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BACKGROUND: In select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA-sequencing (RNA-seq) expression is a robust method for predicting overall survival (OS) and distant metastasis-free survival (DMFS) in patients with resected pancreatic adenocarcinoma. METHODS: Utilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I-III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA-seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA-seq via multivariable models and receiver operator characteristic curves. RESULTS: In TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00-2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87-2.03; p = .19). Low SMAD4 RNA-seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17-2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14-2.54; p = .009). In the ICGC, increased SMAD4 RNA-seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86-.94) and DMFS (AUC, .84; 95% CI, .82-.87). CONCLUSIONS: In patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA-seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA-seq expression may be a useful marker to predict metastatic spread.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Proteína Smad4/genética , Modelos de Riscos Proporcionais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , PrognósticoRESUMO
BACKGROUND: The NCCN Guidelines for Prostate Cancer currently recommend several definitive radiotherapy (RT) options for men with unfavorable intermediate-risk (UIR) prostate cancer: external-beam RT (EBRT) plus androgen deprivation therapy (ADT) or EBRT plus brachytherapy boost with or without ADT. However, brachytherapy alone with or without ADT is not well defined and is currently not recommended for UIR prostate cancer. We hypothesized that men treated with brachytherapy with or without ADT have comparable survival rates to men treated with EBRT with or without ADT. METHODS: A total of 31,783 men diagnosed between 2004 and 2015 with UIR prostate cancer were retrospectively reviewed from the National Cancer Database. Men were stratified into 4 groups: EBRT (n=12,985), EBRT plus ADT (n=12,960), brachytherapy (n=4,535), or brachytherapy plus ADT (n=1,303). Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances, and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios (HRs). RESULTS: Relative to EBRT alone, the following treatments were associated with improved OS: EBRT plus ADT (HR, 0.92; 95% CI, 0.87-0.97; P=.002), brachytherapy alone (HR, 0.90; 95% CI, 0.83-0.98; P=.01), and brachytherapy plus ADT (HR, 0.78; 95% CI, 0.69-0.88; P=.00006). Brachytherapy correlated with improved OS relative to EBRT in men who were not treated with ADT (HR, 0.92; 95% CI, 0.84-0.99; P=.03) and in those receiving ADT (HR, 0.84; 95% CI, 0.75-0.95; P=.004). At 10-year follow-up, 56% and 63% of men receiving EBRT and brachytherapy, respectively, were alive (P<.0001). IPTW was used to determine the average treatment effect of definitive brachytherapy. Relative to EBRT, definitive brachytherapy correlated with improved OS (HR, 0.90; 95% CI, 0.84-0.97; P=.009) on weight-adjusted MVA. CONCLUSIONS: Definitive brachytherapy was associated with improved OS compared with EBRT. The addition of ADT to both EBRT and definitive brachytherapy was associated with improved OS. These results suggest that definitive brachytherapy should be considered as an option for men with UIR prostate cancer.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Braquiterapia/métodos , Neoplasias da Próstata/terapia , Antagonistas de Androgênios/uso terapêutico , Estudos Retrospectivos , Modelos de Riscos ProporcionaisRESUMO
A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.
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Degeneração Macular/genética , Proteínas/genética , Serina Endopeptidases/genética , Idoso , Estudos de Casos e Controles , Cromossomos Humanos Par 10/genética , Estudos de Coortes , Ensaios Enzimáticos , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Haplótipos/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Luciferases/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único/genética , Proteínas/metabolismo , Serina Endopeptidases/metabolismo , UtahRESUMO
Objectives: Radiation therapy (RT) is an integral part of treatment of head/neck cancer (HNC) but is associated with many toxicities. We sought to evaluate sociodemographic, pathologic, and clinical factors associated with emergency department (ED) visits, hospital admissions (HA), and RT breaks in HNC patients undergoing curative-intent RT. Methods: We completed a Level 3 (Oxford criteria for evidence-based medicine) analysis of a cohort of HNC patients who underwent curative-intent RT at our institution from 2013 to 2017. We collected demographic characteristics and retrospectively assessed for heavy opioid use, ED visits or HA during RT as well as RT breaks. Treatment breaks were defined as total days to RT fractions ratio ≥1.6. Multivariable stepwise logistic regression analyses were done to determine the association of various sociodemographic, pathologic, and clinical characteristics with ED visits, HA and RT treatment breaks. Results: The cohort included 376 HNC patients (294 male, 82 female, median age 61). On multivariable analysis, significant factors associated with ED visits during RT were heavy opioid use and black race. Receipt of concomitant chemotherapy was the only factor associated with hospital admissions during RT. Advanced age, lower socioeconomic class, glandular site, and receipt of chemotherapy were all independently associated with RT breaks. Lower cancer stage and lack of substance abuse history were independently associated with lack of treatment breaks. Conclusion: HNC patients with factors such as heavy opioid use, Black race, receipt of concomitant chemotherapy, and lower socioeconomic class may require closer monitoring during RT.
