Purpose: Patients with early stage breast cancer (ESBC) are conventionally treated with breast-conserving surgery (BCS) followed by whole-breast external beam radiation therapy (EBRT). The emergence of targeted intraoperative radiation therapy (TARGIT) with Intrabeam has been used as a therapeutic alternative for patients with risk-adapted ESBC. Here we present our radiation therapy toxicities (RTT), postoperative complications (PC), and short-term outcomes of the prospective phase II trial at the McGill UniversityMethods and Materials: Patients aged =50 years with biopsy-proven hormone receptor-positive, grade 1 or 2, invasive ductal carcinoma of the breast, cT1N0, were eligible for the study. Enrolled patients underwent BCS followed by immediate TARGIT of 20 Gy in 1 fraction. Upon final pathology, patients with low-risk breast cancer (LRBC) received no further EBRT, and those with high-risk breast cancer (HRBC) received further 15 to 16 fractions of whole breast EBRT. HRBC criteria included pathologic tumor size >2 cm, grade 3, positive lympho-vascular invasion, multifocal disease, close margins (<2 mm), or positive nodal disease.Results: A total of 61 patients with ESBC were enrolled in the study; upon final pathology, 40 (65.6%) had LRBC, and 21 (34.4%) had HRBC. The median follow-up was 3.9 years. The most common HRBC criteria were close margins in 66.6% (n = 14) and lymphovascular invasion in 28.6% (n = 6). No grade 4 RTT were observed in either group. The most common PC were seroma and cellulitis for both groups. The rate of locoregional recurrence was 0% in both groups. The overall survival in LRBC was 97.5% and in HRBC 95.2% with no significant differences. Deaths were nonbreast cancer related.Conclusions: In patients with ESBC undergoing BCS, the use of TARGIT shows low rates of RTT and PC complications. Moreover, our short-term outcomes show no significant difference at 3.9 years median follow-up for locoregional recurrence or overall survival

The radiotherapy process is a series of events during which discrepancies between the planned treatment and actual treatment delivered can occur.This necessitates a comprehensive quality assurance (QA) programme, including regular quality control (QC) checks and audits.As more advanced technology is introduced in the clinical setting, QA activities must continually evolve to provide a safe framework for implementation of technical radiotherapy.With image guided and adaptive strategies being increasingly employed to ensure accurate delivery of treatment in scenarios such as dose escalation and hypofractionation; techniques must be implemented in a safe and effective manner.QA in the clinical trial arena has played a leading role in striving for accuracy and consistency of radiotherapy treatment delivery through monitoring protocol compliance in a multi-centre setting.Clinical trials can also evaluate the feasibility and effectiveness of a new technology.A comprehensive trial QA programme not only accredits centres for recruitment to a trial but also benefits the general standard of radiotherapy delivered.This presentation will aim to demonstrate how we can extend the clinical trial QA experience to routine practice to ensure quality of image guidance through discussing examples of clinical trial benchmarking and credentialing processes and their perceived impacts on clinical practice.

