Publications by authors named "Marc Matrana"

44 Publications

Utilization of Nivolumab in Adenoid Cystic Carcinoma After Progression on Platinum-Based Chemotherapy.

Perm J 2021 May;25

Ochsner Cancer Institute, New Orleans, LA.

Introduction: Adenoid cystic carcinoma (ACC) is a rare malignant neoplasm within the secretory glands of the head and neck. Clinical findings include a lump on the palate, tongue, or bottom of the mouth. Because symptoms can be mild, patients go for long periods of time without investigation. ACC is diagnosed using histology. Treatment is by surgical resection because there is no effective chemotherapy. Radiation can be effective adjuvant therapy, and proton therapy and stereotactic irradiation can be used for those who are ineligible for surgery. Immunotherapy has clinical activity for those with metastatic head and neck cancers who progress on proton therapy. This case reviews the use of immunotherapy in a patient with ACC.

Case Presentation: A man in his 20s presented with a 6-month history of nasal congestion, epistaxis, and sinus tenderness. Noncontrast computed tomography of the sinuses revealed a mass of the lateral wall of the nasal cavity, lateral wall of the maxillary sinus, and pterygoid plates. Positron emission tomography confirmed metastatic disease in the right iliac crest and right cervical lymph node; biopsy of the nasopharynx confirmed ACC. The patient received proton therapy and intensity-modulated radiotherapy and completed 2 Phase 1 trails but continued to have progressive disease. The patient started nivolumab and died 12 weeks later.

Conclusion: The patient recently received proton therapy, intensity-modulated radiotherapy, and completed 2 Phase 1 trials but continued to have progressive disease.
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http://dx.doi.org/10.7812/TPP/20.229DOI Listing
May 2021

COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials.

Nat Rev Clin Oncol 2021 05 15;18(5):313-319. Epub 2021 Mar 15.

Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active malignancies, and thus data on the safety, tolerability and efficacy of the vaccines in patients with cancer are currently limited. Given the risk posed by the COVID-19 pandemic, decisions regarding the use of vaccines against COVID-19 in patients participating in trials of investigational anticancer therapies need to be addressed promptly. Patients should not have to choose between enrolling on oncology clinical trials and receiving a COVID-19 vaccine. Clinical trial sponsors, investigators and treating physicians need operational guidance on COVID-19 vaccination for patients with cancer who are currently enrolled or might seek to enrol in clinical trials. Considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. Herein, we provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials. In our perspective, continued quality oncological care requires that patients with cancer, including those involved in trials, be prioritized for COVID-19 vaccination, which should not affect trial eligibility.
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http://dx.doi.org/10.1038/s41571-021-00487-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957448PMC
May 2021

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

Diagnostics (Basel) 2021 Jan 18;11(1). Epub 2021 Jan 18.

Oncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy.

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, = 0.029) and OS (39.4 months vs. 11.5 months, = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.
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http://dx.doi.org/10.3390/diagnostics11010138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831923PMC
January 2021

Artificial Neural Networks as a Way to Predict Future Kidney Cancer Incidence in the United States.

Clin Genitourin Cancer 2021 04 10;19(2):e84-e91. Epub 2020 Nov 10.

Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address:

Introduction: The incidence of kidney cancer is increasing; it could be counteracted with new ways to predict and detect it. We aimed to implement an artificial neural network in order to predict new cases of renal-cell carcinoma (RCC) in the population using population rate, obesity, smoking incidence, uncontrolled hypertension, and life expectancy data in the United States.

Patients And Methods: Statistics were collected on US population numbers, life expectancy, obesity, smoking, and hypertension. We used MATLAB R2018 (MathWorks) software to implement an artificial neural network. Data were repeatedly and randomly divided into training (70%) and validation (30%) subsets.

Results: The number of new RCC cases will grow from 44,400 (2020) to 55,400 (2050), an increase of +24.7%. Our data show that preventing hypertension would have the greatest impact on reduction of the incidence, estimated at -775 and -575 cases per year in 2020 and in 2030, respectively. The prevention of obesity and smoking would have a more limited impact, estimated at -64 and -180 cases per year in 2020 and in 2030, respectively, for obesity, and -173 and -21 cases per year in 2020 and in 2030, respectively, for smoking.

