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.

Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022.

The 24th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Richmond, British Columbia, on 28-29 October 2022. The WCGCCC is an interactive multidisciplinary conference attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals such as dieticians, nurses and a genetic counsellor participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

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.

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.

Is Radiation-Induced Cardiac Toxicity Reversible? Prospective Evaluation of Patients With Breast Cancer Enrolled in a Phase 3 Randomized Controlled Trial.

PURPOSE: Myocardial perfusion defects after breast radiation therapy (RT) correlate with volume of irradiated left ventricle (LV). We aimed to determine the relationship between myocardial perfusion, LV dosimetry, and grade ≥2 late cardiac events in patients with breast cancer undergoing adjuvant RT. METHODS AND MATERIALS: A randomized study evaluated the benefit of inverse-planned intensity modulated radiation therapy over forward-planned intensity modulated radiation therapy for radiation toxicity in breast cancer. A secondary endpoint was evaluating cardiac perfusion by single-photon emission computed tomography done at baseline, 6 months, 1 year, 2 years, and 5 years post-RT. We used receiver operating curve and regression analysis to identify association between perfusion, radiation dose-volumes, and the risk of late cardiac events. RESULTS: Of 181 patients who received adjuvant RT, 102 were patients with cancer in the left breast (called in this study the left-sided group) and 79 were patients with cancer in the right breast (called in this study the right-sided group). Median follow-up was 127 months (range, 19-160 months). A significant worsening of perfusion defects occurred after RT in the left-sided group, which improved by 1 year. Late cardiac events were found among 16 patients (17.2%) in the left-sided group and 4 patients (5.5%) in the right-sided group. Perfusion changes did not correlate with late cardiac events, but LV dose-volumes correlated with late cardiac events. Maintaining the LV volume receiving 5 Gy and 10 Gy to <42 cc and <38cc, respectively, can reduce the risk of radiation-related late cardiac events at 10 years to <5% over baseline. CONCLUSIONS: RT was associated with short-term perfusion defects that improved within 1 year and was not correlated with late cardiac events. The ventricular volumes receiving 5 Gy and 10 Gy were correlated with late cardiac events.

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.

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%.

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.

Adjuvant breast radiotherapy, endocrine therapy, or both after breast conserving surgery in older women with low-risk breast cancer: Results from a population-based study.

BACKGROUND AND PURPOSE: The relative benefit of adjuvant radiotherapy (RT) alone in older women with low-risk early breast cancer (EBC) remains unclear. It is hypothesized that adjuvant RT-alone can improve outcomes of older patients with low-risk EBC, similar to endocrine therapy (ET) alone or combination of RT + ET. METHODS: In this population based study, we identified all women aged ≥70 with T1-2, N0, ER+ve, Her-2/neu-ve EBC treated with breast conserving surgery (BCS), followed by adjuvant treatments (RT-alone, ET-alone, or RT + ET combination) from 2005 to 2015. Primary outcome measures were recurrence-free survival (RFS), overall survival (OS), and breast cancer specific survival (BCSS). Treatment details were collected and Charlson Comorbidity Index (CCI) was calculated. RESULTS: A total of 1166 patients were identified. Median follow-up was 76.5 months. Adjuvant treatments: BCS only 130 (11%), RT 378 (32.5%), ET 161 (14%), and RT + ET 497 (42.5%). Less than 60% of women completed 5-years of ET. Compared to BCS alone, RT resulted in significant improvement in RFS (HR = 0.174; p < 0.001), similar to ET (HR = 0.414; p = 0.007) and RT + ET (HR = 0.236; p < 0.001). Determinants of OS were age, tumor grade, comorbidities, and adjuvant therapy. Increased comorbidity scores (0 vs. 1; 0 vs. ≥2) were associated with reduced OS (HR = 1.40; p = 0.013 and HR = 1.98; p < 0.001), without impact on RFS or BCSS. CONCLUSIONS: Adjuvant RT-alone is a reasonable alternative to ET or RT + ET for older women with biologically favorable EBC. No difference in RFS or BCSS was noted between RT, ET, and RT + ET. Comorbidity was independently associated with reduced overall survival.