PURPOSEIt has been realized that inter-patient radiation sensitivity variability is a multifactorial process involving dosimetric, clinical, and genetic factors. Therefore, we explore a new framework to integrate physical, clinical, and biological data denoted as radiogenomic modeling. In demonstrating the feasibility of this work, we investigate the association of genetic variants (copy number variations [CNVs] and single nucleotide polymorphisms [SNPs]) with radiation induced rectal bleeding (RB) and erectile dysfunction (ED) while taking into account dosimetric and clinical variables in prostate cancer patients treated with curative irradiation.METHODSA cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) was retrospectively genotyped for CNV and SNP rs25489 in the xrcc1 DNA repair gene. Dosevolume metrics were extracted from treatment plans of 54 patients who had complete dosimetric profiles. Treatment outcomes were considered to be a RESULT OF FUNCTIONAL MAPPING OF RADIOGENOMIC INPUT VARIABLES ACCORDING TO A LOGIT TRANSFORMATION. MODEL ORDERS WERE ESTIMATED USING RESAMPLING BY LEAVE-ONE OUT CROSS-VALIDATION (LOO-CV). RADIOGENOMIC MODEL PERFORMANCE WAS EVALUATED USING AREA UNDER THE ROC CURVE (AUC) AND LOO-CV. FOR CONTINUOUS UNIVARIATE DOSIMETRIC AND CLINICAL VARIABLES, SPEARMANS RANK COEFFICIENTS WERE CALCULATED AND P-VALUES REPORTED ACCORDINGLY. IN THE CASE OF BINARY VARIABLES, CHI-SQUARED STATISTICS AND CONTINGENCY TABLE CALCULATIONS WERE USED.RESULTSTen patients were found to have three copies of xrcc1 CNV (RB: χ2=14.6 [p<0.001] and ED: χ2=4.88[p=0.0272]) and twelve had heterozygous rs25489 SNP (RB: χ2=0.278[p=0.599] and ED: χ2=0.112[p=0.732]). LOO-CV identified penile bulb D60 as the only significant QUANTEC predictor (rs=0.312 [p=0.0145]) for ED. Radiogenomic modeling yielded statistically significant, cross-validated NTCP models for RB (rs=0.243[p=0.0443], AUC=0.665) and ED (rs=0.276[p=0.0217], AUC=0.754).CONCLUSIONThe radiogenomic modeling approach presented herein has been shown to identify NTCP models which have increased predictive power. Furthermore, CNVs appears to be useful genetic variants when added to dosimetric NTCP models. This work was partially supported by CIHR grant MOP-114910.

Évaluer les résultats cliniques et dosimétriques du « Body Fit Form », dans le but de diminuer la toxicité aiguë et d’améliorer le profil dosimétrique lors de la radiothérapie de seins ptosés. Le « Body Fit Form » est un maillot de corps fait en nylon extensible et en spandex. Cette étude de phase II concernait six patientes. Deux tomodensitométries de planification ont été faites pour chaque patiente, avec et sans le port du « Body Fit Form ». Il a été délivré avec « Body Fit Form » 50 Gy en 25 fractions, puis un boost dans la cavité chirurgicale. La toxicité aiguë a été évaluée hebdomadairement pendant les traitements. Des plans de traitements ont été générés pour les deux tomodensitométries et comparés. Les patientes avaient un âge médian de 60 ans et les cancers étaient de stade pT1-2N0. Après un suivi médian de 2,8 mois, aucune toxicité aiguë de grade de plus de 2 n’a été rapportée. La dermite aiguë maximale était de grade 2 chez quatre patientes (67 %), et chacune était améliorée lors des visites de suivi. La distribution de la dose dans le poumon était améliorée chez toutes les patientes. Le volume recevant 20 Gy (V20 Gy) du poumon homolatéral était diminué en moyenne de 20,8 % à 12,26 %, et la dose moyenne délivrée dans le poumon était diminuée de 11,4 Gy à 7,7 Gy. Deux patientes étaient atteintes d’un cancer au sein gauche, et la dose maximale cardiaque moyenne était de 6,9 % avec le « Body Fit Form » et 8,5 % sans. Le volume recevant 5 Gy (V5 Gy) moyen était de 45,6 Gy avec le « Body Fit Form », et 50,4 Gy sans. Une toxicité aiguë faible a été observée chez les patientes aux seins ptosés avec le « Body Fit Form », lors de la radiothérapie du sein. De plus, une amélioration de la distribution de dose dans poumon et le cœur lors du port du « Body Fit Form » a été notée.

Inter‐patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation‐induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 & 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross‐validation. Binary variables were evaluated using Chi‐squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ2=14.6, p<0.001 and ED: χ2=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ2=0.278, p=0.599 and ED: χ2=0.112, p=0.732). Radiogenomic modeling yielded significant, cross‐validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

Conclusions: Resolving the difference between CK19 expression in breast cancer (non-proliferating, hypoxic cells) and cervical cancer (proliferating, oxygenated cells) will be an important step in understanding in vivo molecular biology and providing support for the effective application of molecular targeting in cancer therapy.

