Rational treatment options for T1/2N0M0 squamous cell carcinoma of the anal canal: a population-based study combined with external validation.

BACKGROUND: Treatment options for T1/2N0M0 anal squamous cell carcinoma include chemotherapy, radiotherapy, chemoradiotherapy, and local excision, although the optimal treatment method has not been determined. METHODS: The National Cancer Institute Surveillance, Epidemiology and Results database was used to search and screen 1465 patients with cT1/2N0M0 anal squamous cell carcinoma who were clinically diagnosed between 2004 and 2016. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression analysis was performed to screen independent prognostic factors and build a nomogram survival prediction model. According to the risk score, patients were divided into low, medium, and high risk groups using X-tile software. RESULTS: Age, sex, grade and cT stage were identified as independent prognostic factors for cT1/2N0M0 anal squamous cell carcinoma and were included in the nomogram to construct a prediction model. The C-index of the model was 0.770 [95% confidence interval (CI), 0.693-0.856], which was higher than the C-index of T stage 0.565 (95% CI, 0.550-0.612). Low-risk patients benefited from local resection, moderate-risk patients benefited from radiotherapy, and high-risk patients benefited from radiotherapy or chemoradiotherapy. This was confirmed using external validation data from the center. CONCLUSION: The nomogram developed in this study effectively and comprehensively evaluated the prognosis of patients with cT1/2N0M0 squamous cell carcinoma of the anal canal. Local excision is recommended for low risk patients, radiotherapy for moderate-risk patients, and radiotherapy or chemoradiotherapy for high-risk patients.

Socioeconomic Disparities in Anal Cancer: Effect on Treatment Delay and Survival.

BACKGROUND: Socioeconomic inequities have implications for access to health care and may be associated with disparities in treatment and survival. OBJECTIVE: To investigate the impact of socioeconomic inequities on time to treatment and survival of anal squamous-cell carcinoma. DESIGN: This is a retrospective study using a nationwide data set. SETTINGS: The patients were selected from the National Cancer Database and enrolled from 2004 to 2016. PATIENTS: We identified patients with stage I to III squamous-cell carcinoma of the anus who were treated with chemoradiation therapy. MAIN OUTCOMES MEASURES: Socioeconomic factors, including race, insurance status, median household income, and percentage of the population with no high school degrees, were included. The association of these factors with treatment delay and overall survival was investigated. RESULTS: A total of 24,143 patients who underwent treatment for grade I to III squamous-cell carcinoma of the anus were identified. The median age was 60 years, and 70% of patients were women. The median time to initiation of treatment was 33 days. Patients from zip codes with lower median income, patients with a higher percentage of no high school degree, and patients with other government insurance followed by Medicaid insurance had treatment initiated after 60 days from diagnosis. Kaplan-Meier survival analysis showed that the late-treatment group had worse overall survival compared to the early treatment group (98 vs 125 months; p < 0.001). LIMITATIONS: No detailed information is available about the chemoradiotherapy regimen, completion of treatment, recurrence, disease-free survival, and individual-level socioeconomic condition and risk factors. CONCLUSION: Patients from communities with lower median income, level of education, and enrolled in public insurance had longer time to treatment. Lower socioeconomic status was also associated with poorer overall survival. These results warrant further analysis and measures to improve access to care to address this disparity. See Video Abstract . DESIGUALDADES SOCIOECONMICAS EN CASOS DE CNCER ANAL EFECTOS EN EL RETRASO DEL TRATAMIENTO Y LA SOBREVIDA: ANTECEDENTES:Las desigualdades socio-económicas tienen implicaciones en el acceso a la atención médica y pueden estar asociadas con disparidades en el tratamiento y la sobrevida.OBJETIVO:Indagar el impacto de las desigualdades socio-económicas sobre el tiempo de retraso en el tratamiento y la sobrevida en casos de carcinoma a células escamosas del ano (CCEA).DISEÑO:Estudio retrospectivo utilizando un conjunto de datos a nivel nacional.AJUSTES:Todos aquellos pacientes inscritos entre 2004 a 2016 y que fueron seleccionados de la Base Nacional de Datos sobre el Cáncer.PACIENTES:Identificamos pacientes con CCEA en estadíos I-III y que fueron tratados con radio-quimioterápia.PRINCIPALES MEDIDAS DE RESULTADOS:Se incluyeron factores socio-económicos tales como la raza, el tipo de seguro de salud, el ingreso familiar medio y el porcentaje de personas sin bachillerato de secundaria (SBS). Se investigó la asociación entre estos factores con el retraso en iniciar el tratamiento y la sobrevida global.RESULTADOS:Se identificaron un total de 24.143 pacientes que recibieron tratamiento para CCEA estadíos I-III. La mediana de edad fue de 60 años donde 70% eran de sexo femenino. La mediana del tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue de 33 días. Los pacientes residentes en zonas de código postal con ingresos medios más bajos, con un mayor porcentaje de individuos SBS y los pacientes con otro tipo de seguro gubernamental de salud, seguidos del seguro tipo Medicaid iniciaron el tratamiento solamente después de 60 días al diagnóstico inicial de CCEA. El análisis de Kaplan-Meier de la sobrevida mostró que el grupo de tratamiento tardío tuvo una peor supervivencia general comparada con el grupo de tratamiento precoz o temprano (98 frente a 125 meses; p <0,001).LIMITACIONES:No se dispone de información detallada sobre el tipo de radio-quimioterapia utilizada, ni sobre la finalización del tratamiento o la recurrencia, tampoco acerca de la sobrevida libre de enfermedad ni sobre las condiciones socio-económicas o aquellos factores de riesgo a nivel individual.CONCLUSIÓN:Los pacientes de comunidades con ingresos medios más bajos, con un nivel de educación limitado e inscritos en un seguro público tardaron mucho más tiempo en recibir el tratamiento prescrito. El nivel socio-económico más bajo también se asoció con una sobrevida global más baja. Los presentes resultados justifican mayor análisis y medidas mas importantes para mejorar el acceso a la atención en salud y poder afrontar esta disparidad. (Traducción-Dr. Xavier Delgadillo ).