Conclusions: Our predictions underline the need for accurate studies on RCC-related risk factors to reduce the incidence.
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http://dx.doi.org/10.1016/j.clgc.2020.10.008DOI Listing
April 2021

A Contemporary Analysis of the 30-day Morbidity and Mortality Associated With Cytoreductive Nephrectomy.

Urology 2021 Jan 24;147:186-191. Epub 2020 Oct 24.

Department of Urology, University of Queensland, Ochsner Clinic, New Orleans, LA. Electronic address:

Objective: To examine the rates of adverse surgical outcomes in patients undergoing cytoreductive nephrectomy (CN) compared to patients undergoing radical nephrectomy in the nonmetastatic setting using a large administrative database.

Methods: Patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) who underwent a radical nephrectomy between 2011 and 2016 were included. Patients were stratified by the preoperative variable of presence or absence of metastatic cancer. Perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between patients with metastatic cancer and perioperative morbidity and 30-day mortality.

Results: There were 15,869 total patients included in this analysis of whom 1322 (8%) patients had metastatic cancer. Of the entire cohort, the majority of patients were over 60 years old (58%) and 9621 (61%) were male. Seventy-three of the patients were Caucasian. Patients with metastatic cancer had more minor (P< .01) and major (P< .01) complications, a higher rate of reoperation (P< .01), and a higher rate of unplanned readmissions (P< .01). Finally, the cohort with metastatic cancer had a higher rate of postoperative 30-day mortality (P< .01) than patients without metastatic cancer.

Conclusion: Patients undergoing a CN have significantly worse perioperative outcomes than patients undergoing a radical nephrectomy without evidence of metastases. Careful surgical risk stratification and appropriate patient counseling should be undertaken when selecting candidates for CN.
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http://dx.doi.org/10.1016/j.urology.2020.10.016DOI Listing
January 2021

Multivariate mortality analyses in COVID-19: Comparing patients with cancer and patients without cancer in Louisiana.

Cancer 2021 01 28;127(2):266-274. Epub 2020 Oct 28.

Ochsner Cancer Institute, New Orleans, Louisiana.

Background: This is the largest and only multivariate study evaluating the difference in mortality from coronavirus disease 2019 (COVID-19) between patients with cancer and patients without cancer in the United States. The objective was to assess COVID-19 mortality rates in patients with cancer versus patients without cancer and uncover possible statistically significant characteristics contributing to mortality.

Methods: This retrospective study analyzed patients with cancer and patients without cancer who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 1 through April 30, 2020. This was a multicenter study in the state of Louisiana throughout the Ochsner Health System in both tertiary and nontertiary centers. Patients older than 18 years were eligible. Three hundred twelve patients with cancer were compared with 4833 patients without cancer.

Results: Mortality was found to be higher in the cancer group. Patients of advanced age with cancer had a significant increase in mortality (odds ratio [OR], 5.96; P < .001). Other significant risk factors for increased mortality were male sex (OR, 2.15), a history of chronic kidney disease (OR, 3.84), and obesity (OR, 1.30). In hospitalized patients with cancer, adverse vital signs on admission, decreased absolute lymphocyte counts, thrombocytopenia, elevated creatinine, lactic acidosis, and elevated procalcitonin all seemed to increase the risk of death. Among patients with cancer, active or progressive disease (P < .001) and recent therapy (OR, 2.34; 95% confidence interval, 1.08-5.08) were shown to increase mortality.

Conclusions: Patients with cancer have increased mortality in the setting of infection with SARS-CoV-2 in comparison with patients without cancer. Patients with cancer who are 65 years of age or older and those with certain comorbidities have the greatest risk of death. Recent cancer-directed therapy and disease status also seem to play roles in mortality.

Lay Summary: This is the largest study of patients with cancer versus patients without cancer to date and is the first multivariate analysis study comparing these 2 patient populations. This study confirms the hypothesis that patients with cancer are at increased risk for mortality and that there are multiple characteristics posing the potential to risk-stratify these patients in the setting of a future outbreak.
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http://dx.doi.org/10.1002/cncr.33243DOI Listing
January 2021

Gemcitabine/nab-paclitaxel with pamrevlumab: a novel drug combination and trial design for the treatment of locally advanced pancreatic cancer.

ESMO Open 2020 08;5(4)

Clinical Development, FibroGen, Inc, San Francisco, California, USA.

