Squamous Cell Carcinoma Of The Anus Research Articles

Future patterns in burden and incidence of squamous cell carcinoma of the anus in the United States, 2001-2035.

Squamous cell carcinoma of the anus (SCCA) incidence has been rising in the United States, particularly among older adults (≥65 years). We estimated the impact of this rise on future burden (through 2035) using age-period-cohort modeling. The SCCA burden (cases/year) is expected to rise, reaching ∼2700 among men and ∼7000 among women in 2031-2035 (burden during 2016-2020 among men and women was ∼2150 and ∼4600), with most cases aged ≥65 years (61% in men and 70% in women in 2031-2035; from 40% and 46% in 2016-2020). SCCA incidence (per 100,000) is projected to rise among older men aged 65-74, 75-84, and ≥85 years (5.0, 4.9, and 4.3, in 2031-2035 vs 3.7, 3.8, 3.4 in 2016-2020) and women (11.2, 12.6, 8.0 in 2031-2035 vs 8.2, 6.8, 5.2 in 2016-2020). The projected rise in SCCA burden among older adults is troubling and highlights the importance of improving early detection and clinical care.

Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study

The modified docetaxel, cisplatin, and fluorouracil (mDCF) regimen has shown efficacy and safety as first-line treatment for advanced squamous cell carcinoma of the anus, making it a standard regimen. Inhibitors of programmed cell death protein 1 and its ligand, such as pembrolizumab, nivolumab, retifanlimab, avelumab, and atezolizumab, have shown some antitumour activity as monotherapy in advanced squamous cell carcinoma of the anus that is refractory to chemotherapy. This phase 2 study evaluated the combination of mDCF and atezolizumab as first-line treatment in advanced squamous cell carcinoma of the anus. In this randomised, open-label, non-comparative, phase 2 study, participants from 21 centres (academic, private, and community hospitals and cancer research centres) across France with chemo-naive, metastatic, or unresectable locally advanced recurrent squamous cell carcinoma of the anus, aged 18 years or older, and with an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly allocated (2:1) to receive either atezolizumab (800 mg intravenously every 2 weeks up to 1 year) plus mDCF (eight cycles of 40 mg per m2 docetaxel and 40 mg per m2 cisplatin on day 1 and 1200 mg per m2 per day of fluorouracil for 2 days, every 2 weeks intravenously; group A) or mDCF alone (group B). Randomisation was done centrally using a minimisation technique and was stratified by age (<65 years vs ≥65 years) and disease status. The primary endpoint was investigator-assessed 12-month progression-free survival in the modified intention-to-treat population in group A (35% for the null hypothesis and 50% for the alternative hypothesis). This trial is registered with ClinicalTrials.gov, NCT03519295, and is closed to new participants. 97 evaluable participants (64 in group A and 33 in group B) were enrolled between July 3, 2018, and Aug 19, 2020. The median follow-up was 26·5 months (95% CI 24·8-28·4). The median age of participants was 64·1 years (IQR 56·2-71·6), and 71 (73%) were female. 12-month progression-free survival was 45% (90% CI 35-55) in group A and 43% (29-58) in group B. In participants with a PD-L1 combined positive score of 5 or greater, 12-month progression-free survival was 70% (95% CI 47-100) in group A and 40% (19-85) in group B (interaction p=0·051) Both groups showed high compliance. Adverse events of grade 3 or higher were observed in 39 (61%) participants in group A and 14 (42%) in group B. The most common grade 3-4 adverse events were neutropenia (nine [14%] participants in group A vs five [15%] in group B), anaemia (nine [14%] vs one [3%]), fatigue (three [5%] vs four [12%]), and diarrhoea (seven [11%] vs one [3%]). Serious adverse events occurred in 16 (25%) participants in group A and four (12%) in group B, and these were mDCF-related in seven (11%) participants in group A and four (12%) in group B. Atezolizumab-related serious adverse events occurred in nine (14%) participants in group A, including grade 2 infusion-related reaction in three (5%), grade 3 infection in two (3%), and grade 2 colitis, grade 3 acute kidney injury, grade 3 sarcoidosis, and a grade 4 platelet count decrease each in one participant (2%). There were no treatment-related deaths. Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies. GERCOR, Roche.

