RESUMEN
BACKGROUND: National cancer registries are valuable tools to analyze patterns of care and clinical outcomes; yet, missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). METHODS: Using the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, End Results Program), we assessed data missingness among patients diagnosed with invasive breast cancer from 2010 to 2014. Key variables included demographic (age, race, ethnicity, insurance, education, income), tumor (grade, ER, PR, HER2, TNM stages), and treatment (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data using Cox proportional hazards models. RESULTS: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missing at least 1 key variable occurred for 29% and 13%, respectively. Of those, the overwhelming majority (NCDB 80%; SEER 88%) were missing tumor variables. When compared to patients with complete data, missingness was associated with a greater risk of death: NCDB HR 1.23 (99% CI 1.21-1.25) and SEER HR 2.11 (99% CI 2.05-2.18). Patients with complete tumor data had higher unadjusted OS estimates than that of the entire sample: NCDB 82.7% vs 81.8% and SEER 83.5% vs 81.7% for 5-year OS. CONCLUSIONS: Missingness of select variables is not uncommon within large national cancer registries and is associated with a worse OS. Exclusion of patients with missing variables may introduce unintended bias into analyses and result in findings that underestimate breast cancer mortality.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Programa de VERF , Sistema de Registros , Etnicidad , Modelos de Riesgos ProporcionalesRESUMEN
Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To identify uptake and determinants of surveillance imaging in women who underwent treatment for DCIS. Materials and Methods A stratified random sample of women who underwent breast-conserving surgery for primary DCIS between 2008 and 2014 was retrospectively selected from 1330 facilities in the United States. Imaging examinations were recorded from date of diagnosis until first distant recurrence, death, loss to follow-up, or end of study (November 2018). Imaging after treatment was categorized into 10 12-month periods starting 6 months after diagnosis. Primary outcome was per-period receipt of asymptomatic surveillance imaging (mammography, MRI, or US). Secondary outcome was diagnosis of ipsilateral invasive breast cancer. Multivariable logistic regression with repeated measures and generalized estimating equations was used to model receipt of imaging. Rates of diagnosis with ipsilateral invasive breast cancer were compared between women who did and those who did not undergo imaging in the 6-18-month period after diagnosis using inverse probability-weighted Kaplan-Meier estimators. Results A total of 12 559 women (median age, 60 years; IQR, 52-69 years) were evaluated. Uptake of surveillance imaging was 75% in the first period and decreased over time (P < .001). Across the first 5 years after treatment, 52% of women participated in consistent annual surveillance. Surveillance was lower in Black (adjusted odds ratio [OR], 0.80; 95% CI: 0.74, 0.88; P < .001) and Hispanic (OR, 0.82; 95% CI: 0.72, 0.94; P = .004) women than in White women. Women who underwent surveillance in the first period had a higher 6-year rate of diagnosis of invasive cancer (1.6%; 95% CI: 1.3, 1.9) than those who did not (1.1%; 95% CI: 0.7, 1.4; difference: 0.5%; 95% CI: 0.1, 1.0; P = .03). Conclusion Half of women did not consistently adhere to imaging surveillance guidelines across the first 5 years after treatment, with racial disparities in adherence rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rahbar and Dontchos in this issue.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Estados Unidos , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/patología , Estudios Retrospectivos , Neoplasias de la Mama/patología , Mamografía/métodos , Mastectomía Segmentaria , Carcinoma Ductal de Mama/cirugíaRESUMEN
LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. BACKGROUND: The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. METHODS: In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. RESULTS: Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. CONCLUSION: The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.
