Radiation Therapy For Anal Cancer Research Articles

EP-1258: High precision SIB-IMRT versus conventional radiotherapy in anal cancer: a propensity score analysis

EP-1258: High precision SIB-IMRT versus conventional radiotherapy in anal cancer: a propensity score analysis

Feasibility of preference-driven radiotherapy dose treatment planning to support shared decision making in anal cancer

Purpose/Objective: Chemo-radiotherapy is an established primary curative treatment for anal cancer, but clinically equal rationale for different target doses exists. If joint preferences (physician and patient) are used to determine acceptable tradeoffs in radiotherapy treatment planning, multiple dose plans must be simultaneously explored. We quantified the degree to which different toxicity priorities might be incorporated into treatment plan selection, to elucidate the feasible decision space for shared decision making in anal cancer radiotherapy.Material and methods: Retrospective plans were generated for 22 anal cancer patients. Multi-criteria optimization handles dynamically changing priorities between clinical objectives while meeting fixed clinical constraints. Four unique dose distributions were designed to represent a wide span of clinically relevant objectives: high-dose preference (60.2 Gy tumor boost and 50.4 Gy to elective nodes with physician-defined order of priorities), low-dose preference (53.75 Gy tumor boost, 45 Gy to elective nodes, physician-defined priorities), bowel sparing preference (lower dose levels and priority for bowel avoidance) and bladder sparing preference (lower dose levels and priority for bladder avoidance).Results: Plans satisfied constraints for target coverage. A senior oncologist approved a random subset of plans for quality assurance. Compared to a high-dose preference, bowel sparing was clinically meaningful at the lower prescribed dose [median change in V45Gy: 234 cm3; inter-quartile range (66; 247); p < .01] and for a bowel sparing preference [median change in V45Gy: 281 cm3; (73; 488); p < .01]. Compared to a high-dose preference, bladder sparing was clinically meaningful at the lower prescribed dose [median change in V35Gy: 13.7%-points; (0.3; 30.6); p < .01] and for a bladder sparing preference [median change in V35Gy: 30.3%-points; (12.4; 43.1); p < .01].Conclusions: There is decision space available in anal cancer radiotherapy to incorporate preferences, although tradeoffs are highly patient-dependent. This study demonstrates that preference-informed dose planning is feasible for clinical studies utilizing shared decision making.

Capecitabine With Mitomycin Reduces Acute Hematologic Toxicity and Treatment Delays in Patients Undergoing Definitive Chemoradiation Using Intensity Modulated Radiation Therapy for Anal Cancer

To assess the impact on acute toxicity of replacing 5-fluorouracil (5-FU) with capecitabine in definitive chemoradiation for patients with anal squamous cell carcinoma (ASCC). We retrospectively reviewed the records of 107 consecutive patients with nonmetastatic ASCC treated with definitive chemoradiation from January 2009 to May 2014. In 2011, based on the noninferiority of capecitabine versus 5-FU, our institutional practice shifted to use capecitabine instead of 5-FU for ASCC. Of 107 patients, 63 were treated with infusional 5-FU (1000mg/m2/day for 4days) and mitomycin C (MMC) (10mg/m2) during weeks 1 and 5, and 44 patients were treated with capecitabine (825mg/m2 twice daily) Monday through Friday throughout radiation therapy (RT) and MMC (10mg/m2) during weeks 1 and 5. The incidence of grade 3 to 4 acute toxicity was compared between the 2 groups. The median age at diagnosis was 59years, and 78 patients (73%) were female. The patient characteristics were similar between the 2 treatment groups. All patients in both groups were treated with intensity modulated RT (median dose, 56Gy). In the 5-FU group, 52% experienced grade 3 to 4 neutropenia compared with 20% in the capecitabine group (P=.001). Treatment breaks resulting from toxicity, primarily related to grade 3+hematologic toxicity, were necessary for 42% of patients treated with 5-FU versus 16% of those treated with capecitabine (P=.006). Pelvic radiation therapy with MMC plus capecitabine was well tolerated and appeared to have less grade 3+acute hematologic toxicity and fewer treatment interruptions than in a population of ASCC patients undergoing definitive chemoradiation with MMC and 5-FU.

