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The amyloid cascade hypothesis states that Aß aggregates induce pathological changes in tau, leading to neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the spatio-temporal divide between plaques and NFTs. This has been addressed by the inclusion of soluble Aß and tau species in the revised amyloid cascade hypothesis. Nevertheless, despite the potential for non-plaque Aß to contribute to tau pathology, few studies have examined relative correlative strengths between total Aß, plaque Aß and intracellular Aß with tau pathology within a single tissue cohort. Employing frozen and fixed frontal cortex grey and white matter tissue from non-AD controls (Con; n = 39) and Alzheimer's disease (AD) cases (n = 21), biochemical and immunohistochemical (IHC) measures of Aß and AT-8 phosphorylated tau were assessed. Biochemical native-state dot blots from crude tissue lysates demonstrated robust correlations between total Aß and AT-8 tau, when considered as a combined cohort (Con and AD) and when as Con and AD cases, separately. In contrast, no associations between Aß plaques and AT-8 were reported when using IHC measurements in either Con or AD cases. However, when intracellular Aß was measured via the Aß specific antibody MOAB-2, a correlative relationship with AT-8 tau was reported in non-AD controls but not in AD cases. Collectively the data suggests that accumulating intracellular Aß may influence AT-8 pathology, early in AD-related neuropathological change. Despite the lower levels of phospho-tau and Aß in controls, the robust correlative relationships observed suggest a physiological association of Aß production and tau phosphorylation, which may be modified during disease. This study is supportive of a revised amyloid cascade hypothesis and demonstrates regional associative relationships between tau pathology and intracellular Aß, but not extracellular Aß plaques.
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Enfermedad de Alzheimer , Humanos , Neuropatología , Ovillos Neurofibrilares , Proteínas Amiloidogénicas , Anticuerpos , Placa AmiloideRESUMEN
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.
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Oncología por Radiación , Estudiantes de Medicina , Humanos , Canadá , Oncología por Radiación/educación , Pandemias , Selección de ProfesiónRESUMEN
This study sought to report the degree to which postgraduate trainees in radiation oncology perceive their education has been impacted by the COVID-19 pandemic. A cross-sectional online survey was administered from June to July 2020 to trainee members of the Canadian Association of Radiation Oncology (CARO) (n = 203). Thirty-four trainees responded with a 17% response rate. Just under half of participants indicated that COVID-19 had a negative/very negative impact on training (n = 15; 46%). The majority agreed/strongly agreed that they feared family/loved ones would contract COVID-19 (n = 29, 88%), felt socially isolated from friends and family because of COVID-19 (n = 23, 70%), and had difficulty concentrating on tasks because of concerns about COVID-19 (n = 17, 52%). Changes that had a negative/very negative impact on learning included limitations to travel and networking (n = 31; 91%) and limited patient contact (n = 19; 58%). Virtual follow-ups (n = 25: 76%) and in-patient care activities (n = 12; 36%) increased. Electives were cancelled in province (n = 10; 30%), out-of-province (n = 16; 49%), and internationally (n = 15; 46%). Teaching from staff was moderately reduced to completely suppressed (n = 23, 70%) and teaching to medical students was moderately reduced to completely suppressed (n = 27, 82%). Significant changes to radiation oncology training were wrought by the pandemic, and roughly half of trainees perceive that these changes had a negative impact on training. Innovations in training delivery are needed to adapt to these new changes.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Estudios Transversales , Canadá , CurriculumRESUMEN
BACKGROUND: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has been able to predict survival in patients with glioblastoma (GBM). The study explored the role of postoperative radiation (RT) planning MRI-based radiomics to predict the outcomes, with features extracted from the gross tumor volume (GTV) and clinical target volume (CTV). METHODS: Patients with IDH-wildtype GBM treated with adjuvant RT having MRI as a part of RT planning process were included in the study. 546 features were extracted from each GTV and CTV. A LASSO Cox model was applied, and internal validation was performed using leave-one-out cross-validation with overall survival as endpoint. Cross-validated time-dependent area under curve (AUC) was constructed to test the efficacy of the radiomics model, and clinical features were used to generate a combined model. Analysis was done for the entire group and in individual surgical groups-gross total excision (GTR), subtotal resection (STR), and biopsy. RESULTS: 235 patients were included in the study with 57, 118, and 60 in the GTR, STR, and biopsy subgroup, respectively. Using the radiomics model, binary risk groups were feasible in the entire cohort (p < 0.01) and biopsy group (p = 0.04), but not in the other two surgical groups individually. The integrated AUC (iAUC) was 0.613 for radiomics-based classification in the biopsy subgroup, which improved to 0.632 with the inclusion of clinical features. CONCLUSION: Imaging features extracted from the GTV and CTV regions can lead to risk-stratification of GBM undergoing biopsy, while the utility in other individual subgroups needs to be further explored.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Glioblastoma/diagnóstico por imagen , Glioblastoma/radioterapia , Humanos , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Radioterapia Adyuvante , Análisis de SupervivenciaRESUMEN
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.