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BACKGROUND: Definitive treatment options for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost ± androgen deprivation therapy (ADT). The role of brachytherapy ± ADT in the absence of EBRT is not well defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to BT±ADT for UIR-PCa. METHODS AND MATERIALS: Men with UIR-PCa diagnosed between 2004 and 2015 were identified in the National Cancer Database (NCDB). Inverse propensity of treatment weighting was used to balance covariables that influenced treatment allocation and outcomes, and propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare OS hazard ratios. RESULTS: A total of 11,721 men were stratified into four treatment groups: (1) BT without ADT (nâ¯=â¯4,535), (2) BT+ADT (nâ¯=â¯1,303), (3) EBRT+BT (nâ¯=â¯3,446), or (4) EBRT+BT+ADT (nâ¯=â¯2,437). Relative to patients treated with BT alone, BT+ADT (Hazard Ratio (HR): 0.86 [95% Confidence Interval (CI): 0.76-0.99], pâ¯=â¯0.03), EBRT+BT (HR: 0.79 [0.70-0.88], pâ¯=â¯0.00002), and EBRT+BT+ADT (HR: 0.76 [0.67-0.85], pâ¯=â¯0.000003) were associated with improved OS on MVA. Relative to BT alone, EBRT+BT correlated with improved OS on weight-adjusted MVA (HR: 0.82 [0.75-0.89], pâ¯=â¯0.000005). 10-year OS for BT vs. EBRT+BT was 62.4% [60.1-64.7] vs. 69.3% [67.5-71.2], respectively (p <â¯0.0001). CONCLUSIONS: EBRT+BT correlated with improved OS relative to BT alone in men with UIR-PCa, reaffirming current NCCN recommendations recommending EBRT+BT over BT alone. While prior studies reported no benefit to adding EBRT to BT with optimal implant dosimetry, this study suggests men benefit from EBRT in a population of variable implant quality.
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Braquiterapia , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Braquiterapia/métodos , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Objective The objective of this study is to contrast the predictive ability of targeted muscle groups as radiographic proxies of sarcopenia on computerized tomography (CT) with body mass index (BMI) in head and neck cancer patients (H&NCP) undergoing radiation at a safety net hospital, and to evaluate sarcopenia with survival, local progression, toxicities and treatment delays. Methods A retrospective review included 52 H&NCP treated between 2017-2019. The posterior neck muscles (PN), sternocleidomastoids (SCM), and their summed volume (AM) were contoured at C3 on patients' pre-treatment CT scans, then normalized to obtain skeletal muscle index (MI) values. Pre-treatment BMI was also evaluated. Cutoffs for sarcopenia were determined by receiver operating characteristic curves. Overall survival and local recurrence-free survival were evaluated by Kaplan-Meier. Acute grade 3 or higher toxicities were evaluated by binomial logistic regression. Results Using all neck muscles (AM-MI) produced the best model for predicting outcomes, outperforming individual muscle groups and BMI. Local progression-free survival was worse in sarcopenic patients at 25.81 months versus 35.40 months (p=0.026). Acute grade 3 or higher toxicities were associated with sarcopenia (p=0.005). Conclusions In this small, retrospective single-institution experience at a safety net hospital, a single axial slice of the combined sternocleidomastoids and paravertebral muscles at C3 performed better than either muscle group alone or pre-treatment BMI at predicting oncologic outcomes.
