bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of anti-PD(L)1 therapy for patients (Pts) with advanced urothelial carcinoma (aUC) with primary resistance to platinum-based chemotherapy (PC).
Authors: Stewart Tyler F. , Kotha Nikhil V. , Dzimitrowicz Hannah Elizabeth , Makrakis Dimitrios , Khaki Ali Raza , Simon Nicholas I. , Nelson Ariel Ann , Freeman Dory , Rose Tracy L , Beck Wolfgang , Chawla Neal Shiv , Pal Sumanta K. , Kilari Deepak , Milowsky Matthew I. , Apolo Andrea B. , Grivas Petros , Zhang Tian , Sonpavde Guru P. , McKay Rana R.
Published: June 2021

e16515

Background: PC remains standard first-line (1L) therapy for aUC. Approximately 15% of pts exhibit primary resistance (P-R) to PC and ∼25% progress by 4 months. PD(L)1 inhibitors yield objective response rates (ORR) of ∼20% in pts with progression after PC; however, it is unclear if this benefit extends to pts with P-R to PC. We examined the efficacy of anti-PD(L)1 in pts with aUC who experienced P-R to 1L PC. Methods: We conducted a multi-institutional retrospective study of pts with aUC who experienced P-R to PC and were subsequently treated with single-agent anti-PD(L)1 therapy. Eligibility included pts with unresectable or metastatic disease diagnosed after January 1, 2017. P-R to PC was defined as radiographic progression by RECISTv1.1 within 12 weeks from initiation of PC. Pts who developed metastatic disease while receiving (neo)adjuvant PC were eligible. Clinicopathologic variables were collected. ORR to anti-PD(L)1 was the primary endpoint. Secondary endpoints included time to treatment failure (TTF, defined as time from start of anti-PD(L)1 therapy to next line of therapy, hospice or death) and overall survival (OS) were estimated using Kaplan-Meier method. Multivariate (MV) analysis using Cox regression evaluating factors associated with OS was performed. Results: Overall, 42 pts were included: 74% male, median age 65 (28-90); 79% ever smokers; 21% mixed histology; 31% received definitive locoregional therapy. Metastatic sites at diagnosis of aUC included: lymph node only (19%), liver (29%), bone (38%) and lung (33%). At diagnosis of aUC, ECOG PS was 0 in 26%, 1 in 52% and unknown in 21%. 1L PC included cisplatin (76%) and carboplatin (24%) based regimens. Anti-PD(L)1 was received either 2L (98%) or 3L (2%). Overall, ORR to anti-PD(L)1 was 17%: CR (2%), PR (14%), SD (14%), PD (57%) and unknown (12%). Of the 24 pts with PD as best response to anti-PD(L)1, only 9 (38%) received subsequent therapy. Overall, median TTF was 4.2 mo (95% CI 2.8-6.7 mo) and median OS was 7.4 mo (95% CI 4.2-11.1 mo). ORR in patients with a PDL1 combined positive score ≥ 10% (n=6) was 0%: 1 SD and 5 PD. MV analysis for OS from start of anti-PD(L)1 is shown (Table). Conclusions: P-R to PC portends a poor prognosis in pts with aUC. While a subset of patients may respond to anti-PD(L)1 therapy, the majority of pts do not derive benefit. Alternative agents, e.g. antibody drug conjugates and FGFR inhibitors, and combination-therapy should be investigated for this high risk population.[Table: see text]
Intensity of free-radical reactions in metastasizing cervical cancer.
Authors: Chernikova Natalia V. , Goroshinskaya Irina A. , Frantsiyants Elena M. , Verenikina Ekaterina V. , Poryvaev Yuriy A. , Myagkova Tatiana Yu. , Kachesova Polina S. , Nemashkalova Ludmila A.
Published: June 2021

e17508

Background: Cervical cancer (CC) is one of the main causes of death among patients with gynecological tumors. As a rule, patients die from relapses and metastases which rates reach 30-45%. According to research data, treatment of patients with distant metastases is ineffective, and half of them die within 9.7 months, while the average survival is 15.9±0.26 months. The development of many pathological processes is considered to be associated with an increase in free-radical reactions leading to oxidative damage to various biomolecules. The purpose of the study was to analyze some characteristics of the free-radical oxidation and antioxidant defence in metastasizing CC. Methods: The study included 56 patients aged 29-73 years with stage IIB-IV CC after antitumor treatment. The main group – 27 patients who developed metastases within 4 months to 8 years after the CC diagnosis; controls – 29 patients with non-metastatic CC; donors – 19 healthy women aged 27-61 years. The accumulation of carbonyl derivatives in blood plasma proteins was detected in the reaction with 2, 4-dinitrophenylhydrazine. The induced oxidative modification of proteins was stimulated with Fenton's reagent. Free-radical processes was evaluated by the intensity of peroxide-induced luminol-dependent plasma chemiluminescence and the content of nitric oxide metabolites; the intensity of lipid peroxidation - by the content of malondialdehyde (MDA); the activity of catalase and ceruloplasmin was also studied. Results: CC progression was accompanied by increasing lipid peroxidation and spontaneous oxidation of blood plasma proteins. MDA levels in patients with metastases increased by 57.8% compared to donors and by 34.3% compared to patients without metastases (p < 0.05). The concentration of 2, 4-dinitrophenylhydrozones increased on average by 4 times compared to donors and by almost 2 times compared to patients without metastases. Patients with metastasizing CC demonstrated elevated levels of products of the interaction of nitric oxide and its derivatives with proteins and peptides - 3-nitrotyrosine and nitrosoglutathione, compared to both donors (by 31.4% and 55.3%) and patients in remission (by 38.1% and 34.5%). Chemiluminescence activity increased by 54.5% compared to donors (p < 0.05) and by 93% (p < 0.01) compared to controls. Catalase activity in the blood plasma of patients with metastases increased by 54.1% compared to donors, but was lower than the values in the control group (by 22.1%). Ceruloplasmin activity was increased only in patients without metastases (by 33%). Conclusions: The process of CC metastasis is accompanied by a greater intensity of oxidative processes of both proteins and lipids, as well as depletion of the adaptive capabilities of the body's antioxidant system.
Experience of low-intensity LED radiation (LILEDR) in combination treatment of radiation-induced rectal injuries.
Authors: Rodionova Olga G. , Voshedskiy Vitaliy I. , Sakun Pavel G. , Sheiko Elena A. , Gusareva Marina A. , Chalabova Tatiana G. , Pustovalova Alla V. , Solntseva Anna A. , Dontsov Vladimir A. , Vasilieva Ekaterina O. , Kabanov Sergey N. , Karnaukhova Elena A. , Krokhmal Yulia N. , Vlasov Stanislav G.
Published: June 2021

