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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia de Protones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Terapia de Protones/efectos adversos , Estudios de Factibilidad , Estudios Prospectivos , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de NeoplasiasRESUMEN
INTRODUCTION: Many patients with high-risk soft tissue sarcoma (STS) develop distant metastases. Meta-analyses suggest that chemotherapy confers a small survival benefit, though few studies focus on neoadjuvant chemotherapy (NCT). There has been more frequent use of neoadjuvant radiation therapy (NRT) in STS, but the utility of NCT for these patients remains unclear. METHODS: Patients with stage II-III trunk/extremity STS who underwent NRT and resection were identified using the National Cancer Database (2006-2019). Predictors of NCT were analyzed using logistic regression. Change in rate of NCT use over time was assessed using log-linear regression modeling. Survival was examined using Kaplan-Meier (KM) and Cox proportional hazard modeling. RESULTS: Of 5740 patients, 25% underwent NCT. The overall median age was 62, 55% of patients were male, and 67% had stage III disease. The most common histological subtypes were fibrosarcoma/myxofibrosarcoma (39%) and liposarcoma (16%). Use of NCT decreased by 4.0% per year throughout the study period (p < 0.01). Predictors of NCT included younger age (median 54, IQR 42-64 vs. median 65, IQR 53-75, p < 0.01), treatment at an academic center (odds ratio [OR] 1.5, p < 0.01), and stage III disease (OR 2.2, p < 0.01). Histologic predictors of NCT included synovial sarcoma (52%) and angiosarcoma (45%). With a median follow-up time of 77 months, NCT was associated with improved 5-year survival compared to NRT alone on KM analysis (70% vs. 63%, p < 0.01). This difference persisted on multivariate analysis (hazard ratio 0.86, p = 0.027) and after propensity matching (70% vs. 65%, p = 0.0064). CONCLUSION: Despite risk of distant failure in high-risk STS, use of NCT has decreased over time in patients receiving NRT. In this retrospective analysis, NCT was associated with a modestly improved overall survival.
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Fibrosarcoma , Liposarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Terapia Neoadyuvante , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Extremidades/patología , Liposarcoma/patología , Fibrosarcoma/patología , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
PURPOSE: Physical activity is associated with decreased hospitalization during cancer treatment. We hypothesize that activity data can help identify and triage high-risk patients with GI cancer undergoing concurrent chemoradiation. MATERIALS AND METHODS: This prospective study randomly assigned patients to activity monitoring versus observation. In the intervention arm, a 20% decrease in daily steps or 20% increase in heart rate triggered triage visits to provide supportive care, medication changes, and escalation of care. In the observation group, activity data were recorded but not monitored. The primary objective was to show a 20% increase in triage visits in the intervention group. Secondary objectives were estimating the rates of emergency department (ED) visits and hospitalizations. Crude and adjusted odds ratios were computed using logistic regression modeling. RESULTS: There were 22 patients in the intervention and 18 in the observation group. Baseline patient and treatment characteristics were similar. The primary objective was met, with 3.4 more triage visits in the intervention group than in the observation group (95% CI, 2.10 to 5.50; P < .0001). Twenty-six (65.0%) patients required at least one triage visit, with a higher rate in the intervention arm compared with that in the observation arm (86.4% v 38.9%; odds ratio, 9.95; 95% CI, 2.13 to 46.56; P = .004). There was no statistically significant difference in ED visit (9.1% v 22.2%; P = .38) or hospitalization (4.5% v 16.7%; P = .31). CONCLUSION: It is feasible to use activity data to trigger triage visits for symptom management. Further studies are investigating whether automated activity monitoring can assist with early outpatient management to decrease ED visits and hospitalizations.
