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).

A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

BACKGROUND: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer). METHODS: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. A dense-module-searching method identified modules enriched with significant genes from a genome-wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow-up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense-module-searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self-identified as Caucasian. RESULTS: The rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta-analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15-1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal-basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow-up of 4.4 years. CONCLUSIONS: Through its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well-annotated independent cohorts of Caucasian men.

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.

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.

Cost-effectiveness analysis of metformin with enzalutamide in the metastatic castrate-resistant prostate cancer setting.

INTRODUCTION: Enzalutamide (Enza) is an effective treatment for metastatic castrate-resistant prostate cancer (mCPRC). However, Enza is not cost-effective (CE) at willingness to pay (WTP) thresholds from $0-$125 000/quality adjusted life years (QALYs) and is therefore a strain on valuable health care dollars. Metformin (Met) is inexpensive (~$8.00/month) and is thought to improve prostate cancer specific and overall survival compared to those not taking Met. We hypothesized that there must be an added effect Met could provide that would make Enza CE thereby alleviating this financial strain on government health care budgets. MATERIALS AND METHODS: We constructed a Markov model and performed a threshold analysis to narrow in on the added effect needed to make such a combination therapy cost-effective at various WTP thresholds. RESULTS: At a WTP threshold of $50 000/QALY Enza + Met is unlikely to be CE unless it increases Enza's efficacy by more than 30%. At a WTP threshold of $100 000, Enza + Met could be CE barring Met adds 18.73% to the efficacy of Enza. CONCLUSIONS: Enza + Met is unlikely to be CE at WTP thresholds less than $100 000/QALY; these results make sense because a therapy that is not CE at these WTP thresholds by itself is unlikely to be CE with an adjuvant therapy that keep a patient on such a treatment for even longer. Finally, our model suggests that the mCRPC setting is not the optimal place to trial adding Met as the relative costs are high and utility values low.

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.

Exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiotherapy.

PURPOSE: 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. METHODS: 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. RESULTS: 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 %). CONCLUSIONS: 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.

Prostate size, source configuration, and dosimetry dynamics of stranded 125I seed implants.

PURPOSE: To quantify changes in prostate size and seed movement over time after transperineal implantation of stranded 125I seeds, and to determine their impact on prostate dosimetry. METHODS: CT and MR (T2, balanced steady-state free precession) image triplets were acquired on days 0, 3, 10, and 30 for a cohort of 20 patients and registered automatically. Prostate contours were drawn on MR-T2 images; seeds were found and matched in successive CT images. Prostate volume and dimensions, seed movements, and prostate dose metrics V200, V150, V100 and D90 were calculated, and their dynamic behaviors quantified in an operationally defined prostate coordinate system. RESULTS: Cohort-averaged reductions in prostate A-P dimension (∼8%) and L-R dimension (∼5%) inferred from seed movements agreed with those obtained from contour measurements, whereas prostate volume and S-I dimension (implant direction) reductions inferred from seed movements were overestimated by about 30%. Average overall seed movement was 4.8 ± 3.0 mm, of which the only identifiable systematic component was resolution of prostate edema. Cohort-averaged ratios of prostate V200, V150, V100, and D90 on day 30 relative to day 0 were 1.67, 1.33, 1.02, and 1.08, respectively. CONCLUSIONS: Postimplant prostate size reduction in the SI (implant) direction cannot reliably be inferred from stranded seed movements. Apart from large-scale migration, residual seed movements relative to the prostate after accounting for edema resolution appear to be random. Prostate V100 and D90 changes 30 days post implant are modest, whereas those for V150 and V200 are substantial.

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.

Control4Life: A randomized controlled trial protocol examining the feasibility and efficacy of a combined pelvic health rehabilitation and exercise fitness program for individuals undergoing prostatectomy.

BACKGROUND: Urinary incontinence (UI), erectile dysfunction and cardiometabolic conditions are common after prostatectomy for prostate cancer (PCa). Although physical activity could improve overall survival and quality of survivorship, fear of UI can restrict participation in exercise. Individuals with PCa could benefit from therapeutic exercise programming to support continence recovery and cardiometabolic health. AIM: The main objective of this study is to determine the feasibility and the effects of a combined pelvic health rehabilitation and exercise fitness program on UI after prostatectomy. The combined exercise program will be delivered both in-person and virtually. METHODS: This study follows a modified Zelen, two-arm parallel randomized controlled trial design. A total of 106 individuals with PCa will be recruited before prostatectomy surgery. Participants will be randomized between two groups: one receiving usual care and one receiving a combined exercise fitness and intensive pelvic floor muscle training program. Exercise programming will begin 6-8 weeks after prostatectomy and will last 12 weeks. Outcomes include: the 24-h pad test (primary outcome for UI); physical fitness, metabolic indicators, and patient-reported outcomes on erectile function, self-efficacy, severity of cancer symptoms and quality of life. Important timepoints for assessments include before surgery (T0), after surgery (T1), after intervention (T3) and at one-year after surgery (T4). CONCLUSION: This study will inform the feasibility of offering comprehensive exercise programming that has the potential to positively impact urinary continence, erectile function and cardiometabolic health of individuals undergoing prostatectomy for prostate cancer. CLINICALTRIALS REGISTRATION NUMBER: NCT06072911.

