conformal radiation (3D-CRT) for definitive anal cancer treatment due to decreased toxicity and potentially improved outcomes. Convincing data demonstrating its advantages, however, remain limited. We compared outcomes and toxicity with concurrent chemotherapy and IMRT vs 3D-CRT for anal cancer.MethodsWe performed a single-institution retrospective review of patients treated with IMRT or 3D-CRT as part of definitive mitomycin-C/5-fluorouricil-based chemoradiation for anal cancer from January 2003 to December 2012.ResultsOne hundred sixty-five patients were included, with 61 and 104 receiving IMRT and 3D-CRT, respectively. Overall, 92.7% had squamous cell carcinoma. The mean initial pelvic dose was 48.3 and 44 Gy for IMRT and 3D-CRT, respectively. Complete response, partial response, and disease progression rates were similar (IMRT 83.6, 8.2, 8.2%; 3D-CRT 85.6, 6.7, 7.7%; p = 0.608, p = 0.728, p = 0.729). There was no significant difference in overall survival (p = 0.971), event-free survival (p = 0.900), or local or distant recurrence rates (p = 0.118, p = 0.373). IMRT caused significantly less acute grade 1–2 incontinence (p = 0.035), grade 3–4 pain (p = 0.033), and fatigue (p = 0.030). IMRT patients had significantly fewer chronic post-treatment toxicities (p = 0.008), outperforming 3D-CRT in six of eight toxicities reviewed. Though total treatment length was comparable (43.6 and 44.5 days), IMRT recipients had fewer (27.9 vs 41.3% of patients, p = 0.89), shorter treatment breaks (mean 2.9 vs 4.1 days, p = 0.229).ConclusionThis report represents the largest series directly comparing concurrent chemotherapy with IMRT vs 3D-CRT for definitive treatment of anal cancer. IMRT significantly reduced acute and post-treatment toxicities and allowed for safe and effective pelvic dose escalation.

Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750cc of pelvic BM spared from doses of ≥30Gy had 0% grade 3+leukopenia or neutropenia at week 3. Higher V40Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40>23% had higher rates of grade 3+leukopenia (29% vs 4%, P=.02), grade 3+neutropenia (33% vs 8%, P=.04), and grade 2+thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total "marrow reserve" can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40Gy to the lower pelvis may reduce the risk of hematologic toxicity.

EP-1307: Chemoradiation in anal cancer with using VMAT: toxicity and early outcome.

EP-1307: Chemoradiation in anal cancer with using VMAT: toxicity and early outcome.

Late effects and quality of life after chemo-radiation for the treatment of anal cancer

PurposeThe aim of this study was to evaluate the late effects and quality of life of patients following chemo-radiation treatment for anal cancer. MethodsAll surviving anal cancer patients treated within NHS Lothian between 1990 and 2007 were invited to participate. Data were collected using the EORTC QLQ-C30, the EORTC QLQ-CR38 and the Memorial Sloan-Kettering Cancer Centre Bowel Function Instrument (MSKCC). ResultsOverall response rate was 46% (n = 42); mean age 54.7 years and with a median time interval of 63.8 months between treatment and completion of the questionnaires. Thirty-five percent of the participants were ‘rarely’ or ‘never’ able to wait 15 min to get to the toilet; 50% were ‘rarely’ or ‘never’ able to control the passage of gas; 35% limited the types of solid foods they eat; 22% had leakage of stool during the day; 39% required to use a protective pad and 29% altered their daily activities because of bowel function ‘always’ or ‘most of the time’. Seventeen percent of patients reported financial difficulties (‘quite a bit’ and ‘very much’). Both men and women reported high symptomology for sexual problems with a median score of 83.3 (50.0. 100.0). ConclusionThis study has shown that in a sub-set of patients treated with chemo-radiation for anal cancer, persistent treatment related issues are reported at a medium time interval of 5.3 years. Further work is now required to understand the impact of symptoms on day-to-day life and the challenges that people face in managing these inter-related and complex problems.