e17514

Background: Malignant pelvic tumors account for more than 25% of cancer incidence in Russia. Radiation therapy is the most common treatment for such patients; however, 10-15% of patients develop radiation-induced complications of the pelvic organs, and more effective treatments are required to manage these complications. Methods: The study included 30 patients with cervical cancer T3NхM0 after combination treatment. 7-10 months after combined radiation treatment (total radiation dose to the primary focus 80 Gy), patients developed erosive ulcerative radiation rectitis (RTOG grade 1 and 2). Patients were divided into 2 groups: main group (n = 15) – conservative treatment combined with LILEDR. Each course included 10 LILEDR sessions, the red spectrum λ = 640 nm on the cubital vein projection (exposure time 5 minutes, dose 6.86 J/cm2) and locally on the ulcerated zones (exposure time 3 minutes, dose 3.96 J/cm2). Patients received 2 LILEDR courses with a 1-month interval. The control group received only conservative therapy. Results: Main clinical manifestations of rectitis (tenesmus, bloody mucous discharge) disappeared in the main group already on the 3-4th day of the first course, epithelialization of ulcerative defects occurred in a shorter period of 7-10 days. Soft superficial scars not causing rectal stenosis formed at the site of the ulcer by the end of LILEDR courses. The control group showed long periods of the ulcer epithelialization up to 30 days, late remission and a lingering recurrent character of the disease. Conclusions: LILEDR in combination with the main conservative therapy allows rapid managing with the clinical symptoms of radiation rectitis and regression of disorders developed after the complex treatment, which improves the quality of life of patients and shortens the rehabilitation period.
Levels of some cytokines in tumors of ovarian cancer patients with different responses to platinum-containing chemotherapy.
Authors: Sagakyants Aleksandr B. , Shulgina Oksana G. , Yakubova Darya Yu. , Ulianova Elena P. , Zhukova Galina V. , Menshenina Anna P. , Novikova Inna A. , Verenikina Ekaterina V. , Chalabova Tatiana G.
Published: June 2021

e17528

Background: Resistance to chemotherapy is a complex problem in the treatment of patients with ovarian cancer (OC). Various intercellular intermediates are involved in the phenomenon, and cytokines are the most important of them; however, the involvement of individual representatives in the processes is poorly understood. Our purpose was to analyze levels of some cytokines in tumors of OC patients with different responses to chemotherapy they receive. Methods: Samples of ovarian tumors were obtained from 100 patients (aged 29-79 years) with advanced ovarian cancer stage IIIC-IV with/without ascites. All patients recruited in 2016-2020 received standard combination treatment with surgery and platinum-containing polychemotherapy (Pt CT). Based on the results of neoadjuvant Pt CT, patients were divided into groups: patients with stabilization or progression–group 1 “without effect”; patients with complete/partial regression–group 2 with positive effect. All patients gave their informed consent for the study. Levels of IL-6, IL-8 and IL-10 were measured in cytosolic fractions of tissue samples using standard ELISA test systems (Vektor-Best, Russia). Results were presented as Me (LQ; UQ). The significance of differences between the samples was assessed using the Mann-Whitney test (the differences were considered significant at p<0.05). Results: Levels of the anti-inflammatory cytokine IL-10 in tumors of patients did not differ significantly between groups 1 and 2. The local levels of IL-6 in tumors of patients sensitive to Pt CT were 5.5 times higher than in resistant patients–2.41 (1.71;4.55) vs. 0.44 (0.26;1.04), p≤0.05, and IL-8 13 was 13 times higher–27.23 (4.01; 30) vs. 2.1 (1.72; 2.5), p≤0.05. Conclusions: Local levels of anti-inflammatory cytokines IL-6 and IL-8 were significantly higher in patients with sensitivity to platinum-containing chemotherapy, which may reflect characteristics of the microenvironment in OC tumor tissues, while IL-10 levels were similar in all patients. The revealed features of the cytokine profile may be one of the factors determining the treatment outcomes.
Early efficacy prediction of nasopharyngeal carcinoma based on 3D-ADC value acquired during radiotherapy: A phase II prospective study.
Authors: Yan Lu , Wang He , Du Xiaoli , Feng Mei
Published: June 2021

