Unrecognized digestive toxicities of radiation therapy.

The aim of this article is to review unrecognized toxicities resulting from radiation therapy of digestive neoplasms. Due to their precocious occurrence, acute toxicities are well-known by radiation oncologist, and their treatment well-established. Thus, acute toxicities will not be described in this review. We will focus on incidence, diagnosis, and management of late and uncommon toxicities occurring in the digestive tract and digestive organs. Prevention, by respecting healthy tissues constraints, is the main tool to reduce incidence of those rare complications. Nonetheless, once installed, late toxicities remain a major burden in terms of quality of life and can even be life threatening. Hence, information and education about their diagnosis and management is important.

Estimates of Alpha/Beta (α/ß) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial.

PURPOSE: Changes in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/ß ratio. We sought to study individual α/ß ratios for different late rectal effects after prostate external beam radiation therapy. METHODS AND MATERIALS: The CHHiP trial (ISRCTN97182923) randomized men with nonmetastatic prostate cancer 1:1:1 to 74 Gy/37 fractions (Fr), 60 Gy/20 Fr, or 57 Gy/19 Fr. Patients in the study had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhea, pain, proctitis, sphincter control, and stricture. Lyman-Kutcher-Burman models with or without equivalent dose in 2 Gy/Fr correction were log-likelihood fitted by endpoint, estimating α/ß ratios. The α/ß ratio estimate sensitivity was assessed using sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and hemorrhoids. 95% confidence intervals (CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared the models. RESULTS: Late rectal α/ß ratio estimates (without DMF) ranged from bleeding (G1 + α/ß = 1.6 Gy; 95% CI, 0.9-2.5 Gy) to sphincter control (G1 + α/ß = 3.1 Gy; 95% CI, 1.4-9.1 Gy). Bowel pain modelled poorly (α/ß, 3.6 Gy; 95% CI, 0.0-840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (P = .00041) and proctitis G1+ (P = .00046). However, the α/ß ratios were similar in these no-DMF versus DMF models for both stool frequency G2+ (α/ß 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/ß 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/ß ratios produced: G1 + α/ß ratio = 2.4 Gy; G2 + α/ß ratio = 2.3 Gy. CONCLUSIONS: We estimated α/ß ratios for several common late adverse effects of rectal radiation therapy. When comparing dose-fractionation schedules, we suggest using late a rectal α/ß ratio ≤ 3 Gy.

Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.

BACKGROUND: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. OBJECTIVE: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. DESIGN: This is an explorative study. SETTINGS: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. PATIENTS: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. MAIN OUTCOME MEASURES: Cortical evoked potentials were measured. RESULTS: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in ß (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and ß and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. LIMITATIONS: This is an explorative study of limited size. CONCLUSIONS: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Dose-volume analysis of predictors for acute anal toxicity after radiotherapy in prostate cancer patients.

BACKGROUND: This study aimed to evaluate the clinical and dosimetric factors predictive of acute anal toxicity (AAT) after radiotherapy in prostate cancer (PCa) patients with or without hemorrhoids. METHODS: We analyzed data from 347 PCa patients (248 cases treated from July 2013 to November 2017 for training cohort and 99 cases treated in 2018 for validation cohort) treated with pelvic radiotherapy at a single institution. Anal canal dose-volume histogram was used to determine the prescribed dose. Univariate and multivariate analyses were used to evaluate the risk of AAT as a function of clinical and dosimetric factors. RESULTS: Totally, 39.5% (98/248) and 31.3% (31/99) of the PCa patients developed AAT in training and validation cohorts, respectively. The incidence of AAT was much higher in patients with hemorrhoids than in those without hemorrhoids in both training and validation cohorts. Hemorrhoids and volume received more than 20 Gy (V20) were valuated as independent factors for predicting AAT in training cohort. Similar results were also observed in our validation cohort. The combination of hemorrhoids and high anal canal V20 (> 74.93% as determined by ROC curves) showed the highest specificity and positive predictive values for predicting AAT in both training and validation cohorts. CONCLUSIONS: AAT occurs commonly in PCa patients with hemorrhoids during and after pelvic radiotherapy. Hemorrhoids and anal canal V20 are independent predictors of AAT. These factors should be carefully considered during treatment planning to minimize the incidence of AAT.

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT.

