bluuebunny/crossref_metadata_2025 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]
Mutational profiles of ovarian cancer in Chinese patients revealed potential therapeutic targets and prognostic markers.
Authors: Feng Weiwei , Lyu Tianjiao , Liu Hua , Jiang Yahui , Shen Lifei , Long Wenqing , Zhu Lan , Shao Siqi , Ma Jinyan , Wang Jian , Zhou Yuxi , Yang Yuchen
Published: June 2021

e17525

Background: Ovarian cancer (OC) is a common and lethal gynecologic malignancy. The prognosis of OC is variable among different patients treated with standard of care therapies. Herein, we described mutational profiles of OC to identify underlying therapeutic targets and prognostic markers. Methods: The study was performed in 38 Chinese patients with high-grade serous ovarian cancer (HGSC), the most common subtype of OC. Most patients (86.8%) had advanced disease (stage III-IV). Tissue samples were subjected to capture-based targeted sequencing using a panel consisting of 520 cancer related genes. Mutational profiles including gene mutations and copy number variations (CNVs) were evaluated in each patient. Homologous recombination deficiency (HRD) status was also assessed. Analysis of mutational profile with platinum-sensitivity, progression-free survival (PFS) and platinum-free interval (PFI) were performed. Results: Genetic alterations were mainly identified in TP53 (97%), BRCA1 (24%), RB1 (21%), FGF23 (21%), CCND2 (18%), RECQL4 (18%) and NF1 (16%). CNVs were comprehensively distributed in 242 genes with 76% (29/38) of patients harboring at least one CNV. In addition to BRCA1, genetic alterations were also presented in other homologous recombination repair (HRR) genes including CDK12 (5%), BRCA2 (3%), ATM (3%), BRIP1 (3%), CHEK1 (3%) and FANCI (3%). There were 22 of 38 (58%) patients with genetic alterations of the HRR pathway. In the study, 28 patients were platinum-sensitive (74%) and 10 were platinum-resistant (26%). Platinum-sensitivity was significantly associated with BRCA1/2 mutations (p < 0.01). In platinum-resistant patients, 7 of 10 patients harbored genetic alterations of actionable therapeutic targets such as PIK3CA, TSC1 and HER2 alterations. The prognosis analysis indicated that BRCA1/2 mutations were significantly associated with improved PFI (p < 0.05) and marginally associated with improved PFS (p = 0.05). Although no association was observed between HRD status and patient prognosis, subgroup analysis in patients with R0 resection found positive HRD showing significant association with better PFI (p < 0.05) and marginal association with better PFS (p = 0.06). Further analysis of HRD classified by NF1 revealed different PFS and PFI among patients harboring positive HRD, negative HRD with NF1 mutations and negative HRD with wild type NF1 (p < 0.05). The study also observed association of LRP1B mutations and RAD52 amplification with worse PFS (p < 0.05). Conclusions: In OC patients, genetic mutations were frequently occurred in both HRR and non HRR genes. CNVs were widely presented in many genes and patients. The mutational profiling also identified a number of potential therapeutic targets and prognostic markers at molecular level which could contribute to personalized treatment and management of OC.
Outcomes of curative intent treatment in advanced gynecological cancer with recurrent, distant lymph node, or visceral organ metastasis: Retrospective study from a single community center.
Authors: Narayanamoorthy Sujatha , Wu Yunhong , Berlach David , Xu Yiqing
Published: June 2021