A national database analysis of the evolution of outcomes of surgery for anal melanoma.

BACKGROUND: This study assessed trends in treatment and outcomes of anal melanomas over a 17-year period. METHODS: NCDB was searched for patients with anal melanoma (2004-2020). Receiver-operating characteristic curve analysis was used to determine cutoff year marking increased overall survival (OS) of anal melanoma. Characteristics, treatments, and outcomes in consecutive time periods were compared. RESULTS: A total of 815 patients (mean age: 67.2 years; 59.4% female) were included: 354 in Period 1 (2004-2012) and 461 in Period 2 (2013-2020). Period 2 included fewer abdominoperineal resections (18% vs. 28%, p = 0.002), more local tumor excisions (61.1% vs. 55%, p = 0.002), more often immunotherapy (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 2.22-5.22, p < 0.001) and less often chemotherapy (OR: 0.516, 95% CI: 0.352-0.755, p < 0.001) administered and longer median OS (25.2 vs. 19.8 months, p = 0.006). Independent predictors of worse OS were older age (hazard ratio [HR]: 1.02, p = 0.012), higher Charlson score (HR: 2.32, p = 0.02), and greater number of positive lymph nodes (HR: 1.15, p < 0.001); conversely private insurance (HR: 0.385, p = 0.008) was predictive of increased OS. CONCLUSIONS: Anal melanoma patients diagnosed between 2013 and 2020 underwent fewer abdominoperineal resections and more local excisions than patients diagnosed between 2004 and 2013. Increased immunotherapy and longer median OS were noted in period two. Age and private insurance were significant predictors of OS, remaining constant across time periods.

A study of microRNAs as new prognostic biomarkers in anal cancer patients.

