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Brachytherapy is most often applied in the curative or salvage setting, but many forms of brachytherapy can be helpful for symptom palliation. Declining utilization is seen, for multiple reasons, such as lack of awareness, insufficient expertise, or poor access to equipment. High level evidence for many types of palliative brachytherapy has been lacking. The objective of the current study was to review the evidence for utilization and efficacy of brachytherapy to palliate symptoms from cancer.We performed a systematic search in EMBASE and MEDLINE for English-language articles published from January 1980 to May 2022 that described brachytherapy used for a palliative indication in adults with a diagnosis of cancer (any subtype) and at least one symptom related outcome. Individual case reports and conference abstracts were excluded. All publications were independently screened by two investigators for eligibility.The initial search identified 3637 abstracts of which 129 were selected for in-depth review. The number of studies (total number of patients) included in the final analysis varied widely by tumor site with the majority (68.2%) involving either lung or esophageal cancer. Despite a limited number of prospective trials that assessed the efficacy of brachytherapy for symptom management, there was a positive effect on palliation of symptoms across all tumor types. There was no clear trend in the number of publications over time. The most commonly cited symptom indications for palliation by brachytherapy were dysphagia, dyspnea, pain and bleeding.Brachytherapy can provide palliation for patients with advanced cancer, across different tumor sites and clinical scenarios. However, high level evidence in the literature to support palliative applications of brachytherapy is lacking or limited for many tumor sites. There appears to be a strong publication bias towards positive studies in favor of brachytherapy. Beyond anecdotal reports and individual practices, outcomes research can further our understanding of the role of brachytherapy in palliating advanced cancers of all types, and should be encouraged.

Purpose: A simple scoring system (T-score, TS) for integrating findings from clinical examination and magnetic resonance imaging (MRI) of the primary tumor at diagnosis has shown strong prognostic capability for predicting local control and survival in locally advanced cervical cancer treated with chemoradiation and MRI-guided brachytherapy (BT). The aim was to validate the performance of TS using the multicenter EMBRACE I study and to evaluate the prognostic implications of TS regression obtained during initial chemoradiation. Methods and Materials: EMBRACE I recruited 1416 patients, of whom 1318 were available for TS. Patients were treated with chemoradiation followed by MRI-guided BT. A ranked ordinal scale of 0 to 3 points was used to assess 8 anatomic locations typical for local invasion of cervical cancer. TS was calculated separately at diagnosis (TSD) and at BT (TSBT) by the sum of points obtained from the 8 locations at the 2 occasions. Results: Median TSD and TSBT was 5 and 4, respectively. TS regression was observed in 71% and was an explanatory variable for BT technique (intracavitary vs intracavitary/interstitial) and major dose-volume histogram parameters for BT, such as high-risk clinical target (CTVHR), CTVHR D90 (minimal dose to 90% of the target volume), D2cm3 bladder (minimal dose to the most exposed 2 cm3 of the bladder), and D2cm3 rectum. TS regression (TSBT≤5) was associated with improved local control and survival and with less morbidity compared with patients with TSBT remaining high (>5) despite initial chemoradiation. TS regression was significant in multivariate analysis for both local control and survival when analyzed in consort with already established prognostic parameters related to the patient, disease, and treatment. Conclusions: TS was validated in a multicenter setting and proven to be a strong multidisciplinary platform for integration of clinical findings and imaging with the ability to quantitate local tumor regression and its prognostic implications regarding BT technique, dose-volume histogram parameters, local control, survival, and morbidity.

Purpose: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study.Methods and Materials: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradio-therapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade >= 1 or >= 2 was scored in at least half of the follow ups.Results: The median follow-up time was 57 months. Baseline fatigue grade >= 1/>= 2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade >= 1/>= 2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade >= 2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade >= 1 increased by 7% and 4% with V43Gy 3000 cm(3) in patients with and without baseline fatigue, respectively. Late persistent grade >= 1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively.Conclusions: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques. (C) 2021 Elsevier Inc. All rights reserved.

