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Background This study was conducted in order to develop a model for predicting response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) using pretreatment quantitative ultrasound (QUS) radiomics. Methods This was a multicenter study involving four sites across North America, and appropriate approval was obtained from the individual ethics committees. Eighty‐two patients with LABC were included for final analysis. Primary tumors were scanned using a clinical ultrasound system before NAC was started. The tumors were contoured, and radiofrequency data were acquired and processed from whole tumor regions of interest. QUS spectral parameters were derived from the normalized power spectrum, and texture analysis was performed based on six QUS features using a gray level co‐occurrence matrix. Patients were divided into responder or nonresponder classes based on their clinical‐pathological response. Classification analysis was performed using machine learning algorithms, which were trained to optimize classification accuracy. Cross‐validation was performed using a leave‐one‐out cross‐validation method. Results Based on the clinical outcomes of NAC treatment, there were 48 responders and 34 nonresponders. A K‐nearest neighbors (K‐NN) approach resulted in the best classifier performance, with a sensitivity of 91%, a specificity of 83%, and an accuracy of 87%. Conclusion QUS‐based radiomics can predict response to NAC based on pretreatment features with acceptable accuracy., This multi‐institutional study investigated the role of radiomics from quantitative ultrasound (QUS) in predicting the final response to neoadjuvant chemotherapy (NAC) for 82 patients with locally advanced breast cancer (LABC). We had shown the QUS‐radiomics model can predict the response to treatment with an accuracy of 87% from spectroscopic features obtained before the start of NAC.

Cigarette smoking is carcinogenic and has been linked to inferior treatment outcomes and complication rates in cancer patients. Here, we report the results of an 18-month pilot smoking cessation program that provided free nicotine replacement therapy (nrt). In January 2017, the smoking cessation program at our institution began offering free nrt for actively cigarette-smoking patients with cancer. The cost of 4 weeks of nrt was covered by the program, and follow-up was provided by smoking cessation champions. From January 2017 to June 2018, 8095 patients with cancer were screened for cigarette use, of whom 1135 self-identified as current or recent smokers. Of those 1135 patients, 117 enrolled in the program and accepted a prescription for nrt. The rates of patient referral and patients attending a referral appointment were significantly higher in 2018&ndash, 2018 than they had been in 2015&ndash, 2016 (100% vs. 80.3%, p 10 vs. &le, 10 initial cigarettes) was significantly predictive of smoking reduction (odds ratio: 5.04, 95% confidence interval: 1.46 to 17.45, p = 0.011). This pilot study of free nrt demonstrated rates of referral and acceptance of nrt that were improved compared with historical rates, and most referred patients either decreased their use of cigarettes or quit entirely.

PURPOSE In 2015, men undergoing radical prostatectomy in Ontario, Canada were recommended to undergo multidisciplinary care by seeing a radiation oncologist or discussion at multidisciplinary rounds before surgery. The a priori target rate was ≥76%. We used population-based data to explore factors associated with not receiving multidisciplinary care prior to radical prostatectomy. MATERIALS AND METHODS Men who underwent radical prostatectomy for localized prostate cancer in Ontario between 2007 and 2017 were identified using administrative data. Physician billings identified patients who received multidisciplinary care. Multivariable logistic regression was used to predict receipt of multidisciplinary care. RESULTS A total of 31,485 men underwent radical prostatectomy between 2007 and 2017. Of these patients 28.7% saw a radiation oncologist, 1.2% underwent multidisciplinary discussion and 1.9% had both before surgery. Multidisciplinary care receipt increased from 17.8% in 2007 to 47.8% in 2017 (p

Purpose Exercise may be an alternative strategy to helping early-stage breast cancer (ESBC) patients manage their cancer-related fatigue and anxiety during radiation therapy. This observational study aims to investigate the impact of self-reported exercise on fatigue and anxiety levels pre (T0), mid (T1), and post (T2) radiation therapy in patients with ESBC. Methods Following informed consent, subjects completed three standardized questionnaires measuring physical activity, fatigue/quality of life, and anxiety at T0, T1, and T2. Results A total of 58 female patients (57 ± 9 years) completed this study. Mean activity level at T0 was 2548 (3292) metabolic equivalent units (METs), T1 was 3072 (3974) METs, and T2 was 2963 (2442) METs. There was no significant change between the three time points with measures of physical activity. Many patients moved from the moderately active group at T0 to the active group at T1. The mean T0 score using the quality of life questionnaire was 38.97 (11.30), T1 was 36.93 (11.69), and T2 was 35.36 (11.18). There was no significant change between the three time points with measures of quality of life (P = .211). There was statistical significance at P = .025 at T1 for lower quality of life compared to T0 across all exercise types. There was also statistical significance at P = .026 at T1 for the active group with higher quality of life compared to the inactive one. All three physical activity categories showed a decline in quality of life scores over time. Anxiety decreased between the three time point measurements. Mean T0 score for anxiety was 47.33 (5.95), T1 was 43.16 (6.49), and T2 was 38.48 (8.46). The interaction of exercise level and time is not significant for anxiety (P = .91). There was statistical significance (P = .015) for anxiety at T2 compared to T1 across exercise types. Discussion This study demonstrated that ESBC patients showed signs of fatigue and anxiety while undergoing radiation therapy regardless of self-reported exercise measured by a physical activity questionnaire. Several trends were observed that showed improved outcomes for patients consistent with previously published studies. The present study highlights a nonsignificant change in fatigue. As fatigue is one of the main side effects from radiation, it may be difficult to demonstrate significance. There are some studies in the field that demonstrate significance between fatigue and exercise with larger sample sizes. The results also highlight a decrease in anxiety from the baseline to the end of treatment. It is postulated that patients become less anxious as treatment progresses due to familiarity of a routine. The present study is limited by several factors including sample size and the study not being a randomized controlled one. Conclusions Exercise may reduce anxiety during radiation treatment for ESBC patients. Further investigation is required to assess the impact of fatigue.

