A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy.

PURPOSE: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). METHODS: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). RESULTS: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. CONCLUSIONS: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

Long-Term Patient-Reported Quality of Life of Anal Cancer Survivors Treated With Intensity Modulated Radiation Therapy and Concurrent Chemotherapy: Results From a Prospective Phase II Trial.

PURPOSE: Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. METHODS AND MATERIALS: Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. RESULTS: For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months. CONCLUSIONS: Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.

Effects of Exercise on Motivational Outcomes in Rectal Cancer Patients During and After Neoadjuvant Chemoradiation: A Phase II Randomized Controlled Trial.

OBJECTIVES: Understanding exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiation therapy is important to improve adherence and achieve potential benefit. We report the motivational effects of exercise from the Exercise During and After Neoadjuvant Rectal Cancer Treatment trial. DATA SOURCES: We randomized 36 rectal cancer patients to supervised high-intensity interval training during neoadjuvant chemoradiation therapy followed by unsupervised moderate-to-vigorous exercise after therapy, or usual care. Using the theory of planned behavior, we assessed motivation, perceived benefits/harms, and perceived barriers for exercise during and after therapy. Supervised exercise during neoadjuvant chemoradiation therapy was experienced as meaningfully (d≥0.33) more controllable (p=0.08, d=0.60), more enjoyable (p=0.25, d=0.45), and less difficult (p=0.45, d=-0.38) than anticipated. Unsupervised exercise after therapy was experienced as meaningfully more enjoyable (p=0.047, d=0.50) and less difficult (p=0.43, d=-0.36), but also less controllable (p=0.14, d=-0.80) than anticipated. Common self-reported benefits of exercise both during and after neoadjuvant chemoradiation therapy were cardiovascular endurance, physical functioning, and quality of life. Common self-reported harms were exacerbation of treatment side effects. Frequently reported barriers to exercise during therapy were side effects of treatment, whereas exercise barriers after therapy were lack of motivation and lingering side effects. CONCLUSION: Exercise during and after therapy generally had positive effects on exercise motivation, however, perceived harms and barriers related to treatment side effects were identified. IMPLICATIONS FOR NURSING PRACTICE: Nurses can help rectal cancer patients initiate and maintain exercise during and after neoadjuvant chemoradiation by discussing the potential benefits, harms, and barriers to exercise.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We 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 Participants: RTOG 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. Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Main Outcomes and Measures: Overall 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. Results: Overall 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 Relevance: This 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 Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Do Radiation Oncology Residents Have a Preferred Radiation Treatment Planning Review Format?

In an era of increasing virtual communication, we aimed to investigate current formats used by radiation oncology residents for reviewing radiation treatment plans with attendings, preferences for formats, and reasons contributing to preferences. Residents enrolled in Canadian radiation oncology programs received questionnaires examining training level, typical review formats, preferred format, and reasons for preference. Analysis excluded PGY-1s due to insufficient exposure. Fifty-two residents participated. National response rate was 55%. Overall, hybrid review was the most used format (77%). Virtual review was the most preferred format (44%). Preference for virtual review was most common among junior residents (57%), while in-person review was most preferred by senior residents (45.4%). Few residents typically use their preferred format (35%). Reasons for preference varied between groups in convenience (p < 0.01), interactivity (p < 0.01), and teaching quality (p = 0.04). The persistence of e-learning suggests that virtual treatment planning education will continue to some degree. Junior residents prefer virtual review, while a clearly preferred review format was less apparent among senior residents. Preferences are multifactorial, and the trends seen in reasons for preference between formats may reflect advantages inherent to each. Progress is still needed in optimizing treatment planning education, as suggested by few residents using their preferred format. Residents and staff should collectively decide which educational format for treatment planning best meets educational needs.

Effects of exercise during and after neoadjuvant chemoradiation on symptom burden and quality of life in rectal cancer patients: a phase II randomized controlled trial.

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: Exercise exacerbated some symptoms and worsened QoL during NACRT; however, most negative effects dissipated after NACRT. Larger trials are necessary to confirm these findings. IMPLICATIONS FOR CANCER SURVIVORS: 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.