e18018

Background: Concurrent chemoradiotherapy (CCRT) is the main treatment for locally advanced nasopharyngeal carcinoma (LANPC). The prognosis of the patients with the same stage receiving the same treatment varies greatly. We aimed to investigate the dynamic changes of apparent diffusion coefficient (ADC) map from diffusion weighted MRI (DWI) of primary tumor (PT) and metastatic lymph nodes (LN) for NPC patients during RT process, and analyzed the potential correlations with volume reduction and objective response rate (ORR). Methods: A total of 50 NPC patients treated with CCRT were enrolled in this prospective study. All patients received a planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The CCRT protocol was cisplatin (80-100mg/m2) every 3 weeks for 3 cycles. All patients received DWI scan at pre-RT, the 5th and 15th fractions and immediately post-RT on a 3.0T MRI system (b=0, 500, 800s/mm2) system. The ADC values of PT and LN were acquired on ADC map. RECIST1.1criteria was used to evaluate the ORR for both PT and LN. Clinical predictors of complete response (CR) were evaluated using log-rank test. Multivariate analyses were calculated using the logistic regression model. Receiver-operating characteristic (ROC) curve was used to determine the cut-off value of ADC value. P <0.05. Results: After the completion of C CRT, the ORR of the PT was 100% (CR 75%, PR 25%), and that of the LN also reached 100% (CR 52%, PR 48%). Mean ADC increases and volume reductions in PT and LN were observed during RT. In the first stage (from pre-RT to the 5th fraction), the mean ADC increased significantly by 20.78% (PT), 22.96% (LN), while the volumes of PT and LN had minimal changes (PT:18.42cm3vs 16.72cm3, LN: 4.67cm3 vs 4.12cm3). In the second stage (from the 5th fraction to post-RT), the mean ADC increased by 45.58% (PT), 41.2% (LN), the volumes decreased by 86.07% (PT), 61.6% (LN). The increased mean ADC at the first stage had a positive correlation with the volume reduction after RT (r PT=0.32; r LN=0.40). Univariate analysis showed significant differences in the age, the changes of 3D-ADC at the 5th RT and the volume of PT and LN before RT (VPT, VLN) between CR group and PR group(p<0.05), The binary logistic regression analysis demonstrated the ADC changes and the VPT, VLN were predictor of PT and LN efficacy evaluation. ROC analysis suggested the ADC changes had the better performance for PT and LN efficacy evaluation. The cut-off the ADC value changes of PT and LN was 193.52mm2/s (AUC = 0.750, p = 0.008) , 173.80mm2/s (AUC = 0.822, p < 0.001) respectively. Conclusions: 3D-ADC values of PT and LN increased dramatically during RT for NPC patients. The 3D-ADC value of PT and LN was an independent prognostic factor for NPC patients. Early ADC changes at the 5th fraction might be a new and sensitive biomarker to predict the efficacy for NPC patients.
Outcome of neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin and oral metronomic chemotherapy (OMCT) in patients with technically unresectable oral cavity squamous cell carcinoma (SCC).
Authors: Kashyap Lakhan , Patil Vijay Maruti , Dhumal Sachin , Noronha Vanita , Joshi Amit , Menon Nandini , Prabhash Kumar
Published: June 2021

e18034

Background: NACT is often used in technically unresectable oral cavity SCC to improve resection rate. NACT regimen based on combination of maximum tolerated doses (MTD) and metronomic chemotherapy will debulk the tumor and subsequently inhibit angiogenesis which may overcome drug resistance of MTD schedule. We assessed outcome and tolerance of this combination as NACT in patients with technically unresectable oral cavity SCC. Methods: This is retrospective analysis of prospectively maintained data. Fourteen patients having technically unresectable oral cavity SCC received NACT with paclitaxel (175mg/m2) plus carboplatin (AUC5) every 3 weekly (MTD schedule) and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily and erlotinib 150mg once daily). Patient were assessed clinically and radiologically after minimum of two cycles for surgery. Kaplan-Meier method was used for survival analysis. We report resectability, survival and tolerance of this regimen. Results: Median age of the patients was 38 years, and twelve patients (85%) were male. Twelve (85%) and two (15%) patients had buccal mucosa and oral tongue primary, respectively. AJCC 2017 stage IVA and IVB disease was present in twelve (85%) and two (15%) patients, respectively. Reason for technical unresectabilty was skin edema above zygoma in five (36%), high infratemporal fossa involvement in five (36%), nodal encasement of major vessels in two (14%) and posterior extent of oral tongue tumor into oropharynx in two (14%) patients. Median number of NACT administered were three. Tumor of nine patients (65%; 95% CI = 39%-89%) were deemed resectable after NACT. Eight patients underwent surgery and tumor of one patient showed pathologic complete response. Median follow up was 14.6 months (95% CI = 14.1 - 15 months). Median progression free survival was 11.4 months (95% CI = 7.9 – 15 months). Median overall survival (OS) was not reached while OS at 15 months was 63.5% (95% CI = 37.8% - 89.2%). Common grade 3/4 toxicities (CTCAE 5.0) were neutropenia in eight (57%), thrombocytopenia in three (21%), febrile neutropenia, hypokalemia and diarrhoea in two patients (14%) each. Two patients required in-patient supportive care for adverse events. Conclusions: Paclitaxel and carboplatin along with OMCT is well tolerated and less resource intensive regimen which leads to favorable resection rate and survival in patients with technically unresectable oral cavity SCC.
The genomic architechtures of tumor-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.
Authors: Wu Ping , Yu Zicheng , Xie Chubo , Yang Ling , Xia Xuefeng , Yi Xin , Tang Yaoyun
Published: June 2021