e17566

Background: Uterine, cervical and ovarian cancers with isolated recurrences in the pelvic, para-aortic or distant lymph nodes, such as axillary, supraclavicular lymph node, or visceral organs, are uncommon conditions. The standard care is palliative systemic chemotherapy. We hypothesized that combined modality treatment (CMT) incorporating surgery or radiation for curative intent may increase local disease control and delay or mitigate further distant metastasis, thereby increase overall survival (OS). Methods: We retrospectively reviewed characteristics and outcomes of patients who had localized recurrence of gynecological malignancies and who were treated with an aggressive approach of salvage chemotherapy + radiation +/- surgery or radiofrequency ablation. Results: We identified 23 patients, including 6 cervical, 14 uterine and 3 ovarian cancer patients who were treated from 2005 to 2021. The mean age was 68. About 47.8% patients had advanced stages of disease at diagnosis (stage 3+4). Serous carcinoma (n = 7, 30.4%) was the most common uterine cancer pathology. All patients received curative intent therapy at initial diagnosis. The first recurrence sites are shown in the table, and the visceral organs involvement were liver, gluteal muscle, etc. The recurrence was within previous radiation field in 9 patients (39.1%) and outside radiation field in 12 (52.1%). 16 patients had local radiation + chemo, 6 had systemic chemo only and 1 had radiation only (see table below). Only 13 patients had a second recurrence, including 5 from the previous systemic treatment only group. Seven had local recurrence only and all received local therapy. Six patients eventually developed wide spread disease, and 2 died. After a median follow up of 56 months (range 22 to 186 months), 17 patients were alive (4 lost for follow up), and 15 had no evidence of disease (NED). The median time to first recurrence was 14.5 m [Interquartile range (IQR), Q1, Q3 to be 7, 19]. The PFS for those patients who had only 1 recurrence was 41.5 m (IQR 21, 63). The PFS for those who had the second recurrence until the next progression was 15 months (IQR 9, 37). The overall survival in all patients was 56 m (IQR 39, 71). Conclusions: A curative intent, salvage CMT protocol for advanced GYN cancer patients who develop isolated local or distant recurrence may have a therapeutic advantage. It renders a longer PFS and OS than those from systemic therapy alone reported in the historical data.[Table: see text]
Genomic characterization of p16+ compared to p16- HNSCC patients treated with immune checkpoint inhibitors and overall survival.
Authors: Shaikh Hira Ghazal , McGrath Julie Elaine , Xiu Joanne , Hughes Brittany Nicole , Sukari Ammar , Nabhan Chadi , Korn Wolfgang Michael , Darabi Sourat , Grover Punita , Chernock Rebecca , Ikpeazu Chukwuemeka , Wise-Draper Trisha Michel
Published: June 2021

e18024

Background: Multiple studies investigating immune checkpoint inhibitors (ICI) in head and neck squamous cell cancer (HNSCC) patients have demonstrated prolonged survival of p16+ versus p16- tumors. However, the data has been conflicting. Methods: We queried the Caris Life Sciences CODEai database to assess survival outcomes of HNSCC patients who received ICIs comparing p16+ and p16- subgroups. A standard cut-off of 2+, >70% p16 staining was used. Presence of HPV16/18 genomes was tested using whole exome sequencing. Patients were considered smokers if they had >15 pack-years of tobacco use. PD-L1 expression was assessed by the 22c3 antibody, ≥1 being positive. Gene mutations were evaluated using Next-Generation Sequencing (NGS) (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was assessed by somatic nonsynonymous missense mutations. Real world overall survival (rwOS) was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of treatment start to the date of last contact. Time on treatment (TOT) was calculated from date of start to completion of ICIs. Results: 2905 patients with HNSCC were identified in the Caris database. 41% (215/525) were smokers. Among patients who were tested for p16 and/or HPV, 32% (251/791) expressed p16 and 28% (91/236) were HPV+. The majority of p16+ tumors were oropharynx (OP) in origin (68%, 171/251). 87% (970/1111) of tumors expressed PD-L1 and 16% (216/1362) had TMB ≥10/Mb. TP53 (54%, n=1115/2076) and CDKN2A (17%, n=281/1649) were the most common mutations. When compared to p16-, the p16+ group had a higher prevalence of TMB ≥10/Mb (26% vs 17%) and RB1 mutations (21% vs 4%) but lower number of smokers (15% vs 34%) and TP53 mutations (32% vs 58%). Similar to previous reports, p16+ oropharynx squamous cell carcinoma (OPSCC) patients survived longer than p16- patients, rwOS, 47 vs. 20 months (HR=0.55, p = 0.014) respectively. Among patients who were treated with ICIs, p16+ and p16- non-OP HNSCC, rwOS was not reached (NR) for both groups at follow up of 22 months while TOT for p16+ and p16- respectively, was 3.5 vs. 2.7 months, HR 0.507, p=0.039. No statistically significant difference was found in rwOS (19.3 vs. 24 months, HR 1.8, p=0.27) or TOT (3.7 vs. 4.1 months, HR 0.78, p=0.38) between p16+ and p16- OPSCC groups treated with ICIs, respectively. Conclusions: P16+ non-OP HNSCC patients receiving ICIs were found to remain on treatment longer compared to p16- patients which was not reproduced in the OPSCC subgroup. Randomized controlled trials are needed to verify p16 as a prognostic marker for ICI therapy.[Table: see text]
Dissemination of validated health literacy videos: A tailored approach.
Authors: Blee Shannon M. , Dixon Margie D. , Master Viraj A. , Pentz Rebecca D.
Published: June 2021

