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Nonoperative management (NOM) of locally advanced rectal cancer is an emerging approach allowing patients to preserve their anal sphincter. Identifying clinical factors associated with pathologic complete response (pCR) is essential for physicians and patients considering NOM.In total, 412 locally advanced rectal cancer patients were included in this retrospective analysis. Tumor volumes were derived from pretreatment MRI. Clinical parameters such as tumor volume, stage, and location were analyzed by univariate and multivariate analysis, against pCR. A receiver operator characteristic curve was generated to identify a tumor volume cut-off with the highest clinically relevant Youden index for predicting pCR.Seventy-five of 412 patients (18%) achieved pCR. A tumor volume threshold of 37.3 cm 3 was identified as predictive for pCR. On regression analysis, a tumor volume37.3 cm 3 was associated with a greater than 78% probability of not achieving pCR. On multivariate analysis, a GTV37.3 cm 3 [odds ratio (OR)=3.7, P0.0001] was significantly associated with an increased pCR rate, whereas tumor length4.85 cm was associated with pCR on univariate (OR=3.03, P0.01) but not on multivariate analysis (OR=1.45, P =0.261). Other clinical parameters did not impact pCR rates.A tumor volume threshold of 37.3 cm 3 was identified as predictive for pCR in locally advanced rectal cancer patients receiving neoadjuvant chemoradiation. Tumors above this volume threshold corresponded to a greater than 78% probability of not achieving pCR. This information will be helpful at diagnosis for clinicians who are considering potential candidates for NOM.

Introduction The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT). Methods 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.0 m2 and who received Results The median follow-up time was 7.54 years. The rate of disease recurrence was significantly higher in dose-capped patients (35%) compared to those without dose-capping (24%, P = 0.016). The adjusted odds ratio for dose-capped patients experiencing recurrence was 1.64 compared to uncapped patients (95% CI, 1.10–2.43). Overall, dose-capped patients were less likely to experience significant toxicity requiring dose reduction and/or treatment break when compared to uncapped patients (15% and 28% respectively, P = 0.008).There was significant differences in PFS between capped and uncapped group (77% vs. 85%; P = 0.017). The 5-year OS in the capped group was 75.0%, and 80% in the uncapped group ( P = 0.149). Conclusions Rectal cancer patients treated with dose-capped CRT were at increased risk of disease recurrence. Patients dosed by actual BSA did experience excessive toxicity compared to dose-capped group. We recommend that chemotherapy dose-capping based on BSA should not be practiced in rectal cancer patients undergoing CRT.

We previously demonstrated that exercise during and after neoadjuvant chemoradiation (NACRT) for rectal cancer may improve the rate of pathologic complete/near complete response. Here, we report the effects of exercise on symptom management and quality of life (QoL). Rectal cancer patients (N = 36) were randomized to a supervised high-intensity interval training program during NACRT followed by unsupervised continuous exercise after NACRT or usual care. Patient-reported outcomes were assessed at baseline, post-NACRT, and presurgery including symptom burden (M.D. Anderson Symptom Inventory) and QoL (European Organisation for Research and Treatment of Cancer QLQ- C30 and -CR29). During NACRT, exercise significantly worsened stool frequency (adjusted between-group difference, 25.8; 95% CI, 4.0 to 47.6; p = 0.022), role functioning (adjusted between-group difference, -21.3; 95% CI, -41.5 to -1.1; p = 0.039), emotional functioning (adjusted between-group difference, -11.7; 95% CI, -22.0 to -1.4; p = 0.028), and cognitive functioning (adjusted between-group difference, -11.6; 95% CI, -19.2 to -4.0; p = 0.004) compared to usual care. After NACRT, exercise significantly worsened diarrhea (adjusted between-group difference, 1.2; 95% CI, 0.1 to 2.3; p = 0.030) and embarrassment (adjusted between-group difference, 19.7; 95% CI, 7.4 to 32.1; p = 0.003) compared to usual care. Exercise exacerbated some symptoms and worsened QoL during NACRT; however, most negative effects dissipated after NACRT. Larger trials are necessary to confirm these findings. If the clinical benefit of exercise is confirmed, then the modest symptom exacerbation during NACRT may be considered tolerable. However, in the absence of any clinical benefit, exercise may be contraindicated in this clinical setting.

Aim Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC. Methods LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens. Results Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P=0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P=0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P=0.411 and 0.264, respectively).Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio=0.001, P=0.988) or overall survival (hazard ratio=1.179, confidence interval=0.249-5.579, P=0.835). Conclusions Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.

