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INTRODUCTION: Nirogacestat is a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors. In the phase 3 DeFi study (NCT03785964) of nirogacestat, ovarian toxicity (OT) was identified as a safety signal among females of reproductive potential (FORP). This analysis further describes the incidence, presentation, and resolution of OT. METHODS: Patients were randomized to twice-daily oral nirogacestat (150 mg) or placebo, taken in continuous 28-day cycles. Investigator-identified OT in FORP was based on abnormal reproductive hormone values or perimenopausal symptoms (or both). Adverse event follow-up was conducted to assess OT resolution. Post hoc analyses included return of menstruation and return of follicle-stimulating hormone (FSH) to within normal limits (WNL) (≤20.4 mIU/mL). RESULTS: Of 92 randomized females, 73 in the safety population were FORP (n = 36 nirogacestat, n = 37 placebo). OT was identified in 75% (27 of 36) receiving nirogacestat and 0% (0 of 37) receiving placebo. As of October 24, 2022, investigators reported OT resolution in 78% (21 of 27) of patients, with median OT duration of 19.1 weeks. Off-treatment resolution was reported in all 11 patients (100%) who stopped nirogacestat treatment; of these, all nine with available menstruation information experienced return of menstruation and eight had FSH WNL at last reported assessment. Resolution was reported in 10 of 14 (71%) while on nirogacestat; of these, all 10 experienced return of menstruation and seven had FSH WNL. Two patients were lost to follow-up. CONCLUSION: Most FORP treated with nirogacestat experienced OT, with the majority resolving, including all who stopped treatment, suggesting that OT is transient.
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Fibromatosis Agresiva , Humanos , Femenino , Adulto , Persona de Mediana Edad , Fibromatosis Agresiva/tratamiento farmacológico , Ovario/efectos de los fármacos , Adulto Joven , Método Doble Ciego , Hormona Folículo Estimulante , Anciano , AdolescenteRESUMEN
BACKGROUND: An estimated 609,820 child-rearing adults in 2023 died from advanced cancer, affecting 153,675 dependent children. Although children are known to suffer significant distress when a parent is diagnosed with cancer, few studies have described parents' views of their adolescent's behavioral response to their advanced cancer or what the parent did to interpret or manage that response. OBJECTIVES: To describe patient-reported concerns about their adolescent and how they responded to their adolescent's behavior. METHODS: Single occasion interviews were administered to 6 adolescent-rearing parents with Stage IV cancer. Interviews were analyzed using inductive content analysis by trained coders. Trustworthiness of results was protected through peer debriefing, coding to consensus, and maintaining an audit trail. RESULTS: The core construct that explained study data was Being There without Taking Over, comprised of 4 domains: Struggling to Read My Child, Attempting to Talk with My Child about My Cancer, Trying to Maintain Optimism, and Understanding My Child. CONCLUSIONS: Parents were deeply concerned about the impact of their advanced cancer on their adolescent but were unable to distinguish between cancer-related distress and adolescent angst. They feared initiating cancer-related discussions and struggled with their own feelings of guilt and parental inadequacy but did not turn to professionals for help. SIGNIFICANCE OF RESULTS: Adolescent-rearing patients with advanced disease need to be triaged into services that offer a framework from which parents can interpret their child's behavior and learn ways to have adolescent-appropriate conversations about the cancer. Such services should also help parents gain skills to manage feelings of parental inadequacy and guilt. In the absence of services, parents struggle and do not know how to interpret and respond to their adolescent's cancer-related behavior.
