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Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.
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Antagonistas de Andrógenos , Enfermedades Cardiovasculares , Neoplasias de la Próstata , Humanos , Masculino , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Medición de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Previous studies have shown an increasing incidence of pancreatic cancer (PC), especially in younger women; however, this has not been externally validated. In addition, there are limited data about contributing factors to this trend. We report age and sex-specific time-trend analysis of PC age-adjusted incidence rates (aIRs) using the National Program of Cancer Registries database without Surveillance Epidemiology and End Results data. METHODS: PC aIR, mortality rates, annual percentage change, and average annual percentage change (AAPC) were calculated and assessed for parallelism and identicalness. Age-specific analyses were conducted in older (≥55 years) and younger (<55 years) adults. PC incidence based on demographics, tumor characteristics, and mortality were evaluated in younger adults. RESULTS: A total of 454,611 patients were diagnosed with PC between 2001 and 2018 with significantly increasing aIR in women (AAPC = 1.27%) and men (AAPC = 1.14%) without a difference (P = .37). Similar results were seen in older adults. However, in younger adults (53,051 cases; 42.9% women), women experienced a greater increase in aIR than men (AAPCs = 2.36%, P < .001 vs 0.62%, P = 0.62) with nonparallel trends (P < .001) and AAPC difference of 1.74% (P < .001). This AAPC difference appears to be due to rising aIR in Blacks (2.23%; P < .001), adenocarcinoma histopathologic subtype (0.89%; P = .003), and location in the head-of-pancreas (1.64%; P < .001). PC mortality was found to be unchanged in women but decreasing in counterpart men (AAPC difference = 0.54%; P = .001). CONCLUSION: Using nationwide data, covering ≈64.5% of the U.S. population, we externally validate a rapidly increasing aIR of PC in younger women. There was a big separation of the incidence trend between women and men aged 15-34 years between 2001 and 2018 (>200% difference), and it did not show slowing down.
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Neoplasias Pancreáticas , Masculino , Humanos , Femenino , Estados Unidos/epidemiología , Anciano , Incidencia , Sistema de Registros , Neoplasias Pancreáticas/epidemiología , Páncreas , Neoplasias PancreáticasRESUMEN
BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes. METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m2) was categorized into 'normal weight', 'overweight', and 'obese'. Patients were further classified into combined physical activity and BMI groups. Cox-proportional hazard models with Firth correction were computed to assess associations [hazard ratio (HR), 95% profile HR likelihood confidence interval (95% CI) between individual and combined physical activity and BMI groups with overall and disease-free survival in colorectal cancer patients. RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk of death or recurrence (HR: 1.41 (95% CI: 0.99-2.06), p = 0.03; HR: 1.49 (95% CI: 1.02-2.21) and HR: 1.51 (95% CI: 1.02-2.26), p = 0.04, respectively). 'Not-highly active' patients had worse disease-free survival outcomes, regardless of their BMI, compared to 'highly active/normal weight' patients. 'Not-highly active/obese' patients had a 3.66 times increased risk of death or recurrence compared to 'highly active/normal weight' patients (HR: 4.66 (95% CI: 1.75-9.10), p = 0.002). Lower activity thresholds yielded smaller effect sizes. CONCLUSION: Physical activity and BMI were individually associated with disease-free survival among colorectal cancer patients. Physical activity seems to improve survival outcomes in patients regardless of their BMI.
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Neoplasias Colorrectales , Obesidad , Humanos , Índice de Masa Corporal , Obesidad/complicaciones , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Ejercicio Físico , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Although bariatric surgery is the most effective treatment of severe obesity, a proportion of patients experience clinically significant weight regain (WR) with further out from surgery. The purpose of this review is to summarize the prevalence, predictors, and causes of weight regain. RECENT FINDINGS: Estimating the prevalence of WR is limited by a lack of consensus on its definition. While anatomic failures such as dilated gastric fundus after sleeve gastrectomy and gastro-gastric fistula after Roux-en-Y gastric bypass can lead to WR, the most common causes appear to be dysregulated/maladaptive eating behaviors, lifestyle factors, and physiological compensatory mechanisms. To date, dietary, supportive, behavioral, and exercise interventions have not demonstrated a clinically meaningful impact on WR, and there is limited evidence for pharmacotherapy. Future studies should be aimed at better defining WR to begin to understand the etiologies. Additionally, there is a need for non-surgical interventions with demonstrated efficacy in rigorous randomized controlled trials for the prevention and reversal of WR after bariatric surgery.