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BACKGROUND: The site of prostate cancer metastasis is an important predictor of oncologic outcomes, however, the clinicogenomic characteristics associated with the site are not well-defined. Herein, we characterize the genomic alterations associated with the metastatic site of prostate cancer. METHODS: We analyzed clinical and genomic data from prostate cancer patients with metastatic disease and known metastatic sites from publicly available targeted sequencing data. RESULTS: Prostate cancer metastasis to the liver versus other sites of metastasis conferred a high hazard for death in patients with metastatic prostate cancer (HR: 3.96, 95% CI: 2.4-6.5, p < 0.0001). Genomic analysis of metastatic tissues of prostate cancer-specific genes demonstrated that liver metastases were more enriched with MYC amplification (29.5% vs. 9.8%, FDR = 0.001), PTEN deletion (42% vs. 20.8%, FDR = 0.005), and PIK3CB amplification (8.2% vs. 0.9, FDR = 0.005) compared to other sites. No point mutations were significantly associated with liver metastasis compared to other metastatic sites. CONCLUSION: Liver metastases in prostate cancer are associated with poor survival and aggressive genomic features, including MYC-amplification, PTEN-deletion, and PIK3CB-amplification. These findings could have prognostic, treatment, and trial implications.
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Neoplasias Hepáticas , Neoplasias da Próstata , Humanos , Neoplasias Hepáticas/genética , Masculino , Prognóstico , Próstata/patologia , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Current recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa. MATERIALS AND METHODS: The National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (nâ¯=â¯13,265), EBRT+ADT (nâ¯=â¯13,123), EBRT+BT (nâ¯=â¯3440), or EBRT+BT+ADT (nâ¯=â¯2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios. RESULTS: Median follow-up was 60 months (range: 3-168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.98], pâ¯=â¯0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69-0.85], pâ¯=â¯3â¯×â¯10-7) and EBRT+BT+ADT (HR: 0.75 [0.67-0.83], pâ¯=â¯6â¯×â¯10-8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, pâ¯=â¯0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87-1.11], pâ¯=â¯0.82). CONCLUSIONS: In a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.
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Braquiterapia , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Braquiterapia/métodos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Estudos RetrospectivosRESUMO
BACKGROUND: Prostate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in ≤5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; â¼44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) versus CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa). METHODS: Men with UIR-PCa treated with SBRT (35-40Gy in ≤5 fractions) or biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (≥60Gy in 2.4-3.2Gy/fraction; biologically effective doses ≥120) were identified in the National Cancer Database (NCDB). Unweighted and propensity-weighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios. RESULTS: Of 28,028 men with UIR-PCa who received CFRT with (n = 12,872) or without ADT (n = 12,984); MFRT with (n = 251) or without ADT (n = 281); and SBRT with (n = 212) or without ADT (n = 1,428) were identified. Relative to CFRT without ADT, CFRT+ ADT (HR 0.92, 95% CI 0.87-0.97, P = .002) and SBRT without ADT (HR 0.74, 95% CI 0.61-0.89, P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95% CI 0.67-0.99, P = .04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95% CI 0.65-0.98, P = .036) and ADT (HR:0.91, 95% CI 0.86-0.97, P = .002) correlated with improved OS. SBRT was not associated with improved OS versus MFRT. CONCLUSION: SBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS versus CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials.
