Radiation Therapy For Anal Cancer Research Articles

ROAR-A: re-optimization based Online Adaptive Radiotherapy of anal cancer, a prospective phase II trial protocol

BackgroundChemo-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/designThe 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.ResultsAccrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026.DiscussionThis 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 registrationClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093

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.

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

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

PO-1399 Bowel delineation methods and prediction of acute and late diarrhea in radiotherapy of anal cancer

PO-1399 Bowel delineation methods and prediction of acute and late diarrhea in radiotherapy of anal cancer

Estimated dose to site of loco-regional recurrence after radiotherapy in anal cancer using point of origin methods

Loco-regional recurrence (LRR) dominates the failure pattern after curative radiotherapy in anal cancer. The aim of this study was to estimate dose of LRRs in anal cancer using a point of origin-based method. Of 321 patients with squamous cell carcinoma of the anus, 31 patients with LRR (29 local recurrences and 5 regional lymph node recurrences) were available for analysis. The recurrence volumes were delineated on recurrence magnetic resonance imaging (rMRI). Rigid and subsequent deformable co-registration of planning computerised tomography scans and rMRI were performed. Point of origin was estimated as the centre of mass (COM) and an observer-based point of origin (obs-PO). Doses to COM and obs-PO, as well as the full recurrence volume, were estimated and the relation to target volumes was extracted. The median minimum dose to COM was 63.8Gy (range 32.5-65.1Gy) and 63.7Gy (range 35.5-65.2Gy) to obs-PO of local recurrences. COM was included in the high dose volume (64Gy) in 86% of cases, and obs-PO was included in 75% of cases. There was no difference in minimum dose to COM and obs-PO, and the median distance between the two points was 3.3mm (range 0.6-19.8mm). No recurrences occurred in primarily boosted lymph nodes. The majority of LLRs were located within the high dose volume indicating radioresistance as the primary cause of recurrence in anal cancer. No difference between the use of COM and obs-PO was evident.

Concurrent chemotherapy and radiation therapy for anal cancer: quality of life evaluation to improve person-centred care

Concurrent chemotherapy and radiation therapy for anal cancer: quality of life evaluation to improve person-centred care

Predict Post-Radiotherapy PET Image for Anal Cancer Patients Treated with Chemoradiation Using 3D U-Net Deep Learning

<h3>Purpose/Objective(s)</h3> This study aims to predict voxel-wise therapy response PET image for anal cancer radiotherapy utilizing pre-radiotherapy PET/CT, planning targets and dose, toward estimating the treatment outcome and reducing hematologic toxicity. <h3>Materials/Methods</h3> 18FDG-PET/CT scans were obtained from locally advanced anal cancer patients with 2-week prior to (pre-RT), 12-week following treatment (post-RT). All PET/CT images were registered to the planning CT. Patients were treated with the IMRT with the mean dose of 55.8Gy. The prediction of post-RT PET image was constructed by 3D U-Net deep learning with five spatial levels. The input of 3D U-Net has seven separate channels, including PTV, V40, pelvic bone, bladder, Pre-RT PET, planning CT, and planned dose. All images were resized to the volumes with 128 × 128 × 128 voxels. The prediction was calculated in the volume of interested (VOI) where the dose is larger than 5% prescribed dose. To reduce the bias due to high bladder uptake, the SUV in the bladder of post-RT PET was reduced to the mean liver uptakes, and the resultant post-RT PET images were used in the study. Online data augmentation was applied during both training and testing stages. The performance of the prediction model was evaluated by the voxel-based mean absolute error and joint histograms. The ANVOA was used to identify difference between the predicted post-RT PET images and ground truth images for VOIs, including PTV and OARs. <h3>Results</h3> Fifty-five patients with pre-RT and post-RT PET images were included in the study. Among them, 30 patients were randomly selected as training data set, and 10 patients were used for the validation set, and 15 patients were used as the test set. For the evaluated volumes (> 5% prescribed dose), the similarity of predicted image and ground truth were evaluated by the joint histogram with voxelwise correlation (mean correlation coefficient, 91. 21% +/- 5.36). The difference between the mean SUV of predicated PET image and the ground truth was evaluated by ANOVA with p=0.422. In the volume of PTV, the mean SUV of predicted image was 1.10+/-0.11, and 1.08+/-0.30 for ground truth, p=0.988. In the volume of V40, the mean SUV of predicted image was 1.00+/-0.06, and 1.05+/-0.20 for ground truth, p=0.549. We also evaluated the mean uptake of pelvic bone marrow with results of 0.89+/-0.20 for predicated image, and 0.81+/-0.11 for ground truth, p=0.261. Our results show that there is no significant difference in the target volumes and OARs between predicted PET image and ground truth images. <h3>Conclusion</h3> Our approach can effectively predict the post-RT PET image based on the pre-treatment image and treatment information. 3D deep learning prediction of metabolic treatment outcome provides a feasible approach for evaluating efficacy of local control of anal cancer treatment. The results can be used to predict local failure of disease, toward implementing response-driven adaptive radiotherapy.