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Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Humanos , Aumento de Peso/fisiología , Estudios Retrospectivos , Cirugía Bariátrica/efectos adversos , Obesidad/epidemiología , Obesidad/cirugía , Obesidad/etiología , Obesidad Mórbida/cirugíaRESUMEN
BACKGROUND AND OBJECTIVES: Demographic and socioeconomic disparities affect cancer specific outcomes in numerous malignancies, but the impact of these for patients with small bowel neuroendocrine tumors (SBNETs) is not well understood. The primary objective was to investigate the impact of demographic and socioeconomic factors on overall survival (OS) for patients with SBNETs. METHODS: We performed a retrospective cohort study utilizing the National Cancer Database to assess patients diagnosed with SBNET between 2004 and 2015. Patients were stratified by demographics, socioeconomic factors, insurance status, and place of living. RESULTS: The 5-year OS for the entire cohort was 78.5%. The 5-year survival was worse in patients with lower income (p < 0.0001), lower education (p < 0.0001), not in proximity to a metro area (p = 0.0004), and treatment at a community cancer center (p < 0.0001). Adjusting for age and sex, factors associated with worse OS were lower income (<$38 000) (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.04-1.28), lower education (>20% no HSD) (HR: 1.14, 95% CI: 1.02-1.26), no insurance (HR: 1.66, 95% CI: 1.33-2.06), and not living in proximity to a metro area (HR: 1.27, 95% CI: 1.10-1.47). CONCLUSIONS: Patient demographics and socioeconomic factors play an important role in survival of patients with SBNETs, specifically proximity to a metro area, median income, education level, and type of treatment center. Strategies to improve access to care must be considered in this at-risk population.
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Tumores Neuroendocrinos , Humanos , Tumores Neuroendocrinos/terapia , Estudios Retrospectivos , Disparidades Socioeconómicas en Salud , Factores Socioeconómicos , Disparidades en Atención de SaludRESUMEN
OPINION STATEMENT: Despite extensive research that has identified new risk factors, genetic mutations, and therapeutic options, pancreatic ductal adenocarcinoma continues to be a leading cause of cancer related death. Patients with pancreatic cancer, along with their clinicians, must balance realistic hope alongside a life-threatening diagnosis. As the search for treatments to reduce the morbidity and mortality continues, symptom management and quality of life remain the focus of our efforts. In addition to side effects of cancer-directed therapy, patients are at risk for malnutrition, pain, and fatigue. These factors are often overlooked in practice, so a multidisciplinary team is critical in optimizing the care of patients.
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Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/terapia , Manejo del Dolor , Dolor/epidemiología , Adenocarcinoma/complicaciones , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/epidemiología , Carcinoma Ductal Pancreático/genética , Fatiga/complicaciones , Fatiga/epidemiología , Fatiga/genética , Fatiga/terapia , Humanos , Mutación/genética , Dolor/patología , Cuidados Paliativos , Calidad de VidaRESUMEN
BACKGROUND: Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. METHODS: Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. RESULTS: After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. CONCLUSIONS: Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society.
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Antagonistas de Andrógenos/uso terapéutico , Androstenos/uso terapéutico , Biomarcadores de Tumor/sangre , Docetaxel/uso terapéutico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Testosterona/sangre , Anciano , Antineoplásicos/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
PURPOSE: Whether brachytherapy based microboosting of the dominant intraprostatic lesion (DIL) improves outcomes over standard approaches is not known. The purpose of this study is to perform a systematic review on brachytherapy microboosting of the DIL to evaluate clinical outcomes and toxicities with this treatment approach. MATERIALS AND METHODS: This review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Databases including Pubmed, Embase, and Google Scholar were queried. About 16 studies met our inclusion criteria. These studies reported PSA control and/or toxicities based on standardized scales. RESULTS: There were 10 studies (two monotherapy, eight combination) that used HDR microboosting on a total of 516 patients. HDR dose (EQD2 assuming alpha/beta of 1.5) to the DIL ranged from 90 to 180 Gy. Most patients were low/intermediate risk. PSA control rates at 5-8 years ranged from 69% to 100%. Acute/late G3-G4 GU/GI toxicities ranged from 0% to 12%. There were six studies (five monotherapy, one combination) that used LDR microboosting on a total of 1041 patients. Studies performed a microboost of 130-150% of the whole gland prescription to the DIL. Most patients were low/intermediate risk. PSA control rates at 5 years ranged from 69% to 98%. Acute/late G3-4 GU/GI toxicities ranged from 0% to 4%. CONCLUSIONS: Over 1000 patients have been treated with a brachytherapy based microboost in published series. Severe acute/late toxicities appear limited. PSA control rates with more than 5 years of follow-up are limited. Longer-term follow-up is needed to determine ideal utilization of this approach.