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Neoplasias Colorrectales , Factor A de Crecimiento Endotelial Vascular , Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Panitumumab/farmacología , Panitumumab/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras) , PiridinasRESUMEN
BACKGROUND: Although the management of localized anal canal squamous cell carcinomas is well established, the role of pelvic chemoradiation (CRT) in the treatment of patients presenting with synchronous metastatic (stage IV) disease is poorly defined. This study used a national cancer database to compare the overall survival (OS) rates of patients with synchronous metastatic disease receiving CRT to the pelvis and patients treated with chemotherapy (CT) alone. METHODS: This study included adult patients with anal canal squamous cell carcinomas presenting with synchronous metastases diagnosed from 2004 to 2012. Multiple imputation and 2:1 propensity score matching were used to create a matched data set for testing. The proportional hazards model was used to estimate the hazard ratio (HR) for the effect of the treatment group on OS. With only patients in the matched data set, the OS of the treatment groups was estimated with the Kaplan-Meier method by treatment group. RESULTS: This study started with an unmatched data set of 978 patients, and 582 patients were selected for the matched data set: 388 in the CRT group and 194 in the CT-alone group. The HR for the group effect was 0.75 (95% confidence interval [CI], 0.61-0.92; P = .006). The median OS was 21.1 months in the CRT group (95% CI, 17.4-24.0 months) and 14.6 months in the CT group (95% CI, 12.2-18.4 months). The corresponding 5-year OS rates were 23% (95% CI, 18%-28%) and 14% (95% CI, 7%-21%), respectively. CONCLUSIONS: In this large series analyzing OS in patients with stage IV anal cancer, CRT was associated with improved OS in comparison with CT alone. Because of the lack of prospective data in this setting, this evidence will help to guide treatment approaches in this group of patients.
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Neoplasias del Ano/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/mortalidad , Neoplasias Pélvicas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/patología , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Pélvicas/secundario , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Cancer treatment costs are not routinely addressed in shared decisions for breast cancer surgery. Thus, we sought to characterize cost awareness and communication among surgeons treating breast cancer. METHODS: We conducted a self-administered, confidential electronic survey among members of the American Society of Breast Surgeons from 1 July to 15 September 2018. Questions were based on previously published or validated survey items, and assessed surgeon demographics, cost sensitivity, and communication. Descriptive summaries and cross-tabulations with Chi-square statistics were used, with exact tests where warranted, to assess findings. RESULTS: Of those surveyed (N = 2293), 598 (25%) responded. Surgeons reported that 'risk of recurrence' (70%), 'appearance of the breast' (50%), and 'risks of surgery' (47%) were the most influential on patients' decisions for breast cancer surgery; 6% cited out-of-pocket costs as significant. Over half (53%) of the surgeons agreed that doctors should consider patient costs when choosing cancer treatment, yet the majority of surgeons (58%) reported 'infrequently' (43%) or 'never' (15%) considering patient costs in medical recommendations. The overwhelming majority (87%) of surgeons believed that patients should have access to the costs of their treatment before making medical decisions. Surgeons treating a higher percentage of Medicaid or uninsured patients were more likely to consistently consider costs (p < 0.001). Participants reported that insufficient knowledge or resources (61%), a perceived inability to help with costs (24%), and inadequate time (22%) impeded cost discussions. Notably, 20% of participants believed that discussing costs might impact the quality of care patients receive. CONCLUSIONS: Cost transparency remains rare, however in shared decisions for breast cancer surgery, improved cost awareness by surgeons has the potential to reduce financial hardship.
