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To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) from the perspective of the Canadian public healthcare system. We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%. In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER) of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab. The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

AbstractObjectiveTo provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes.DesignSystematic review and meta-analysis.Data sourcesOvid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023).Study selectionIncluded studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions).Data extractionTwo independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration’s tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively.Data synthesisPooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran’s Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence.Main outcome measuresThe pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics.ResultsFrom 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF.ConclusionsMHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings.Systematic review registrationPROSPERO CRD42023460249.

In this work, the feasibility of using flattening filter free (FFF) beams in volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning to decrease protracted beam‐on times for these treatments was investigated. In addition, a methodology was developed to generate standardized VMAT TBI treatment plans based on patient physical dimensions to eliminate plan optimization time. A planning study cohort of 47 TBI patients previously treated with optimized VMAT ARC 6 MV beams was retrospectively examined. These patients were sorted into six categories depending on height and anteroposterior (AP) width at the umbilicus. Using Varian Eclipse, clinical 40 cm × 10 cm open field arcs were substituted with 6 MV FFF. Mid‐plane lateral dose profiles in conjunction with relative arc output factors (RAOF) yielded how far a given multileaf collimator (MLC) leaf must move in order to achieve a mid‐plane 100% isodose for a specific control point. Linear interpolation gave the dynamic MLC aperture for the entire arc for each patient AP width category, which was subsequently applied through Python scripting. All FFF VMAT TBI plans were then evaluated by two radiation oncologists and deemed clinically acceptable. The FFF and clinical VMAT TBI plans had similar Body–5 mm D98% distributions, but overall the FFF plans had statistically significantly increased or broader Body–5 mm D2% and mean lung dose distributions. These differences are not considered clinically significant. Median beam‐on times for the FFF and clinical VMAT TBI plans were 11.07 and 18.06 min, respectively, and planning time for the FFF VMAT TBI plans was reduced by 34.1 min. In conclusion, use of FFF beams in VMAT TBI treatment planning resulted in dose homogeneity similar to our current VMAT TBI technique. Clinical dosimetric criteria were achieved for a majority of patients while planning and calculated beam‐on times were reduced, offering the possibility of improved patient experience.

Cancer is the leading cause of mortality in Canada. Undergraduate medical education therefore must ensure adequate oncology education for all physicians and inspire some to make oncology their career specialty, in an effort to ensure public care needs are met in the future. Medical student-led oncology interest groups (OIGs) are a subset of specialty interest groups that supplement formal didactic and clinical learning to increase exposure to oncology and access to mentors. We conducted a survey of OIG leaders to ascertain their goals, activities, barriers, future directions, and perceptions about employment prospects. OIG leaders from 12/17 Canadian medical schools responded. Medical oncology was the most represented specialty in OIGs. Half of OIGs had faculty mentors. Self-reported goals were to increase exposure to oncology disciplines (n = 12), assist students with career selection (n = 11) and finding mentors (n = 7), and enhance oncology education (n = 10). OIGs held on average 5 events per year (range 1–12). Reported barriers were finding time to plan events, declining student interest over academic year, and limited funding. Many OIGs showed interest in more standardized resources about oncology disciplines (n = 9), access to presentations (n = 10), more funding (n = 7), and collaboration (n = 7). Employment in many oncology specialties was perceived poorly, and the most important career selection considerations were ease of employment, practice location, and partner/family preference. Our survey highlights common goals, barriers, and perceptions in OIG medical student leaders across Canada and provides guidance for future interventions.

The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60–86), median KPS was 80 (range 30–100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI , 4.5–8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked ( P -value 0.045.) Median OS was 9.3 months (95% CI , 5.9–11.8) ( P -value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI , 9.9–19.3) ( P -value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy.

Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat hippocampus by a presynaptic action. The Y2 (Y2R) and the Y5 (Y5R) receptors have both been implicated in this action. We used the non‐peptide, Y2R‐selective antagonist, BIIE0246, to test the hypothesis that the Y2R mediates both the presynaptic inhibitory and anti‐epileptic actions of NPY in rat hippocampus in vitro. NPY and the Y2R‐selective agonist, [ahx5‐24]NPY, both inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area CA1 by stratum radiatum stimulation in a concentration‐dependent manner. BIIE0246 suppressed the inhibitory effects of both agonists, suppressing the maximal inhibition without causing a change in the agonist EC50, in a manner inconsistent with competitive antagonism. BIIE0246 washed out from hippocampal slices extremely slowly. Application of agonist at high concentrations (1–3 μM) for prolonged periods did not alter the rate of washout, but did partially overcome the antagonism, inconsistent with an insurmountable antagonism by BIIE0246. In the stimulus train‐induced bursting (STIB) model of ictal activity in hippocampal slices, both NPY and [ahx5‐24]NPY inhibited primary afterdischarge (1°AD) activity. BIIE0246 (100 nM) completely suppressed the actions of NPY and [ahx5‐24]NPY in this model. In contrast, the potent Y5R‐selective agonist, Ala31Aib32NPY, affected neither 1°AD activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1. BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a dominant role for Y2R there. The apparently insurmountable antagonism observed may result from the lipophilic nature of the antagonist. British Journal of Pharmacology (2002) 136, 502–509; doi:10.1038/sj.bjp.0704751

Background Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. Methods A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or dressings to the standard of care (SOC) or other interventions were included. We estimated summary odds ratios and mean differences using network meta-analysis with random effects. This study was registered with PROSPERO (ID: CRD42023475021). Results Fourteen RCTs met inclusion criteria. Six interventions were analysed: 3M™ Moisturizing Double Barrier Cream (MDBC), 3M™ No Sting Barrier Film (BF), Hydrofilm® (HF), Mepitel® Film (MF), Silver Leaf Nylon Dressing and StrataXRT®. HF, MF and StrataXRT® reduced the incidence of moist desquamation compared to SOC (HF: OR = 0.08; p  = 0.02; MF: OR = 0.31 p  < 0.01; StrataXRT®: OR = 0.22, p  = 0.04). The ranking of agents from most to least effective in preventing moist desquamation according to P-scores was HF (92.5%), MF (78.5%), StrataXRT® (70.1%), BF (46.4%), Silver Leaf Nylon Dressing (24.9%), MDBC (22.9%) and SOC (14.7%). Only four RCTs on HF and MF included patient-reported outcome (PRO) assessments that allowed pooling for analysis. HF and MF were more effective in reducing pain, itchiness and burning sensation compared to SOC ( p  < 0.01 for all symptoms). Conclusion HF and MF were effective in preventing RD in breast cancer. Future RCTs should compare these interventions to effective cream preparations, such as topical corticosteroids.

BackgroundIdentification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score®) and clinicopathological features (CPFs), on its ability to change radiation oncologists’ recommendations for RT after BCS for DCIS.MethodsProspective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45 years, tumor ≤ 2.5 cm, and margins ≥ 1 mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation.Results217 patients were evaluable, with mean age = 63 years, mean tumor size = 1.1 cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39–54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1–41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22–35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict.ConclusionThe DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.

Exposure to radiation oncology in medical school curricula is limited; thus, mentorship and research opportunities like the Dr. Pamela Catton Summer Studentship Program attempt to bridge this gap and stimulate interest in the specialty. In 2021, the studentship was redesigned as virtual research, mentorship, and case-based discussions due to the COVID-19 pandemic. This study explores the impact of COVID-19 on the studentship, on students’ perceptions of the program, and on medical training and career choice. Fifteen studentship completion essays during 2021–2022 were obtained and anonymized. Thematic analysis was performed to interpret the essays with NVivo. Two independent reviewers coded the essays. Themes were established by identifying connections between coded excerpts. Consensus was achieved through multiple rounds of discussion and iteratively reviewing each theme. Representative quotes were used to illustrate the themes. The themes confirmed the studentship was feasible during the pandemic. Perceived benefits of the program included mentorship and networking opportunities; gaining practical and fundamental knowledge in radiation oncology; developing clinical and research skills; and creating positive attitudes towards radiation oncology and the humanistic aspect of the field. The studentship supported medical specialty selection by helping define student values, shaping perceptions of the specialty, and promoting self-reflection upon students’ personal needs. This study informs future iterations of the studentship to promote radiation oncology in Canadian medical school curricula. It serves as a model for studentships in other specialties that have limited exposure and similar challenges with medical student recruitment.