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.

Peri-anal surface dose in anal canal VMAT radiotherapy.

INTRODUCTION: Skin bolus may routinely be used in the perineum to build up the surface dose in the treatment of anal cancer (ACC); this may contribute to significant acute skin toxicity. Skin bolus may not be needed with the introduction of modern radiotherapy techniques if these planning techniques would achieve adequate surface dose. Our study is to ascertain if appropriate skin dose can be achieved without the use of bolus when VMAT is used in the treatment of ACC. METHODS: The study includes 10 ACC patients treated with VMAT radiotherapy. Optically stimulated luminescence dosimeters (OSLD) are used to evaluate whether the calculated dose for the VMAT planning technique (VMAT-PT) accurately predicted the dose delivered to peri-anal target region without bolus. The OSLD recorded the dose at the anal verge or at the lower most extent of the tumour for each patient over two fractions. The OSLD was read after each of the two fractions, and the average value was reported. The mean dose over a volume centred on the anal marker was calculated in the treatment planning system (TPS). RESULTS: The mean TPS-calculated dose was 186.1 cGy. The mean of the OSLD-measured doses was 205.7 cGy for a single fraction. The mean of the measured doses was 10.6% higher than the mean of the calculated doses. CONCLUSIONS: The calculated dose for the VMAT-PT consistently under-predicted the dose delivered to the peri-anal target region without bolus. Routine use of skin bolus could be avoided with VMAT-PT when the patient is treated in a supine position.

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.

Cardiac-sparing radiation therapy using positioning breast shell for patients with left-sided breast cancer who are ineligible for breath-hold techniques.

PURPOSE: Patients with left-sided breast cancer (LSBC) are at increased risk of cardiac morbidity from adjuvant breast radiation therapy (ABRT). Breath-hold (BH) techniques substantially reduce the radiation received by heart during radiation therapy for LSBC. However, a subset of patients with LSBC are ineligible for BH techniques due to an inability to breath-hold or because of other comorbidities. To reduce radiation to the heart, we routinely use a custom-made breast shell for the treatment of patients with LSBC who are ineligible for BH techniques. This study evaluates the dosimetric impact of using a breast shell for patients with LSBC undergoing ABRT. METHODS AND MATERIALS: Sixteen consecutive patients with LSBC who failed BH and underwent ABRT using a breast shell during the period of 2014 to 2016 were identified. Treatment was planned using field-in-field tangents with a prescribed dose of 42.5 Gy in 16 fractions. Comparisons between plans with and without a shell were made for each patient using a paired t test to quantify the sparing of organs at risk (OARs) and target coverage. RESULTS: There was no statistically significant difference in the planning target volume of breast coverage. A statistically significant improvement was observed in sparing the heart, left ventricle (LV), and ipsilateral lung (P-value < .001). Plans with the shell spared OARs better than the no-shell plans with a mean dose of 2.15 Gy versus 5.15 Gy (58.2% reduction) to the heart, 3.27 Gy versus 9.00 Gy (63.7% reduction) to the LV, and 5.16 Gy versus 7.95 Gy (35% reduction) to the ipsilateral lung. The irradiated volumes of OARs for plans with and without shell are 13.3 cc versus 59.5 cc (77.6% reduction) for the heart, 6.2 cc versus 33.2 cc (81.2% reduction) for the LV, and 92.8 cc versus 162.5 cc (42.9% reduction) for the ipsilateral lung. CONCLUSIONS: A positioning breast shell offers significant benefit in terms of sparing the heart for patients with LSBC who are ineligible for BH techniques. It also can be used as a simple cardiac-sparing alternative in centers without BH capability.

Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms.

PURPOSE: To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. METHODS AND MATERIALS: Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ2 analysis, and multivariate ordinal regression. RESULTS: Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy. CONCLUSIONS: Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer.

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.