Treatment options for localized prostate cancer.

OBJECTIVE: To describe treatment options for clinically localized prostate cancer: radical prostatectomy, prostate brachytherapy, external beam radiation, and active surveillance. QUALITY OF EVIDENCE: Prostate-specific antigen (PSA) outcomes presented are from non-randomized, cohort, and other comparisons trials (level II evidence). We describe PSA outcomes from Canadian centres when they are available. One small randomized controlled trial (level I evidence) in localized prostate cancer is available to compare radical prostatectomy with brachytherapy. MAIN MESSAGE: Treatment choice in prostate cancer is based on initial PSA level, clinical stage of disease, and Gleason score, together with baseline urinary function, comorbidities, and patient age. In this article, we describe patients' eligibility for and the common side effects of all treatment options. Prostate brachytherapy and active surveillance have evolved as new standard treatments of localized prostate cancer. We give a brief overview of the brachytherapy procedure, side effects, and PSA outcomes across Canada, as well as active surveillance guidelines. CONCLUSION: Prostate cancer treatment requires a multidisciplinary approach, with input from both urology and radiation oncology. Input from family physicians is often as important in helping guide patients through the treatment decision process.

Seminal Vesicle Treatment for Localized Prostate Cancer Treated with External Beam Radiotherapy.

This study retrospectively reviewed data from men with localized prostate cancer treated with external beam radiotherapy (EBRT). We identified 359 men with localized prostate cancer treated with curative EBRT at the Cross Cancer Institute between 2010-2011. The volume of seminal vesicles (SVs) treated as well as dose values were extracted. These volumes were compared to gold standard contours drawn by a trained expert based on consensus European Society for Radiotherapy and Oncology (ESTRO) contouring guidelines. Patient and tumor characteristics were extracted for these patients. Memorial Sloan Kettering prostate cancer nomogram was used to assign a predicted risk of SV involvement for each patient based on baseline tumor characteristics. In patients with a predicted risk of SV involvement greater than 15% (n = 184), 86.5% (SD = 18.6) of the base of the SVs were treated with EBRT, compared to 66.7% (SD = 32.6) for patients with a predicted risk of SV involvement less than 15% (n = 175, p < 0.0001). Similarly, the mean percentage of proximal and total SV volumes treated with EBRT was 75.6% (SD = 24.4) and 68.7% (SD = 26.0) for patients with a predicted risk of SV involvement of greater than 15%, compared to 50.3% (SD = 31.0, p < 0.0001) and 41.0% (SD = 27.8, p < 0.0001) for patients with a risk of less than 15%. The results indicate that all parts of the SVs are more likely to be contoured in men with >15% risk of SV involvement than those with <15% risk. However, radiation oncologists still contour a high percentage of SVs in men with <15% risk of SV involvement, suggesting that there may be over-treatment of SVs that increases the risk of rectal or bladder toxicity.

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.

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.

Metformin for Prevention of Anthropometric and Metabolic Complications of Androgen Deprivation Therapy in Prostate Cancer Patients Receiving Radical Radiotherapy: A Phase II Randomized Controlled Trial.

BACKGROUND: Patients with prostate cancer undergoing treatment with radical radiation therapy (RT) plus androgen deprivation therapy (ADT) experience a constellation of deleterious metabolic and anthropometric changes related to hypogonadism that are associated with increased morbidity and mortality. We assessed the effect of metformin versus placebo to blunt the adverse effects of ADT on body weight, waist circumference, and other metabolic parameters. METHODS AND MATERIALS: This phase 2, multicenter, randomized controlled trial (RCT) randomized normoglycemic men with locally advanced prostate cancer receiving radical RT and ADT (18-36 months) in a 1:1 ratio to receive metformin 500 mg by mouth 3 times a day (for 30-36 months) versus identical placebo. RESULTS: From December 2015 to October 2019, 83 men were randomized with median follow-up of 23 months. Baseline mean body mass Index (BMI) of the cohort was 30.2 (range 22.2-52.5). Change in mean weight relative to baseline was lower among men who received metformin compared with placebo at 5 months (-1.80 kg, P = .038), but was not significant with longer follow-up (1 year: +0.16 kg, P = .874). Although participants on ADT had increases in waist circumference in both study arms, metformin did not significantly reduce these changes (1 year: +2.79 cm (placebo) versus +1.46 cm (metformin), P = .336). Low-density lipoprotein (LDL) cholesterol was lower in the metformin arm (-0.32 mmol/L) compared with the placebo arm (-0.03 mmol/L) at 5 months (P = .022), but these differences were not significant with longer follow-up (1 year: -0.17 mmol/L vs -0.19 mmol/L, P = .896). There were no differences in HbA1C, triglyceride, high-density lipoprotein (HDL) cholesterol, and total cholesterol by study arm. CONCLUSIONS: Men receiving radical RT and ADT gained weight and had increases in waist circumference over time that metformin did not significantly mitigate. Although this study did not observe any preventive effect of metformin on the anthropometric and metabolic complications of ADT, metformin continues to be studied in phase 3 RCTs in this patient population to assess its potential antineoplastic effects.

