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Working parents, and a rising number of adults delivering care for ageing relatives, experience numerous challenges in their personal, family, professional and financial lives due to multiple responsibilities. This study describes the experiences of Canadian radiation oncology (RO) parents and family caregivers, reporting challenges that may exist in providing family care with clinical/academic work commitments.Canadian RO's were invited to participate in an anonymous online survey, via RO heads of departments in cancer centres across Canada and to physician members of the Canadian Association of Radiation Oncology between November 2021 and January 2022. The survey focused on demographics, experiences of pregnancy and leave, parenting and adult caregiving responsibilities, and self-care.103 (38%) staff RO completed the survey, 78 (75.7%) identified as having a parental (76, 89.7%) and/or other family caregiver (8, 10.3%) role. 41% were female (59% male), with no difference between gender and number of children (median 2, IQR 1-3, p=0.17). More female respondents took parental leave for their first child compared to male (mean 29 versus 6 weeks, p0.001). 27% of male respondents who started caring for their first child during residency took parental leave compared to 77% (p=0.003) as a staff. The majority of respondents described "always/usually" collegial support for each pregnancy and parental leave. Both genders described parental responsibilities as negatively impacting attendance at conferences (male - 65%, female - 77%, p=0.31) and early/late work-related meetings (male - 76%, female 79%, p=1.0). More female respondents described parental responsibilities as negatively impacting their career (50% vs 29%, p=0.085). 52% of female respondents (vs 26% male respondents, p=0.044) identified a physician mentor or positive role model around parenting issues.Parental and other family caregiving responsibilities are not gender unique in Canadian ROs but competing work and family roles may impact genders differently.

IntroductionGrowing data support the safe and efficacious use of ablative radiotherapy in the setting of liver metastases, with some studies suggesting that patients with metastatic breast cancer (MBCa) do better than patients with metastases from other cancers. This study aims to retrospectively review clinical outcomes of patients with MBCa following liver radiotherapy (RT).Materials and MethodsPatients with MBCa who received liver hypo fractionated ablative RT between 2004 – 2020 were classified according to metastatic classification and treatment intent (i.e., oligo-metastatic (OM) or oligo-progressive (OP)). Demographics, disease characteristics and treatment characteristics were collated. Primary outcome was local control (LC) of treated metastases. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and time to next line systemic therapy (ST), analyzed by univariate (UVA) and multi-variable analysis (MVA).ResultsThirty MBCa patients with 50 liver metastases treated with 5 – 10 fraction ablative intent RT were identified for analysis. Median follow-up was 14.6 months (range 0.9 - 156.2 months). Mean age was 55.6 years (range 32.1 - 79.3 years); 53% were ER+/HER2-ve and 33% HER2+ve. Class of metastatic disease was described as – induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (3 patients, 10%) (1 synchronous, 2 metachronous). Indication of treatment was OP (73%) and OM (27%). Median size of treated liver metastases (LM) was 3.1 cm (range 1cm – 8.8 cm) and the median dose delivered was 40Gy (range 30Gy-60Gy). 1 and 3-year LC rates were 100%. Median OS was 57.7-months with size of treated liver metastases predictive of overall survival (HR 1.35, p=0.023) on UVA. Median time to progression post treatment was 4.8 months (0.8 – 114.7). Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p=0.01) on UVA compared to others, which trended to significance on MVA (HR 3.23, p=0.051).ConclusionHypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC. Further studies assessing the impact, ideal sequencing, and indications of RT in each metastatic class in MBCa are required.