e18046

Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by dismal prognosis, nonetheless limited studies have unveiled the mechanisms underlying HNSCC relapse. Methods: Next-generation sequencing 1 5 was performed to identify somatic mutations in 188 matched samples including primary tumors, tumor adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. Evolutionary relationship between TATs and tumors were analyzed. The dynamic changes of tumor- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. Results: Alterations were detected in 27/27 and 19/26 tumors and TATs respectively. TP53 was the most prevalent genes mutated in TATs. Some TATs shared mutations with primary tumors, while some other TATs were evolutionarily unrelated to tumors. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and indicative of worse survival (HR=14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies, and indicative of disease relapse. Conclusions: TATs might undergo the processes of premalignant transformation, tumorigenesis, and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where tumor originated or gaining private mutations independent to primary tumor. Detection of tumor- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.
The effect of household wealth on financial debt after cancer diagnosis.
Authors: Hussaini Syed , Dana Mia , Nicholas Lauren
Published: June 2021

e18552

Background: Cancer is the 2nd most common cause of death in the country, eclipsed only by heart disease. Cancer care is increasingly characterized by financial toxicity related to high-cost treatments, though it is unknown whether other chronic conditions impose similar financial harms. Methods: We conducted a retrospective analysis of the Health and Retirement Study participants interviewed between 2012-2018. This is a national, longitudinal survey conducted every two years of adults 50 and older and their spouses. We used fixed effect regression models to compare changes in financial debt among households with new diagnosis of cancer, other major chronic conditions (diabetes, stroke, or heart disease), and no new health diagnosis (or health shock). Since more affluent households may respond to health shocks differently, we estimated separate comparisons for households above versus below median wealth in 2012, prior to new health conditions. We assessed use of any non-housing financial debt, credit card debt, and home equity lines of credit among the subset of homeowning households. Results: In this study of 14,153 households, average age at interview was 62 years, with 43% male, 70% White, 22% Black, 13% Hispanic, and 70% with up to high school education. Of this population, 25% held credit card debt, 70% owned a home, 18% had a home equity line of credit, and 9% used a home equity line of credit. Among households with below median wealth when they entered the study in 2012 ( < $23,000 in $2016), a new cancer diagnosis was associated with a 4.7 percentage point increase in financial debt (12.5% effect size, p < 0.05). Participants diagnosed with a chronic condition (heart condition, stroke or diabetes) were 3.6 percentage points more likely to develop financial debt (9.6%, p < 0.05) compared to households that did not develop a new chronic condition. Such differences were eliminated in participants in a house with above median wealth. There was no difference in credit card debt, availability of home equity line of credit, or use of home equity line of credit for participants with a new diagnosis. Conclusions: New diagnosis of cancer or a chronic condition were associated with increased financial debt for older Americans living in a household that were below median wealth.
Health disparities in New Zealand Māori with pancreatic cancer at Lakes District health board.
Authors: Camburn Laura , Hari Dass Prashanth
Published: June 2021

e18554

Background: Global health disparities between ethnicities have been well documented in pancreatic cancer treatment & outcomes. However, pancreatic cancer treatment & survival outcomes between ethnicities, particularly NZ Māori have been poorly documented in our region. Aim to review whether health disparities existed between Māori and New Zealand European patients (NZE) treated with pancreatic cancer. Methods: Patients diagnosed with pancreatic cancer at LDHB between 01 Jul 2014 to 31 Mar 2020 were identified using the faster cancer treatment data. This was cross checked against surgical and Oncology referrals. Electronic notes were reviewed to collect data on ethnicity, patient demographics, presentation, treatment and survival. Results: A total of 69 patients; 25 identified as Māori and 44 NZE. Performance status at presentation was similar between Māori and NZE patients; 64% and 61% respectively, having ECOG 0-1. Majority of patients presented with unresectable locally advanced or metastatic disease (Māori 92% vs NZE 82%). 9% presented with resectable disease, 4% were borderline resectable, only 4 (6%) patients underwent surgical resection. Median overall survival was 34 days for Māori versus 94 days for NZE patients. 72% of Māori patients had an OS < 60 days compared to 39% of NZE, however OS at 6 months was similar in both groups (28% Māori v 27% NZE). For locally advanced disease, similar rates of receipt of chemotherapy (71% vs 62%) were documented between Māori and NZE respectively. Of the 16 Māori patients with metastatic disease at presentation none received palliative chemotherapy compared to 6 / 23 (26%) NZE. Conclusions: Regardless of ethnicity relatively small numbers of our patients have curative surgery which is of concern. Despite adequate performance status at presentation and comparable outcomes in the locally advanced setting, NZ Māori were less likely to receive palliative chemotherapy in the metastatic setting. Further research is warranted to explain and reduce this disparity.
Is chimeric antigen receptor T cell (CART) a destination procedure? Lower socioeconomic class who live farther from center have less access to CART.
Authors: Ahmed Nausheen , Shippey Ernie , Kus Crissy , Appenfeller Allison , Hoffmann Marc Steven , Tun Aung M. , Ganguly Siddhartha , Shune Leyla , Devine Clint , Bansal Rajat , Abhyankar Sunil H. , Mushtaq Muhammad Umair , McGuirk Joseph
Published: June 2021