Background and purpose This study aimed to determine the effects of reducing the dose of contrast agent (CA) in a DCE-MRI scan on inter- and intra-observer variability in the context of MRI-guided target volume delineation for stereotactic body radiation therapy of early stage breast cancer patients. This is in hopes of reducing risks to patients due to findings of residual CA in brain and bone. Materials and methods Twenty-three patients receiving neoadjuvant radiation therapy were enrolled. Five observers delineated the gross target volume (GTV) using DCE-MRI for guidance. 14/23 patients received the full clinical dose of CA and 9/23 received half. Clinical target volumes (CTV) were created through a 0.5 cm uniform expansion. Several metrics were used to quantify the inter and intra-observer reliability including differences in delineation volume and the reliability coefficient. Results There were no significant differences in the volume, though half contrast patients had a lower median for both the GTV and CTV (difference of 0.26 cm3 and 1.27 cm3, respectively). All indicated a high degree of agreement between and within observers for both dose groups. However, the full dose group had a greater inter-observer variability, most likely due to the full CA causing more pronounced enhancement in the periphery. Conclusions Reducing the dose of contrast agent did not significantly alter inter- or intra-observer variability. These results have prompted our centre to reduce the dose of gadolinium in all patients enrolled in the SIGNAL trial.

Purpose/objective(s) Men with localized prostate cancer have many options for initial definitive treatment. In 2015, Cancer Care Ontario Quality Based Procedures (QBP) recommended that men undergoing radical prostatectomy (RP) in Ontario be seen by a radiation oncologist (RO) or discussed at a multidisciplinary case conference (MCC) prior to surgery. An a-priori target rate of 76% was set by QBP, but to our knowledge, has not been reported upon to date. Our objective was to use population-based data to explore factors associated with not receiving RO consult/MCC prior to RP. Materials/methods Men with localized prostate cancer diagnosed and treated in Ontario, Canada with RP between 2007 and 2017 were identified using administrative data from the Institute for Clinical Evaluative Sciences. Physician billing data was utilized to identify patients who received RO consult/MCC prior to RP. Trends were evaluated using the Cochran-Armitage test. Multivariable logistic regression was used to identify patient and provider factors predictive of RO/MCC prior to RP. Results 31,467 men with localized prostate cancer underwent RP between 2007 and 2017. Prior to RP, 29.3% of men were seen by RO, 1.0% underwent MCC, and 1.6% had both. RO consult/MCC prior to RP increased from 18.0% in 2007 to 47.8% in 2017 (P Conclusion Despite increasing rates of utilization, a large proportion of men are not seen by RO or MCC prior to RP in Ontario, Canada. While the largest factors predicting RO consult/MCC discussion appear to be geographic and which urologist performs the RP, these factors are closely intertwined. In addition, these factors may be related to RO availability and radiation system capacity, which would need to be addressed to meet patient demand should QBP consultation rates be mandated to reduce disparities in pre-RP consultation practices.

Early-stage breast cancer patients comprise a large proportion of patients treated with radiotherapy in Canada. Proponents have suggested that five-fraction hypofractionated radiotherapy for these patients would result in significant cost savings. An assessment of this argument is thus warranted. The FAST-Forward and UK FAST clinical trials each demonstrated that their respective hypofractionated regimens provided equivalent outcomes compared with standard regimens. Thus, a cost-minimization analysis was performed to quantify the potential savings associated with these regimens, which were designated as FAST-Forward 1 (26 Gy/5 fractions/1 week) and FAST-Forward 2 (27 Gy/5 fractions/1 week), and UK FAST 1 (28.5 Gy/5 fractions/5 weeks) and UK FAST 2 (30 Gy/5 fractions/5 weeks). A standard regimen of 42.5 Gy/16 fractions/5 weeks was also included. A comprehensive model of radiotherapy costs for a Canadian cancer centre was created. Time, labour costs, and capital costs were calculated for each regimen and applied using established measures. The total costs per patient for the FAST-Forward trials were $851.77 for FAST-Forward 1 and $874.77 for FAST-Forward 2, providing a total savings of $487.99 and $464.99, respectively. Similarly, the total costs per patient for the FAST trials were $979.75 for UK FAST 1 and $1017.70 for UK FAST 2, providing savings of $360.01 and $322.06, respectively. Following the FAST-Forward 1 regimen results in the greatest reduction of infrastructure and human resources costs at 36.42% compared with the standard. Sensitivity analysis shows a maximum per-patient costs savings ranging from $474.60 to $508.53 for the FAST-Forward 1 trial, which translates to an annual savings of $174,700/year locally and $2.06 million/year province-wide, based on a moderate-to-large size department workload. Compared with a standard radiotherapy regimen, all FAST-Forward and UK FAST hypofractionated regimens provide cost savings for the treatment of early-stage breast cancer. The cost savings associated with each of these equivalent regimens can be directly calculated, activities in this model can easily be adjusted to account for cost variations, allowing other centres to calculate cost impacts specific to their own centres.

Background and purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system. Materials and methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization. Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22–1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02–1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93–0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11–6.26, p < 0.01) and 2.88 (95% CI: 2.60–3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed. Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.

// Ali Hosni 1 , Kathy Han 1 , Lisa W. Le 2 , Jolie Ringash 1 , James Brierley 1 , Rebecca Wong 1 , Robert Dinniwell 1 , Anthony Brade 1 , Laura A. Dawson 1 , Bernard J. Cummings 1 , Monika K. Krzyzanowska 3 , Eric X. Chen 3 , David Hedley 3 , Jennifer Knox 3 , Alexandra M. Easson 4 , Patricia Lindsay 1 , Tim Craig 1 and John Kim 1 1 Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada 2 Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada 3 Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada 4 Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada Correspondence to: John Kim, email: john.kim@rmp.uhn.ca Keywords: anal cancer; chemoradiotherapy; IMRT; pattern of failure; outcomes Received: November 11, 2017 Accepted: February 27, 2018 Published: April 17, 2018 ABSTRACT Purpose: Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer. Methods: Between 2008–2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27–36 Gy for elective target, and 45–63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed. Results: Overall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF ( n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF ( n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%]). Conclusions: Individualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).