Squamous cell carcinoma of the anus successfully treated with multidisciplinary therapy for metachronous metastatic and local recurrences after DCF chemotherapy: a case report

BackgroundDocetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy is reportedly an effective treatment strategy for squamous cell carcinoma of the anus (SCCA). However, studies regarding its use in Japanese patients remain scarce.Case presentationHere, we present the case of an 82-year-old woman with SCCA, cStage IIIB. Chemoradiotherapy was initiated after colostomy of the anorectal mass; however, para-aortic lymph node recurrence was observed 3 months after treatment completion. Five courses of DCF chemotherapy were subsequently administered, resulting in a complete response (CR). Two years and 1 month later, the aortic lymph node was enlarged again, and the patient achieved CR again after radiotherapy. Nine months later, local recurrence was detected in the anal canal, and laparoscopic perineal rectal amputation was performed. The patient remains progression-free 5 years and 10 months after the initial treatment and 1 year and 7 months after the final treatment.ConclusionsOur findings suggest that complementary treatment after DCF chemotherapy may be efficacious in Japanese patients with SCCA and help achieve CR. Despite occasional local recurrences, this approach may help achieve long-term progression-free survival.

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.

Accuracy and Clinical Impact of Persistent Disease Diagnosed on Diffusion-Weighted Imaging and Accuracy of Pelvic Nodal Assessment on Magnetic Resonance Imaging for Squamous Cell Carcinoma of the Anus in the 6-Month Interval Post Chemoradiotherapy

To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) in the 6-month interval post chemoradiation therapy (CRT) in determining persistent disease and whether persistent diffusion restriction on DWI at 6 months is associated with overall survival; and secondarily, to investigate the accuracy of pelvic lymph node assessment on T2-weighted imaging and DWI in the 6-month interval post CRT, in patients with squamous cell carcinoma of the anus. This retrospective study included patients with squamous cell carcinoma of the anus who underwent CRT followed by restaging rectal MRI from January 2010 to April 2020, with ≥1 year of follow-up after CRT. DW images were qualitatively evaluated by 2 junior and 2 senior abdominal radiologists to determine anal persistent disease. The reference standard for anal persistent disease was digital rectal examination/endoscopy and histopathology. Diagnostic performance was estimated using sensitivity, specificity, negative predictive value, and positive predictive value. Survival outcomes were evaluated via Kaplan-Meier analysis, and associations between survival outcomes and DWI status were tested for significance using the log-rank test. Additionally, DW and T2-weighted images were evaluated to determine lymph node status. Among 84 patients (mean age, 63 ± 10.2 years; 64/84 [76%] female), 14 of 84 (17%) had confirmed persistent disease. Interreader agreement on DWI between all 4 radiologists was moderate (Light's κ = 0.553). Overall, DWI had a sensitivity of 71.4%, specificity of 72.1%, positive predictive value of 34.5%, and negative predictive value of 92.5%. Patients with a negative DWI showed better survival than patients with a positive DWI (3-year overall survival of 92% vs 79% and 5-year overall survival of 87% vs 74%), although the difference did not reach statistical significance (P = .063). All patients with suspicious lymph nodes (14/14, 100%) showed negative pathology or decreased size during follow-up. At 6 months post CRT, DWI showed value in excluding anal persistent disease. Persistent diffusion restriction on DWI was not significantly associated with overall survival. Pelvic nodal assessment on DWI and T2-weighted imaging was limited in predicting persistent nodal metastases.

The accuracy of anal self- and companion exams among sexual minority men and transgender women: a prospective analysis

Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men with and without HIV is 85/100,000 and 19/100,000 persons, respectively, which is significantly higher than the overall incidence (2/100,000). Incidence may also be higher in transgender women. Since SCCA tumours average ≥30mm at diagnosis, we assessed the accuracy of individuals to self-detect smaller anal abnormalities. Using convenience sampling, the study enrolled sexual minority men and transgender women, aged 25-81 years, in Chicago, Illinois and Houston, Texas, USA, during 2020-2022. Individuals were taught the anal self-examination and anal companion examination (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. The sensitivity, specificity and concordance of the ASE/ACE to detect an abnormality were measured along with factors associated with ASE/ACE and DARE concordance. Among 714 enrolled individuals, the median age was 40 years (interquartile range, 32-54), 36.8% (259/703) were living with HIV, and 47.0% (334/710), 23.4% (166/710), and 23.0% (163/710) were non-Hispanic white, non-Hispanic Black, and Hispanic, respectively. A total of 94.1% (671/713) identified as cisgendered men, and 5.9% (42/713) as gender minorities. A total of 658 participants completed an ASE and 28 couples (56 partners) completed an ACE. Clinicians detected abnormalities in 34.3% (245/714) of individuals. The abnormalities were a median of 3mm in diameter. Sensitivity and specificity of the ASE/ACE was 59.6% (95% CI 53.5-65.7%) and 80.2% (95% CI 76.6-83.8%), respectively. Overall concordance was 0.73 (95% CI 0.70-0.76) between ASE/ACE and DARE and increased with increasing anal canal lesion size (p=0.02). Concordance was lower when participants were older and received ASE/ACE training from a lay person rather than a clinician. Sexual minority men/transgender women may self-detect SCCA when malignant lesions are much smaller than the current mean dimension at presentation of ≥30mm. National Cancer Institute.

Long-Term Patient-Reported Dyspareunia After Definitive Chemoradiation for Anal Cancer: Using the Anterior Vaginal Wall as an Organ-at-Risk to Define an Actionable Dosimetric Goal

Chemoradiation therapy (CRT) is the standard treatment for squamous cell carcinoma of the anus (SCCA). This study aimed to investigate the relationship between vaginal dosimetry and long-term patient-reported dyspareunia after treatment. We further aimed to use the anterior vaginal wall (AVW) as an organ at risk to define an actionable dosimetric clinical goal to decrease the risk of patient-reported dyspareunia. Women with SCCA treated with intensity modulated radiation therapy-based CRT were surveyed at least 2 years after successfully completing therapy. A Female Sexual Function Index (FSFI) pain subscore ≤4 was used to define dyspareunia. Dosimetric parameters were calculated for both the full vaginal canal and AVW. Multivariable linear regression models were created to identify predictors of FSFI pain subscore using backward selection to identify final variables include in the models. An actionable dosimetric predictor for dyspareunia was established using the Youden index method for cutoff optimization. Of 184 women who were contacted, 90 (49%) returned completed surveys. Of those who completed surveys, 51 (56.7%) reported being sexually active, and 47 had dosimetric data available for review. Of sexually active respondents, 32 (68%) had an FSFI pain subscore ≤4. Multiple regression models were generated using the full vaginal canal and AVW as organs at risk, and both models showed similar predictive relationships with volumetric dose parameters emerging as the best dosimetric predictors for dysparenuia. Age over 65 years was also associated with higher FSFI pain subscores (eg, less pain with intercourse) in both models. AVW V35 Gy < 60% was identified as the optimal cutoff to reduce the risk of patient-reported dyspareunia. Increased dose to the vaginal canal is significantly associated with worse patient-reported dyspareunia following CRT for SCCA. Minimizing dose to the AVW to V35 Gy < 60% may reduce the risk of this quality of life-limiting toxicity. Further prospective evaluation is needed to validate these findings.

Management of non-metastatic anal cancer in the elderly: ancillary study of the French multicenter prospective cohort FFCD-ANABASE.

Standard care for non-metastatic squamous cell carcinoma of the anus (SCCA) is chemoradiotherapy, data about elderly patients are scarce. All consecutive patients treated for non-metastatic SCCA from the French multicenter FFCD-ANABASE cohort were included. Two groups were defined according to age: elderly (≥75 years) and non-elderly (<75). Of 1015 patients, 202 (19.9%) were included in the elderly group; median follow-up was 35.5 months. Among the elderly, there were more women (p = 0.015); frailer patients (p < 0.001), fewer smokers (p < 0.001) and fewer HIV-infected (p < 0.001) than in the non-elderly group. Concomitant chemotherapy and inguinal irradiation were less frequent (p < 0.001 and p = 0.04). In the elderly group; 3-year overall survival (OS), recurrence-free survival (RFS) and colostomy-free survival (CFS) were 82.9%, 72.4% and 78.0%, respectively; complete response rate at 4-6 months was 70.3%. There were no differences between groups for all outcomes and toxicity. In multivariate analyses for the elderly, PS ≥ 2 and locally-advanced tumors were significantly associated with poor OS (HR = 3.4 and HR = 2.80), RFS (HR = 2.4 and HR = 3.1) and CFS (HR = 3.8 and HR = 3.0); and treatment interruption with poor RFS (HR = 1.9). In the FFCD-ANABASE cohort, age did not influence tumor and tolerance outcomes of non-metastatic SCCA. Optimal curative treatment should be offered to elderly patients.