Purpose: The aim of this work was to determine how the spatial pattern of dose in the ano-rectal wall is related to late gastro-intestinal toxicity for prostate cancer patients treated with mainly IMRT.Patients and methods: Patients from the DUE-01 multicentre study with patient-reported (prospective) follow-up and available dosimetric data were included. Conventionally fractionated patients received 74-80 Gy and hypofractionated patients received 65-75.2 Gy. A large majority of the patients were treated with intensity-modulated radiotherapy (IMRT). Dose-surface maps (DSMs) for the anal canal and rectum as a single structure, and for the anal canal and the rectum separately, were co-registered rigidly in two dimensions and, for the patients with and without toxicity, respectively, the mean value of the dose in each pixel was calculated. A pixel-wise t-test was used to highlight the anatomical areas where there was a significant difference between the 'mean dose maps' of each group. Univariate models were also fitted to a range of spatial parameters. The endpoints considered were a mean grade ≥1 late fecal incontinence and a maximum grade ≥2 late rectal bleeding.Results: Twenty-six out of 213 patients had fecal incontinence, while 21/225 patients had rectal bleeding. Incontinence was associated with a higher dose in the caudal region of the anal canal; the most relevant spatial parameter was the lateral extent of the low and medium isodoses (5-49 Gy in EQD2). Bleeding was associated with high isodoses reaching the posterior rectal wall. The spatial dose parameters with the highest AUC value (.69) were the lateral extent of the 60-70 Gy isodoses.Conclusions: To avoid fecal incontinence it is important to limit the portion of the anal canal irradiated. Our analysis confirms that rectal bleeding is a function of similar spatial dose parameters for patients treated with IMRT, compared to previous studies on patients treated with three-dimensional conformal radiotherapy.

Impact of radiotherapy on anorectal function in patients with rectal cancer following a watch and wait programme.

BACKGROUND AND PURPOSE: To assess the long-term anorectal function in rectal cancer patients following a watch-and-wait policy after chemoradiotherapy and to investigate the dose-volume effects of radiotherapy on the anorectal function. METHODS AND MATERIALS: Thirty-three patients with primary rectal cancer who were treated with chemoradiotherapy and a watch-and-wait policy with minimum follow-up of 2  years were included. We assessed the anorectal function using anorectal manometry and patient reported outcomes (Vaizey and LARS score). Dose-volume histograms were calculated for the rectum and anal sphincter complex, and associations between the dose-volume parameters and anorectal function were assessed. RESULTS: Dmean to the rectum and anal sphincter complex was 50.5 Gy and 44.7 Gy, respectively. After a median follow-up of 38 (range 23-116) months, 33.3% of the patients reported major LARS. Mean LARS score was 23.4 ±â€¯11.3 and mean Vaizey score was 4.3 ±â€¯4.1. The most frequent complaints were clustering of defaecation and faecal urgency. Trends towards a higher Vaizey and LARS score after higher anal sphincter complex dose were observed, although these associations were not statistically significant. CONCLUSIONS: This is the first study to investigate the late dose-volume effects of radiotherapy specifically on the anorectal function in rectal cancer patients. One-third of the patients had major LARS and the most frequent reported complaints were clustering and faecal urgency. Additionally, we observed trends towards worse long-term anorectal function after higher anal sphincter complex radiotherapy dose. However, this should be evaluated on a larger scale. Future efforts to minimise the dose to the sphincters could possibly reduce the impact of radiotherapy on the anorectal function.

Impact of VMAT-IMRT compared to 3D conformal radiotherapy on anal sphincter dose distribution in neoadjuvant chemoradiation of rectal cancer.

BACKGROUND: Neoadjuvant radio- or chemoradiation (nIRT) therapy is the standard treatment for loco-regional advanced rectal cancer patients of the lower or middle third. Currently, intensity modulated radiation therapy (IMRT) is not the recommended radiation technique even though IMRT has advantages compared to 3D-radiation regarding dose sparing to organs at risk like small bowel and urinary bladder. So far, the benefit of IMRT concerning the anal sphincter complex is not examined. With this study we intended to evaluate the dose distribution on the anal sphincters of rectal cancer patients treated with IMRT in comparison with 3D-techniques. METHODS: We selected 16 patients for the IMRT-group and 16 patients for the 3D-group with rectal cancer of the middle third who were treated in our institute. All patients received 45 Gy in a chemoradiation protocol. Patients in both groups were matched regarding stage, primary tumor distance to the anal verge and size of the tumor. We delineated the internal and external anal sphincters, the addition of both sphincters and the levator ani muscle in all patients. Subsequently, we evaluated and compared dose parameters of the different sphincters in both groups and analysed the configuration of the isodoses in the area of the caudal radiation field, respectively. RESULTS: Most of the relevant dose parameters of the caudal sphincters (Dmean, Dmedian, V10-V40) were significantly reduced in the IMRT-group compared to the 3D-group. Accordingly, the isodoses at the caudal edge of the target volume in the IMRT group demonstrated a steep dose fall. The levator ani muscle always was included into the planned target volumes and received the full dose in both groups. CONCLUSIONS: The modern VMAT-IMRT can significantly reduce the dose to the anal sphincters for rectal cancer patients of the middle third who were treated with conventional chemoradiation therapy.

Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review.

INTRODUCTION: There is a paucity of data on incidence and mechanisms of long-term gastrointestinal consequences after chemoradiotherapy for anal cancer. Most of the adverse effects reported were based on traditional external beam radiotherapy whilst only short-term follow-ups have been available for intensity-modulated radiotherapy, and there is lack of knowledge about consequences of dose-escalation radiotherapy. METHOD: A systematic literature review. RESULTS: Two thousand nine hundred and eighty-five titles (excluding duplicates) were identified through the search; 130 articles were included in this review. The overall incidence of late gastrointestinal toxicity was reported to be 7-64.5%, with Grade 3 and above (classified as severe) up to 33.3%. The most commonly reported late toxicities were fecal incontinence (up to 44%), diarrhea (up to 26.7%), and ulceration (up to 22.6%). Diarrhea, fecal incontinence and buttock pain were associated with lower scores in radiotherapy specific quality of life scales (QLQ-CR29, QLQ-C30, and QLQ-CR38) compared to healthy controls. Intensity-modulated radiation therapy appears to reduce late toxicity. CONCLUSION: Late gastrointestinal toxicities are common with severe toxicity seen in one-third of the patients. These symptoms significantly impact on patients' quality of life. Prospective studies with control groups are needed to elucidate long-term toxicity.

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) is the standard therapy for localized anal cancer (AC), but this treatment is associated with substantial toxicity. However, there is a lack of prospectively collected toxicity and patient reported outcome (PRO) data from larger cohorts. The purpose was to prospectively collect and determine agreement between physician assessed toxicity (CTCAE) and PRO during and after CRT and to compare IMRT, VMAT and proton-based planning in a subgroup of patients. MATERIAL AND METHODS: Patients, treated with CRT for AC, were included between 2015 and 2017. NCI-CTCAE v.4.0, EORTC QLQ-C30 and CR29 data were collected baseline, mid-therapy, end-of therapy and 2-4 weeks posttherapy. Treatment planning with 5- or 6-fixed field IMRT, 2 and 3 arc VMAT, and 3- and 4-field proton plans were compared. RESULTS: One-hundred patients were included. Both CTCAE and PROs related to acute toxicity reached a maximum at end of therapy. Incidences of PROs were markedly higher with only slight to fair agreement to CTCAE, (κ 13-37). Comparative planning revealed dosimetric equality of IMRT and VMAT plans, but superiority of proton plans. CONCLUSIONS: The high incidence of PRO scores and weak agreement to CTCAE suggest that PROs are important tools complementary to CTCAE in evaluating patient symptoms during and after CRT. Proton therapy has the potential to lower radiation doses to most organs at risk.

Abnormal neuronal response to rectal and anal stimuli in patients treated with primary radiotherapy for anal cancer.

INTRODUCTION: Sphincter-sparing radiotherapy or chemoradiation (RT/CRT) have become the standard treatments for most patients with anal cancer. Unfortunately, long-term survivors often suffer from severe bowel symptoms indicating sensory dysfunction. The aim of the present study was to characterize the sensory pathways of the brain-gut axis after radiotherapy for anal cancer. METHOD: Cortical evoked potentials (CEPs) were recorded during repeated, rapid balloon distensions of the rectum and anal canal in 13 patients with anal cancer treated with radiotherapy or chemoradiation and in 17 healthy volunteers. Latencies and amplitudes of rectal CEPs were compared between the groups. CEPs from both rectal and anal distensions were examined using single sweep spectral band analysis to determine the relative amplitude of five spectral bands as a proxy of neuronal processing. RESULTS: Groups were comparable by age (62.4 ±â€¯7.8 vs 58.9 ±â€¯8.9, p < 0.32) and gender. Patients had a mean Wexner fecal incontinence score of 5.5 (±3.8) and median LARS Score of 29 (0-39). Rectal CEP latencies were prolonged in patients (F = 11.7; p < 0.001), whereas amplitudes were similar (F = 0.003; p = 0.96). Spectral analysis of CEPs from rectal distensions showed significant differences between groups in theta (4-8 Hz), alpha (8-12 Hz), beta (12-32 Hz) and gamma (32-70 Hz) bands (all p < 0.001) and CEPs from anal distensions showed significant differences in the alpha, beta and gamma bands (all p ≤ 0.002). CONCLUSION: Patients treated with RT/CRT for anal cancer have impaired ano-rectal sensory pathways and abnormal cortical processing. This may play a central role for the pathogenesis of late proctopathy.