e17052 Background: Men with localized prostate cancer have many options for initial definitive treatment. In 2015, Cancer Care Ontario Quality Based Procedures (QBP) recommended that men undergoing radical prostatectomy (RP) in Ontario be seen by a radiation oncologist (RO) or discussed at a multidisciplinary case conference (MCC) prior to surgery. An a-priori target rate of 76% was set by QBP, but to our knowledge, has not been reported upon to date. Our objective was to use population-based data to explore factors associated with not receiving RO consult/MCC prior to RP. Methods: Men with localized prostate cancer diagnosed and treated in Ontario, Canada with RP between 2007 and 2017 were identified using administrative data from the Institute for Clinical Evaluative Sciences. Physician billing data was utilized to identify patients who received RO consult/MCC prior to RP. Trends were evaluated using the Cochran-Armitage test. Multivariable logistic regression was used to identify patient and provider factors predictive of RO/MCC prior to RP. Results: 31,467 men with localized prostate cancer underwent RP between 2007 and 2017. Prior to RP, 29.3% of men were seen by RO, 1.0% underwent MCC, and 1.6% had both. RO consult/MCC prior to RP increased from 18.0% in 2007 to 47.8% in 2017 ( p

A prospective study was conducted to assess the acute and late toxicity of hypofractionated whole breast irradiation with a weekly concomitant boost for women with early breast cancer (EBC). Women with EBC who underwent breast-conserving surgery were eligible. A dose of 40Gy in 15 fractions over 3 weeks was delivered to the whole breast with a concomitant weekly boost to the post-operative cavity of 3Gy in three fractions. Toxicity was graded using the Radiation Therapy Oncology Group (RTOG) acute toxicity and RTOG/EORTC late toxicity scales. A total of 67 women were enrolled with a median age of 49 years (range 31–69). Median follow-up was 25 months (range 11–34). Acute skin reactions included grade (G) 1 (n = 47, 70%), G2 (n = 10, 13%), and G3 (n = 1, 1.5%). Late skin toxicity was observed in 13 patients (19%), all of whom experienced G1 toxicity only. On multivariable analysis, diabetes mellitus was predictive of acute skin toxicity (p = 0.003), while age less than 50 years (p = 0.029) and diabetes mellitus (p = 0.013) were predictive of late skin toxicity. Whole breast irradiation with concomitant weekly boost appears feasible and safe. Further investigation is required to fully evaluate this schedule as an alternative to conventional whole breast irradiation with a sequential boost.

Purpose Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. Methods and Materials Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. Results Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. Conclusion Cisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

Purpose To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). Methods and Materials Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: ( 1 ) low effective irradiated liver volume (veff) 2 ) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. Results Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level −1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. Conclusions Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.

e17608 Background: A worldwide decline in prostate brachytherapy (BT) utilization has been reported in multiple health care settings/jurisdictions, despite strong evidence for efficacy and safety compared to other alternatives. We sought to evaluate contemporary trends in BT, EBRT and prostatectomy utilization in a publicly funded healthcare system. Methods: Men with localized prostate cancer diagnosed and treated between 2007 and 2017 in Ontario, Canada were identified using administrative data from the Institute for Clinical Evaluative Sciences. Men were coded to have received EBRT, BT (monotherapy or boost) or prostatectomy as initial definitive management. Trends were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to evaluate patient-, tumour-, and provider-factors on treatment utilization over time. Results: 57,655 men were included in our study. Prostate BT use increased from 7.5% of all treatments in 2007 to 15.4% in 2017 ( p< 0.01), primarily due to increased use of BT boost (1.7% in 2007 to 10.4% in 2017, p < 0.01). Relative to EBRT, BT use increased from 17.9% in 2007 to 28.1% in 2017 ( p< 0.01). On multivariate analysis (MVA), BT boost use increased by 28% per year (OR 1.28, 95% CI 1.26–1.31, p< 0.01) and BT monotherapy use increased by 12% per year (OR 1.12, 95% CI 1.10–1.14, p< 0.01), offset by decreasing prostatectomy use (12% per year, OR 0.88, 95% CI 0.87–0.89, p< 0.01). Comparing BT to EBRT, the strongest predictors of receiving BT were geographic residence (OR 27.6, 95% CI: 20.3–37.6, p< 0.01 between highest/lowest Local Health Integration Networks) and whether the first consulting radiation oncologist performed BT (OR 3.46, 95% CI: 3.15–3.80, p< 0.01). Other significant factors predicting BT use vs. EBRT included lower age, lower PSA, lower Charlson comorbidity score and increasing neighborhood income quintile. Low-intermediate, high-intermediate and high-risk groups were predictive of receiving BT boost, whereas BT monotherapy was predominantly used in low-risk disease. Conclusions: Contrary to trends observed in other jurisdictions, utilization of prostate BT is increasing over time in Ontario. However, substantial variation in BT utilization was found, strongly driven by both geographic region and radiation oncologist BT practice patterns. To our knowledge, this is the first study to report increasing BT utilization in the era of dose-escalated EBRT, with Ontario potentially serving as a model to promote BT utilization elsewhere.

The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia. We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms. More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P

Background Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide. Methods Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine guideline-based indications for proton radiotherapy. Univariate and multivariate logistic regression models were used to determine the characteristics of PTC websites that indicated proton radiotherapy offered greater disease control or cure rates. Results Forty-eight PTCs with 46 English websites were identified. 60·9% of PTC websites claimed proton therapy provided improved disease control or cure. U.S. websites listed more indications than international websites (15·5 ± 5·4 vs. 10·4 ± 5·8, p = 0·004). The most common disease sites advertised were prostate (87·0%), head and neck (87·0%) and pediatrics (82·6%), all of which were indicated in least one international guideline. Several disease sites advertised were not present in any consensus guidelines, including pancreatobiliary (52·2%), breast (50·0%), and esophageal (43·5%) cancers. Multivariate analysis found increasing number of disease sites and claiming their centre was a local or regional leader in proton radiotherapy was associated with indicating proton radiotherapy offers greater disease control or cure. Conclusions Information from PTC websites often differs from recommendations found in international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PTC providers. Electronic supplementary material The online version of this article (10.1186/s13014-018-0988-z) contains supplementary material, which is available to authorized users.