Tumor Volume Predicts for Pathologic Complete Response in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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 volume >37.3 cm 3 was associated with a greater than 78% probability of not achieving pCR. On multivariate analysis, a GTV <37.3 cm 3 [odds ratio (OR)=3.7, P <0.0001] was significantly associated with an increased pCR rate, whereas tumor length > 4.85 cm was associated with pCR on univariate (OR=3.03, P <0.01) but not on multivariate analysis (OR=1.45, P =0.261). Other clinical parameters did not impact pCR rates. CONCLUSIONS: 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.

More Is Not Better When It Comes to Treating Rectal Cancer With Multimodal Chemoradiation Beyond the Standard Radiation Dose of 5040 cGy.

BACKGROUND: Radiation dose schedules for neoadjuvant chemoradiation for rectal cancers differ, with the most common dose schedule using 5040 cGy in 28 fractions. OBJECTIVES: The aim of this retrospective study was to assess the benefit of higher radiation doses beyond 5040 cGy in the context of pathological response and follow-up events. SETTING: The database from a provincial tertiary cancer center in Canada was the source of information for this study. PATIENTS: Included in this study were 508 consecutive patients with rectal cancer with locally advanced disease (clinical T3/T4 or N1/N2) who received neoadjuvant chemoradiation followed by surgery. Of the 508 patients, 281 received the standard radiation dose of 4500 to 5040 cGy and 227 received a dose >5040 cGy. MAIN OUTCOME MEASURE: The postsurgical pathology, late toxicities, and follow-up outcomes were analyzed. The outcomes were evaluated in relation to the dose of radiation received. RESULTS: Data regarding the clinical outcomes were comparable between the 4500 to 5040 cGy and >5040 cGy radiation groups with pathological complete response rates of 20.9% and 15.4% (p = 0.104); distant recurrence rates of 17.4% and 19.4% (p = 0.36); local recurrence rates of 3.2% and 3.5% (p = 0.36); and the median overall survival rates of 61 and 60.5 months (p = 0.8). No statistically significant correlation of improvement in outcomes was noted with radiation doses beyond 5040 cGy. LIMITATIONS: This is a retrospective study. CONCLUSION: Our study showed that dose escalation beyond the standard dose of 4500 to 5040cGy failed to achieve meaningful clinical outcomes. See Video Abstract at http://links.lww.com/DCR/B633. MS NO ES MEJOR CUANDO SE TRATA DE TRATAR EL CNCER DE RECTO CON QUIMIORRADIACIN MULTIMODAL MS ALL DE LA DOSIS DE RADIACIN ESTNDAR DE CGY: ANTECEDENTES:En neoadyuvancia de cáncer rectal es posible encontrar muchas variaciones, en radioterapia la dosis más común que usa 5040 cGy en 28 fracciones.OBJETIVOS:El objetivo de este estudio retrospectivo fue evaluar el beneficio de dosis de radiación más altas más allá de 5040cGy en el contexto de la respuesta patológica y en su seguimiento.AJUSTE:Base de datos de un centro de cáncer terciario provincial en Canadá.PACIENTES:Se incluyeron en este estudio quinientos ocho pacientes consecutivos con cáncer de recto y enfermedad localmente avanzada (clínica T3 / T4 o N1 / N2) que recibieron quimiorradiación neoadyuvante seguida de cirugía. De los 508 pacientes, 281 recibieron la dosis de radiación estándar de 4500-5040 cGy y 227 recibieron una dosis > 5040 cGy.PRINCIPAL MEDIDA DE RESULTADO:Se analizo evolucion posquirúrgica, toxicidad tardía y seguimiento. Los resultados se evaluaron en relación con la dosis de radiación recibida.RESULTADOS:Los datos con respecto a los resultados clínicos fueron comparables entre los grupos de radiación de 4500-5040 cGy y> 5040 cGy con tasas de respuesta patológica completa de 20,9% y 15,4% respectivamente (p = 0,104); tasas de recurrencia a distancia de 17,4% y 19,4%, respectivamente (p = 0,36); tasas de recurrencia local de 3,2% y 3,5%, respectivamente (p = 0,36); y la mediana de las tasas de supervivencia global de 61 y 60,5 meses, respectivamente (p = 0,8). No se observó una correlación estadísticamente significativa de mejoría en los resultados con dosis de radiación superiores a 5040 cGy.LIMITACIONES:Este es un estudio retrospectivo.CONCLUSIONES:Nuestro estudio mostró que el aumento de la dosis más allá de la dosis estándar de 4500-5040cGy no logró resultados clínicos significativos. Consulte Video Resumen en http://links.lww.com/DCR/B633. (Traducción-Dr. Gunther Bocic).

