Colostomy-free Survival Rates Research Articles

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Long-term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre.

Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines. All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained. In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%. Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.

Real-World Experience of Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Anal Cancer with Long-Term Follow up and Clinical Outcomes

The standard treatment for epidermoid anal cancer (AC) is concurrent chemoradiation (CRT). Here we present real world evidence of the safety and outcomes of AC patients managed by IMRT and concurrent chemotherapy at a single academic cancer center. We retrospectively reviewed the outcomes of 180 AC patients treated with definitive CRT between 2011 and 2018. Patients were managed according to a prospectively designed protocol of IMRT with radiation dose escalated according to tumor stage: 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively, and 36 Gy for elective nodal RT. Involved nodes were given the same dose based on T category. Concurrent chemotherapy consisted of two cycles of mitomycin C (MMC, 12 mg/m2) and 5-fluorouracil (5FU, 1000 mg/m2/day x 4 days) given on week 1 and 5. There was no planned treatment break. Univariate and multivariate analysis for outcomes were performed using Cox proportional hazard method and likelihood ratio statistics. Overall survival (OS) disease free (DFS), colostomy-free survival (CFS) and local failure rates (LFR) were described by Kaplan-Meier methods. There were 128 female and 52 male patients with a median age of 64 (IQR 55-74). The median size of the primary was 4.0 cm (0.6-11.0 cm). There were 18 T1, 91 T2, 38 T3 and 33 T4 lesions; 50.6% (91/180) of the patients had N0 disease. Thirteen (7.2%) did not receive concurrent chemotherapy, and 16 (8.9%) failed to complete treatment as planned. Forty-three (23.9%) patients had a treatment gap >5 (6-33) days. Eighteen of 147 (12%) with T1-3 disease failed locally, LF was observed in 13/33 (39%) T4 lesions (P = 0.0002). The 5-year OS, DFS, CFS and LFR were 85.1%, 75.6%, 87.6% and 15.5% respectively. On multivariate analysis, increasing age and N+ disease were significant for worse OS, and increasing size of the primary tumor was the only significant factor for worse DFS, CFS and LFR. Grade ≥3 acute toxicities were observed in 42.8% of patients, with grade ≥3 neutropenia and febrile neutropenia observed in 18.9% and 13.9% of patients respectively. Six patients (3.3%) died of acute toxicities. Thirteen (7%) patients experienced grade ≥3 late toxicities. Size of the primary appears to be the most important determinant of outcome following standard CRT using IMRT for AC. Despite IMRT, almost 1 in 4 patients required a treatment break, and over 40% experienced grade ≥3 acute toxicities including neutropenia and febrile neutropenia. Future studies with RT dose escalation or de-escalation, stratifying patients based on tumor size, HPV status and molecular markers are necessary to improve outcomes and decrease treatment related toxicity.

Capecitabine/Mitomycin versus 5-Fluorouracil/Mitomycin in Combination with Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy for Anal Cancer.

Since EXTRA, a non-randomized phase II trial with 31 patients, explored the use of capecitabine, mitomycin and radiation therapy (RT) in the treatment of localized squamous cell carcinoma of the anal canal (SCCAC), this treatment has been considered as an acceptable alternative to infusional 5-FU. However, the differences in efficacy between capecitabine and 5-FU in chemoradiation therapy (CRT) with simultaneous integrated boost (SIB) radiation therapy (SIB-IMRT) for local SCCAC are not well documented. Patients included in this prospective monocentric cohort study were treated with SIB-RapidArc (a unique RT method treatment for all patients: identical technique, volume and constraints for at-risk organs), mitomycin C and 5-FU each day of RT for 7 weeks (group 1) or capecitabine each day of RT (group 2). Patients treated between July 2009 and August 2017 (group 1) and between November 2012 and April 2018 (group 2) for local SCCAC T2-4 classified as N, M0 or T, N1-3, M0 were included. Primary endpoints were progression-free survival (PFS) and acute toxicities. Results: One hundred forty-seven patients were included, 91 in group 1 and 56 in group 2. The two groups were statistically comparable in terms of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and TNM. With a median duration of follow-up of 53.5 months, the PFS rate at 3 years was 80% for group 1 and 75% for group 2 (p = 0.32). The 3-year colostomy-free survival rate was 92% for group 1 and 85% for group 2 (p = 0.11). The rate of patients with at least one grade 3 or higher acute toxicity was 35.5% in group 1 and 21.4% in group 2 (p = 0.10), with a trend of fewer acute toxicities with capecitabine. Conclusion: Capecitabine/mitomycin in combination with SIB RapidArc radiation therapy for anal cancer seems as effective as 5-FU-based chemotherapy and is well tolerated with minimal toxicity.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5days, P = 0.042) than in the MF group. The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments

PURPOSETo analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC). METHODS AND MATERIALSA total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed. RESULTSWith a median followup (FU) of 59.8 months (95% CI [55.8–64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83–96%]. The 5-year DFS rate was 86% [76–93%]. The 5-year OS was 96% [88–99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79–94%]. CONCLUSIONSHDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.