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Neoplasias de la Mama/economía , Comunicación , Costo de Enfermedad , Costos de los Medicamentos/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Cirujanos/psicología , Neoplasias de la Mama/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sociedades Médicas , Cirujanos/estadística & datos numéricosRESUMEN
BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS: A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9 months (95% CI, 2.3-4.5) and 7.1 months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION: The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION: This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Recruitment into clinical trials for retroperitoneal sarcoma has been challenging, resulting in termination of the only randomised multicentre trial in the USA investigating perioperative radiotherapy. Nonetheless, use of radiotherapy for retroperitoneal sarcoma has increased over the past decade, substantiated primarily by its established role in extremity sarcoma. In this study, we used a nationwide clinical oncology database to separately compare overall survival for patients with retroperitoneal sarcoma who had surgery and preoperative radiotherapy or surgery and postoperative radiotherapy versus surgery alone. METHODS: We did two case-control, propensity score-matched analyses of the National Cancer Data Base, which included adult patients with retroperitoneal sarcoma who were diagnosed from 2003 to 2011. Patients were included if they had localised, primary retroperitoneal sarcoma. Patients were classified into three groups based on use of radiotherapy: preoperative radiotherapy, postoperative radiotherapy, and no radiotherapy (surgery alone). Patients were excluded if they received both preoperative radiotherapy and postoperative radiotherapy, or if they received intraoperative radiotherapy. Parallel propensity score-matched datasets were created for patients who received preoperative radiotherapy versus those who received no radiotherapy and for patients who received postoperative therapy versus those who received no radiotherapy. Propensity scores were calculated with logistic regression, with multiple imputation and backwards elimination, with a significance level to stay of 0·05. Matching was done with a nearest-neighbour algorithm and matched 1:2 for the preoperative radiotherapy dataset and 1:1 for the postoperative radiotherapy dataset. The primary objective of interest was overall survival for patients who received preoperative radiotherapy or postoperative radiotherapy compared with those who received no radiotherapy within the propensity score-matched datasets. FINDINGS: 9068 patients were included in this analysis: 563 in the preoperative radiotherapy group, 2215 in the postoperative radiotherapy group, and 6290 in the no radiotherapy group. Matching resulted in two comparison groups (preoperative radiotherapy vs no radiotherapy, and postoperative radiotherapy vs no radiotherapy) with negligible differences in all demographic, clinicopathological, and treatment-level variables. In the matched case-control analysis for preoperative radiotherapy median follow-up time was 42 months (IQR 27-70) for the preoperative radiotherapy group versus 43 months (25-64) for the no radiotherapy group; median overall survival was 110 months (95% CI 75-not estimable) versus 66 months (61-76), respectively. In the matched case-control analysis for postoperative radiotherapy median follow-up time was 54 months (IQR 32-79) for patients in the postoperative radiotherapy group and 47 months (26-72) for patients in the no radiotherapy group; median overall survival was 89 months (95% CI 79-100) versus 64 months (59-69), respectively. Both preoperative radiotherapy (HR 0·70, 95% CI 0·59-0·82; p<0·0001) and postoperative radiotherapy (HR 0·78, 0·71-0·85; p<0·0001) were significantly associated with improved overall survival compared with surgery alone. INTERPRETATION: To the best of our knowledge, this is the largest study to date of the effect of radiotherapy on overall survival in patients with retroperitoneal sarcoma. Radiotherapy was associated with improved overall survival compared with surgery alone when delivered as either preoperative radiotherapy or postoperative radiotherapy. Together with the results from the ongoing randomised EORTC trial (62092-22092; NCT01344018) investigating preoperative radiotherapy for retroperitoneal sarcoma pending, these data might provide additional support for the increasing use of radiotherapy for patients with retroperitoneal sarcoma undergoing surgical resection. FUNDING: Department of Surgery, Duke University School of Medicine.