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Neoplasias Gastrointestinales , Hospitalización , Servicio de Urgencia en Hospital , Neoplasias Gastrointestinales/terapia , Humanos , Estudios Prospectivos , TriajeRESUMEN
BACKGROUND AND OBJECTIVES: Neoadjuvant radiation (NRT) is frequently utilized in soft tissue sarcomas to increase local control. Its utility in cutaneous and soft tissue angiosarcoma remains poorly defined. METHODS: This retrospective cohort study was performed using the National Cancer Database (2004-2016) evaluating patients with clinically localized, surgically resected angiosarcomas. Factors associated with receipt of NRT in the overall cohort and margin positivity in treatment naïve patients were identified by univariate and multivariable logistic regression analyses. Survival was assessed using Kaplan-Meier analysis. RESULTS: Of 597 patients, 27 (4.5%) received NRT. Increasing age (odds ratio [OR] 0.95, p = 0.025), tumor size more than or equal to 5 cm (OR 3.16, p = 0.02), and extremity tumor location (OR 3.99, p = 0.04) were associated with receipt of NRT. All patients who received NRT achieved an R0 resection (p = 0.03) compared with 17.9% of patients without NRT. Factors associated with risk of margin positivity included tumor size more than or equal to 5 cm (OR 1.85, p = 0.01), and head/neck location (OR 2.24, p = 0.006). NRT was not significantly associated with improved survival (p = 0.21). CONCLUSIONS: NRT improves rates of R0 resection but is infrequently utilized in cutaneous and soft tissue angiosarcoma. Increased usage of NRT, particularly for patients with lesions more than or equal to 5 cm, or head and neck location, may help achieve complete resections.
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Hemangiosarcoma/radioterapia , Hemangiosarcoma/cirugía , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugía , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Hemangiosarcoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias de los Tejidos Blandos/mortalidadRESUMEN
INTRODUCTION: Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought to understand the type and thresholds of clinical evidence required for experts to adopt hypofractionated RT as a standard-of-care option for patients with STS. METHODS: An electronic survey was distributed to multidisciplinary sarcoma experts. The survey queried whether data from a theoretical, multi-institutional, phase II study of 5-fraction preoperative RT could change practice. Using endpoints from RTOG 0630 as a reference, the survey also queried thresholds for acceptable local control, wound complication, and late toxicity for the study protocol to be accepted as a standard-of-care option. Responses were logged from 8/27/2020 to 9/8/2020 and summarized graphically. RESULTS: The survey response rate was 55.3% (47/85). Local control is the most important clinical outcome for sarcoma specialists when evaluating whether an RT regimen should be considered standard of care. 17% (8/47) of providers require randomized phase III evidence to consider hypofractionated preoperative RT as a standard-of-care option, whereas 10.6% (5/47) of providers already view this as a standard-of-care option. Of providers willing to change practice based on phase II data, most (78%, 29/37) would accept local control rates equivalent to or less than those in RTOG 0630, as long as the rate was higher than 85%. However, 51.3% (19/37) would require wound complication rates superior to those reported in RTOG 0630, and 46% (17/37) of respondents would accept late toxicity rates inferior to RTOG 0630. CONCLUSION: Consensus building is needed among clinicians regarding the type and threshold of evidence needed to evaluate hypofractionated RT as a standard-of-care option. A collaborative consortium-based approach may be the most pragmatic means for developing consensus protocols and pooling data to gradually introduce hypofractionated preoperative RT into routine practice.