Background Neoadjuvant chemoradiation (NACRT) improves outcomes for patients with rectal cancer; however, there are dose-limiting toxicities and only a 15% to 27% pathologic complete response (pCR) rate. Exercise may help manage toxicities and improve treatment response, but feasibility and early efficacy have not been established. EXERT was a phase II trial designed to establish the feasibility and safety of exercise and provide the first evidence of efficacy. Materials and Methods Patients with rectal cancer scheduled to receive NACRT were randomly assigned to usual care (n = 18) or exercise (n = 18) involving supervised exercise during NACRT and unsupervised exercise after NACRT. The primary outcome was cardiorespiratory fitness (VO2 peak). Clinical outcomes included treatment toxicities, treatment completion, and treatment response. Results Median attendance at supervised exercise sessions during NACRT was 82%, and median self-reported exercise after NACRT was 90 min/wk. From baseline to post-NACRT, VO2 peak increased by 0.4 mL·kg−1·min−1 in the exercise group and decreased by 0.8 mL·kg−1·min−1 in the usual care group (P = .47). There were no significant differences between groups for grade 3/4 toxicities or treatment completion. Of 18 patients in the exercise group, 10 (56%) achieved pCR/near pCR compared with 3 of 17 (18%) in the usual care group (P = .020). Conclusion Exercise during and after NACRT is feasible for many patients with rectal cancer and may improve pCR despite limited fitness improvements. Larger trials are warranted to confirm if exercise is an effective intervention for improving treatment outcomes in this clinical setting.

The aim of this study was to identify dosimetric parameters that predict late small bowel (SB) toxicity after neoadjuvant long course chemoradiation (CRT) for rectal cancer.Four hundred eighty-six consecutive patients with locally advanced rectal cancers (clinical T3/T4 or N1/N2) who received CRT followed by surgery and had dosimetric data available for analysis were included in this study. The dose-volume relationship between small bowel irradiation and late small bowel toxicity was evaluated and a mathematical model to predict for late SB toxicity was derived.Among the 486 patients with a median follow-up of 60 months from completion of radiation, 36 (7.4%) patients experienced ≥ grade 2 and 21 (4.3%) developed ≥ grade 3 late SB toxicity. A statistically significant association between the development of grade ≥3 late small bowel toxicity and the volume of small bowel irradiated was found at each dose level from 5 to 40 Gy (P.001 for all dose volumes) in 5 Gy intervals. The average SB volume for patients who experienced grade ≥2 SB toxicity was 2149.9 cmThis study demonstrates the significant dose-volume relationship between volume of small bowel receiving 30 Gy (V30 Gy) and late grade ≥3 SB toxicity. When planning CRT for patients with rectal cancer, restricting V30 to200 cm

3 Background: Concurrent chemoradiation (CRT) with 2 doses of 5-fluorouracil (5-FU) and mitomycin C (MMC) is the standard of care for anal canal cancer (ACC) in North America while 1 dose of MMC is an acceptable practice. Given the lack of randomized data of 1 vs 2 doses of MMC on disease outcomes, we have conducted a population-based study to elucidate the impact of 1 vs. 2 doses of MMC on patterns of treatment failure (POF) and outcomes in ACC treatment. Zainab Al Habsi, Aswin Abraham, Mustafa Al Balushi, Gabriella Tankel, Karen Mulder, Heather Warkentin, Dan Schiller, Keith Tankel, Nawaid Usmani, Diane Severin, Kim Paulson, Hatim Karachiwala, Clarence Wong, Tirath Nijjar, Kurian Joseph. Methods: Data was collected from the provincial cancer registry of patients with stage I-III ACC who were treated with concurrent CRT from 2000 to 2018. Recurrence free survival (RFS), overall survival (OS), and ACC specific survival were calculated. Results: 428 patients with a median age of 58 years (29-88 years) were included in this analysis. 234 (54.7%) patients received 1 dose of MMC and 194 (45.3%) received 2 doses of MMC. At a median follow-up of 78.5 months (5-252 months), 89 (20.8%) patients developed disease recurrence: 44 (10.3%) loco-regionally, 39 (9.1%) distally and 6 (1.4%) had both local and distant recurrences. Cox Regression analysis showed that the dosage of MMC did not have an impact on overall recurrence (HR = 0.883, p = 0.561), whereas stage III was associated with increased risk for recurrence (HR = 5.238, p = 0.021). Subgroup analysis showed an association of stage IIIb and IIIc with recurrence (HR = 13.33, p = 0.008 and HR = 6.933, p = 0.011 respectively), but was not impacted by the use of 1 vs. 2 doses of MMC. The dosage of MMC did not show any association with local recurrence (HR = 1.136, p = 0.655) or distant recurrence (HR = 0.743, p = 0.267). However, in Stage IIIc patients, 2 doses of MMC showed a trend towards improved distant RFS (HR = 0.626,p = 0.084). Conclusions: Our analysis showed that the patterns of failure and the risk of loco-regional and distant failures were similar between patients who received 1 vs. 2 doses of MMC for stage groups I to IIIc. These finding support routine use of single dose of MMC along with 5FU and radiotherapy for definite chemoradiation. However, a trend towards better RFS was demonstrated with a second dose of MMC in patients with stage IIIc disease.

