RESUMO
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.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Humanos , Neoplasias do Ânus/patologia , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adulto , Elétrons/uso terapêutico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Margens de Excisão , Dosagem RadioterapêuticaRESUMO
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.
Assuntos
Neoplasias do Ânus , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/mortalidade , Idoso , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Estudos Retrospectivos , Canal Anal/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidadeRESUMO
BACKGROUND: Chemo-radiotherapy with curative intent for anal cancer has high complete remission rates, but acute treatment-related gastrointestinal (GI) toxicity is significant. Toxicity occurs due to irradiation of surrounding normal tissue. Current radiotherapy requires the addition of large planning margins to the radiation field to ensure target coverage regardless of the considerable organ motion in the pelvic region. This increases the irradiated volume and radiation dose to the surrounding normal tissue and thereby toxicity. Online adaptive radiotherapy uses artificial intelligence to adjust the treatment to the anatomy of the day. This allows for the reduction of planning margins, minimizing the irradiated volume and thereby radiation to the surrounding normal tissue.This study examines if cone beam computed tomography (CBCT)-guided oART with daily automated treatment re-planning can reduce acute gastrointestinal toxicity in patients with anal cancer. METHODS/DESIGN: The study is a prospective, single-arm, phase II trial conducted at Copenhagen University Hospital, Herlev and Gentofte, Denmark. 205 patients with local only or locally advanced anal cancer, referred for radiotherapy with or without chemotherapy with curative intent, are planned for inclusion. Toxicity and quality of life are reported with Common Terminology Criteria of Adverse Events and patient-reported outcome questionnaires, before, during, and after treatment. The primary endpoint is a reduction in the incidence of acute treatment-related grade ≥ 2 diarrhea from 36 to 25% after daily online adaptive radiotherapy compared to standard radiotherapy. Secondary endpoints include all acute and late toxicity, overall survival, and reduction in treatment interruptions. RESULTS: Accrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026. DISCUSSION: This is the first study utilizing online adaptive radiotherapy to treat anal cancer. We hope to determine whether there is a clinical benefit for the patients, with significant reductions in acute GI toxicity without compromising treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093.
Assuntos
Neoplasias do Ânus , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Humanos , Qualidade de Vida , Estudos Prospectivos , Inteligência Artificial , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/etiologia , Resultado do Tratamento , Planejamento da Radioterapia Assistida por Computador/métodos , Diarreia/etiologia , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Ensaios Clínicos Fase II como AssuntoRESUMO
PURPOSE: To investigate the differences in baseline staging of anal squamous cell carcinoma based on CT, MRI, and PET/CT, and the resultant impact on the radiation plan. METHODS: This retrospective study included consecutive patients with anal squamous cell carcinoma who underwent baseline pelvic MRI, CT, and PET/CT (all examinations within 3 weeks of each other) from January 2010 to April 2020. CTs, MRIs, and PET/CTs were re-interpreted by three separate radiologists. Several imaging features were assessed; tumor stage was determined based on the eight edition of the American Joint Committee on Cancer (AJCC) staging manual; and T (tumor), N (node), and M (metastasis) categories were determined based on National Comprehensive Cancer Network (NCCN) guidelines. Radiologist assessments were then randomly presented to a radiation oncologist who formulated the radiation plan in a blinded fashion. RESULTS: Across 28 patients (median age, 62 years [range, 31-78], T-category classification was significantly different on PET/CT compared to MRI and CT (p = 0.037 and 0.031, respectively). PET/CT staged a higher proportion of patients with T1/T2 disease (16/28, 57%) compared to MRI (11/28, 39%) and CT (10/28, 36%). MRI staged a higher proportion of patients with T3/T4 disease (14/28, 50%) compared to CT (12/28, 43%) and PET/CT (11/28, 39%). However, there was no significant difference between the three imaging modalities in terms of either N-category, AJCC staging, or NCCN TNM group classification, or in treatment planning. CONCLUSION: Our exploratory study showed that MRI demonstrated a higher proportion of T3/T4 tumors, while PET/CT demonstrated more T1/T2 tumors; however, MRI, CT, and PET/CT did not show any significant differences in AJCC and TNM group categories, nor was there any significant difference in treatment doses between them when assessed independently by an experienced radiation oncologist.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Adulto , Tomografia Computadorizada por Raios X/métodos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Anal and rectal cancers were some of the first disease sites treated with brachytherapy due to the anatomic ease of implantation. As external beam radiotherapy grew in popularity the use of ano-rectal brachytherapy declined. However, the past few years have seen a steady resurgence in the use of brachytherapy in the ano-rectum supported by the use of large clinical series and randomized trials. The increasing acceptance by the surgical community of organ preservation as a valid treatment strategy for rectal cancer has encouraged the use of nonsurgical approaches and brachytherapy has shown itself to be a valuable tool for this. The current role of anal and rectal brachytherapy is presented with perspectives on its future use.