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Braquiterapia , Neoplasias de la Próstata , Humanos , Masculino , Braquiterapia/efectos adversos , Braquiterapia/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
Cardiac risk mitigation is a major priority in improving outcomes for cancer survivors as advances in cancer screening and treatments continue to decrease cancer mortality. More than half of adult cancer patients will be treated with radiotherapy (RT); therefore it is crucial to develop a framework for how to assess and predict radiation-induced cardiac disease (RICD). Historically, RICD was modelled solely using whole heart metrics such as mean heart dose. However, data over the past decade has identified cardiac substructures which outperform whole heart metrics in predicting for significant cardiac events. Additionally, non-RT factors such as pre-existing cardiovascular risk factors and toxicity from other therapies contribute to risk of future cardiac events. In this review, we aim to discuss the current evidence and knowledge gaps in predicting RICD and provide a roadmap for the development of comprehensive models based on three interrelated components, (1) baseline CV risk assessment, (2) cardiac substructure radiation dosimetry linked with cardiac-specific outcomes and (3) novel biomarker development.
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ABSTRACT: The oligometastatic disease state, defined as a cancer with 5 or fewer sites of metastasis, is a therapeutic opportunity to improve oncologic outcomes. Colorectal cancer (CRC) was among the first for which oligometastatic treatment was used in routine clinical practice, and recent studies have shown potential for improved overall survival with metastasis-directed therapies. As CRC is the third most common cause of cancer death in men and women, improving oncologic outcomes in this population is of paramount importance. The relatively recent identification of this treatment paradigm and paucity of high-quality data have led to heterogeneity in clinical practice. This review will explore perspectives of a panel of surgical and radiation oncologists for complex or controversial cases of metastatic CRC.
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Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Masculino , Metástasis de la Neoplasia , Persona de Mediana Edad , Anciano , Terapia Combinada/métodos , Resultado del TratamientoRESUMEN
Background: Arrhythmias are common following radiotherapy for non-small cell lung cancer. Objectives: The aim of this study was to analyze the association of distinct arrhythmia classes with cardiac substructure radiotherapy dose. Methods: A retrospective analysis was conducted of 748 patients with locally advanced non-small cell lung cancer treated with radiotherapy. Cardiac substructure dose parameters were calculated. Receiver-operating characteristic curve analyses for predictors of Common Terminology Criteria for Adverse Events grade ≥3 atrial fibrillation (AF), atrial flutter, non-AF and non-atrial flutter supraventricular tachyarrhythmia (SVT), bradyarrhythmia, and ventricular tachyarrhythmia (VT) or asystole were calculated. Fine-Gray regression models were performed (with noncardiac death as a competing risk). Results: Of 748 patients, 128 (17.1%) experienced at least 1 grade ≥3 arrhythmia, with a median time to first arrhythmia of 2.0 years (Q1-Q3: 0.9-4.2 years). The 2-year cumulative incidences of each arrhythmia group were 8.0% for AF, 2.7% for atrial flutter, 1.8% for other SVT, 1.4% for bradyarrhythmia, and 1.1% for VT or asystole. Adjusting for baseline cardiovascular risk, pulmonary vein (PV) volume receiving 5 Gy was associated with AF (subdistribution HR [sHR]: 1.04/mL; 95% CI: 1.01-1.08; P = 0.016), left circumflex coronary artery volume receiving 35 Gy with atrial flutter (sHR: 1.10/mL; 95% CI: 1.01-1.19; P = 0.028), PV volume receiving 55 Gy with SVT (sHR: 1.03 per 1%; 95% CI: 1.02-1.05; P < 0.001), right coronary artery volume receiving 25 Gy with bradyarrhythmia (sHR: 1.14/mL; 95% CI: 1.00-1.30; P = 0.042), and left main coronary artery volume receiving 5 Gy with VT or asystole (sHR: 2.45/mL; 95% CI: 1.21-4.97; P = 0.013). Conclusions: This study revealed pathophysiologically distinct arrhythmia classes associated with radiotherapy dose to discrete cardiac substructures, including PV dose with AF and SVT, left circumflex coronary artery dose with atrial flutter, right coronary artery dose with bradyarrhythmia, and left main coronary artery dose with VT or asystole, guiding potential risk mitigation approaches.