Summary Background A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone for dysphagia relief in the palliative setting. Methods This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0–2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1–4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m 2 on day 1 or 20 mg/m 2 per day on days 1–4 of radiotherapy at clinician's discretion) and intravenous fluorouracil 800 mg/m 2 per day on days 1–4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed. Findings Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36–55) patients in the chemoradiotherapy group and 38 (35%, 26–44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI −2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5–4·8) versus 3·4 months (3·1–4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1–8·3) versus 6·7 months (4·9–8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3–4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy. Interpretation Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting. Funding National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.

Background Standard treatment for locally advanced rectal cancer includes 5–6 weeks of neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision 6–8 weeks later. NACRT improves local disease control and surgical outcomes but also causes side effects including fatigue, diarrhea, hand-foot syndrome, and physical deconditioning that may impede quality of life (QoL), treatment completion, treatment response, and long-term prognosis. Interventions to improve treatment outcomes and manage side effects that are safe, tolerable and low-cost are highly desirable. Exercise has been shown to improve some of these outcomes in other cancer patient groups but no study to date has examined the potential benefits (and harms) of exercise training during and after NACRT for rectal cancer. Methods/design The Exercise During and After Neoadjuvant Rectal Cancer Treatment (EXERT) trial is a single-center, prospective, two-armed, phase II randomized controlled trial designed to test the preliminary efficacy of exercise training in this clinical setting and to further evaluate its feasibility and safety. Participants will be 60 rectal cancer patients scheduled to receive long-course NACRT followed by total mesorectal excision. Participants will be randomly assigned to exercise training or usual care. Participants in the exercise training group will be asked to complete three supervised, high-intensity interval training sessions/week during NACRT and ≥ 150 min/week of unsupervised, moderate-to-vigorous-intensity, continuous exercise training after NACRT prior to surgery. Participants in the usual care group will be asked not to increase their exercise from baseline. Assessments will be completed pre NACRT, post NACRT, and pre surgery. The primary endpoint will be cardiorespiratory fitness (VO2 peak) at the post-NACRT time point assessed by a graded exercise test. Secondary endpoints will include functional fitness assessed by the Senior’s Fitness Test, QoL assessed by the European Organisation of Research and Treatment of Cancer, and symptom management assessed by the M.D. Anderson Symptom Inventory. Exploratory clinical endpoints will include treatment toxicities, treatment completion, treatment response, and surgical complications. Discussion If the preliminary findings of EXERT are positive, additional research will be warranted to confirm whether exercise is an innovative treatment to maintain QoL, manage side effects, and/or improve treatment outcomes in rectal cancer patients. Trial registration ClinicalTrials.gov, ID: NCT03082495. Registered on 9 February, 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2398-1) contains supplementary material, which is available to authorized users.

Purpose/Objective(s) Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is a standard treatment for patients with stage II and III rectal cancer. However, non-operative management of rectal cancer is an emerging approach to allow patients to preserve their anal sphincter. Factors that may help identify patients most likely to have a pathological complete response (pCR) would be helpful for physicians and patients considering a non-operative approach. Materials/Methods A total of 377 patients from our institution who had clinical stage II or III rectal cancer treated with neoadjuvant chemoradiation were included in the analysis. Patients were grouped based on their pCR status. Clinical parameters including overall stage, gross tumor volume (GTV), and radiation dose were analyzed by univariate and multivariate analysis, with pCR being the dependent variable. A Receiver Operator Characteristic (ROC) curve was generated in order to identify a tumor volume cutoff with the highest sensitivity for predicting pCR. Results The cohort had a median age at diagnosis of 61 years, 68% were male, and 85% presented with stage III disease. 68 of the 377 patients (18%) included in our analysis achieved pCR. A tumor volume of Conclusion Our analysis identified a GTV volume of