Sexual dysfunction and infertility as late effects of cancer treatment

Sexual dysfunction is a common consequence of cancer treatment, affecting at least half of men and women treated for pelvic malignancies and over a quarter of people with other types of cancer. Problems are usually linked to damage to nerves, blood vessels, and hormones that underlie normal sexual function. Sexual dysfunction also may be associated with depression, anxiety, relationship conflict, and loss of self-esteem. Innovations in cancer treatment such as robotic surgery or more targeted radiation therapy have not had the anticipated result of reducing sexual dysfunction. Some new and effective cancer treatments, including aromatase inhibitors for breast cancer or chemoradiation for anal cancer also have very severe sexual morbidity. Cancer-related infertility is an issue for younger patients, who comprise a much smaller percentage of total cancer survivors. However, the long-term emotional impact of being unable to have a child after cancer can be extremely distressing. Advances in knowledge about how cancer treatments may damage fertility, as well as newer techniques to preserve fertility, offer hope to patients who have not completed their childbearing at cancer diagnosis. Unfortunately, surveys in industrialised nations confirm that many cancer patients are still not informed about potential changes to their sexual function or fertility, and all modalities of fertility preservation remain underutilised. After cancer treatment, many patients continue to have unmet needs for information about restoring sexual function or becoming a parent. Although more research is needed on optimal clinical practice, current studies suggest a multidisciplinary approach, including both medical and psychosocial treatment options.

Comparing outcomes and toxicities from intensity-modulated radiation therapy and three-dimensional conformal radiation therapy for anal cancer: Is one really better?

589 Background: Intensity-modulated radiation therapy (IMRT) has largely supplanted 3-dimensional conformal radiation (3D-CRT) for definitive treatment of anal cancer due to its decreased toxicity and potentially improved outcomes. Convincing data directly demonstrating its advantages, however, remain limited. We compared outcomes, acute, and post-treatment toxicity of patients with anal cancer treated with concurrent chemotherapy and IMRT vs. 3D-CRT. Methods: We performed a single institution retrospective review of patients treated with IMRT or 3D-CRT as part of definitive Mitomycin-C/5-FU based chemoradiation for anal cancer from January 2003-December 2012. Results: 61 and 104 patients received IMRT and 3D-CRT respectively. Overall, 92.7% had squamous cell carcinoma. The mean pelvic dose before boost was 48.3Gy and 44Gy for IMRT and 3D-CRT respectively. Complete response, partial response, and disease progression rates were similar (83.6%, 8.2%, 8.2% for IMRT; 85.6%, 6.7%, 7.7% for 3D-CRT; p = ns). There was no significant difference in overall survival (p = 0.971), event free survival (p = 0.900), and local or distant recurrence rates (p = 0.118, p = 0.373). IMRT caused significantly less acute grade 1-2 incontinence (p = 0.035), grade 3-4 pain (p = 0.033) and fatigue (p = 0.030). Patients receiving IMRT had significantly fewer post-treatment toxicities (p = 0.008), outperforming 3D-CRT in 7/8 toxicities reviewed. Though total length of treatment was comparable between IMRT and 3D-CRT (43.6 and 44.5 days), the IMRT group had fewer, shorter treatment breaks (p = ns). Conclusions: This report represents the largest series directly comparing concurrent chemotherapy with IMRT vs. 3D-CRT for definitive treatment of anal cancer. IMRT significantly reduced acute and post-treatment toxicities and allowed for safe and effective pelvic dose escalation.

37. ADXS11-001, mitomycin, 5-FU and radiation for anal cancera A phase I/II study

Background Human papillomavirus (HPV) DNA is present in the majority of squamous cell cancers of the anus. ADXS11–001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete an HPV-16-E7 fusion protein targeting HPV-transformed cells. The Lm vector infects antigen-presenting cells, stimulating both MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumours. The Brown University Oncology Research Group has initiated a phase I/II study evaluating two treatment schedules of ADXS11–001 with standard chemoradiation for anal cancer. Methods: Patients with newly diagnosed anal cancer with a primary tumour &gt;4 cm or lymph node involvement, without distant metastases, are eligible. All patients receive two courses of mitomycin, 5-FU with concurrent radiation (54 Gy in 30 fractions by IMRT). Patients receive four treatments of ADXS11–001, 1 × 109 colony-forming units intravenously once approximately every 28 days. In treatment schedule 1, the first dose is given before chemoradiation and the second to fourth doses are given every 28 days after completion of radiation. In treatment schedule 2, the second dose of ADXS11–001 is administered during chemoradiation. Results: Three patients have been treated with ADXS11–001 and chemoradiation on treatment schedule 1. One patient developed grade 3 chills and one patient experienced grade 2 flu-like symptoms post-infusion, both resolved with symptomatic treatment. Conclusions: ADXS11–001 is a highly novel form of immunotherapy designed to generate an immune response against HPV transformed cells. Accrual is continuing to evaluate safety and efficacy for patients with anal cancer.

Comparative Outcomes of Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal

Comparative Outcomes of Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal