bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) versus gemcitabine, and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer, a systematic review and meta-analysis.
Authors: Benkhadra Raed , Nayfeh Tarek , Patibandla Naga Sai Krishna , Peterson Chelsea , Prokop Larry , Alhalabi Omar , Murad M. Hassan , Mao Shifeng 
Published: June 2021

e16522 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC) in cisplatin-eligible patients. This systematic review and meta-analysis provide an updated efficacy and safety comparison between the two most commonly used cisplatin-based regimens; dose-dense (dd) or conventional MVAC versus GC. Methods: We searched different databases for studies comparing MVAC versus GC in the neoadjuvant setting. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. Results: We identified 24 studies from inception to March 2020; among them 17 were peer reviewed and 7 were only reported as abstracts in national or international meetings, including a phase 3, randomized-controlled clinical trial. Among peer-reviewed published studies, efficacy outcomes such as OS, downstaging and pCR were comparable between conventional MVAC and GC for MIBC. If including non-peer-reviewed studies, dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95% CI 1.15–1.82), and OS at longest follow-up (OR 0.63; 95% CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95% CI 0.13–0.80), anemia (OR 0.32; 95% CI 0.18–0.54), nausea and vomiting (OR 0.27; 95% CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95% CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95% CI 0.01-0.31). Certainty in the estimates was very low for most outcomes. Conclusions: Among peer-reviewed published studies, efficacy and safety outcomes were comparable between conventional MVAC and GC for MIBC. However, If including non-peer-reviewed studies, this analysis showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice
Role of partial cystectomy for muscle invasive bladder cancer: Impact on morbidity and overall survival, a population-based study, 2006-2017.
Authors: Posielski Natasza , Koenig Hannah , Jung Nathan , Ho On , Flores John Paul , Porter Christopher 
Published: June 2021

e16530 Background: National Comprehensive Cancer Network (NCCN) guidelines state partial cystectomy (PC) may be offered in select patients with clinical T2 (cT2) muscle invasive bladder cancer (MIBC) utilizing neoadjuvant chemotherapy (NAC) and pelvic lymphadenectomy (PLND). Our objective was to investigate utilization and survival outcomes of PC in a large contemporary cohort. Methods: Propensity matching was used to compare pathological and surgical outcomes in non-metastatic MIBC patients in the National Cancer Database undergoing PC or radical cystectomy (RC). Multivariate logistic regression was used to determine predictors of NAC, LND, peri-operative morbidity and mortality outcomes. This analysis was repeated in the subset with cT2 MIBC. Results: Of 31,306 T2-T4N0M0 patients, 1543 (4.9%) underwent PC. PC use was higher in older patients and most often (85%) performed for cT2 disease. The PC group was less likely to receive standard of care including NAC (11.4 vs 27.9%, p<0.001) and PLND (58.7 vs 92.5%, p<0.001) than the RC group. Pathological ≥T3 disease (pT3) was found in 39.4% and pos. nodes in 6.9% of PCs. Positive margins were higher in PC, 15.7 vs 10.6%, p<0.001. PC patients had shorter inpatient stay (4.2 vs 8.7 days, p<0.001), lower 30-day readmission (6.7 vs 9.6%, p<0.001), and decreased 30- and 90-day mortality (1.3 vs 1.8%, p<0.001 & 4.8 vs 4.9%, p=0.04). PC was an independent predictor of lack of NAC (OR 0.49, p<0.001) and PLND (OR 0.11, p<0.001), shorter LOS (b -4.66, <0.001), readmission rate (OR 0.72, p<0.001), and improved 30- and 90- day mortality (OR 0.55 & 0.75, p<0.001). In cT2 patients only: PLND and NAC were less utilized in PC (p<0.001), 32% were ≥pT3 and 6.6% node pos. In both full cohort and cT2 subset, PC was associated with slight improvement in time to mortality (Table) and overall survival (OS) (OR 1.44, p<0.001). Conclusions: PC is rarely used in treatment of MIBC. Despite guidelines, NAC and PLND are underutilized in PC. Care is required in selecting patients for PC as up to one third of cT2 patients have ≥pT3. In these likely highly selected patients, PC had lower peri-operative mortality and comparable OS to RC. Selection bias may play a role in these results and further investigation is needed to determine optimal candidates for PC.[Table: see text]
Patterns and predictors of treatment in muscle-invasive bladder cancer (MIBC): A real-world study.
Authors: Lu Zengqi , Clement Jessica M. , Pan Qi , Swede Helen , Mehta Rajni , Wang Xiaoyan 
Published: June 2021