Comparing the Diagnostic Performance of Quantitative PCR, Digital Droplet PCR, and Next-Generation Sequencing Liquid Biopsies for Human Papillomavirus–Associated Cancers

HPV-associated cancers, including oropharyngeal squamous cell carcinoma(HPV+OPSCC), cervical cancer(HPV+CC), and squamous cell carcinoma of the anus(HPV+SCCA), release circulating tumor HPV DNA(ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches utilized and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn impacts clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ctHPVDNA detection across cancer anatomic sites, detection platforms, and blood components. The population included HPV+OPSCC, HPV+CC, and HPV+SCCA patients with pre-treatment samples analyzed by quantitative PCR(qPCR), digital droplet PCR(ddPCR), or next generation sequencing(NGS). 36 studies involving 2,986 patients met the inclusion criteria. The sensitivity, specificity and quality of each study were assessed and pooled for each analysis.The sensitivity of ctHPVDNA detection was greatest with NGS, followed by ddPCR and lastly qPCR when pooling all studies, while specificity was similar(sensitivity: ddPCR>qPCR, p<0.001; NGS>ddPCR, p=0.014). ctHPVDNA from OPSCC was more easily detected compared to CC and SCCA, overall(p=0.044). In conclusion, detection platform, anatomic site of the cancer and blood component utilized impacts ctHPVDNA detection and must be considered when interpreting results. Plasma NGS-based testing should be considered the most sensitive approach for ctHPVDNA overall.

Recent Advances in the Management of Anal Cancer

The incidence and mortality of squamous cell carcinoma of the anus (SCCA) is on the rise, which highlights the unmet need for advances in treatment options. The landscape of treatment for this cancer is rapidly evolving with novel combination strategies including immunotherapy, radiation therapy and biomarker-guided therapy. This review article features an overview of recent advancements in both locoregional and metastatic SCCA. The recent focus on locoregional SCCA management is to tailor treatment according to tumor burden and minimize treatment-related toxicities. Mitomycin plus either infusional 5-fluorouracil (5-FU) or capecitabine is used for first-line chemoradiotherapy (CRT), and intensity-modulated radiotherapy (IMRT) is the preferred modality for radiation for locoregional anal cancer. Locally recurrent disease is managed with surgical resection. Systemic treatment is first-line for metastatic SCCA and immunotherapy with nivolumab and pembrolizumab being included as second-line agents. Current and future clinical trials are evaluating treatments for SCCA including immunotherapy alone or in combination regimens, radiotherapies, targeted treatments and novel agents. Another critical aspect of current research in SCCA is the personalization of CRT and immunotherapies based on molecular characterization and biomarkers such as the programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) and circulating tumor DNA.

Daily Vaginal Dilator Use During Radiation for Women With Squamous Cell Carcinoma of the Anus: Vaginal Wall Dosimetry and Patient-Reported Sexual Function