BACKGROUND: MicroRNA (MiR) influences the growth of cancer by regulation of mRNA for 50-60% of all genes. We present as per our knowledge the first global analysis of microRNA expression in anal cancer patients and their prognostic impact. METHODS: Twenty-nine patients with T1-4 N0-3 M0 anal cancer treated with curative intent from September 2003 to April 2011 were included in the study. RNA was extracted from fresh frozen tissue and sequenced using NGS. Differentially expressed microRNAs were identified using the R-package DEseq2 and the endpoints were time to progression (TTP) and cancer specific survival (CSS). RESULTS: Five microRNAs were significantly associated with 5-year progression free survival (PFS): Low expression of two microRNAs was associated with higher PFS, miR-1246 (100% vs. 55.6%, p = 0.008), and miR-135b-5p (92.9% vs. 59.3%, p = 0.041). On the other hand, high expressions of three microRNAs were associated with higher PFS, miR-148a-3p (93.3% vs. 53.6%, p = 0.025), miR-99a-5p (92.9% vs. 57.1%, p = 0.016), and let-7c-3p (92.9% vs. 57.1%, p = 0.016). Corresponding findings were documented for CSS. INTERPRETATION: Our study identified five microRNAs as prognostic markers in anal cancer. MiR-1246 and microRNA-135b-5p were oncoMiRs (miRs with oncogene effects), while miR-148a-3p, miR- 99a-5p, and let-7c-3p acted as tumour suppressors in anal cancer patients.

Electron beam radiotherapy for the management of squamous cell carcinoma of the anal margin.

PURPOSE AND OBJECTIVE: Squamous cell carcinoma of the anal margin (SCCAM) is an uncommon lesion that comprises one-third to a quarter of all anal squamous cell carcinoma. Treatment involves surgery or exclusive radiotherapy for small tumours, whereas the preferred treatment for larger tumours is chemoradiotherapy. In our department, selected patients with SCCAM are treated with electron beam radiotherapy using one perineal field. The present study evaluates this strategy. MATERIAL AND METHODS: All consecutive patients with SCCAM and treated with electron beam radiotherapy from 2012 to 2022 were included. Data were retrospectively extracted from the medical records and analysed descriptively. Local control (LC) and overall survival (OS) were analysed using Kaplan-Meier statistics. RESULTS: Forty patients were evaluated. Primary radiotherapy was delivered in 35 (87.5%) patients. Five (12.5%) patients had postoperative radiotherapy. Median prescription dose was 60.0 (range 45.0-60.2) Gy in 28 (range 10-30) fractions delivered with 8 (range 4-18) MeV using a standard circular aperture and bolus. At a median follow-up of 73 (range 9-135) months, 7 (17.5%) patients were diagnosed with local recurrences. The 5-year LC rate was 84.3% (95% CI: 71.4%-97.2%). Analysis of LC according to T-stage revealed a 5-year LC of 100% (95% CI: 100%-100%) in T1 tumours compared to 57.0% (95% CI: 27.4%-86.6%) in T2 tumours (p < 0.001). 5-year OS was 91.6% (95% CI: 83.0%-100%). Late grade 3 toxicity included ulceration in the skin and subcutis in 2 (5.0%) patients. INTEPRETATION: Electron beam radiotherapy enables the delivery of 'eye-guided' radiotherapy directly to the tumour. LC is good in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy. Electron beam radiotherapy enables the delivery of "eye-guided" RT directly to the tumour. LC is excellent in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy.

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

Significance of lateral lymph node dissection in squamous cell carcinoma of the anal canal: a retrospective cohort study.

PURPOSE: The JCOG (Japan Clinical Oncology Group) 0212 study did not confirm the noninferiority of mesorectal excision (ME) alone to ME with LLND for rectal or anal adenocarcinomas. Furthermore, the significance of LLND for SCCs remains unknown. We evaluated the significance of lateral lymph node dissection (LLND) of squamous cell carcinoma (SCC) of the anal canal. METHODS: This retrospective cohort study was conducted in 435 patients with SCCs among 1,781 patients with anal canal tumors. In 40 patients who underwent LLND, the 5-year relapse-free survival (5y-RFS) and 5-year overall survival (5y-OS) were compared between groups with positive and negative histopathological findings. In 71 patients with negative lateral lymph node metastasis in the preoperative diagnosis, the 5y-RFS, 5y-OS, and 5-year local recurrence-free survival were compared between patients who did and did not undergo LLND. RESULTS: The clinical and pathological T stages predicted pathological lateral pelvic lymph node metastasis. There was no statistically significant difference in 5y-RFS and 5y-OS between patients who did and did not undergo LLND. Among patients who underwent LLND, 5y-RFS in those with positive histopathological findings (15.0%) was worse than that in those without (59.2%) (p = 0.002). CONCLUSIONS: In patients who underwent LLND, 5y-RFS in those with positive histopathological findings than in those without LLND did not contribute to prognosis.