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Recurrencia Local de Neoplasia/diagnóstico , Complicaciones Posoperatorias/radioterapia , Puntaje de Propensión , Neoplasias Retroperitoneales/radioterapia , Neoplasias Retroperitoneales/cirugía , Sarcoma/radioterapia , Sarcoma/cirugía , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Oncología Médica , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Cuidados Preoperatorios , Pronóstico , Radioterapia Adyuvante , Neoplasias Retroperitoneales/patología , Sarcoma/patología , Tasa de SupervivenciaRESUMEN
PURPOSE: Women with early-stage breast cancer face the complex decision to undergo one of three equally effective oncologic surgical strategies: breast-conservation surgery with radiation (BCS), mastectomy, or mastectomy with breast reconstruction. With comparable oncologic outcomes and survival rates, evaluations of satisfaction with these procedures are needed to facilitate the decision-making process and to optimize long-term health. METHODS: Women recruited from the Army of Women with a history of breast cancer surgery took electronically administered surgery-specific surveys, including the BREAST-Q© and a background survey evaluating patient-, disease-, and procedure-specific factors. Descriptive statistics and regression analysis were used to evaluate the effect of procedure type on breast satisfaction scores. RESULTS: Overall, 7,619 women completed the questionnaires. Linear regression revealed that women who underwent abdominal flap, or buttock or thigh flap reconstruction reported the highest breast satisfaction score, scoring an average of 5.6 points and 14.4 points higher than BCS, respectively (p < 0.0001 and p = 0.027, respectively). No difference in satisfaction was observed in women who underwent latissimus dorsi flap reconstruction compared with those who underwent BCS. Women who underwent implant reconstruction reported scores 8.6 points lower than BCS (p < 0.0001). Those with mastectomies without reconstruction or complex surgical histories scored, on average, 10 points lower than BCS (p < 0.0001). CONCLUSION: Women who underwent autologous tissue reconstruction reported the highest breast satisfaction, while women undergoing mastectomy without reconstruction reported the lowest satisfaction. These findings emphasize the value of patient-reported outcome measures as an important guide to decision making in breast surgery and underscore the importance of multidisciplinary participation early in the surgical decision-making process.
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Neoplasias de la Mama/cirugía , Mamoplastia , Mastectomía , Satisfacción del Paciente , Implantación de Mama , Neoplasias de la Mama/radioterapia , Toma de Decisiones , Femenino , Humanos , Modelos Lineales , Mastectomía Segmentaria , Persona de Mediana EdadRESUMEN
PURPOSE: Patients with advanced non-small cell lung cancer (aNSCLC) face a significant symptom burden. Little is known about the frequency and severity of symptoms over time, so we longitudinally characterized patients' symptoms using the Patient Care Monitor (PCM) version 2.0, an electronic symptom-assessment tool. METHODS: Ninety-seven patients with aNSCLC completed the PCM at up to four clinic visits. We analyzed symptom data by incidence, severity, type (functional vs. nonfunctional), proximity to death, and cancer anorexia-cachexia syndrome status (CACS). RESULTS: Functional concerns predominated, even in the non-CACS group. Average severity among the top 5 symptoms was worse for functional than nonfunctional items (mean difference 0.62, 95% CI 0.22-1.01, P = 0.003). Severe dyspnea and fatigue were the most prevalent nonfunctional symptoms; moderate/severe dyspnea was reported by at least 29% of patients, and fatigue by over 50%. Depression was reported infrequently, with over half of patients at each visit reporting "none"; moderate or severe depression was reported in only 2.5-9.3 and 3.4-6.2% of patients, respectively. The average number of moderate/severe symptoms increased with proximity to death; 84% reported moderate/severe fatigue in the last 3 months of life, compared to 48% at ≥ 12 months from death (P = 0.007). CONCLUSIONS: Patients with aNSCLC face a significant symptom burden, which increases with proximity to death. Symptom type and severity vary by proximity to death, but even patients without overt CACS report significant functional symptoms throughout. We recommend an individualized approach to palliative symptom intervention in advanced lung cancer, based on detailed symptom assessment and tracking.