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Educación de Pregrado en Medicina , Estudiantes de Medicina , Canadá , Selección de Profesión , Humanos , Oncología Médica/educación , Opinión Pública , Facultades de MedicinaRESUMEN
BACKGROUND: The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is composed of microscopic tumor and edema. Infiltrative low grade glioma (LGG) comprises tumor cells that seem similar to GBM PTR on MRI. The work here explored if a radiomics-based approach can distinguish between the two groups (tumor and edema versus tumor alone). METHODS: Patients with GBM and LGG imaged using a 1.5 T MRI were included in the study. Image data from cases of GBM PTR, and LGG were manually segmented guided by T2W hyperintensity. A set of 91 first-order and texture features were determined from each of T1W-contrast, and T2W-FLAIR, diffusion-weighted imaging sequences. Applying filtration techniques, a total of 3822 features were obtained. Different feature reduction techniques were employed, and a subsequent model was constructed using four machine learning classifiers. Leave-one-out cross-validation was used to assess classifier performance. RESULTS: The analysis included 42 GBM and 36 LGG. The best performance was obtained using AdaBoost classifier using all the features with a sensitivity, specificity, accuracy, and area of curve (AUC) of 91%, 86%, 89%, and 0.96, respectively. Amongst the feature selection techniques, the recursive feature elimination technique had the best results, with an AUC ranging from 0.87 to 0.92. Evaluation with the F-test resulted in the most consistent feature selection with 3 T1W-contrast texture features chosen in over 90% of instances. CONCLUSIONS: Quantitative analysis of conventional MRI sequences can effectively demarcate GBM PTR from LGG, which is otherwise indistinguishable on visual estimation.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Imagen por Resonancia Magnética , Neoplasias Encefálicas/diagnóstico por imagen , Diagnóstico Diferencial , Glioblastoma/diagnóstico por imagen , Glioma/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Clasificación del Tumor , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: The peritumoral region (PTR) in glioblastoma (GBM) represents a combination of infiltrative tumor and vasogenic edema, which are indistinguishable on magnetic resonance imaging (MRI). We developed a radiomic signature by using imaging data from low grade glioma (LGG) (marker of tumor) and PTR of brain metastasis (BM) (marker of edema) and applied it on the GBM PTR to generate probabilistic maps. METHODS: 270 features were extracted from T1-weighted, T2-weighted, and apparent diffusion coefficient maps in over 3.5 million voxels of LGG (36 segments) and BM (45 segments) scanned in a 1.5T MRI. A support vector machine classifier was used to develop the radiomics model from approximately 50% voxels (downsampled to 10%) and validated with the remaining. The model was applied to over 575,000 voxels of the PTR of 10 patients with GBM to generate a quantitative map using Platt scaling (infiltrative tumor vs. edema). RESULTS: The radiomics model had an accuracy of 0.92 and 0.79 in the training and test set, respectively (LGG vs. BM). When extrapolated on the GBM PTR, 9 of 10 patients had a higher percentage of voxels with a tumor-like signature over radiological recurrence areas. In 7 of 10 patients, the areas under curves (AUC) were > 0.50 confirming a positive correlation. Including all the voxels from the GBM patients, the infiltration signature had an AUC of 0.61 to predict recurrence. CONCLUSION: A radiomic signature can demarcate areas of microscopic tumors from edema in the PTR of GBM, which correlates with areas of future recurrence.