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Efforts to mitigate radiation therapy (RT)-associated cardiotoxicity have focused on constraining mean heart dose. However, recent studies have shown greater predictive power with cardiac substructure dose metrics, such as the left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) ≥10%. Herein, we investigated the feasibility of LAD radiation sparing in contemporary intensity modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) lung cancer plans. Single institution retrospective analysis of 54 patients with locally advanced lung cancer treated with thoracic RT was conducted between February 2018 and August 2021. After excluding 33 (5 = non-IMRT/VMAT or intentionally LAD-optimized; 28 = LAD V15Gy <10%), 21 plans with LAD V15Gy ≥10% were identified for LAD reoptimization with intent to meet LAD V15Gy <10% while maintaining meeting organ at risk (OAR) metrics and target coverage with original plan parameters. Dosimetric variables were compared using paired t tests. Most patients (57.1%, 12/21) were treated with definitive RT, 8 of 21 patients (38.1%) with postoperative RT, and 1 with neoadjuvant RT. The median prescribed RT dose was 60 Gy (range, 50.4-66 Gy) in 30 fractions (range, 28-33 fractions). LAD reoptimized plans (vs original) led to significant reductions in mean LAD V15Gy (39.4% ± 13.9% vs 9.4% ± 13.0%; P < .001) and mean LAD dose (12.9 Gy ± 4.6 Gy vs 7.6 Gy ± 2.8 Gy; P < .001). Most (85.7%; 18/21) LAD reoptimized plans achieved LAD V15Gy <10%. There were no statistically significant differences in overall lung, esophageal, or spinal cord dose metrics. Only 1 reoptimization (1/21) exceeded an OAR constraint that was initially met in the original plan. To our knowledge, this is the first report describing the feasibility of LAD-optimized lung cancer RT planning using the newly identified LAD V15Gy constraint. We observed that LAD V15Gy <10% is achievable in more than 85% of plans initially exceeding this constraint, with minimal dosimetric tradeoffs. Our results support the feasibility of routine incorporation of the LAD as an OAR in modern thoracic IMRT/VMAT planning.
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In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.
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Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection. Methods and Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC. Patients who underwent preoperative chemotherapy and SBRT followed by surgical resection were reviewed. SBRT was delivered to a dose of 33 Gy in 5 fractions. Kaplan-Meier overall survival and progression-free survival estimates were calculated. Results: In total, 18 patients (12 BRPC, 6 LAPC) were included. Median age was 69 years (range 41-84 years). Median follow-up was 30 months (range 13-59 months). Seventeen patients (94%) had a R0 resection and 13 (72%) underwent vascular reconstruction. Median overall survival and progression-free survival was 42 months (range 13-59 months) and 23 months (range 1-45 months), respectively. In total, 61% (11/18) patients experienced progression at any point during follow-up. Of the patients who experienced recurrence, 27% (3/11) experienced local progression as component of their first recurrence, whereas 100% (11/11) experienced distant progression as a component of their first recurrence. When examining all recurrences that occurred at any point in follow-up, 28% (5/18) of patients experienced local or locoregional recurrence and 61% (11/18) experienced distant progression. Conclusions: Local control and margin negative resection rates were excellent with preoperative chemotherapy and nondose-escalated SBRT in surgically resected patients with BR/LAPC. Distant recurrence was the predominant site of failure with lower incidences of isolated locoregional recurrences. Additional research is needed to determine the ideal treatment volume and patients who may benefit from dose escalation.
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BACKGROUND: HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex. RESULTS: Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin-substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T-cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades. CONCLUSIONS: Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I.