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Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/psicología , Evaluación de Síntomas/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Progresión de la Enfermedad , Femenino , Humanos , Internet , Estudios Longitudinales , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Prevalencia , Calidad de Vida , AutoinformeRESUMEN
BACKGROUND: Quality measurement has become a priority for national healthcare reform, and valid measures are necessary to discriminate hospital performance and support value-based healthcare delivery. The Commission on Cancer (CoC) is the largest cancer-specific accreditor of hospital quality in the United States and has implemented Quality of Care Measures to evaluate cancer care delivery. However, none has been formally tested as a valid metric for assessing hospital performance based on actual patient outcomes. METHODS: Eligibility and compliance with the Quality of Care Measures are reported within the National Cancer Database, which also captures data for robust patient-level risk adjustment. Hospital-level compliance was calculated for the core measures, and the association with patient survival was tested using Cox regression. RESULTS: Seven hundred sixty-eight thousand nine hundred sixty-nine unique cancer cases were included from 1323 facilities. Increasing hospital-level compliance was associated with improved survival for only two measures, including a 35% reduced risk of mortality for the gastric cancer measure G15RLN (HR 0.65, 95% CI 0.58-0.72) and a 19% reduced risk of mortality for the colon cancer measure 12RLN (HR 0.81, 95% CI 0.77-0.85). For the lung cancer measure LNoSurg, increasing compliance was paradoxically associated with an increased risk of mortality (HR 1.14, 95% CI 1.08-1.20). For the remaining measures, hospital-level compliance demonstrated no consistent association with patient survival. CONCLUSION: Hospital-level compliance with the CoC's Quality of Care Measures is not uniformly aligned with patient survival. In their current form, these measures do not reliably discriminate hospital performance and are limited as a tool for value-based healthcare delivery.
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Hospitales/normas , Neoplasias/mortalidad , Neoplasias/terapia , Calidad de la Atención de Salud , Acreditación , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias del Colon/mortalidad , Neoplasias del Colon/terapia , Bases de Datos Factuales , Femenino , Hospitales/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Neoplasias/epidemiología , Modelos de Riesgos Proporcionales , Mejoramiento de la Calidad , Neoplasias del Recto/mortalidad , Neoplasias del Recto/terapia , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/terapia , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma. PATIENTS AND METHODS: Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550-4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy. RESULTS: Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%-83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets. CONCLUSIONS: Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.
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Quimioradioterapia Adyuvante/mortalidad , Ipilimumab/uso terapéutico , Melanoma/terapia , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Dosificación Radioterapéutica , Tasa de Supervivencia , Adulto JovenRESUMEN
The human hepatoma cell lines HepG2 and Huh7 have been used extensively to study hepatitis B virus (HBV) transcription and replication. Both cell lines support transcription of the 3.5-kb viral pregenomic RNA and subsequent viral DNA synthesis by reverse transcription. The effects of the coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) and corepressor small heterodimer partner (SHP) on HBV transcription and replication mediated by nuclear receptors were examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells in an attempt to determine the relative contribution of the various nuclear receptors to viral biosynthesis in the hepatoma cells. PGC1alpha and SHP modulated viral biosynthesis differently in the human hepatoma cell lines HepG2 and Huh7, indicating distinct modes of transcriptional regulation. Consistent with this suggestion, it appears that retinoid X receptor alpha/farnesoid X receptor alpha and liver receptor homolog 1 or estrogen-related receptor beta (ERRbeta) may contribute to the majority of the viral replication observed in HepG2 cells, whereas ERRalpha and ERRgamma are probably responsible for the majority of viral biosynthesis in Huh7 cells. Therefore, this approach indicates that the transcriptional regulation of HBV biosynthesis in HepG2 and Huh7 cells is primarily controlled by different transcription factors.