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BACKGROUND: Dedifferentiated chondrosarcoma is a chondrosarcoma subtype associated with high rates of recurrence and a poor prognosis. Others have proposed treatment of dedifferentiated chondrosarcoma using osteosarcoma protocols, including perioperative chemotherapy. However, the rarity of this condition poses difficulties in undertaking single- institution studies of sufficient sample size. QUESTION/PURPOSE: Is perioperative chemotherapy associated with improved overall survival in patients with dedifferentiated chondrosarcoma? METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) 1973 to 2016 database for patients with a diagnosis of dedifferentiated chondrosarcoma (n = 308). As dedifferentiated chondrosarcoma was only classified as a distinct entity in SEER starting in 2000, only patients treated in 2000 and later were included. We excluded from our analyses those patients with distant disease at diagnosis, a primary site of disease other than bone or joints, and those who did not receive cancer-directed surgery. These criteria yielded 185 dedifferentiated chondrosarcoma patients for inclusion. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the association of clinical, demographic, and treatment characteristics on overall survival (OS). RESULTS: After controlling for confounding variables, including age, sex, tumor size, stage, grade, location, and radiation treatment status, and after adjusting for missing data, no overall survival benefit was associated with receipt of chemotherapy in patients with dedifferentiated chondrosarcoma (hazard ratio 0.75 [95% confidence interval 0.49 to 1.12]; p = 0.16). CONCLUSION: Chemotherapy treatment of dedifferentiated chondrosarcoma was not associated with improved OS. These results must be viewed cautiously, given the limited granularity of information on chemotherapy treatment, the concerns regarding chemotherapy misclassification in SEER data, and the small sample of patients with dedifferentiated chondrosarcoma, all of which limit the power to detect a difference. Our findings are nevertheless consistent with those of prior reports in which no benefit of chemotherapy could be detected. Lack of clear benefit from perioperative chemotherapy in dedifferentiated chondrosarcoma argues that it should be used only after careful consideration, and ideally in the context of a clinical trial. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Neoplasias Óseas , Condrosarcoma , Osteosarcoma , Neoplasias Óseas/tratamiento farmacológico , Condrosarcoma/diagnóstico , Condrosarcoma/tratamiento farmacológico , Humanos , Estimación de Kaplan-Meier , Pronóstico , Estudios Retrospectivos , Programa de VERFRESUMEN
Outcomes for patients (pts) with sarcoma and COVID-19 are unknown. This is a single institution retrospective study of adults with sarcoma and COVID-19. Ten pts [median age 60 (range 24-69)] were identified. Five were hospitalized; two died from COVID-19 complications; another died from sarcoma. Time between last systemic treatment dose and COVID-19 diagnosis was 6-41 days in pts who died. 5 underwent prior radiation (RT); time between RT and COVID-19 diagnosis was 20-62 days for pts who died. All three pts with WBC differential data (two died) were lymphopenic. Efforts to capture outcomes for a larger cohort are urgently needed.
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COVID-19/prevención & control , SARS-CoV-2/aislamiento & purificación , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Adulto , Anciano , COVID-19/complicaciones , COVID-19/virología , Prueba de COVID-19/métodos , Quimioradioterapia/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/fisiología , Sarcoma/complicaciones , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/complicaciones , Neoplasias de los Tejidos Blandos/cirugía , Análisis de Supervivencia , Adulto JovenRESUMEN
Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.