Purpose: Pancreatic ductal adenocarcinomas exhibit a high degree of desmoplasia due to extensive extracellular matrix deposition. Encasement of mesenteric vessels by stroma in locally advanced pancreatic cancer (LAPC) prevents surgical resection. This study sought to determine if the addition of a monoclonal antibody to connective tissue growth factor, pamrevlumab, to neoadjuvant chemotherapy would be safe and lead to improved resectability in this surgically adverse patient population.

Methods: In this phase I/II trial, 37 patients with LAPC were randomised 2:1 to gemcitabine/nab-paclitaxel plus (Arm A, n=24) or minus (Arm B, n=13) pamrevlumab. Those who completed six cycles of treatment were assessed for surgical eligibility by protocol-defined criteria. Resection rates, progression-free and overall survival were evaluated.

Results: Eighteen (75%) patients in Arm A and seven (54%) in Arm B completed six cycles of therapy with similar toxicity patterns. In Arms A and B, carbohydrate antigen 19-9 response, as defined by ≥50% decline from baseline, occurred in 13 (65%) and 5 (42%), respectively. Sixteen (16%) per cent of patients were radiographically downstaged by National Comprehensive Cancer Network criteria (5 in Arm A (21%) and 1 (8%) in Arm B). Positron emission tomography normalised in 9 (38%) vs 3 (23%) of patients in Arm A vs Arm B, respectively, and correlated with surgical exploration. Eligibility for surgical exploration was 17 (71%) vs 2 (15%) (p=0.0019) and resection was achieved in 8 (33%) vs 1 (8%) of patients in Arm A vs Arm B (p=0.1193), respectively. Postoperative complication rates were not different between arms.

Conclusions: Neoadjuvant chemotherapy with pamrevlumab holds promise for enhancing resection rates in patients with LAPC without added toxicity. This combination merits evaluation in a larger patient cohort.
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http://dx.doi.org/10.1136/esmoopen-2019-000668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440698PMC
August 2020

Precision Medicine and the Institutional Review Board: Ethics and the Genome.

Ochsner J 2020 ;20(1):98-103

Ochsner Institutional Review Board, Ochsner Clinic Foundation, New Orleans, LA.

Clinical research studies often integrate precision medicine technologies and techniques, offering novel treatment opportunities for patients but also posing significant challenges for regulatory authorities and local institutional review boards (IRBs) as they attempt to protect patient safety and privacy. We review the basics of precision medicine and discuss how IRBs are addressing new challenges associated with the era of precision medicine. Precision medicine trials rely on genomic testing for inclusion criteria and investigational drug therapy choices. The vast amounts of complex information that can be obtained from basic genetic sequencing tests must be stored, analyzed, and interpreted, creating challenges for clinicians, researchers, and regulatory staff who are concerned with complex ethical, security, and legal issues surrounding patients' personal genetic data in the digital age. All members of the IRB face a rapidly changing environment. The traditional areas of primary concern, such as patient privacy, terminology, and financial benefits, have been joined by issues associated with precision medicine, such as accelerated US Food and Drug Administration drug approval, multiple informed consent form modifications, increasing length and complexity of informed consent forms, and participant genetic privacy. The challenge to the IRB is to remain focused on the prior areas of significance while also adapting the evaluation process to the novel science of precision medicine. In this era of exponentially increasing big data and easy-to-access genetic sequencing data, IRBs will be tasked with adapting their processes and adjusting to the new technology and its corresponding complexities. Such adaptation has always been required of IRBs, but now it will need to occur rapidly as technology and data analysis capabilities accelerate.
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http://dx.doi.org/10.31486/toj.19.0098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122257PMC
January 2020

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

Clin Cancer Res 2020 05 22;26(10):2290-2296. Epub 2020 Jan 22.

University of California at San Diego Moores Cancer Center, La Jolla, California.

Purpose: Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).

Patients And Methods: We performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.

Results: Thirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; = 15) and lung (19%; = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, = 1; PR, 22%, = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.

Conclusions: Ipilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231627PMC
May 2020

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors.

Cancers (Basel) 2019 Dec 30;12(1). Epub 2019 Dec 30.

Urologic Oncology, Champalimaud Clinical Center, 1400-038 Lisbon, Portugal.

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.
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http://dx.doi.org/10.3390/cancers12010084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016527PMC
December 2019

Tumor response criteria for assessing pazopanib first-line therapy in patients with metastatic renal cell carcinoma (mRCC).