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Proteínas de Choque Térmico/metabolismo , Virus de la Hepatitis B/fisiología , Interacciones Huésped-Patógeno , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Replicación Viral , Línea Celular , Humanos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , ARN Viral/biosíntesis , Transcripción GenéticaRESUMEN
Hepatitis B virus (HBV) biosynthesis involves the transcription of the 3.5-kb viral pregenomic RNA, followed by its reverse transcription into viral DNA. Consequently, the modulation of viral transcription influences the level of virus production. Nuclear receptors are the only transcription factors known to support viral pregenomic RNA transcription and replication. The coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) and corepressor small heterodimer partner (SHP) have central roles in regulating energy homeostasis in the liver by modulating the transcriptional activities of nuclear receptors. Therefore, the effect of PGC1alpha and SHP on HBV transcription and replication mediated by nuclear receptors was examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells. This analysis indicated that viral replication mediated by hepatocyte nuclear factor 4alpha, retinoid X receptor alpha (RXRalpha) plus peroxisome proliferator-activated receptor alpha (PPARalpha), and estrogen-related receptor (ERR) displayed differential sensitivity to PGC1alpha activation and SHP inhibition. The effects of PGC1alpha and SHP on viral biosynthesis in the human hepatoma cell line Huh7 were similar to those observed in the nonhepatoma cells expressing ERRalpha and ERRgamma. This suggests that these nuclear receptors, potentially in combination with RXRalpha plus PPARalpha, may have a major role in governing HBV transcription and replication in this cell line. Additionally, this functional approach may help to distinguish the transcription factors in various liver cells governing viral biosynthesis under a variety of physiologically relevant conditions.
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Proteínas de Choque Térmico/metabolismo , Virus de la Hepatitis B/fisiología , Interacciones Huésped-Patógeno , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Replicación Viral , Línea Celular , Humanos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , ARN Viral/biosíntesis , Transcripción GenéticaRESUMEN
PURPOSE: Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes. METHODS AND MATERIALS: Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of â¼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs). RESULTS: From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively. CONCLUSIONS: PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.
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Recurrencia Local de Neoplasia , Neoplasias Orofaríngeas/radioterapia , Infecciones por Papillomavirus/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Análisis de Varianza , Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Femenino , Fluorodesoxiglucosa F18 , Papillomavirus Humano 16 , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Orofaríngeas/diagnóstico por imagen , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Radiofármacos , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: Breast cancer survival continues to improve, with women living longer after treatment. It is not well understood how long-term satisfaction and well-being differ following treatment or how types of reconstruction differ when compared to the norm. METHODS: In a propensity-matched sample, the authors compared patient-reported outcomes in breast cancer patients at various time intervals from surgery with normative BREAST-Q data. All data were obtained using the Army of Women, an online community fostering breast cancer research. Breast cancer patients were stratified by surgical treatment and reconstruction type. Regression lines were estimated and differences in slope tested between cancer patients and noncancer controls. RESULTS: The authors compared normative (n = 922) and breast cancer (n = 4343) cohorts in a propensity-matched analysis. Among the breast cancer patients, 49.4 percent underwent lumpectomy, 17.0 percent underwent mastectomy, 21.7 percent underwent implant reconstruction, and 11.9 percent underwent autologous reconstruction. Median time since surgery was 4.7 years, with 21.1 percent more than 10 years after surgery. At the time of survey, breast cancer patients reported higher Satisfaction with Breasts and Psychosocial Well-being scores compared to noncancer controls (p < 0.01), with the cohorts undergoing lumpectomy and autologous reconstruction both reporting higher scores than the normative controls. After mastectomy, scores averaged lower than the noncancer controls, but improved over time. However, all breast cancer groups reported significantly lower Physical Well-being scores than the noncancer cohort (all p < 0.01). CONCLUSIONS: Breast cancer patients undergoing lumpectomy or autologous reconstruction reported higher psychosocial well-being compared to noncancer controls. These differences were influenced both by time since treatment and by choice of surgical procedure.