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.

High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy.

Traditional external light-based Photodynamic Therapy (PDT)'s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in penetrating deep-seated tumors. To address this, the emerging field of radiation-activated PDT (radioPDT) uses X-rays to trigger photosensitizer-containing nanoparticles (NPs). A key consideration in radioPDT is the energy transfer efficiency from X-rays to the photosensitizer for ultimately generating the phototoxic reactive oxygen species (ROS). In this study, we developed a new variant of pegylated poly-lactic-co-glycolic (PEG-PLGA) encapsulated nanoscintillators (NSCs) along with a new, highly efficient ruthenium-based photosensitizer (Ru/radioPDT). Characterization of this NP via transmission electron microscopy, dynamic light scattering, UV-Vis spectroscopy, and inductively coupled plasma mass-spectroscopy showed an NP size of 120 nm, polydispersity index (PDI) of less than 0.25, high NSCs loading efficiency over 90% and in vitro accumulation within the cytosolic structure of endoplasmic reticulum and lysosome. The therapeutic efficacy of Ru/radioPDT was determined using PC3 cell viability and clonogenic assays. Ru/radioPDT exhibited minimal cell toxicity until activated by radiation to induce significant cancer cell kill over radiation alone. Compared to protoporphyrin IX-mediated radioPDT (PPIX/radioPDT), Ru/radioPDT showed higher capacity for singlet oxygen generation, maintaining a comparable cytotoxic effect on PC3 cells.

Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types.

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). METHODS: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10‒8 < P < 1.0 × 10‒5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size ‒0.17; P = 1.7 × 10‒7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10‒6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected). CONCLUSIONS: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.

A Contouring Strategy and Reference Atlases for the Full Abdominopelvic Bowel Bag on Treatment Planning and Cone Beam Computed Tomography Images.

Purpose: To establish a practical contouring strategy with reference atlases for the abdominopelvic bowel bag on treatment planning computed tomography (TPCT) and cone beam computed tomography (CBCT) images. Methods and Materials: A scoping literature review was done to evaluate the existing definitions and contouring guidelines for bowel bag and small bowel planning-at-risk volume-like structures. A comprehensive definition was proposed for the abdominopelvic bowel bag that expanded the Radiation Therapy Oncology Group Pelvic Normal Tissue Consensus definition. Seven patients with TPCT and first-treatment-day CBCT images were selected from an institutional database to represent a range of normal anatomy and CBCT image quality. The TPCT and CBCT images were contoured using the proposed definition. During contouring, the Radiation Therapy Oncology Group definition's list of inclusion and exclusion structures was expanded. For areas with limited visibility of the bowel bag on either TPCT or CBCT, a set of operational definitions was developed based on consistently visible reference structures. Results: A literature review showed that previously existing bowel bag definitions predominantly focused on the pelvic region and did not provide a complete and practical description of the full abdominopelvic contour relative to structures consistently visible in all radiation therapy images. The proposed contouring strategy had 4 components: a definition, a list of inclusion and exclusion structures, 15 tabulated operational definitions, and a set of atlases. The bowel bag was defined as the peritoneal cavity and retroperitoneal duodenum and ascending and descending colon, as visualized at the time of image acquisition. The operational definitions formalized the location of the peritoneal fascial planes through a simple look-up table. The proposed contouring strategy and reference atlases were successfully used on both TPCT and CBCT images. Conclusions: This study produced a practical contouring strategy and reference atlases to enable reproducible delineation of the full bowel bag on TPCT and CBCT images. The strategy is a necessary first step toward consensus contouring with reduced observer variability, which is a prerequisite for evaluation of cumulative dose and its correlation with toxic effects, adaptive planning strategies, and automated contouring potential.