Abdom Radiol (NY) 2020 06;45(6):1872-1882

Department of Abdominal Imaging, Unit 1473, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Purpose: To identify the optimum response criteria for first-line targeted pazopanib therapy in patients with mRCC using solid tumor response criteria and clinical risk factors.

Methods: Pre- and post-treatment CTs of patients (n = 43) with mRCC treated with first-line pazopanib therapy were analyzed retrospectively. Treatment response was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Choi, modified Choi (mChoi), revised Choi (rChoi), MASS (Morphology, Attenuation, Size, and Structure), 10% threshold criteria, and subjective assessment. Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium clinical risk factors were also used to define response groups. Response evaluations were correlated with overall survival (OS) and progression-free survival (PFS) using log-rank test.

Results: Patients with partial response (PR) by mChoi and rChoi had longer OS than those with stable disease (SD) (P < 0.001). Responders by 10% threshold criteria also had better OS, without or combined with clinical criteria. Patients with PR by rChoi, mChoi, RECIST v1.1, MASS criteria, and by subjective assessment had longer PFS than those with SD. rChoi and mChoi criteria best delineated the difference in PFS for patients with PR versus SD, without or combined with clinical criteria.

Conclusion: For mRCC patients treated with pazopanib, OS and PFS for PR and SD groups were best predicted by rChoi and mChoi criteria, without or combined with clinical risk factors. 10% threshold criteria also predicted OS and PFS, whereas RECIST did so only in a limited number of patients.
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http://dx.doi.org/10.1007/s00261-019-02354-zDOI Listing
June 2020

Chemotherapy Toxicity Confirms Diagnosis of Urachal Carcinoma.

Clin Genitourin Cancer 2019 10 2;17(5):e913-e915. Epub 2019 Jul 2.

Ochsner Cancer Institute, New Orleans, LA. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2019.06.017DOI Listing
October 2019

Effect of the Need for Preoperative Dialysis on Perioperative Outcomes on Patients Undergoing Laparoscopic Nephrectomy: An Analysis of the National Surgical Quality Improvement Program Database.

Urology 2019 02 15;124:154-159. Epub 2018 Nov 15.

Department of Urology, University of Queensland, Ochsner Clinic, New Orleans, LA. Electronic address:

Objective: To investigate whether patients requiring dialysis are a higher risk surgical population and would experience more perioperative adverse events even when undergoing a perceived less invasive operation as a laparoscopic radical nephrectomy (LRN). LRN is generally a well-tolerated surgical procedure with minimal morbidity and mortality. Prior to transplantation, dialysis patients will often have to undergo a LRN to remove a native kidney with a suspicious mass.

Materials And Methods: Patients in the American College of Surgeons National Surgical Quality Improvement Program who underwent a LRN between 2011 and 2016 were included. Patients were stratified by the need for preoperative dialysis 2 weeks prior to surgery, and perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between the need for preoperative dialysis and perioperative risk.

Results: There were 8315 patients included in this analysis of which 445 (5.4%) patients required preoperative dialysis. Patients who required preoperative dialysis had more minor (P <.0001) and major (P = .0025) complications, a higher rate of return to the operating room (P = .002), and a longer length of stay (P <.0001) than those patients not requiring preoperative dialysis. In a multivariate analysis, the need for preoperative dialysis was independently associated with adverse perioperative outcomes (OR= 1.45, CI = 1.08-1.95, P = .015).

Conclusion: Patients requiring preoperative dialysis were more likely to experience a perioperative complication and have a longer length of stay. For LRNs performed prior to transplantation, further risk stratification is needed, and treatment sequencing may need to be reconsidered.
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http://dx.doi.org/10.1016/j.urology.2018.11.010DOI Listing
February 2019

A patient-derived orthotopic xenograft model enabling human high-grade urothelial cell carcinoma of the bladder tumor implantation, growth, angiogenesis, and metastasis.

Oncotarget 2018 Aug 24;9(66):32718-32729. Epub 2018 Aug 24.

Institution of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, USA.