Initial Results from the Royal College of Radiologists' UK National Audit of Anal Cancer Radiotherapy 2015

AimsUK guidance was recently developed for the treatment of anal cancer using intensity-modulated radiotherapy (IMRT). We audited the current use of radiotherapy in UK cancer centres for the treatment of anal cancer against such guidance. We describe the acute toxicity of IMRT in comparison with patient population in the audit treated with two-phase conformal radiotherapy and the previous published data from two-phase conformal radiotherapy, in the UK ACT2 trial. Materials and methodsA Royal College of Radiologists' prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 6 month period between February and July 2015. ResultsTwo hundred and forty-two cases were received from 40/56 cancer centres (71%). In total, 231 (95%) underwent full dose radiotherapy with prophylactic nodal irradiation. Of these, 180 (78%) received IMRT or equivalent, 52 (22%) two-phase conformal (ACT2) technique. The number of interruptions in radiotherapy treatment in the ACT2 trial was 15%. Interruptions were noted in 7% (95% confidence interval 0–14%) of courses receiving two-phase conformal and 4% (95% confidence interval 1–7%) of those receiving IMRT. The percentage of patients completing the planned radiotherapy dose, irrelevant of gaps, was 90% (95% confidence interval 82–98%) and 96% (95% confidence interval 93–99%), in two-phase conformal and IMRT respectively. The toxicity reported in the ACT2 trial, in patients receiving two-phase conformal in the audit and in patients receiving IMRT in the audit was: any toxic effect 71%, 54%, 48%, non-haematological 62%, 49%, 40% and haematological 26%, 13%, 18%, respectively. ConclusionsIMRT implementation for anal cancer is well underway in the UK with most patients receiving IMRT delivery, although its usage is not yet universal. This audit confirms that IMRT results in reduced acute toxicity and minimised treatment interruptions in comparison with previous two-phase conformal techniques.

Early dose-dependent cortical thinning of the femoral neck in anal cancer patients treated with pelvic radiation therapy

Background and purposeAnal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT). Materials and methodsRT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤4months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed. ResultsTwenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p<0.05). FN volume receiving ≥40Gy (V40Gy) was a significant predictor of focal cortical thinning ≥30% (p=0.03). A significant decrease in FN trBMD was observed (−6.4% [range −34.4 to 3.3%]; p=0.01). ConclusionSignificant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.

Stepwise Multicenter Introduction of Intensity Modulated Radiation Therapy for Anal Cancer in the United Kingdom: From Consensus Guidance to Large-Scale Prospective Audit, Prior to Future Clinical Trials

Purpose/Objective(s) The ACT 2 trial determined the standard UK radiotherapy technique in chemoradiotherapy for anal cancer. Intensity-modulated radiotherapy (IMRT) is increasingly used due to reduced acute toxicity, however the implementation in a multicenter setting is challenging. We planned a stepwise implementation of IMRT prior to the PLATO study; an anal cancer trial due to open in 2016, investigating optimization of radiotherapy dose. We developed a consensus guidance document, adapting the ACT 2 doses and volumes for IMRT, and this was presented and published in 2014 [1]. We then performed an audit of clinical practice prior to the opening of the PLATO trial. Materials/Methods The Royal College of Radiologists carried out a prospective national audit, over a 6-month period between February and July 2015. All UK cancer centers were asked to submit details of consecutive anal cancer patients receiving radiotherapy over that period. Results Two hundred and forty-two cases were received from 41 centers. Median age was 62 (range = 29 to 90), with a female to male ratio of 2.8. 99% had invasive squamous cell, basaloid, or cacogenic carcinoma. T1/2 and T3/4 constituted 53.5% and 46.7% of tumors respectively. 49.6% had positive lymph nodes. 64.5% and 28.1% underwent Mitomycin / 5FU and Mitomycin / Capecitabine respectively. Initial analysis reveals 187 (77.3%) received treatment using inverse planning of which 148 patients received full dose radiotherapy using the doses and delivery proposed in the guidance. For toxicity comparisons the grade 3 + 4 toxicity in 3 groups were compared; those treated as per consensus guidance, those treated using the ACT 2 protocol within the audit and the published toxicity from the ACT 2 trial. Toxicity was as follows: Non-hematological - 40%, 49%, and 62%; hematological - 17%, 13%, and 26%; skin - 26%, 43%, 48%; and pain - 12%, 17%, 26%. Diarrhea was reported in 12%, 2%, and 9%. Further analysis demonstrated this was different in capecitabine-based and 5FU-based chemotherapy regimens; 16% versus 6%. The median treatment time was 38, 39, and 38 days; the number of interruptions in radiotherapy treatment was 5%, 11%, and 15%; the number of patients completing chemotherapy was 84%, 89%, and 77%; treatment-related deaths were 0%, 4%, and <1%. Conclusion This large-scale UK audit demonstrates the reduced toxicity of IMRT, implemented using consensus guidance, in comparison to the previous ACT 2 protocol. This stepwise implementation of novel radiotherapy techniques, prior to their use in a large trial, is likely to have beneficial implications for investigators due to reduced requirements for training, education, and possibly quality assurance. [1] Muirhead R, Adams RA, Gilbert DC, Glynne-Jones R, Harrison M, Sebag-Montefiore D, Hawkins MA. Anal cancer: developing an intensity-modulated radiotherapy solution for ACT2 fractionation. Clin Oncol 2014;26:720-721