e18562

Background: Axicabtagene ciloleucel and tisagenlecleucel are commercially available CD19 chimeric antigen receptor T-cell (CART) therapies for B cell malignancies. Manufacturing pharmaceutical companies require patients to stay within 2 hours of the center for 4 weeks post infusion. Most centers require local lodging for that period if residence is over 30 minutes away. Financial burden may limit access. We therefore hypothesized that those who were likely to receive CART therapies were from higher income neighborhoods or lived closer to the facility. Methods: Since most patients get admitted for CART infusion, we used the Vizient CDB database for CART infusion admissions as well as other admissions. Patients over the age of 18 yrs who got commercially available CART between 2018 to 2020 were included. Distance was calculated in miles from patient zip code to treating center. Using census data, lower income neighborhoods (less than $40,000 median household income) were flagged. Results: 81 centers administered CART. We calculated the distance in miles between the patient and the center for both CART admissions as well as for all-cause inpatient admissions. Most admissions (81.2% all-cause vs 78.6% CART) were from neighborhoods with median income > $40,000. Most of the low-income admissions were from neighborhoods <10 miles (13.3% all admissions vs 15.7% CART). 80.6% of all CART patients came from neighborhoods over 10 miles, with 38.2% living over 60 miles away, while only 15.4% all-cause admissions were from > 60 miles. (p<.0001) While 74.9% of higher income CART patients lived beyond 10 miles from center, only 5.7% CART patients lived beyond 10 miles. Results summarized in Table. Conclusions: Most CART patients lived over 10 miles from the center, however less than 10% of them were from lower income neighborhoods. Neighborhood location relative to center and household income influence access and need to be addressed.[Table: see text]
Prognostic impact of obesity in cancer patients with COVID-19 infection: A systematic review and meta-analysis.
Authors: Park Robin , Wulff-Burchfield Elizabeth Marie , Mehta Kathan , Sun Weijing , Kasi Anup
Published: June 2021

e18578

Background: Obesity is a bona fide risk factor for ICU admission, mechanical ventilation, and mortality in patients (pts) with COVID-19 in the general population. However, whether obesity is a risk factor in cancer pts remains unknown. Herein, we have conducted a systematic review/meta-analysis of obesity and all-cause mortality in cancer pts with COVID-19. Methods: Following PRISMA guidelines,a systematic search of PubMed and Embase as well as major conference proceedings (ASCO/ESMO/AACR) was conducted for publications from inception to 14 January 2020. Observational studies that reported all-cause mortality in cancer pts with lab confirmation or clinical diagnosis of COVID-19 and BMI (obese (>30 kg/m2) vs. non-obese) were included in the analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated with the fixed-effects model based on low heterogeneity. Small sample publication bias was evaluated using the Begg’s Funnel Plot and Egger’s test. Results: After reviewing 3387 studies,3 retrospective cohort studies of 419 obese and 1694 non-obese cancer pts (N=2117) with COVID-19 in both inpatient/outpatient settings that reported outcomes based on obesity were found. The 3 studies were conducted multi-nationally in North America, in France, and in the Netherlands respectively. The median ages of the cohorts ranged 66-68. All studies included various cancers of various stages and were of high quality per Newcastle Ottawa scale (scores 7-9). Fixed effects meta-analysis showed no association between obesity and all-cause mortality (OR 0.95, 95% CI 0.74-1.23) in cancer pts with COVID-19. Heterogeneity was low (I2 = 33%). No significant funnel plot asymmetry was detected per Egger’s test (P=0.2273). The reported OR of each study is outlined in the table. Conclusions: In contrast to the general population, our analysis reveals that obesity is not associated with increased all-cause mortality in cancer pts with COVID-19. Limitations of this study include a limited number of included studies, reliance on retrospective studies, non-use of ethnicity-specific WHO BMI criteria, and limited granularity of the study-reported BMI. Future prospective studies are warranted to assess the complex interplay among anthropomorphic measures, cachexia/sarcopenia, comorbidities associated with the metabolic syndrome, and COVID-19 outcomes in the cancer pt population.[Table: see text]
Estimates of stage-specific preclinical sojourn time across 21 cancer types.
Authors: Broder Michael S. , Ailawadhi Sikander , Beltran Himisha , Blakely L. Johnetta , Budd George Thomas , Carr Laurie , Cecchini Michael , Cobb Patrick Wayne , Gibbs Sarah N. , Kansal Anuraag , Kim Ashley , Monk Bradley J. , Schwartzberg Lee S. , Wong Deborah J.L. , Yermilov Irina
Published: June 2021