Purpose/Objective(s)To report acute toxicities from a phase II study in high-risk prostate cancer patients treated with androgen suppression and intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost.Materials/MethodsThirty-six prostate cancer patients with clinical stage ≥T3, or initial PSA ≥20 ng/mL, or Gleason score of 8-10 entered in the study. IMRT plans were designed to deliver 60 Gy in 20 fractions of 3 Gy over 4 weeks to the prostate and base of seminal vesicle (CTV60), while simultaneously delivering 44 Gy in 20 fractions of 2.2 Gy to the pelvic lymph nodes (CTV44). All patients had daily image guidance with ultrasound and/or cone-beam. PTVs were CTVs with a 7mm margin. Whole bladder and rectum constraints were as follows: V56 Gy<25%; V48 Gy<50% for the rectum and V60 Gy<25%; V52 Gy<50% for the bladder. Acute toxicity was recorded prospectively, weekly during treatment and every 3-6 months post IMRT, using the NCI CTC version 3 scoring system.ResultsMedian age is 72 years (56-85). One 80 year-old patient interrupted treatment at 54 Gy due to medical reasons diagnosed prior to IMRT. All other patients completed IMRT without interruption, and were followed for more than 3 months. Acute genito-urinary (GU) and gastro-intestinal (GI) toxicities are summarized in the table below, and were compared to EORTC data using standard fractionation (70 Gy/35 to prostate and 45 Gy/25 to pelvis). There was no grade ≥ 4 acute toxicity. Acute toxicity did not correlate with any of the dosimetric parameters examined. Of interest, beyond a follow-up of 90 days, all acute grade 3 toxicity improved.ConclusionsPoster Viewing Abstract 2389; TableAcute toxicity rates in McGill study compared to EORTC dataGrade0123McGillGU27.8%52.8%16.7%2.7%GI47.2%36.1%16.7%0%EORTCGU25.2%43.2%24.7%6.%GI3.5%33.6%18.3%8.6% Open table in a new tab Purpose/Objective(s)To report acute toxicities from a phase II study in high-risk prostate cancer patients treated with androgen suppression and intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost. To report acute toxicities from a phase II study in high-risk prostate cancer patients treated with androgen suppression and intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost. Materials/MethodsThirty-six prostate cancer patients with clinical stage ≥T3, or initial PSA ≥20 ng/mL, or Gleason score of 8-10 entered in the study. IMRT plans were designed to deliver 60 Gy in 20 fractions of 3 Gy over 4 weeks to the prostate and base of seminal vesicle (CTV60), while simultaneously delivering 44 Gy in 20 fractions of 2.2 Gy to the pelvic lymph nodes (CTV44). All patients had daily image guidance with ultrasound and/or cone-beam. PTVs were CTVs with a 7mm margin. Whole bladder and rectum constraints were as follows: V56 Gy<25%; V48 Gy<50% for the rectum and V60 Gy<25%; V52 Gy<50% for the bladder. Acute toxicity was recorded prospectively, weekly during treatment and every 3-6 months post IMRT, using the NCI CTC version 3 scoring system. Thirty-six prostate cancer patients with clinical stage ≥T3, or initial PSA ≥20 ng/mL, or Gleason score of 8-10 entered in the study. IMRT plans were designed to deliver 60 Gy in 20 fractions of 3 Gy over 4 weeks to the prostate and base of seminal vesicle (CTV60), while simultaneously delivering 44 Gy in 20 fractions of 2.2 Gy to the pelvic lymph nodes (CTV44). All patients had daily image guidance with ultrasound and/or cone-beam. PTVs were CTVs with a 7mm margin. Whole bladder and rectum constraints were as follows: V56 Gy<25%; V48 Gy<50% for the rectum and V60 Gy<25%; V52 Gy<50% for the bladder. Acute toxicity was recorded prospectively, weekly during treatment and every 3-6 months post IMRT, using the NCI CTC version 3 scoring system. ResultsMedian age is 72 years (56-85). One 80 year-old patient interrupted treatment at 54 Gy due to medical reasons diagnosed prior to IMRT. All other patients completed IMRT without interruption, and were followed for more than 3 months. Acute genito-urinary (GU) and gastro-intestinal (GI) toxicities are summarized in the table below, and were compared to EORTC data using standard fractionation (70 Gy/35 to prostate and 45 Gy/25 to pelvis). There was no grade ≥ 4 acute toxicity. Acute toxicity did not correlate with any of the dosimetric parameters examined. Of interest, beyond a follow-up of 90 days, all acute grade 3 toxicity improved. Median age is 72 years (56-85). One 80 year-old patient interrupted treatment at 54 Gy due to medical reasons diagnosed prior to IMRT. All other patients completed IMRT without interruption, and were followed for more than 3 months. Acute genito-urinary (GU) and gastro-intestinal (GI) toxicities are summarized in the table below, and were compared to EORTC data using standard fractionation (70 Gy/35 to prostate and 45 Gy/25 to pelvis). There was no grade ≥ 4 acute toxicity. Acute toxicity did not correlate with any of the dosimetric parameters examined. Of interest, beyond a follow-up of 90 days, all acute grade 3 toxicity improved. ConclusionsPoster Viewing Abstract 2389; TableAcute toxicity rates in McGill study compared to EORTC dataGrade0123McGillGU27.8%52.8%16.7%2.7%GI47.2%36.1%16.7%0%EORTCGU25.2%43.2%24.7%6.%GI3.5%33.6%18.3%8.6% Open table in a new tab