Clinical outcomes and prognostic factors of concurrent chemoradiotherapy for anal squamous cell carcinoma in Japan.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregional anal squamous cell carcinoma (ASCC) in western countries. However, there have been few reports on the clinical outcomes of CCRT in Japan. This study aimed to evaluate the clinical outcomes of CCRT, prognostic factors, and the clinical impact of programmed cell death-ligand 1 (PD-L1) expression of ASCC in Japan. METHODS: Patients with locoregional ASCC were enrolled between 2007 and 2017. All patients received CCRT consisting of ≥ 45 Gy of radiation, 5-fluorouracil, and mitomycin C. Disease-free survival (DFS), overall survival (OS), and adverse events (AEs) were estimated. Expression of p16 and PD-L1 were assessed by immunohistochemical staining (IHC). RESULTS: This study included 36 patients, of whom 30 (83.3%) were female. Among the participants, 32 (88.9%) achieved complete clinical remission, while six (16.7%) experienced recurrence. The five-year DFS and five-year OS were 72.2% and 84.7%, respectively. Grades ≥ 3 serious AEs included neutropenia in 10 (27.7%) and perianal dermatitis in eight (22.2%). In a univariate analysis, male sex, lymph node metastasis, and large tumor size were significantly associated with worse outcome. In a multivariate analysis, tumor size was an independent factor associated with short DFS. Of the 30 patients whose biopsy specimens were available for IHC, 29 (96.7%) were positive for p16, and 13 (43.3%) were positive for PD-L1. However, PD-L1 expression did not show any clinical impact. CONCLUSIONS: The comparative etiology, clinical outcomes, and prognostic factors of CCRT observed in Japanese patients with locoregional ASCC were consistent with western data.

Comparison of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma treated nonsurgically and proposal of a new stage grouping system.

OBJECTIVE: To compare the survival discrimination of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma (ASCC) treated nonsurgically and suggest a simple revised staging system with data from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Overall survival (OS) was the primary endpoint. Survival comparisons between the T and N stages and the different staging systems were performed using the Kaplan-Meier method and log-rank test, followed by correlation analysis and variable importance analysis (VIA). Additionally, multivariate analysis was employed to identify significant predictors, which were further visualized using a nomogram. Finally, calibration curve, C-index, and decision curve analysis (DCA) were applied to assess the performance of the different staging systems. RESULTS: A total of 5384 patients with ASCC were analyzed, revealing superior discrimination OS by the TNM9th edition compared to that by the TNM8th edition. Multivariate analysis identified the T and N stages as significant OS predictors (all p < 0.001). However, ambiguity persisted in stage III subgroups within the TNM9th edition, showing OS times of 102 months for stage IIIA disease, 88 months for stage IIIB disease, and 128 months for stage IIIC disease (all p > 0.05). Correlation analysis demonstrated an increased correlation for the T stage between the TNM8th and 9th editions (ρ value from 0.7 to 0.89), while the N stage correlation decreased (ρ value from 0.84 to 0.56). VIA and the prognostic nomogram highlighted the greater importance of the T stage over the N stage. Based on these findings, a new staging system was developed, and its clinical utility was confirmed through calibration curves, C-index values (from 0.598 to 0.604), and DCAs. CONCLUSIONS: Our new staging system exhibited slightly better prognostic value compared to the TNM9th staging systems for nonmetastatic ASCC and warrants further validation.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.

Prognostic value of PD-L1 expression in patients with anal cancer: a meta-analysis.

Background: The present meta-analysis was performed to evaluate the prognostic and clinicopathological significance of PD-L1 in anal cancer (AC). Methods: Hazard ratios (HRs) and 95% CIs regarding overall survival (OS) and progression-free survival (PFS) were calculated based on PD-L1 levels. Results: According to the combined data, PD-L1 showed no significant relationship with OS (HR = 0.76; 95% CI = 0.35-1.67; p = 0.502) or PFS (HR = 0.88; 95% CI = 0.35-2.33; p = 0.789) in patients with AC. Based on subgroup analysis, PD-L1 overexpression significantly predicted prolonged OS (HR = 0.38; 95% CI = 0.17-0.84; p = 0.017) in tumor node metastasis stages I-III and inferior PFS (HR = 2.73; 95% CI = 1.32-5.65; p = 0.007) in patients with stage I-IV AC. Conclusion: PD-L1 level assessed by immunohistochemistry did not significantly predict survival outcomes in AC cases.