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COVID-19 , Neoplasias da Próstata , Radiocirurgia , Antagonistas de Androgênios/uso terapêutico , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Radiocirurgia/métodos , Estudos Retrospectivos , Análise de SobrevidaRESUMO
There are limited data on the role of local therapy for metastatic urothelial carcinoma of the bladder (mUC). In this retrospective cohort analysis, we queried the National Cancer Data Base for patients with newly diagnosed mUC (cT1-4 N0-3 M1). Overall survival (OS) was compared between treatment with chemotherapy (CT) alone (n = 4122) and CT plus bladder-directed radiation therapy (CT + RT; n = 337). Multivariable Cox proportional-hazards analyses and matching and landmark analyses were performed. CT + RT was independently associated with better OS (hazard ratio 0.70, 95% confidence interval 0.62-0.79; p < 0.0001) and this result persisted in matched and landmark analyses. These findings are hypothesis-generating and limited by inherent confounding factors; however, a prospective trial evaluating the impact of bladder RT in mUC is warranted. PATIENT SUMMARY: For patients with bladder cancer that has already spread to other parts of the body, it is unclear if radiation therapy directed at the primary bladder tumor would provide any improvement in survival. In this study, we found that aggressive radiation therapy directed at the bladder combined with chemotherapy may provide a survival benefit in some patients with metastatic bladder cancer compared to chemotherapy alone.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/radioterapia , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapiaRESUMO
PURPOSE: This study seeks to characterize magnetic resonance imaging (MRI) changes following stereotactic radiosurgery (SRS) of pediatric brain malignancies. METHODS: Serial MRI evaluations were performed on 21 lesions treated with SRS for either medulloblastoma (n=12), juvenile pilocytic astrocytoma (n=4), ependymoma (n=2), atypical rhabdoid teratoid tumor (n=2), or pineocytoma (n=1). Prescription doses ranged from 14 to 30 Gy in one to five fractions. Tumor response was qualified as complete (CR), partial (PR), stable disease (SD), or progressive disease (PD) according to the RECIST v1.1. Median radiographic follow-up after SRS was 17 months. RESULTS: A total of 80 follow-up MRI scans were reviewed with a median of eight per patient. During serial MRI evaluation, eight lesions met criteria for PD at a median of 6 months. However, of these, three (37%) represented transient tumor edema with two lesions later developing a CR at a median of 15 months and one persisting as SD at 12 months. The remaining five lesions were true local failures. Of the 13 lesions that did not show evidence of PD, a CR was obtained in 11 lesions at a median of 3 months (range, 2-6), and SD was seen in the remaining two tumors at last follow-up. CONCLUSION: Lesion enlargement following SRS for pediatric intracranial tumors is common, and a proportion of patients meeting requirements for PD at early radiographic follow-up may later develop complete resolution of their lesions. Physicians should be aware of these radiographic changes to avoid unwarranted medical and surgical interventions.
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Neoplasias Encefálicas/cirurgia , Encéfalo/cirurgia , Glioma/cirurgia , Radiocirurgia/métodos , Adolescente , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Although proton beam therapy (PBT) is a rapidly expanding modality to treat prostate cancer compared with intensity modulated radiation therapy (IMRT), data comparing disease control outcomes and patterns of failure in the postprostatectomy setting remain substantially limited. METHODS AND MATERIALS: All patients who underwent postoperative IMRT or PBT to the prostate bed only at a single institution were included (2009-2017). Endpoints included biochemical failure (BF; using institutional and recent cooperative group trial definitions), local failure (LF), regional failure (RF), distant failure (DF), and all-cause mortality. A case-matched cohort analysis was performed using 3-to-1 nearest-neighbor matching; multivariable Cox proportional hazards modeling (MVA) estimated hazard ratios for disease-related outcomes by treatment modality. RESULTS: Of 295 men, 260 were matched (n = 65 PBT, 195 IMRT); after matching, only age at diagnosis (P < .01) significantly differed between cohorts. At a median follow-up of 59 months, BF (institution-defined), LF, RF, DF, and mortality rates were 45% (n = 29), 2% (n = 1), 9% (n = 6), 9% (n = 6), and 2% (n = 1) for PBT, and 41% (n = 80), 3% (n = 5), 7% (n = 13), 9% (n = 18), and 5% (n = 9) for IMRT (all P > .05). RT modality was not significantly associated with BF on MVA using institutional or cooperative group definitions (all P > .05), nor with LF (P = .82), RF (P = .11), DF (P = .36), or all-cause mortality (P = .69). Patterns of failure were qualitatively similar between cohorts (DF: bone, retroperitoneal nodes, lung). CONCLUSIONS: In this single institution, case-matched analysis, PBT yielded similar long-term disease-related outcomes and patterns of failure to IMRT in the postprostatectomy setting.