Purpose: To identify patient- and treatment-related risk factors and dose-effects for urinary frequency and incontinence in locally advanced cervical cancer (LACC) treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Material and methods: Physician-assessed (CTCAE) and patient-reported (EORTC) frequency and incontinence recorded in the EMBRACE-I study were analysed. Risk factors analysis was performed in patients without bladder infiltration and with baseline morbidity available. Cox regression was used for CTCAE grade (G) ≥ 3 and G ≥ 2 and for EORTC “very much” and “quite a bit” or worse. Logistic regression was used for late persistent morbidity defined when CTCAE G ≥ 1 or EORTC ≥ “quite a bit” were scored in at least half of follow-ups. Results: Longitudinal data on 1153 and 884 patients were available for CTCAE and EORTC analysis, respectively. Median follow-up was 48[3-120] months. Crude incidence rates of G≥2 were 13% and 11% for frequency and incontinence, respectively. Baseline morbidity and overweight-obesity were risk factors for both symptoms. Elderly patients were at higher risk for incontinence. Patients receiving conformal-radiotherapy were at higher risk for frequency. ICRU bladder point (ICRU-BP) dose was a stronger predictor for incontinence than bladder D2cm3. The 5-year actuarial estimate of G ≥ 2 incontinence increased from 11% to 20% with ICRU-BP doses > 75 Gy compared to ≤ 65 Gy. Frequency showed weaker associations with dose. Conclusion: ICRU-BP dose, in addition to clinical parameters, is a risk factor for urinary incontinence and shows a dose–effect after radio(chemo)therapy and IGABT. ICRU-BP dose should be monitored during treatment planning alongside volumetric parameters. Frequency seems associated with larger irradiated volumes.

Purpose: This report describes the persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional EMBRACE study on magnetic resonance image guided adaptive brachytherapy in locally advanced cervical cancer (LACC).Methods and Materials: Patient-reported symptoms (European Organization for Research and Treatment of Cancer [EORTC]-C30/CX24) and physician-assessed morbidity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were assessed at baseline and regular timepoints during follow-up. Patients with sufficient EORTC follow-up (baseline and >= 3 late follow-up visits) were analyzed. LAPERS events were defined as the presence of substantial EORTC symptoms (quite a bit/very much) for at least half of the assessments (persistence) and progression beyond baseline condition (treatment-related). For each EORTC symptom, the ratio between LAPERS rates and crude incidence rates of substantial symptoms was calculated to represent the proportion of symptomatic patients with persisting symptoms. For 9 symptoms with a corresponding EORTC/CTCAE assessment, the overlap of LAPERS and severe morbidity events (grades 3-5) was evaluated.Results: Of 1047 patients with EORTC available, 741 had sufficient follow-up for the LAPERS analyses. The median follow-up was 59 months (interquartile range, 42-70 months). Across all symptoms, the proportion of patients with LAPERS events (LAPERS rates) was in median 4.6% (range, 0.0% vaginal bleeding to 20.4% tiredness). Urinary frequency, neuropathy, fatigue, insomnia, and menopausal symptoms revealed LAPERS rates of >10%. Vomiting, blood in stool, urinary pain/burning, and abnormal vaginal bleeding displayed LAPERS rates of

Global Oncology capacity in Radiation Oncology (RO) needs development. We report on early outcomes of a Canadian Global Oncology elective scholarship program for trainees (2014-2019). The number of global oncology electives increased. Academic deliverables and collaborations were observed. There was evidence of personal and professional development.