Prophylactic cranial irradiation (PCI) improves survival and prevents intracranial recurrence (IR) in limited stage (LS) and extensive stage (ES) small cell lung cancer (SCLC). However, despite PCI, IR affects 12%-45%, and limited data exist regarding salvage brain reirradiation (ReRT). We performed a population-based review of IR in SCLC.Demographic, treatment, and outcome data of consecutive patients (N = 371) with SCLC assessed at a tertiary cancer centre (01/2013-12/2015) were abstracted, and summary statistics calculated. Kaplan-Meier estimates and univariate and multivariate analysis (MVA) via the Cox proportional hazard model were performed.Median age was 66.1 years, and 59.8% were Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Median survival was 24 months (95% CI 18.3-29.7 months) for LS (N = 103) and 7 months (95% CI 6.1-7.9 months) for ES (N = 268). 72 of 103 patients with LS and 97 of 214 of those with ES received PCI. 54 of 268 ES presented with brain metastases (BM) of whom 46 of 54 received whole brain RT (WBRT). 18.9% (32/169) recurred post-PCI (13 LS; 19 ES) and 30.4% (14/46) recurred after WBRT. Of those who recurred/progressed after cranial RT, 56.5% (26/46) had5 BM, 39.1% had no extracranial disease, and 50% were ECOG 0-2. In retrospect, 17 of 46 would have been candidates for salvage stereotactic radiosurgery: 13 post-PCI and 4 post-WBRT.This cohort challenges commonly held beliefs that IR is always diffuse, associated with clinical deterioration, and synchronous with systemic failure. Approximately 1 in 3 SCLC patients with IR after PCI or WBRT appear clinically appropriate for salvage stereotactic radiosurgery.

PURPOSE/OBJECTIVES To assess the feasibility and safety of an aerobic exercise intervention in patients with rectal cancer during and after neoadjuvant chemoradiotherapy (NACRT). . DESIGN A prospective, single-group design with assessments at pre-NACRT, post-NACRT, and presurgery. . SETTING The Cross Cancer Institute and University of Alberta in Edmonton, Canada. . SAMPLE 18 patients with rectal cancer scheduled to receive long-course NACRT followed by definitive surgery. . METHODS Participants received a supervised moderate-intensity aerobic exercise program three days per week during six weeks of NACRT followed by an unsupervised aerobic exercise program for 150 minutes or more per week for 6-8 weeks prior to surgery. . MAIN RESEARCH VARIABLES Eligibility rate, recruitment rate, follow-up rate, exercise adherence, serious adverse events, health-related fitness outcomes, and patient-reported outcomes. . FINDINGS Follow-up rates post-NACRT were 83% for health-related fitness outcomes and 94% for patient-reported outcomes. Patients attended a median of 83% of their supervised exercise sessions and completed a mean of 222 minutes per week (SD = 155) of their unsupervised exercise. No serious adverse events were observed or reported. Most health-related fitness outcomes and patient-reported outcomes declined during NACRT and recovered after NACRT. . CONCLUSIONS Aerobic exercise is feasible and safe for patients with rectal cancer during and after NACRT. . IMPLICATIONS FOR NURSING Patients with rectal cancer are able to engage in moderate-intensity aerobic exercise during NACRT.

Background and purpose We prospectively assessed the contributions of PET to initial staging, early detection of treatment failures, and prognostication in patients with anal squamous cell carcinoma (ASCC). Materials and methods Consecutive patients with ASCC referred for radical chemoradiotherapy (CRT) consented to undergo FDG-PET imaging pre-treatment and at 3 and 6 months post-treatment. Clinicopathologic data were collected and CT and PET imaging reviewed for contribution to staging and recurrence detection. Maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were assessed for association with progression-free survival (PFS), cause-specific survival (CSS), and overall survival (OS) using the Kaplan–Meier and Cox regression models. Results Between 2009 and 2016, 73 patients with clinical stages I-IIIB ASCC completed curative-intent CRT. Median follow-up was 48 months. 14 patients died and 18 patients experienced disease progression. 4-year PFS, CSS, and OS were 73%, 87%, and 84%, respectively. A pre-treatment MTV >35 cm3 predicted for worse PFS (p = 0.011) and CSS (p = 0.024) on univariate and multivariate analyses, employing an MTV definition of voxels ≥25% of SUVmax. Higher 6-month post-treatment SUVmax and SUVpeak predicted for worse PFS and OS (p ≤ 0.011). Pre-treatment SUVmax, SUVpeak, and TLG, and 3-month post-treatment SUVmax and SUVpeak did not significantly correlate with survival outcomes. Conclusions Our findings support that pre-treatment MTV provides meaningful prognostic information, with suggestion that an MTV delineation threshold of voxels ≥25% of SUVmax is appropriate in the anal region. Post treatment, the combination of clinical examination and PET effectively detected all treatment failures. Higher 6-month post-treatment SUVmax and SUVpeak predicted worse PFS and OS; however, the optimal timing of post-treatment PET imaging remains unclear.