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Neoplasias , Cuidados Paliativos , Humanos , Oncología Médica , Neoplasias/terapia , Calidad de VidaRESUMEN
BACKGROUND: Epithelioid sarcoma is a rare and aggressive soft-tissue sarcoma subtype. Over 90% of tumours have lost INI1 expression, leading to oncogenic dependence on the transcriptional repressor EZH2. In this study, we report the clinical activity and safety of tazemetostat, an oral selective EZH2 inhibitor, in patients with epithelioid sarcoma. METHODS: In this open-label, phase 2 basket study, patients were enrolled from 32 hospitals and clinics in Australia, Belgium, Canada, France, Germany, Italy, Taiwan, the USA, and the UK into seven cohorts of patients with different INI1-negative solid tumours or synovial sarcoma. Patients eligible for the epithelioid sarcoma cohort (cohort 5) were aged 16 years or older with histologically confirmed, locally advanced or metastatic epithelioid sarcoma; documented loss of INI1 expression by immunohistochemical analysis or biallelic SMARCB1 (the gene that encodes INI1) alterations, or both; and an Eastern Cooperative Oncology Group performance status score of 0-2. Patients received 800 mg tazemetostat orally twice per day in continuous 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints were duration of response, disease control rate at 32 weeks, progression-free survival, overall survival, and pharmacokinetic and pharmacodynamic analyses (primary results reported elsewhere). Time to response was also assessed as an exploratory endpoint. Activity and safety were assessed in the modified intention-to-treat population (ie, patients who received one or more doses of tazemetostat). This trial is registered with ClinicalTrials.gov, NCT02601950, and is ongoing. FINDINGS: Between Dec 22, 2015, and July 7, 2017, 62 patients with epithelioid sarcoma were enrolled in the study and deemed eligible for inclusion in this cohort. All 62 patients were included in the modified intention-to-treat analysis. Nine (15% [95% CI 7-26]) of 62 patients had an objective response at data cutoff (Sept 17, 2018). At a median follow-up of 13·8 months (IQR 7·8-19·0), median duration of response was not reached (95% CI 9·2-not estimable). 16 (26% [95% CI 16-39]) patients had disease control at 32 weeks. Median time to response was 3·9 months (IQR 1·9-7·4). Median progression-free survival was 5·5 months (95% CI 3·4-5·9), and median overall survival was 19·0 months (11·0-not estimable). Grade 3 or worse treatment-related adverse events included anaemia (four [6%]) and weight loss (two [3%]). Treatment-related serious adverse events occurred in two patients (one seizure and one haemoptysis). There were no treatment-related deaths. INTERPRETATION: Tazemetostat was well tolerated and showed clinical activity in this cohort of patients with advanced epithelioid sarcoma characterised by loss of INI1/SMARCB1. Tazemetostat has the potential to improve outcomes in patients with advanced epithelioid sarcoma. A phase 1b/3 trial of tazemetostat plus doxorubicin in the front-line setting is currently underway (NCT04204941). FUNDING: Epizyme.
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Benzamidas/administración & dosificación , Piridonas/administración & dosificación , Proteína SMARCB1/genética , Sarcoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas/efectos adversos , Benzamidas/farmacocinética , Compuestos de Bifenilo , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/farmacocinética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Morfolinas , Supervivencia sin Progresión , Piridonas/efectos adversos , Piridonas/farmacocinética , Sarcoma/genética , Sarcoma/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
LESSONS LEARNED: The results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist. BACKGROUND: Regorafenib is a multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients. METHODS: Patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1. RESULTS: Forty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI], 0.92-3.67) months for regorafenib versus 2.07 (95% CI, 1.64-3.44) months for placebo; stratified hazard ratio [HR], 0.85 (95% CI, 0.46, 1.58), p = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI, 4.16-23.48) months for regorafenib and 4.89 (95% CI, 3.02-9.77) months for placebo, stratified HR, 0.66 (95% CI, 0.31-1.40), p = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib. CONCLUSION: Regorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.
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Liposarcoma , Compuestos de Fenilurea , Piridinas , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Liposarcoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas , Piridinas/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: US Hispanics are more likely to be diagnosed with advanced cancer as parents than their non-Hispanic white counterparts but little is known about Hispanic parents' willingness to discuss a terminal cancer diagnosis with dependent children, potentially resulting in suboptimal child coping. Therefore, we investigated Hispanic mothers' willingness to communicate with dependent children about her actual or hypothetical advanced cancer diagnosis. METHODS: Two focus groups (n = 6 participants) and three one-on-one interviews (n = 3) were conducted in either Spanish or English among adult, Mexican-American mothers with a current cancer diagnosis of any stage residing in US-Mexico border communities. Participants reported their perceived concerns, parenting challenges, and openness to discussing an incurable cancer diagnosis with a dependent child. Audio files were transcribed into English and qualitatively coded using content analysis. RESULTS: Participants, most with breast cancer, ranged in age from 25 to 47. Five had considered the possibility of their own death from advanced cancer and three had previously discussed this with their children. While many expected their children would carry on well without them, seven expressed concern for the emotional/spiritual well-being of their children. Mothers anticipated physical and time-based parenting challenges but wanted the opportunity to focus on themselves and their children in advance of death. All but one would be willing to discuss an advance cancer diagnosis with dependent children; four expressed the value of doing so or the potential harm of abdicating this responsibility. CONCLUSIONS: If faced with an advanced cancer diagnosis, Mexican-American mothers are open to communicating with dependent children.