e16531 Background: Among the approaches to curative-intent therapy for MIBC, neoadjuvant cisplatin-based chemotherapy (NAC) is recognized as the gold standard. The combined modality approach of concurrent chemo-radiation is also considered a standard of care. Despite guidelines recommending multidisciplinary care, studies have shown a low adoption rate of multidisciplinary approaches for MIBC. This study aimed to describe the treatment patterns for MIBC pts using real world data. Methods: Following the appropriate IRB approvals, investigators followed a common protocol under the auspices of the Rapid Case Ascertainment at the Yale Cancer Center. Manual chart review was performed on MIBC pts diagnosed in Connecticut from 2004 –2015 and treated at investigator-affiliated hospitals. Information on medical history, comorbidity, and treatment types were recorded. This data set was linked to the Surveillance, Epidemiology, and End Results (SEER) database for demographic information. The descriptive and logistic regression were used to analyze treatment patterns and predicators in each treatment lines: surgery alone, chemotherapy alone, radiation alone and standard care (NAC followed by surgery; surgery followed by adjuvant chemotherapy and concurrent chemo-radiation). Results: The number of adult MIBC pts in the cohort was 1,198. Among them, 290 (24.2%) received surgery as the only treatment; 117 (9.8%) received chemotherapy only; 100 (8.3%) received concurrent chemo-radiation; 96 (8.0%) received NAC followed by surgery. Besides age ( OR: 0.546, 95% CI: 0.289-0.986), when comparing female to male patients on the likelihood of receiving NAC to the alternative treatment types (radiation or surgery), female pts were less likely to receive NAC than males (OR: 0.421, 95% CI: 0.184-0.930). Conclusions: Regardless of demographics, the overall adoption rate of standard care was low, consisting of 236 pts (19.7%) of the population. From the logistic regression results, age was consistently shown as a predictor for receiving NAC over the alternative treatment types, and sex was identified as another strong predictor. Older and female patients were less likely to receive NAC than younger males.[Table: see text]
Assessment of the alignment between research funding allocation and consensus research priority areas in kidney cancer.
Authors: Lu Steven , Kaiser Jeenan , Jewett Michael A.S. , Heng Daniel Yick Chin , Alimohamed Nimira S. , Bhindi Bimal 
Published: June 2021

e16538 Background: Finite resources are available to fund research, and it is important to ensure stakeholder input is identified and prioritized. In this light, the KCRNC and CIHR sponsored a consensus-based priority-setting partnership that brought together a group of patients, caregivers, and clinicians to identify the top 10 research priorities in kidney cancer (Table), with a consensus document published in 2017. The final step of the prioritization process was to determine how research funding allocation has aligned with these previously identified priority areas. We report the results of this assessment. Methods: We queried publicly available Canadian and American research databases to identify all research funds allocated to kidney cancer from 2018-2020. Each funded project was assessed to determine which priority areas were addressed. We evaluated the percent of projects and percent of funding dollars (converted to USD) allocated to priority areas. Projects were stratified by country, type of research (basic science/translational or clinical), and cancer stage of focus (localized and/or metastatic). Results: A total of 121 kidney cancer research projects were funded between 2018-2020, with 15 Canadian projects (total $ = 1,906,398 USD) and 106 American projects (total $ = 56,317,386 USD). Most projects were basic science or translational (88%). Half (50%) of the projects focused on localized cancer while 26% of projects focused on metastatic kidney cancer. Overall, 49% of projects aligned to one priority area, 47% of projects aligned to multiple priority areas, and 4% of projects were not aligned to priority areas. The priority areas which received the most funding were causes of kidney cancer (priority #10, 64% of funds), biomarkers (priorities #1b+1c+5, 59%), and immunotherapies (priority #4, 41%)(Table). Unfunded priority areas were supportive care (priority #6) and the role of biopsy in kidney cancer management (priority #8). Conclusions: Nearly all kidney cancer projects funded since 2018 were aligned with one or multiple stakeholder-identified research priority areas, although some priority areas remain underfunded. Mechanisms to improve distribution of funding to all priority areas may be warranted.[Table: see text]
Association of chronic use of proton pump inhibitors with an increased risk of immune checkpoint inhibitor-induced colitis in renal cell carcinoma.
Authors: Elias Roy , Yin Jianyi , Peng Lan , Christie Alana , Kubiliun Nisa , Brugarolas James , Hammers Hans J. 
Published: June 2021