Purpose High-precision radiotherapy relies on accurate anatomic localisation. Urethrography is often used to localise the prostatic apex. However, urethrography is an invasive localisation procedure and may introduce a systemic error. The penile bulb (PB) is contoured to minimise the risk of erectile dysfunction. The purpose of this study is to assess the value of using the PB, as an alternative to urethrography, to localise the prostate. Methods and Materials The PB was localised on 10 patients treated with simplified intensity-modulated arc radiotherapy at computed tomography simulation during treatment weeks 1 and 7. All patients underwent placement of fiducial markers. Urethrography was used only at simulation. Distances from the superior PB contour to the inferior prostate contour, the apex fiducial marker, and to the inferior prostate contour were obtained as well. The PB was contoured by two observers independently. Agreement coefficients and analysis of variance were used to assess reliability between rates and consistency of measurements over time. Results The PB-apex distance was greater than or equal to the urethrogram-apex distance in 24/30 (80%) measurements, and the median difference was 3 mm and was consistent between raters. The greatest variation in PB-IM distance between weeks was 6 mm, the median was 3 mm, and the agreements of measurements between weeks for raters 1 and 2 were 0.79 and 0.69, respectively. These differences were not statistically different and were consistent with the computed tomography slice thickness. Conclusions The PB can be used to identify the prostate apex and can be reliably contoured between observers. Measurements are consistent between patients and through the duration of treatment. The PB distance measurements support studies indicating that urethrography causes a shift of the prostate superiorly. The distance from the PB to prostate apex remains stable during treatment for individual patients but varies between patients.

Summary The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m2) + Cisplatin (30 mg/m2) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4–8. Sunitinib was commenced 4–13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer.

Background and purposeThis study aims to develop an expedited radiotherapy (RT) process and evaluate its time savings in women requiring whole breast RT.Material and methodsAn inter-professional RT team streamlined the computed tomography (CT) simulation and treatment pathway for a ‘QuickStart’ process. Target delineation was performed by an advanced practice radiation therapist and approved by the radiation oncologist (RO) for planning. Automated breast planning software was used for treatment planning and standard quality checks were performed. To assess time savings, the initial 25 QuickStart patients were matched with women who underwent whole breast simulation on the same day (±3 days), treated using the conventional process.ResultsA total of 73 post-lumpectomy women were treated through the QuickStart process; the median consent-to-RT was 2 days (range: 0–13) and the mean CT simulation-to-RT treatment was 2 hours and 42 minutes (SD 0:30). In the subgroup analysis, QuickStart patients saved an average of 11 days from CT simulation-to-RT and had shorter median wait-times for both surgery/chemotherapy-to-RT (60 versus 38 days;p=0·002) and consultation-to-RT (7 versus 20 days;pConclusionsThrough inter-professional team efforts and the application of automated planning software, we have achieved a process that significantly decreases patient wait-times while maintaining the quality of whole breast RT.

Purpose To demonstrate the large-scale clinical implementation and performance of an automated treatment planning methodology for tangential breast intensity modulated radiation therapy (IMRT). Methods and Materials Automated planning was used to prospectively plan tangential breast IMRT treatment for 1661 patients between June 2009 and November 2012. The automated planning method emulates the manual steps performed by the user during treatment planning, including anatomical segmentation, beam placement, optimization, dose calculation, and plan documentation. The user specifies clinical requirements of the plan to be generated through a user interface embedded in the planning system. The automated method uses heuristic algorithms to define and simplify the technical aspects of the treatment planning process. Results Automated planning was used in 1661 of 1708 patients receiving tangential breast IMRT during the time interval studied. Therefore, automated planning was applicable in greater than 97% of cases. The time for treatment planning using the automated process is routinely 5 to 6 minutes on standard commercially available planning hardware. We have shown a consistent reduction in plan rejections from plan reviews through the standard quality control process or weekly quality review multidisciplinary breast rounds as we have automated the planning process for tangential breast IMRT. Clinical plan acceptance increased from 97.3% using our previous semiautomated inverse method to 98.9% using the fully automated method. Conclusions Automation has become the routine standard method for treatment planning of tangential breast IMRT at our institution and is clinically feasible on a large scale. The method has wide clinical applicability and can add tremendous efficiency, standardization, and quality to the current treatment planning process. The use of automated methods can allow centers to more rapidly adopt IMRT and enhance access to the documented improvements in care for breast cancer patients, using technologies that are widely available and already in clinical use.

PurposeThe clinical specialist radiation therapist (CSRT) is a radiation therapist with advanced site-specific clinical skills and knowledge that can be utilised to enhance the education of radiation therapy (RT) students within an academic setting. The aim of this study is to assess the students’ perception of the teaching provided by a CSRT within a case-based learning workshop tailored for breast cancer.MethodsA workshop that followed the patient's RT treatment pathway (consultation, CT simulation, treatment planning and delivery) was led by a breast-site CSRT to 16 third-year students. Following completion of the workshop, a 4-point Likert-scale survey was distributed to explore the students’ didactic and clinical experiences and their general perceptions of the CSRT's contribution to their breast-site module education.ResultsThe median didactic experience reported by the students were ‘a lot’ in patient care and ‘some’ in treatment unit and treatment planning. In contrast, the students reported less clinical experience; the median response for patient care and treatment unit experience was ‘a little’ and ‘none’ for treatment planning. All 13 students who responded to the survey agreed that the CSRT enhanced their understanding of the material. The students felt engaged in the CSRT-lecture and perceived it as value added. The majority of the students (92%) indicated the CSRT to be a useful learning resource in their training and education. Additional comments provided by the students noted the utility of the CSRT-led lecture in consolidating their knowledge of the breast cancer treatment planning and delivery and suggest further expansion of this learning format to other disease sites.ConclusionsThird-year RT students commencing their clinical practicum will have had a greater proportion of their learning from didactic teaching as opposed to clinical experience. In transitioning to their final year, the focus of the curriculum shifts to the application of theory into the clinical environment. The students perceived the CSRT to be a useful resource to enhance their understanding of the breast-site module and their feedback supports the instructional quality and effectiveness of the CSRT in this clinical teaching role.

Background and purpose To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases. Material and methods Eligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I – SBRT: effective liver volume irradiated ( V eff ) V eff >80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2–3, was delivered at 3 escalating dose levels (200–400mg twice daily). Dose limiting toxicity was defined as any grade 3+ liver toxicity, or grade 4+ treatment-related toxicity. Results Thirty-three patients were treated: 18 in stratum I (median dose 42Gy), 15 in stratum II. The MTD was not reached. Grade 3+ toxicity was seen in 33% of patients, at a median of 10days. Two deaths from non-classic liver toxicity occurred post WLRT in stratum II. The median overall survival was 22.3 and 5.7months for strata I and II respectively. Conclusions Sorafenib and 21.6Gy in 6 fraction WLRT resulted in unacceptably high rates of liver toxicity. Although sorafenib combined with SBRT was tolerable, the observed efficacy does not merit further clinical evaluation.