Pelvic Insufficiency Fractures and Bone Pain after Radiation Therapy for Anal Cancer: Relation to Pelvic Bone Dose-Volume Parameters

PurposeChemoradiation therapy is the primary treatment for anal cancer. Radiation therapy (RT) can weaken the pelvic bone structure, but the risk of pelvic insufficiency fractures (PIFs) and derived pain in anal cancer is not yet established. We determined the frequency of symptomatic PIFs after RT for anal cancer and related this to radiation dose to specific pelvic bone substructures. Methods and MaterialsIn a prospective setting, patients treated with RT for anal cancer had magnetic resonance imaging 1 year after RT. PIFs were mapped to 17 different bone sites, and we constructed a guideline for detailed delineation of pelvic bone substructures. Patients were interviewed regarding pain and scored according to Common Terminology Criteria for Adverse Effects. Dose-volume relationships for specific pelvic bone substructures and PIFs were determined for V20 to V40 Gy mean and maximum doses. ResultsTwenty-seven patients were included, and 51.9% had PIFs primarily located in the alae of the sacral bone. Patients with PIFs had significantly more pelvic pain (86% vs 23%, P = .001) and 43% had grade 2 bone pain. Dose-volume parameters for sacral bone and sacral alae were significantly higher in patients with PIFs (P < .05). V30 Gy (%) for sacral bone and alae implied an area under the curve of 0.764 and 0.758, respectively, in receiver operating characteristic analyses. ConclusionsWe observed a high risk of PIFs in patients treated with RT for anal cancer 1 year after treatment. A significant proportion had pain in the sites where PIFs were most frequently found. Radiation dose to pelvic bone substructures revealed relation to risk of PIFs and can be used for plan optimization in future clinical trials.

Online adaptive radiotherapy of anal cancer: Normal tissue sparing, target propagation methods, and first clinical experience

Background and purposeOnline adaptive radiotherapy (oART) potentially spares OARs as PTV margins are reduced. This study evaluates dosimetric benefits, compared to standard non-adaptive radiotherapy (non-ART), target propagation methods, and first clinical treatments of CBCT-guided oART of anal cancer. Materials and methodsTreatment plans with standard non-ART and reduced oART PTV margins were retrospectively generated for 23 consecutive patients with anal cancer. For five patients randomly selected among the 23 patients, weekly CBCT-guided oART sessions were simulated, where the targets were either deformed or rigidly propagated. Preferred target propagation method and dose to OARs were evaluated. Ten consecutive patients with anal cancer were treated with CBCT-guided oART. Target propagation methods and oART procedure time were evaluated. ResultsFor the retrospective treatment plans, oART resulted in median reductions in bowel bag V45Gy of 11.4 % and bladder V35Gy of 16.1%. Corresponding values for the simulated sessions were 7.5% and 27.1%. In the simulated sessions, 35% of all targets were deformed while 65% were rigidly propagated. Manual editing and rigid propagation were necessary to obtain acceptable target coverage. In the clinical treatments, the primary and some elective targets were rigidly propagated, while other targets were deformed. The median oART procedure time, measured from CBCT acquisition to completion of plan review and QA, was 23 min. ConclusionsSimulated oART reduced the dose to OARs, indicating potential reduction in toxicity. Rigid propagation of targets was necessary to reduce the need for manual edit. Clinical treatments demonstrated that oART of anal cancer is feasible but time-consuming.