e16550 Background: Immune checkpoint inhibitors (ICI) have become standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including immune-related colitis (irC). Growing evidence suggests that proton pump inhibitors (PPIs) are associated with an increased risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and irC, we sought to evaluate the relationship between PPI use and irC in mRCC patients. Methods: We performed a retrospective study of adult patients who received ICI for mRCC between 2015 and 2018 at two tertiary care centers. Clinical characteristics, oncological outcomes, irC details, and PPI use were collected by manual chart review. The diagnosis of irC was made via biopsy when available, or when unavailable (or inconclusive) by clinical criteria. Univariable and multivariable logistic regression analyses were conducted to assess PPI use and other potential risk factors of irC. Results: A total of 176 patients received immunotherapy for mRCC, of which 16 (9.1%) were diagnosed with irC. There were no significant differences between patients with and without irC in age, gender, medical comorbidities, RCC subtype, treatment history, and overall survival. However, Caucasian race, exposure to ipilimumab, and PPI use were more frequently observed in patients with irC than those without. Patients with irC presented with elevated stool lactoferrin and calprotectin and a wide range of endoscopic and histologic findings. In univariable and multivariable logistic regression analyses, Caucasian race, exposure to ipilimumab and chronic use of PPIs >8 weeks were significantly associated with irC (Table). Conclusions: PPI use may be a modifiable risk factor for irC development in patients with mRCC.[Table: see text]
Potential role of dose escalation in overcoming acquired resistance to cabozantinib in metastatic renal cell carcinoma (mRCC).
Authors: Sharma Akanksha , Elias Roy , Christie Alana , Williams Noelle S , Pedrosa Ivan , Brugarolas James 
Published: June 2021

e16568 Background: Cabozantinib is among the most potent tyrosine kinase inhibitors (TKI) approved for use in mRCC. Cabozantinib is available in tablet (CABOMETYX) and capsule (COMETRIQ) formulations at 60 mg daily (RCC and hepatocellular carcinoma) and 140 mg daily (medullary thyroid cancer), respectively. The two formulations are not bioequivalent, and effective drug exposures may be lower with the 60 mg tablet in certain populations. We evaluated cabozantinib 80 mg at the time of progression as salvage therapy. Methods: Using Kidney Cancer Explorer, a centralized database for clinical, pathological and experimental genomic data, we systematically identified all patients (pts) with mRCC at the University of Texas Southwestern Medical Center from Jan 2014 – Mar 2020 who had been prescribed cabozantinib. Results: During this period, we identified 107 mRCC pts prescribed cabozantinib. Two patients and a third subsequently, received 80 mg daily after having previously progressed on cabozantinib 60 mg (Table). Cabozantinib 80 mg was prescribed late in the disease course (fourth - seventh line) as salvage therapy. In the first case, cabozantinib 80 mg as fourth-line therapy resulted in disease control for 18 months. In the second and third cases, cabozantinib 80 mg resulted in deep partial responses (PRs) using RECIST principals ongoing at 20 and 5.5 months respectively. There were no grade III/IV adverse events noted. Conclusions: For mRCC pts with cabozantinib-responsive disease and good tolerability, salvage therapy with cabozantinib 80 mg at progression may be an effective treatment strategy, especially when there are limited alternatives.[Table: see text]
Characteristics and comorbidities of veterans treated with enzalutamide or abiraterone.
Authors: Patel Mukti , Riekhof Forest , Sanfilippo Kristen Marie , Carson Kenneth Robert , Schoen Martin W. 
Published: June 2021