Anal adenocarcinoma is a rare clinical entity for which the optimal management is not defined.This study aimed to describe the multidisciplinary management and outcomes of patients with anal adenocarcinoma.This is a retrospective cohort study.This study was conducted at a quaternary cancer center.Men and women with anal adenocarcinoma treated between 1995 and 2016 were selected.Fifty-two patients were treated with either chemoradiotherapy or trimodality therapy including radiation therapy, chemotherapy, and surgical resection.Local failure, regional failure, and distant metastasis rates were estimated using the cumulative incidence method. The Kaplan-Meier method was used to estimate progression-free survival and overall survival. The multivariable Cox proportional hazards model was used to evaluate the clinical predictors of outcome.There was a higher 5-year rate of local failure in patients treated with chemoradiotherapy compared with trimodality therapy (53% vs 10%; p0.01). The 5-year incidence of distant metastases was 29% (trimodality therapy) versus 30% (chemoradiotherapy; p = 0.9); adjuvant chemotherapy did not reduce the incidence of distant metastases (p = 0.8). Five-year overall survival was 73% (trimodality therapy) versus 49.4% (chemoradiotherapy; p = 0.1). On multivariable analysis, factors associated with worse overall survival were treatment with chemoradiotherapy, cT3-4 category disease, and node-positive disease.This study is limited by its small sample size and retrospective nature.Although treatment may continue to be tailored to individual patients, better outcomes with a trimodality therapy approach were observed. See Video Abstract at http://links.lww.com/DCR/B708.ADENOCARCINOMA ANAL: UNA ENTIDAD POCO FRECUENTE EN NECESIDAD DE UN MANEJO MULTIDISCIPLINARIO.El adenocarcinoma anal es una entidad clínica poco frecuente por lo que aún no se define el manejo óptimo.Describir el manejo multidisciplinario y los resultados de los pacientes con adenocarcinoma anal.Estudio de cohorte retrospectivo.Centro de cáncer cuaternario.Hombres y mujeres con adenocarcinoma anal tratados entre 1995 y 2016.Cincuenta y dos pacientes fueron tratados con quimiorradioterapia o terapia trimodal que incluyó: radioterapia, quimioterapia y resección quirúrgica.Se estimaron las tasas de falla local, falla regional y metástasis a distancia mediante el método de incidencia acumulada. Se utilizó el método de Kaplan-Meier para estimar la supervivencia libre de progresión y la supervivencia global. Los riesgos proporcionales de multivariable Cox se utilizaron para evaluar los predictores clínicos de los resultados.Hubo una mayor tasa de falla local a cinco años en pacientes tratados con quimiorradioterapia en comparación con terapia trimodal (53% vs 10%; p0,01). La incidencia a cinco años de metástasis a distancia fue del 29% (terapia trimodal) versus 30% (quimiorradioterapia) (p = 0,9); la quimioterapia adyuvante no redujo la incidencia de metástasis a distancia (p = 0,8). La supervivencia global a cinco años fue del 73% (terapia trimodal) versus 49,4% (quimiorradioterapia); p = 0,1. En el análisis multivariable, los factores asociados con una peor supervivencia general fueron el tratamiento con quimiorradioterapia, enfermedad de categoría cT3-4 y enfermedad con ganglios positivos.Este estudio está limitado por su pequeño tamaño de muestra y su naturaleza retrospectiva.Aunque el tratamiento puede seguir adaptándose a pacientes individuales, se observaron mejores resultados con un enfoque TTM. Conslute Video Resumen en http://links.lww.com/DCR/B708. (Traducción- Dr. Francisco M. Abarca-Rendon).

Purpose This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). Methods The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the indications, techniques, and outcomes of EBRT in HCC and IHC. It is intended to cover the definitive, consolidative, salvage, preoperative (including bridge to transplant), and adjuvant settings as well as palliative EBRT for symptomatic primary lesions. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Results Strong recommendations are made for using EBRT as a potential first-line treatment in patients with liver-confined HCC who are not candidates for curative therapy, consolidative therapy after incomplete response to liver-directed therapies, and as a salvage option for local recurrences. The guideline conditionally recommends EBRT for patients with liver-confined multifocal or unresectable HCC, or those with macrovascular invasion, sequenced with systemic or catheter-based therapies. Palliative EBRT is conditionally recommended for symptomatic primary HCC and/or macrovascular tumor thrombi. EBRT is conditionally recommended as a bridge to transplant or prior to surgery in carefully selected patients. For patients with unresectable IHC, consolidative EBRT with or without chemotherapy should be considered, typically after systemic therapy. Adjuvant EBRT is conditionally recommended for resected IHC with high-risk features. Selection of dose-fractionation regimen and technique should be based on disease extent, disease location, underlying liver function, and available technologies. Conclusions The task force has proposed recommendations to inform best clinical practices on the use of EBRT for HCC and IHC with strong emphasis on multidisciplinary care. Future studies should focus on further defining the role of EBRT in the context of liver-directed and systemic therapies and refining optimal regimens and techniques.