[Box: see text].

A five-year review of chemoradiotherapy practice in anal cancer: Radiotherapy audit results from a cancer centre in Wales, UK.

AIM: To review a five-year clinical practice of radical chemoradiotherapy (CRT) for anal cancers at a cancer centre in Wales. METHODS: A retrospective audit examined the quality of radical CRT for anal cancers treated between November 2016 and November 2021 by investigating seven critical indicators set by Radiation Therapy Oncology Group and ACT II trials, (1) 95% completion of computed tomography simulation within 14 days of consent, (2) 100% CRT delivery within 28 days of computed tomography simulation, (3) 100% CRT delivery within 28 days of consent, (4) overall treatment time of RT 38 days with > 2 days breaks <5%, (5) 75% completion of concurrent chemotherapy, (6) <2% CRT related colostomies, and (7) <2% the 30-days mortality rate. RESULTS: A total of 80 anal cancers received CRT over five years. Around 95.0% underwent computed tomography simulation within 14 days of consent. The observed slight deviation was related to the Covid pandemic in 2020. About 96.3% started CRT within 28 days of computed tomography simulation. The mean duration of CRT was 37.9 days. Radiotherapy (RT) interruptions > 2 days were about 5%, and 67.5% started CRT within 28 days of consent. About 92.5% and 76.2% completed mitomycin and capecitabine without breaks, respectively. The colostomy rate was 1.2%, and the 30-day mortality was 1.2%. CONCLUSION: Audit results matched with the standards in six domains. Overall treatment time of 37.9 days, colostomy rates of 1.2%, and the 30-day mortality rate of 1.2% were commendable. Overall time interval between consent and CRT delivery can be achieved by time-constrained measures.

A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy.

PURPOSE: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). METHODS: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). RESULTS: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. CONCLUSIONS: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

Simultaneous Integrated Boost (SIB) Versus Sequential Boost in Anal Cancer Patients: A Single-Center Experience.

PURPOSE: Concurrent chemoradiation is the standard of care for the treatment of anal cancer. Radiation can be delivered by sequential or simultaneous integrated boost (SIB) approach. The present study was conducted to compare the treatment outcomes and toxicity profile of patients with anal cancer treated with sequential boost and SIB approach. METHODS: A single-institution retrospective analysis of patients with squamous cell carcinoma of the anal canal treated between 2019 and 2022 with radical chemoradiation was performed. The sequential boost schedule consisted of 45 Gy in 25 fractions (1.8 Gy daily) to the gross tumor, nodes, and elective nodal volume, followed by a 9 Gy in five fractions boost to the gross disease. Patients receiving SIB were treated as per RTOG 0529 protocol. In both the groups, patients were treated with volumetric modulated arc therapy (VMAT). The two groups were compared in terms of overall survival (OS), colostomy-free survival (CFS), relapse-free survival (RFS), and acute toxicity profile. p-values < 0.05 were considered statistically significant. RESULTS: The patient and disease characteristics in both treatment arms were comparable. The only difference was a significantly longer overall treatment time of ≥ 50 days in the sequential arm (77.8% vs 43.8%, p = 0.04). The median follow-up was 18 months. The 2-year CFS was 80% in sequential vs 87.5% at 2 years for the SIB arm, 2-year OS 83.3% vs 58.6%, and 2-year RFS was 38.9% vs 41.7%, respectively. A total of 14 (77.8%) in sequential and 8 (50%) in the SIB arm had disease relapse. On univariate analysis, the involved pelvic lymph node significantly affected OS (HR 10.45, p = 0.03) while inguinal lymph node involvement adversely affected RFS (HR 6.16, p = 0.02). The most common acute toxicity was radiation-induced dermatitis, 15 (83.4%; 5 grade II, 10 grade III) in sequential vs 7 (43.8%; 3 each grade II and III) in the SIB group followed by hematological (61.1% vs 68.75%). However, the incidence of overall acute toxicities was significantly less in the SIB arm (p = 0.006). CONCLUSION: Our study showed that concurrent chemoradiation with the SIB-VMAT approach is well tolerated in patients of anal carcinoma and resulted in lesser treatment interruptions and comparable outcomes as compared to the sequential approach. Our results warrant further evaluation in a prospective study.