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Neoplasias de la Mama/cirugía , Mamoplastia/psicología , Mastectomía/efectos adversos , Medición de Resultados Informados por el Paciente , Satisfacción del Paciente , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Mama/cirugía , Neoplasias de la Mama/psicología , Estudios Transversales , Conjuntos de Datos como Asunto , Femenino , Estudios de Seguimiento , Humanos , Mastectomía/métodos , Persona de Mediana Edad , Puntaje de Propensión , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to identify differences in patient-reported abdominal well-being, satisfaction, and quality of life in women with muscle-preserving free abdominal versus pedicle transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction. METHODS: Women with a history of breast cancer surgery were recruited from the Army of Women foundation to take the BREAST-Q and a background questionnaire. Descriptive statistics and regression analyses were used to compare abdominal physical well-being, breast satisfaction, chest physical, psychosocial well-being, and sexual well-being in women undergoing free versus pedicle TRAM flaps. RESULTS: Of 657 women, 273 (41 percent) underwent free flap surgery and 384 (58 percent) underwent pedicle TRAM flap surgery. Compared with unilateral pedicle TRAM flaps, those with unilateral free flaps scored an average of 9.5 points higher (95 percent CI, 5.4 to 13.6; p < 0.0001) and those with bilateral free flaps reported no difference in physical well-being of the abdomen. Compared with bilateral pedicle TRAM flaps, the following groups scored higher in physical well-being of the abdomen: unilateral free flaps, an average of 17.4 (95 percent CI, 11.5 to 23.3; p < 0.0001); bilateral free flaps, an average of 6.8 (95 percent CI, 0.3 to 13.3; p = 0.04); and unilateral pedicle TRAM flaps, an average of 7.9 (95 percent CI, 2.4 to 13.4; p = 0.005) higher. Women with bilateral pedicle flaps reported sexual well-being scores 7.4 (95 percent CI, 0.6 to 14.3; p = 0.03) and 6.8 (95 percent CI, 0.3 to 13.2; p = 0.04) points lower than those with unilateral free and unilateral pedicle flaps. CONCLUSIONS: Muscle-preserving techniques result in improved abdominal wall function and decreased morbidity compared with pedicle TRAM flap reconstruction. These data highlight the importance of offering patients the option of microsurgical techniques.
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Colgajos Tisulares Libres/trasplante , Mamoplastia/métodos , Colgajo Miocutáneo/trasplante , Medición de Resultados Informados por el Paciente , Sitio Donante de Trasplante/fisiopatología , Pared Abdominal/fisiopatología , Pared Abdominal/cirugía , Anciano , Neoplasias de la Mama/cirugía , Estudios de Cohortes , Femenino , Colgajos Tisulares Libres/efectos adversos , Humanos , Mamoplastia/efectos adversos , Mastectomía/efectos adversos , Microcirugia/efectos adversos , Microcirugia/métodos , Persona de Mediana Edad , Colgajo Miocutáneo/efectos adversos , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/métodos , Selección de Paciente , Calidad de Vida , Recto del Abdomen/trasplante , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodosRESUMEN
BACKGROUND: Evidence increasingly supports the integration of specialist palliative care (PC) into routine cancer care. A novel, fully integrated PC and medical oncology inpatient service was developed at Duke University Hospital in 2011. OBJECTIVE: To assess the impact of PC integration on health care utilization among hospitalized cancer patients before hospice enrollment. METHODS: Retrospective cohort study. Patients in the solid tumor inpatient unit who were discharged to hospice between September 1, 2009, and June 30, 2010 (pre-PC integration), and September 1, 2011, to June 30, 2012 (postintegration). Cohorts were compared on the following outcomes from their final hospitalization before hospice enrollment: intensive care unit days, invasive procedures, subspecialty consultations, radiographic studies, hospital length of stay, and use of chemotherapy or radiation. Cohort differences were examined with descriptive statistics and nonparametric tests. RESULTS: Two hundred ninety-six patients were included in the analysis (133 pre-PC integration; 163 post-PC integration). Patient characteristics were similar between cohorts. Health care utilization was relatively low in both groups, although 26% and 24% were receiving chemotherapy at the time of admission or during hospitalization in the pre- and post-PC integration cohorts, respectively, and 6.8% in each cohort spent time in an intensive care unit. We found no significant differences in utilization between cohorts. DISCUSSION: PC integration into an inpatient solid tumor service may not impact health care utilization during the final hospitalization before discharge to hospice. This likely reflects the greater benefits of integrating PC farther upstream from the terminal hospitalization, if one hopes to meaningfully impact utilization near the end of life.