Anal and rectal function after intensity-modulated prostate radiotherapy with endorectal balloon.

BACKGROUND AND PURPOSE: Late anorectal toxicity influences quality of life after external beam radiotherapy (EBRT) for prostate cancer. A daily inserted endorectal balloon (ERB) during EBRT aims to reduce anorectal toxicity. Our goal is to objectify anorectal function over time after prostate intensity-modulated radiotherapy (IMRT) with ERB. MATERIAL AND METHODS: Sixty men, irradiated with IMRT and an ERB, underwent barostat measurements and anorectal manometry prior to EBRT and 6 months, one year and 2 years after radiotherapy. Primary outcome measures were rectal distensibility and rectal sensibility in response to stepwise isobaric distensions and anal pressures. RESULTS: Forty-eight men completed all measurements. EBRT reduced maximal rectal capacity 2 years after EBRT (250 ±â€¯10 mL vs. 211 ±â€¯10 mL; p < 0.001), area under the pressure-volume curve (2878 ±â€¯270 mL mmHg vs. 2521 ±â€¯305 mL mmHg; p = 0.043) and rectal compliance (NS). Sensory pressure thresholds for first sense and first urge (both p < 0.01) increased. Anal maximum pressure diminished after IMRT (p = 0.006). CONCLUSIONS: Rectal capacity and sensory function are increasingly affected over time after radiotherapy. There is an indication that these reductions are affected less with IMRT + ERB compared to conventional radiation techniques.

Peri-anal surface dose in anal canal VMAT radiotherapy.

INTRODUCTION: Skin bolus may routinely be used in the perineum to build up the surface dose in the treatment of anal cancer (ACC); this may contribute to significant acute skin toxicity. Skin bolus may not be needed with the introduction of modern radiotherapy techniques if these planning techniques would achieve adequate surface dose. Our study is to ascertain if appropriate skin dose can be achieved without the use of bolus when VMAT is used in the treatment of ACC. METHODS: The study includes 10 ACC patients treated with VMAT radiotherapy. Optically stimulated luminescence dosimeters (OSLD) are used to evaluate whether the calculated dose for the VMAT planning technique (VMAT-PT) accurately predicted the dose delivered to peri-anal target region without bolus. The OSLD recorded the dose at the anal verge or at the lower most extent of the tumour for each patient over two fractions. The OSLD was read after each of the two fractions, and the average value was reported. The mean dose over a volume centred on the anal marker was calculated in the treatment planning system (TPS). RESULTS: The mean TPS-calculated dose was 186.1 cGy. The mean of the OSLD-measured doses was 205.7 cGy for a single fraction. The mean of the measured doses was 10.6% higher than the mean of the calculated doses. CONCLUSIONS: The calculated dose for the VMAT-PT consistently under-predicted the dose delivered to the peri-anal target region without bolus. Routine use of skin bolus could be avoided with VMAT-PT when the patient is treated in a supine position.

Anal sphincter dysfunction in patients treated with primary radiotherapy for anal cancer: a study with the functional lumen imaging probe.

BACKGROUND: Sphincter-sparing radiotherapy or chemoradiation are standard treatments for patients with anal cancer. The ultimate treatment goal is full recovery from anal cancer with preserved anorectal function. Unfortunately, long-term survivors often suffer from severe anorectal symptoms. The aim of the present study was to characterize changes in anorectal physiology after radiotherapy for anal cancer. METHOD: We included 13 patients (10 women, age 63.4 ± 1.9) treated with radiotherapy or chemoradiation for anal cancer and 14 healthy volunteers (9 women, age 61.4 ± 1.5). Symptoms were assessed with scores for fecal incontinence and low anterior resection syndrome. Anorectal physiology was examined with anorectal manometry and the Functional Lumen Imaging Probe. RESULTS: Patients had a median Wexner fecal incontinence score of 5 (0-13) and a median LARS score of 29 (0-39). Compared to healthy volunteers, patients had lower mean (±SE) anal -resting (38 ± 5 vs. 71 ± 6, p < .001) and -squeeze pressures (76 ± 11 vs. 165 ± 15, p < .001). Patients also had lower anal yield pressure (15.5 ± 1.3 mmHg vs. 28.0 ± 2.0 mmHg, p < .001), higher distensibility, and lower resistance to flow (reduced resistance ratio of the anal canal during distension, q = 5.09, p < .001). No differences were found in median (range) rectal volumes at first sensation (70.5 (15-131) vs. 57 (18-132) ml, p > .4), urge (103 (54-176) vs. 90 (32-212), p > .6) or maximum tolerable volume (173 (86-413) vs. 119.5 (54-269) ml, p > .10). CONCLUSION: Patients treated with radiotherapy or chemoradiation for anal cancer have low anal resting and squeeze pressures as well as reduced resistance to distension and flow.

