Publications by authors named "Brian A Costello"

Objectives: Choriocarcinoma is associated with high mortality in multiply relapsed patients. Herein, we assessed immunohistochemistry (IHC) expression of TROP2 and nectin-4 in choriocarcinoma and other germ cell tumors (GCT), as antibody drug conjugates (ADCs) targeting these markers are entering the therapeutic landscape of many tumors.

Methods: Archival cases of choriocarcinoma and controls (non-choriocarcinoma GCT) were evaluated for TROP2 and nectin-4 IHC, performed on whole-slide sections, and results were quantified using H-scores (range: 0-300) based on membranous staining.

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Context: Side effects from tyrosine kinase inhibitors (TKIs) are common and burdensome. Olanzapine is useful for managing symptoms from conventional chemotherapy, but its role in treating TKI-related side effects is unclear.

Objectives: Examine the efficacy of olanzapine for TKI-induced nausea, vomiting, anorexia, weight loss, and insomnia.

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Objective: To investigate the association between venous tumor thrombus (VTT) and the risk of pulmonary metastases in patients with clear cell renal cell carcinoma (ccRCC).

Methods: We queried our institutional registry for ccRCC patients undergoing radical nephrectomy (1970-2019). Cox proportional hazards regression models, adjusting for factors associated with ccRCC progression, were used to determine whether VTT was associated with pulmonary metastases.

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Purpose: The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.

Patients And Methods: A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network.

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Article Synopsis
  • Metastasis-directed spine SBRT has been shown to improve local control and overall survival in selected patients, with a focus on clinical and dosimetric factors influencing local failure rates.
  • A study analyzed 522 treatments, highlighting that a minimum dose of 15.3 Gy in single-fraction deliveries significantly improves local control, with local failure rates being lower when this dose is achieved.
  • Epidural and soft tissue involvement are significant predictors of local failure, emphasizing the importance of targeting and dosing in SBRT for better treatment outcomes.
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Article Synopsis
  • - Patients who had no evidence of disease (NED) after surgery for metastatic renal cell carcinoma (mRCC) were studied to see if pazopanib, a cancer medication, could improve their disease-free survival (DFS) compared to a placebo.
  • - The trial included 129 patients, and after thorough analysis, it found no significant difference in 3-year DFS rates between the pazopanib group (27.4%) and placebo group (21.9%).
  • - Additionally, the overall survival rate was better for the placebo group (91.4%) compared to pazopanib (81.9%), raising concerns about the drug's effectiveness and quality of life for patients on it.
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Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease.

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The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

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Navitoclax (ABT-263) is an oral BCL2 homology-3 mimetic that binds with high affinity to pro-survival BCL2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor also promotes apoptosis and inhibits tumor angiogenesis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib.

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Objectives: To assess the safety, technical success, disease progression, and survival associated with percutaneous image-guided cryoablation of renal cell carcinoma metastasis (mRCC) in the adrenal gland.

Methods: Retrospective, single-institution review of adult patients undergoing percutaneous cryoablation for adrenal mRCC between the years of 2007-2021. Technical parameters, technical success, safety, and survival were analyzed according to standard criteria.

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Background: The Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection as first-line treatment for patients with isolated 1-3 cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either chemotherapy or radiotherapy. Herein, we evaluated the relative cost-effectiveness of these management strategies.

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Introduction: Systemic immunotherapy has changed the paradigm of treatment of advanced renal cell carcinoma, but nephrectomy continues to benefit selected patients. While we continue to identify mechanisms behind drug resistance, the effect of surgery on natural anti-tumor immunity is poorly understood. Specifically, peripheral blood mononuclear cell (PBMC) profile and tumor reactive cytotoxic T lymphocytes changes secondary to tumor resection have not been extensively characterized.

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Purpose: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma. However, the relative contribution of histopathological features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma.

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Background: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments.

Patients And Methods: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution.

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Background: Though metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT.

Patients And Methods: We assembled a multi-institutional cohort of patients treated with MDT (stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy).

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Objective: Elevated serum chromogranin A (CGA) is associated with intrinsic or treatment-related neuroendocrine differentiation (NED) in men with metastatic castration-resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy.

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Deferred cytoreductive nephrectomy (dCN) after upfront systemic therapy has been utilized in the management of select patients with metastatic renal cell carcinoma (mRCC). Herein, we sought to review the current evidence and define oncologic and perioperative outcomes associated with deferred surgical management of newly diagnosed mRCC. Our objective was to critically evaluate the role of dCN in the targeted and immunotherapy eras, comparing oncologic and perioperative outcomes between dCN and upfront CN.

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Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved.

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Background: This study was aimed at developing and validating a decision-making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal metastases.

Methods: Three hundred sixty-one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT.

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Background: Surgical resection of metastatic renal cell carcinoma (mRCC) has been associated with better cancer-specific survival; however, high-quality data on its perioperative morbidity are lacking. Existing population-based data are severely limited by reliance on billing claims to identify outcomes, which may overestimate events owing to a lack of code specificity.

Objective: To study 30-d complications after metastasectomy for mRCC.

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Background: The VESPER trial demonstrated improved progression-free (PFS) and (preliminarily) overall survival (OS) with six cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVACx6) versus four cycles of gemcitabine and cisplatin (GCx4) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), but with increased toxicity. This study compares the cost-effectiveness of these regimens.

Methods: A cost-effectiveness analysis of neoadjuvant ddMVACx6 and GCx4 was performed using a decision-analytic Markov model with 5-year, 10-year, and lifetime horizons.

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Purpose: The KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab after nephrectomy for clear cell renal cell carcinoma decreased the risk of disease progression and potentially overall mortality as well. Herein, we used a Markov model to weigh the costs, toxicities, and efficacy of pembrolizumab to further investigate its utility.

Materials And Methods: Decision-analytic Markov modeling was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus observation after nephrectomy for high-risk clear cell renal cell carcinoma, using data from KEYNOTE-564 to inform model probabilities.

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Prostate cancer ranges from localized, low risk to metastatic, morbid disease. Although radiation therapy (RT) is commonly incorporated in the treatment of early disease or for palliation of symptomatic lesions, its role in extending survival in metastatic disease is less well-established. Here, we review the available evidence surrounding localized RT in the presence of oligometastatic disease and metastasis-directed therapy in both hormone-sensitive and hormone-resistant prostate cancer.

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Introduction And Objectives: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy.

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Article Synopsis
  • Second-generation antiandrogens have received multiple FDA approvals for treating specific subsets of prostate cancer, demonstrating their growing importance in clinical practice.
  • The review includes a comprehensive overview of phase II-III trials, alongside a rational sequencing strategy for using these agents in relation to chemotherapy and other treatments for advanced prostate cancer.
  • Recommendations based on current evidence suggest prioritizing abiraterone before chemotherapy, using chemotherapy after antiandrogen failure, and administering enzalutamide post-chemotherapy for select patients to enhance treatment effectiveness and tolerability.
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