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.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Estudio comparativo de los resultados del tratamiento del carcinoma anal escamoso en los pacientes HIV positivos y negativos / Comparative study of the results of the treatment of squamous anal carcinoma in HIV positive and negative patients

Introducción: El tratamiento del carcinoma anal escamoso (CAE) en los pacientes HIV positivos resulta controvertido. Si bien las guías actuales recomiendan realizar en los pacientes con buen estado inmunológico la quimiorradioterapia (QRT) concurrente estándar, algunos autores consideran que estos pacientes presentan mayor toxicidad y peores resultados a largo plazo, por lo que requerirían un abordaje diferente. El objetivo de este trabajo es comparar los resultados del tratamiento del CAE en los pacientes VIH positivos y negativos. Diseño: Estudio retrospectivo comparativo. Pacientes y métodos: Se revisaron retrospectivamente las historias clínicas de los pacientes tratados en el Sector Coloproctología, Hospital Fernández, entre 01/2007 y 10/2018. Los del conducto anal se dividieron en: Grupo I: VIH negativos y Grupo II: VIH positivos. Se compararon variables demográficas, factores de riesgo específicos, estadificación, QRT (drogas, toxicidad y respuesta), tratamiento quirúrgico curativo/paliativo, persistencia/recurrencia y supervivencia específica y global. Resultados: Se incluyeron 28 pacientes (18 mujeres); margen: 2, conducto: 26 (Grupo I: 15. Grupo II: 11). Los VIH positivos eran en su mayoría hombres que tienen sexo con hombres vs. 100% de mujeres VIH negativas (p<0,01), más jóvenes (45,2±0,9 vs. 63,6±8; p<0,01) y tabaquistas (82% vs. 27%; p=0,005). No hubo diferencia significativa en la estadificación, aunque el Grupo II tuvo tumores con complicaciones más severas. Pudieron completar el tratamiento: Grupo I: 93%, Grupo II: 64% (p<0,05). Tuvieron respuesta completa a la QRT 13/14 (93%) pacientes del Grupo I y 3/7 (43%) del Grupo II (p<0,01). Hubo 3 recurrencias, 2 locorregionales y 1 a distancia (p=NS). Los VIH positivos requirieron más cirugías (82% vs. 27%; p<0,01). A 5 pacientes (4 del Grupo II) se les realizó una resección abdominoperineal (RAP). Tuvieron colostomía definitiva, con o sin RAP, el 46% de los pacientes, la mayoría VIH positivos (82% vs. 27%; p=0,002). En los VIH positivos el RR de mortalidad por cáncer fue 4 (IC95%: 1,01-16,5; p=0,02) y el RR de mortalidad global fue 5,45 (IC95%: 1,42-20,8; p=0,002). Tuvieron menor supervivencia, tanto global (p=0,001) como libre de enfermedad (p=0,01). Mediana de seguimiento: 27 meses (4-216).Conclusiones: Los pacientes VIH positivos con CAE se diferenciaron de los VIH negativos en una menor tasa de respuesta completa a la QRT y una mayor necesidad de tratamiento quirúrgico. Además, tuvieron una supervivencia global y libre de enfermedad significativamente menor que los VIH negativos. (AU)