Aims The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF. Materials and methods A retrospective review was conducted on patients with stages I–III pancreatic adenocarcinoma who underwent surgery at our institution (2005–2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF. Results In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5–52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P Conclusion This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.

Online adaptive MR-guided radiotherapy allows for the reduction of safety margins in dose escalated treatment of rectal tumors. With the use of smaller margins, precise tumor delineation becomes more critical. In the present study we investigated the impact of rectal ultrasound gel filling on interobserver variability in delineation of primary rectal tumor volumes.Six patients with locally advanced rectal cancer were scanned on a 1.5 T MRI-Linac without (MRI_e) and with application of 100 cc of ultrasound gel transanally (MRI_f). Eight international radiation oncologists expert in the treatment of gastrointestinal cancers delineated the gross tumor volume (GTV) on both MRI scans. MRI_f scans were provided to the participating centers after MRI_e scans had been returned. Interobserver variability was analyzed by either comparing the observers' delineations with a reference delineation (approach 1) and by building all possible pairs between observers (approach 2). Dice Similarity Index (DICE) and 95 % Hausdorff-Distance (95 %HD) were calculated.Rectal ultrasound gel filling was well tolerated by all patients. Overall, interobserver agreement was superior in MRI_f scans based on median DICE (0.81 vs 0.74, p 0.005 for approach 1 and 0.76 vs 0.64, p 0.0001 for approach 2) and 95 %HD (6.9 mm vs 4.2 mm for approach 1, p = 0.04 and 8.9 mm vs 6.1 mm, p = 0.04 for approach 2). Delineated median tumor volumes and inter-quartile ranges were 26.99 cc [18.01-50.34 cc] in MRI_e and 44.20 [19.72-61.59 cc] in MRI_f scans respectively, p = 0.012.Although limited by the small number of patients, in this study the application of rectal ultrasound gel resulted in higher interobserver agreement in rectal GTV delineation. The endorectal gel filling might be a useful tool for future dose escalation strategies.

Background In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). Methods Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed. Results 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT. Conclusions SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.

Purpose: Peer review is an essential quality assurance component of radiation therapy planning. A growing body of literature has demonstrated substantial rates of suggested plan changes resulting from peer review. There remains a paucity of data on the impact of peer review rounds for stereotactic body radiation therapy (SBRT). We therefore aim to evaluate the outcomes of peer review in this specific patient cohort. Methods and materials: We conducted a retrospective review of all SBRT cases that underwent peer review from July 2015 to June 2018 at a single institution. Weekly peer review rounds are grouped according to cancer subsite and attended by radiation oncologists, medical physicists and medical radiation technologists. We prospectively compiled ‘learning moments’, defined as cases with suggested changes or where an educational discussion occurred beyond routine management, and critical errors, defined as errors which could alter clinical outcomes, recorded prospectively during peer review. Plan changes implemented after peer review were documented. Results: Nine hundred thirty-four SBRT cases were included. The most common treatment sites were lung (518, 55%), liver (196, 21%) and spine (119, 13%). Learning moments were identified in 161 cases (17%) and translated into plan changes in 28 cases (3%). Two critical errors (0.2%) were identified: an inadequate planning target volume margin and an incorrect image set used for contouring. There was a statistically significantly higher rate of learning moments for lower-volume SBRT sites (defined as ≤30 cases/year) versus higher-volume SBRT sites (29% vs 16%, respectively; p = 0.001). Conclusions: Peer review for SBRT cases revealed a low rate of critical errors, but did result in implemented plan changes in 3% of cases, and either educational discussion or suggestions of plan changes in 17% of cases. All SBRT sites appear to benefit from peer review, though lower-volume sites may require particular attention.