Assuntos
Neoplasias do Ânus , Braquiterapia , Neoplasias Retais , Humanos , Braquiterapia/métodos , Reto , Neoplasias do Ânus/radioterapia , Neoplasias Retais/radioterapia , Canal AnalRESUMO
PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.
Assuntos
Neoplasias do Ânus , Gastroenteropatias , Humanos , Algoritmo Florestas Aleatórias , Cavidade Peritoneal , Neoplasias do Ânus/radioterapia , Quimiorradioterapia/efeitos adversos , Gastroenteropatias/etiologiaRESUMO
PURPOSE: To evaluate the variability of the 18F-FDG-PET/CT-based metabolic tumor volume (MTV) in anal cancers during fractionated chemoradiotherapy (CRT), and assess the impact of this variability on dosimetric accuracy in MTV-targeted dose painting. METHODS: Eleven patients with anal squamous cell carcinoma who received fractionated chemoradiotherapy with curative intent were included. 18F-FDG PET/CT images were acquired at pre- and mid-treatment. Target volumes and organs at risk (OARs) were contoured manually on both image series. The MTV was generated from the PET images by thresholding. Treatment plans were retrospectively optimized for both image series using volumetric modulated arc therapy (VMAT). Standard plans prescribed 48.6 Gy, 54 Gy and 57.5 Gy in 27 fractions to elective regions, lymph node metastases and primary tumor, respectively. Dose painting plans included an extra dose level of 65 Gy to the MTV. Pre-treatment plans were transferred and re-calculated at mid-treatment basis. RESULTS: MTV decreased from pre- to mid-treatment in 10 of the 11 patients. On average, 71 % of MTVmid overlapped with MTVpre. The median and mean doses to the MTV were robust against anatomical changes, but the transferred dose painting plans had lower D98% values than the original and re-optimized plans. No major differences were found between standard and dose painting plans for OARs. CONCLUSIONS: Despite volumetric changes in the MTV, adequate dose coverage was observed in most dose painting plans. The findings indicate little or no need for adaptive dose painting at mid-treatment. Dose painting appears to be a safe treatment alternative with similar dose sparing of OARs.
Assuntos
Neoplasias do Ânus , Radioterapia de Intensidade Modulada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Carga Tumoral , Estudos Retrospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapiaRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Neoplasias do Ânus , Motivação , Humanos , Qualidade de Vida , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/tratamento farmacológico , Resultado do Tratamento , QuimiorradioterapiaRESUMO
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.