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BACKGROUND: Brain metastases are the most common central nervous system (CNS) tumors, occurring in 300,000 people per year in the US. While there are immediate local benefits to surgical resection for dominant lesions, including reduction of tumor burden and edema, the survival benefits of surgical resection, over radiosurgery, remains unclear. METHODS: The University of Pennsylvania Health System database was retrospectively reviewed for patients presenting with multiple brain metastases from 1/1/16-8/31/18 with one dominant lesion > 2 cm in diameter, who underwent initial treatment with either resection of the dominant lesion or Gamma Knife radiosurgery (GKS). Inclusion criteria were age > 18, > 1 brain metastasis, and presence of a dominant lesion (>2 cm). We analyzed factors associated with mortality. RESULTS: 129 patients were identified (surgery=84, GKS=45). The median number of intracranial metastases was 3 (IQR: 2-5). The median diameter of the largest lesion was 31 mm (IQR: 25-38) in the surgery group vs 21 mm (IQR: 20-24) in the GKS group (p < 0.001). Mortality did not differ between surgery and GKS patients (69.1% vs 77.8%, p = 0.292). In a multivariate survival analysis, there was no difference in mortality between the surgery and GKS cohorts (aHR: 1.35, 95% CI: 0.74-2.45 p = 0.32). Pre-operative KPS (aHR: 0.97, 95% CI: 0.95-0.99, p = 0.004), CNS radiotherapy (aHR: 0.33, 95% CI: 0.19-0.56 p < 0.001), chemotherapy (aHR: 0.27, 95% CI: 0.15-0.47, p < 0.001), and immunotherapy (aHR: 0.41, 95% CI: 0.25-0.68, p = 0.001) were associated with decreased mortality. CONCLUSION: In our institution, patients with multiple brain metastases and one symptomatic dominant lesion demonstrated similar survival after GKS when compared with up-front surgical resection of the dominant lesion.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Radiocirugia , Anciano , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Análisis de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
The management of patients with metastatic cancer is rapidly changing. Historically, radiotherapy was utilized for the treatment of localized disease or for palliation. While systemic therapy remains the mainstay of management for patients with metastatic cancer, radiotherapy is becoming increasingly important not only to palliate symptoms, but also to ablate oligometastatic or oligoprogressive disease and improve local control in the primary site. There is emerging evidence in multiple solid malignancies that patients with low volume metastatic disease that undergo local ablative therapy to metastatic sites may have improved progression free survival and potentially overall survival. In addition, there is increasing evidence that select patients with metastatic disease may benefit from aggressive treatment of the primary site. Patients with metastatic soft tissue sarcoma have a poor overall prognosis. However, there may be opportunities in patients with low volume metastatic soft tissue sarcoma to improve outcomes with local therapy including surgery, ablation, embolization, and radiation therapy. Stereotactic body radiation therapy (SBRT) offers a safe, convenient, precise, and non-invasive option for ablation of sites of metastases. In this review article, we explore the limited yet evolving role of radiotherapy to metastatic and primary sites for local control and palliation, particularly in the oligometastatic setting.
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PURPOSE: Practice patterns for treatment of localized adult pleomorphic rhabdomyosarcoma (PRMS) remain quite variable given its rarity. Current national guidelines recommend management similar to that of other high-grade soft tissue sarcomas (STS), which include surgery with perioperative radiation (RT) with or without chemotherapy. Using the National Cancer Database (NCDB), we assessed practice patterns and overall outcomes of patients with localized PRMS. Patients and Methods. Patients with stage II/III PRMS treated with surgical resection from 2004 to 2015 were identified from the NCDB. Predictors of RT and chemotherapy use were assessed using multivariable logistic regression analysis. The association of radiation and chemotherapy status on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Of 243 total patients, RT and chemotherapy were not uniformly utilized, with 44% receiving chemotherapy and in those who did not undergo amputation 62% receiving RT. In those who did not undergo amputation, RT was associated with improved survival on both univariate (HR: 0.49, 95% CI 0.32-0.73, P < 0.001) and multivariate analysis (HR: 0.40, 95% CI 0.26-0.62, P < 0.001), corresponding to greater 5-year overall survival (59% vs. 38%, P < 0.001). Chemotherapy was associated with a higher rate of 5-year overall survival (63% vs. 39%, P < 0.001). However, the survival benefit of chemotherapy did not reach statistical significance on multivariate analysis (HR: 0.65, 95% CI 0.41-1.03, P=0.064). Notable predictors of omission of RT included female gender (OR: 0.40, 95% CI 0.22-0.74, P < 0.01) and age ≥ 70 (OR: 0.55, 95% CI 0.30-1.00, P=0.05). Correspondingly, factors associated with omission of chemotherapy included age ≥70 (OR: 0.17, 95% CI 0.08-0.39, P < 0.001). CONCLUSIONS: A significant proportion of patients with localized adult PRMS are not receiving RT. Likewise, use of chemotherapy was heterogeneous. Our findings note potential benefits and underutilization of RT, for which further investigation is warranted.