Purpose Mitigation strategies to balance the risk of coronavirus disease 2019 (COVID-19) infection against oncologic risk in patients with breast cancer undergoing radiation therapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiation therapy by oncologic risk and omission or deferral of radiation therapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers and preserves resources. Herein, we present our early response and adaptation of breast radiation therapy utilization during the COVID-19 pandemic at a large academic cancer center in Canada. Methods and Materials A state of emergency was announced in Ontario on March 17, 2020, owing to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast radiation therapy starts, type of breast radiation therapy, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. Results After the declaration of emergency in Ontario, there was a decrease of 39% in radiation therapy starts in 2020 compared with 2019 (79 vs 129, P < .001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared with 2019 (46% vs 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiation therapy were aged >50 years in 2020, 66% (78 of 118) versus 83% (132 of 160) in 2019, P = .0027. Conclusions A significant reduction in breast radiation therapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiation therapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical and is of particular importance for higher volume cancer sites where the potential effect on resources is greater.

Purpose: Partial Breast Irradiation (PBI) treats the tumor bed plus a margin in low risk early stage breast cancers, reducing exposure to organs at risk. Randomized trials have shown that PBI with external beam radiotherapy is non-inferior to whole breast irradiation in terms of local control with fewer late normal tissue adverse events. We aimed to determine the proportion of women with early stage breast cancer suitable for external beam PBI at our institution using adapted ASTRO guidelines for accelerated PBI whereby both clinical-pathological factors and visualization of the tumor bed/cavity on planning scans were determined to quantify PBI eligibility. Methods: Patients were identified retrospectively from January 1, 2013 to November 1, 2018 based on age (≥55), tumor size (≤2cm invasive, ≤2.5cm DCIS), nodal negativity and grade (1 or 2). Cases identified were unifocal, lymphovascular invasion negative, ER positive, HER2 negative, with margins ≥2mm (invasive) and ≥3mm (DCIS), no chemotherapy, non-lobular, no extensive intraductal component, no previous/ bilateral cancers and endocrine therapy optional. Planning scans were reviewed to assess for presence of surgical clips and assigned cavity visualization scores (CVS); CVS 1=cavity not visualized, CVS 2=cavity visualized with indistinct margins, CVS 3=cavity visualised with some distinct margins and heterogeneous appearance, CVS 4= cavity visualised with mostly distinct margins and mildly heterogeneous appearance, CVS 5= all cavity margins clearly defined and homogeneous appearance. These features were used to determine if cases were considered radiologically suitable for PBI. Results: Thirty-seven percent (1051/2824) of cases identified were deemed eligible based on age, grade and T1N0/Tis. Of the 1051, 306 (29%) met all the pathologic criteria; the main reasons for exclusion were previous breast cancer, lobular histology, or multifocality. Median age of eligible cases was 65 years (range 55-88 years). The majority (254) had invasive disease (T1mi: 6, T1a: 17, T1b: 98, T1c: 133); 52 had DCIS. There were 169 right-sided and 137 left-sided cases. Endocrine therapy was documented in 55% of cases. CVS (1-5) were: 11%, 22%, 30%, 29%, 8%. Overall, 66% (201/306) of cases were considered radiologically suitable for PBI (of the 201 cases, 97% had CVS ≥3). Seventy-two cases (72/306; 24%) had tumor bed clips, of which, 34 were considered suitable for PBI (91% CVS ≥3; 9% CVS 2). Conclusions: Overall, a low proportion of all patients were eligible for PBI based on clinical features, but two-thirds of eligible cases were suitable for PBI based on CVS score alone. In contrast, the suitability for PBI within the cohort with surgical clip placement was low. Visualization of the tumor bed is essential to safely deliver PBI and is guided by identification of the cavity seroma and/or surgical clips. Development of standard practice guidelines for surgical clip positioning to identify the tumor bed will potentially assist in increasing the proportion of early stage breast cancer patients suitable to receive PBI, even if the CVS is less favorable. Citation Format: Christine Anne Koch, Gemma Corey, Kathy Han, Grace Lee, Tom Purdie, Chris McIntosh, Patricia Lindsay, Fei-Fei Liu, Anthony Fyles, Wilf Levin, Jennifer Croke, Aisling Barry, Danielle Rodin, Nhu Tram Nguyen, Tatiana Conrad. Evaluation of partial breast irradiation suitability in early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-24.