e17022 Background: Prostate cancer (PCa) is the most common male malignancy and is the fourth leading cause of cancer-related death in males worldwide. Enzalutamide (ENZ) and Abiraterone (AA) are used in the treatment of castrate resistant PCa after androgen deprivation therapy (ADT), however these agents have not been directly compared. These drugs have various adverse effects with different mechanisms of action and may be selected based on comorbid conditions. In this study, we aim to identify patient characteristics and comorbidities of patients treated with ENZ versus AA. Methods: Patients treated with AA or ENZ between September 10, 2014 and June 3, 2017 were identified in the Veterans Health Administration and followed until April 2020. Only patients with a pathologic diagnosis of PCa and treatment with ADT prior to AA or ENZ were included. Age at initiation of treatment, Elixhauser comorbidity score, PSA at initiation of AA or ENZ, Gleason score at diagnosis, treatment with ADT, docetaxel, and cabazitaxel was collected. Months of filled prescriptions were used to determine length of treatment. Results: Of 2575 patients, 1095 (42.5%) were initially treated with ENZ, 1480 (57.5%) with AA, and 1330 (51.7%) received both agents. Overall, 756 (29.4%) of patients were of black race. Docetaxel was used in 32.3% of patients and cabazitaxel in 11.7% of patients, with no differences between ENZ or AA cohorts. There were no significant differences in time from pathologic diagnosis to initial ADT therapy, or subsequently to treatment with ENZ or AA in either group. Furthermore, there were no differences in PSA (n = 1243, median AA 33.7 vs ENZ 30.7, p = 0.538) or Gleason scores (n = 1816, mean AA 7.85 vs ENZ 7.94, p = 0.142). Patients initially treated with ENZ compared to AA were older (mean 74.2 vs. 73.7 years, p = 0.032), had higher mean comorbidity score (7.1 vs. 6.7, p = 0.002), and had a longer duration of first treatment (median 10.5 months vs. 9.0 months, p < 0.001). As a second agent, ENZ also had a longer duration of treatment (median 5.0 vs. 4.2 months, p < 0.001). Patients treated initially with ENZ were more likely to have heart failure (18.2% vs. 13.7%, p = 0.002), cardiac arrhythmia (42.1% vs 36.6%, p = 0.004), valvular disease (13.7% vs 10.3%, p = 0.009), peripheral vascular disorders (26.8% vs 22.7%, p = 0.016), uncomplicated hypertension (86.8% vs 83.6%, p = 0.024), complicated hypertension (20.2% vs 16.9%, p = 0.033), uncomplicated diabetes (43.9% vs 37.4%, p = 0.001), complicated diabetes (26.0% vs 19.9%, p = 0.000), renal failure (28.3% vs 22.6%, p = 0.001). Conclusions: Overall, we found that patients initially treated with ENZ were older and had higher rates of cardiovascular disease and diabetes compared to those initially treated with AA. Assessment of comorbidities may be helpful in treatment selection to facilitate personalized medicine in prostate cancer, prevent adverse events, and improve outcomes.
Stereotactic body radiation therapy (SBRT) versus conventionally fractionated external beam radiation therapy in unfavorable intermediate-risk prostate cancer: An inverse propensity matched analysis.
Authors: Andruska Neal , Fischer-Valuck Benjamin Walker , Agabalogun Temitope , Carmona Ruben , Brenneman Randall , Gay Hiram Alberto , Michalski Jeff M. , Baumann Brian Christopher 
Published: June 2021