Background and purpose Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced anal canal carcinoma, although treatment-related side effects can affect patient quality of life (QOL). The purpose was to prospectively evaluate the effects of Tomotherapy (HT) based CCRT on patient reported QOL in locally advanced anal cancer. Patients and Methods Fifty-four patients treated with HT and concurrent 5-fluorouracil/mitomycin-C underwent QOL evaluation at baseline, after treatment, and during follow-up with EORTC core (QLQ-C30) and colorectal (QLQ-CR29) questionnaires. The QOL scores at baseline and post-treatment were compared. Results All C30 functional symptoms, except emotional and cognitive functioning, were impaired end-of-treatment and recovered by 3months follow-up. The majority of symptom scores were worse end-of-treatment but recovered by 3months except for fecal incontinence (FI), diarrhea, urinary incontinence (UI), and dyspareunia which persisted. FI returned to baseline at 12months while diarrhea, UI, and dyspareunia persisted. Conclusions Most impaired functions and symptoms following HT based CCRT were temporary and improved by 3months post-therapy. Late complications affecting QOL were FI, sexual function, UI, and diarrhea. Our observations support routine use of IMRT and emphasize the significance of precise evaluation of sexual, urinary, and anorectal functions before starting CCRT and routine incorporation of QOL evaluations.

Background: Non-small-cell lung cancer (NSCLC) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. MicroRNAS (miRNAS) are a class of short, noncoding RNA molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting NSCLC. We investigated the stage-specific NSCLC detection potential of an efficient panel of 3 miRNAS (MIR-21, MIR-210, MIR-372) using a single sputum sample. Methods: A single spontaneously expectorated sputum sample was prospectively collected from 21 early NSCLC (≤stage II) patients, 22 advanced NSCLC (≥stage III) patients, and 10 control subjects. MiRNA expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. Results: Mean tumour size (±95% confidence interval) in the early and advanced NSCLC patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced NSCLC cases respectively. In comparing the early NSCLC group with the control group, the miRNA panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced NSCLC group, the miRNA panel detected NSCLC with a sensitivity and specificity of 64% and 100% respectively. Conclusions: A sputum MIR-21, MIR-210, and MIR-372 expression profile might provide a sensitive and highly specific means for detecting NSCLC. Sputum miRNA analysis demonstrates promise as a potential complementary screening tool.

Aerobic exercise is safe and feasible for rectal cancer patients during and after neoadjuvant chemoradiotherapy (NACRT), but their motivation to perform such exercise is unknown. Here, we explore the motivational outcomes, perceived benefits and harms, and perceived barriers to exercise during and after NACRT. Rectal cancer patients (n = 18) participated in supervised aerobic exercise during NACRT followed by unsupervised exercise after NACRT. Using the theory of planned behavior, we assessed perceived benefits, harms, enjoyment, support, difficulty, and barriers for exercise both during and after NACRT. Patients reported that exercise during NACRT was more enjoyable (p = 0.003) and less difficult (p = 0.037) than initially anticipated. The most common perceived benefits of exercise during NACRT were cardiovascular endurance (75 %), quality of life (75 %), and self-esteem (65 %). After NACRT, the most common perceived benefits were physical functioning (93 %), cardiovascular endurance (86 %), and quality of life (79 %). The most common perceived harms of exercise during NACRT were fatigue (31 %), diarrhea (31 %), and skin irritation (24 %). After NACRT, the most common perceived harms were fatigue (21 %) and hand-foot-syndrome (15 %). Side effects from NACRT were the most common exercise barrier during NACRT (88 %) whereas lack of motivation was the most common barrier after NACRT (79 %). Rectal cancer patients reported aerobic exercise during NACRT to be more enjoyable and less difficult than anticipated despite significant barriers. This positive motivational response may facilitate recruitment and adherence in future interventions. Moreover, rectal cancer patients identified potential benefits and harms that should be closely monitored in future interventions.

Background and purpose To evaluate toxicity, local control, and survival of anal cancer patients treated with helical tomotherapy (HT) and concurrent 5-fluorouracil and mitomycin-C (5FU/MMC). Materials and methods Fifty-seven patients were treated with HT and concurrent 5FU/MMC. The planning objectives were to deliver 54Gy to the tumor (PTV 54 ) and 45Gy to the nodes at risk (PTV 45 ) in 30 fractions. Patients were reviewed for toxicity weekly during HT, every 6weeks for 3months, and then every 3–4months for 5years. Results The median follow-up was 40months. The median age was 58years (range: 37–83). Stage distribution: stage II-48%, IIIA-18%, IIIB-34%. The majority of patients developed ⩽grade 2 acute toxicity scores. The most common ⩾grade 3 acute toxicity was neutropenia (40%). Common late toxicities were grade 2 anal incontinence (16%) and telangiectasia (12%). The 3year colostomy-free survival rate was 77% (95% CI: 61–87%), 3year disease-free survival rate was 80% (CI: 66–89%), and 3year overall survival was 91% (CI: 77–96%). Conclusions Incorporation of HT with concurrent 5FU/MMC had low treatment-related acute and late morbidity with few treatment breaks. However, the expected dosimetric benefit for hematological toxicity was not experienced clinically.