High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph node stromal cells (HK cells). Mice were monitored weekly with bioluminescence imaging to assess tumor growth and metastasis. Primary tumors and organs were harvested for bioluminescence imaging, weight, and formalin-fixed for hematoxylin and eosin and immunohistochemistry staining. In this patient-derived orthotopic xenograft model, xenograft tumors showed better implantation rates than currently reported using other models. Xenograft tumors histologically resembled pre-implanted primary specimens from patients, presenting muscle-invasive growth patterns. In the presence of HK cells, tumor formation, tumor angiogenesis, and distant organ metastasis were significantly enhanced in both UM-UC-3 cells and patient-derived specimens. Thus, we established a unique, reproducible patient-derived orthotopic xenograft model using human high-grade urothelial cell carcinoma cells and lymph node stromal cells. It allows for investigating the mechanism involved in tumor formation and metastasis, and therefore it is useful for future testing the optimal sequence of conventional drugs or the efficacy of novel therapeutic drugs.
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http://dx.doi.org/10.18632/oncotarget.26024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135689PMC
August 2018

-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.PS2 Study in Patients With NSCLC and a Performance Status of 2.

Front Oncol 2018 24;8:253. Epub 2018 Jul 24.

Department of Internal Medicine, Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, United States.

Introduction: The phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified -paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2.

Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of -paclitaxel 100 mg/m days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received -paclitaxel monotherapy (100 mg/m days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs).

Results: 11/40 treated patients (27.5%; 95% CI, 14.60-43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued -paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99-7.00) and 7.7 (95% CI, 4.93-13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%).

Conclusion: This -paclitaxel-based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data.
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http://dx.doi.org/10.3389/fonc.2018.00253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066533PMC
July 2018

Primary Undifferentiated Pleomorphic Sarcoma of the Penis.

Ochsner J 2017 ;17(4):434-437

The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA.

Background: Primary penile sarcoma is a rare disease that affects men of all ages. Different subtypes of primary penile sarcoma exist, with the rarest being pleomorphic sarcoma. Delays in presentation and diagnosis of primary penile sarcoma have been reported because of its benign-appearing presenting features and rarity. If penile sarcoma is left untreated, the clinical consequence is metastasis that is fatal in most cases.

Case Report: We report an extremely rare case of undifferentiated pleomorphic sarcoma of the penis in a 59-year-old patient who initially presented with a slow-growing penile nodule. The tumor was surgically excised, but the patient experienced local recurrence and, despite receiving chemotherapy and surgery, died of metastatic disease 15 months after initial presentation.

Conclusion: Vigilance regarding biopsy and intervention for penile nodules may lead to early diagnosis and improved clinical outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718460PMC
January 2017

Outcomes of Patients With Late-Relapse Metastatic Renal Cell Carcinoma Treated With Targeted Therapies: A Single Institution Experience.

Ochsner J 2017 ;17(4):331-334

Department of Hematology and Oncology, Ochsner Clinic Foundation, New Orleans, LA.

Background: Late relapse with presentation of metastatic disease >5 years after nephrectomy with curative intent is a known behavior of renal cell carcinoma (RCC), but data on outcomes, especially regarding targeted therapies, are limited. In this study, we analyze clinicopathologic features and response to targeted therapy in patients with late-relapse metastatic RCC (mRCC).

Methods: We retrospectively reviewed clinical data on consecutive patients treated with targeted therapy for mRCC diagnosed >5 years after nephrectomy with curative intent.

Results: A total of 24 patients (100% clear cell histology, median age 72 years, 83% males, all with prior nephrectomies) met inclusion criteria; 71% had favorable risk, and 25% had intermediate risk by International Metastatic Renal Cell Carcinoma Database Consortium criteria. The estimated median overall survival for all patients was 60.5 months, and the 3-year overall survival rate was 71.78% (95% confidence interval, 47.98%-84.77%). All patients were treated with targeted therapy; first-line treatments included pazopanib (46%), sorafenib (25%), sunitinib (17%), and cytokine (13%), with no significant difference in time to treatment failure between therapies. Median time on first-line therapy was 19.7 months; 67% of patients received second-line treatment. Metastases were detected at considerable rates in sites considered historically uncommon, such as the pancreas, adrenal glands, and soft tissue.

Conclusion: Patients with late-relapse mRCC treated with targeted therapy had prolonged survival that compared favorably to historical controls, and metastases in uncommon sites were noted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718445PMC
January 2017

Building a Phase 1 Cancer Research Program: Lessons Learned and Progress Made.