We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (bmsc), a novel self-report measure of common symptoms experienced by patients with brain metastases. Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (wbrt) completed the bmsc at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after wbrt to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated. The symptoms reported on the bmsc were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test&ndash, retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23&ndash, 0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the bmsc and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively. The bmsc captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test&ndash, retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the bmsc itself or correlation with more symptom-specific measures will enhance validity.

Background/Rationale: Patients with locally advanced, triple negative(TN) breast cancer may undergo neo-adjuvant chemotherapy(NAC) prior to definitive surgery. For tumours that demonstrate progression during NAC or rapid recurrence, the optimal second-line or ‘salvage’ therapy is not well defined. Purpose: To examine the efficacy and toxicity of salvage radiotherapy (XRT) and Cisplatin(CDDP) in patients with locally advanced, triple-negative breast cancer. Methods: A retrospective review of LABC databases was performed at 3 quaternary cancer centres to identify patients with TN disease who had salvage XRT +/− CDDP. (Local research ethics board approval was obtained at each centre independently.) Patient demographics, initial staging information and primary pathology reports were reviewed to confirm eligibility. Details of NAC and salvage treatments were collected. Clinical tumour response was determined by physical assessments and imaging and categorized retrospectively using standardized definitions of response and progression. Pathological response was evaluated in all cases if available. Toxicity, loco-regional control, distant disease progression and survival were assessed up to the last available follow-up and reported. Patients who underwent previous XRT were excluded. Results: 12 patients who underwent salvage treatment were identified. All patients had TN, LABC, including 10 patients with invasive ductal carcinoma; 1 metaplastic carcinoma; 1 poorly differentiated carcinoma with neuroendocrine features. The most common indications for salvage treatment were tumour progression during NAC (n = 6) and loco-regional recurrence shortly after NAC and mastectomy (n = 3). The median age was 48 (range, 30–85). 9 patients underwent concurrent XRT + CDDP; 3 patients had salvage radiotherapy only due to poor performance status or co-morbidities. Cisplatin was administered weekly, median dose was 30mg/m2 (range, 25–40mg/m2). Median XRT dose was 65 Gy (range, 50–70 Gy) with 5 patients receiving a BID hyper-fractionated regimen. The median follow-up duration was 8 months (range, 2–60 months). 11 of 12 patients demonstrated a partial or complete clinical response to XRT +/− CDDP. 4 out of 8 patients who had surgery following salvage treatment achieved a complete pathological response (pCR). All patients developed grade 2 or 3 radiation dermatitis. No grade 4–5 toxicity was observed. One patient missed one cycle of CDDP due to grade 1 thrombocytopenia. At the last available follow-up, 4 patients were deceased or developed distant metastasis, 5 patients were alive with no evidence of disease, 3 patients had partial tumour response with surgery pending. Conclusions: Patients with locally advanced, triple-negative breast cancer who progressed during or shortly after NAC had a high clinical response rate when treated with salvage XRT+ CDDP. In patients who underwent surgery after salvage treatment, 50% achieved pCR. Salvage treatments appeared to be relatively well tolerated and safe. This subset of patients is at very high risk for tumour recurrence. Prospective, multi-centre studies of concurrent cisplatin and radiotherapy in the setting of locally advanced, triple negative breast cancer are needed to further assess efficacy and toxicity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-14.

We present a patient with lymphoepithelioma-like carcinoma (lelc) of the breast whose diagnosis is illustrative of the pathology nuances that must be taken into account to successfully reach correct identification of the disease. We also present an overview of our patient&rsquo, s proposed treatment in the context of 16 other reported lelc cases. Although lelc cases are rare, a sufficient number have been reported to discern the natural history of this pathologic entity and to undertake a review of those cases and of the application of oncologic first principles in their management. Given the potential for locoregional spread and distant metastases in lelc, adjuvant therapy has a role in the treatment of this entity.

Breast cancer is managed by a multidisciplinary team with a goal for the timely provision of high quality care. Given radiation oncologist (RO) time constraints, an opportunity arises for task delegation of breast seroma target delineation to an advanced practice clinical specialist radiation therapist (CSRT) with clinical and technical expertise to facilitate treatment planning. To explore this further, we quantitatively evaluated the variability in post-surgical seroma delineation between the CSRT and ROs.Specialized site specific training was provided to the CSRT, who, with 7 ROs, independently contoured the seroma and graded its clarity, using the cavity visualization score (CVS), for 20 patients with clinical stage Tis-2N0 breast tumors. The conformity indices were analyzed for all possible pairs of delineations. The estimated "true" seroma contour was derived from the RO contours using the simultaneous truth and performance level estimation algorithm. Generalized kappa coefficient and center of mass metrics were used to examine the performance level of the CSRT in seroma delineations.The CVS of the CSRT correlated well with the mean RO-group CVS, (Spearman ρ = 0.87, P.05). The mean seroma conformity index for the RO group was 0.61 and 0.65 for the CSRT; a strong correlation was observed between the RO and CSRT conformity indices (Spearman ρ = 0.95, P.05). Almost perfect agreement levels were observed between the CSRT contours and the STAPLE RO consensus contours, with an overall kappa statistic of 0.81 (P.0001). The average center of mass shift between the CSRT and RO consensus contour was 1.69 ± 1.13 mm.Following specialized education and training, the CSRT delineated seroma targets clinically comparable with those of the radiation oncologists in women with early breast tumors suitable for accelerated partial breast or whole breast radiotherapy following lumpectomy. This study provides support for potential task delegation of breast seroma delineation to the CSRT in our current multidisciplinary environment. Further study is needed to assess the impact of this role expansion on radiotherapy system efficiency.