Assuntos
Neoplasias do Ânus , Radioterapia de Intensidade Modulada , Humanos , Mitomicina/uso terapêutico , Capecitabina/uso terapêutico , Fluoruracila/uso terapêutico , Estudos de Coortes , Estudos Prospectivos , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapiaRESUMO
Background: To date, anal cancer patients are treated with radiotherapy to similar volumes despite a marked difference in risk profile based on tumor location and stage. A more individualized approach to delineation of the elective clinical target volume (CTVe) could potentially provide better oncological outcomes as well as improved quality of life. The aim of the present work was to establish Nordic Anal Cancer (NOAC) group guidelines for delineation of the CTVe in anal cancer.Methods: First, 12 radiation oncologists reviewed the literature in one of the following four areas: (1) previous delineation guidelines; (2) patterns of recurrence; (3) anatomical studies; (4) common iliac and para-aortic recurrences and delineation guidelines. Second, areas of controversy were identified and discussed with the aim of reaching consensus.Results: We present consensus-based recommendations for CTVe delineation in anal cancer regarding (a) which regions to include, and (b) how the regions should be delineated. Some of our recommendations deviate from current international guidelines. For instance, the posterolateral part of the inguinal region is excluded, decreasing the volume of irradiated normal tissue. For the external iliac region and the cranial border of the CTVe, we agreed on specifying two different recommendations, both considered acceptable. One of these recommendations is novel and risk-adapted; the external iliac region is omitted for low-risk patients, and several different cranial borders are used depending on the individual level of risk.Conclusion: We present NOAC consensus guidelines for delineation of the CTVe in anal cancer, including a risk-adapted strategy.
Assuntos
Neoplasias do Ânus , Radioterapia de Intensidade Modulada , Humanos , Anticoagulantes , Qualidade de Vida , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/patologia , Planejamento da Radioterapia Assistida por ComputadorRESUMO
The hybrid magnetic resonance image (MRI) scanner and radiation therapy linear accelerator (MR-Linac) has the potential to enhance clinical outcomes for anal cancer (AC) patients with improved soft tissue visualization and daily plan adaption but has planning and delivery limitations due to the incorporation of MRI. We aimed to identify if Elekta Unity MR-Linac-based radiation therapy is feasible for anal cancer. Ten prospectively enrolled AC patients treated with radical chemoradiotherapy were replanned for MR-Linac treatment using departmental planning criteria. For comparison, and to reduce interobserver variability, volumetric modulated arc radiation therapy (VMAT) plans were also created for each patient by the same single senior radiation therapist. Plans were compared using departmental dosimetric plan criteria, as well as conformity and homogeneity indices, monitor units (MUs) and measured plan delivery (beam-on) time. Results were deemed clinically acceptable. Target and organ at risk (OAR) doses were comparable between MR-Linac plans and VMAT plans, although PTV45Gy D98% coverage was compromised in 3 of 10 MR-Linac plans due to caudocranial length exceeding the limits of the MR-Linac. MR-Linac plans had lower MUs, median of 689.1 vs 849.65 (p = 0.002), but took over twice as long to deliver, 529.5s vs 224s (p = <0.0001) as VMAT plans. MR-Linac planning and treatment of AC is feasible for a subset of patients. The current physical limitations of the Elekta Unity system mean patients with large caudocranial elective PTV45Gy target volumes may not be covered dosimetrically to the required clinical standard. Longer image verification and treatment delivery times of the MR-Linac also mean patient selection and intrafractional IGRT are likely to be integral to ensuring high quality clinical outcomes in this rare cancer.