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Hijo de Padres Discapacitados , Hispánicos o Latinos , Madres , Neoplasias , Relaciones Padres-Hijo , Enfermo Terminal , Adaptación Psicológica/fisiología , Adolescente , Adulto , Niño , Hijo de Padres Discapacitados/psicología , Hijo de Padres Discapacitados/estadística & datos numéricos , Preescolar , Progresión de la Enfermedad , Emociones , Femenino , Grupos Focales , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Entrevistas como Asunto , Masculino , México/etnología , Persona de Mediana Edad , Madres/psicología , Madres/estadística & datos numéricos , Neoplasias/diagnóstico , Neoplasias/etnología , Neoplasias/patología , Cuidados Paliativos/psicología , Cuidados Paliativos/estadística & datos numéricos , Relaciones Padres-Hijo/etnología , Proyectos Piloto , Investigación Cualitativa , VoliciónRESUMEN
OBJECTIVE: The outcome for patients with unresectable hepatic sarcoma is poor with a median survival period of 12-16 months. The purpose of this study was to evaluate liver-directed transcatheter therapies for the treatment of hepatic sarcomas. MATERIALS AND METHODS: In a retrospective study, the cases of patients with primary and metastatic hepatic sarcoma treated by transcatheter embolization, chemoembolization, and 90Y radioembolization between 2004 and 2015 were identified. Response Evaluation Criteria in Solid Tumors version 1.1 response was assessed for the target tumor. Survival was assessed by means of Kaplan-Meier analysis. RESULTS: Twenty-eight patients (17 [61%] men, 11 [39%] women; median age, 47 years) were included. Eighteen patients were treated electively. Two of the electively treated patients underwent embolization; eight, chemoembolization; six, radioembolization; and two, a combination of transcatheter treatments. Treatment was well tolerated; only one patient had grade 3 hepatic toxicity. The objective response rate of the index tumor was 61%, and the median overall survival period was 26.7 months. Ten patients underwent emergency embolization to control acute hemorrhage from tumor rupture. The median overall survival periods were 611 days for the patients with ruptured gastrointestinal stromal tumors (GIST) (n = 3) and 19 days for the patients with ruptured angiosarcoma (n = 7). CONCLUSION: Liver-directed transcatheter therapies are safe and may have a role in the elective management of unresectable primary and metastatic liver sarcomas. Emergency embolization for ruptured GIST may be effective for stabilizing the patient's condition and allowing more definitive therapy in the future. However, emergency embolization has limited efficacy in treating patients with ruptured angiosarcoma, likely because of substantial venous bleeding at rupture and the aggressive behavior of this lesion.
