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BACKGROUND: The authors hypothesized that patients developing immune-related adverse events (irAEs) while receiving immune checkpoint inhibition (ICI) for recurrent/metastatic head and neck cancer (HNC) would have improved oncologic outcomes. METHODS: Patients with recurrent/metastatic HNC received ICI at 2 centers. Univariate and multivariate logistic regression, Kaplan-Meier methods, and Cox proportional hazards regression were used to associate the irAE status with the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in cohort 1 (n = 108). These outcomes were also analyzed in an independent cohort of patients receiving ICI (cohort 2; 47 evaluable for irAEs). RESULTS: The median follow-up was 8.4 months for patients treated in cohort 1. Sixty irAEs occurred in 49 of 108 patients with 5 grade 3 or higher irAEs (10.2%). ORR was higher for irAE+ patients (30.6%) in comparison with irAE- patients (12.3%; P = .02). The median PFS was 6.9 months for irAE+ patients and 2.1 months for irAE- patients (P = .0004), and the median OS was 12.5 and 6.8 months, respectively (P = .007). Experiencing 1 or more irAEs remained associated with ORR (P = .03), PFS (P = .003), and OS (P = .004) in multivariate analyses. The association between development of irAEs and prolonged OS persisted in a 22-week landmark analysis (P = .049). The association between development of irAEs and favorable outcomes was verified in cohort 2. CONCLUSIONS: The development of irAEs was strongly associated with an ICI benefit, including overall response, PFS, and OS, in 2 separate cohorts of patients with recurrent/metastatic HNC.
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Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Recurrencia Local de Neoplasia , Supervivencia sin Progresión , Estudios RetrospectivosRESUMEN
The term "oligometastatic prostate cancer" refers to a heterogeneous group of disease states currently defined solely on the basis of clinical features. Oligorecurrent disease, de novo oligometastases, and oligoprogressive disease likely have unique biologic underpinnings and natural histories. Evidence suggesting the existence of a subset of patients who harbor prostate cancer with limited metastatic potential currently includes disparate and overwhelmingly retrospective reports. Nevertheless, emerging prospective data have corroborated the "better-than-expected," retrospectively observed outcomes, particularly in the setting of oligorecurrent prostate cancer. Improved functional imaging with prostate-specific membrane antigen-targeted strategies may enhance the identification of patients with oligometastatic prostate cancer in the short term. In the long term, refinement of the oligometastatic case definition likely will require biologic risk-stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis-directed therapy, future efforts should focus on conducting high-quality, prospective trials with much-needed molecular correlative studies.
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Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Humanos , Masculino , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/terapia , Resultado del TratamientoRESUMEN
PURPOSE: CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor). PATIENTS AND METHODS: This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies. SBRT was delivered to 1-4 metastases with nivolumab+urelumab or nivolumab+cabiralizumab given concurrently and following SBRT. Dose-limiting toxicity (DLT) was the primary endpoint with anatomic location-specific SBRT doses deemed safe if ≤33% DLT frequency was observed. Secondary endpoints included RECISTv1.1 response, progression-free survival (PFS), overall survival (OS), and molecular correlative studies. RESULTS: Sixty patients were enrolled, and median follow-up for living patients is 13.8 months. Of these, 23 (38%) received SBRT+nivolumab+urelumab and 37 (62%) received SBRT+nivolumab+cabiralizumab. Seven patients (12%) experienced a DLT (n = 3 grade 3, n = 4 grade 4) in the following anatomic cohorts: abdominal/pelvic (3/17, 18%), liver (1/13, 8%), central lung (2/14, 14%), and peripheral lung (1/12, 8%). Of 41 patients radiographically evaluable for best overall response including 55 radiated and 23 unirradiated RECIST target lesions, 2 had complete responses (5%), 7 had partial responses (17%), 12 had stable disease (29%), and 20 had progression (49%). Median estimated PFS and OS are 3.0 months [95% confidence interval (CI), 2.9-4.8] and 17.0 months (95% CI, 6.8-undetermined), respectively. No patients with elevated pre-SBRT serum IL8 experienced a response. CONCLUSIONS: SBRT to ≤4 sites with nivolumab+urelumab or nivolumab+cabiralizumab for treating advanced solid tumors is feasible with acceptable toxicity and modest antitumor activity.See related commentary by Rodriguez-Ruiz et al., p. 5443.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias , Nivolumab , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Estadificación de Neoplasias , Neoplasias/patología , Neoplasias/terapia , Nivolumab/uso terapéutico , Resultado del TratamientoRESUMEN
Historical theories of metastasis have been informed by the seed and soil hypothesis, the Halsteadian paradigm proposing an orderly spread from local to distant sites, and the presumption that cancer is an inherently systemic process even in the earliest cases. The more contemporary spectrum theory now suggests that the propensity for distant spread exists along a continuum of metastatic virulence. Tumors with limited metastatic potential represent one subset along this spectrum that could potentially be cured with local ablative therapy. Integrating clinical and molecular features to biologically inform the classification of not only oligometastatic or oligoprogressive disease but also the entire metastatic spectrum holds great promise to improve prognostication and inform clinical decision making. To this end, the inclusion of molecular correlative studies and biospecimen collection on prospective protocols is imperative.
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Biomarcadores de Tumor/análisis , Metástasis de la Neoplasia/diagnóstico , Neoplasias/diagnóstico , Toma de Decisiones Clínicas , Progresión de la Enfermedad , Humanos , Oncología Médica/métodos , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/terapia , Neoplasias/mortalidad , Neoplasias/patología , Neoplasias/terapia , Pronóstico , Medición de Riesgo/métodosRESUMEN
Anterior skull base tumors represent a challenge for radiation therapy (RT) planning given the close proximity of the target lesion to numerous critical structures in this complex anatomic location. Despite this challenge, surgery followed by postoperative RT is a common treatment paradigm for malignant sinonasal tumors that has been associated with improved outcomes compared to single-modality treatment. Therefore, technological advancements allowing for increasingly conformal target coverage and sparing of organs at risk are important to accomplish the goal of delivering RT with the highest therapeutic ratio possible. Such advances include both intensity-modulated RT and volumetric-modulated arc therapy, which allow RT to be delivered more precisely than ever before. Furthermore, stereotactic radiosurgery can deliver highly conformal doses of external beam RT in a single or limited number of fractions for the definitive or postoperative management of benign lesions of the anterior base of the skull. These sophisticated photon-based RT strategies have allowed for exciting advances in the contemporary treatment of anterior skull base tumors that will continue to improve patient outcomes and reduce toxicity for years to come.
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Terapia de Protones , Radioterapia/métodos , Neoplasias de la Base del Cráneo/radioterapia , Humanos , Terapia de Protones/efectos adversos , Radiocirugia , Radioterapia/efectos adversos , Radioterapia de Intensidad ModuladaRESUMEN
PURPOSE: To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT). METHODS AND MATERIALS: Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ2 test, or Fisher's exact test as appropriate. RESULTS: Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05). CONCLUSIONS: Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.
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Alphapapillomavirus/fisiología , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/virología , Dosis de Radiación , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/uso terapéutico , Deglución/efectos de la radiación , Supervivencia sin Enfermedad , Nutrición Enteral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/tratamiento farmacológico , Neoplasias Orofaríngeas/fisiopatología , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
Locally recurrent head and neck malignancies after definitive radiation or chemoradiation represent challenging clinical scenarios requiring careful consideration of individualized risks and benefits before deciding upon the next best course of therapy. Herein, a case-based approach to personalized decision making highlights the expert opinions of leaders in head and neck oncology. Topics of interest include optimal candidacy for reirradiation or salvage surgical resection, the judicious use of chemotherapy as induction therapy or as a radiosensitizing agent, the incorporation of immunotherapy into the treatment paradigm for locally recurrent disease, and the impact of various treatment modalities on quality of life and functional outcomes. Interestingly, the lack of consensus among the experts on topics as fundamental as the appropriateness of offering reirradiation at all and as nuanced as target volume delineation for the reirradiated field suggests that there is no straightforward approach in this scenario. Common to all opinions is a desire to maximize the therapeutic ratio for a patient potentially facing a grim prognosis, and honest discussions about goals of care and expectations for post-treatment quality of life should be central to the clinical approach to this and similar cases.