Ochsner J 2017 ;17(4):319-321

Department of Hematology and Oncology, Ochsner Clinic Foundation, New Orleans, LA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718442PMC
January 2017

Alternative Response Criteria and Clinical Risk Factors for Assessing Tumor Response in Patients With Metastatic Renal Cell Carcinoma Who Are Receiving Salvage Therapy.

AJR Am J Roentgenol 2017 Dec 24;209(6):1278-1284. Epub 2017 Oct 24.

1 Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1473, Houston, TX 77030.

Objective: The purpose of this study is to compare the prognostic value of various solid tumor response criteria as well as the additive value of clinical risk factors in patients with advanced renal cell carcinoma (RCC).

Materials And Methods: Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months after treatment) were reviewed for 57 patients with metastatic RCC treated with pazopanib in the salvage setting. Tumor response on the posttherapy scan was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi, modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and 10% threshold criteria. In addition, combined Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors plus imaging criteria were used to define response groups. Response evaluations using these criteria were correlated with overall survival (OS) and progression-free survival (PFS), with use of the log-rank test.

Results: Patients classified as having progressive disease (PD) on the basis of RECIST, mChoi, and MASS criteria had a significantly worse OS than patients with stable disease (SD) and partial response (PR). With the addition of MSKCC risk factors, all groups with PD defined by combined criteria had significantly worse OS. For 37 patients with no or one MSKCC risk factor, response groups defined by Choi, mChoi, MASS, and 10% threshold criteria did not differ in PFS or OS. However, among 20 patients with two to three MSKCC risk factors, those classified as having PR had longer PFS than did those with SD and had longer OS than did those with PD.

Conclusion: For patients with advanced RCC for which prior therapies have failed, the prognostic value of various imaging-based tumor response criteria differs on the basis of the MSKCC clinical risk status.
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http://dx.doi.org/10.2214/AJR.17.18018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722466PMC
December 2017

Outcomes of Patients With Metastatic Non-Clear-Cell Renal Cell Carcinoma Treated With Pazopanib.

Clin Genitourin Cancer 2017 04 22;15(2):e205-e208. Epub 2016 Jul 22.

Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.

Background: Pazopanib is associated with increased progression-free survival (PFS) in clear-cell renal cell carcinoma (RCC) and has become a standard of care in this disease. The drug is used in metastatic non-clear-cell RCC, but data on outcomes in this setting are limited.

Patients And Methods: We conducted a retrospective data analysis of records of consecutive metastatic non-clear-cell RCC patients who received pazopanib in front-line and salvage settings between November 2009 and November 2012. Tumor response rate was assessed by a blinded radiologist using Response Evaluation Criteria in Solid Tumors version 1.1. PFS and overall survival (OS) times were estimated using Kaplan-Meier methods.

Results: Twenty-nine patients were identified with non-clear-cell metastatic RCC, 9 received pazopanib in the front-line setting, 20 in the salvage setting after progression of disease with other targeted therapies. Seven patients (24%) had papillary RCC, 4 (14%) had chromophobe, 5 (17%) had unclassified histopathology, and 13 (45%) had other subtypes including collecting duct, translocation Xp11.2, and various subtypes with sarcomatoid differentiation. All patients discontinued pazopanib before analysis. Median PFS was 8.1 months (95% CI, 5.7-NA [not available]) in the front-line group, and 4 months (95% CI, 2.1-9.9) in the salvage group. Median OS was 31 months (95% CI, 9.2-NA) in the front-line group, and 13.6 months (95% CI, 6.4-NA) in the salvage group.

Conclusion: Pazopanib showed efficacy in patients with metastatic non-clear-cell RCC in the front-line and salvage settings. Toxicity was mild to moderate and manageable. Further studies are needed to evaluate pazopanib's role in non-clear-cell RCC in terms of efficacy and safety.
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http://dx.doi.org/10.1016/j.clgc.2016.07.016DOI Listing
April 2017

An Abundance of Polyps: An Intriguing Case of Lymphomatous Polyposis.

J La State Med Soc 2015 Jul-Aug;167(4):183-5. Epub 2015 Aug 15.

University of Queensland School of Medicine.