Quantifying target-specific motion in anal cancer patients treated with intensity modulated radiotherapy (IMRT)

Background and purposeIntensity modulated radiotherapy requires all target areas to be treated by a single radiotherapy plan. In anal cancer, the pelvic nodes, inguinal nodes and primary tumour represent three different targets. We aim to calculate target-specific motion in anal cancer radiotherapy, when delivered using a single pelvic online auto-match. Materials and methodsTwenty consecutive patients treated using IMRT at a single institution were studied. CBCTs were retrospectively re-matched around the inguinal nodes and primary tumour. Match values were recorded relative to origin, defined as pelvic CBCT auto-match. Systematic and random errors were quantified to determine target-specific motion and suggested margins calculated using van Herk formulae. ResultsThe suggested margins to cover the independent motion of the inguinal and anal targets for LR, CC and AP set up around the inguinal nodes were 1.5mm, 2.7mm and 2.8mm; and the primary tumour were, 4.6mm, 8.9mm and 5.2mm respectively. ConclusionsTarget-specific set up will likely result in reduced treatment volumes and as such reduced toxicity. This is the first time a relationship has been described between pelvic bones, inguinal nodes and primary tumour. The PLATO study will prospectively assess the toxicity and outcomes of this target-specific margins strategy.

Colloidal oatmeal emollient as an alternative skincare approach in radiotherapy: a feasibility study

AbstractAimTo assess the feasibility of a randomised controlled trial (RCT) on patients receiving radical radiotherapy for carcinoma of the anus in order to compare the present skincare advice at the time of the study with an alternative product, Aveeno, used primarily for dermatological and chemotherapeutic-induced skin conditions.Materials and methodStandardised Radiation Therapy Oncology Group (RTOG) grading and skincare assessments were used primarily to inform on physical reactions within a RCT. A pre-existing morbidity/quality-of-life instrument ‘the Head and Neck Radiotherapy Questionnaire’, which was validated for use with radiotherapy patients in preceding studies, was adapted for anus patients and formed the secondary basis for data collection. In all, 24 participants undergoing radical radiotherapy for anal cancer were randomised into two arms, Aveeno cream versus Aqueous Cream BP, and reviewed weekly to collect data and perform analysis and Mann–Whitney U non-parametric statistical tests.ResultsRTOG gradings for skin reactions were comparable week by week across the cohorts, with a baseline 100% of participants exhibiting RTOG 0 at week 1 in all areas, through to week 6 where both cohorts had progressed to higher RTOG grades. The Aveeno cohort, however, indicated ap-value approaching significance in regards to epidermal regeneration at follow-up 1 (p=0·0543). Questionnaires yielded diminishing responses as treatment progressed correlating with advancing RTOG grades, and exhibited increasing negativity in responses in correlation with advancing RTOG grade exhibited.ConclusionThe study was the first to recognise colloidal oatmeal as a skincare approach in the radiotherapy setting and recognises the potential benefits of Aveeno in radiation-induced skin reactions. The study determined the RTOG grading system to be robust as a method of evaluation of skin reactions and the questionnaires deemed the quality-of-life assessment to be a necessity in order to address patients’ psychological needs in addition to the physical needs.