Target volume motion during anal cancer image guided radiotherapy using cone-beam computed tomography.

OBJECTIVE: Literature regarding image-guidance and interfractional motion of the anal canal (AC) during anal cancer radiotherapy is sparse. This study investigates interfractional AC motion during anal cancer radiotherapy. METHODS: Bone matched cone beam CT (CBCT) images were acquired for 20 patients receiving anal cancer radiotherapy allowing population systematic and random error calculations. 12 were selected to investigate interfractional AC motion. Primary anal gross tumour volume and clinical target volume (CTVa) were contoured on each CBCT. CBCT CTVa volumes were compared to planning CTVa. CBCT CTVa volumes were combined into a CBCT-CTVa envelope for each patient. Maximum distortion between each orthogonal border of the planning CTVa and CBCT-CTVa envelope was measured. Frequency, volume and location of CBCT-CTVa envelope beyond the planning target volume (PTVa) was analysed. RESULTS: Population systematic and random errors were 1 and 3 mm respectively. 112 CBCTs were analysed in the interfractional motion study. CTVa varied between each imaging session particularly T location patients of anorectal origin. CTVa border expansions ≥ 1 cm were seen inferiorly, anteriorly, posteriorly and left direction. The CBCT-CTVa envelope fell beyond the PTVa ≥ 50% imaging sessions (n = 5). Of these CBCT CTVa distortions beyond PTVa, 44% and 32% were in the upper and lower thirds of PTVa respectively. CONCLUSION: The AC is susceptible to volume changes and shape deformations. Care must be taken when calculating or considering reducing the PTV margin to the anus. Advances in knowledge: Within a limited field of research, this study provides further knowledge of how the AC deforms during anal cancer radiotherapy.

Dynamics of rectal balloon implant shrinkage in prostate VMAT : Influence on anorectal dose and late rectal complication risk.

PURPOSE: To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy. METHODS: In 15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate-rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V75Gy) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2-3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated. RESULTS: A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate-rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V75Gy of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings. CONCLUSIONS: Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall.

Pudendal nerve injury impairs anorectal function and health related quality of life measures ≥2 years after 3D conformal radiotherapy for prostate cancer.

PURPOSE: To compare GI symptoms, measures of generic and disease specific health related quality of life (HRQoL), anorectal and pudendal nerve function and anal sphincter morphology between (i) patients ≥2 years after 3D conformal radiotherapy (3D-CRT)±high dose rate (HDR) brachytherapy for carcinoma of the prostate and aged matched patients before radiotherapy and (ii) symptomatic and asymptomatic patients ≥2 years after 3D-CRT ± HDR brachytherapy. MATERIAL AND METHODS: Methodology included: (i) modified LENT-SOMA scales for GI symptoms, (ii) EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires for generic and disease specific HRQoL, (iii) anorectal manometry and terminal motor latency for anorectal and pudendal nerve function and (iv) endorectal ultrasound for anal sphincter morphology. GI symptoms, parameters of HRQoL, anorectal and pudendal nerve function and anal sphincter morphology were compared using Mann-Whitney's U, unpaired t and χ2 tests. RESULTS: Impairment of HRQoL bowel symptoms in the patients ≥2 years after 3D-CRT ± HDR brachytherapy was associated with worse anorectal motor and sensory function, internal and external anal sphincter morphology and 5× greater prevalence of pudendal nerve dysfunction compared with age matched patients before radiotherapy. Symptomatic patients had worse (i) HRQoL measures including global quality of life and bowel and urinary symptom scores, (ii) rectal bleeding, fecal urgency and incontinence scores and (iii) a 2× higher prevalence of pudendal nerve dysfunction compared with asymptomatic patients. Rectal and anal (i) V 40 Gy >65%, (ii) Dmax >60 Gy, (iii) pudendal nerve Dmax >60 Gy and (iv) Anal V 60 Gy >40% were associated with a greater prevalence of pudendal nerve dysfunction. CONCLUSIONS: 3D-CRT ± HDR brachytherapy for prostate carcinoma, impairs late functional measures including HRQoL, anorectal and pudendal nerve function. Rectal, anal and pudendal nerve radiation dose constraints are proposed for reducing the prevalence of pudendal nerve dysfunction.