39 Background: Tumour factors (eg primary site, size) helpful in prognostication in early stage cancer may be less important than patient factors, such as Karnofsky performance status (KPS), later in the disease trajectory. We evaluated the utilization of the parameters attitude (ATT) and psychosocial support (PSS) in predicting remaining lifespan by two experienced multidisciplinary teams (MDT). Methods: After clinical assessment of consecutive patients, a quantitative clinical prediction of survival (CPS) was made prospectively, independently and anonymously by each health care provider (HCP). HCP recorded up to 4 factors (free-text) influencing their CPS. The Palliative Radiation Oncology (06/2010-12/2014) and Palliative Care (06/2012-01/2014) teams participated. Demographics, disease information, and date of death were abstracted. Summary statistics (means, standard deviations, and proportions) were calculated. Estimates for actual survival (AS) were obtained. Wilcoxon tests compared continuous variables and chi-square tests were used for categorical variables. Results: 2,582 predictions were made by 11 disciplines for 881 unique patients over 1,054 clinic visits. Median age was 66 years, 58.6% were male and 37.3% had lung cancer. KPS, when recorded, was ≥ 70 at 46.3% of visits. Cognitive status was below expected for 174/460 visits. Mean AS was 177 ± 190 days and mean CPS was 258 ± 300 days. The median number of factors cited was 4 (range 0-4), with disease extent most common. ATT and PSS as perceived by the HCP influenced 6.7% and 5.8% of CPS respectively, varying across disciplines (p < 0.0001). Overall, mean CPS was significantly longer when ATT (337d vs 252d; p < 0.0001) or PSS (310d vs 254d; p < 0.004) was quoted. CPS estimates by Nursing and Students were longer when ATT was mentioned (both p < 0.004). Students’ CPS were longer when PSS was described (p = 0.048). Mean AS was also longer when ATT (259d vs 178d; p < 0.0001) or PSS (224d vs 181d; p = 0.03) were cited overall, as well as within the Nursing, Student and Pharmacist groups (all p < 0.05). Conclusions: Attitude and available psychosocial support as evaluated by MDT appeared to correlate with both clinical prediction of survival and actual survival in this cohort.

219 Background: The optimal dose for palliative whole brain radiotherapy (WBRT) continues to be debated. Common regimens include 20 Gy in five and 30 Gy in 10 fractions. We aimed to identify factors associated with WBRT dose schedules, hypothesizing that clinical prediction of survival (CPS) would influence prescribing practice. Methods: Demographic and clinicopathologic data were collected for consecutive patients with brain metastases receiving WBRT through a dedicated palliative radiation oncology clinic. At initial consultation, CPS were prospectively collected from treating radiation oncologists. Karnofsky performance status (KPS) and Mini-Mental Status Examination were available for 88.6% and 75.1%, respectively. Dose fractionation was collected and summary statistics calculated. Parameters were assessed for association with five fraction schedules using binary logistic regression, with odds ratios and 95% CI reported. Results: 193 patients underwent WBRT (N = 102 from 2010-2012; N = 91 from 2013-2014); 38/193 had 48 extracranial sites irradiated concurrently. 46.1% were male, mean age was 64.7 years (SD 11.6), and 63.7% had lung cancer. Median KPS was 70 (range 20-100) and median MMSE score was 27/30 (range 13-30). Median CPS and actual survival were 150 days (range 21-730d) and 96 days (range 11-1029d), respectively. 18.7% received WBRT within 30 days of death. 78.2% (151/193) and 17.6% (34/193) received five and 10 fractions, respectively; 8/193 were prescribed other schedules. On multivariate analysis, patients with KPS ≤ 70 were 5.93 times more likely to have received 5-fractions (95% CI 2.51-14.1; p < 0.0001). Those treated 2010-2012 were less likely to have received 5 fractions (OR 0.28; 95% CI 0.11-0.68; p = 0.005). CPS, age, gender, MMSE, histology, disease extent, and extracranial irradiation were not predictive of WBRT schedule. Conclusions: Patients treated with WBRT with KPS ≤70 and those treated more recently were more likely to receive five fractions. Oncologist CPS was not a statistically significant predictor of schedule in this cohort.