Intensity-modulated Radiotherapy and Anal Cancer: Clinical Outcome and Late Toxicity Assessment

AimsTo assess the potential impact on long-term consequences of treatment (intensity-modulated radiotherapy with concomitant chemotherapy) in patients diagnosed with anal cancer. Materials and methodsWe identified 43 eligible patients treated with concomitant chemoradiotherapy (pelvic intensity-modulated radiotherapy) at the Royal Marsden Hospital between 2010 and 2013. We determined late genitalia and bowel side-effects using specific questionnaires [Pelvic Symptom Questionnaire, Vaizey Incontinence Questionnaire, Inflammatory Bowel Disease Questionnaire (IBDQ) and IBDQ-B]. Using descriptive statistics, we report clinical outcomes in all patients, by time, since the end of treatment (grouped as 1–1.5, 1.5–2.5 and 2.5–3.5 years). ResultsTwenty-seven of 43 (63%) patients were identified as available for questionnaire follow-up. Reasons for unavailability were death (n = 3), lost to palliative care service (n = 1), referred to surgery (n = 4), lost to follow-up (n = 8). In the 27 patients studied, bowel toxicity was assessed by IBDQ, IBDQ-B and the Vaizey Incontinence Questionnaire. The median value was 208 for IBDQ, 38 for IBDQ-B and 3.0 for the Vaizey Incontinence Questionnaire, as assessed at 1 year or more post-completion of treatment. Treatment was reported to affect quality of life/sexual function in two of the female patients (n = 21) and three male patients (n = 6). No insufficiency fractures have been reported. Bone marrow function remained stable over the time of the follow-up. ConclusionsAlthough there are data supporting a reduction in acute effects using intensity-modulated radiotherapy in anal cancer, there is very little in the literature to establish the late toxicity profile. Our results indicate that there is an effect on bowel and sexual function, but it does not increase over the period observed. These data provide a benchmark against which to compare outcomes with future manipulation in treatment, and provide us with real information to give patients as to the expectation of their functional outcome after treatment.

EP-1304: Image guided intensity modulated radiotherapy for anal cancer: a multi institutional study

EP-1304: Image guided intensity modulated radiotherapy for anal cancer: a multi institutional study

Intensity-modulated Radiation Therapy for Anal Cancer: Results From a Multi-Institutional Retrospective Cohort Study.

To assess toxicity and efficacy of intensity-modulated radiation therapy (IMRT) for anal cancer. Records of 152 patients were reviewed retrospectively from multiple institutions. Data on disease control and toxicity were collected as well as patient and treatment characteristics. Acute (<6 mo) and late (≥6 mo) severe toxicity (grade ≥3) were graded. Four patients were excluded due to the presence of metastatic disease or stage TX. Late toxicity data were available for 120 patients. Median cumulative IMRT dose was 51.25 Gy (median, 28 fractions). All but 2 patients received chemotherapy. With median follow-up of 26.8 months, local control at 3 years was 87%, worse for patients with T3-T4 than T1-T2 disease on univariate analysis (79% vs. 90%; P=0.04). Regional control, distant control, and overall survival were 97%, 91%, and 87%, respectively, at 3 years. Nodal status was associated with regional control, distant control, and overall survival (P<0.01 for each). Most common severe acute toxicity was hematologic (41%), skin (20%), and gastrointestinal tract (11%). Two grade 5 toxicities occurred (hematologic and gastrointestinal tract). Severe late toxicity affected skin (1%) and gastrointestinal tract (3%). IMRT with chemotherapy resulted in excellent local control. Although T stage predicted worse local control, most T3-T4 disease was controlled with IMRT. Nodal status predicted regional and distant control and overall survival. Severe toxicity was acceptable.

Scanning proton beam therapy reduces normal tissue exposure in pelvic radiotherapy for anal cancer

An inter-comparison planning study between photon beam therapy (IMRT) and scanning proton beam therapy (SPBT) for squamous cell carcinoma of the anus (SCCA) is presented. SPBT plans offer significant reduction (>50%, P=0.008) in doses to small bowel, and bone marrow thereby offering the potential to reduce bowel and hemotoxicities.

Long-term anorectal, urinary and sexual dysfunction causing distress after radiotherapy for anal cancer: a Danish multicentre cross-sectional questionnaire study.

The objective of primary radiotherapy for anal cancer is to remove cancer while maintaining anorectal function. However, little is known about anorectal function among long-term survivors without colostomy. Using a cross-sectional questionnaire study, we examined symptoms and distress related to the dysfunction of pelvic organs after radiotherapy for anal cancer. A questionnaire regarding anorectal, urinary and sexual symptoms was sent to anal cancer patients without recurrence or colostomy, diagnosed during 1996-2003, and treated with curative intent (chemo)radiotherapy at three Danish centres. For each symptom we assessed frequency and severity and the level of symptom-induced distress (no, little, moderate or great distress). Of 94 eligible patients, 84 (89%) returned the completed questionnaire at a median of 33 months after radiotherapy. Incontinence for solid stools, liquid stools and gas occurred at least monthly in 31%, 54% and 79% of patients, respectively. Overall 40% of patients reported great distress from incontinence for solid or liquid stools at least monthly. Faecal urgency occurring at least monthly was experienced by 87% of patients and caused great distress in 43%. Stress, urge or another type of urinary incontinence occurred at least monthly in 45% and caused great distress in 21%. Urinary urgency occurred at least monthly in 48% but only caused great distress in 14%. Sexual desire was severely decreased in 58% and only 24% were satisfied with their sexual function. Distressing long-term anorectal and sexual dysfunction was common after radiotherapy for anal cancer, and morbidity due to urinary dysfunction was moderate.