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Embolización Terapéutica , Neoplasias Hepáticas/terapia , Sarcoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoma/mortalidad , Sarcoma/secundario , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vß gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Receptor de Muerte Celular Programada 1/genética , Sarcoma/genética , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/mortalidad , Linfocitos T/citología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biopsia con Aguja , Células Clonales , Análisis por Conglomerados , Estudios de Cohortes , Terapia Combinada , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Sarcoma/patología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Análisis de Supervivencia , Linfocitos T/inmunología , Adulto JovenRESUMEN
PURPOSE: The purposes of the study were to (1) test the short-term impact of a telephone-delivered cancer parenting education program, the Enhancing Connections-Telephone (EC-T) Program, on maternal anxiety, depressed mood, parenting competencies, and child behavioral-emotional adjustment and (2) compare those outcomes with outcomes achieved from an in-person delivery of the same program (EC). METHODS: Thirty-two mothers comprised the sample for the within-group design and 77 mothers for the between-group design. Mothers were eligible if they had one or more dependent children and were recently diagnosed with stages 0-III breast cancer. Mothers in both groups received five intervention sessions at 2-week intervals from a patient educator using a fully scripted intervention manual. RESULTS: Outcomes from the within-group analysis revealed significant improvements on maternal anxiety, parenting competencies, and the child's behavioral-emotional functioning. Outcomes from the between-group analysis showed the EC-T did as well or better than EC in positively affecting maternal anxiety, depressed mood, parenting competencies, and the child's behavioral-emotional adjustment. Furthermore, the EC-T had a significantly greater impact than the EC on maternal confidence in helping their family and themselves manage the cancer's impact and in staying calm during emotionally charged conversations about the breast cancer with their child. CONCLUSIONS: Regardless of the channel of delivery, the Enhancing Connections Program has the potential to positively affect parenting competencies and behavioral-emotional adjustment in mothers and dependent children in the first year of stages 0-III maternal breast cancer. Its positive impact from telephone delivery holds promise for sustainability.
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Neoplasias de la Mama/psicología , Relaciones Madre-Hijo/psicología , Neoplasias/terapia , Responsabilidad Parental/psicología , Adulto , Niño , Preescolar , Estudios de Factibilidad , Femenino , Educación en Salud , Humanos , Proyectos Piloto , TeléfonoRESUMEN
Early palliative care (EPC) for patients with metastatic solid tumors is now standard of care, but the effect of EPC in hematopoietic cell transplantation (HCT) is less well understood. We studied the acceptability of pre-HCT EPC as measured by trial participation, changes in patient-reported outcomes, and follow-up with palliative care providers. English-speaking adults (age >17 years) with an HCT comorbidity index of ≥ 3, relapse risk > 25%, or planned HLA-mismatched allogeneic or myeloablative HCT received EPC before HCT admission with monthly or more frequent visits. Twenty-two (69%) of 32 subjects provided consent; 2 were later excluded (HCT cancelled, consent retracted) for a 63% participation rate. Comfort with EPC was high (82% very comfortable). Subjects reported stable or improved mood and sense of hope, without apparent negative effects with a median of 3 visits. Follow-up surveys were returned by 75% of participants at 60 days and by 65% at 90 days. Four (20%) were admitted to the intensive care unit before day 100 and 3 (15%) received life-support measures. Five (25%) died with median follow-up of 14 months. EPC is feasible, acceptable, and has the potential to improve the HCT experience, whether or not the patient survives. EPC for HCT patients should be tested in a randomized trial.
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Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/psicología , Cuidados Paliativos/métodos , Medición de Resultados Informados por el Paciente , Adulto , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos/psicología , Cuidados Paliativos/normas , Derivación y Consulta , Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas.