Radiation therapy uses high-energy radiation from X-rays, γ-rays, neutrons, electrons, protons and other sources to kill cancer cells and shrink tumours. External-beam radiation therapy (EBRT) is delivered by a machine outside the body, while brachytherapy or internal radiation therapy comes from radioactive material placed in the body near or within the tumour. EBRT is the most common method of delivering radiation treatment. Curative and palliative treatment regimens are usually given on an outpatient basis over 1–8 weeks. Chemotherapy is sometimes given concurrently with radiation therapy and acts as a radiation sensitizer. Brachytherapy is most frequently used to treat prostate and gynaecological cancers and can require hospital admission. Although radiation therapy is usually described as a ‘local’ treatment, systemic radiation therapy uses a radioactive substance, such as a radiolabelled monoclonal antibody, that travels throughout the body via the bloodstream. This article describes the role of radiation therapy and its adverse effects in various clinical situations.

ObjectivesTo measure pregnancy outcome following attendance at a recurrent miscarriage service and identify factors that influence outcome.DesignProspective, observational electronic cohort study.SettingParticipants attending a specialist recurrent miscarriage clinic, with a history of two or more pregnancy losses. 857 new patients attended over a 30-month period and were invited to participate. Participant data were recorded on a bespoke study database, ‘Tommy’s Net’.Participants777 women consented to participate (90.7% of new patients). 639 (82%) women continued within the cohort, and 138 were lost to follow-up. Mean age of active participants was 34 years for women and 37 years for partners, with a mean of 3.5 (1–19) previous pregnancy losses. Rates of obesity (maternal: 23.8%, paternal: 22.4%), smoking (maternal:7.4%, paternal: 19.4%) and alcohol consumption (maternal: 50%, paternal: 79.2%) were high and 55% of participants were not taking folic acid.Outcome measuresBiannual collection of pregnancy outcomes, either through prompted self-reporting, or existing hospital systems.Results639 (82%) women were followed up. 404 (83.4%) reported conception and 106 (16.6%) reported no pregnancy, at least 6 months following registration. Of those that conceived, 72.8% (294/404) had a viable pregnancy. Maternal smoking and body mass index (BMI) over 30 were significantly higher in those who did not conceive (p=0.001)ConclusionsTommy’s Net provides a secure electronic repository on data for couples with recurrent pregnancy loss and associated outcomes. The study identified that subfertility, as well as repeated miscarriage, maternal BMI and smoking status, contributed to failure to achieve live birth. Study findings may enable comparison of clinic outcomes and inform the development of a personalised holistic care package.

Purpose: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow’s clinical feasibility and early experience in the case of 16 liver and pancreas patients. Methods: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. Results: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70–90 min for a single fraction and 55–90 min for five fractions. The pancreas sessions were 54–85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9–96.1% and 99/95.4–100%, respectively. Conclusion: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy.Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 15). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea).In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder DStatistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour control in silico in several sites. Pancreatic cancer presents a more stringent challenge, given its proximity to critical organs-at-risk (OARs) and anatomic motion. A radiobiological model was developed to estimate clonogen survival fraction (SF), using 18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with pancreatic cancer to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: 1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, 2) dose painting plans delivering escalated doses to FAZA-avid hypoxic sub-volumes, 3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and 4), plans with integrated boosts to geometric contractions of the tumour (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (~10^-5) well above levels required to completely ablate a ~10 cm^3 tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