Patients with advanced cancer often experience symptoms including pain, nausea, anorexia, fatigue, and depression. High symptom burden can be alleviated by multidisciplinary palliative care (PC) teams practicing symptom-directed management. Patients who are unable to access such services may be at higher risk of increased symptoms and poor outcomes. A sequential exploratory mixed methods study was performed to explore the burden of symptoms experienced by Northern Alberta patients with advanced cancer. The symptom burden among patients from rural and remote communities was characterized in a retrospective review capturing basic demographic and clinicopathologic information, in addition to patient-reported outcomes. Symptom prevalence was evaluated against the nature and range of supportive care services available. Service accessibility was assessed at community level by surveying health care providers (HCPs) and performing thematic analysis on their responses. From January 1 to December 31, 2017, 607 outpatients were seen in consultation in an integrated palliative radiotherapy clinic in Edmonton, Alberta. A total of 166 (27.3%) patients resided in Alberta communities designated as rural or remote. Patient-reported symptom prevalence and intensity of scores did not differ significantly between rural/remote and urban populations. Unmet practical needs were flagged significantly more often by patients from rural communities (p = 0.05). HCPs from rural community health centers in Northern Alberta were knowledgeable regarding PC services availability and referral processes within their communities. Although the symptom burden experienced by patients living with advanced cancer in rural and remote areas of Northern Alberta does not differ significantly from their urban counterparts, and community HCPs are knowledgeable regarding PC services, unmet needs within these communities remain. Continuing support for PC services in rural communities, as well as establishing care pathways for patients from rural populations traveling to urban centers to receive treatment, will help to minimize the unmet needs these patients experience.

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.

Estrogen is thought to cause proliferation of all estrogen receptor positive (ER+) breast cancers. Paradoxically, in the Women's Health Initiative Trial, estrogen-only hormone replacement therapy reduced the incidence and mortality of low grade, ER+, HER2- breast cancer. We gave estradiol to 19 post-menopausal women with newly diagnosed low-grade, ER+, HER2- breast cancer in a prospective window of opportunity clinical trial and examined the changes in proliferation and gene expression before and after estradiol treatment. Ki67 decreased in 13/19 (68%) patients and 8/13 (62%) showed a decrease in Risk of Recurrence Score. We chose three prototypical estrogen responders (greatest decrease in ROR) and non-responders (no/minimal change in ROR) and applied a differential gene expression analysis to develop pre-treatment (PRESTO-30core) and post-treatment (PRESTO-45surg) gene expression profiles. The PRESTO-30core predicted adjuvant benefit in a published series of tamoxifen, the partial estrogen agonist. Of the 45 genes in the PRESTO-45surg, thirty contain the Cell cycle genes Homology Region (CHR) motif that binds the class B multi-vulva complex (MuvB) a member of the DREAM (Dimerization partner, retinoblastoma-like proteins, E2F, MuvB) complex responsible for reversible cell cycle arrest or quiescence. There was also near uniform suppression (89%) of the remaining DREAM genes consistent with estrogen induced activation of the DREAM complex to mediate cell cycle block after a short course of estrogens. To our knowledge, this is the first report to show estrogen modulation of DREAM genes and suggest involvement of DREAM pathway associated quiescence in endocrine responsive post-menopausal ER+ breast cancers., Highlights • WHI trial found that estrogen decreases some ER+ post-menopausal breast cancers. • Our prospective clinical trial confirmed an anti-proliferative effect of estradiol. • DREAM pathway genes were downregulated during the anti-proliferative response. • This suggests that estrogen may activate DREAM quiescence of ER+ breast cancers., Breast Cancer, Estrogen, DREAM, Hormone therapy.