6599 Background: Proton beam therapy (PBT) is a radiotherapy platform that purports an improved therapeutic ratio by way of a rapid radiation dose fall-off. Despite this technology being hindered by significant capital and patient costs, the number of centres offering PBT is increasing exponentially. Consensus guidelines support PBT use in a limited number of disease sites or on clinical trials. As patients frequently obtain information about PBT from hospital or cancer centre websites, the purpose of this study was to evaluate direct to consumer advertising (DTCA) content and claims made by proton therapy centre (PTC) websites. Methods: English PTC websites worldwide were identified using the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine indications for PBT. Univariate and multivariate logistic regression models were used to identify website characteristics that were associated with a higher likelihood to make non-evidence-based claims of PBT such as improved disease control or cure. Results: From the 48 PTCs with 46 English websites, most (58%) did not provide any references for claims made regarding PBT. These included: improved disease control or cure (61%), fewer side effects (85%), or was the standard of care (13%). Prostate (87%), head and neck (87%) and pediatric (83%) cancers were the most frequently listed PBT-indicated disease sites, consistent with international guidelines. However, pancreatobiliary (52%), breast (50%) and esophageal (44%) cancers were frequently advertised despite not being endorsed in any consensus guidelines. On multivariate analysis, an increasing number of listed disease sites and claims of being a regional PTC leader were associated with indicating that PBT offers greater disease control or cure. The availability of PBT through a clinical trial was mentioned on 57% of websites. Conclusions: PTC websites often contain information and DTCA claims inconsistent with international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PBT providers.

Purpose Interfraction and intrafraction changes in amplitude of liver motion were assessed in patients with liver cancer treated with kV cone beam computed tomography (CBCT)-guided stereotactic body radiation therapy (SBRT). Methods and Materials A total of 314 CBCTs obtained with the patient in the treatment position immediately before and after each fraction, and 29 planning 4DCTs were evaluated in 29 patients undergoing six-fraction SBRT for unresectable liver cancer, with (n = 15) and without (n = 14) abdominal compression. Offline, the CBCTs were sorted into 10 bins, based on phase of respiration. Liver motion amplitude was measured using liver-to-liver alignment from the end-exhale and end-inhale CBCT and four-dimensional CT reconstructions. Inter- and intrafraction amplitude changes were measured from the difference between the pre-SBRT CBCTs relative to the planning four-dimensional CT, and from the pre-SBRT and post-SBRT CBCTs, respectively. Results Mean liver motion amplitude for all patients (range) was 1.8 (0.1–7.0), 8.0 (0.1–18.8), and 4.3 (0.1–12.1) mm in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) directions, respectively. Mean absolute inter- and intrafraction liver motion amplitude changes were 1.0 (ML), 1.7 (CC), and 1.6 (AP) mm and 1.3 (ML), 1.6 (CC), and 1.9 (AP) mm, respectively. No significant correlations were found between intrafraction amplitude change and intrafraction time (range, 4:56–25:37min:sec), and between inter- and intrafraction amplitude changes and liver motion amplitude. Intraobserver reproducibility (σ, n = 29 fractions) was 1.3 (ML), 1.4 (CC), and 1.4 (AP) mm. Conclusions For the majority of liver SBRT patients, the change in liver motion amplitude was minimal over the treatment course and showed no apparent relationships with the magnitude of liver motion and intrafraction time.

Purpose To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases. Patients and Methods Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks. Results Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months). Conclusion Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.

Purpose Internal tumor and organ movement is important when considering intensity-modulated radiotherapy for patients with cancer of the cervix because of the tight margins and steep dose gradients. In this study, the internal movement of the tumor, cervix, and uterus were examined using serial cinematic magnetic resonance imaging scans and point-of-interest analysis. Methods and Materials Twenty patients with Stage IB-IVA cervical cancer underwent pelvic magnetic resonance imaging before treatment and then weekly during external beam radiotherapy. In each 30-min session, sequential T 2 -sagittal magnetic resonance imaging scans were obtained. The points of interest (cervical os, uterine canal, and uterine fundus) were traced on each image frame, allowing the craniocaudal and anteroposterior displacements to be measured. The mean displacements and trends were analyzed using mixed linear models. Prediction intervals were calculated to determine the internal target margins. Results Large interscan motion was found for all three points of interest that was only partially explained by the variations in bladder and rectal filling. The intrascan motion was much smaller. Both inter- and intrascan motion was greatest at the fundus of the uterus, less along the canal, and least at the cervical os. The isotropic internal target margins required to encompass 90% of the interscan motion were 4 cm at the fundus and 1.5 cm at the os. In contrast, smaller margins of 1 cm and 0.45 cm, respectively, were adequate to encompass the intrascan motion alone. Conclusion Daily soft-tissue imaging with correction for interfractional motion or adaptive replanning will be important if the benefits of intensity-modulated radiotherapy are to be maximized in women with cervical cancer.

Purpose To measure regression of cancer of the uterine cervix during external beam radiotherapy using magnetic resonance imaging, derive radiobiologic parameters from a mathematical model of tumor regression, and compare these parameters with the pretreatment measurements of tumor hypoxia. Methods and Materials A total of 27 eligible patients undergoing external beam radiotherapy for cervical cancer underwent weekly magnetic resonance imaging scans. The tumor volume was assessed on each of these scans and the rate of regression plotted. A radiobiologic model was formulated to simulate the effect on tumor regression of the surviving proportion of cells after 2 Gy ( SP 2 ), the cell clearance constant (clearance of irreparably damaged cells from the tumor [ T c ]), and accelerated repopulation. Nonlinear regression analysis was used to fit the radiobiologic model to the magnetic resonance imaging-derived tumor volumes and to derive the estimates of SP 2 and T c for each patient. These were compared to the pretreatment hypoxia measurements. Results The initial tumor volume was 8–209 cm 3 . The relative reduction in volume during treatment was 0.02–0.79. The simulations using representative values of the independent biologic variables derived from published data showed SP 2 and T c to strongly influence the shape of the volume–response curves. Nonlinear regression analysis yielded a median SP 2 of 0.71 and median T c of 10 days. Tumors with a high SP 2 >0.71 were significantly more hypoxic at diagnosis ( p = 0.02). Conclusion The results of our study have shown that cervical cancer regresses during external beam radiotherapy, although marked variability is present among patients and is influenced by underlying biologic processes, including cellular sensitivity to radiotherapy and proliferation. Better understanding of the biologic mechanisms might facilitate novel adaptive treatment strategies in future studies.

The abscopal effect is a phenomenon observed in the treatment of metastatic cancer where localized irradiation of a particular tumor site causes a response in a site distant to the irradiated volume. The mechanisms of the abscopal effect are speculated to be of several origins, including distant effects on p53, elaboration of inflammatory agents including cytokines, and, most recently, secondary to immune mechanisms. In this case report, we present a rare report of a patient with hepatocellular carcinoma with lung metastases who, after receiving radiation treatment to the liver, had a treatment response in the liver and a complete response in the lung. Recent advances in the understanding of the primary role of immune-modulated cytotoxicity, especially with the success of immune checkpoint inhibitors, have the potential to turn the abscopal effect from a rare phenomenon into a tool to guide antineoplastic therapy and provide a new line of research.