Multiple lymphomatous polyposis (MLP) is a rare condition in which non-Hodgkin lymphoma (NHL), typically mantle cell lymphoma, presents as multiple mucosal polyps of the intestine. We present the case of a 66-year-old man who presented with newly acquired polyps throughout the colon, detected by endoscopy. Endoscopic biopsies confirmed the diagnosis of mantle cell lymphoma. The patient underwent treatment on a research protocol. Our case illustrates the importance of considering MLP or other forms of NHL in elderly patients found to have multiple gastrointestinal polyps, especially those who have a history of clear colonoscopy within the previous one to two years.
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September 2017

Emerging Immunotargets and Immunotherapies in Prostate Cancer.

Curr Drug Targets 2016 ;17(7):777-82

Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.

Innate and adaptive immunity are both involved in prostate cancer (PCa) carcinogenesis and progression. On this scenario, several immunotherapeutic approaches have been proposed and are presently under extensive investigation in PCa patients. Among emerging immune targets, immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), anti-Programmed death-1 (PD-1) and anti-Programmed death-ligand-1 (PD-L1) agents seem to represent the most promising candidate for these patients, together with oncolytic viruses and vaccines, used alone or in combined strategies. In this review, we focused on emerging immunotherapeutic approaches in patients with PCa, showing the rational for their association with current standard therapies including anti-androgen agents, chemo- or radiation therapy.
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http://dx.doi.org/10.2174/1389450117666160217123304DOI Listing
December 2016

Emerging Immunotargets in Bladder Cancer.

Curr Drug Targets 2016 ;17(7):757-70

Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.

Bladder cancer treatment, namely systemic therapy, was dominated in the last three decades due to the absence of newer therapeutic options other than chemotherapy regimens. Chemotherapy, by itself, both in first and second-line seems to have achieved the modest plateau of its possibilities at the cost of non-negligible toxicity. Targeted therapies, which changed the therapy of many different tumors, seem rather ineffective in bladder cancer. More recently, a new generation of Immunotherapy based regimens represent the most promising avenue for the future systemic treatment of bladder cancer. Checkpoint inhibition, namely PD1/PD-L1 pathway inhibition, showed impressive results in many other tumor types and are expected to become a major player in the treatment of bladder cancer. Other immunotherapy strategies such as fusion proteins represent distant, although promising, options. A brief overview of the current status of bladder cancer immunotherapy is presented.
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http://dx.doi.org/10.2174/1389450117666160201105537DOI Listing
December 2016

Metastatic Prostate Cancer 35 Years After Sex Reassignment Surgery.

Clin Genitourin Cancer 2016 Apr 17;14(2):e207-9. Epub 2015 Nov 17.

Ochsner Cancer Institute, Ochsner Clinic Foundation, New Orleans, LA; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2015.11.007DOI Listing
April 2016

An Overview of Emerging Immunotargets of Genitourinary Tumors.

Curr Drug Targets 2016 ;17(7):750-6

Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.

Emerging immunotherapies targeting immune checkpoints and tumor associated antigens are leading to important clinical advances and providing a new weapon in patients with prostate (PCa) and bladder cancer (BC) and, in particular, with renal cell carcinoma (RCC). The possibility to integrate these agents in the current therapeutic scenario or genitourinary tumors, both in sequential or combined approaches, relies on a more profound comprehension of the protumorigenic activity of the immune system and of the mechanisms of cancer-related immunosuppression. In this regards, neutrophils, T and B lymphocytes and tumor-associated macrophages (TAMs) are implicated in the pathogenesis, progression and development of drug resistance in genitourinary tumors. This review is an overview on the recent insights concerning the role of immune cells in this context.
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http://dx.doi.org/10.2174/1389450117666151209144649DOI Listing
December 2016

Emerging Immunotargets in Metastatic Renal Cell Carcinoma.

Curr Drug Targets 2016 ;17(7):771-6

Gayle and Tom Benson Cancer Center, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, Louisiana 70121, USA.

Renal cell carcinoma (RCC) is one of the most immunoresponsive human cancers. High-dose IL-2 and Interferon-α were once the principle therapies for metastatic RCC, however they had harsh-tolerance profiles and limited response rates. In the last decade, targeted therapies have supplanted cytokine therapy due to higher response rates and more favorable toxicity profiles. Emerging immunotherapies targeting the PD-1 receptor and PD-L1 ligand have shown promising results. Likewise, other novel targeted immunotherapies are currently under evaluation. The safety profiles and response rates of new generation immunotherapies are encouraging and justify the progression of clinical trials. However, longer follow-up data are needed to confirm these promising results. In addition, it is still unclear if an optimal sequence or combinations of new immunotherapies paired with current targeted therapies will emerge.
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http://dx.doi.org/10.2174/1389450117666151209115753DOI Listing
December 2016

Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors: a single institution experience.