Definitive chemoradiation in nonmetastatic squamous cell carcinoma anal canal: A single-institution experience.

The purpose of the study was to analyze the survival outcomes and toxicities in squamous cell carcinoma anal canal treated with definitive chemoradiotherapy. Retrospective analysis of 51 patients with squamous cell carcinoma anal canal treated with chemoradiotherapy was done. Data were collected and analyzed for disease-free survival (DFS), colostomy-free survival (CFS), overall survival (OS), and acute/late toxicities. Out of total 51 patients, only 44 patients had a follow-up of more than 36 months and were analyzed. After a median follow-up of 46 months (range 10-68 months), the 3-year DFS was 73.9%. Three patients developed locoregional recurrence, while one patient developed distant metastasis. At 3-year OS rate was 77%. Out of 44 patients, six patients lost to follow-up, while two patients died due to progressive disease and two due to noncancer causes. 3-year CFS rate was 59%. Most common grade >3 acute toxicities were skin reactions in nine (18%), followed by hematological in eight (16%) patients. Definitive chemoradiotherapy in anal canal results in good oncological outcomes with sphincter preservation. No severe treatment-related toxicities were observed.

Intersphincteric Resection for Low Rectal Cancer: Parameters Affecting Functional Outcomes and Survival Rates

Introduction: The development of new surgical techniques and devices, as well as the improvements in neoadjuvant chemoradiotherapy enabled intersphincteric resection (ISR), has reduced permanent colostomy usage. The aim of this study was to assess the long-term oncological and functional outcomes of patients who underwent partial ISR for rectal cancer located less than 5cm from the anal verge. Materials and Methods: A series of 106 consecutive patients with very low rectal cancer underwent curative partial ISR from January 2006 to September 2019 were retrospectively evaluated. One-hundred-three (97%) of 106 patients received neoadjuvant chemo-radiotherapy. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) rates were calculated using Kaplan–Meier methods. The Wexner incontinence score and Kirwan classification were used to evaluate patients’ functional results. Results: The median follow up was 60 months (range, 18–174). The estimated five-year overall and disease-free survival rates were 89% and 81.6%, respectively. Five-year local recurrence and distant metastasis rates were 6.6% and 10.4%, respectively. There was no in-hospital and 30-day mortality. The median Wexner score was 9 (range, 0–20) for 72 patients. Age (<65 years, p=0.027) and gender (male, p=0.019) had a positive effect on functional outcomes after surgery. One and five years colostomy-free survival rates were 96% and 89%, respectively. Conclusion: Intersphincteric resection techniques are feasible for patients with very low rectal cancer, providing good oncological and functional outcomes.

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

Simple SummaryConcurrent chemo-radiotherapy is the standard treatment in anal cancer. Intensity-modulated radiotherapy (IMRT) was proved to reduce severe, acute and late toxicities. Moreover, IMRT techniques allow for the planning and delivery of a simultaneous integrated boost (SIB), with a differential dose per fraction given to selected sub-regions during the same treatment session. This boost modality provides the chance to employ a dose-painted approach with a reduction in overall treatment time that could result in a potential clinical advantage. Since a large variability in dose prescription to the primary tumor and elective or involved lymph nodes can be found in available guidelines and clinical practice, a multicenter analysis was conducted to evaluate the pattern of care and the impact of radiotherapy parameters on clinical outcomes for anal cancer patients treated with IMRT techniques within a national cohort.A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Pulse-dose-rate interstitial brachytherapy in anal squamous cell carcinoma: clinical outcomes and patients' health quality perception.