e18505

Background: Previously, we showed that chemotherapy and precision medicine terminology are remarkably difficult for patients to understand. Therefore, we developed short, animated videos explaining key terminology and demonstrated that they significantly improved understanding. These videos, though effective and published, including freely downloadable, will only be helpful if appropriately disseminated. In the past, even after a video-based educational tool for prostate cancer was proven effective for improving patient comprehension, no dissemination plan was implemented due to copyright issues. Therefore, in order to propel these validated health literacy videos from the academic community into clinic workflow, we aimed to determine the best dissemination method at two different hospitals with disparate populations just six miles apart: an underserved, inner-city hospital and a higher SES hospital. Methods: The dissemination interview was developed in collaboration with an expert Intervention Development, Dissemination, and Implementation team. The draft was cognitively tested with physicians and staff who were not oncologists and finalized. With consent, interviews were conducted with both Winship Cancer Institute and Grady Memorial Hospital providers (GMH). All interviews were audio recorded, transcribed and analyzed using a semantic content analysis method. Results: Eleven providers at GMH and 22 providers at Winship were interviewed, reaching saturation of themes. 72% (n = 8) of the GMH providers felt that the best place for patients to view the videos was in the clinic, compared to 27% (n = 6) of the Winship providers. 68% (n = 15) of the Winship providers stated an app would be the most useful format, compared to 27% (n = 3) at GMH. All agreed that it would be useful for the patient’s family or caregiver to view the videos (GMH = 100%, Winship = 72%), that translation of the videos to Spanish would be beneficial (GMH = 90%, Winship = 63%), and that a nurse would be best to introduce the videos (GMH = 81%, Winship = 68%). Conclusions: Educational materials explaining complicated oncology treatment terminology enhance patient-centered care, yet without proper dissemination these crucial educational tools may never reach the intended patient population. The hospitals examined in this study served significantly different patient populations and the dissemination recommendations were quite different. Providers believed that the underserved patients needed the videos accessible in the clinic whereas providers serving higher SES patients thought that a web-based app, requiring a smart device or internet access, was more appropriate. Our study shows that it is crucial to ensure that educational materials are accessible to all populations, not just those with more means. Without a location-specific dissemination plan, educational tools may only further exacerbate disparities, rather than alleviate them.
Racial disparities and medical care accessibility in cancer statistics.
Authors: Soror Noha , Keruakous Amany
Published: June 2021