Single-centre experience with intensity-modulated radiotherapy for anal cancer: A retrospective analysis

Single-centre experience with intensity-modulated radiotherapy for anal cancer: A retrospective analysis

PD-0499 Bonesparing radiotherapy for anal cancer. -Initial planning quality for the DACG II trial

PD-0499 Bonesparing radiotherapy for anal cancer. -Initial planning quality for the DACG II trial

Practice of Radiation Therapy for Anal Cancer in Austria: A Survey on Behalf of the Austrian Radiation Oncology Society Gastrointestinal Tumor Group (ÖGRO-GIT)

The general indication for chemoradiation in locally confined anal cancer is widely accepted but international consensus for staging procedures, radiation technique, dose/fractionation, target volume definition, supportive care, follow-up and treatment of early lesions is less uniform. We conducted a nationwide patterns-of-care survey in Austria to evaluate areas of disagreement and to identify possible targets for further standardization.We developed an anonymous questionnaire (38 questions) for the above-mentioned issues. The survey was sent to all 14 Austrian radiation oncology departments. Results were analyzed descriptively and compared to two major international guidelines (NCCN, ESMO) in their latest version.We received 13 answers (response rate of 93%). Median number of treated patients per year and institution was 14. Work-up generally included DRE, endoscopy and cross-sectional imaging of chest, abdomen (mainly CT) and pelvis (mainly MRI). PET-CT was used by 38%. Screening for HIV and biopsies of suspicious lymph nodes (LN) (15% each) were infrequently used. All centers use IMRT with some kind of (mainly daily) IGRT. Median doses to the primary tumor were 54.7 Gy (50.4-59.4) for T1-2 and 59.4 Gy (55-64.4) for T3-4 lesions. Boosts are applied mainly sequentially. Doses to elective nodal areas varied from 30.6-60 Gy depending on whether the patient was cN0 or cN+, but most centers prescribe 45-50.4 Gy to all elective nodal areas. Suspicious nodes usually receive a boost independent of their size to a median dose of 54 Gy (50-60 Gy). Target delineation of elective nodal areas seems generally uniform with inclusion of the common iliac nodes as the only area of disagreement. No agreement was found for OAR delineation and dose constraints. Concurrent chemotherapy was mitomycin and 5-fluorouracil /Capecitabine in all centers with 54% favoring capecitabine. Supportive care like nutritional counseling or psycho-oncological care was infrequently offered. Intensive follow-up was performed by all institutions for at least 5 years. Treatment of T1N0 showed considerable disagreement (46% surgery, 31% RT alone, 23% chemoradiation). Median dose to primary tumor was 57.2 Gy (50-60 Gy) and 2/7 centers favoring (C)RT indicated to treat no elective nodal areas in this situation.We found a high rate of agreement between the centers and concordance with the guideline recommendations at least for the main issues of work-up, treatment and follow-up. PET-CT, routine HIV testing and biopsies of suspicious LN seem underrepresented. The largest controversy regarding elective nodal target volumes concerns inclusion of the common iliac nodes. Doses to primary tumor, suspicious LN and elective nodal areas vary to some extent and are mainly in line with the recommendations, although sometimes above. OAR delineation, dose constraints, supportive care and treatment of early anal cancer are highly variable and represent areas for further standardization.