BJU Int 2016 08 13;118(2):264-71. Epub 2015 Dec 13.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objective: To explore the efficacy and safety of pazopanib in a 'real-world' setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited.

Patients And Methods: We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables.

Results: In all, 88 patients were identified; 74 were evaluable for response: two (3%) had a complete response, 27 (36%) a partial response, 36 (49%) had stable disease and nine (12%) had progressive disease. The median PFS was 13.7 months [95% confidence interval (CI) 8.7-18.3]. PFS was correlated with a Karnofsky Performance Status score of <80 [hazard ratio (HR) 3.26, P < 0.001] and serum lactate dehydrogenase of >1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95% CI 20.2-not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95% CI 3.3-25.7) with VEGFR-TKI and 5 months (95% CI 3.5-15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95% CI 12.9-not reached) and 14.2 months (95% CI 8.1-not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37).

Conclusions: In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.
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http://dx.doi.org/10.1111/bju.13374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870151PMC
August 2016

BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies.

Expert Rev Mol Diagn 2015 11;15(9):1201-10. Epub 2015 Jul 11.

a 1 Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, Italy.

Several novel recurrent mutations of histone modifying and chromatin remodeling genes have been identified in renal cell carcinoma. These mutations cause loss of function of several genes located in close proximity to VHL and include PBRM1, BAP1 and SETD2. PBRM1 encodes for BAF180, a component of the SWI/SNF chromatin remodeling complex, and is inactivated in, on average, 36% of clear cell renal cell carcinoma (ccRCC). Mutations of BAP1 encode for the histone deubiquitinase BRCA1 associated protein-1, and are present in 10% of ccRCCs. They are largely mutually exclusive with PBRM1 mutations. Mutations to SETD2, a histone methyltransferase, occur in 10% of ccRCC. BAP1- or SETD2-mutated ccRCCs have been associated with poor overall survival, while PBRM1 mutations seem to identify a favorable group of ccRCC tumors. This review describes the roles of PBRM1, BAP1 and SETD2 in the development and progression of ccRCC and their potential for future personalized approaches.
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http://dx.doi.org/10.1586/14737159.2015.1068122DOI Listing
May 2016

Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases.

BJU Int 2016 May 6;117(5):761-5. Epub 2015 Jul 6.

University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objectives: To identify the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) treated with either pazopanib or sunitinib and assess whether PM is an independent prognostic variable in the current therapeutic environment.

Patients And Methods: A retrospective review of patients with mRCC in an outpatient clinic was carried out for the period January 2006 to November 2011. Patient characteristics, including demographics, laboratory data and outcomes, were analysed. Baseline characteristics were compared using chi-squared and t-tests and overall survival (OS) and cancer-specific survival (CSS) rates were estimated using Kaplan-Meier methods. Predictors of OS were analysed using Cox regression.

Results: A total of 228 patients were reviewed, of whom 44 (19.3%) had PM and 184 (81.7%) had metastases to sites other than the pancreas. The distribution of baseline characteristics was equal in both groups, with the exception of a higher incidence of previous nephrectomy, diabetes and number of metastatic sites in the PM group. Four patients had isolated PM, but the majority of patients (68%) with PM had at least three different organ sites of metastases, as compared with 29% in patients without PM (P < 0.01). The distribution of organ sites of metastases was similar, excluding the pancreas, in those with and those without PM (P > 0.05). The median OS was 39 months (95% confidence interval [CI] 24-57, hazard ratio 0.66, 95% CI 0.42-0.94; P = 0.02) for patients with PM, compared with 26 months (95% CI 21-31) for patients without PM (P < 0.01). CSS was 42 months (95% CI 30-57) in the PM group and 27 months (95% CI 22-33) in the control group (P = 0.05).

Conclusions: Despite a higher number of affected organ sites in the PM cohort, mRCC behaviour in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumour features associated with PM may represent a less aggressive tumour phenotype.
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http://dx.doi.org/10.1111/bju.13185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666814PMC
May 2016