The initial bedside care of premature babies with an intact cord has been shown to reduce mortality; there is evidence that resuscitation of term babies with an intact cord may also improve outcomes. This process has been facilitated by the development of bedside resuscitation surfaces. These new devices are unaffordable, however, in most of sub-Saharan Africa, where 42% of the world’s 2.4 million annual newborn deaths occur. This paper describes the rationale and design of BabySaver, an innovative low-cost mobile resuscitation unit, which was developed iteratively over five years in a collaboration between the Sanyu Africa Research Institute (SAfRI) in Uganda and the University of Liverpool in the UK. The final BabySaver design comprises two compartments; a tray to provide a firm resuscitation surface, and a base to store resuscitation equipment. The design was formed while considering contextual factors, using the views of individual women from the community served by the local hospitals, medical staff, and skilled birth attendants in both Uganda and the UK.

PURPOSE/OBJECTIVE(S) The management of oligo-metastatic disease (OMD) is evolving, with increasing data supporting the use of stereotactic body radiotherapy. The aim of this systematic review and meta-analysis is to analyses health related quality of life (HRQOL) outcomes and the side-effects of SBRT in patients with OMD. MATERIALS/METHODS We searched MEDLINE, Epub Ahead of Print, EMBASE, Cochrane CT, Cochrane SR, Emcare, and PsycInfo databases (from inception to March 2020). Randomized clinical trials (RCTs) or observational studies were included if HRQOL outcomes were reported from patients with defined OMD (£5 metastases) who received SBRT as metastasis-directed therapy, and who completed validated HRQOL questionnaires at baseline and 12-months. Meta-analysis using weighted mean difference was performed to estimate a difference between baseline and 12-month scores. Secondary outcome, calculated by the pooled incidence rate approach using the inverse variance method, was the estimated event rate of clinically significant Common Terminology Criteria for Adverse Events (CTCAE) grade 2-4 and grade 5 toxicity, expressed per person-time of follow-up. Authors of studies included were contacted to obtain additional information. Methods adhered to PRISMA guidelines. RESULTS Four of 7,545 studies screened were eligible for inclusion. Two studies were phase II RCTs and two were prospective single arm studies. Among 277 patients who received SBRT, median follow-up was 31 months (range 24-41 months). Two studies included only prostate cancer patients and two studies included mixed histologies. Two studies measured European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and two measured Functional Assessment of Cancer Therapy - General (FACT-G) scores. Using a fixed effects model, the mean change in 12-month EORTC QLQ-C30 global health QOL score from baseline demonstrated a statistically significant decline (pooled weighted mean difference -5.2, 95% CI -9.3 to -1.2, both prostate cancer studies, 57 patients total). Meta-analysis of total FACT-G scores in the other two studies was not possible as mean difference results for one study were unavailable. For the available multi-histology study, no statistically significant difference was seen in baseline to 12-month mean FACT-G total scores in the SBRT arm. We estimated an event rate of 0.06 (95% CI: 0.024, 0.15) CTCAE grade 2-4 toxicities per person-year and 0.008 (95% CI: 0.002, 0.031) grade 5 toxicities per person-year. CONCLUSION Although a statistically significant decline in the EORTC QLQ C30 global health/QOL measure was seen, it was small and unlikely to be of clinical importance. Rates of SBRT-related clinical toxicities are low. There is limited QOL data published for patients with OMD, with varying HRQOL tools used.