Modeling early haematologic adverse events in conformal and intensity-modulated pelvic radiotherapy in anal cancer

Background and purposeTo determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+). Methods and materialsTwo groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats).Percent volume of PBM and sub structures receiving 5–25Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed. ResultsPMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05). ConclusionWhilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.

Quality of life after intensity-modulated radiation therapy for anal cancer

The aim of this study was to evaluate quality of life after intensity-modulated radiation therapy (IMRT) for anal cancer. Between 2007 and 2011, 63 patients with anal cancer were treated with IMRT and concurrent chemotherapy, and achieved complete response. These patients completed Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and Medical Outcomes Study Sexual Problems Scale (MOS-SPS) questionnaires during follow-up visits. Thirty-four patients (54 %) answered at least one questionnaire. Among them, the median radiation dose was 54 Gy to the tumor and 45 Gy to the pelvis. The median interval between treatment and the latest questionnaire was 33 months. On the latest questionnaires, the median total FACT-C score was 111, out of maximum (best possible) score 136. The median scores on the Physical, Social/Family, Emotional Functional, and Colorectal subscales were 24, 24, 19, 21, and 21, out of maximum (best possible) scores 28, 28, 24, 28 and 28, respectively. The median score on the MOS Sexual Problems Scale was 62, out of maximum (worst possible) score 100. Patients with lymph node involvement reported worse total FACT-C scores (p = 0.048), as well as worse Social/Family (p = 0.026) and Emotional (p = 0.032) subscale scores. A history of depression/anxiety was significantly associated with worse Physical (p = 0.034) and Emotional (p = 0.003) subscale scores. The use of vaginal dilator during treatment significantly improved Social/Family subscale scores (p = 0.031). Overall quality of life scores were acceptable, but sexual functioning scores were suboptimal after IMRT for anal cancer.

EP-1479: NTCP modeling of acute hematologic toxicity in conformal and intensity-modulated radiotherapy in anal cancer

EP-1479: NTCP modeling of acute hematologic toxicity in conformal and intensity-modulated radiotherapy in anal cancer

What does the general and abdominal surgeon need to know about radiotherapy? - aspects of radiotherapy in general and abdominal surgery

Radiooncological therapies are an integral part of the multimodal oncological treatment concepts in general and abdominal surgery. These include therapeutic approaches with a curative intention such as the neoadjuvant (pre-operative) radiotherapy of locoregionally advanced and/or N+ oesophageal and rectal cancer, definitive combined chemoradiotherapy of locally advanced, unresectable oesophageal cancer or oesophageal tumour lesions of the upper third, definitive radiotherapy of anal cancer (sphincter sparing) and pre- or post-operative radiotherapy of soft tissue sarcoma on the one hand. A yT0 stage achieved as characteristic of a curative effect by radiation in oesophageal and rectal cancer (omitting subsequent surgical intervention, naturally under clinical and imaging-based controls within short-term follow-up intervals) can be considered as a very interesting set-up with regard to its reasonable integration in daily clinical practice, which needs to be further and critically discussed. By integrating radiotherapy in interdisciplinary therapy concepts, improved tumour control and survival rates with clinically acceptable toxicity can be achieved. On the other hand, non-invasive, locally ablative radiooncological therapies such as extracranial stereotactic body radiotherapy constitute an effective and feasible treatment method for liver metastases in oligometastatic colorectal cancer or other tumour entities according to the decisions by the institutional tumour board, offering high local tumour control rates which can be part of multistep, multimodal procedures with curative intention. This review aims at providing an overview for the general and abdominal surgeon, outlining relevant radiooncological treatment aspects in the multimodal cancer therapy with a focus on the treatment of rectal, oesophageal and anal cancer as well as soft tissue sarcoma and hepatic metastases in oligometastatic colorectal cancer.