Background: At our institution, we treat patients with a daily vaginal dilator (VD) during chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). We evaluated compliance with daily VD use, radiation dose to the vaginal wall (VW) and anterior vaginal wall (AVW), and patient-reported long-term sexual function. Methods: We included women with SCCA who received definitive, intensity-modulated radiotherapy-based CRT. Women who were alive without evidence of disease received a patient-reported outcome survey, which included the Female Sexual Function Index (FSFI). We identified factors associated with FSFI such as radiation dose to the VW and AVW using linear regression models and used Youden index analysis to estimate a dose cutoff to predict sexual dysfunction. Results: Three hundred thirty-nine consecutively treated women were included in the analysis; 285 (84.1%) were treated with a daily VD. Of 184 women alive without disease, ninety patients (49%) completed the FSFI, and 51 (56.7%) were sexually active with valid FSFI scores. All received therapy with a daily VD. Forty-one women (80%) had sexual dysfunction. Univariate analysis showed higher dose to 50% (D50%) of the AVW correlated with worse FSFI (β -0.262; p=.043), worse desire FSFI subscore (β -.056; p=.003) and worse pain FSFI subscore (β -.084; p=.009). Younger age correlated with worse pain FSFI subscale (β .067; p=.026). Age (β 0.070; p=.013) and AVW D50% (β -0.087; p=.009) were significant on multivariable analysis. AVW D50% >48Gy predicted increased risk of sexual dysfunction. Conclusion: Daily VD use is safe and well tolerated during CRT for SCCA. Using a VD during treatment to displace the AVW may reduce the risk for sexual dysfunction. Limiting the AVW D50% <48Gy may further reduce the risk but additional data are needed to validate this constraint.

The Patient's perspective on radiation therapy for anal cancer: Evaluation of expectations and stigma.

Little is known regarding anal cancer patients' perspectives on undergoing radiation therapy. Additionally, the stigma surrounding anal cancer diagnosis warrants a better understanding of the barriers to complete disclosure in patient-healthcare team interactions. Included patients had squamous cell carcinoma of the anus treated with definitive chemoradiation (CRT) from 2009 to 2018. Survey questions were adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Discrimination and Stigma Scale. A total of 46 anal cancer patients who underwent CRT were surveyed, of which 72% responded. 73% of respondents indicated little to no pre-treatment knowledge of CRT. 70% reported overall short-term effects as worse than expected, most commonly with bowel habits (82%), energy (73%), and interest in sexual activity (64%). 39% reported overall long-term effects to be worse than expected, most commonly with changes to bowel habits (73%), sexual function (67%), and interest in sexual activity (58%). However, 94% agreed they were better off after treatment. Regarding stigma, a subset reported hiding their diagnosis (12%, 24%) and side effects (24%, 30%) from friends/family or work colleagues, respectively, and 15% indicating they stopped having close relationships due to concerns over stigma. Although patients' perceptions of the severity of short-term CRT side effects were worse than 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.

Outcomes and after Hyperfractionated, Accelerated Reirradiation for Recurrent Anal Squamous Cell Carcinoma

Abdominoperineal resection (APR) is the standard salvage treatment for recurrent or persistent squamous cell carcinoma of the anus (SCCA). However, reirradiation (reRT) can be used preoperatively or for those who are not candidates for surgery. Using a single institutional database, patients were identified who underwent reRT for SCCA from 2003 to 2022. Response to reRT and outcomes after reRT were recorded. Variables analyzed included age at reRT, sex, reason for reRT (recurrent SCCA vs new SCCA after pelvic radiation for a different malignancy), interval between initial radiation and reRT, reRT dose, concurrent chemotherapy, receipt of APR and the presence of distant metastases at the time of reRT. Cox Proportional Hazard Model was used; multivariable analysis for all factors with a univariate P-value <0.1 on univariable analysis. A total of 42 patients received reRT, which consisted of 1.5 Gray (Gy) twice daily fractions with ≥6-hour interval to a total dose ranging 30Gy to 54Gy (median [IQR] 39Gy [39-42Gy]. Thirty-eight patients (90.5%) received concurrent chemotherapy; most often with weekly cisplatin and 5-fluorouracil (N = 23, 54.8%). Median [IQR] follow-up after reRT was 11.4 months [4.9-40.8 months]. Median [IQR] initial radiation dose was 54Gy [54-58Gy], and median [IQR] interval between initial radiation and reRT was 3.6 years [2.1-6.0 years]. For 8 patients (19.1%), the initial radiation was given for a different pelvic malignancy prior to being diagnosed with SCCA. Four of these patients received brachytherapy alone or in conjunction with external beam. For the remaining 34 patients, the initial radiation was for SCCA and the reRT was for recurrent SCCA either in the anal canal (N = 23, 67.6%) or regional nodes (N = 11, 32.3%). Four patients (9.5%) had distant disease at the time of reRT. Eleven patients (26.2%) had planned APR after preoperative reRT; 1 patient had a pathologic complete response (pCR), 2 patients had a near pCR (<5% viable cancer). Twenty-nine patients (69.0%) were treated with reRT alone; 15 (51.7%) attained a clinical CR. Two patients (4.8%) were treated with palliative intent and response was not assessed. Median local recurrence free survival (LRFS) was 9.9 months; 2- and 3-year LRFS were both 41%. Median distant metastasis free survival (DMFS) was 11.8 months; 2- and 3-year DMFS were 38% and 34%, respectively. Median overall survival (OS) was 40.5 months; 2- and 3-year OS were 54% and 51%, respectively. On multivariable analysis, only the presence of distant disease at the time of reRT was significantly associated with worse LRFS (HR (95% CI) 4.14 (1.34-12.81); P = .014), worse DMFS (4.06 (1.37-12.06); P = .012) and worse OS (5.73 (1.57-20.9); P = .008). ReRT is an option for patients presenting with either recurrent SCCA or new SCCA after prior pelvic radiation for a different malignancy. ReRT can be given prior to planned salvage APR or alone for patients who are not surgical candidates with an approximate 50% cCR rate.