Purpose With multiple phase 2 trials supporting the use of stereotactic body radiation therapy (SBRT) in oligo-metastatic disease, we evaluated practices that could inform effective implementation of an oligo-metastasis SBRT program. Methods and Materials Using a context-focused realist methodology, an advisory committee of interprofessional clinicians met over a series of semistructured teleconference meetings to identify challenges in implementing an oligo-metastasis SBRT program. Consideration was given to 2 models of care: a subspecialist anatomic expertise model versus a single-practitioner “quarterback” model. Results The advisory committee structured recommendations within a context-mechanism-outcome framework. In summary, the committee recommends that during patient workup, a single practitioner arranges the minimum number of necessary tests, with case presentation at an appropriate multidisciplinary tumor board, including careful review of all previous treatments, and enrollment on clinical trials when possible. At simulation, common patient positions and immobilization on a single simulation scan for multiple sites is recommended. During radiation planning, dose-fractionation regimens should safely facilitate cumulative dose calculations, a single isocenter should be considered for multiple close targets to reduce treatment time, and adherence to strict quality assurance protocols is strongly recommended. Treatment duration should be minimized by treating multiple sites on the same day or choosing shorter dose fractionations. Team communication, thorough documentation, and standardized nomenclature can reduce system errors. Follow-up should aim to minimize redundant clinical appointments and imaging scans. Expert radiology review may be required to interpret post-SBRT imaging. Conclusions These guidelines inform best clinical practices for implementing an oligo-metastasis SBRT program. Iterations using a realist approach may further expand on local contexts.

Summary Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19.

We thank Wu and colleagues for their important commentary regarding potential psychological effects of coronavirus disease 2019 (COVID-19) on health care providers.[1][1] Our group of multidisciplinary oncology providers was formed to support oncology health care providers, a group at high risk of

Accelerated partial breast irradiation is a potential alternative to standard whole breast irradiation, following breast-conserving surgery, in the management of breast cancer. The MammoSite applicator–based technique allows for the delivery of a higher dose of radiation to the tumour bed and adjacent area, over a shorter treatment period. To investigate the long-term feasibility of the MammoSite technique in early stage breast cancer in an Irish cohort. Sixty-two patients with early stage breast cancer were enrolled in this prospective study between November 2005 and October 2012 at the University Hospital Galway. A single-entry MammoSite applicator was inserted post-operatively. A CT scan was performed to assess the balloon to skin distance, the conformance of target tissue to balloon surface and balloon symmetry. A total dose of 34 Gy was delivered over 10 fractions twice daily. Median follow-up was 10 years. 91.9% (57/62) completed the full course of MammoSite treatment. Technical issues with the MammoSite balloon precluded three patients from completing the full course of treatment. On last follow-up, 6.4% (4/62) of patients had developed an ipsilateral breast recurrence. Half of these recurrences occurred more than 10 years after the initial breast cancer treatment. The most common toxicities observed were fibrosis (67.7%), pain (61.3%) and skin erythema (35.5%). The use of the MammoSite technique, as an alternative to standard whole breast irradiation, is feasible in a typical Irish clinical setting with integrated multidisciplinary team input.

IntroductionPancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer.Methods and analysisA single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients" be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association.Ethics and disseminationEthic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications.Trial registration numberNCT03323489.

Surgical resection or liver transplantation offers the best chance of cure for patients with hepatocellular carcinoma (HCC). Unfortunately, most patients are not good candidates for liver resection due to locally advanced disease or compromised liver function. Moreover, liver transplantation waiting lists are long. For those cases not amenable for resection, a variety of local treatment modalities are available, such as image-guided ablative procedures, transarterial chemoembolization, and radioembolization, as well as external beam radiation. HCC presentation can vary considerably in size, number, and location of lesions. The management of inoperable HCC is, therefore, quite complex, and there is a lack of consensus on the best local treatment modality for each type tumor presentation. Here, we present 4 clinical case scenarios representative of commonly seen cases in the clinical setting, with different therapeutic perspectives from institutions with high expertise in the management of HCC.