e18584

Background: Cancer progression rates following diagnosis are readily measured. However, the progression rate of cancer during the preclinical sojourn time is generally unobserved. Understanding the duration of preclinical stages (“dwell time”) would allow clinicians to better identify appropriate screening intervals for cancer. We therefore elicited estimates of progression rate during the preclinical sojourn time for a wide variety of malignancies from a panel of clinical experts. Methods: We used a validated consensus methodology (RAND/UCLA modified Delphi panel method) to elicit per-stage dwell time estimates for 20 solid cancers and lymphoma from experts. Eleven experienced oncologists (general and subspecialists) from community and academic centers reviewed literature on the natural history of disease and estimated in number of years (<1 to 9+ years) how long it would take each cancer to progress from the beginning of clinically detectable Stage I/II/III to the beginning of the next stage in untreated adults. Cancer histological subtypes were grouped and experts were asked to provide an overall rating. Ratings were completed before and after a discussion of areas of disagreement. Results: Expert estimates and range of dwell time for 21 cancer types are provided in Table. Prostate and thyroid cancer were estimated to be the slowest growing, taking approximately 7 and 5 years respectively to progress through Stage I (range 4-8), 5 years to progress through Stage II (range 3-7), and 3 and 4 (range 2-5) years respectively to progress through Stage III. Esophageal, lung, liver/intrahepatic bile-duct, gallbladder, and pancreatic cancers were estimated to progress quickly through all three stages (1-2 years per stage). Conclusions: These findings summarize practicing oncologists’ estimates of dwell time in preclinical disease. Experts agreed on dwell times although ranges were large and differences in cancer subtypes were not captured. Generally, estimates trend with published data on survival with treatment: cancers with higher survival (e.g., prostate, thyroid) were estimated to grow slower, while cancers with lower survival (e.g., pancreatic, liver/intrahepatic bile-duct, gallbladder) were estimated to grow faster. These estimates could be useful when determining screening intervals for these or any subset of these cancers. [Table: see text]
Changes in prescribing of oral capecitabine versus intravenous (IV) 5-fluorouracil (5-FU) in gastrointestinal (GI) cancers during the COVID-19 pandemic.
Authors: Civelek Yasin , Cullen Daniel , Debono David Joseph , Fisch Michael Jordan , Barron John , Sylwestrzak Gosia
Published: June 2021

e18596

Background: Several oncology guidelines recommend using oral drugs vs. IV to minimize COVID-19 risk for patients with cancer. We examined the association between prescribing patterns of oral capecitabine vs. IV 5FU for GI cancers and social distancing, measured by the change in population mobility patterns in response to shelter-in place policies, during the pandemic. Methods: Using claims data for commercially insured members, we included patients 18 years of age or older with colorectal, gastroesophageal, or pancreatic cancer, who had continuous health plan coverage for at least 2 months before and 1 month after initiating chemotherapy with capecitabine or 5-FU from January 2017 to August 2020. We analyzed unadjusted trends in proportion of chemotherapy that was oral during pandemic (March 1st to August 31st, 2020) compared to previous years. Then, we conducted difference-in-differences analysis using COVID-19 Community Mobility Reports, by Google, and utilizing different levels of changes in mobility trends across states over time. In our main model, we used a 20% decrease in retail and recreation visits as our threshold and compared the prescribing rates in states below and above the threshold as well as before and after the pandemic began. We also used different thresholds and categories of places to check the sensitivity of our findings. Models are adjusted for age, gender, month of year, urban status, comorbidities, and state of residence at chemotherapy start date. Results: A total of 17,414 nationally distributed patients (69% colorectal, 13% gastroesophageal, 18% pancreatic) were included (mean age, 58.8 years; 41% female). During the pandemic, 1,875 patients (65% colorectal, 15% gastroesophageal, 20% pancreatic) were identified. The proportion of oral regimens did not change significantly for colorectal and gastroesophageal patients and decreased by 7.4 percentage points (pp) (p < 0.01) for pancreatic patients. In regression modelling with mobility data, oral prescribing rates for colorectal patients increased by 3.1 pp (p < 0.01), largely driven by increases for female patients (9.2 pp, p = 0.02). We observed a decrease in oral prescribing rates among pancreatic patients (-1.20 pp, p = 0.04) and did not observe a significant change for gastroesophageal patients. Our results are not sensitive to different social distancing specifications. Conclusions: We observed differential impact of the pandemic on oral prescribing rates by GI cancer type and gender. Oral prescribing increased among colorectal cancer patients driven mostly by higher oral prescribing in females. For pancreatic and gastroesophageal patients, oral prescriptions either remained unchanged or decreased. This observation may reflect a variable impact of the pandemic on women as compared to men and might involve heightened caregiving responsibilities for women.
Cancer care in the time of COVID-19: A conceptual framework to improve cancer outcomes during a pandemic.
Authors: Milch Vivienne , Anderiesz Cleola , Hector Debra , Turnbull Scott , Austen Melissa , Wang Rhona , Der Vartanian Carolyn , Keefe Dorothy Mary Kate
Published: June 2021