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Background: Definitive local therapy is often utilized in patients with metastatic soft tissue sarcomas (STS) to reduce morbidity associated with local tumor progression. We hypothesize that it is associated with improved overall survival (OS). Methods: Patients with newly diagnosed metastatic STS treated with chemotherapy were identified from the National Cancer Database and dichotomized into cohorts: 1. definitive local therapy (defined as either definitive dose radiotherapy, definitive surgery, or surgery with perioperative radiotherapy) or 2. conservative therapy (defined as systemic therapy with or without palliative therapy). The association between definitive local therapy and OS, and factors associated with the receipt of definitive local therapy were assessed. Results: Total of 4180 patients were identified. Compared with the conservative therapy, receipt of any definitive local therapy was associated with improved OS (median 17.9 vs. 10.1 months). The survival benefit remained on multivariate analyses and propensity-score matched analyses, with a stepwise improvement with surgery and combined modality local therapy, specifically radiotherapy (HR: 0.77; p < 0.001), surgery (HR: 0.67; p < 0.001), and combined surgery and radiotherapy (HR: 0.42; p < 0.001). Conclusions: Analysis of a large national cancer registry of patients with metastatic STS suggests that chemotherapy plus definitive local therapy is associated with a significant survival benefit compared to the standard chemotherapy alone.
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BACKGROUND: Practice patterns of radiation therapy (RT) use for soft-tissue sarcoma (STS) remain quite variable, despite clinical practice guidelines recommending the addition of RT to surgery for patients with high-grade STS, particularly for larger tumors. Using the National Cancer Database (NCDB), we assessed patterns of overall RT use, neoadjuvant versus adjuvant treatment, and specific RT modalities in this population. PATIENTS AND METHODS: Patients aged ≥18 years with stage II/III STS in 2004 through 2015 were identified from the NCDB. Patterns of care were assessed using multivariable logistic regression analysis. RESULTS: Of 27,426 total patients, 11,654 (42%) were treated with surgery alone versus 15,772 (58%) with RT in addition to surgery, with no overall increase in RT use over the study period. Notable clinical predictors of receipt of RT included tumor size (>5 cm), grade III, and tumors arising in the extremities. Conversely, female sex, older age (≥70 years), Black race, noncommercial insurance coverage, farther distance to treatment, and poor performance status were negative predictors of RT use. Of those receiving RT, 27% were treated with neoadjuvant RT and 73% with adjuvant RT. The proportion of those receiving neoadjuvant RT increased over time. Relevant factors associated with neoadjuvant RT included treatment at academic centers, larger tumor size, and extremity tumors. Of those who received RT with a modality specified as either intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT), 61% were treated with IMRT and 39% with 3DCRT. The proportion of patients treated with IMRT increased over time. Relevant factors associated with IMRT use included treatment at academic centers, commercial insurance coverage, and larger and nonextremity tumors. CONCLUSIONS: Although use of neoadjuvant RT and IMRT has increased over time, a significant number of patients with STS are not receiving adjuvant or neoadjuvant RT. Our findings also note potential sociodemographic disparities and highlight the concern that not all patients with STS are being equally considered for RT.
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BACKGROUND: Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS: Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. RESULTS: There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P <.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR = 2.78, 95% CI = 1.31 to 5.87; P =.007). When limited to only patients who received adjuvant ICI (n = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR = 4.84, 95% CI = 1.09 to 21.50; P =.04). The antibiotic group had a greater incidence of colitis (HR = 2.14, 95% CI = 1.02 to 4.52; P =.046). CONCLUSION: Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.