Background. Oligodendrogliomas are rare central nervous system (CNS) tumors. Although surgery remains the primary treatment, the role of postoperative radiation treatment remains a matter of controversy. This study assesses whether postoperative radiation improves survival and local tumor control when compared with surgical treatment alone. Methods. The medical records of 72 patients with the diagnosis of oligodendroglioma, registered at the Princess Margaret Hospital (PMH) between 1958 and 1984, were reviewed retrospectively. The data of 68 patients were evaluated, but 4 patients were excluded from the analysis because of inadequate follow-up. The median follow-up period at the time of analysis was 7.5 years. Tumors were classified as oligodendrogliomas, malignant oligodendrogliomas, or mixed oligoastrocytomas. Fifty-eight (85%) patients received postoperative irradiation at initial diagnosis, and 10 (15%) patients were treated with surgery alone. In most patients (76%), the radiation dose was 5000 cGy in 25 fractions given during a period of 5 weeks. Results. Five- and 10-year overall survival was 66% and 30%, respectively. Forty-two (62.0%) patients experienced disease relapse during the follow-up period. The median time to relapse from initial diagnosis was 2.6 years. Most tumor recurrences were at the primary site. Two patients developed distant metastasis within the CNS axis. Histologic subtype was the only significant prognostic factor for survival. The patients with oligodendroglioma and malignant oligodendroglioma had 5-year survival rates of 73% and 32%, respectively (P = 0.033). Conclusions. The authors drew three conclusions. (1) Most patients eventually died with this tumor from local recurrence without distant metastasis. Local tumor control remains the major problem. (2) Tumor histologic subtype is a significant prognostic factor. (3) No statistically significant benefit can be attributed to postoperative irradiation; however, the number of patients not receiving radiation therapy was small (10). Thus, the role of radiation therapy remains a matter of controversy.

Purpose A planning study to compare helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for the treatment of anal canal cancer. Materials and methods Sixteen (8 males and 8 females) patients with anal cancer previously treated radically were identified. HT and IMRT plans were generated and dosimetric comparisons of the plans were performed. The planning goals were to deliver 54Gy to the tumor (PTV 54Gy ) and 48Gy to the nodes at risk (PTV Node ) in 30 fractions. Results PTVs: HT plans were more homogeneous for both men and women. Male patients: HT vs. IMRT: D max : 55.87±0.58 vs. 59.17±3.24 ( p =0.036); D min : 52.91±0.36 vs. 44.09±6.84 ( p =0.012); female patients: HT vs. IMRT: D max : 56.14±0.71 vs. 59.47±0.81 ( p =0.012); D min : 52.36±0.87 vs. 50.97±1.42 ( p =0.028). OARs: In general, HT plans delivered a lower dose to the peritoneal cavity, external genitalia and the bladder and IMRT plans resulted in greater sparing of the pelvic bones (iliac crest/femur) for both men and women. Iliac crest/femur: the difference was significant only for the mean V10Gy of iliac crest in women ( p ⩽0.012). External genitalia: HT plans achieved better sparing in women compared to men ( p ⩽0.046). For men, the mean doses were 18.96±3.17 and 15.72±3.21 for the HT and IMRT plan, respectively ( p ⩽0.017). Skin: both techniques achieved comparable sparing of the non-target skin ( p =NS). Conclusions HT and IMRT techniques achieved comparable target dose coverage and organ sparing, whereas HT plans were more homogeneous for both men and women.

35 Background: Survival is often overestimated, yet physicians rely on such predictions to recommend appropriate therapy and assist with end-of-life planning. Administration of radiotherapy (RT) within the last 30 days of life has been suggested as an indicator of poor quality care, since acute side effects reduce quality of life with insufficient time for symptomatic benefit. We investigated whether life expectancy predicted at the time of consultation correlates with palliative RT recommendations. Methods: Radiation oncologists from a dedicated palliative Radiation Oncology outpatient clinic anonymously completed survival estimations after clinical assessment, and recorded factors upon which each estimate was based. Demographics, primary histology, RT details, and date of death were abstracted. Summary statistics and Kaplan-Meier estimates of actual survival (AS) were obtained. Correlations between AS and clinical predictions of survival (CPS) were calculated using Spearman’s correlation coefficient (r). Multivariate logistic regression analysis explored factors associated with RT recommendations. Results: 476 survival predictions were made for 420 unique patients (06/2010-01/2014). Median age was 67.7 years, 61.9% were male and 44.0% had lung cancer. Karnofsky Performance Status (KPS) was > 70 at 23.9% of clinic visits. At 84.5% of consultations, RT was prescribed to 538 separate volumes (29.2% receiving 8Gy, 54.8% 20Gy, 6.3% 30Gy, 9.7% other). Mean AS was 179 days (SD 187d), moderately correlating with mean CPS of 242 days (SD 261d) with r = 0.38 (p < 0.0001). Factors most frequently cited as influencing CPS were KPS and extent of disease. At the time of 30/476 visits, CPS was < 30 days; at 19 of these visits, RT was prescribed to 26 volumes (21 bone, 3 whole brain, 2 chest), 2/3 as single fractions, finishing a median of 17 days before death. Expected survival was predictive of prescribed RT dose on univariate logistic regression, but did not retain significance on multivariate analysis. Conclusions: Despite international surveys in which prognosis has been cited as the main factor affecting treatment decisions, in this cohort, other aspects appear to have more strongly influenced palliative RT recommendations.