e18510

Background: Cancer is one of the leading causes of death worldwide. It continues to be the second leading cause of death in the United States despite all national efforts aiming to reduce cancer burden and mortality. Delays in medical care and subsequently age-appropriate screening leads to increased cancer burden which reflect on the overall prognosis. Medical care accessibility has been a challenge that is reported by approximately one third of the USA adult population. We aimed to identify health care disparities and its correlation with prevalence of cancer as well as delays in medical care due to financial challenges among Texas residents. Methods: We analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) 2017. We measured specific health care disparities including patient’s gender, age, race/ethnicity, body mass index (BMI), annual income, alcohol consumption, history of cancer, and delays in medical care due to financial burden, among respondents to the 2017 BRFSS survey from Texas. We computed the difference between our comparison groups using chi-square test for categorical variables and t-test for continuous variables. Results: We analyzed the differences in health care disparities among respondents with and without history of cancer. We report results from 11,165 adult respondents who reside in Texas, among which nine percent were diagnosed with cancer. We noticed a higher proportion of females than males among participants with a history of cancer (64% females p < 0.0001). Age did differ between both groups, with the majority of participants with cancer are aged 50 years and older. Interestingly, BMI did not differ between both groups (p-value = 0.6930). Although annual income did not differ between both groups, twelve percent of participants with cancer diagnosis suffered from delays in medical care due to financial burden. Racial disparities were statistically different between participants with or without cancer (p < .0001). Seventy seven percent of patients with cancer diagnosis were White and non-Hispanic with a cancer prevalence rate of 12% in that racial group. On a stratified analysis to compute the relationship between delayed medical care due to financial burden and cancer diagnosis among all ethnic groups, it was not statistically different (p-value = 0.1063). We showed that prevalence of cancer among multiracial participants and other racial minorities was higher in the group of participants who reported delays in medical care due to financial burden (11% versus 7%). Conclusions: Racial and ethnic disparities could affect accessibility to medical services. Race is a significant variable that is associated with cancer, with higher prevalence of cancer in White and non-Hispanic. Delayed medical care due to financial burden is more pronounced in multiracial population and racial minorities and should be targeted in future quality improvement projects.
Health disparities experienced by Black Americans with multiple myeloma in the United States: A population-based study.
Authors: Al Hadidi Samer , Dongarwar Deepa , Salihu Hamisu , Kamble Rammurti T. , Lulla Premal D. , Hill LaQuisa , Carrum George , Ramos Carlos Almeida , Heslop Helen E. , Usmani Saad Zafar
Published: June 2021

e18512

Background: Multiple Myeloma (MM) is the most common hematologic malignancy in Black Americans. Incidence and death rates for MM in Black Americans are more than double those in Whites. Our study aimed to evaluate trends of all cause in-hospital mortality among Black Americans with MM and to investigate characteristics of MM-related hospitalizations. Methods: We conducted a retrospective cross-sectional study of hospitalizations in adult patients with MM during 2008-2017 using the National Inpatient Sample (NIS), the largest all-payer inpatient care database in the US. We used joinpoint regression to assess temporal trends in the national incidence of in-hospital death. We conducted adjusted survey logistic regression to generate adjusted odds ratios to measure the likelihood of in-hospital death among MM related hospitalizations. Results: Admissions related to MM constituted 0.32% of all hospitalizations in the study period (913,967 out of 285,876,821). The prevalence of MM related hospitalizations was higher in Black Americans when compared with Whites (476.0 vs 305.6 per 100,000 hospitalizations, p <0.01). In-hospital mortality with MM was higher in older patients, males, those belonging to lowest zip code quartile, and who self-paid for their treatment. Average Annual Percent Change (AAPC) showed a statistically significant decline of in-hospital mortality among all MM patients except Black Americans who had the highest inpatient mortality in 2016 and 2017. Black Americans received less autologous stem cell transplantation (ASCT) (2.8% vs. 3.8%, p <0.01), more blood product transfusions (23.0% vs. 21.1%, p <0.01), less palliative care consultation (4.0% vs. 4.6%, p <0.01), less chemotherapy (10.8% vs. 11.2%, p <0.01), and more intensive care utilization (5.3% vs. 4.3%, p <0.01), when compared with Whites. Adjusted association between race/ethnicity and various outcomes confirmed observed differences [Table]. Conclusions: Black Americans with MM had the slowest improvement and highest inpatient mortality in recent years. Data suggests higher disease burden, more frequent hospitalizations, delay in accessing care and lower utilization of supportive care measures compared with White MM patients. Data highlight disparities in MM care for Black Americans necessitating a clarion call for urgent changes in health care systems.[Table: see text]
Social vulnerability and clinical trial access for older adults with myeloma in North Carolina.
Authors: Grant Shakira Jeanene , Jansen Matthew , Tuchman Sascha , Rubinstein Samuel M. , Lichtman Eben I. , Charlot Marjory
Published: June 2021