Robotic Placement of the FENIX Continence Restoration System in a Patient with Previous Radiation to the Pelvis: A Case Report.

Fecal incontinence (FI) is a disabling problem affecting women. Conservative treatment includes dietary modification, antimotility agents, and pelvic floor physical therapy. If conservative medical management is unsuccessful, surgical intervention may be required. Surgical options include rectal sphincteroplasty, bulking agent injection, radiofrequency anal sphincter remodeling, and sacral nerve stimulation therapy. Recently, a new therapy for FI, the FENIX Continence Restoration System (Torax Medical, Inc., Shoreview, MN), has become available. The FENIX device is placed through a perineal incision; however, pelvic radiation and previous anal carcinoma are both contraindications. We report the case of a 62-year-old woman with FI after anal carcinoma. Treatment included surgery, chemotherapy, and pelvic radiation. Initially, she was treated with conservative therapy and sacral nerve stimulation, which were only partially effective. A physical examination showed perineal skin changes consistent with previous radiation, which increased the patient's risk of infection and a nonhealing wound. Therefore, a robotic approach was used to place the FENIX device and improve the patient's quality of life. Our case sets a precedent for expanding the treatment options of FI in patients with previous pelvic radiation and using a robotic approach for the placement of the FENIX device.

Local Protocol Variations for Image Guided Radiation Therapy in the Multicenter Dutch Hypofractionation (HYPRO) Trial: Impact of Rectal Balloon and MRI Delineation on Anorectal Dose and Gastrointestinal Toxicity Levels.

PURPOSE: The phase 3 HYpofractionated irradiation for PROstate cancer (HYPRO) trial randomized patients with intermediate- to high-risk localized prostate cancer to conventionally fractionated (78 Gy in 39 fractions) or hypofractionated (64.6 Gy in 19 fractions) radiation therapy. Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers. METHODS AND MATERIALS: From the trial population, we selected patients (N=572) from 4 treatment centers who received image guided (IG) intensity modulated radiation therapy (IMRT). Center A (n=242) applied planning target volume (PTV) margins of 5 to 6 mm and was considered the reference center. In center B (n=170, 7-mm margins), magnetic resonance imaging (MRI) was integrated in treatment planning. An endorectal balloon (ERB) was applied in center C (n=85, 7-mm margins). Center D (n=75) applied the largest PTV margins of 8 mm. The study protocol provided identical anorectal dose constraints, and local protocols were applied for further treatment optimization. Anorectal dose-surface histograms were compared by applying t tests. Rectal complaints during follow-up (6 months to 4 years) were compared in a generalized linear model, adjusting for age, follow-up, treatment arm, and hormone therapy. RESULTS: Favorable anorectal dose distributions were found for center B (MRI delineation) and center C (ERB application) as compared with centers A and D. These were associated with significantly lower incidences of patient-reported complaints of rectal incontinence, use of incontinence pads, and rectal discomfort in these centers. Furthermore, lower incidences of increased stool frequency (≥4 per day) and mucous loss were observed for center C. CONCLUSIONS: Despite comparable IG-IMRT techniques and predefined dose constraints, pronounced differences in dose distributions and toxicity rates were observed. MRI delineation and ERB application were associated with favorable rectal dose parameters and toxicity profiles, whereas a 2- to 3-mm difference in PTV margins did not translate into observed differences. We conclude that choices for treatment optimization of IG-IMRT are important and clinically relevant for patients since these affect symptoms experienced in daily life.

Fecal incontinence and radiation dose on anal sphincter in patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy: a retrospective, single-institutional study

Background. The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. Methods. We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0-20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V20, V30, V40, V50, mean dose (Dmean), minimum dose (Dmin), D90 (dose received by 90% of the sphincter) and D98. Statistical analysis. The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann-Whitney test. Results. Mean Wexner score was 5.5 points higher in those patients with V20 > 0 compared to those for which V20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. Conclusions. In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy (AU)

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