e17054 Background: Conventionally fractionated radiotherapy (CFRT) or moderately hypofractionated radiotherapy (MFRT) ± short-course androgen deprivation therapy (ADT) is commonly employed for unfavorable intermediate-risk (UIR) prostate cancer. Stereotactic body radiation therapy (SBRT) has not been widely adopted, but may have radiobiologic advantages over more conventionally fractionated treatments. We hypothesized that radiotherapy dose-escalation with SBRT (35-40Gy in ≤5 fractions) is associated with improved overall survival (OS) relative to biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MFRT (≥60Gy in 2.4-3.2Gy/fraction) ± ADT. Methods: The National Cancer Database (NCDB) was used to identify 28,028 men with UIR prostate cancer 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). SBRT+ADT patients were excluded due to low patient numbers. Inverse probability of treatment weighting was used to balance measured confounders. Unweighted- and weighted- multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios. Results: Relative to CFRT without ADT, CFRT+ADT (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.97], P = .002) and SBRT without ADT (HR: 0.74 [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 [0.67-0.99], P = .04). Weight-adjusted MVA demonstrated that SBRT (HR: 0.80 [0.65-0.98], P = .036) and ADT (HR: 0.91 [0.86-0.97], P = .002) correlated with improved OS. SBRT was not associated with improved OS relative to MFRT. Conclusions: Using inverse propensity treatment weighting, we adjusted for age, comorbidity score, and tumor factors, and observed a significant overall survival benefit in favor of administering dose-escalated SBRT over CFRT+ADT. To our knowledge, this is the first study to show that SBRT is associated with improved OS relative to CFRT for men with UIR prostate cancer. Together, this suggests that SBRT offers a cheaper and shorter course of therapy that mitigates COVID-19 exposure, which also is associated with improved OS relative to CFRT for UIR prostate cancer and may obviate the need for ADT in this population. While we await results from several ongoing clinical trials, we believe this study lends support to the use of SBRT in men with UIR prostate cancer.
Associations of pre-existing cardiovascular disease (CVD) with treatment patterns and survival outcomes in patients with metastatic prostate cancer: A real-world, population-based study.
Authors: Batra Atul , Kong Shiying , Cheung Winson Y. 
Published: June 2021

e17056 Background: Prior cardio-oncology research has focused on examining the future risk of CVD as a result of cancer treatments. The impact of pre-existing CVD on cancer treatments is less clear. This study aimed to identify the associations of baseline CVD on treatment patterns and survival outcomes in metastatic prostate cancer where older age and exposure to androgen deprivation therapy can potentiate cardiac risks. Methods: We identified all patients diagnosed with metastatic prostate cancer in a large Canadian province from 2004 to 2017 using the population-based cancer registry. Administrative claims were linked to ascertain any diagnoses of pre-existing CVD, defined as any of arrythmias [AR], cerebrovascular accidents [CVAs], myocardial infarctions [MIs], or congestive heart failure [CHF] that preceded the diagnosis of metastatic prostate cancer. Logistic and Cox regression models were constructed to determine the associations of baseline CVD with receipt of cancer treatments (such as radiation, or systemic therapy) and overall survival (OS). Results: A total of 3,257 patients were included. The median age was 66 years (interquartile range, 46-95 years). At diagnosis of advanced prostate cancer, 993 (30.5%) had pre-existing CVD: 10.0% AR, 4.3% CVAs, 3.0% MIs, 2.8% CHF and 10.4% multiple CVDs. The Charlson comorbidity index (CCI) was 0, 1 and >1 in 53.4%, 27.3% and 19.3%, respectively. Overall, 2078 (63.8%) patients received chemotherapy, while 747 (22.9%) received radiotherapy. After adjusting for age and CCI, pre-existing CVD was associated with a lower likelihood of chemotherapy (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.61-0.75; P=0.001) and radiotherapy (OR, 0.87; 95% CI, 0.85-0.91; P<0.001). Likewise, CVD was associated with worse OS, after adjusting for measured confounding variables (see table). Conclusions: One-third of patients with metastatic prostate cancer had pre-existing CVD, which was associated with a lower likelihood of chemotherapy and worse OS. In the context of an aging general population, early cardio-oncology consultations to optimize CVD management may lead to safer and broader uptake of appropriate prostate cancer treatments.[Table: see text]