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagen , Edema , Glioblastoma/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: To investigate the relationship between attendance to a pre-treatment psychoeducational intervention (prehab) with treatment outcomes and toxicities in patients receiving radiotherapy for head and neck cancers (HNCs). METHODS: Patients were included from prehab inception in 2013 to 2017, comparing overall survival (OS), locoregional recurrence-free survival (LRFS), and locoregional recurrence (LRR) between prehab attendees (PA) and non-attendees (PNA). Multivariable analysis was performed for OS and LRFS. RESULTS: Among 864 PA and 1128 PNA, 2-year OS was 88% vs 80% (p < 0.001), and LRFS was 84% vs 75% (p < 0.001). On multivariable analysis (MVA), OS and LRFS were independently and unfavourably associated with PNA. The PA cohort had a lower frequency of a "rocky treatment course" compared with the PNA cohort (52/150, 35% vs 71/150, 47%; p = 0.034). CONCLUSIONS: Prehab at our institution is associated with improved long-term oncologic outcomes. Prospective data is needed to better understand this association.
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Neoplasias de Cabeza y Cuello/radioterapia , Terapia Cognitivo-Conductual/métodos , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Interprofessional education (IPE) is being increasingly recognised and prioritised in undergraduate medical education. While efforts are underway to integrate IPE into health professional curricula across Canada, the state of IPE in Canadian medical schools remains unclear. This study aims to assess the current practice of IPE in Canadian undergraduate medical curricula. An online survey was distributed to IPE directors (or designees) of all Canadian medical schools. The survey gathered details of the IPE experiences offered, curriculum structure, and perceived barriers to the programmes. The survey was completed by 12 of 17 Canadian medical schools and revealed that IPE is generally well represented in Canadian undergraduate medical education curricula. Reported barriers to IPE efforts included scheduling and funding limitations. By comparison, student interest was one of the least commonly cited issues. It would appear that students and faculty are interested in advancing the state of IPE in undergraduate medical education. The results of this study are crucial as IPE continues to evolve as a component of undergraduate medical curricula across the globe.
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Educación de Pregrado en Medicina/organización & administración , Empleos en Salud/educación , Relaciones Interprofesionales , Facultades de Medicina/organización & administración , Canadá , Educación de Pregrado en Medicina/estadística & datos numéricos , Humanos , Facultades de Medicina/estadística & datos numéricosRESUMEN
BACKGROUND: Neighborhood socioeconomic deprivation impacts outcomes in various cancers. We examined this association in nasopharyngeal carcinoma (NPC) patients using the area deprivation index (ADI). METHODS: We conducted a single-institution retrospective cohort study on NPC patients treated with definitive radiotherapy from 1980 to 2023. ADI was used as the primary exposure measure. Higher ADI indicates higher levels of socioeconomic deprivation. RESULTS: Of 561 patients, those with higher ADI (6-10 vs. 1-5) presented more commonly with AJCC stage III/IV compared to I/II (87% vs. 76%, p = 0.03). Increasing ADI decile score correlated with poorer overall survival (HR 1.14, 95% CI 1.01-1.28, p = 0.04). Local control was worse in patients from the most deprived quartile in the cohort ADI 5-10 (HR 2.11, 95% CI 1.01-4.41, p = 0.05). CONCLUSIONS: NPC patients from more disadvantaged neighborhoods undergoing radiotherapy had worse local control and survival outcomes. Interventions to address structural determinants of health and neighborhood disparities may improve these outcomes.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/terapia , Persona de Mediana Edad , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/radioterapia , Adulto , Anciano , Estudios de Cohortes , Factores Socioeconómicos , Estadificación de Neoplasias , Tasa de Supervivencia , Características del VecindarioRESUMEN
Introduction: Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. Material and methods: We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. Results: Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. Conclusions: HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.