PurposeTo examine clinical outcomes and quality of life of patients with anal squamous cell carcinoma treated with interstitial pulsed-dose-rate brachytherapy (PDR-BT) with a boost to residual tumor after external radiotherapy.Material and methodsMedical records of patients receiving a brachytherapy boost after radiotherapy for anal squamous cell carcinoma in our Institute between 2008 and 2019 were retrospectively reviewed. After receiving pelvic irradiation ± concurrent chemotherapy, patients received PDR-BT boost to residual tumor, in order to deliver a minimal total dose of 60 Gy. Patients’ outcomes were analyzed, with primary focus on local control, sphincter preservation, morbidity, and quality of life.ResultsA total of 42 patients were identified, included 24, 13, and 5 patients with I, II, and III tumor stages, respectively. Median brachytherapy (BT) dose was 20 Gy (range, 10-30 Gy). Median dose per pulse was 42 cGy (range, 37.5-50 cGy). With median follow-up of 60.4 months (range, 5.4-127.4 months), estimated local control and colostomy-free survival rates at 5 years were both 88.7% (95% CI: 67.4-96.4%). The largest axis of residual lesion after external beam radiation therapy (EBRT) and poor tumor shrinkage were associated with more frequent relapses (p = 0.02 and p = 0.007, respectively). Out of 40 patients with more than 6 months follow-up, only one experienced severe delayed toxicity (fecal incontinence). Health quality perception was very good or good in 20 of 22 (91%) patients, according to their replies of quality-of-life surveys. A total dose ≥ 63 Gy was associated with higher number of anorectal grade 1+ toxicities (n = 1.5 vs. n = 0.61, p = 0.02).ConclusionsIn this cohort of 42 patients with mainly I and II tumor stages, PDR-BT boost allowed for local control in 88.7% of patients, with only one grade 3 anorectal toxicity.

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center.

Background and Aims:The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1–2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT).Patients and Methods:We carried out a retrospective study on 67 patients affected by stage I–III ASCC, treated with CDDP (60–70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent.Results:At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively.Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3–4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%).Conclusion:In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

High-dose-rate vs. low-dose-rate interstitial brachytherapy boost for anal canal cancers

PurposeThe purpose of this study was to analyze and compare clinical outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after EBRT or radio chemotherapy for the treatment of anal canal cancers. Methods and MaterialsOne hundred patients with anal canal cancers were treated at our institution by ISBT [LDR (n = 50); HDR (n = 50)]. Chronic toxicity rates, local control, disease-free survival, overall survival, and colostomy-free survival of the two different dose-rate brachytherapy modalities were analyzed and compared. ResultsWith a median followup of 42.2 months (95% CI, [34.5–48.8]), 9 (9% [4.8–16.2%]) local recurrences were observed, 4 (8% [3.2–18.8%]) in LDR vs. 5 (10% [4.4–21.4%]) in HDR group (odds ratio [OR] = 1.28 [0.32–5.07], p = 0.73). The 5-year rate of local control for the entire population was 90% [81–95%], 93% [79–98%] vs. 86% [69–94%] for LDR and HDR, respectively (p = 0.38). The 5-year disease-free survival rate for all patients was 82% [71–90%], 88% [73–95%] vs. 72% [44–88%] for LDR and HDR, respectively (p = 0.21). The 5-year overall survival rate for global population was 94% [84–98%], with no significant differences between LDR (97% [79–100%]) and HDR (93% [80–98%]) (p = 0.27). The 5-year colostomy-free survival rate was 92% [83–96%], respectively, 95% [83–99%] vs. 86% [69–94%] for LDR and HDR (p = 0.21). Significant differences were found in terms of chronic toxicity rates, with 28 (56% [42.3–68.8%]) patients concerned in low-dose-rate brachytherapy vs. 17 (34% [22.4–47.9%]) in high-dose-rate brachytherapy (OR = 0.40 [0.18–0.91], p = 0.03). ConclusionsLocal recurrence rates were comparable between both groups; HDR brachytherapy seem to have a better toxicity profile. Our data confirmed the finding that HDR can be used to safely administer ISBT without increasing chronic toxicity.

The Role of Multiagent Chemoradiation in the Management and Prognosis of Anal Squamous Cell Carcinoma

IntroductionThe standard treatment for anal squamous cell carcinoma (ASCC) is multiagent chemotherapy with radiation (CRT). This is based on several randomized trials demonstrating lower recurrence and colostomy-free survival rates with multiagent CRT; however, these studies could not confirm an overall survival (OS) benefit. We hypothesized that the lack of improved OS was due to limited sample sizes and follow-up, and that multiagent CRT is associated with higher OS. MethodsThe National Cancer Database was queried for patients diagnosed with stages I, II, and II ASCC and received between 45 and 59.4 Gy of radiation between 2004 and 2015. OS of patients receiving multiagent CRT compared to monoagent CRT and radiation alone was analyzed across stages. ResultsA total of 10,438 patients received multiagent CRT, 1163 had monoagent CRT and 446 received radiation alone. Compared to the other two groups, patients receiving multiagent CRT were younger, had fewer comorbidities, and more advanced disease (all p < 0.001). After adjusting for available confounders, multiagent CRT remained independently associated with higher OS for stages II and III ASCC. A subset analysis of patients ≥ 70 years demonstrated similar survival between monoagent versus multiagent CRT across all stages. ConclusionMultiagent CRT is associated with an OS benefit compared to monoagent CRT or radiation alone for stages II and III, but not stage I ASCC. Monoagent CRT may represent an adequate treatment for selected patients ≥ 70 years. The benefit of multiagent CRT should be balanced against treatment-related toxicities depending on disease stage and patient physiology.