INTRODUCTION: The treatment of anal squamous cell carcinoma (SCC) in HIV-positive patients is controversial. Although current guidelines recommend performing standard concurrent chemoradiotherapy (CRT) in patients with good immune status, some authors believe that these patients have greater toxicity and worse long-term results, so they would require a different approach. The purpose of this study was to compare the results of SCC treatment in HIV-positive and HIV-negative patients.DESIGN: Comparative retrospective study.PATIENTS AND METHODS: The records of patients treated in the Coloproctology Section, Hospital Fernández, between 01/2007 and 10/2018 were retrospectively reviewed. Those of the anal canal were divided into: Group I: HIV-negative and Group II: HIV-positive. Demographic variables, specific risk factors, staging, CRT (drugs, toxicity, and response), curative/palliative surgical treatment, persistence/recurrence, and cancer-specific and global survival were compared.RESULTS: 28 patients (18 women), margin: 2, conduit: 26 (Group I: 15. Group II: 11). The HIV-positive were mostly men who have sex with men (vs. 100% HIV-negative women; p<0.01), younger (45.2 ± 0.9 vs. 63.6 ± 8; p<0.01) and smokers (82% vs. 27%; p=0.005). There was no significant difference in staging, although Group II had tumors with more severe complications. Completed the treatment: Group I: 93%, Group II: 64% of patients (p<0,05). Thirteen out of 14 (93%) patients in Group I, and 3/7 (43%) patients in Group II had a complete response to CRT (p<0.01). There were 3 recurrences, 2 loco-regional and 1 distance (p=NS). HIV-positive required more surgery (82% vs. 27%; p<0.01). 5 patients (4 of Group II) underwent an abdominal-perineal resection (APR). Forty six percent of patients had permanent colostomy, with or without APR, most of them were HIV-positive (82% vs. 27%; p=0.002). In HIV-positive patients, the RR of cancer mortality was 4 (95% CI: 1.01-16.5; p=0.02) and the RR of overall mortality was 5.45 (95% CI: 1.42-20, 8; p=0.002). They also had lower overall (p=0.001) and disease-free survival (p=0.01). Median follow-up: 27 months (4 - 216).CONCLUSION: HIV-positive patients with anal SCC were different from HIV-negative patients in that they had a lower complete response rate to CRT, and a greater need for surgical treatment. They had a significantly lower overall and disease-free survival than HIV-negative patients. (AU)

Extended pelvic resections for the treatment of locally advanced and recurrent anal canal and colorectal cancer: technical aspects and morbimortality predictors aftet 24 consecutive cases / Ressecções pélvicas alargadas no tratamento do câncer colorretal e de canal anal localmente avançado ou recidivado: análise dos aspectos técnicos e fatores de morbimortalidade em 24 casos consecutivos

ABSTRACT Objective: to evaluate the profile of morbidity and mortality and its predictors related to extensive pelvic resections, including pelvic exenteration, to optimize the selection of patients and achieve better surgical results. Methods: we performed 24 major resections for anorectal pelvic malignancy from 2008 to 2015 in the Instituto do Câncer do Ceará. The factors analyzed included age, weight loss, resected organs, total versus posterior exenteration, angiolymphatic and perineural invasion, lymph node metastasis and overall and disease-free survival. Results: the median age was 57 years and the mean follow-up was ten months. Overall morbidity was 45.8%, with five (20.8%) serious complications. There were no deaths in the first 30 postoperative days. The median overall survival was 39.5 months, and disease-free survival, 30.7 months. Concomitant resection of the bladder was an isolated prognostic factor for higher risk of complications (87.5% vs. 26.7%, p = 0.009). Angiolymphatic invasion and lymph node metastasis did not reach significance with respect to disease-free survival. Conclusion: treatment of advanced anorectal tumors is challenging, often requiring combined resections, such as cystectomy and sacrectomy, and complex reconstructions. The magnitude of the operation still carries a high morbidity rate, but is a procedure considered safe and feasible, with a low mortality and adequate locoregional tumor control when performed in referral centers.

RESUMO Objetivos: avaliar o perfil de morbimortalidade e seus fatores preditivos relacionados às ressecções pélvicas extensas, incluindo a exenteração pélvica, com o intuito de otimizar a seleção dos pacientes e obtenção de melhores resultados cirúrgicos. Métodos: foram realizadas 24 grandes ressecções pélvicas por neoplasia maligna anorretal de 2008 a 2015 no Instituto do Câncer do Ceará. Os fatores analisados incluíram idade, perda de peso, órgão ressecados, exenteração total versus posterior, invasão angiolinfática e perineural, metástase linfonodal e sobrevida global e livre de doença. Resultados: a mediana de idade foi 57 anos e o tempo médio de seguimento foi dez meses. A morbidade global foi 45,8%, com cinco (20,8%) complicações graves. Não houve óbito nos primeiros 30 dias de pós-operatório. A sobrevida global média foi 39,5 meses e a sobrevida livre de doença foi 30,7 meses. A ressecção concomitante da bexiga foi fator prognóstico isolado com maior risco para complicações (87,5% vs. 26,7%, p=0.009). Invasão angiolinfática e metástase linfonodal não alcançaram significância com relação à sobrevida livre de doença. Conclusão: o tratamento dos tumores anorretais avançados é desafiador, necessitando frequentemente de ressecções combinadas, como a cistectomia e sacrectomia, além de reconstruções complexas. A magnitude da cirurgia ainda carrega uma elevada taxa de morbidade, porém é um procedimento considerado seguro e factível, com uma baixa mortalidade e adequado controle locorregional tumoral quando realizado em centros de referência.