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Antibacterianos/efectos adversos , Microbioma Gastrointestinal/genética , Variación Genética/efectos de los fármacos , Melanoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Supervivencia sin Enfermedad , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Variación Genética/genética , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Factores Inmunológicos/antagonistas & inhibidores , Factores Inmunológicos/genética , Inmunoterapia/efectos adversos , Masculino , Melanoma/microbiología , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Adulto JovenRESUMEN
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. As the clinical course can be variable, prognostic markers are needed to better stratify patients. Prior literature, composed of small series with limited sample size, has demonstrated that tumor-infiltrating lymphocytes (TILs) are an important prognostic marker in MCC. To validate these findings on a population level, we sought to analyze and report the prognostic value of TILs in a large national data set. MATERIALS AND METHODS: A retrospective observational cohort study was conducted of patients with nonmetastatic MCC from 2010 to 2015 using the National Cancer Database. Individual variables trending toward significance using a univariable analysis were included in a multivariable Cox proportional hazards model to assess their independent effect on overall survival (OS). TILs were subclassified into none, nonbrisk, and brisk and the survival analysis was performed. Propensity score-weighted multivariable analysis (PS MVA) was performed to adjust for additional confounding. RESULTS: A total of 2,182 patients met inclusion criteria: 611 (28.0%) were identified as having TILs present, and 1,571 (72.0%) had TILs absent in the tumor. On MVA, subdivision of TIL status into nonbrisk (hazard ratio [HR], 0.750; 95% confidence interval [CI], 0.602-0.933) and brisk (HR, 0.499; 95% CI, 0.338-0.735) was associated with incrementally improved OS compared with no TILs. The association of nonbrisk and brisk TILs with improved OS was retained on PS MVA (Nonbrisk: HR, 0.720; 95% CI, 0.550-0.944; Brisk: HR, 0.483; 95% CI, 0.286-0.814). CONCLUSION: The presence of nonbrisk and brisk TILs is associated with incrementally improved OS in patients with nonmetastatic MCC in a large national data set. This pathologic feature can aid with risk stratification, estimation of prognosis, and, importantly, decision-making with respect to treatment intensification in high-risk patients. IMPLICATIONS FOR PRACTICE: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous malignancy with variable clinical course. Prognostic markers are needed to better risk stratify patients. We present the largest retrospective observational cohort study of patients with nonmetastatic MCC using the National Cancer Database. Our analysis demonstrates an association between increasing degrees of tumor-infiltrating lymphocytes and incrementally improved survival. These conclusions improve pathologic risk stratification, and decision-making with respect to treatment intensification. Intensification may include adjuvant radiation therapy to the primary site after wide excision despite small tumor size, to the nodal basin in sentinel lymph node-negative patients, or offering closer follow-up.
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Carcinoma de Células de Merkel , Neoplasias Cutáneas , Humanos , Linfocitos Infiltrantes de Tumor , Pronóstico , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy. We then examined associations between timing of multi-agent chemotherapy (neoadjuvant or adjuvant) and OS. We used a Cox proportional hazards model and propensity score matching (PSM) to account for covariates including demographic, patient, clinical, treatment, and facility factors. In the overall cohort, we observed no association between multi-agent chemotherapy or its timing and improved OS. Multi-agent chemotherapy was associated with improved OS in several subgroups, including patients with larger tumors (>5 cm), those treated at high-volume centers, or those who received radiation. We also identified an OS benefit to multi-agent chemotherapy among the elderly (>70 years) and African American patients. Multi-agent chemotherapy was associated with improved survival for patients with tumors >5 cm, who receive radiation, or who receive care at high-volume centers. Neither younger age nor chemotherapy timing was associated with better outcomes. These 'real-world' findings align with recent randomized trial data supporting the use of multi-agent chemotherapy in high-risk patients with localized STS.
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BACKGROUND: There is conflicting evidence regarding the role of chemotherapy for high-grade soft tissue sarcoma (STS) in adults. We sought to characterize patterns of chemotherapy use, including multiagent and neoadjuvant chemotherapy, in the United States. PATIENTS AND METHODS: Using the National Cancer Database, we identified 19,969 adult patients who underwent surgical resection for primary high-grade STS from 2004 to 2016. Using logistic regression, we examined factors associated with overall, multiagent, and neoadjuvant chemotherapy use. RESULTS: Chemotherapy was administered to 22% (n=4,377) of the study population. Among patients treated using chemotherapy, 85% received multiagent treatment and 47% received neoadjuvant treatment. On multivariate analysis, factors associated with chemotherapy use included tumor size, depth, histology, and primary site; receipt of radiation treatment; younger age; higher patient income; and academic treatment facility. Factors associated with multiagent chemotherapy use included tumor histology, tumor primary site, and younger age. Factors associated with neoadjuvant chemotherapy use included tumor size, depth, margin status, and primary site; receipt of radiation treatment; higher patient income; academic treatment facility type; and distance to treatment facility. Treatment at a high-volume facility was the only factor associated with overall, multiagent, and neoadjuvant chemotherapy use. No significant temporal trend was seen in overall, multiagent, or neoadjuvant chemotherapy use. CONCLUSIONS: Overall chemotherapy use was low (22%). The variability in chemotherapy use was driven by clinical, patient, demographic, and facility factors. Among patients treated with chemotherapy, the use of multiagent chemotherapy was high (85%), and nearly half received neoadjuvant therapy. There was a discrepancy in the use of chemotherapy-including neoadjuvant and multiagent chemotherapy-between high- and low-volume treatment centers.