Simulated Cone-Beam Computed Tomography Based Online Adaptive Radiotherapy of Anal Cancer — Potential Dosimetric Benefit

To evaluate the dosimetric benefit of cone beam computed tomography (CBCT) based online adaptive radiotherapy (oART) with full re-optimization on the anatomy of the day, for patients with anal cancer.CBCT-based oART was simulated using a novel commercial solution in research mode. Twenty-three consecutive patients with anal cancer, treated with radiotherapy from January to November 2020, were retrospectively included. Treatments were delivered in 30 fractions with a prescribed dose of 60 and 48 Gy to the primary and elective targets, respectively. Sixteen patients were also prescribed 60 Gy to positive lymph nodes. Two reference treatment plans were generated based on the planning CT for each patient; one with clinically used clinical target volume (CTV) to planning target volume (PTV) margins for image guided radiotherapy (non-ART) and one with expected clinical oART CTV-PTV margins. The oART margins were reduced 5 mm isotropically and 5 mm anteriorly for the positive lymph nodes and elective target, respectively, compared to non-ART; corresponding to a 50 % reduction from non-ART. Treatment sessions were simulated on six weekly CBCT images for one of the patients. Bladder, rectum and bowel cavity structures were automatically delineated and manually adjusted to match the anatomy on the CBCT. For non-ART, the reference plan was re-calculated on the anatomy of the day with rigidly propagated targets. For oART, the plan was re-optimized using targets that were either deformed or rigidly propagated, according to the expected clinical workflow. The volume of bowel cavity receiving 30 and 45 Gy (V30Gy and V45Gy, respectively) was evaluated and compared between the two workflows.For the reference treatment plans, the CTV-PTV margin reduction in oART resulted in a median reduction (interquartile range) for bowel cavity V30Gy and V45Gy of 6.4 (3.8 - 8.5) % and 11.4 (9.7 - 14.0) %, respectively. This corresponded to 39.4 (17.9 - 80.2) cc and 48.5 (35.6 - 61.3) cc, respectively. Re-optimizing the plan to the anatomy of the six CBCT images lead to a median reduction [minimum; maximum] for bowel cavity V30Gy and V45Gy of 9.2 [7.5; 12.3] % and 13.1 [10.8; 15.3] %, respectively, corresponding to 58.0 [46.5; 86.0] cc and 56.9 [46.4; 70.3] cc.Simulated oART of anal cancer resulted in reduced dose to the bowel cavity, indicating potential reduction in gastrointestinal toxicity. Early results demonstrated that the superiority of oART compared to non-ART was consistent during the course of treatment. Further oART sessions of other patients are planned to be simulated before the ASTRO conference. A single-arm phase II trial to investigate the clinical impact has been developed and awaits approval.

Long-Term Patient-Reported Quality of Life and Functional Outcomes After Chemoradiation Using Intensity Modulated Radiotherapy for Anal Cancer