PURPOSE/OBJECTIVE(S) In response to the COVID-19 pandemic, radiotherapy (RT) departments around the world created new policies as a means of reducing risk of exposure for patients and staff, while attempting to maintain high-quality RT. We aim to describe the impact of the pandemic on changes in breast cancer RT patterns of practice for new patient referrals at a tertiary cancer center. MATERIALS/METHODS Newly diagnosed breast cancer patients referred to our department from March 17-June 30, 2020 were included. Referrals for palliative RT were excluded. Demographic characteristics, COVID-19 status (if available) and RT treatment information, including deviations from usual practice because of the pandemic, were extracted from medical records by independent reviewers, and validated by the treating radiation oncologist. Descriptive statistics were used to summarize the data. The results were compared to breast cancer patients treated from March 17-June 30, 2019. RESULTS A total of 271 and 306 patients met selection criteria for the 2020 and 2019 cohorts, respectively. The majority of consultations in 2020 were virtual (96%), conducted via telephone or videoconference, whereas in 2019 all were conducted in-person. Median age of the cohorts was similar: 58 years (range: 24-86) in 2020 and 59 years (range: 26-88) in 2019. Of those treated with adjuvant RT (n = 209), 56% of patients received whole breast (WB), 36% regional nodal irradiation (RNI) and 8% partial breast (PB) RT in 2020, whereas in 2019 (n = 284), 60% received WB, 31% RNI and 9% PB (Chi-squared test P = 0.43). As a result of the pandemic, 78% of cases (n = 211) received one or more deviations in RT practice compared to pre-pandemic institutional policies. The most common was an "altered dose/fractionation protocol" (n = 197; 93%), such as use of hypofractionated RNI (2020: 97%, 74/76 cases vs. 2019: 3%, 3/87 cases) or the FAST Forward regimen (2020: 43%, 57/134 WB/PB cases vs. 2019: 0/197 cases). Other deviations included a delay in RT start (defined as > 12 weeks post-op) noted in 11% (n = 29) and omission of RT in only 8% (n = 17), both were recommended when the risks associated with COVID-19 were felt to outweigh the benefit of RT. One patient had a deviation in RT as a result of testing positive for COVID-19. CONCLUSION In order to minimize hospital visits in response to the COVID-19 pandemic, a substantial proportion of breast cancer patients were seen virtually and treated with newer hypofractionated dose schedules, while total omission of adjuvant RT was infrequently observed. Continuously tracking patterns of practice provides an opportunity to evaluate the impact of the pandemic on clinical outcomes and help inform post-pandemic value-enhancing practices.

Purpose The aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiation therapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity. Methods and materials Between 2002 and 2009, 81 evaluable patients with liver metastases were treated on 2 prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated. Toxicity was defined as grade ≥2 classic or nonclassic radiation induced liver disease (RILD). Specific toxicity endpoints evaluated were worsening transaminases and albumin levels within 3 months of SBRT. Results Seventy percent of patients had colorectal carcinoma, 55% had extrahepatic disease, 1 patient had hepatitis B, and 54% had received prior chemotherapy. Baseline transaminases were elevated at Common Terminology Criteria for Adverse Effects, V4.0, grade 1, 2, and 3 levels in 33 (41%), 2 (2%), and 0 (0%) patients. The mean prescription dose was 43 Gy (27.7-60 Gy) in 6 fractions. The mean liver (minus gross tumor volume) dose (MLD) was 16 Gy (3-25.6 Gy) in 6 fractions. No classic or nonclassical ≥grade 2 RILD was observed. Within 3 months of SBRT, 49 (61%) patients had worsening of grade of transaminase and 23 (28%) patients had a reduction in albumin, all transient (majority grade ≤2 toxicity) without subsequent clinical toxicity. Seventeen patients exceeded Quantitative Analysis of Normal Tissue Effects in the Clinic MLD guidelines (≤20 Gy), 13 (76%) of whom had worsening of transaminase grade. On multivariate analysis, worsening of liver enzymes was more likely in patients with higher doses to the spared 700 mL of liver (P = .026), and reduction of albumin was more likely with higher effective liver volume (odds ratio, 1.53 [range, 1.08-2.16]) P = .016). Conclusions Liver metastases SBRT is safe with a low risk of transient biochemical liver toxicity, more likely in patients with a higher effective liver volume and higher doses to the spared uninvolved liver volume.