A retrospective analysis of concurrent chemoradiation for squamous cell carcinoma of the anus in Johannesburg

Background: Anal cancer is a major cause of mortality and morbidity in low- and middle-income countries (LMICs).Aim: A retrospective analysis to understand presentation and outcomes of patients with anal cancer, who were treated with a curative intent.Setting: A radiation oncology unit in quaternary level hospital in South Africa.Methods: Medical records of patients with invasive squamous cell carcinoma (SCC) of the anal canal who were treated between 2014 and 2019 were reviewed with follow-up until June 2021. The 2D-radiotherapy planning and delivery techniques were used to a dose of 50 Gy, with a boost dose of 6 Gy – 10 Gy for patients with residual disease and concurrent chemotherapy.Results: Eighty-four patients were included in the analysis. Median age was 45 years (range: 25–73 years), 75% were female patients, 80% of the cohort was human immunodeficiency virus (HIV)-positive, and 17% with a CD4 count below 200 cells/mm3. Eighty-seven percent had locally advanced stage three disease. Concurrent 5-fluorouracil (5-FU) and mitomycin C-based chemotherapy was given in four patients, while 50% had 5-FU plus cisplatin and 16% had radiotherapy alone. Complete clinical response was observed in 54 out of 66 evaluable patients (81.8%) at 6 months post-chemoradiation. Overall survival at 2 years could not be determined because of a significant loss to follow-up rate.Conclusion: A high HIV-postive rate and an advanced disease stage were observed among cohorts with anal canal SCC treated with a definitive curative intent. Tumour response rates at 6 months were favourable although the 2-year overall survival could not be established.Contribution: This study contributes to the growing body of research on anal cancer outcomes in LMICs.

Immediate and long-term results of radiation therapy in combination with capecitabine and oxaliplatin in the treatment of patients with asquamous cell carcinoma of the anus

Introduction. The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT. The purpose of the study: a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine. Material and Methods. The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m2 twice a day in combination with intravenous administration of oxaliplatin 50 mg/m2 on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery. Results. All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively. Conclusion. Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.

Risk factors and outcome following salvage surgery for squamous cell carcinoma of the anus

BackgroundChemoradiotherapy is the primary treatment for anal cancer. 15–33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery. Relapse after surgery, postoperative complications, and mortality as well as possible risk factors are not fully understood due to the rareness of the disease. The aim of the study was to report outcomes after salvage surgery as well as evaluate risk factors for postoperative complications, cancer relapse and survival. MethodsData were retrospectively collected from electronical patients charts and pathology reports from all patients undergoing salvage surgery from July 1st, 2011 to July 1st, 2021 at the Department of Surgery, Aarhus University Hospital, Denmark. ResultsA total of 98 patients were included in the study. The 5-year overall survival was 61.8%. Relapse after surgery occurred in 36.7% of patients and was significantly associated with R1-resection (HR = 4.4) and preoperative nodal metastases (HR = 4.5). Negative prognostic factors for survival were found to be R1-resection (HR = 3.2), preoperative nodal metastases (HR = 2.9), and male gender (HR = 0.5). There was no association found between complications and survival (HR 1.2). None of the possible risk factors were associated with major postoperative complications. ConclusionsAn acceptable overall survival after surgery was found. Survival and relapse-free survival was negatively associated with R1 resections and positive preoperative lymph nodes. Complications did not influence long-term survival.

Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States.

Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex. We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.

Random Forest Modeling of Acute Toxicity in Anal Cancer: Effects of Peritoneal Cavity Contouring Approaches on Model Performance

Our purpose was to analyze the effect on gastrointestinal (GI) toxicity models when their dose-volume metrics predictors are derived from segmentations of the peritoneal cavity after different contouring approaches. A random forest machine learning approach was used to predict acute grade ≥3 GI toxicity from dose-volume metrics and clinicopathologic factors for 246 patients (toxicity incidence=9.5%) treated with definitive chemoradiation for squamous cell carcinoma of the anus. Three types of random forest models were constructed based on different bowel bag segmentation approaches: (1) physician-delineated after Radiation Therapy Oncology Group (RTOG) guidelines, (2) autosegmented by a deep learning model (nnU-Net) following RTOG guidelines, and (3) autosegmented but spanning the entire bowel space. Each model type was evaluated using repeated cross-validation (100 iterations; 50%/50% training/test split). The performance of the models was assessed using area under the precision-recall curve (AUPRC) and the receiver operating characteristic curve (AUROCC), as well as optimal F1 score. When following RTOG guidelines, the models based on the nnU-Net auto segmentations (mean values: AUROCC, 0.71 ± 0.07; AUPRC, 0.42 ± 0.09; F1 score, 0.46 ± 0.08) significantly outperformed (P < .001) those based on the physician-delineated contours (mean values: AUROCC, 0.67 ± 0.07; AUPRC, 0.34 ± 0.08; F1 score, 0.36 ± 0.07). When spanning the entire bowel space, the performance of the autosegmentation models improved considerably (mean values: AUROCC, 0.87 ± 0.05; AUPRC, 0.70 ± 0.09; F1 score, 0.68 ± 0.09). Random forest models were superior at predicting acute grade ≥3 GI toxicity when based on RTOG-defined bowel bag autosegmentations rather than physician-delineated contours. Models based on autosegmentations spanning the entire bowel space show further considerable improvement in model performance. The results of this study should be further validated using an external data set.

Mesenchymal Stem Cells and Regenerative Therapy with Bilateral Gracilis Flaps for Perineal Reconstruction of a Wound Infection in the Setting of Anal Squamous Cell Carcinoma.

Many patients are affected by HIV/AIDS, and these conditions are highly prevalent worldwide. Patients with HIV/AIDS can experience debilitating wound infections that often require flap reconstruction and become challenging for surgeons to treat. In the past 5 years, mesenchymal stem cells have been tested and used as regenerative therapy to promote the growth of tissues throughout the body because of their ability to successfully promote cellular mitogenesis. To the authors' knowledge, the use of mesenchymal stem cell grafting following necrosis of a myocutaneous gracilis flap (as part of perineal wound reconstruction) has never been reported in the literature.In addition, the use of mesenchymal stem cells and regenerative medicine combined in the setting of squamous cell carcinoma of the anus with prior radiation (along with comorbid AIDS) has not been previously documented.In this report, the authors outline the case of a 60-year-old patient who had a recipient bed (perineum) complication from prior radiation therapy. Complicating the clinical picture, the patient also developed a Pseudomonal organ space infection of the pelvis leading to the failure of a vertical rectus abdominis myocutaneous flap and myocutaneous gracilis flaps. As a result, the patient underwent serial operative debridements for source control, with the application of mesenchymal stem cells, fetal bovine dermis, porcine urinary bladder xenograft, and other regenerative medicine products, achieving a highly successful clinical outcome. A procedural description for future use and replication of this method is provided.

Pelvic Exenteration for Squamous Cell Carcinoma of the Anus: Oncological, Morbidity, and Quality-of-Life Outcomes.