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PURPOSE: A history of prior pelvic radiation therapy (RT) for rectal cancer is a relative contraindication for definitive RT for prostate cancer. High-dose-rate (HDR) brachytherapy can significantly limit the dose to surrounding tissues compared to external beam RT. However, there is limited data surrounding its safety in patients with prior pelvic RT. METHODS AND MATERIALS: A retrospective chart review was performed at the University of California, San Francisco to identify patients diagnosed with prostate cancer with a history of pelvic RT for rectal cancer who were treated with high-dose-rate brachytherapy (HDR-BT) between 2006 and 2022. Inclusion criteria were biopsy-confirmed prostate cancer with no evidence of distant disease on clinical examination or imaging, and at least one post-treatment clinic appointment. RESULTS: Seven patients were treated with salvage HDR-BT at a median interval of 17.7 years after RT for rectal cancer. HDR-BT doses included 3600 cGy in six fractions (nâ¯=â¯5), 2700 cGy in 2 fractions (n=1), or 2800 cGy in four fractions (nâ¯=â¯1). There was no acute grade ≥2 gastrointestinal toxicity, and 1 patient developed late grade 2 rectal bleeding. Two patients developed acute grade 2 genitourinary toxicity consisting of urinary frequency and urgency, which persisted through long-term follow up. At a median follow up of 29.5 months after HDR brachytherapy, one patient developed regional and distant failure, and another had seminal vesicle recurrence. CONCLUSIONS: HDR-BT is a safe treatment for patients with prostate cancer who previously received RT for rectal cancer. Further studies are needed to better characterize the long-term toxicity of HDR-RT in this population.
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Braquiterapia , Neoplasias de la Próstata , Neoplasias del Recto , Masculino , Humanos , Braquiterapia/métodos , Estudios Retrospectivos , Neoplasias de la Próstata/radioterapia , Sistema Urogenital , Neoplasias del Recto/radioterapia , Dosificación RadioterapéuticaRESUMEN
Purpose: The effect of climate-driven events, such as wildfires, on health care delivery and cancer care is a growing concern. Patients with cancer undergoing radiation therapy are particularly vulnerable to treatment interruptions, which have a direct effect on survival. We report the results of a study characterizing the effect of wildfires on radiation oncology clinics and their patients. Methods and Materials: A survey of California radiation oncologists was used to evaluate emergency preparedness and the effect of wildfires on the delivery of radiation therapy services between 2017 and 2022. Descriptive statistics and Pearson's χ2 tests were performed to investigate potential relationships between provider characteristics, practice settings, and perceptions of the effect of wildfire events. California Department of Forestry and Fire Protection data were employed to map the geographic distribution of wildfires to clinic locations. Results: Response rate was 12.3% (51/415 radiation oncologists), representing 25% of clinics (43/176) in 41% (24/58) of California counties. Sixty-one percent (31/51) of respondents reported being affected by a wildfire, 2 of which are rural clinics (100%, 2/2) and 29 are (59%, 29/49) metropolitan practices. Of these, 18% (9/51) reported a clinic closure, and 29% (15/51) reported staffing shortages. Respondents reported effects on patients, including having to evacuate (55%, 28/51), cancel/reschedule treatments (53%, 27/51), and experiencing physical, mental, or financial hardship due to wildfires (45%, 23/51). Respondents described effects on clinical operations, including being forced to transfer patients (24%, 12/51), transportation interruptions (37%, 19/51), regional/community evacuations (35%, 18/51), and physical/mental health effects (27%, 14/51) on clinic personnel. Less than half of the respondents (47%, 24/51) reported their workplace had a wildfire emergency preparedness plan. Additionally, geographic analysis revealed that 100% (176/176) of clinics were located within 25 miles of a wildfire. Conclusions: This study highlights the effects of wildfires on radiation oncology clinics and patients and underscores the need for emergency preparedness planning to minimize the consequences of such disasters.