Concomitant Use of Proton Pump Inhibitors With Capecitabine Based Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: Is it Safe?

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.

Feasibility, Safety, and Preliminary Efficacy of Exercise During and After Neoadjuvant Rectal Cancer Treatment: A Phase II Randomized Controlled Trial.

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.

Impact of dose-capping chemotherapy in concurrent chemoradiotherapy in rectal cancer patients.

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 <95% full weight-based chemotherapy dose. Binary logistic regression was used to study the factors associated with the outcome variables (capped vs. uncapped). Kaplan-Meier estimation evaluated significant predictors of survival. 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.

Dosimetric Parameters Predicting Late Small Bowel Toxicity in Patients With Rectal Cancer Receiving Neoadjuvant Chemoradiation.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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 cm3 and the average SB volume for patients who experienced grade ≥3 SB toxicity was 2179.9 cm3. The predicted V30 for a 5% risk for grade ≥2 SB toxicity was 101.5 cm3 and for grade ≥3 SB toxicity was 201.5 cm3. The volume of small bowel receiving at least 30 Gy (V30) was most strongly associated with grade ≥3 SB toxicity. CONCLUSIONS: This 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 to <200 cm3 will be a useful guideline to minimize the 5 year grade ≥3 late SB toxicity to <5%.

Profiling Determinants of Resting Energy Expenditure in Colorectal Cancer.

Background: Understanding resting energy expenditure (REE) is important for determining energy requirements; REE might be altered in individuals with cancer. The objective of this study was to characterize determinants of REE in patients with stages II-IV colorectal cancer (CRC).Methods: REE was measured via indirect calorimetry in patients with newly diagnosed CRC. Computerized tomography images from medical records ascertained skeletal muscle and total adipose tissue cross-sectional areas, which were then transformed to lean soft tissue (LST) and fat mass (FM) values (in kg). Linear regression assessed determinants of REE.Results: 86 patients were included (n = 55, 64.0% male; 60 ± 12 years old; median body mass index: 27.6, interquartile range: 24.3-31.2 kg/m2), with most (n = 40) having stage III disease. Age, sex, and weight were significant predictors of REE [R2 = 0.829, standard error of the estimate (SEE): 128 kcal/day, P < 0.001]. Replacing weight with LST and FM yielded a similar model, with age, sex, LST, and FM predictive of REE (R2 = 0.820, SEE: 129 kcal/day, p < 0.001).Conclusion: Age, sex, weight, LST, and FM were the main contributors to REE. Further investigation of REE changes over time and its relationship to total energy expenditure, dietary intake, and clinical outcomes should be explored.

Informal caregiver quality of life in a palliative oncology population.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Should Stereotactic Radiosurgery Be Considered for Salvage of Intracranial Recurrence after Prophylactic Cranial Irradiation or Whole Brain Radiotherapy in Small Cell Lung Cancer? A Population-Based Analysis and Literature Review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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) had <5 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. CONCLUSIONS: 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.

Prognostic utility of pre- and post-treatment FDG-PET parameters in anal squamous cell carcinoma.

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.

Evolution of the Radiation Therapist Role in a Multidisciplinary Palliative Radiation Oncology Clinic.

BACKGROUND: Palliative radiation therapists (PRTs) have been integrated in varying capacities into outpatient palliative radiation therapy (RT) services across Canada for over 2 decades. At our institution, PRTs have developed an essential role over 11 years within a palliative radiation oncology (PRO) clinic that focuses on integrating symptom management with radiation oncology assessment for palliative RT. PRTs have had direct clinical, technical, research, and administrative involvement as the clinic evolved from a pilot in 2007 supporting one half-day per week to the current model of five full clinical days. METHODS: Using collaborative reflection, we explored the PRTs' experience and insight. Twelve PRTs who contributed to the PRO clinic for varying lengths of time from 2007 through to 2016 were invited to participate in the development of a collective expression of the PRT experience. Seven PRTs consented to completing an electronic survey consisting of fifteen open-ended questions regarding individual roles and perspectives relating to our PRO clinic. Survey answers were enhanced by semistructured interviews when needed for clarification. Responses were contextualized within the operational changes to our multidisciplinary clinical model, from pilot to integrated service. RESULTS/DISCUSSION: Five respondents answered all of the questions. From the narratives, PRT roles and responsibilities were outlined and their insights and reflections included to contextualize clinical changes. Four phases of the clinic were identified and elucidated. Beginning in January 2007, three PRTs staffed a multidisciplinary clinical pilot one half-day per week for single-fraction, symptomatic bone metastases. The clinic has now evolved through various iterations to the current model with four PRTs sharing a "navigator" role with two registered nurses five full clinic days per week. The range of PRT experiences, responsibilities, and challenges encountered reflected specific clinical and operational conditions. CONCLUSION: As our clinical service model evolved from short-term pilot to fully integrated departmental service, so did the PRT role. PRTs contributing to RT as part of a multidisciplinary model support and advance nontraditional involvement in the holistic care of patients with advanced cancer.