e18628

Background: At the start of the COVID-19 pandemic, a plan for cancer management during a pandemic did not exist. It soon became clear that without proper planning, cancer outcomes would worsen. Cancer patients are at increased risk of COVID-19 infection, morbidity, and mortality. Health sectors internationally reduced or paused non-urgent cancer care to protect cancer patients from COVID-19. However, disproportionate delays in screening, diagnosis, and treatment can unduly impact cancer outcomes, and backlogs can further burden a strained health system. Tailored approaches to cancer management are required which balance health resource availability along with the risks of exposure and benefits of treatment. Australia’s relatively low COVID-19 case numbers afforded Cancer Australia an opportunity to proactively plan for optimal cancer management during this, and future, pandemics. Methods: Cancer Australia’s Cancer care in the time of COVID-19: A conceptual framework for the management of cancer during a pandemic (the framework) maps evidence-based cancer care considerations in relation to a health system’s capacity across acute and recovery pandemic phases, in relation to steps of the cancer care pathway. The framework promotes infection control and resource prioritisation in the context of innovative care models, triaging approaches and individualised treatment plans, underpinned by effective communication and shared decision-making. Results: The framework supports health system planning and risk-stratified approaches to guide decision-making and improve cancer outcomes. Many aspects of cancer care are recommended to continue (to varying degrees) in most pandemic phases, with modifications or pauses in some aspects of care as the pandemic curve approaches or exceeds health system capacity. Principles of the framework were employed during the second wave of COVID-19 in the Australian state of Victoria, with continuation of cancer screening programs, diagnostic investigations, and treatments wherever it was safe to do so. This resulted in reductions in cancer services and treatment being relatively smaller than in the first wave. Conclusions: Cancer management in a pandemic is not a one-size-fits-all. Countries and jurisdictions need to tailor cancer care according to the risk of the health system becoming overwhelmed. The framework guides optimal cancer care to improve outcomes for people with cancer, while minimising COVID-19 infection. As further evidence becomes available from this pandemic or in future pandemics, this framework can be refined to inform ongoing and future pandemic health system planning.
Impact of psychosocial factors on the receipt of guideline concordant care in adolescent and young adults with localized Ewing sarcoma and osteosarcoma.
Authors: Machhi Rushad , Parkes Amanda Marie
Published: June 2021

e18658

Background: Adolescent and young adults (AYAs) experience poorer outcomes, including lower survival improvements, compared to younger and older patients. As higher compliance with National Comprehensive Cancer Network (NCCN) guidelines has been associated with improved outcomes, we sought to understand the influence of psychosocial factors on receipt of care concordant with NCCN guidelines in AYAs with bone sarcomas. Methods: Retrospective chart review was performed on adult AYA patients (18-39 years) with localized Ewing sarcoma (ES) or high-grade conventional osteosarcoma (OS) seen at least once between 2015-2019 at the University of Wisconsin (UW). These tumor types were selected given uniform guideline-based care recommendations. Chart review identified receipt of standard care as per NCCN Bone Cancer guidelines, defined as neoadjuvant chemotherapy, local therapy (surgery/radiation), and adjuvant chemotherapy with receipt of at least 75% of recommended chemotherapy cycles, and compared to interpersonal relationships (marital status and presence of children at cancer diagnosis), changes in school or work following cancer diagnosis, substance use, and residential location. Results: We identified 21 AYA patients with localized ES (10/21, 48%) or OS (11/21, 52%), with 67% (14/21) receiving NCCN guideline concordant care. Receipt of guideline concordant care was associated with interpersonal relationships, with only 33% (1/3) of patients with children versus 72% (13/18) of patients without children receiving guideline concordant care. Additionally, the one patient noted to divorce following cancer diagnosis did not receive guideline concordant care (0/1, 0%) as compared with 67% (10/15) of single patients and 80% (4/5) of married patients. Vocational changes also affected care, with only 56% (5/9) of patients with work change following cancer diagnosis receiving guideline concordant care versus 75% (9/12) without work changes. Guideline concordant care was less common in patients with alcohol use (5/10, 50%) as compared with patients without alcohol use (9/11, 82%). Residential distance to UW was also associated with receipt of guideline concordant care, which was more common in patients living 0-20 miles from UW (86%, 6/7) as compared with those 21-100 miles from UW (60%, 6/10) or > 100 miles from UW (50%, 2/4). Conclusions: Given the occurrence of cancer during a complex developmental time, AYAs have a relatively high occurrence of psychosocial changes and needs, which we found to be associated with receipt of NCCN guideline concordant care in patients with localized ES and OS. While a limited sample size, as the first study to define specific psychosocial factors that affect receipt of guideline concordant care, these finding suggest the need to improve identification and support of these discrete patient factors.
Real-world clinical adverse events (AEs) among nonmetastatic castration-resistant prostate cancer (nmCRPC) patients treated with novel anti-androgen (AA) therapies: A retrospective database study.
Authors: Freedland Stephen J. , Appukkuttan Sreevalsa , Yao Jianying , Du Yuxian , Parkin Jacqueline , Partridge Jamie , Kong Sheldon
Published: June 2021

e18675

Background: Novel AA agents, such aspalutamide (Apa), enzalutamide (Enza) and darolutamide (Daro) are approved for the treatment of nmCRPC. In clinical trials, they were associated with AEs such as fatigue, fractures and falls. This study aimed to describe the real-world incidence of AEs among nmCRPC patients who initiated treatment with AA agents. Methods: Claims from Optum Clinformatics Data Mart, a large single-payer claims database were used to retrospectively identify adult males with prostate cancer (PC), evidence of castration, absence of metastases codes and >1 claim for AA therapies Apa and Enza (index date) from Jan 2017 through Dec 2019. Daro, a more recently approved AA, was not included due to lack of data. Incidence of central nervous system (CNS) (including but not limited to fatigue, falls and cognitive impairment) and any AE (fracture, rash, hypertension among others) were estimated and Kaplan-Meier analyses were used to quantify the median time from therapy initiation to clinical event occurrence. Multivariable Cox-proportional hazards model was used to identify clinical event predictors. A washout of previous AE events in the 1-year baseline was applied to identify true incident events. Results: A total of 605 patients (156 Apa and 449 Enza) were included in the study. The majority were ≥65 yrs (94.0%), white (56.0%), resided in the south (47.1%), and had Medicare insurance (86.4%). Almost all were medically castrated (99.0%) and mean Charlson Comorbidity Index (CCI) Score was 2.28. Incidence rates of all clinical events and CNS-related events were high (71.2% and 46.1%, respectively) with no major differences between Apa and Enza (Table). The median time from Apa or Enza treatment initiation to any clinical event was 71 and 64 days, respectively, and 282 and 209 days for CNS-related events, respectively. Significant predictors of having any events included age >75 yrs and high CCI score. Similar predictors were found for any CNS events. Conclusions: More than 70% of Apa and Enza treated nmCRPC patients had at least 1 clinical AE. Given the lack of a control cohort, further study is needed to assess whether these events are related to AAs or represent inherent risks of these events in the underlying population of largely older men with advanced PC. Future studies are warranted with all approved agents including Daro. [Table: see text]
Identifying pre-existing dementia in older adults diagnosed with cancer using a national claims database.
Authors: Schiaffino Melody K. , Moore Alison , Schumacher Jessica R. , Gilbert Paul , Nalawade Vinit , Schempp Timothy , Murphy James
Published: June 2021