Purpose: To determine the maximal tolerated dose of hypofractionated thoracic radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer patients. Methods and Materials: Three radiotherapy regimens were used. Radiotherapy was given in two phases: patients initially received 20 Gy in 10 fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned with conformal techniques. All patients received four cycles of cisplatin (25 mg/m2) and etoposide (100 mg/m2) chemotherapy. Radiotherapy commenced with Day 1 of Cycle 2 of chemotherapy. All complete/near-complete responders were offered prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was based on the dose that caused unacceptably high rates of radiotherapy-related toxicity. Results: Thirteen patients were accrued. All patients who commenced radiotherapy received all prescribed chemo- and radiotherapy. There were no treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3 esophagitis. With a median follow-up of 7 months, median overall survival was 9.5 months. Conclusions: The maximal tolerated dose of thoracic radiotherapy with concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.

163 Background: The dominant symptom for pts with esophageal cancer is dysphagia. Palliative radiotherapy is commonly employed for symptom relief. We report the effect on QoL in our study comparing a 2-3 week course of RT alone vs the same RT with a single cycle of concomitant CT. Methods: 220 pts with malignant dysphagia were randomized to receive RT (30-35Gy in 10-15 fr) (n=109) ± concomitant CT (5FU and cisplatin D1-4) cycle. The primary outcome was dysphagia relief. QoL was evaluated using EORTC QLQ30/OES18 at baseline, wk 9, 13 and mthly x1yr. Group mean scores were compared between arms using Wilcoxon Rank-Sum test. Proportion of pts with improved, stable or worsened QoL (≥10 point change at any time compared with baseline) using chi square and MH chi-square test (for trend), while time to dysphagia improvement was compared using K-M estimates. Results: QoL compliance ranged from 77% (169/220) at baseline to 62% (36/58) at mth12 and was similar between groups. Baseline mean scores were equivalent between arms with the exception of physical [79 (SD19) CRT vs. 83.84 (SD19) RT; p=0.016] and role domains [61 (SD34) CRT vs. 72 (SD32) RT; p = 0.01]. There was no significant difference in QoL between the arms. The proportion of pts with improvement in the dysphagia domain was 50% CRT vs 64% RT (ns) while the time to improvement was 2.6m CRT vs 2.3m RT (ns). The eating domain was improved in 68% CRT and 74% RT (ns) while global QoL was 46% in both arms. Other symptom domains/items that were improved in more than half of the pts included 62% in pain and 52% in appetite. Functional domain improvements were moderate ranging from 41% emotional, 39% role, 38% social, 28% cognitive to 18% physical (average of scores in both arms). Conclusions: QoL data showed improvement in domains associated with nutritional intake for 50-70% of pts depending on the symptom measured. This was accompanied by moderate improvement in functional domains. No significant benefit was observed when CT was added to RT alone. Clinical trial information: NCT00193882.

Best Practice in Advanced Esophageal Cancer: A Report on TransTasman Radiation Oncology Group TROG 03.01 and NCIC CTG ES.2 Multinational Phase 3 Study in Advanced Esophageal Cancer (OC) ComparingQualityofLife(QOL)andPalliationofDysphagia inPatients TreatedWith Radiation Therapy (RT) or Chemoradiation Therapy (CRT) M.G. Penniment, J.A. Harvey, R. Wong, S. Stephens, H. Au, C.J. O’Callaghan, A.B. Kneebone, S. Ngan, I.G. Ward, R. Roy, T. Sullivan, T. Nijjar, J. Biagi, and L.A. Mulroy; Royal Adelaide Hospital, Adelaide, Australia, Princess Alexandra Hospital, Wooloongabba, Australia, Princess Margaret Hospital, Toronto, ON, Canada, Cross Cancer Institute, Edmonton, AB, Canada, National Cancer Institute of Canada Clinical Trials Group, Kingston, ON, Canada, Royal North Shore Hospital, St Leonards, Australia, Peter MacCallum Cancer Centre, East Melbourne, Australia, Canterbury Regional Cancer and Hematology Service Christchurch Hospital, Christchurch, New Zealand, Castle Hill Hospital, Queen’s Centre for Oncology and Hematology, Hull, United Kingdom, University of Adelaide, Adelaide, Australia, Department of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada, QEII Health Sciences Centre, Halifax, NS, Canada