To report the frequency, timing and magnitude of PSA bounce (PB) in patients who have received HDR-brachytherapy (HDRB) plus hypofractionated external beam RT (HyRT) and to assess whether there is an association between PB, time to PSA nadir and biochemical failure (BF). One hundred fifteen patients with intermediate risk prostate cancer who received 10 Gy single fraction 192Ir HDRB followed by 50 Gy in 20 daily fractions of HyRT without androgen deprivation therapy between 2001 and 2009 were eligible for analysis. All patients had a minimum of 2 year follow-up with at least 4 PSA results. Median follow-up was 67 months. Patients who had BF within 2 years were excluded. PB was defined as PSA elevation >0.1ng/mL from previous measurement with subsequent drop to pre-bounce level. BF was defined as PSA nadir+ 2ng/mL. Bounce occurred in 51(44%) patients with a median time to bounce 16.5 months and range of 3-76 months. The Table demonstrates the number of patients who had a PB at different cut-off levels. The median time to PSA normalization following a PB was 7 months (range, 2-32 months). The median magnitude of PB was 0.425ng/mL (range, 0.11-6.62). BF occurred in 13 (11%) patients, of whom 3 (23%) had a PB. The median magnitude of PB in these patients was 0.432ng/mL (range, 0.23-0.53). Median time to PB in BF group was 11 months and 17 months in non-BF group. Four patients (3.5%) in PB group fit the criteria for BF. The time to nadir in all patients was 52 months, 55.5 months for patients with a PB and 46 months for patients with no PB. The time to nadir in patients with BF was 28 months. The median nadir value was 0.17 but 0.685 in patients with BF. PB is common after HDRB and HyRT and can occur up to 76 months after treatment. It can rarely fit the criteria for BF. There is a lower incidence of BF (6%) in patients with a PB, but those that do fail have a shorter time to PB. An acknowledgement of this phenomenon should be made when interpreting PSA results during follow-up to prevent unnecessary interventions.Poster Viewing Abstract 2494; TablePSA Bounce≥0.1≥0.2≥0.5≥1≥2Patient number51 (44%)46 (40%)25(22%)13 (11%)4 (3.5%) Open table in a new tab

Purpose: For patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients.Methods and Materials: A total of 42 rectal or anal canal cancer patients were randomized to either a SCND or standard skin care group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after treatment completion. In the control arm, sulfadiazine cream was applied at the time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on the last day, and two weeks after the treatment completion were scored by 10 blinded readers, who used the common toxicity scoring system for skin dermatitis.Results: The radiation dose ranged from 50.4 to 59.4 Gy, and there were no differences between the 2 groups. On the last day of RT, when the most severe RID occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for the standard and 1.67 (SD, 1.2; P = .01) for the SCND arm. At 2 weeks after RT, the difference was 0.39 points in favor of SCND (P = .39). There was considerable intraclass correlation among the 10 observers.Conclusions: Silver clear nylon dressing is effective in reducing RID in patients with lower gastrointestinal cancer treated with combined chemotherapy and radiation treatment. (C) 2012 Elsevier Inc.