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Fármacos Anti-VIH/farmacología , Evaluación Preclínica de Medicamentos/métodos , Proteínas Proto-Oncogénicas c-hck/antagonistas & inhibidores , Quinoxalinas/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Sulfonamidas/farmacología , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/antagonistas & inhibidores , Fármacos Anti-VIH/aislamiento & purificación , Humanos , Simulación del Acoplamiento Molecular , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-hck/genética , Quinoxalinas/aislamiento & purificación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Sulfonamidas/aislamiento & purificación , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/genética , BencenosulfonamidasRESUMEN
PURPOSE: Accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy is a standard of care treatment typically delivered over 10 fractions. The TRIUMPH-T multi-institutional study recently demonstrated promising results using a shorter three fraction regimen, however there are limited additional published series using this regimen. Here, we report our experience and outcomes for patients treated as per the TRIUMPH-T regimen. METHODS AND MATERIALS: This study was a retrospective single-institution analysis of patients who underwent lumpectomy followed by APBI (22.5 Gy in 3 fractions delivered over 2-3 days) using a Strut Adjusted Volume Implant (SAVI) applicator between November 2016 and January 2021. Dose-volume metrics were obtained from the clinically treated plan. Chart review was performed to determine locoregional recurrence and toxicities according to CTCAE v5.0. RESULTS: Between 2016 and 2021, 31 patients were treated per the TRIUMPH-T protocol. Median followup was 31 months from completion of brachytherapy. There were no acute/late Grade 3 or higher toxicities. Cumulative late Grade 1 and 2 toxicities were seen in 58.1% and 9.7% of patients, respectively. Of note, four patients experienced locoregional recurrence: three ipsilateral breast tumor recurrences and one nodal recurrence. All three ipsilateral breast tumor recurrences occurred in patients who would be classified as "cautionary" based on ASTRO consensus guidelines due to age ≤50, lobular histology, or high grade. CONCLUSIONS: Three-fraction HDR brachytherapy APBI was well-tolerated with no grade 3 or higher toxicities and an acceptably small percentage of grade 2 toxicities. Given the small sample size, the number of recurrences suggests that attention to appropriate patient selection is necessary until more long-term followup data is available.
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Braquiterapia , Neoplasias de la Mama , Humanos , Femenino , Braquiterapia/métodos , Estudios Retrospectivos , Dosificación Radioterapéutica , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/etiología , Mastectomía Segmentaria , Neoplasias de la Mama/radioterapiaRESUMEN
Objective: Patients now have direct access to their radiology reports, which can include complex terminology and be difficult to understand. We assessed ChatGPT's ability to generate summarized MRI reports for patients with prostate cancer and evaluated physician satisfaction with the artificial intelligence (AI)-summarized report. Methods: We used ChatGPT to summarize five full MRI reports for patients with prostate cancer performed at a single institution from 2021 to 2022. Three summarized reports were generated for each full MRI report. Full MRI and summarized reports were assessed for readability using Flesch-Kincaid Grade Level (FK) score. Radiation oncologists were asked to evaluate the AI-summarized reports via an anonymous questionnaire. Qualitative responses were given on a 1-5 Likert-type scale. Fifty newly diagnosed prostate cancer patient MRIs performed at a single institution were additionally assessed for physician online portal response rates. Results: Fifteen summarized reports were generated from five full MRI reports using ChatGPT. The median FK score for the full MRI reports and summarized reports was 9.6 vs. 5.0, (p < 0.05), respectively. Twelve radiation oncologists responded to our questionnaire. The mean [SD] ratings for summarized reports were factual correctness (4.0 [0.6], understanding 4.0 [0.7]), completeness (4.1 [0.5]), potential for harm (3.5 [0.9]), overall quality (3.4 [0.9]), and likelihood to send to patient (3.1 [1.1]). Current physician online portal response rates were 14/50 (28%) at our institution. Conclusions: We demonstrate a novel application of ChatGPT to summarize MRI reports at a reading level appropriate for patients. Physicians were likely to be satisfied with the summarized reports with respect to factual correctness, ease of understanding, and completeness. Physicians were less likely to be satisfied with respect to potential for harm, overall quality, and likelihood to send to patients. Further research is needed to optimize ChatGPT's ability to summarize radiology reports and understand what factors influence physician trust in AI-summarized reports.