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Antineoplásicos Alquilantes/uso terapéutico , Dioxoles/uso terapéutico , Sarcoma/tratamiento farmacológico , Tetrahidroisoquinolinas/uso terapéutico , Animales , Antineoplásicos Alquilantes/efectos adversos , Ensayos Clínicos Fase II como Asunto , Dioxoles/efectos adversos , Humanos , Tetrahidroisoquinolinas/efectos adversos , TrabectedinaRESUMEN
PURPOSE: Retroperitoneal sarcomas (RPS) are rare malignancies, comprising just 10-15 % of all soft-tissue sarcomas. These are challenging tumors to treat, with surgical resection being the only modality capable of providing a cure. This study analyzed the management and survival of patients resected at a large academic institution. METHODS: A retrospective study of all patients with primary localized RPS referred to the University of Washington between January 2000 and January 2013 was performed. Univariate and multivariate Cox regression models were used to analyze progression-free survival (PFS) and overall survival (OS) by patient, tumor, and treatment variables. RESULTS: The study identified 132 patients. Median follow-up was 31.8 months. Median PFS was 33 months, and median OS was 111 months. Sixty patients (45.5 %) underwent a margin-negative resection (R0), 59 (44.7 %) had a microscopic margin-positive resection (R1), and 7 (5.3 %) had a macroscopic margin-positive resection (R2). Forty (30.3 %) patients received preoperative radiation, 28 (21.2 %) received neoadjuvant chemotherapy, and 7 (5.3 %) received both. Tumor grade and microscopic margin status emerged as statistically significant predictors for both PFS and OS. Tumor size was also found to correlate with PFS. No significant difference in OS or PFS was observed for histologic subtype, neoadjuvant chemotherapy, or neoadjuvant radiation. CONCLUSIONS: Complete surgical resection should remain the mainstay of management for RPS, with emphasis on achieving negative microscopic margins. Neither neoadjuvant chemotherapy nor radiation was shown to significantly improve survival, and their unclear role in the management of RPS requires evaluation in a prospective setting.
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Recurrencia Local de Neoplasia/cirugía , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/patología , Estudios Retrospectivos , Sarcoma/mortalidad , Sarcoma/secundario , Tasa de SupervivenciaRESUMEN
Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed. Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US. Design, Setting, and Participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19â¯289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023. Main Outcomes and Measures: Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation. Results: The study included 19â¯289 patients (median age, 71 years [IQR, 59-80 years]; 10â¯506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1â¯000â¯000 person-years (95% CI, 3.1-3.5 cases per 1â¯000â¯000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1â¯000â¯000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13â¯955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001). Conclusions and Relevance: This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.
Asunto(s)
Neoplasias de la Mama , Hemangiosarcoma , Masculino , Humanos , Femenino , Anciano , Incidencia , Hemangiosarcoma/epidemiología , Estudios Transversales , Estudios RetrospectivosRESUMEN
Breast cancer tends to arise in older women who are also burdened with comorbidities such as cardiovascular disease (CVD). Increasing numbers of breast cancer survivors and an aging population warrant a better understanding of CVD management and adherence to preventive therapies. We estimated adherence to statins and therapeutic goal lipid values during the year before breast cancer diagnosis or baseline, treatment period, and in subsequent years of clinical management among breast cancer survivors. We sampled women from an existing cohort of 4,221 women diagnosed with incident early stage (I, II) invasive breast cancer from 1990 to 2008 and enrolled in a large integrated group practice health plan. Among prevalent statin users (N = 1,393), medication adherence and persistence were measured by medication possession ratio (MPR), % adherent (MPR < 0.80), and discontinuation rates. Laboratory data on LDL and HDL were obtained for the coinciding periods. Mean MPR for statin use (0.78 vs. 0.68; P < 0.001) and proportion adherent (67.0 vs. 51.9 %; P < 0.001) declined from baseline to the treatment period. Mean LDL (143 mg/dL baseline vs. 150 mg/dL treatment period; P < 0.001) and proportion not at LDL goal (60.1 vs. 70.8 %; P < 0.001) coincided with decreases in adherence. During treatment, non-adherent statin users had the highest mean LDL (160.4 mg/dL) and proportion not at goal LDL (91.8 %) overall. Adherence did not return to baseline in subsequent years following treatment although LDL levels did. HDL did not differ by periods of interest or adherence levels. Adherence to statins in this population was poor, particularly in the treatment period, and lagged in returning to baseline. Understanding the influence of life events such as cancer diagnosis and treatment on management of comorbidities and adherence to preventive therapies are important to the growing population of breast cancer survivors.