e18678

Background: Older adults over the age of 65 represent the majority of patients diagnosed with (60%), among them, 15-30% have a pre-existing Alzheimer’s disease or related dementia (ADRD) that puts them at higher risk for over and under treatment. Studying the role of pre-existing ADRD in cancer patients is vital to understanding treatment planning behavior, patterns of health care utilization, and adverse treatment outcomes. Massive administrative datasets, or “big data” represent the information rich environment that is useful for this endeavor. Methods: Our study utilized a clinically validated algorithm to assess the prevalence of pre-existing ADRD and cancer across six cancer types. We utilized the SEER-Medicare dataset for analyzing the study years 2004-2015 (N = 337 932). We extracted ICD-9 codes to identify ADRD using the Centers for Medicaid Services Chronic Conditions Warehouse (CCW) algorithm. In sensitivity analysis we compared the prevalence of ADRD+Cancer using the NCI (2014) and CCW algorithms. Results: We found a significant difference between the two algorithms (p < .0001) and a higher overall prevalence of comorbid ADRD+Cancer using the CCW (6.6%). Additionally, we found ADRD+Cancer prevalence was significantly higher among racial and ethnic subgroups compared to White and unstaged tumors compared with any numbered American Joint Committee on Cancer (AJCC) stages (p < .0001). Conclusions: Using a clinically validated algorithm we were able to identify more cases of ADRD+Cancer in big data. This figure remains underestimated for ADRD+cancer compared to clinically-validated studies. Further research into the validation approach and codes that are used for ADRD classification can improve how we identify ADRD in massive administrative data. This is critical given the growing population of diverse older adults in the U.S.
Off-label targeted therapy (TT) use in recurrent/metastatic NSCLC.
Authors: Wang Victoria , Cui Chenming , Yang Lei , Li Gerald , Schrock Alexa Betzig , Li Meijuan , Venstrom Jeffrey Michael , Tolba Khaled A.
Published: June 2021

e18688

Background: Comprehensive genomic profiling (CGP) is an established diagnostic approach to select patients for TT. As CGP gains wide adoption, an increasing number of patients are found to harbor driver mutations for which no approved TT is available. This is often addressed through use of matched TKI and mAb approved for other mutations or anatomic sites. In this work, we examined the clinical efficacy of off-label TT in R/M NSCLC. Methods: Using a de-identified NSCLC clinico-genomic database (CGDB), we identified 6590 NSCLC patients who underwent Foundation Medicine CGP, of whom 17.8% harbored an actionable genomic alteration (GA) for which an FDA-approved TT was available and 2% (133) whose GA (MET ex-14, uncommon EGFRm, EGFR ex20ins, HER2 amp/mut, RET fusion, BRAF class 2/3) lacked an FDA-approved TT (62 in 1L and 71 in ≥2L ) who received matched off-label TT. ESMO Scale for Clinical Actionability (ESCAT) was used to grade levels of evidence. For patients who progressed on initial chemotherapy (range 2 – 9 lines, median 3), we calculated clinical efficacy using the ratio of real world PFS on targeted therapy (rw-PFS2) to rw-PFS on the last prior line of therapy (rw-PFS1) and used a cut-off of PFS2/PFS1 > 1.3 to determine off-label drug efficacy. Results: Of the 133 patients reviewed, 72 were classified as ESCAT level IB (uncommon EGFRm, MET-ex14), 45 IIB (HER2m/amp, EGFR ex-20ins), 7 IC (RET fusions). PFS varied significantly by mutation and line of therapy (table 1) with uncommon EGFRm+ and MET-ex14 exhibiting best response while EGFR ex20 ins, BRAF class 2/3 and HER2 amp fared significantly worse. 55.8% of the patients (39 of 71) reached a PFS2/PFS1 ratio > 1.3 (two-sided 95% CI, 45.3 % – 68.7 %), ranging from 93% in uncommon EGFRm+ down to 20% in HER2 amp and 44% in ex20ins. Conclusions: We provide real-world evidence to assess off-label TT in NSCLC. Clinical benefit derived from off-label TT is unevenly distributed across various mutations with most survival advantage accruing to specific mutations (MET-ex14 and uncommon EGFRm) at the expense of others (HER2 amp). Survival advantage was highly influenced by two factors: A) the timing of CGP with the earlier recipients of genomic profiling achieving better outcome, B) the identity of the driver mutation, highlighting the role of clinical actionability tier system to define level of evidence supporting such intervention.[Table: see text]