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Reirradiación/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Toma de Decisiones , Humanos , Recurrencia Local de Neoplasia/radioterapia , Calidad de Vida , Dosificación Radioterapéutica , Reirradiación/efectos adversos , Terapia RecuperativaRESUMEN
OBJECTIVES: Adjuvant chemotherapy is routinely offered post-surgical resection for early stage non-small-cell lung cancer (NSCLC) ≥4 cm; however, its role following definitive stereotactic body radiotherapy (SBRT) has not been well defined. We investigated the association between receipt of adjuvant chemotherapy post-SBRT and overall survival (OS) for patients with T1-T3N0M0 NSCLC in the National Cancer Database (NCDB). MATERIALS AND METHODS: The NCDB was queried for patients with T1-T3N0M0 NSCLC treated with definitive SBRT from 2004 to 2014. The association between non-randomized receipt of adjuvant chemotherapy and OS was analyzed for all patients (n = 24,011) and a propensity-matched cohort (n = 608) using Kaplan-Meier methods and Cox proportional hazard models. A subset analysis was performed for patients with tumors ≥4 cm (n = 2,323). RESULTS: There were 24,011 patients in the cohort with a median follow-up of 32.5 months. Of these, 322 (1.3%) received adjuvant chemotherapy. Three-year OS was 41.3% with adjuvant chemotherapy compared to 50.6% without adjuvant chemotherapy (p = 0.001). On multivariate analysis, adjuvant chemotherapy was independently associated with higher overall mortality (hazard ratio:1.22, 95% confidence interval:1.06-1.40, p = 0.005). For tumors ≥4 cm, 3-year OS was 38.2% with adjuvant chemotherapy (n = 80) compared to 33.0% without adjuvant chemotherapy (p = 0.81). After propensity-score matching, there was a persistent association between lower OS and adjuvant chemotherapy with those receiving adjuvant chemotherapy (n = 322) having 3-year OS of 41.3% compared to 60.9% without adjuvant chemotherapy (p < 0.0001). CONCLUSION: Adjuvant chemotherapy following definitive SBRT for T1-3N0M0 NSCLC is associated with lower OS and is not associated with a survival benefit for patients with tumors ≥4 cm.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioterapia Adyuvante/métodos , Neoplasias Pulmonares/terapia , Radiocirugia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Supervivencia , Carga Tumoral , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Preclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy. We hypothesized that radiation (RT) + immunotherapy would associate with improved overall survival (OS) compared to immunotherapy or chemotherapy alone for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC). METHODS: The National Cancer Database was queried for patients with stage IV NSCLC receiving chemotherapy or immunotherapy from 2013 to 2014. RT modality was classified as stereotactic radiotherapy (SRT) to intra- and/or extracranial sites or non-SRT external beam RT (EBRT). OS was analyzed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: In total, 44,498 patients were included (13% immunotherapy, 46.8% EBRT, and 4.7% SRT). On multivariate analysis, immunotherapy (hazard ratio [HR]:0.81, 95% confidence interval [CI]:0.78-0.83) and SRT (HR:0.78, 95%CI:0.70-0.78) independently associated with improved OS; however, the interaction term for SRT + immunotherapy was insignificant (p = 0.89). For immunotherapy patients, the median OS for no RT, EBRT, and SRT was 14.5, 10.9, and 18.2 months, respectively (p < 0.0001), and EBRT (HR:1.37, 95%CI:1.29-1.46) and SRT (HR:0.78, 95%CI:0.66-0.93) associated with OS on multivariate analysis. In the SRT subset, median OS for immunotherapy and chemotherapy was 18.2 and 14.3 months, respectively (p = 0.004), with immunotherapy (HR:0.82, 95%CI:0.69-0.98) associating with OS on multivariate analysis. Furthermore, for patients receiving SRT, biologically effective dose (BED) > 60 Gy was independently associated with improved OS (HR:0.79, 95%CI:0.70-0.90, p < 0.0001) on multivariate analysis with a significant interaction between BED and systemic treatment (p = 0.008). CONCLUSIONS: Treatment with SRT associated with improved OS for patients with metastatic NSCLC irrespective of systemic treatment. The high survival for patients receiving SRT + immunotherapy strongly argues for evaluation in randomized trials.
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Adenocarcinoma/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Bases de Datos Factuales , Inmunoterapia/mortalidad , Neoplasias Pulmonares/mortalidad , Radiocirugia/mortalidad , Planificación de la Radioterapia Asistida por Computador/métodos , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Tasa de Supervivencia , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0194234.].