Assuntos
Neoplasias do Ânus , Radioterapia de Intensidade Modulada , Humanos , Estudos de Viabilidade , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Aceleradores de Partículas , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Ânus/radioterapiaRESUMO
BACKGROUND: Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus mitomycin-C is a standard treatment for stage II/III squamous cell carcinoma of the anal canal (SCCA). We performed this dose-finding and single-arm confirmatory trial of CRT with S-1 plus mitomycin-C to determine the recommended dose (RD) of S-1 and evaluate its efficacy and safety for locally advanced SCCA. METHODS: Patients with clinical stage II/III SCCA (UICC 6th) received CRT comprising mitomycin-C (10 mg/m2 on days 1 and 29) and S-1 (60 mg/m2/day at level 0 and 80 mg/m2/day at level 1 on days 1-14 and 29-42) with concurrent radiotherapy (59.4 Gy). Dose-finding used a 3 + 3 cohort design. The primary endpoint of the confirmatory trial was 3-year event-free survival. The sample size was 65, with one-sided alpha of 5%, power of 80%, and expected and threshold values of 75% and 60%, respectively. RESULTS: Sixty-nine patients (dose-finding, n = 10; confirmatory, n = 59) were enrolled. The RD of S-1 was determined as 80 mg/m2/day. Three-year event-free survival in 63 eligible patients who received the RD was 65.0% (90% confidence interval 54.1-73.9). Three-year overall, progression-free, and colostomy-free survival rates were 87.3%, 85.7%, and 76.2%, respectively; the complete response rate was 81% on central review. Common grade 3/4 acute toxicities were leukopenia (63.1%), neutropenia (40.0%), diarrhea (20.0%), radiation dermatitis (15.4%), and febrile neutropenia (3.1%). No treatment-related deaths occurred. CONCLUSIONS: Although the primary endpoint was not met, S-1/mitomycin-C chemoradiotherapy had an acceptable toxicity profile and favorable 3-year survival and could be a treatment option for locally advanced SCCA. CLINICAL TRIAL INFORMATION: jRCTs031180002.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Humanos , Mitomicina , Canal Anal/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Fluoruracila , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , CisplatinoRESUMO
PURPOSE: To compare toxicity of radiotherapy (RT) with concomitant chemotherapy (CHT) in patients (pts) with anal cancer treated with simultaneous integrated boost (SIB) versus sequential boost (SeqB). METHODS: Sixty-six patients were treated from 2007 to 2021. Thirty patients underwent to SeqB concurrent to CHT and 37 to SIB-group. Toxicity assessment has been considered in acute and in late toxicities for gastrointestinal (GI), genitourinary (GU), cutaneous (CU) districts, according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. The Wexner scale among summary scoring systems has been used as a tool to measure fecal incontinence. The chi-square test for ordinal variables were used to evaluate the association between patient and treatment characteristics and acute or late severe toxicity. Univariable logistic regression models were fit to evaluate predictive factors associated with fecal incontinence. RESULTS: Median follow-up was 61.5 months (IQR, 27.1-121.7 months) for all patients. Severe acute toxicity (≥ G2) was observed in 49 patients (74.2%). Late toxicity (≥ G2) occurred in 13 cases (19.6%). In assessment of cutaneous toxicity, there was also a significant reduction in ≥ G1 in SIB group with 29 patients (80.5%) vs SeqB group with 29 patients (96.6%) (p-value = 0.046). Of both groups 11 patients (16.6%) developed fecal incontinence, 8 (22%) in the SIB group and 3 (10%) in the SeqB. CONCLUSION: SIB for anal cancer treatment results in reduced acute and late cutaneous toxicity compared to SeqB. According to our results the rate of other acute and late toxicities are low and comparable between the two groups.
Assuntos
Neoplasias do Ânus , Incontinência Fecal , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Incontinência Fecal/etiologia , Dosagem Radioterapêutica , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapiaRESUMO
PURPOSE: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT). METHODS: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529. RESULTS: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment. CONCLUSIONS: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.