Background: Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (nat) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (rcts) in this area. Methods: A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing nat for breast cancer. All rcts published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the rcts were analyzed to determine if the methods used matched the expert consensus for specific areas of nat management. A scoring system determined the strength of the agreement between the literature and the expert consensus. Results: Consensus was achieved for all areas of the pathway of care for patients undergoing nat for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published rcts varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. Conclusions: A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving nat for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of nat management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving nat.

Purpose: To assess the feasibility and morbidity of sequential cytoreductive surgery, carboplatin/paclitaxel chemotherapy, and consolidative abdominopelvic radiotherapy (APRT) in ovarian cancer. Methods and Materials: Between 1998 and 2000, 29 patients with optimally cytoreduced epithelial ovarian cancer were treated with carboplatin (135 mg/m 2 ) and paclitaxel (area under the curve [AUC] of 6) followed by APRT in a prospective protocol. All patients were clinically, radiographically, and biochemically (CA-125) free of disease at the completion of chemotherapy. Abdominopelvic radiotherapy was delivered using 6 MV anterior-posterior photon fields to encompass the peritoneal cavity. Median follow-up was 4 years. Results: Two patients experienced Radiation Therapy Oncology Group Grade 3 gastrointestinal toxicity during APRT; 6 patients, Grade 3 or 4 neutropenia; and 3 patients, Grade 3 or 4 thrombocytopenia. Overall, 10 patients had Grade 3 or 4 acute toxicity. All of the acute side effects resolved after treatment was completed, and there were no serious consequences such as sepsis or hemorrhage. Abdominopelvic radiotherapy was abandoned prematurely in 3 patients. Late side effects were seen in 5 patients, including 1 small bowel obstruction, 2 symptomatic sacral insufficiency fractures, 1 case of severe dyspareunia, and 1 case of prolonged fatigue. All resolved with supportive management. The 4-year actuarial disease-free survival was 57%, and the overall survival was 92%. Eleven of 12 patients who relapsed received salvage chemotherapy, which was well tolerated. Conclusions: Abdominopelvic radiotherapy after optimal surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late side effects and does not limit subsequent salvage chemotherapy. Consolidative APRT warrants further investigation as a means of improving the outcome of patients with ovarian cancer.

Aims Whole-brain radiotherapy (WBRT) is a standard treatment recommendation for patients with brain metastases. The goal of treatment is symptom control, which in the short run can be often achieved by steroids. Patients with a short life expectancy may not derive benefit from the addition of radiation. The ability to identify this group would aid the decision of whether to recommend WBRT. Materials and methods Data on all patients referred for WBRT to palliative radiotherapy teams at two comprehensive cancer centres were prospectively collected over a 2-year period. The most frequent radiation dose and fractionation was 2000cGy in 5 fractions over 1 week. Multivariate logistic regression analysis using forward stepwise selection process was used to develop a prediction model for early death (before 8 weeks). The variables considered were sex, performance status, primary disease, weight loss, age, time from primary diagnosis to brain metastases diagnosis, number of metastatic sites and Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) status. Results Two hundred and seventy-five patients with brain metastases were assessed. The median follow-up was 19 weeks, and estimated median overall survival was 5.3 months. Multivariate regression revealed Eastern Cooperative Oncology Group (ECOG) performance status and number of metastatic sites to be significant predictors of early death. The odds ratios were 2.38 (95% confidence interval [CI] 1.77–3.19) and 1.39 (95% CI 1.07–1.81), respectively. Sixty-eight per cent of patients could be correctly classified; however, 55% would have been incorrectly predicted to die early. Conclusions Poor performance status and number of metastatic sites are useful predictors of early death. A regression model was highly predictive overall, but this was primarily due to a high negative predictive value of 86%. The ability to predict patients who would die early (positive predictive value) was only 45%. Thus, despite the understanding that we are over-treating a subset of patients, further research is required to identify patients who do not require radiotherapy.

Left-sided breast radiotherapy (RT) can result in cardiac exposure. This study aims to identify predictive anatomic features in women requiring breath-hold (RT(BH)) for cardiac sparing during adjuvant whole breast RT.We retrospectively reviewed free-breathing (FB) CT scans of 80 women previously treated with left-sided breast RT. Unfavourable cardiac anatomy was defined as the number of consecutive axial CT slices (2 mm) in which the anterior chest wall contacted the heart (Contact(Heart)) or left ventricle (Contact(LV)). The sternal angle and Haller Index (HI) were used to measure chest concavity. Position and volume of post-operative cavity was also quantified.Heart mean dose (D(mean)) was strongly correlated with Contact(LV) (r=0.625, p0.001) and Contact(Heart) (r=0.524, p0.001) but not significantly correlated with tumor size, cavity volume, heart volume, cavity distance to chest wall, sternal angle, or HI. ROC analysis of Contact(Heart) was most predictive of the need for breath-hold (RT(BH)) technique [Area Under Curve=0.815 (SE: 0.048; 95% CI: 0.721-0.91)] and ⩾25 Contact(Heart) CT slices predicted for heart D(mean) ⩾1.7 Gy (68% sensitivity and 82% specificity).Contact(Heart) on FB CT of ⩾25 axial slices (2 mm), ⩾50 mm of para-sagittal heart contact, was predictive of higher heart D(mean) and suggest a potential need for RT(BH).

Purpose A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were significantly better at 12 months than at baseline. Multiple dose-volume parameters correlated moderately with diarrhea, skin, and hematologic toxicity scores. Conclusion IMRT reduces acute grade 3 + hematologic and gastrointestinal toxicities compared with reports from non-IMRT series, without compromising locoregional control. The reported QOL scores most relevant to acute toxicities returned to baseline by 3 months after treatment.