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Neoplasias da Próstata , Terapia com Prótons , Radioterapia de Intensidade Modulada , Estudos de Coortes , Humanos , Masculino , Período Pós-Operatório , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgiaRESUMO
OBJECTIVES: To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy. MATERIALS AND METHODS: This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy]. RESULTS: Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004). CONCLUSION: In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.
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Neoplasias Orofaríngeas , Infecções por Papillomavirus , Procedimentos Cirúrgicos Robóticos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Alphapapillomavirus , Humanos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologiaRESUMO
BACKGROUND: The significance of perineural invasion (PNI) in prostate cancer (PC) is unclear. A recent report of patients with pT2N0R0 PC found that PNI at prostatectomy was independently associated with higher Gleason score and more diffuse prostatic disease. We aimed to test our hypothesis that PNI on prostate biopsy in pT2N0R0 patients is associated with increased Gleason score upgrading at prostatectomy. METHODS: We identified 2892 patients status post prostatectomy with pT2N0R0 PC from three institutions, diagnosed between 1 January 2008 and 31 December 2014. Multivariable logistic regression (MVA) was used to evaluate the association between prostate biopsy PNI status and surgical Gleason upgrading, while controlling for potential confounders. RESULTS: Of the 2892 patients identified, 14% had PNI on biopsy, of whom 21% had surgical Gleason upgrading, while 28% without PNI on biopsy had such upgrading (P < .01). On MVA, the odds ratio (OR) of surgical Gleason upgrading for patients with biopsy PNI relative to patients without biopsy PNI was 0.69 (P < .01). The variables associated with surgical Gleason upgrading were age ≤60 years (OR 1.22, P = .02) and preoperative PSA >4 ng/mL (OR 1.26, P = .02). CONCLUSIONS: In post-prostatectomy patients with favorable-risk PC, PNI on prostate biopsy was not associated with surgical Gleason score upgrading. This may be due to the association of PNI with more diffuse disease, leading to increased biopsy tumor yield and grading accuracy. These findings suggest that in this setting, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision-making for men debating active surveillance, radiation, and surgery.
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Adenocarcinoma/patologia , Nervos Periféricos/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Adenocarcinoma/cirurgia , Idoso , Biópsia com Agulha de Grande Calibre , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Neoplasias da Próstata/cirurgiaRESUMO
BACKGROUND: Reliability refers to the precision of an assessment, so it is a critical topic to take the right decisions related to health management. People usually perform several tasks at the same time in their daily life. The aim of this study was to examine the reliability of the 30-s chair stand test in people with type 2 Diabetes Mellitus (T2DM) with test-retest, with and without dual-task (motor + cognitive task). METHODS: Twenty-six subjects with T2DM and 30 subjects without T2DM performed the 30-s Chair Stand Test (30sCST) in which they must sit and stand as many times as possible in 30 s. They performed the test in the usual way (30sCST) and also with an additional cognitive task (30sCST-DT). A retest was conducted 7-14 days later. RESULTS: Relative reliability was excellent in both groups (intraclass correlation coefficient > 0.9). In 30sCST-DT, relative reliability was high in the T2DM group (intraclass correlation coefficient > 0.7) and excellent in subjects without T2DM (intraclass correlation coefficient > 0.9). CONCLUSIONS: The 30sCST and the 30sCST-DT tests are reliable tools for people with T2DM to measure changes after an intervention. The smallest real difference was 15% and 20% upper in the T2DM group in the 30sCST and 30sCST-DT tests, respectively.
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Cognição , Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Esforço/normas , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
Radiation therapy plays a significant role in management of benign and malignant diseases of the central nervous system. Patients may be at risk of acute and late toxicity from radiation therapy due to dose deposition in critical normal structures. In contrast to conventional photon delivery techniques, proton therapy is characterized by Bragg peak dose deposition which results in decreased exit dose beyond the target and greater sparing of normal structure which may reduce the rate of late toxicities from treatment. Dosimetric studies have demonstrated reduced dose to normal structures using proton therapy as compared to photon therapy. In addition, clinical studies are being reported demonstrating safety, feasibility, and low rates of acute toxicity. Technical challenges in proton therapy remain, including full understanding of depth of proton penetration and the biological activity in the distal Bragg peak. In addition, longer clinical follow-up is required to demonstrate reduction in late toxicities as compared to conventional photon-based radiation techniques. In this review, we summarize the current clinical literature and areas of active investigation in proton therapy for adult central nervous system malignancies.