Assuntos
Neoplasias do Ânus , Gastroenteropatias , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Terapia com Prótons/efeitos adversos , Estudos de Viabilidade , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/etiologia , Dosagem RadioterapêuticaRESUMO
PURPOSE: Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. METHODS: Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020â¯at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). RESULTS: The 87 patients received treatment with a median boost of 63â¯Gy to the primary tumor. With a median follow-up of 32 months, the 3year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to >â¯63â¯Gy (maximum 66.6â¯Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3year CFS (82.4% vs. 97%, Pâ¯= 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, Pâ¯= 0.008), and a significantly improved 3year PFS for T1/T2 tumors (76.7% vs. 100%, Pâ¯= 0.035). While acute toxicities did not differ, dose escalation >â¯63â¯Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, Pâ¯= 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3year OS (75.4% vs. 53.8%, Pâ¯= 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation >â¯63â¯Gy was also apparent in multivariate analysis (Pâ¯= 0.067). CONCLUSION: Dose escalation >â¯63â¯Gy (maximum 66.6â¯Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Radioterapia de Intensidade Modulada , Humanos , Recidiva Local de Neoplasia/etiologia , Resultado do Tratamento , Radioterapia de Intensidade Modulada/efeitos adversos , Quimiorradioterapia/efeitos adversos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/tratamento farmacológico , Células Epiteliais/patologia , Estudos RetrospectivosRESUMO
PURPOSE: To optimize inguinal nodal clinical target volume (CTV) delineation based on analysis of the anatomical locations and embryonic development of normal and metastatic inguinal lymph nodes (ILNs) in patients with pelvic malignant tumors, including cervical, vaginal, vulvar, and anal tumors. MATERIALS AND METHODS: One hundred and eighty-one patients with pelvic malignancies and 415 involved ILNs treated with intensity-modulated radiation therapy were selected. First, the inguinal nodal CTV was divided into three fields as follows: I, horizontal superficial inguinal field; II, vertical superficial inguinal field; and III, deep inguinal field. Initial CTV delineation of each field was based on analysis of the anatomical locations and embryonic development of normal ILNs. Subsequently, the positions of metastatic ILNs relative to the proper anatomical landmarks or vessels were determined to optimally delineate the final ILN CTV contours. Eighty percent of the data acquired (n = 145) were used as test data for optimization and analysis, the remaining 20% (n = 36) were used for delineation validation. RESULTS: In total, 252 positive ILNs in 103 cervical cancer patients, 94 positive ILNs in 41 vulvar cancer patients, 8 positive ILNs in 3 vaginal cancer patients, and 61 positive ILNs in 34 anal cancer patients were enrolled. Detailed target volume contouring guidelines for the three divisions were determined on images. All positive ILNs from the remaining 20% patients were located in the CTV boundaries delineated based on analysis of 80% of the data acquired. Importantly, the final inguinal nodal CTV field determined using our method was substantially smaller than defined by existing atlases, and the femoral vessels were excluded in the delineation. CONCLUSIONS: This study provided anatomical, embryonic, surgical, and statistical evidence to facilitate ILN CTV delineation in radiotherapy planning for patients with pelvic malignancies.
Assuntos
Neoplasias do Ânus , Neoplasias Pélvicas , Radioterapia de Intensidade Modulada , Feminino , Humanos , Neoplasias Pélvicas/radioterapia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/patologia , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
OBJECTIVE: To identify best treatment practices by examining outcomes of anal margin cancer patients treated with radiotherapy. METHODS: Relevant literature was compared with 38 patients at our institution treated 1979 to 2019 with curative radiotherapy. Median age was 51. Four patients had T1, 22 had T2, and 12 had T3 disease based on the American Joint Committee on Cancer (AJCC) staging at time of diagnosis. Nodal staging distribution was: N0=33; N1=2; N2=2; N3=1. Median radiation dose was 56 Gy/30 fractions. Five received nodal radiation for node positivity, 29 received elective nodal radiation, and 29 had perineal boost. Twenty-seven received concurrent chemotherapy. RESULTS: Three patients experienced isolated local recurrence, 2 had isolated inguinal node recurrences, and 2 developed distant metastases, 1 of whom also had local and regional recurrence. Ten-year disease-free survival (DFS), cause-specific survival, and overall survival were 87%, 92%, and 68%, respectively. One patient did not complete radiation, and 4 had unexpected treatment breaks. Two received salvage abdominoperineal resections. At last follow-up, 17 were alive with no evidence of disease, 2 were alive with anal margin cancer present, 3 had died with anal margin cancer present at 11, 18, and 21 months from radiation therapy, and 16 had died from intercurrent disease. Median follow-up was 6.6 years (range 0.9 to 29.0 y). Age ≥51 was associated with worse locoregional control ( P =0.018) and DFS ( P =0.0233), males had worse DFS ( P =0.0311), and HIV-positive patients had worse overall survival ( P =0.006). CONCLUSIONS: Radiation provides high locoregional control of anal margin cancer with good long-term outcomes.