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Neoplasias de la Mama/sangre , Neoplasias de la Mama/complicaciones , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Enfermedades Cardiovasculares/complicaciones , Femenino , Humanos , Cumplimiento de la Medicación , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Most data regarding medical care for cancer patients in the United States comes from Surveillance, Epidemiology and End Results-linked Medicare analyses of individuals aged 65 years or older and typically excludes Medicare Advantage enrollees. OBJECTIVES: To assess the accuracy of chemotherapy and hormone therapy treatment data available through the Cancer Research Network's Virtual Data Warehouse (VDW). RESEARCH DESIGN: Retrospective, longitudinal cohort study. Medical record-abstracted, tumor registry-indicated treatments (gold standard) were compared with VDW-indicated treatments derived from health maintenance organization pharmacy, electronic medical record, and claim-based data systems. SUBJECTS: Enrollees aged 18 years and older diagnosed with incident breast, colorectal, lung, or prostate cancer from 2000 through 2007. MEASURES: Sensitivity, specificity, and positive predictive value were computed at 6 and 12 months after cancer diagnosis. RESULTS: Approximately 45% of all cancer cases (total N=23,800) were aged 64 years or younger. Overall chemotherapy sensitivity/specificities across the 3 health plans for incident breast, colorectal, lung, and prostate cancer cases were 95%/90%, 95%/93%, 93%/93%, and 85%/77%, respectively. With the exception of prostate cancer cases, overall positive predictive value ranged from 86% to 89%. Small variations in chemotherapy data accuracy existed due to cancer site and data source, whereas greater variation existed in hormone therapy capture across sites. CONCLUSIONS: Strong concordance exists between gold standard tumor registry measures of chemotherapy receipt and Cancer Research Network VDW data. Health maintenance organization VDW data can be used for a variety of studies addressing patterns of cancer care and comparative effectiveness research that previously could only be conducted among elderly Surveillance, Epidemiology and End Results-Medicare populations.
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Antineoplásicos/uso terapéutico , Quimioterapia/estadística & datos numéricos , Registros Electrónicos de Salud/normas , Sistemas Prepagos de Salud/estadística & datos numéricos , Hormonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Neoplasias Colorrectales/tratamiento farmacológico , Bases de Datos Factuales , Femenino , Humanos , Estudios Longitudinales , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Registro Médico Coordinado , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias de la Próstata/tratamiento farmacológico , Sistema de Registros/normas , Sistema de Registros/estadística & datos numéricos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Programa de VERF/estadística & datos numéricos , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
Patients with cutaneous T-cell lymphoma (CTCL) often experience debilitating symptoms that impair health-related quality of life (HRQoL). Existing evidence for HRQoL differences with respect to gender is conflicting. Objective: To investigate potential gender differences in HRQoL for patients with CTCL. Methods: We performed a cross-sectional study to assess HRQoL in patients with CTCL by partnering with the Cutaneous Lymphoma Foundation to distribute an electronic survey from February to April 2019. Results: A total of 292 patient responses (66% women, mean age 57 years) were included in the analysis. Most of the cohort had early-stage (IA-IIA) (74%; 162/203) mycosis fungoides (MFs) (87%; 241/279), followed by Sézary syndrome (SS) (12%; 33/279). Women with CTCL experienced significantly worse HRQoL compared with men (Skindex-16: 51±26 vs. 36±26, P ≤ 0.001; FACT-G: 69±21 vs. 77±16, P = 0.005). This gender difference was present even when controlling for stage of disease. Women experienced worse HRQoL in all three of the Skindex-16 subscales (symptoms: ß = 14.0, P ≤ 0.001; emotions: ß = 15.1, P ≤ 0.001; functioning: ß = 11.3, P = 0.006), but only two of the four FACT-G subscales (physical: ß =-2.8, P ≤ 0.001; emotional: ß = -2.0, P = 0.004). Limitations: Due to the method of distribution of the survey, we were unable to estimate a participant response rate. Participants' diagnosis and stage were self-reported. Conclusion: In this cohort women with CTCL experienced significantly worse HRQoL when compared to men. Additional studies are necessary to determine what factors contribute to this gender disparity.