Clonogenic assays are the gold standard for measuring cell clonogenic survival and enable quantification of a cell line's radiosensitivity through the calculation of the surviving fraction, the ratio of cell clusters (colonies) formed after radiation exposure compared to the number formed without exposure. Such studies regularly utilize Cs-137 irradiators. While uncertainties for specific procedural aspects have been described previously, a comprehensive review has not been completed. We therefore quantified uncertainties associated with clonogenic assays performed using a Cs-137 Shepherd irradiator, and a recently established brachytherapy afterloader in vitro radiation delivery apparatus (BAIRDA), through a series of experiments and a literature review. The clonogenic assay is subject to uncertainties that affect the determination of the surviving fraction (e.g., accuracy of the number of cells seeded, potential effects of hypothermia, and the threshold number of cells for a cluster to be identified as a colony). Furthermore, dose delivery uncertainties related to both the Cs-137 irradiator and BAIRDA were also quantified. The combined standard (k = 1) uncertainty was ± 6.0% in the surviving fraction for the Cs-137 irradiator (±6.3% for BAIRDA), up to ± 2.2% in the dose delivered by the Cs-137 irradiator, and up to ± 4.3% in the dose delivered by BAIRDA. The largest individual uncertainties were associated with the number of cells seeded on a plate (3.4%) and inter-observer variability in counting (4.1%), suggesting that effective reduction of uncertainties in the conduct of the clonogenic assay may provide the greatest relief on the uncertainty budget. Finally, measurable impact on experimental findings was assessed by applying this uncertainty to clonogenic assays of SW756 cells using either a Cs-137 irradiator or BAIRDA, introducing a maximum shift in the reported radiobiological parameters α/β and T1/2 of 0.3 Gy and 0.4 h, respectively, while the 95% confidence interval increased by 0.5 Gy and decreased by 0.4 h, respectively. Though the overall impact on radiobiological parameter estimation was small, the individual uncertainties could have a significant influence in other applications of in vitro experiments in radiation biology. Hence, better understanding of the uncertainties associated with both clonogenic assays and the radiation source used can improve the accuracy of experimental analysis and reproducibility of the results.

Purpose Interstitial brachytherapy (ISBT) can be effective for vaginal tumors due to its ability to deliver conformal treatment with 3D planning. As there is no consensus for 3D vaginal brachytherapy (BT) contouring, the goals of this study are to evaluate the variability in practices and contouring, and to develop consensus concepts on target definitions. Methods A survey/contouring study was conducted with 16 radiation oncologists from 10 Canadian academic centers. The study included three vaginal ISBT cases. Participants were provided staging, prebrachytherapy (pre-BT), and BT MRIs. Participants responded to a questionnaire and contoured on the provided images. Agreement between contours was analyzed. A meeting was held to develop consensus definitions of targets. Results Median ISBT experience was 3.5 years. All 16 participants regularly contour with MRI, whereas three also plan on MRI. For the three cases, there was variation into how CTV HR and CTV IR was defined. Kappa statistics showed higher agreement with bulky tumors (mean 0.59) as compared with small residual tumors (mean 0.29). For all cases, kappa was highest in pre-BT GTV res as compared with BT GTV res (mean 0.58, 0.46). Consensus concepts to define targets were developed. Conclusions Variations exist in how ISBT targets are defined for vaginal tumors. Highest contouring variability was seen with small residual at BT. Contouring is more consistent on pre-BT MRI as compared with BT MRI suggesting a needle distortion effect. Consensus CTV HR and CTV IR definitions have been developed and further work is warranted to establish international standards.

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

Purpose: To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Material and methods: Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) ≥ 3 cystitis, for G ≥ 2 fistula, bleeding and cystitis, and for EORTC “very much” and “quite a bit” or worse. Results: Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3–120] months. Crude incidence rates for G ≥ 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for ”quite a bit” or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D2cm3 correlated with G ≥ 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain “quite a bit” or worse. An increase from 75 Gy to 80 Gy in bladder D2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G ≥ 2 cystitis. Conclusion: Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose–effect was established with bladder D2cm3, reinforcing the importance of continued optimization during individualized IGABT planning.