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Sarcoma , Adulto , Quimioterapia Adyuvante , Bases de Datos Factuales , Humanos , Terapia Neoadyuvante , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Sarcoma/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Management of melanoma has been revolutionized by the use of immune checkpoint inhibitors. Immune system changes associated with aging may affect the efficacy of immune-based therapies. Using the National Cancer Database, we evaluated the impact of age on the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. We identified 11,944 patients from 2011-2015, of whom 25% received immunotherapy. Older (≥60 years), compared with younger, patients were less likely to receive immunotherapy (odds ratio, 0.69; 95% confidence interval [CI], 0.61-0.78; p < .001). Immunotherapy was associated with a survival benefit in both younger and older patients (<60 years: hazard ratio [HR], 0.64; 95% CI, 0.57-0.72; p < .001; ≥60 years: HR, 0.55; 95% CI, 0.50-0.60; p < .001). Importantly, there was a statistically significant interaction between age and survival with immunotherapy, where a greater benefit was observed for older patients (pinteraction = 0.013). Further work studying the age-related response to immunotherapy is warranted.
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Melanoma , Neoplasias Primarias Secundarias , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Melanoma/tratamiento farmacológicoRESUMEN
The effect of health insurance on management and outcomes in melanoma is unclear. Using the National Cancer Database (NCDB), we evaluated the effect of insurance on (1) stage at diagnosis, (2) receipt of immunotherapy, and (3) overall survival (OS) among patients with melanoma. We included patients with stage I-IV melanoma diagnosed from 2011 to 2015. Patients were stratified by age (below 65 vs. 65 y or above) and insurance (commercial, Medicare, Medicaid and uninsured). We evaluated the association between insurance and (1) stage at diagnosis (stage I-III vs. IV) and (2) receipt of immunotherapy (stage IV) using multivariable logistic regression. The association of insurance status with OS in metastatic patients who received immunotherapy was assessed using Kaplan-Meier and Cox proportional hazards analyses. The study included 167,130 patients; 52% had commercial insurance, 43% had Medicare, 3% had Medicaid and 2% were uninsured. In patients below 65 years, those with Medicaid and the uninsured had a higher likelihood of presenting with metastatic melanoma and were less likely to receive immunotherapy compared with those with commercial insurance. Further among those who received immunotherapy, patients with Medicaid (hazard ratio: 1.51, P=0.001) and no insurance (hazard ratio: 1.37, P=0.046) had an inferior OS. In patients 65 years or above, whereas Medicare was associated with an increased likelihood of presenting with metastatic disease, there was no significant difference in receipt of immunotherapy or OS as compared with commercial insurance. In this large modern cohort, insurance was associated with stage at diagnosis, receipt of immunotherapy, and OS for patients below 65 years old with melanoma.
