Search

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.

ImportancePathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).ObjectiveWe sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.Design, Setting, and ParticipantsRTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes.InterventionPatients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone.Main Outcomes and MeasuresOverall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017.ResultsOverall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45).Conclusions and RelevanceThis ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies.Trial RegistrationClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791)

131 Background: Pre-clinical evidence suggest that statins have antiproliferative, proapoptotic, and anti-invasive properties. Also, statins can sensitize cancer tissues and protect normal tissues to the effects of radiation. A standard treatment of locally advanced rectal cancer (LARC) involves neoadjuvant CRT followed by surgery and adjuvant chemotherapy. Retrospective analyses of statin use in rectal cancer patients receiving CRT suggest a higher pathological complete response rate (pCRr). Methods: Patients with clinical stage II-III rectal adenocarcinoma, within 5 cm of the anal verge (AV) or less than 12cm from the AV with threatened circumferential resection margin were treated with rosuvastatin 40 mg daily starting 2 weeks prior to the start and until 4 weeks after the end of CRT. The primary objective of the study was pCRr. Secondary objectives included, near-CRr, Ro resection rate (RR), sphincter preservation, 3-year relapse free survival (RFS), 3-year overall survival (OS), toxicity and safety. A Simon’s minimax two-stage design was used to determine significance. A pCRr of ≥25% was required to reject the null hypothesis. RFS and OS rates were calculated using the Kaplan-Meier product-limit method. Results: Forty-five patients were enrolled from 2016 to 2021. Sixty-seven percent were male with a median age of 54 (IQR 37- 61), 97.8% (44/45) had ECOG PS of 0-1, 15.6% (7/45) were cT4, 73.3% (33/45) were cN+. Of the 38 evaluable patients, 9 had a pCR (23.7%), an additional 9 had a near-pCR (23.7%). With a median follow-up of 3.26 years, the 3-year OS rate was 96.3% (95% CI (0.765, 0.995)) and the 3-year DFS rate was 77.9% (95% CI (0.604, 0.883)) in the evaluable patients. One patient elected for non-operative management and has an on-going clinical CR for the last 15 months. Surgery was sphincter sparing in 17 patients (43.6%) and an 87.2% Ro RR was observed. Toxicities attributable to rosuvastatin included: two patients with elevations in liver enzymes, grade 3. Remaining toxicities were grade 2 or less, with the most common toxicities being fatigue (n = 5) and pain (n = 3). Only 2 patients experienced CPK elevations, both grade 2. Conclusions: The addition of rosuvastatin to nCRT resulted in a considerable complete and near-complete response rate with an acceptable toxicity profile. Rosuvastatin treatment should be studied further in the total neoadjuvant and non-operative management settings for locally advanced rectal cancer. Clinical trial information: NCT02569645 .

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.

Many patients with advanced cancer receive primary supports from informal caregivers (IC). As patient health deteriorates, IC assume increasing responsibility, often accompanied by distress. We investigated the quality of life (QOL) of IC of patients referred to a palliative radiotherapy (PRT) program. IC accompanying patients to a dedicated PRT clinic completed a survey based on the validated Caregiver Quality of Life Index-Cancer (CQOLC). Demographics, burden, and engagement in support services were evaluated. Summary statistics were calculated, and parameters were assessed for association with CQOLC scores by a generalized linear model. Two hundred one surveys were analyzed representing 197 unique patients. The mean age was 68.3 years, with predominantly lung (25.0%) and prostate (19.3%) malignancies. 24.4% had been in hospital/long-term care within the previous 7 days. IC were 60.8% female, and 60.6% were the patient’s spouse. 69.5% lived with the patient and 38.3% were additionally employed. IC spent a daily mean of 6.6 h (SD 7) assisting with instrumental (72.5%) and basic (37.5%) activities of daily living. Mean CQOLC score was 82.1/140 (SD 20). 63.8% of IC had previously accessed support service(s), most commonly home care (37.2%) and pharmacy (29.1%). 55.9% indicated interest in services not yet accessed. Multivariate analysis revealed additional employment, cohabitation, poor patient performance status, and interest in accessing more support services significantly correlated with higher IC burden. Employing the CQOLC to screen IC of patients referred to a PRT program permits early identification of vulnerable IC to facilitate linkage with appropriate supports.

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.

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.

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

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

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.

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: Identifying the most radiosensitive patient group would have huge clinical implications. Methods: A tissue bank containing skin fibroblasts, whole blood, lymphocytes, plasma and lymphoblastoid cell lines from clinically radiation hypersensitive patients was established from patients in Europe and Canada. Over-reacting individuals had CTCAE3.0 severe acute side effects grade 2 or more occurring at very low radiation doses where these side effects are unexpected or grade 3-4 lasting more than 4 weeks after the end of radiotherapy and/or requiring surgical intervention at any time or severe late side effects grade 3-4. Results: Eleven patients have been identified with a mean age of 61.6 ± 8.5 years (range 49-74). Two patients were male, 9 female. One patient had non-small cell lung cancer, 6 breast cancer, 2 head and neck cancer, one lymphoma and one meningioma. The mean follow-up time after radiotherapy was 1658 ± 1048 days (range 84-3752). Conclusions: The establishment of an international tissue bank of the rare group of patients with extreme hypersensitivity to radiotherapy was proven to be feasible and should enable in-depth molecular studies. © 2010 Elsevier Ireland Ltd. All rights reserved.

Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10–100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. Early needs assessment was advantageous in determining the optimal team and methods of assessment for our ‘one-stop’ BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.

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.

This study evaluated the dosimetric effect of small bowel oral contrast on conventional radiation therapy, linear accelerator-based intensity modulated radiation therapy (IMRT), and helical tomotherapy (HT) treatment plans.Thirteen patients with rectal cancer underwent computed tomography (CT) simulation with oral contrast (CCT) in preparation for chemoradiation therapy. The contrast in the small bowel was contoured, and a noncontrast CT scan (NCCT) was simulated by reassigning a CT number of 0 Hounsfield units to the contrast volume. Conventional, IMRT, and HT plans were generated with the CCT. The plan generated on the CCT was then recalculated on the NCCT, maintaining the same number of monitor units for each field, and the plans were not renormalized. Dosimetric parameters representing coverage of the planning target volume with 45 Gy (D98%, D95%, D50%, and D2%) and sparing of the bladder and peritoneal cavity (D50%, D30%, and D10%) were recorded. The ratio of dose calculated in the presence of contrast to dose with contrast edited out was recorded for each parameter. A paired Student t test was used for comparison of plans.For conventional plans, there was0.1% variance in the dose ratio for all volumes of interest. For IMRT plans, there was a 1% decrease in the mean dose ratio, and the range of dose ratios for all volumes was greater than that for HT or conventional plans. For HT plans, for all volumes of interest, the mean dose ratio was0.2%, and the range for all patients was1%. For all IMRT dosimetric parameters, the difference was in the order of 1% of the mean dose (P.05). The dose difference was not statistically significant for the conventional or HT plans.The use of CCT during CT simulation has no clinically significant effect on dose calculations for conventional, IMRT, and HT treatment plans and may not require replacement of the contrast with a CT number of 0 Hounsfield units.

Purpose: Radiation therapy is an important treatment modality for oncology patients. DNA sequence variants have so far been identified in only a few genes in radiosensitive cancer patients. Patients known to be clinically radiosensitive were tested for mutation of a gene involved in DNA double-strand break repair and sister chromatid cohesion— hHR21. Methods and Materials: Clinically radiation-sensitive patients were accrued to the study after giving informed consent. Blood samples were obtained and lymphoblastoid cell lines established. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the hHR21 gene, and the DNA product was sequenced to identify any genetic abnormalities. Northern blot analysis, cell survival, and growth assays were performed on control cells and cells with hHR21 variants, and a restriction digest assay was developed to screen for carriers of a detected gene variant. Results: The DNA sequence of the hHR21 gene was determined in 19 radiation-sensitive cancer patients. In 6 of the 19 patients, a thymidine (T) to cytosine (C) transition was detected at position 1440 of the hHR21 open reading frame (T1440C). This variant did not alter the amino acid sequence and was likely to be a polymorphism. One patient with a particularly severe radiation reaction had a second sequence variant immediately adjacent to the first. This was a guanine (G) to adenine (A) transition (G1441A), resulting in a change of the amino acid sequence (glycine → arginine) in a portion of the protein conserved in evolution. This suggests that this DNA alteration may be biologically significant. Restriction digest with the HpaII enzyme confirmed the presence of both sequence variants on the same allele. Conclusions: We describe the first two DNA sequence variants ever found in the hHR21 gene, in patients with clinical radiation hypersensitivity. Although no direct evidence for the involvement of hHR21 alterations in the radiosensitivity of the cancer patients examined has been demonstrated, the possibility exists that homozygous mutations or other mutations of this gene could contribute to radiosensitivity. A simple test is described that could be applied to screening for these variants in relevant populations.

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.

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.

Purpose: To evaluate the feasibility of skin-sparing by configuring it as an organ-at-risk (OAR) while delivering whole-breast intensity-modulated radiotherapy (IMRT) in early breast cancer. Methods and Materials: Archival computed tomography scan images of 14 left-sided early‐breast tumor patients who had undergone lumpectomy were selected for this study. Skin was contoured as a 4- to 5-mm strip extending from the patient outline to anterior margin of the breast planning target volume (PTV). Two IMRT plans were generated by the helical tomotherapy approach to deliver 50 Gy in 25 fractions to the breast alone: one with skin dose constraints (skin-sparing plan) and the other without (non‐skin-sparing plan). Comparison of the plans was done using a two-sided paired Student t test. Results: The mean skin dose and volume of skin receiving 50 Gy were significantly less with the skin-sparing plan compared with non‐skin-sparing plan (42.3 Gy vs. 47.7 Gy and 12.2% vs. 57.8% respectively; p < 0.001). The reduction in skin dose was confirmed by TLD measurements in anthropomorphic phantom using the same plans. Dose‐volume analyses for other OARs were similar in both plans. Conclusions: By configuring the skin as an OAR, it is possible to achieve skin dose reduction while delivering whole-breast IMRT without compromising dose profiles to PTV and OARs. 2008 Elsevier Inc. Early breast cancer, Skin-sparing radiation, Intensity-modulated radiotherapy, Helical tomotherapy, Organat-risk.

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.