Objective: To assess risk factors for nodal failure (NF) after definitive (chemo)radiotherapy and image-guided brachytherapy for locally advanced cervical cancer (LACC) for patients treated in the EMBRACE I study. Materials and methods: Data for pelvic NF and para-aortic (PAO) NF (NFPAO) were analysed. After multiple imputation, univariable and multivariable Cox-regression was performed for clinical and treatment-related variables. For patients with affected pelvic nodes but no PAO nodes at diagnosis, additional analyses were performed for two subgroups: 1. ‘small pelvis’ nodes in internal and external iliac, obturator, parametrial, presacral and/or common iliac (CI) region and 2. any CI nodes (subgroup of 1). Results: 1338 patients with 152 NF and 104 NFPAO events were analysed with a median follow-up of 34.2 months (IQR 16.4–52.7). For the entire group, larger tumour width, nodal risk groups (in particular any CI nodes without PAO nodes), local failure, and lower Hb-nadir increased the risk of NF. Elective PAO-irradiation was independently associated with a decreased risk of NFPAO (HR 0.53, 95%-CI 0.28–1.00, p = 0.05). For subgroup 1, having ‘any CI nodes without PAO nodes’ and local failure significantly increased NF risk. Additionally, elective PAO-irradiation was associated with less risk of NFPAO (HR 0.38, 95%-CI 0.17–0.86, p = 0.02). For subgroup 2 only local failure was associated with higher risk of NF. Conclusion: In this patient cohort, nodal disease and tumour width at diagnosis, as well as local failure, are risk factors for NF after definitive treatment. Having either ‘any PAO nodes’ (with or without pelvic nodes) or ‘any CI nodes’ (without PAO nodes) are stronger risk factors than involvement of nodes in the small pelvis alone. Elective PAO-irradiation was associated with significantly less NFPAO, particularly in patients with nodal disease in the ‘small pelvis’ and/or CI region at time of diagnosis.

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.

Objective. Brachytherapy (BT) dose prescriptions for locally advanced cervical cancer are made with account for the radiobiological parameters, α/β ratio and halftime of repair (T 1/2 ). However, a wide range of parameter values has been reported which can challenge commonly held equivalencies between dose prescriptions. This is the first reported study that aims to develop an in vitro experimental technique using clinical high-dose-rate (HDR) and pulsed-dose-rate (PDR) Ir-192 brachytherapy afterloaders to quantify these parameters in vitro and to contextualize findings within contemporary practice. Approach. To efficiently quantify α/β and T 1/2 , in vitro experiments more reflective of clinical BT practice than traditional clonogenic survival assays were developed and applied to four squamous cell carcinoma cell lines (CaSki, C-33A, SiHa, and SW756). Radiation was delivered using single acute and fractionated dose treatments with a conventional irradiator and clinical HDR and PDR BT afterloaders. For the latter, a novel brachytherapy afterloader in vitro radiation delivery apparatus (BAIRDA) was developed. Main Results. The α/β and T 1/2 values determined using BAIRDA and the conventional irradiator showed close agreement, validating the novel apparatus and technique. For CaSki, C-33A, SiHa, and SW756, the BAIRDA-measured α/β ratios (5.2 [4.6–5.8], 5.6 [4.5–6.6], 6.3 [4.9–7.7], and 5.3 [4.7–6.0] Gy, respectively) were consistently smaller, while the T 1/2 (3.3 [2.7–3.9], 2.7 [2.0–3.3], 2.8 (2.4–3.1], and 4.8 [4.1–5.4] hours) larger, than the widely accepted values in clinical practice (α/β = 10 Gy; T 1/2 = 1.5 h). Significance. In vitro experiments using BAIRDA provided evidence for differences between the conventionally selected and experimentally determined α/β ratio and T 1/2 . Treatment regimens using HDR-BT and PDR-BT, designed to deliver equivalent radiobiological doses based on conventional values, were shown to differ by up to 27 Gy EQD2 – an effect that could impact treatment outcomes in cervical cancer. Furthermore, with BAIRDA, we have developed a novel method for radiobiological research in BT.