Few studies have long-term follow-up assessing patient-reported outcomes (PROs) after intensity-modulated radiation therapy (IMRT)-based chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). There is poor agreement between physician-graded toxicity and PROs regarding quality of life (QOL) in patients with SCCA. Therefore, we surveyed SCCA survivors ≥ 2 years out from CRT with validated PRO instruments assessing bowel, bladder, and sexual function.We identified 248 patients with SCCA treated with definitive IMRT-based CRT at a large tertiary cancer center from 2010-2018, who were alive and without recurrence. Patients were asked to complete five PRO instruments: Fecal Incontinence QOL Scale (FIQOL), Low Anterior Resection Syndrome Score (LARS), International Consultation on Incontinence Questionnaire (ICIQ), male and female lower urinary tract symptoms (MLUTS and FLUTS, respectively), International Index of Erectile Function (IIEF), and Female Sexual Function Index (FSFI). FIQOL, LARS, IIEF, and FSFI scores were dichotomized and logistic regression used to identify predictors of QOL scores.One hundred eight (44%) patients completed the PROs. Respondents' median [interquartile range, (IQR)] age was 66 [59-72] years, 80% were female, and 95% were white. Median [IQR] gross tumor volume (GTV) was 45 [27-71] cc; dose to GTV was 50 Gray (Gy), 54 Gy and 58 Gy in 25%, 53%, and 22%, respectively. Median [IQR] time from CRT was 51 [37-84] months. Median [IQR] FIQOL score was 14.3/20 [11.2-16.1]; higher is better. Larger GTV size (OR 0.99; P = 0.03) was associated with lower FIQOL score. Sixty-one (56%) patients met major LARS criteria. There was a trend towards a higher incidence of major LARS with GTV dose ≥ 54 Gy (OR 2.39; P = 0.08). Men had median [IQR] ICIQ MLUTS voiding and incontinence scores of 5/20 [2-6] and 1/24 [1-3], respectively. Women had median [IQR] ICIQ FLUTS voiding and incontinence scores of 1/12 [1-3] and 5/20 [3-8], respectively; higher is worse. Fifty-nine (55%) patients reported being sexually active in the last month. Men had a median [IQR] IIEF score of 14/25 [6-19]; higher is better. Only age (OR 1.17; P = 0.04) was significantly associated with IIEF ≤ 11 (moderate or severe ED). Women had a median [IQR] FSFI score of 20.2/26 [13.6-24.9]; higher is better. Age < 65 was associated with sexual dysfunction, defined as FSFI < 26.55 (OR, 5.5; P = 0.04). Forty (37%) patients disagreed or strongly disagreed that they were prepared for long-term side effects. Seventy (65%) patients agreed or strongly agreed that educational materials would have been helpful.SCCA survivors experience significant long-term bowel and sexual toxicities from modern CRT. Larger tumors and higher RT doses may be associated with worse function. Interventions to reduce toxicities and improve patient education are needed.

Trigger-Based Adaptive Planning to Reduce Bowel Dose in Patients Receiving Radiotherapy for Anal Cancer

<h3>Purpose/Objective(s)</h3> Standard of care for locally advanced anal carcinoma is definitive chemoradiation with IMRT. Currently, target and organ-at-risk (OAR) volumes are created using a pre-treatment CT-simulation scan. However, during the course of radiotherapy, there is often change in the size and/or position of the tumor and surrounding normal structures. Therefore, we hypothesize that the implementation of an adaptive radiation therapy treatment protocol in anal cancer may reduce radiation dose to critical surrounding normal structures, such as the bowel, through the use of anatomy-adapted replanning. <h3>Materials/Methods</h3> Retrospective daily adaptive CTs were created for 4 patients (54 Gy, 30 fraction VMAT) in an oncology imaging informatics system using the Adaptive Calculation and Tracking for Offline Plan Review (ACTOR) toolkit. Each adaptive CT was created by deformable image registration (dir) of the planning CT to the daily CBCT. The structure sets from the planning CT were deformed onto each adaptive CT and ultimately corrected and revised by two qualified radiation oncologists. The adaptive CTs were transferred to a treatment planning system for recalculation. The original treatment plan was recalculated on each fraction adaptive CT to establish the real dose received during treatment. A two-sample t-test was used to compare the average real dose received dosimetric values to the values obtained on trigger-based adaptive planning. <h3>Results</h3> Using dose prescriptions for target volumes and normal tissue dose constraints as defined in RTOG 0529 (Kachnic et al 2013), normal bowel dose metrics, including bowel V45 < 20cc, were tracked as possible triggers for adaptation. Using bowel V45 > 20cc as trigger 1, there was a significant reduction in bowel V45 for each patient (table), with an average reduction in bowel V45 of 86.7% (<i>P</i> = 0.0001) across all patients. Adapting only the 5 fractions with the highest values for bowel V45 (trigger 2), we also found a significant reduction for each patient (table), with an average reduction of 20.8 % (<i>P</i> = 0.0011) across all patients. <h3>Conclusion</h3> Our study demonstrated that triggered adaptive re-planning using bowel V45 > 20cc could likely achieve reductions in normal tissue dose. Adaptive planning during radiation treatment of anal cancer may therefore be beneficial for reduction of treatment-related GI toxicity. These results can help inform a future randomized trial of adaptive therapy vs. standard planning.