Long-term results of chemoradiation plus pulsed-dose-rate brachytherapy boost in anal canal carcinoma: A mono-institutional retrospective analysis.

PurposeConcurrent chemoradiation (CCRT) is the standard curative treatment of anal canal cancer (ACC). The role of a brachytherapy (BRT) boost in this setting is still debated. Therefore, the aim of this analysis was to retrospectively evaluate the clinical outcomes in a large cohort of ACC patients treated with CCRT plus BRT boost or external beam radiotherapy (EBRT) boost.Material and methodsPatients with non-metastatic ACC, treated in our department between January 2003 and December 2014 were included in this analysis. The initial treatment was based on EBRT to the pelvis (prescribed dose, 45 Gy/1.8 Gy) plus concurrent chemotherapy (5-fluorouracil and mitomycin-C). Patients received a pulsed-dose-rate BRT boost on the primary tumor (median dose, 20 Gy; range, 13-25 Gy) 2-3 weeks after the end of CCRT. In patients with contraindications to BRT, an EBRT boost (prescribed dose, 16 Gy, 2 Gy/fraction) was delivered immediately after CCRT.ResultsOne-hundred-twenty-three patients were included in this analysis (median age, 61 years; range, 36-93 years; squamous-cell carcinoma, 78%; HIV+, 6%; median follow-up, 71 months; range, 2-158 months). The actuarial 5-year local control (LC), distant metastasis-free survival, colostomy-free survival, and overall survival (OS) rates were 81.7%, 92.3%, 62.3%, and 74.0%, respectively. At univariate analysis, patients aged ≤ 65 years (p < 0.010), cT1-2 stage (p = 0.004), and receiving a BRT boost (p = 0.015) showed significantly improved OS. At multivariate analysis, advanced tumor stage cT3-cT4 (HR, 2.12; 95% CI: 1.09-4.14; p = 0.027), and age > 65 years (HR, 3.03; 95% CI: 1.54-5.95; p = 0.001) significantly predicted increased risk of mortality. The crude rate of toxicity-related colostomies was 4.9%.ConclusionsThe role of BRT boost in ACC remains unclear since the outcomes were not clearly different compared to CCRT alone. However, further improvement of clinical results in ACC treatment is needed, and therefore prospective trials based on advanced (image-guided/adapted) BRT techniques are warranted.

Real world survival data of a rare malignancy: Anal cancer results in HIV negative patients from Turkey.

An organ preservation approach using chemoradiotherapy has been established for anal cancer. This retrospective cohort study aimed to define the clinico-demographic characteristics and outcomes of cases of human immunodeficiency virus (HIV)-negative anal carcinoma during a period of 20 years in a single comprehensive cancer institute. This was a single-center retrospective cohort study of patients who were treated between January 1995 and January 2015. The primary outcome measures that were investigated included overall survival (OS), progression-free survival (PFS), colostomy rates, and colostomy-free survival (CFS). A total of 28 patients who were principally treated with standard 5-fluorouracil + mitomycin combination chemoradiotherapy were eligible for analysis. The 3- and 5-year PFS rates were 92.4% and 63%, respectively. The lower T stage was found to be associated with a prolonged PFS (p=0.001). The 3- and 5-year CFS rates were 84.3% and 74.9%, respectively. A longer CFS was observed with lower T stages (p=0.05). At the last follow-up, 75% of the patients with anal cancer were alive, and 71.4% of the patients were disease free. The median OS was not reached with a median follow-up of 54 months (range, 6-115 months). The 3- and 5-year OS rates were 82% and 71.1%, respectively. No late toxicity was observed during the follow-up period. The short- and long-term prognoses of HIV-negative patients with anal squamous cell carcinoma were good, and low-grade toxicity was rare, thereby demonstrating that these patients can be successfully treated in a real-life setting with favorable outcomes.

Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer.