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Neoplasias do Sistema Nervoso Central/radioterapia , Terapia com Prótons/métodos , Adulto , HumanosRESUMO
INTRODUCTION: Squamous cell carcinoma (SqCC) is the second most common histology of primary bladder cancer, but still very limited information is known about its treatment outcomes. Most bladder cancer trials have excluded SqCC, and the current treatment paradigm for localized SqCC is extrapolated from results in urothelial carcinoma (UC). In particular, there is limited data on the efficacy of definitive chemo-radiotherapy (CRT). In this study, we compare overall survival outcomes between SqCC and UC patients treated with definitive CRT. MATERIALS/METHODS: We queried the National Cancer Database (NCDB) for muscle-invasive (cT2-T4 N0 M0) bladder cancer patients diagnosed from 2004 to 2013 who underwent concurrent CRT. Propensity matching was performed to match patients with SqCC to those with UC. OS was analyzed using the Kaplan-Meier survival method, and the log-rank test and Cox regression were used for analyses. RESULTS: 3332 patients met inclusion criteria of which 79 (2.3%) had SqCC. 73.4% of SqCC patients had clinical T2 disease compared to 82.5% of UC patients. Unadjusted median OS for SqCC patients was 15.6â¯months (95% CI, 11.7-19.6) versus 29.1â¯months (95% CI, 27.5-30.7) for those with UC (Pâ¯<â¯0.0001). On multivariable analysis, factors associated with worse OS included: SqCC histology [HR: 1.53 (95% CI, 1.19-1.97); Pâ¯=â¯0.001], increasing age [HR: 1.02 (95% CI, 1.02-1.03); Pâ¯<â¯0.0001], increasing clinical T-stage [HR: 1.21 (95% CI, 1.13-1.29); Pâ¯<â¯0.0001], and Charlson-Deyo comorbidity index [HR: 1.26 (95% CI, 1.18-1.33); Pâ¯<â¯0.0001]. Seventy-seven SqCC patients were included in the propensity-matched analysis (154 total patients) with a median OS for SqCC patients of 15.1â¯months (95% CI, 11.1-18.9) vs. 30.4â¯months (95% CI, 19.4-41.4) for patients with UC (Pâ¯=â¯0.013). CONCLUSIONS: This is the largest study to-date assessing survival outcomes for SqCC of the bladder treated with CRT. In this study, SqCC had worse overall survival compared to UC patients. Histology had a greater impact on survival than increasing T-stage, suggesting that histology should be an important factor when determining a patient's treatment strategy and that treatment intensification in this subgroup may be warranted.
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BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P < 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted.
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Cuidados Pós-Operatórios , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Comorbidade , Cistectomia , Bases de Dados Factuais , Feminino , Humanos , Seguro Saúde , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Resultado do Tratamento , Neoplasias da Bexiga Urinária/epidemiologia , Adulto JovemRESUMO
Importance: Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. Objective: To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. Design, Setting, and Participants: This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Exposures: Receipt of adjuvant endocrine therapy. Main Outcomes and Measures: Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. Results: The primary study cohort comprised 10â¯173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961â¯676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P < .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P < .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P < .001) or chemotherapy (odds ratio, 1.20; 95% CI, 1.07-1.34; P < .001) were statistically significantly associated with adjuvant endocrine therapy use in men. A propensity score-weighted analysis indicated that relative to no use, adjuvant endocrine therapy use in men was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.63-0.77; P < .001). Conclusions and Relevance: There is a sex disparate underuse of adjuvant endocrine therapy among men with HR-positive breast cancer despite the use of this treatment being associated with improved overall survival. Further research and interventions may be warranted to bridge gaps in care in this population.
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Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama Masculina/tratamento farmacológico , Receptores de Esteroides/metabolismo , Adolescente , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama Masculina/metabolismo , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
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.