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Cobertura del Seguro , Seguro de Salud , Melanoma/epidemiología , Anciano , Atención a la Salud/métodos , Atención a la Salud/normas , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Terapia Molecular Dirigida , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Evaluación de Resultado en la Atención de Salud , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Numerous studies across a variety of malignancies have demonstrated that health insurance status is associated with differences in clinical presentation, type of treatments received, and survival. The effect of insurance status on the management of soft tissue sarcoma is unknown. We assessed the association of insurance on (a) stage at diagnosis, (b) receipt of neoadjuvant/adjuvant radiation therapy, and (c) overall survival (OS) in patients with soft tissue sarcoma. METHODS: The study cohort was identified from the National Cancer Database (NCDB) and consisted of patients with stage I-IV soft tissue sarcoma of various histologies diagnosed from 2004 to 2015. The patients were stratified by age (<65 and ≥65 years) and by insurance status (commercial, Medicare, Medicaid and uninsured). Using multivariable logistic regression analysis, we evaluated the association between insurance status and (a) stage at diagnosis (Stage I-III vs IV), and (b) receipt of neoadjuvant/adjuvant radiation therapy in patients with locally advanced disease. The association of insurance status on OS was assessed using Kaplan-Meier and multivariable Cox proportional hazards analyses. A propensity score matched survival analysis was performed to account for measured confounders. RESULTS: 49 754 patients were identified of whom 23 677 (48%) had commercial insurance, 20 867 (42%) had Medicare, 3229 (6%) had Medicaid, and 1981 (4%) were uninsured. In patients <65 years, those with Medicaid (OR = 1.74, 95% CI: 1.57-1.93, P < .001) and the uninsured (OR = 1.71, 95% CI: 1.51-1.94, P < .001) were more likely to present with stage IV vs Stage I-III disease. Furthermore, among patients with locally advanced disease treated with limb sparing surgery, those with Medicaid (OR = 0.87, 95% CI: 0.77- 0.98, P = .021) and the uninsured (OR = 0.73, 95% CI: 0.63-0.85, P < .001) were less likely to receive neoadjuvant or adjuvant radiotherapy as compared to those with commercial insurance. Lastly, having Medicaid (HR = 1.26, 95% CI: 1.17-1.34, P < .001) and no insurance (HR = 1.30, 95% CI: 1.20-1.41, P < .001) was associated with worse OS compared to having commercial insurance, a finding which remained significant after propensity score matching. In contrast, in patients ≥65 years, there were no statistically significant differences between those with Medicare and commercial insurance with regards to disease presentation, receipt of radiotherapy, or survival. CONCLUSIONS: In a large modern cohort identified from the NCDB, commercial insurance status in patients <65 years was associated early diagnosis, receipt of neoadjuvant/adjuvant radiation therapy, and overall survival for patients with soft tissue sarcoma. Further efforts are warranted to understand disparities in care based on health insurance in the United States.
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Cobertura del Seguro , Seguro de Salud , Sarcoma/epidemiología , Anciano , Anciano de 80 o más Años , Terapia Combinada , Bases de Datos Factuales , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Sistema de Registros , Sarcoma/diagnóstico , Sarcoma/terapia , Evaluación de Síntomas , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: There has been limited progress in the development of novel therapeutics for the treatment of sarcomas. A review of phase I and II clinical trials for sarcomas may give insight into factors influencing sarcoma drug development. METHODS: An exhaustive analysis of phase I and II clinical trials testing drugs for human sarcoma patients between 1 January 2000 and 1 June 2018 was performed using the PubMed search engine, the Thomson Web of Science, and the National Clinical Trials registry. Recorded outcomes included tested drugs, tested histological subtypes, whether the drug was initially developed for sarcoma, reported funding sources, and whether studies led to phase III trials. RESULTS: Out of 238 studies meeting inclusion criteria, 87% (207 studies) reported funding sources. Of these, 59.9% (124/207) reported industry funding, 52.7% (109/207) reported government funding, and 27.5% (57/207) reported private funding. Only 5% (12/238) of phase I and II trials resulted in phase III trials, with 11 of 12 studies funded by industry. Approximately 90% (214/238) of studies tested drugs that were not initially tested in sarcoma, and 60.1% (143/238) of studies grouped different sarcoma histological subtypes together in the same study. CONCLUSION: Industry has funded the majority of phase I and II sarcoma clinical trials that have led to phase III trials. There was a high rate of drugs approved for other cancers and then secondarily tested in sarcoma. Most trials tended to group different sarcoma subtypes rather than studying each subtype separately.
Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Desarrollo de Medicamentos , Descubrimiento de Drogas , HumanosRESUMEN
PURPOSE: Definitive local therapy is often used in metastatic cervical cancer to reduce morbidity associated with local tumor progression. However, the potential benefit of this therapeutic approach has not been rigorously investigated. We hypothesized that definitive local therapy is associated with improved overall survival (OS) in metastatic cervical cancer. METHODS AND MATERIALS: Patients aged ≥18 years with newly diagnosed metastatic cervical cancer who were treated with chemotherapy were identified from the National Cancer Database. Patients were dichotomized into the following cohorts: definitive local therapy (defined as either concurrent chemoradiation therapy or definitive surgery) or conservative therapy (defined as systemic therapy with or without palliative radiation therapy). The association between definitive local therapy and OS was assessed using propensity score-weighted Cox proportional hazards models. Potential unmeasured confounding was assessed through sensitivity analyses. Factors associated with the receipt of definitive local therapy were identified with multivariable logistic regression. RESULTS: A total of 2838 patients were identified, of whom 1194 (42%) and 1644 (58%) were treated with definitive local and conservative therapy, respectively. Receipt of definitive local therapy was statistically significant, associated with less comorbidity, lower clinical T stage, and node negative disease. Compared with conservative therapy, definitive local therapy was associated with improved OS (hazard ratio: 0.57; 95% confidence interval, 0.52-0.62; P ≤ .001). The median OS rate was 19.2 months in the definitive local therapy cohort and 10.1 months in the conservative therapy cohort. These findings were robust to potential unmeasured confounding in sensitivity analyses and on landmark analyses of patients who survived at least 12 months (hazard ratio: 0.71; 95% confidence interval, 0.62-0.82; P ≤ .001). CONCLUSIONS: Definitive local therapy is associated with improved OS in patients with metastatic cervical cancer. These findings suggest a novel setting for the use of definitive local therapy in the metastatic setting.
Asunto(s)
Adenocarcinoma/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias del Cuello Uterino/mortalidad , Adenocarcinoma/secundario , Adenocarcinoma/terapia , Anciano , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapiaRESUMEN
PURPOSE: The benefit of perioperative radiation therapy in elderly patients with soft-tissue sarcoma (STS) is unclear due to the underrepresentation of elderly patients in clinical trials. We assessed patterns of care and overall survival (OS) associated with perioperative radiation therapy use in this population. METHODS AND MATERIALS: Elderly patients (≥70 years) with high-grade STS who underwent surgery with or without perioperative radiation therapy from 2004 to 2013 were identified from the National Cancer Database. A nonelderly cohort (<70 years) was also identified for secondary comparative analyses. The association between perioperative radiation therapy use and OS was assessed using propensity score-weighted Cox proportional hazards analyses. Relative survival was calculated using national life tables to assess the impact of radiation therapy on estimated sarcoma-specific survival in elderly and nonelderly patients. Patterns of care were assessed using multivariable logistic regression analyses. RESULTS: Of 6978 elderly patients, 3549 (51%) underwent surgery alone, and 740 (11%) and 2,679 (38%) received pre- and postoperative radiation therapy, respectively. Elderly patients received radiation therapy less commonly than did nonelderly patients (49% vs 52%, P < .001) despite presenting with higher grade tumors (grade 3, 86% vs 80%, P < .001) and experiencing more frequent positive surgical margins (23% vs 16%, P < .001). On propensity score-weighted analyses, preoperative (hazard ratio = 0.64, 95% confidence interval: 0.54-0.77, P < .001) and postoperative (hazard ratio = 0.72, 95% confidence interval: 0.67-0.77, P < .001) radiation therapy use was associated with improved OS compared with surgery alone. These associations were robust to landmark analyses of patients surviving at least 12 months. Radiation therapy use resulted in a greater magnitude of 5-year relative survival improvement in elderly than nonelderly patients. CONCLUSIONS: There is an overall and an age-disparate underuse of perioperative radiation therapy in elderly patients with high-grade STS despite radiation therapy being associated with improved OS. Further research is warranted to minimize gaps in care for elderly patients.