To report on clinical outcomes of simultaneous integrated boost intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy as per Radiation Therapy Oncology Group (RTOG) 0529 protocol in anal cancer patients. Clinical stage T1-T4 N0-N3 anal cancer patients were submitted to concomitant chemoradiation. Patients with cT2N0 disease were prescribed 50.4Gy/28 fractions to the gross tumor planning target volume (PTV) and 42Gy/28 fractions to the elective nodal PTV. Patients staged as cT3-T4/N0-N3 were given 54Gy/30 fractions to the macroscopic anal PTV, while clinical nodes were prescribed 50.4Gy/30 fractions if<3cm or 54Gy/30 fractions if≥3cm; elective nodal PTV was prescribed 45Gy/30 fractions. Two cycles of concomitant 5-fluorouracil and mitomycin C were planned for all patients. Oncological outcomes, acute and late toxicity profiles and pattern of failure were reported. The 3-year colostomy-free survival rate was 64% (95% CI 0.52-0.75). The 3-year local control, disease-free and overall survival rates were 69% (95% CI 0.57-0.79), 71% (95% CI 0.59-0.80) and 79% (95% CI 0.66-0.87), respectively. The cumulative incidence of colostomies was 15.1% (95% CI 8.15-23.88) at 24 months. The cumulative incidence of cancer-specific deaths was 16.4% (95% CI 8.60-26.47) at 36 months. Major acute toxicity consisted of hematological (G3-G4: 26%) and cutaneous (G3-G4: 16%) events. Only one case of≥G3 late toxicity was documented. Simultaneous integrated boost IMRT and concurrent chemotherapy as per RTOG 0529 protocol seems to be safe and feasible with consistent oncological outcomes and a mild acute and late toxicity profile in anal cancer patients.

Interstitial brachytherapy as a boost to patients with anal carcinoma and poor response to chemoradiation: Single-institution long-term results

PurposeTo analyze the efficacy of a protocol-based brachytherapy (BT) boost after external beam radiation therapy (EBRT) with simultaneous chemotherapy in patients with anal carcinoma. Methods and MaterialsAbout 190 patients have been analyzed. Around 143 patients were identified with a good clinical response at the end of EBRT. Another 47 patients received an additional BT boost to the residual tumor at 6 weeks after end of chemoradiation. ResultsThe 5-year incidence of local recurrence was 24% in patients with BT boost and 19% in patients without BT boost (p = 0.238). The 5-year disease-free survival rate, overall survival rate, and colostomy-free survival rate were 64% and 75% and 76.1% in the BT group and 69% (p = 0.212), 72% (p = 0.924), and 82.7% (p = 0.488) in the non-BT group. We found no differences in late toxicity between the groups. ConclusionsFor patients with anal cancer with not a good response to 50–59 Gy EBRT with simultaneous chemotherapy, the further dose escalation using the BT boost up to a mean of 67.5 Gy seems to improve the clinical outcome to the same level as observed in patients with a good response to ERBT, without an increase in late side effects.

Palliative Short-Course Radiation Therapy in Rectal Cancer: A Phase 2 Study

The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25Gy; 5 fractions in 5days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomatic response rate, toxicity, colostomy-free survival, and overall survival. From October 2003 to November 2012, 18 patients (median age, 77.5years) were enrolled. The median follow-up was 11.5months (range, 3-36months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response.The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients.

Chemoradiation in rectal squamous cell carcinoma: Bi-institutional case series

Background and purposePrimary rectal squamous cell carcinoma (SCC) is an uncommon disease. Early reports stated that surgery is the most effective treatment. However, recent publications suggest conservative strategy with chemoradiation provides satisfactory results. Patients and methodsWe have retrospectively studied the medical charts of 23 patients treated for a rectal SCC in two teaching hospitals in France between 1992 and 2013. Twenty-one patients received an exclusive chemoradiotherapy (CRT) and two a pre-operative CRT followed by a planned surgery. Patients received pelvic irradiation with a dose ranging from 36–45 Gy followed by a boost of 15–23 Gy. Twenty-two patients received a concurrent chemotherapy. ResultsAfter CRT, the rate of clinical complete response was 83%. With a median follow-up of 85 months, 5-year overall survival rate was 86%. Five patients presented with a relapse. The 5-year disease-free survival rate was 81%. The 5-year colostomy-free survival rate was 65%. Three patients (13%) presented with grade III–IV late rectal toxicity. ConclusionsAlthough retrospective, this is the largest cohort of patients treated with CRT for a rectal SCC. Exclusive CRT could result in high local control rate and prolonged survival in rectal SCC patients with a high rate of organ preservation.

HIV Infection Is Associated With Poor Outcomes for Patients With Anal Cancer in the Highly Active Antiretroviral Therapy Era

HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. 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. This was a retrospective chart review. The study was conducted at an outpatient oncology clinic at large academic center. A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. 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. 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. This study was limited by its retrospective design and small patient numbers. 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.