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PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.
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Carcinoma de Células Escamosas , Neoplasias Laríngeas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Carcinoma de Células Escamosas/patología , Carga Tumoral , Canadá , Neoplasias Laríngeas/patología , Supervivencia sin Enfermedad , Estadificación de NeoplasiasRESUMEN
PURPOSE: In this scoping review, we evaluated existing literature related to factors influencing treatment decision-making for patients diagnosed with cancer in low- and middle-income countries, noting factors that influence decisions to pursue treatment with curative versus non-curative intent. We identified an existing framework for adult cancer developed in a high-income country (HIC) context and described similar and novel factors relevant to low-and middle-income country settings. METHODS: We used scoping review methodology to identify and synthesize existing literature on factors influencing decision-making for pediatric and adult cancer in these settings. Articles were identified through an advanced Boolean search across six databases, inclusive of all article types from inception through July 2022. RESULTS: Seventy-nine articles were identified from 22 countries across six regions, primarily reporting the experiences of lower-middle and upper-middle-income countries. Included articles largely represented original research (54%), adult cancer populations (61%), and studied patients as the targeted population (51%). More than a quarter of articles focused exclusively on breast cancer (28%). Approximately 30% described factors that influenced decisions to choose between therapies with curative versus non-curative intent. Of 56 reported factors, 22 novel factors were identified. Socioeconomic status, reimbursement policies/cost of treatment, and treatment and supportive care were the most commonly described factors. CONCLUSIONS: This scoping review expanded upon previously described factors that influence cancer treatment decision-making in HICs, broadening knowledge to include perspectives of low- and middle-income countries. While global commonalities exist, certain variables influence treatment choices differently or uniquely in different settings. Treatment regimens should further be tailored to local environments with consideration of contextual factors and accessible resources that often impact decision-making.
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Neoplasias de la Mama , Países en Desarrollo , Adulto , Humanos , Niño , Femenino , RentaRESUMEN
Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors. Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study. Design, Setting, and Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria. Exposures: Tumor volume as measured on diagnostic imaging by expert neuroradiologists. Main Outcomes and Measures: Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study. Results: The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76). Conclusions and Relevance: Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.
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Carcinoma de Células Escamosas , Neoplasias Laríngeas , Neoplasias de la Lengua , Masculino , Humanos , Anciano , Femenino , Neoplasias Laríngeas/patología , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Carga Tumoral , Canadá , Neoplasias de la Lengua/terapiaRESUMEN
Background Aberrant phenotype expression in acute myeloid leukemia (AML) may be due to genetic defects and is associated with a poor prognosis. CD7 is the first T-cell-associated antigen to be expressed during T-lymphocyte maturation. Aberrant expression of CD7 in AML influences clinical response, remission rate, and overall survival in these patients. Objective To determine the frequency of aberrant CD7 expression in patients with AML. Materials and methods This cross-sectional study was performed over a period of 12 months from July 2020 to June 2021 in the Hematology Department, Chughtai Lab, Lahore. This study included 120 patients who were newly diagnosed with AML. The following tests were performed for included patients: complete blood count (CBC), peripheral blood smear analysis, and flow cytometric analysis using a blood sample or bone marrow aspirate. Blast cells were analyzed for aberrant CD7 expression. Calculation of the sample size was performed by using the Select Statistics calculator. All statistical analyses were performed using SPSS ver. 23 software (IBM Corp., Armonk, NY). Data were expressed as frequencies, means ± standard deviation (SD), and percentages. Results Of 120 patients newly diagnosed with AML, the CD7 antigen was aberrantly expressed in 36 cases (30%). Of these patients, the AML2 subtype was the most common type of AML with aberrant CD7 expression, followed by AML M4, AML M1, M3, AML M5, and AML M0, respectively. Conclusion In our study, aberrant CD7 expression occurred at a high frequency in acute myeloid leukemia. Thus, this marker should be added to the current flow cytometry panels.