Background and objective:Late oral radiation toxicity occurs in about half of the patients who undergo head-and-neck radiotherapy, reducing the quality of life drastically. The total delivered radiation dose has been shown to be one of the predictors of these late complications. To demonstrate this, the studies carried out so far have used either visual observation together with symptom-based scoring systems or histology to evaluate the tissue response. However, the former lacks imaging information on tissue subsurface and the latter is invasive and exposes the patients to additional risks. Therefore, there is a need for a non-hazardous, non-invasive subsurface monitoring tool that can provide more objective information on dose-dependent response of normal oral tissue to radiation.Materials and methods:To address this unmet clinical need, optical coherence tomography (OCT) was used. A clinical study was conducted on 14 late oral radiation toxicity patients and 5 age-matched healthy volunteers. OCT structural images were acquired from different oral regions in both cohorts and were then de-speckled in order to provide a better visualization of the subsurface layers and features. The alterations in patients’ de-speckled OCT images compared to the healthy cohort are reviewed, and potential correlations between the total dose to specific regions and the abnormal features observed in the OCT images of the same sites are discussed.Results:OCT images were acquired from 32 sites in 14 patients, 15 of these sites belonged to the regions which received >50 Gy radiation dose and the rest to the region which was irradiated to 70 Gy) and contralateral (dose Conclusion:This preliminary clinical study showed the ability of OCT to differentiate subsurface features in the oral regions that received high radiation dose (>50 Gy) compared to healthy oral tissue. These results can be used to design a prospective study to monitor oral subsurface changes periodically (e.g., every 6 months) following radiotherapy, to further understand the mechanism of late radiation toxicity and its relation to dose.

Late oral radiation toxicity is a common condition occurring in a considerable percentage of head and neck cancer patients after radiation therapy which reduces their quality of life. The current examination of these patients is based on a visual inspection of the surface of the oral cavity; however, it is well known that many of the complications start in the subsurface layers before any superficial manifestation. Considering the currently suboptimal examination techniques, we address this clinical problem by using optical coherence tomography (OCT) to monitor the subsurface oral layers with micron-scale resolution images. A spectral-domain OCT system and a specialized oral imaging probe were designed and built for a clinical study to image late oral radiation toxicity patients. In addition to providing qualitative 2D and 3D images of the subsurface oral layers, quantitative metrics were developed to assess the back-scattering and thickness properties of different layers. Metric derivations are explained and preliminary results from late radiation toxicity patients and healthy volunteers are presented and discussed.

164 Background: Adjuvant chemoradiotherapy improves overall and relapse free survival in patients with completely resected gastric cancer, but confers toxicity. This prospective phase I/II clinical trial assessed the toxicity, efficacy and QOL when adding bi-weekly cisplatin to adjuvant chemoradiotherapy with infusional 5-fluorouracil (5-FU). Phase I data showed promising outcomes with acceptable toxicity. Methods: Treatment comprised 45 Gy in 25 fractions of image-guided 3D-CRT or IMRT concurrently with weeks 3-7 of 12 weeks of infusional 5-FU. Cisplatin (up to bi-weekly) was added in a standard dose-escalation protocol. Patients completed the EORTC QLQ-C30 at baseline, end of radiotherapy, 4 weeks post chemotherapy and at 1 and 2 years. Results: Among 55 participants (mean age 54, range 28 to 77; 55% male; median follow-up 3.03 years), QOL compliance ranged from 93% at baseline to 70% at 4 weeks post-treatment. Maximal tolerable dose of cisplatin was 40 mg/m2 bi-weekly for 4 cycles. OS and DFS rates are 85% and 74% respectively at 2 years. Mean scores for global QOL (median difference = -25, p < 0.0001), role and social functioning, fatigue, nausea and vomiting, and appetite declined at completion of radiation; physical functioning showed a statistically significant decline of borderline clinical importance (median difference = -6.7, p

To reduce local recurrence, adjuvant locoregional radiotherapy is given routinely for post-mastectomy breast patients with 4 or more positive lymph nodes. Most institutions adopt a 3- or 4-field radiotherapy technique, in which the field and shielding placements are informed by bony anatomic landmarks viewed on digitally reconstructed radiographs.Here, we report on a 40-year-old woman who underwent a lumpectomy with axillary node dissection, followed by chemotherapy, completion mastectomy, and adjuvant locoregional radiotherapy (50 Gy in 25 fractions) for a multicentric pT1cN2aM0 invasive ductal carcinoma of the right breast. At 9 months after radiotherapy, she presented with a palpable brachial lymph node, a major draining node of the upper extremity, in the axilla, abutting the previous anterior supraclavicular and axillary radiation fields. This occurrence highlights the potential superolateral border of the level i axillary nodal chain and its relationship to the upper extremity lymphatics via the brachial ("sentry") node. Adapting the delineated nodal target volume in locoregional radiotherapy of the breast for disease with extensive nodal involvement or other high-risk pathologic indications may be warranted in certain situations. Careful imaging and an informed discussion with the patient is needed before deciding to treat the sentry node and including the acromial-clavicular joints, balanced with the potential increased risk of lymphedema.

Purpose Adjuvant whole breast radiotherapy (WBRT) for ductal carcinoma in situ (DCIS) improves local control, however an optimal dose fractionation remains undefined. WBRT following breast-conserving surgery for invasive breast cancer demonstrates equivalent efficacy and morbidity for conventional and hypofractionated treatment. Our group policy allowed for the use of both schedules, therefore we compared local control in women with DCIS following breast-conserving surgery. Patients and methods Two hundred and sixty-six patients treated between January 1999 and December 2004 with conventional (50Gy in 25 fractions) or hypofractionated (42.4Gy in 16 fractions or 40Gy/16+12.5Gy boost) WBRT after breast-conserving surgery for DCIS were retrospectively reviewed. Median follow-up was 3.76years (range 0.1–8.9years). Results One hundred and four patients (39%) were treated with conventional and 162 (61%) with hypofractionated WBRT. The median age was 56.7years (range 32.2–83.8years), and prognostic features were well matched in both groups, apart from a small increase in tumour size in the conventional arm (1.75 vs. 2.12cm, p =0.05). Actuarial risk of recurrence at 4years was 7% with hypofractionated WBRT and 6% with the conventional schedule ( p =0.9). Univariate analysis showed an increased risk of recurrence with high nuclear grade tumours (11% at 4years for grade 3 vs. 4% for grade 1/2, p =0.029). Conclusions Hypofractionated adjuvant WBRT following breast-conserving surgery for DCIS has comparable local control to a conventional radiation schedule. Hypofractionated WBRT is more convenient for patients, has equivalent morbidity and should be considered in this patient group.