Intensified intensity-modulated radiotherapy in anal cancer with prevalent HPV p16 positivity.

To investigate the toxicity and response of intensity-modulated radiotherapy schedule intensified with a simultaneous integrated boost in anal canal cancer. From March 2009 to March 2014, we retrospectively analyzed 41 consecutive patients treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for anal canal squamous cell carcinoma at our center. Radiotherapy was delivered via simultaneous integrated boost (SIB) technique by helical tomotherapy, and doses were adapted to two clinical target volumes according to the tumor-node-metastasis (TNM) stage: 50.6 Gy and 41.4 Gy in 23 fractions in T1N0, 52.8 Gy and 43.2 Gy in 24 fractions in T2N0, and 55 Gy and 45 Gy in 25 fractions in all patients with N positive and/or ≥ T3, respectively, to planning target volumes 1 and 2. The most common chemotherapy regimen was 5-fluorouracil and mitomycin-based. Human papilloma virus (HPV) p16 expression was performed by immunohistochemistry and evaluated in the majority of patients. Acute and late toxicity was scored according to CTCAe v 3.0 and RTOG scales. The median follow-up was 30 mo (range: 12-71). Median age was 63 years (range 32-84). The stage of disease was: stage I in 2 patients, stage II in 13 patients, stage IIIA in 12 patients, and stage IIIB in 14 patients, respectively. Two patients were known to be HIV positive (4.9%). HPV p16 expression status was positive in 29/34 (85.3%) patients. The 4-year progression-free survival and overall survival in HPV-positive patients were 78% and 92%, respectively. Acute grade 3 skin and gastrointestinal toxicities were reported in 5% and 7.3% of patients, respectively; patients' compliance to the treatment was good due to a low occurrence of severe acute toxicity, although treatment interruptions due to toxicity were required in 7.3% of patients. At 6 mo from end of treatment, 36/40 (90%) patients obtained complete response; during follow-up, 5 (13.8%) patients presented with disease progression (local or systemic). In our experience, intensified SIB-IMRT with chemotherapy is very feasible in clinical practice, with excellent results in terms of overall survival and local control.

MITHRA - multiparametric MR/CT image adapted brachytherapy (MR/CT-IABT) in anal canal cancer: a feasibility study.

PurposeThe aim of this study is to test a novel multiparametric imaging guided procedure for high-dose-rate brachytherapy in anal canal cancer, in order to evaluate the feasibility and safety.Material and methodsFor this analysis, we considered all consecutive patients who underwent magnetic resonance/computed tomography image adapted brachytherapy (MR/CT-IABT) treated from February 2012 to July 2014. To conduct this project, we formed a working group that established the procedure and identified the indicators and benchmarks to evaluate the feasibility and safety. We considered the procedure acceptable if 90% of the indicators were consistent with the benchmarks. Magnetic resonance imaging with contrast and diffusion weighted imaging were performed with an MRI-compatible dummy applicator in the anus to define the position of the clinical target volume disease and biological information. A pre-implantation treatment planning was created in order to get information on the optimal position of the needles. Afterwards, the patient underwent a simulation CT and the definite post-implantation treatment planning was created.ResultsWe treated 11 patients (4 men and 7 women) with MR/CT-IABT and we performed a total of 13 procedures. The analysis of indicators for procedure evaluation showed that all indicators were in agreement with the benchmark. The dosimetric analysis resulted in a median of V200, V150, V100, V90, V85, respectively of 24.6%, 53.4%, 93.5%, 97.6%, and 98.7%. The median coverage index (CI) was 0.94, the median dose homogeneity index (DHI) was 0.43, the median dose non-uniformity ratio (DNR) resulted 0.56, the median overdose volume index (ODI) was 0.27. We observed no episodes of common severe acute toxicities.ConclusionsBrachytherapy is a possible option in anal cancer radiotherapy to perform the boost to complete external beam radiotherapy (EBRT). Magnetic resonance can also have biological advantages compared to the US. Our results suggest that the multiparametric MR/CT-IABT for anal cancer is feasible and safe. This new approach paves the way to prospective comparison studies between MRI and ultrasound-guided brachytherapy (USBT) in anal canal cancer.

Robust Scanned Proton Treatment Plans Provide Large Reductions in Bone Marrow Exposure for Pelvic Radiation Therapy for Anal Cancer

Robust Scanned Proton Treatment Plans Provide Large Reductions in Bone Marrow Exposure for Pelvic Radiation Therapy for Anal Cancer