RESUMEN
BACKGROUND: Malignant hemangioendothelioma is an endothelial cancer with heterogeneous clinical behavior that can range from indolent to aggressive, of which the majority are epithelioid (EHE). Its incidence and demographics have not been previously well defined in a large cohort. METHODS: This retrospective analysis used the US Cancer Statistics National Program of Cancer Registries - Surveillance Epidemiology End Results (SEER) combined database to identify patients in the US newly diagnosed with hemangioendothelioma between the years of 2001 and 2017 (n = 1986). Survival analyses were performed on a subset of patients within the SEER-18 database with survival information available (n = 417). Outcomes included incidence, demographics of patients newly diagnosed with hemangioendothelioma, extent of disease at presentation, and overall survival. RESULTS: The incidence of hemangioendothelioma in the US is 0.4 cases per million person-years. Although cases rose to 122 newly diagnosed in the year 2017 (90 EHE, 32 other hemangioendothelioma), incidence rates were stable. Skin and connective tissues were the most common presenting sites (33.4%), followed by liver (24.5%), lung (17.6%), and bone (12.5%). Median age at diagnosis was 55 years; 27.2% of patients were pediatric, adolescent, or young adult (<40 years). At presentation, 36.4% of patients had localized disease; 21.6% presented with regional and 41.7% with distant metastases. Observed survival at 3 years was 79.7%, 70.7%, and 46.0% for patients presenting with local, regional, and distant disease and most deaths occurred within the first 2 years. CONCLUSIONS: Malignant hemangioendothelioma is ultra-rare but meaningfully impacts affected patients. These data may provide benchmarks for comparison of new approaches to hemangioendothelioma therapy and highlight poor survival outcomes.
Asunto(s)
Hemangioendotelioma Epitelioide , Hemangioendotelioma , Hemangiosarcoma , Adolescente , Adulto Joven , Humanos , Niño , Estados Unidos/epidemiología , Persona de Mediana Edad , Incidencia , Hemangioendotelioma Epitelioide/epidemiología , Hemangioendotelioma Epitelioide/patología , Estudios Retrospectivos , Hemangiosarcoma/patología , Hemangioendotelioma/epidemiología , Hemangioendotelioma/patologíaRESUMEN
PURPOSE: Continuous intravenous infusion (CIV) of doxorubicin (DOX) versus bolus (BOL) may minimize dose-dependent DOX cardiomyopathy, but it is unclear whether this advantage is evident as employed in typical soft-tissue sarcoma (STS) treatment. The impact of administration mode on adverse events (AE) and efficacy were compared using data from a randomized trial of DOX-based therapy (SARC021/TH CR-406). EXPERIMENTAL DESIGN: In this post hoc analysis, CIV versus BOL was at discretion of the treating physician. Likelihood of AEs, and objective responses were assessed by adjusted logistic regression. Progression-free (PFS) and overall survival (OS) were compared using Kaplan-Meier, log-rank test, and adjusted Cox regression. RESULTS: DOX was administered by BOL to 556 and by CIV to 84 patients. Proportions experiencing hematologic, non-hematologic, or cardiac AEs did not differ by administration mode. Hematologic AEs were associated with age, performance status, and cumulative DOX. Non-hematologic AEs were associated with age, performance status, and cumulative evofosfamide. Cardiac AEs were only associated with cumulative DOX; there was no interaction between DOX dose and delivery mode. PFS and OS were similar (median PFS 6.14 months BOL vs. 6.11 months CIV, P = 0.47; median OS 18.4 months BOL vs. 21.4 months CIV, P = 0.62). PFS, OS, and objective responses were not associated with delivery mode. CONCLUSIONS: CIV was not associated with superior outcomes over BOL within DOX dosing limits of SARC021. Cardiac AEs were associated with increasing cumulative DOX dose. While not randomized with respect to DOX delivery mode, the results indicate that continued investigation of AE mitigation strategies is warranted.