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BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported. MATERIALS AND METHODS: 52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded. RESULTS: Median follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively. CONCLUSIONS: In this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.
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Neoplasias del Ano/etiología , Neoplasias del Ano/terapia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/mortalidad , Neoplasias del Ano/patología , Quimioradioterapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC. MATERIALS AND METHODS: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75â¯Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test. RESULTS: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7â¯years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (Pâ¯=â¯0.90), DC (Pâ¯=â¯0.24), PFS (Pâ¯=â¯0.38), OS (Pâ¯=â¯0.10), or ORN (Pâ¯=â¯0.38) were not significant across treatment decades. CONCLUSION: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.
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Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Neoplasias de la Boca/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/fisiopatología , Nutrición Enteral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/fisiopatología , Análisis de SupervivenciaAsunto(s)
Anetodermia , Exantema , Proteínas de Neoplasias/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Anetodermia/inducido químicamente , Apoptosis , Exantema/inducido químicamente , HumanosAsunto(s)
Neoplasias/patología , Neoplasias/terapia , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Análisis de SupervivenciaAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Cuidados Paliativos/métodos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Terapia Combinada/métodos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Metástasis de la NeoplasiaAsunto(s)
Médicos Mujeres , Oncología por Radiación , Sexismo , Docentes Médicos/economía , Docentes Médicos/estadística & datos numéricos , Femenino , Humanos , Internado y Residencia/estadística & datos numéricos , Médicos Mujeres/economía , Médicos Mujeres/estadística & datos numéricos , Médicos Mujeres/tendencias , Oncología por Radiación/economía , Oncología por Radiación/estadística & datos numéricos , Oncología por Radiación/tendencias , Salarios y Beneficios , Países Escandinavos y Nórdicos , Sexismo/economía , Sexismo/prevención & control , Sexismo/estadística & datos numéricos , Sexismo/tendencias , Estados Unidos , Derechos de la MujerRESUMEN
BACKGROUND: The optimal clinical context for initiation of salvage androgen deprivation therapy (SADT) following the biochemical recurrence of localized prostate cancer remains controversial. We chose to investigate if disease burden at time of SADT initiation is associated with clinical outcomes following biochemical failure (BF) post-salvage radiation therapy (SRT). METHODS: Medical records of 575 patients receiving SRT at a single institution from 1986-2010 were retrospectively reviewed. Of 250 patients experiencing BF post-SRT, 172 had a calculable prostate-specific antigen doubling time (PSADT) prior to SADT initiation. These patients comprise the analyzed cohort and were divided into four groups based on characteristics at SADT initiation: those with PSADTs >3 months without distant metastasis (DM) (group 1 [less advanced disease], n=62), those with PSADTs <3 months without DM (group 2 [more advanced disease], n=28), those with DM (group 3 [more advanced disease], n=32), and those not receiving SADT during follow-up (group 4, n=50). Endpoints included prostate cancer-specific mortality (PCSM) and overall mortality (OM). Kaplan-Meier methods were used to estimate survival, and Cox proportional hazards models were used for multivariate analysis. RESULTS: Median follow-up post-SRT was 7.9 years. Patients starting SADT with more advanced disease were at significantly increased risk for PCSM (hazard ratio [HR]:2.8, 95% confidence interval [CI]: 1.4-5.6, p=0.005) and OM (HR:1.9, 95% CI: 1.0-3.5, p=0.04) compared to those receiving SADT with less advanced disease. PCSM and OM did not significantly differ between groups 1 and 4 or groups 2 and 3. Of note, patients in group 4 had very long PSADTs (median = 27.0 months) that were significantly longer than those of group 1 (median = 6.0 months) (p<0.001). Multivariate analysis including groups 1-3 found a pre-SADT PSADT <3 months to be the most significant predictor of PCSM (HR:4.2, 95% CI: 1.6-11.1, p=0.004) and the only significant predictor of OM (HR:2.9, 95% CI: 1.3-6.7, p=0.01). CONCLUSIONS: Less advanced disease at initiation of SADT is associated with decreased PCSM and OM following BF post-SRT; however, observation may be reasonable for patients with very long PSADTs. A PSADT <3 months prior to SADT initiation significantly predicts an increased risk of PCSM and OM in this patient demographic.