e18540

Background: Multiple myeloma (MM) is a disease of aging, associated with one of the greatest black-white disparities in incidence and mortality among all US cancer types. Clinical trials provide the critical evidence-base to inform clinical management in all cancers, including MM. However, clinical trial participants are often younger (age < 65 years) and white, limiting the generalizability of published data to real-world MM care. Although geographical and financial barriers to clinical trial participation are well recognized, less is known about the association of county-level social vulnerability with MM trial availability. We examined county-level variation in the number of registered myeloma trials per 10,000 North Carolina (NC) residents age ≥ 65 years as a function of social vulnerability and the presence of a National Cancer Institute Comprehensive Cancer Center (CCC). Methods: We conducted a cross-sectional study using data from ClinicalTrials.gov to identify all registered interventional myeloma trials involving adults age ≥ 65 years with sites in NC. Records were downloaded on January 24th, 2021. This strategy yielded 456 non-unique NC sites for 223 trials. We obtained county locations for all trial sites by matching city, zip code, or institution name. We obtained NC population data for residents age ≥ 65 years (in 2019) from the American Community Survey. The four themes (socioeconomic status, household composition, ethnic and racial minority status/language, housing/transportation) within the Centers for Disease Control Social Vulnerability Index (CDC SVI) (composite score: 0-1, with a higher number indicating more vulnerability) were used to characterize county-level social vulnerability. We performed negative binomial regression and tabulations using R, version 3.6.1. A p-value < 0.05 was considered statistically significant. Results: Across 100 counties in NC, trial site counts by county per 10,000 residents age ≥ 65 years ranged from 0 to 23.2 (mean: 1.5, median: 0; IQR, 0-0.7). Controlling for the 4 SVI themes, counties with CCCs (Durham, Forsyth, Orange) had 77% more trials than those without CCCs [Incidence Rate Ratio (IRR): 7.74; p = 0.05]. We observed a 3.3% reduction in trial counts with each percentile increase in socioeconomic vulnerability (IRR: 0.97; p = 0.008). Counties with higher representation by racial and ethnic minorities had similar trial site counts to counties with lower minority populations (IRR: 1.01; p = 0.08). Sub-group analyses of early-stage studies (phase 1/2 and phase 2; n = 268) and late-stage studies (phase 2/3 and phase 3; n = 168) were similar. Conclusions: Our preliminary results suggest county-level socioeconomic status is associated with the distribution of MM clinical trial sites across NC. Further work is planned to explore whether additional variances in trial distribution could be explained by site- and study-specific characteristics.
Trends in breast cancer survival by race-ethnicity in Florida.
Authors: Hines Robert Brooks , Johnson Asal , Lee Eunkyung , Erickson Stephanie , Rahman Saleh M.M.
Published: June 2021

e18556

Background: Considerable efforts to improve disparities in breast cancer outcomes for underserved women have occurred over the past 3 decades. This study was conducted to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer in Florida over a 26-year period to assess potential improvement in racial-ethnic disparities. Methods: This was a retrospective cohort study of women diagnosed with invasive breast cancer in Florida between 1990-2015. Data were obtained from the Florida Cancer Data System. Women in the study were categorized according to race (white/black) and Hispanic ethnicity (yes/no) as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic white (HW), and Hispanic black (HB). Cumulative incidence estimates of 5- and 10-year breast cancer death with 95% confidence intervals (CI) were obtained by race-ethnicity, according to diagnosis year. Subdistribution hazard models were used to obtain subdistribution hazard ratios (sHR) for the relative rate of breast cancer death accounting for competing causes. Results: Compared to NHW women, minority women were more likely to be younger, be uninsured or have Medicaid as health insurance, live in high poverty neighborhoods, have more advanced disease at diagnosis, have high grade tumors, have hormone receptor negative tumors, and receive chemotherapy as treatment. Minority women were less likely to receive surgery. Over the course of the study, breast cancer mortality decreased for all racial-ethnic groups, and racial-ethnic minorities had greater absolute and relative improvement in breast cancer survival for nearly all metrics compared to non-Hispanic white (NHW) women. However, for the most recent time period (2010-2015), black women still experienced significant survival disparities with non-Hispanic black (NHB) women having twice the rate of 5-year (sHR = 2.04: 95% CI; 1.91-2.19) and 10-year (sHR = 2.02: 95% CI; 1.89-2.16) breast cancer death. Conclusions: Despite efforts to improve disparities in breast cancer outcomes for underserved women in Florida, additional targeted approaches are needed to reduce the poorer survival in black (especially NHB) women. Our next step is to conduct a mediation analysis of the most important factors driving racial/ethnic disparities in breast cancer outcomes for women in Florida.