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Management of locoregionally advanced head and neck cancers (HNCs) remains a challenge. Some groups have attempted to use stereotactic radiotherapy (SBRT) to deliver "boost" treatment following conventional radiotherapy to improve local control (LC) and overall survival (OS), while aiming for acceptable toxicities. Medline, EMBASE, and Cochrane Library databases were queried for SBRT as curative-intent planned boost in HNC after conventional radiotherapy. Individual studies were reviewed from inception until January 2021, extracting patient, treatment, and outcome data. Nine studies met inclusion criteria, representing 454 unique patients treated with curative intent across multiple head and neck sites with conventional radiotherapy. At 3 years, median LC was 92% (90%-98%), and median OS was 80% (75%-91%). Seven treatment-related grade 5 toxicities (1.5%) were reported. Despite acceptable LC and OS rates, there were severe treatment-related late toxicities. As such, SBRT boost should only be used in investigational settings until more data is available.
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Neoplasias de Cabeza y Cuello , Radiocirugia , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Cuello , Radiocirugia/efectos adversos , Tasa de SupervivenciaRESUMEN
Purpose: Canadian radiation oncology (RO) trainees have experienced employment challenges after residency training. The present study was conducted to evaluate current employment trends and perform comparisons to prior reported assessments. Methods and Materials: A survey was administered to all 13 Canadian RO program directors requesting the employment status and location of their graduates during the past 3 years, and their perceptions on graduates' employment challenges. Visa trainees were excluded. Findings were compared with surveys performed in 2014, 2016, and 2018. Results: The response rate from RO program directors was 100%. There were 77 graduates identified who completed their residency training between 2017 and 2020. All had known employment status and location. Two (17%) 2020 graduates, 16 (84%) 2019 graduates, 17 (81%) 2018 graduates, and 24 (100%) 2017 graduates had staff employment. Of the 59 graduates with staff positions, 86% were in Canada. Some graduates (28%) obtained staff or locum employment in a province other than their training program. The proportion of graduates obtaining staff positions 1 year after residency increased to 84% from 46%-48% in prior assessments. Most program directors (62%) did not perceive any difficulties with their graduates finding staff employment or trainees transferring to training programs in other disciplines owing to perceived workforce challenges. Conclusions: Compared with 3 prior employment outcome assessments, this study observed a higher proportion of graduates with staff positions in Canada, fewer total graduates, fewer graduates seeking staff employment or in fellowship positions, and a trend for fewer graduates seeking employment or fellowships abroad. These findings support the view that the Canadian RO job market continues to improve. Although employment challenges for newly certified, Canadian-trained radiation oncologists still exist, national corrective measures to regulate resident intake in 2011 appear to have had a positive effect on the employment outcomes of recent Canadian RO graduates.
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PURPOSE: Stereotactic body radiation therapy (SBRT) for de novo (previously untreated) head and neck cancers (HNCs) is increasingly being used in medically unfit patients. A systematic review of SBRT was conducted for previously untreated HNCs. METHODS AND MATERIALS: Medline (PubMed), excerpta medica database, and Cochrane Library databases were queried from inception until July 2020. Comparative outcome data were extracted where available up to 5 years. Results from random-effect models were presented in forest plots, with between-study heterogeneity evaluated by I2 statistics and Q-tests. RESULTS: Nine studies met inclusion criteria, representing 157 patients. Local control rates at 1, 2, and 3 years were as follows: 90.7% (95% confidence interval, 80.6%-95.6%), 81.8% (67.2%-90.7%), and 73.5% (40.4%-90.5%), respectively. Overall survival at 1, 2, and 3 years was 75.9% (75.1%-76.6%), 61.1% (60.3%-61.9%), and 50.0% (48.8%-51.4%), respectively. Late grade 3 to 4 toxicity rate was 3.3% (0.2%-10.2%), and late grade 5 toxicity rate was 0.1% (0.0%-1.0%). CONCLUSIONS: SBRT for de novo HNC is safe and effective in providing locoregional control, with acceptable toxicities in most subsites. This finding warrants broader validation to guide its scope.