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PURPOSE: A left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15 Gy) ≥10% has been recently observed to be an independent risk factor of major adverse cardiac events and all-cause mortality in patients with locally advanced non-small cell lung cancer treated with radiation therapy. However, this dose constraint has not been validated in independent or prospective data sets. METHODS AND MATERIALS: The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0617 data set from the National Clinical Trials Network was used. The LAD coronary artery was manually contoured. Multivariable Cox regression was performed, adjusting for known prognostic factors. Kaplan-Meier estimates of overall survival (OS) were calculated. For assessment of baseline cardiovascular risk, only age, sex, and smoking history were available. RESULTS: There were 449 patients with LAD dose-volume data and clinical outcomes available after 10 patients were excluded owing to unreliable LAD dose statistics. The median age was 64 years. The median LAD V15 Gy was 38% (interquartile range, 15%-62%), including 94 patients (21%) with LAD V15 Gy <10% and 355 (79%) with LAD V15 Gy ≥10%. Adjusting for prognostic factors, LAD V15 Gy ≥10% versus <10% was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.43; 95% confidence interval, 1.02-1.99; P = .037), whereas a mean heart dose ≥10 Gy versus <10 Gy was not (adjusted HR, 1.12; 95% confidence interval, 0.88-1.43; P = .36). The median OS for patients with LAD V15 Gy ≥10% versus <10% was 20.2 versus 25.1 months, respectively, with 2-year OS estimates of 47% versus 67% (P = .004), respectively. CONCLUSIONS: In a reanalysis of RTOG 0617, LAD V15 Gy ≥10% was associated with an increased risk of all-cause mortality. These findings underscore the need for improved cardiac risk stratification and aggressive risk mitigation strategies, including implementation of cardiac substructure dose constraints in national guidelines and clinical trials.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Vasos Coronarios , Neoplasias Pulmonares/radioterapia , Estudios Prospectivos , Dosis de Radiación , Dosificación RadioterapéuticaRESUMEN
BACKGROUND AND AIMS: Pancreatic cancer (PC) incidence is increasing at a greater rate in young women compared to young men. We performed a race- and ethnicity-specific evaluation of incidence trends in subgroups stratified by age and sex to investigate the association of race and ethnicity with these trends. METHODS: Age-adjusted PC incidence rates (IR) from the years 2000 to 2018 were obtained from the SEER 21 database. Non-Hispanic White (White), Non-Hispanic Black (Black) and Hispanic patients were included. Age categories included older (ages ≥ 55) and younger (ages < 55) adults. Time-trends were described as annual percentage change (APC) and average APC (AAPC). RESULTS: Younger White [AAPC difference = 0.73, p = 0.01)], Black [AAPC difference = 1.96, p = 0.01)] and Hispanic [AAPC difference = 1.55, p = 0.011)] women experienced a greater rate of increase in IR compared to their counterpart men. Younger Hispanic women experienced a greater rate of increase in IR compared to younger Black women [AAPC difference = -1.28, p = 0.028)] and younger White women [AAPC difference = -1.35, p = 0.011)]. CONCLUSION: Younger women of all races and ethnicities experienced a greater rate of increase in PC IR compared to their counterpart men; however, younger Hispanic and Black women experienced a disproportionately greater increase. Hispanic women experienced a greater rate of increase in IR compared to younger Black and White women.
RESUMEN
Importance: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited. Objective: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians. Design, Setting, and Participants: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers. Main Outcomes and Measures: Tumor board burden was measured on a 4-point scale (1, not at all burdensome; 2, slightly burdensome; 3, moderately burdensome; and 4, very burdensome). Univariable and multivariable probabilistic index (PI) models were performed. Results: Surveys were completed by 111 physicians (median age, 42 years [IQR, 36-50 years]; 58 women [52.3%]; 60 non-Hispanic White [54.1%]). On multivariable analysis, factors associated with higher probability of tumor board burden included radiology or pathology specialty (PI, 0.68; 95% CI, 0.54-0.79; P = .02), attending 3 or more hours per week of tumor boards (PI, 0.68; 95% CI, 0.58-0.76; P < .001), and having 2 or more children (PI, 0.65; 95% CI, 0.52-0.77; P = .03). Early or late tumor boards (before 8 am or at 5 pm or after) were considered very burdensome by 33 respondents (29.7%). Parents frequently reported a negative burden on childcare (43 of 77 [55.8%]) and family dynamics (49 of 77 [63.6%]). On multivariable analysis, a higher level of burden from early or late tumor boards was independently associated with identifying as a woman (PI, 0.69; 95% CI, 0.57-0.78; P = .003) and having children (PI, 0.75; 95% CI, 0.62-0.84; P < .001). Independent assessment of 358 tumor boards from 22 institutions revealed the most common start time was before 8 am (88 [24.6%]). Conclusions and Relevance: This survey study of tumor board burden suggests that identifying as a woman or parent was independently associated with a higher level of burden from early or late tumor boards. The burden of early or late tumor boards on childcare and family dynamics was commonly reported by parents. Having 2 or more children, attending 3 or more hours per week of tumor boards, and radiology or pathology specialty were associated with a significantly higher tumor board burden overall. Future strategies should aim to decrease the disparate burden on parents and women.