Salvage surgery is the only potentially curative treatment option for recurrent squamous cell carcinoma of the anus. Where adjacent pelvic viscera, soft tissues, and bone are involved, pelvic exenteration with a wide perineal excision may be required to ensure clear surgical margins and increase the likelihood of long-term survival. To report oncological, morbidity, and quality-of-life outcomes of pelvic exenteration for anal squamous cell carcinoma. Cohort study with retrospective analysis of prospectively collected data. This study was conducted at a high-volume pelvic exenteration center. Those who underwent pelvic exenteration for anal squamous cell carcinoma between 1994 and 2022. Local recurrence-free and overall survival, intraoperative and postoperative complication rates, R0 resection rate, and long-term quality-of-life outcomes. Of 958 patients who underwent pelvic exenteration, 66 (6.9%) had anal squamous cell carcinoma. Thirty-two patients (48.5%) were male and the median age was 57 years (range, 31-79). Ten patients (15%) had primary anal squamous cell carcinoma, 49 (74%) had a recurrent tumor, and 7 (11%) had a re-recurrent tumor. Twenty-two patients (33%) and 16 patients (24%) had a major complication and unplanned return to the operating theater, respectively. Of the 62 patients who underwent pelvic exenteration with curative intent, 50 (81%) had R0 resection, and the 5-year overall and local recurrence-free survival rates were 41% and 37%, respectively. R0 resection was associated with a higher 5-year overall survival (50% vs 8%, p < 0.001). The mental health component scores and several individual quality-of-life domains presented improved trajectories postoperatively (all p values <0.05). The generalizability of the findings outside specialist pelvic exenteration centers may be limited. Morbidity, long-term survival, and quality-of-life outcomes after pelvic exenteration for anal squamous cell carcinoma are comparable to published outcomes of pelvic exenteration for other tumor types. ANTECEDENTES:La cirugía de rescate es la única opción de tratamiento potencialmente curativa para el carcinoma de células escamosas del ano recurrente. Cuando están involucradas vísceras pélvicas, tejidos blandos y huesos adyacentes, puede ser necesaria una exenteración pélvica con una escisión perineal amplia para asegurar márgenes quirúrgicos claros y aumentar la probabilidad de supervivencia a largo plazo.OBJETIVO:Informar sobre los resultados oncológicos, de morbilidad y de calidad de vida de la exenteración pélvica por carcinoma anal de células escamosas.DISEÑO:Estudio de cohortes con análisis retrospectivo de datos recogidos prospectivamente.ENTORNO CLINICO:Este estudio se realizó en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos que se sometieron a exenteración pélvica por carcinoma anal de células escamosas entre 1994 y 2022.PRINCIPALES MEDIDAS DE VALORACIÓN:Supervivencia global y libre de recidiva local, tasas de complicaciones intraoperatorias y posoperatorias, tasa de resección R0 y resultados de calidad de vida a largo plazo.RESULTADOS:De 958 pacientes que se sometieron a exenteración pélvica, 66 (6,9%) tenían carcinoma anal de células escamosas. 32 pacientes (48,5%) eran varones y la mediana de edad fue de 57 años (rango 31-79). 10 pacientes (15%) tenían carcinoma anal primario de células escamosas, 49 (74%) tenían un tumor recurrente y 7 (11%) tenían una segunda recurrencia. 22 (33%) y 16 pacientes (24%) tuvieron una complicación mayor y regreso no planificado al quirófano, respectivamente. De los 62 pacientes que se sometieron a una exenteración pélvica con intención curativa, 50 (81%) tuvieron una resección R0, las tasas de supervivencia global y libre de recidiva local a los 5 años fueron del 41% y el 37%, respectivamente. La resección R0 se asoció con una mayor supervivencia general a los 5 años (50% frente a 8%, p < 0,001). Las puntuaciones del componente de salud mental y varios dominios de calidad de vida individuales presentaron trayectorias mejoradas después de la operación (todos los valores de p < 0,05).LIMITACIONES:La generalización de los hallazgos fuera de los centros especializados en exenteración pélvica puede ser limitada.CONCLUSIONES:Los resultados de morbilidad, supervivencia a largo plazo y calidad de vida después de la EP para el carcinoma anal de células escamosas son comparables a los resultados publicados de la exenteración pélvica para otros tipos de tumores. (Traducción-Dr. Ingrid Melo ).