Low-Activity Radioactive Iodine Therapy for Thyroid Carcinomas Exhibiting Nodal Metastases and Extrathyroidal Extension May Lead to Early Disease Recurrence.

BACKGROUND: The application of radioactive iodine in differentiated thyroid carcinomas has become more selective in an attempt to decrease morbidity. While ablative success has been documented, it is less clear how changes in radioactive iodine treatment strategies will influence long-term recurrence rates for patients with larger tumors and adverse pathological features, including extrathyroidal extension and nodal metastases. METHODS: Patients diagnosed between 1995 and 2008 with differentiated thyroid carcinoma treated with thyroidectomy followed by radioactive iodine treatment were eligible. All patients were followed for a minimum of five years using a standardized follow-up protocol requiring both biochemical and imaging assessments for recurrent disease (n = 219). Patients were stratified by initial radioactive iodine activity, and disease-free survival was calculated using the Kaplan-Meier method, with significant differences defined by the log-rank test. RESULTS: In this cohort, 46% of patients had clinical metastases and 74% had primary tumors >1.5 cm. Patients who had recurrences were more likely to present with extrathyroidal extension (p = 0.002) and lymph node metastases at diagnosis (p < 0.001). Patients presenting with both extrathyroidal extension and lymph node metastases had a significantly worse time to progression if treated with <1850 MBq radioactive iodine compared to those patients treated with >1850 MBq (25 months vs. 121 months; p = 0.004). The use of lower-activity radioactive iodine ablative therapy was associated with more early recurrences (p = 0.003). Being aged younger or older than 45 years did not impact the time to recurrence nor did the use of level 6 dissection. On multivariate analysis, lymph node metastases at diagnosis and multiple applications of radioactive iodine were linked to increased risk of recurrence. Patients with neither, or only one, adverse pathologic feature had excellent outcomes, regardless of initial ablative activity, with <10% of patients recurring over a 10-year time span. CONCLUSIONS: Recurrent disease in differentiated thyroid carcinoma is more common in patients treated with low-activity radioactive iodine in patients with lymph node metastases and extrathyroidal extension. These recurrences typically occur within four years of initial treatment. Patients lacking both of these risk factors treated with low radioactive iodine activity (<1850 MBq) have excellent outcomes, even after 10 years.

Exercise during and after neoadjuvant rectal cancer treatment (the EXERT trial): study protocol for a randomized controlled trial.

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.

Predictors of adherence to aerobic exercise in rectal cancer patients during and after neoadjuvant chemoradiotherapy.

This pilot study explored predictors of adherence to exercise during and after neoadjuvant chemoradiotherapy (NACRT) in rectal cancer patients. Eighteen rectal cancer patients were prescribed three supervised aerobic exercise sessions/week during NACRT followed by ≥150 min/week of unsupervised aerobic exercise after NACRT. Although not statistically significant, adherence to supervised exercise during NACRT was meaningfully better for patients who were women (d = .82; P = .12), younger (d = -.62; P = .30), married (d = .62; P = .42), with better mental health (r = .32; P = .21), fewer diarrhea symptoms (r = .48; P = .052), and higher anticipated enjoyment (r = .31; P = .23), support (r = .32; P = .22), and motivation (r = .31; P = .23). After NACRT, adherence was significantly better for patients who reported worse mental health (r = -.56; P = .046) and meaningfully better for patients who were women (d = .54; P = .38), better educated (d = .77; P = .22), had no comorbidities (d = -.63; P = .17), and exercised at baseline (d = 1.05; P = .12). Demographics, tumor side effects, and motivational variables may predict adherence to exercise during and after NACRT.