Assuntos
Neoplasias do Ânus , Masculino , Humanos , Pessoa de Meia-Idade , Terapia Combinada , Intervalo Livre de Doença , Neoplasias do Ânus/radioterapia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologiaRESUMO
PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.
Assuntos
Neoplasias do Ânus , Estomas Cirúrgicos , Feminino , Humanos , Qualidade de Vida , Reprodutibilidade dos Testes , Neoplasias do Ânus/radioterapia , Inquéritos e Questionários , Psicometria/métodosRESUMO
BACKGROUND AND PURPOSE: Patients with anal squamous cell carcinoma (SCC) are treated with sphincter-preserving radiation therapy and concurrent chemotherapy, achieving excellent oncologic outcomes. Patients, however, may experience treatment-related morbidity including sexual dysfunction. The objective of this systematic review was to review the literature on sexual dysfunction in female patients treated for anal cancer and to identify knowledge gaps. MATERIALS AND METHODS: This systematic review was registered in PROSPERO prior to initiation. Databases searched included MEDLINE, Embase, PubMed, Cochrane, and Google Scholar. There were no restrictions on the study time period. Studies were limited to English. All study designs were included except review articles, letters to the editor, and case reports with less than ten patients. RESULTS: In total, 1801 studies were retrieved and 19 met the inclusion criteria, including: 13 cross-sectional surveys, 3 prospective studies, 1 longitudinal intervention study, 1 retrospective chart review, 1 case control study. Sexual function was assessed using the female sexual functioning index (FSFI), EORTC-QLQ-CR30 and -CR38; response rates were low (<50 % in most studies). Sexual dysfunction was reported by up to 85 % of women; the most common symptoms being dyspareunia (17-65 %), vaginal dryness (22-88 %), and loss of libido (38-95 %). Gastrointestinal issues, such as bowel problems, and body image concerns additionally affected sexual function and quality of life. CONCLUSION: Sexual dysfunction is a common issue affecting most female patients treated for anal cancer and there is a paucity of evidence on the management of this important survivorship issue. There is additionally a lack of ethnic, economic, and educational diversity and there are no studies addressing the unique needs of LGBTQ individuals - future studies should make a concerted effort to include a diverse patient population.
Assuntos
Neoplasias do Ânus , Disfunções Sexuais Fisiológicas , Humanos , Feminino , Qualidade de Vida , Estudos de Casos e Controles , Estudos Retrospectivos , Estudos Transversais , Estudos Prospectivos , Neoplasias do Ânus/radioterapia , Disfunções Sexuais Fisiológicas/etiologiaRESUMO
PURPOSE: Pelvic recurrence of rectal or anal cancers is associated with considerable morbidity and mortality. We report our initial experience with an aggressive intra-operative radiotherapy (IORT) program. METHODS: Patients with locally advanced or recurrent rectal or anal cancers considered to have a high likelihood of R1 or R2 resection after multi-disciplinary review underwent surgical excision and IORT using a high-dose-rate afterloader (Ir-192) and HAM applicator. Endpoints included local or distant recurrence, and acute and late toxicity graded using the American College of Surgeons (ACS) NSQIP and the LENT-SOMA scale. RESULTS: Twenty-one patients, largely with prior history of both pelvic external beam radiotherapy (EBRT, median 50.4 Gy) and surgical resection, underwent excision with IORT (median dose 12.5 Gy, range 10-15). Median follow-up was 20 months. Twelve (57%) patients had failure at the IORT site. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF at 1 year 75% for R0 vs 15% for R1/2, p = 0.0065) but not re-irradiation EBRT or IORT dose (p > 0.05). Twelve, 5, and 13 patients experienced local, regional, and distant failure, respectively; 3 (14%) patients were disease-free at last follow-up. The most frequent acute toxicity was sepsis/abscess (24%). One patient (5%) required a ureteral stent; no patients developed neuropathy attributable to IORT. CONCLUSIONS: In patients treated with excision and IORT for locally recurrent cancer, R0 resection is a critical determinant of local control. For patients with R1/2 resection, poor disease-free outcomes warrant consideration of a different treatment strategy.