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Prestación Integrada de Atención de Salud/organización & administración , Enfermería de Cuidados Paliativos al Final de la Vida/organización & administración , Oncología Médica/organización & administración , Neoplasias/enfermería , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , North Carolina , Estudios RetrospectivosRESUMEN
BACKGROUND: Controversy exists over the use of adjuvant chemotherapy for locally advanced (stages II-III) rectal cancer (LARC) patients who demonstrate pathologic complete response (pCR) following neoadjuvant chemoradiation. We conducted a retrospective analysis to determine whether adjuvant chemotherapy imparts survival benefit among this population. METHODS: The National Cancer Database (NCDB) was queried to identify LARC patients with pCR following neoadjuvant chemoradiation. The cohort was stratified by receipt of adjuvant chemotherapy. Multiple imputation and a Cox proportional hazards model were employed to estimate the effect of adjuvant chemotherapy on overall survival. RESULTS: There were 24,418 patients identified in the NCDB with clinically staged II or III rectal cancer who received neoadjuvant chemoradiation. Of these, 5606 (23.0%) had pCR. Among patients with pCR, 1401 (25%) received adjuvant chemotherapy and 4205 (75%) did not. Patients who received adjuvant chemotherapy were slightly younger, more likely to have private insurance, and more likely to have clinically staged III disease, but did not differ significantly in comparison to patients who did not receive adjuvant chemotherapy with respect to race, sex, facility type, Charlson comorbidity score, histologic tumor grade, procedure type, length of stay, or rate of 30-day readmission following surgery. On adjusted analysis, receipt of adjuvant chemotherapy was associated with a lower risk of death at a given time compared to patients who did not receive adjuvant chemotherapy (HR 0.808; 95% CI 0.679-0.961; p = 0.016). CONCLUSION: Supporting existing NCCN guidelines, the findings from this study suggest that adjuvant chemotherapy improves survival for LARC with pCR following neoadjuvant chemoradiation.
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Estadificación de Neoplasias , Proctectomía/métodos , Neoplasias del Recto/terapia , Quimioradioterapia/métodos , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Pronóstico , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Antibodies against programmed cell death protein 1 (PD-1) are standard treatments for advanced melanoma. Palliative radiation therapy (RT) is commonly administered for this disease. Safety and optimal timing for this combination for melanoma has not been established. MATERIALS AND METHODS: In this retrospective cohort study, records for melanoma patients who received anti-PD-1 therapy at Duke University or Emory University (1/1/2013-12/30/2015) were reviewed. Patients were categorized by receipt of RT and RT timing relative to anti-PD-1. RESULTS: 151 patients received anti-PD-1 therapy. Median follow-up was 12.9â¯months. Patients receiving RT (nâ¯=â¯85) had worse baseline prognostic factors than patients without RT (nâ¯=â¯66). One-year overall survival (OS) was lower for RT patients than patients without RT (66%, 95% CI: 55-77% vs 83%, 95% CI: 73-92%). One-year OS was 61% for patients receiving RT before anti-PD-1 (95% CI: 46-76%), 78% for RT during anti-PD-1 (95% CI: 60-95%), and 58% for RT after anti-PD-1 (95% CI: 26-89%). On Cox regression, OS for patients without RT did not differ significantly from patients receiving RT during anti-PD-1 (HR 1.07, 95% CI: 0.41-2.84) or RT before anti-PD-1 (HR 0.56, 95% CI: 0.21-1.45). RT and anti-PD-1 therapy administered within 6â¯weeks of each other was well tolerated. CONCLUSION: RT can be safely administered with anti-PD-1 therapy. Despite worse baseline prognostic characteristics for patients receiving RT, OS was similar for patients receiving concurrent RT with anti-PD-1 therapy compared to patients receiving anti-PD-1 therapy alone.