Caring for patients with incurable cancer presents unique challenges. Managing symptoms that evolve with changing clinical status and, at the same time, ensuring alignment with patient goals demands specific attention from clinicians. With care needs that often transcend traditional service provision boundaries, patients who seek palliation commonly interface with a team of providers that represents multiple disciplines across multiple settings. In this case study, we explore some of the dynamics of a cross-disciplinary approach to symptom management in an integrated outpatient radiotherapy service model. Providers who care for patients with incurable cancer must rely on one another to secure delivery of the right services at the right time by the right person. In a model of shared responsibilities, flexibility in who does what and when can enhance overall team performance. Adapting requires within-team and between-team monitoring of task and function execution for any given patient. This can be facilitated by a common understanding of the purpose of the clinical team and an awareness of the particular circumstances surrounding care provision. Backup behavior, in which one team member steps in to help another meet an expectation that would otherwise not be fulfilled, is a supportive team practice that may follow naturally in high-functioning teams. Such team processes as these have a place in the care of patients with incurable cancer and help to ensure that individual provider efforts more effectively translate into improved palliation for patients with unmet needs.

OBJECTIVE: To evaluate the pattern of manifestation of fatigue, insomnia and hot flashes within the prospective, observational, multi-center EMBRACE study.METHODS: Morbidity was prospectively assessed according to CTCAE v.3 and patient-reported outcome with EORTC QLQ-C30/CX24 at baseline and regular follow-up. Analyses of crude incidence, prevalence rates and actuarial estimates were performed.RESULTS: A total of 1176 patients were analyzed with a median follow-up of 27 months. At baseline, CTCAE G1/G2 prevalence rates for fatigue were 29%/6.2%, for insomnia 18%/3.1% and for hot flashes 7.9%/1.6% with respective 3-year prevalence rates of 29%/6.8%, 17%/4.4% and 19%/5.9%. Similar patterns of manifestation were seen in patient-reported EORTC outcomes. The 3-year actuarial estimates for G ≥ 3 CTCAE fatigue, insomnia and hot flashes were 5.5%, 4.7% and 1.9%. Younger age was associated with significantly higher risk for fatigue, insomnia and hot flashes.CONCLUSION: Fatigue, insomnia and hot flashes occurred mainly in the mild to moderate range. Fatigue and insomnia were already present before treatment and showed minor fluctuations or recovery during follow-up, whereas hot flashes showed a considerable increase after treatment. More research is needed to evaluate contributing risk factors in order to define intervention strategies.

Patients with advanced cancer often experience symptoms including pain, nausea, anorexia, fatigue, and depression. High symptom burden can be alleviated by multidisciplinary palliative care (PC) teams practicing symptom-directed management. Patients who are unable to access such services may be at higher risk of increased symptoms and poor outcomes.A sequential exploratory mixed methods study was performed to explore the burden of symptoms experienced by Northern Alberta patients with advanced cancer. The symptom burden among patients from rural and remote communities was characterized in a retrospective review capturing basic demographic and clinicopathologic information, in addition to patient-reported outcomes. Symptom prevalence was evaluated against the nature and range of supportive care services available. Service accessibility was assessed at community level by surveying health care providers (HCPs) and performing thematic analysis on their responses.From January 1 to December 31, 2017, 607 outpatients were seen in consultation in an integrated palliative radiotherapy clinic in Edmonton, Alberta. A total of 166 (27.3%) patients resided in Alberta communities designated as rural or remote. Patient-reported symptom prevalence and intensity of scores did not differ significantly between rural/remote and urban populations. Unmet practical needs were flagged significantly more often by patients from rural communities (p = 0.05). HCPs from rural community health centers in Northern Alberta were knowledgeable regarding PC services availability and referral processes within their communities.Although the symptom burden experienced by patients living with advanced cancer in rural and remote areas of Northern Alberta does not differ significantly from their urban counterparts, and community HCPs are knowledgeable regarding PC services, unmet needs within these communities remain. Continuing support for PC services in rural communities, as well as establishing care pathways for patients from rural populations traveling to urban centers to receive treatment, will help to minimize the unmet needs these patients experience.

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