Melanoma anorrectal / Anorectal melanoma

Los tumores de conducto y margen de ano son raros. De ellos, las neoplasias más frecuentes son las de origen epidermoide y las provenientes de las glándulas anales. El melanoma anorrectal representa una frecuencia menor al 5 por ciento de todos los tumores del ano. Se caracterizan por tener un mal pronóstico, gran tendencia a las metástasis a distancia, diagnóstico tardío y no presentar un consenso con respecto al tratamiento quirúrgico y falta o pobre respuesta a la adyuvancia. Las únicas series publicadas corresponden a experiencias de centro de referencia seguidas a lo largo de décadas. El resto son en su mayoría, reportes de casos clínicos, tanto en la literatura nacional como internacional. Tenemos como objetivo revisar los distintos aspectos de esta patología y analizar los resultados de las principales series publicadas en referencia al tipo de tratamiento quirúrgico y su impacto en la sobrevida y en los índices de recurrencia.

Tumors of the anal canal and those which compromise the anal margin are unfrequent. Epidermoid followed by adenocarinoma are the most frequent types of anal cancer. Primary anorectal melanoma reports a low incidence, below 5 per cent according to different reports. Anorectal melanoma has poor prognosis, diagnosis is often made as an advanced disease with distant metastasis, surgical treatment is controversial and there is no consensus, and the response to adyuvant therapy is depressing. There are a few published series following through decades. Mostly the literature reffers case reports. The objetive of this review is to analyze aspects and results of this entity and different types of surgical treatment, live-free survival and recurrence.

Operación de Lockhart Mummery / Lockhart-Mummery surgery

La operación de Lockhart Mummery, difundida por este autor entre 1907 y 1926, constituyó por esos años la primera indicación en el tratamiento del cáncer de recto, debido a la inaceptable mortalidad de la amputación abdomino-perineal. Los avances en el manejo peroperatorio, sumado a los malos resultados oncológicos de este procedimiento, lo relegaron marcadamente. Sin embargo creemos que aún puede tener un rol en enfermos tratados con fines paliativos y con un elevado riesgo quirúrgico, y en menor medida en otras patologías como por ejemplo el cáncer de ano. Entre 1964 y 1995 realizamos 22 operaciones de Lockhart Mummery, 16 de ellas por cáncer de recto, lo que constituyó el 4,7 por ciento del total de pacientes tratados con este tumor. Otras indicaciones fueron cáncer de ano en 5 casos, y enfermedad de Crohn en el restante. Se analizaron retrospectivamente los resultados inmediatos. Se registró una morbilidad del 32 por ciento, se debió reoperar el 13,6 por ciento de los enfermos, y la mortalidad fue del 4,5 por ciento. Estos resultados son comparables a los registrados en nuestro medio con la operación de Miles, teniendo en cuenta que optamos por la operación de Lockhart Mummery en pacientes con enfermedad avanzada y de alto riesgo. En base a los resultados observados en una población de muy alto riesgo, consideramos a esta operación una aceptable opción para el tratamiento de casos seleccionados de cáncer de recto, fundamentalmente con fines paliativos

Segunda encuesta, cáncer de colon, recto y ano / Second survey, colon, rectum and anus cancer

Esta encuesta cubre los años 1985 a 1989 y sumada a la primera, estudia en conjunto 15 años, de 1975 a 1989 y suma en total 9392 pacientes. Se interrogó sexo, edad, localización tumoral, histopatología, estadío, presencia de oclusión intestinal y metástasis alejadas. Así también en el aspecto terapéutico se inquirió sobre los procedimientos efectuados, número de pacientes resecados, criterios de resección, complicaciones y tratamientos complementarios. Se solicitaron datos sobre mortalidad y recidivas locales. Se efectuaron consideraciones sobre los resultados hallados y sobre la comparación de ambas encuestas, que señalan una notable evolución en los procedimientos efectuados. Esta revisión cooperativa permite reunir datos sobre la patología y tratamiento del cáncer de colon, recto y ano en un número importante de pacientes en Argentina