To evaluate the dosimetry of volumetric modulated arc therapy (VMAT) and three-dimensional conformal electron radiotherapy (3D-ERT) for the tumor bed boost in breast cancer patients and to report the acute toxicity of a series of patients treated with a VMAT tumor bed boost. Fifteen patients with breast cancer treated by lumpectomy and post-operative whole breast radiotherapy and requiring tumor bed boost were planned using both VMAT and 3D-ERT. The tumor bed dose evaluation volume (DEV) was prescribed 10 Gy in 4 fractions and dosimetry for the 2 techniques were compared. The acute toxicity in the first 25 patients treated with VMAT tumor bed boost was analyzed. Coverage of the tumor bed DEV was adequate in all VMAT plans but only in 13 of 15 3D-ERT plans: V95% = 99.1% vs. 97.6%, with VMAT and 3D-ERT respectively; p = 0.42. High dose to the breast outside the tumor bed DEV was significantly lower with VMAT (V107% = 0.01% vs. 2.13%; p<0.01). Ipsilateral lung V2Gy (2.13% vs. 19.21%; p<0.0001), V7Gy (0.00% vs. 2.03%; p = 0.0001) and mean dose (0.33 Gy vs. 1.29 Gy; p<0.001) were significantly lower with VMAT. In patients with left-sided tumors, heart V2Gy (1.11% vs. 6.17%; p<0.05) was significantly lower with VMAT, but V5Gy and mean dose were comparable. Contralateral lung and breast doses were minimal and not significantly different for the 2 techniques. Maximal acute dermatitis due to whole breast RT followed by VMAT tumor bed boost was grade 2 in 72% of patients and grade 1 in 28% of patients. For the tumor bed boost for patients with breast cancer, both VMAT and 3D-ERT provide adequate target volume coverage and low heart doses, but VMAT avoids unnecessary breast overdosage while improving ipsilateral lung dosimetry. The VMAT tumor bed boost was well tolerated, with an acceptable early toxicity profile.

To report late gastrointestinal (GI) and genitourinary (GU) toxicity rates and biochemical control using hypofractionated external beam radiotherapy (HEBRT) without androgen deprivation for intermediate risk prostate cancer (PC) patients. Between October, 2002 and September, 2009, 82 men with intermediate risk PC (T2b-T2c or PSA 10-20 ng/dL or GS7) received HEBRT without androgen deprivation. The total dose of 66 Gy in 22 daily fractions was prescribed at the isocenter using 3D conformal technique. This regimen is biologically equivalent to 78 Gy in 39 fractions or 79.4 Gy in 44 fractions (alpha/beta = 3 Gy). Daily image guidance of the prostate was performed by transabdominal ultrasound system. PTV was defined as prostate with 7mm margin in all directions. There were no rectal or bladder constraints. Biochemical failure was defined according to Phoenix criteria (nadir + 2ng/dL). GI and GU toxicity were reported using common terminology criteria for adverse events (CTCAE) v3. Median follow-up was 41 months (range: 7-88.2). Median age was 71 years (range: 51-83). Sixty percent of the patients had Gleason score 7. Median initial PSA was 9 ng/dL (range: 1.8-18.6) and 43% had stage T2. Four patients (4%) presented biochemical failure followed by distant metastasis few months later. The actuarial biochemical recurrence free survival (bNED) was 95.4%. There was no death related to prostate cancer. The 5-year overall survival was 93%. Grade ≥ 2 late GI and GU toxicity rates at any time during the follow-up were 18% and 24%, respectively. At last follow-up, grade ≥ 2 late GI and GU toxicity rates were 2% and 7%, respectively. No grade 4 or 5 late toxicity has occurred. Men with intermediate risk PC treated with HEBRT using 66 Gy/22fractions and without androgen deprivation experienced excellent bNED. The treatment is well-tolerated with few patients remaining with GU or GI toxicity at the last follow-up. Results from ongoing phase 3 trials will help to define the role of hypofractionation in the treatment of intermediate risk prostate cancer.