Practice of radiation therapy for anal cancer in Austria\u2014a\xa0survey on behalf of the Austrian radiation oncology society gastrointestinal tumor group (\xd6GRO-GIT)

PurposeWe conducted a patterns-of-care survey on chemoradiation for locoregionally confined anal cancer in Austria to evaluate areas of disagreement and to identify possible targets for further standardization.MethodsAn anonymous questionnaire comprising 38 questions was sent to all Austrian radiation oncology departments. Results were analyzed descriptively and compared to two international guidelines.ResultsThe response rate was 93%. Work-up generally includes DRE, endoscopy, and cross-sectional imaging of chest/abdomen and pelvis. PET-CT is used by 38%. Screening for HIV and biopsies of suspicious lymph nodes are infrequently used. All centers perform IMRT, mainly with daily IGRT. Median doses to the primary are 54.7 Gy (T1–2) and 59.4 Gy (T3–4). Suspicious nodes receive a boost (median dose 54 Gy), while elective nodal areas are mainly treated with 45–50.4 Gy. Target delineation of elective nodal areas seems generally uniform, although disagreement exists regarding inclusion of the common iliac nodes. No agreement was found for OAR-delineation and dose constraints. Concurrent chemotherapy is mitomycin and 5‑FU/capecitabine. Supportive care beyond skin care is infrequently offered. Intensive follow-up is performed for at least 5 years. Treatment of T1N0 shows considerable disagreement.ConclusionWe found a high rate of agreement between the centers and concordance with major guidelines. PET-CT, routine HIV testing, and biopsies of suspicious LN seem underrepresented. The largest controversy regarding target volumes concerns inclusion of the common iliac nodes. Prescribed doses are generally in line with the recommendations or higher. OAR delineation, dose constraints, supportive care, and treatment of early anal cancer represent areas for further standardization.

PO-1277 Practice of Radiation Therapy for Anal Cancer in Austria –A Survey on behalf of the ÖGRO-GIT

PO-1277 Practice of Radiation Therapy for Anal Cancer in Austria –A Survey on behalf of the ÖGRO-GIT

Patterns of pathologic lymph nodes in anal cancer: a PET-CT-based analysis with implications for radiotherapy treatment volumes

BackgroundThis study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines.MethodsThe baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed.ResultsPET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region.ConclusionsThe results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.

Evolution of the Role of Radiotherapy for Anal Cancer.

Simple SummaryPrior to the 1980s, primary management of localized anal cancer was surgery. Dr. Norman Nigro and colleagues found that neoadjuvant chemoradiotherapy with 5-fluorouracil and mitomycin C afforded complete response, obviating the need for surgery upfront. Advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guided radiation have resulted in reductions in radiation-associated adverse effects, allowing for the delivery of greater doses of radiation. Ongoing prospective trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Trials of newer modalities such as proton therapy are underway. In this review, we present the evolution of radiotherapy for anal cancer and describe recent advances to contextualize ongoing studies and inform future directions in efforts to mitigate treatment toxicities, further personalize treatment, and improve oncologic outcomes.Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy’s role in locally persistent or recurrent anal cancer.

Impact of tobacco smoking on the patient's outcome after (chemo)radiotherapy for anal cancer.

Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer. We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival(OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS). Patients' characteristics were as follows: median age, 62 years (range=36-89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86patients (50%), among whom 28patients and 58patients were current and former smokers, respectively. Tumours were classified as locally limited (T1-2, N0, M0) for 86patients (50%) and locally advanced (T3-4 or N+, M0) for 85patients (50%). The median total dose was 64.4Gy (range = 54-76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio=2.85, 95% confidence interval [1.25-6.50], p=0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p=0.038). Tobacco smoking was also associated with poor overall survival (p=0.03), locoregional relapse-free survival (LRFS; p=0.05) and CFS (p=0.02). Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose±chemotherapy.