bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of anti-cancer therapy on immunological response to COVID-19 vaccination.
Authors: Jackson-Spence Francesca , Toms Charlotte , Yang Yu-Hsuen , Walshaw Lani , Riddell Anna , Cutino-Moguel Maria-Teresa , Szabados Bernadett , Propper David , Powles Thomas 
Published: February 2022

319 Background: The efficacy of SARS-COV-2 vaccination has been demonstrated in healthy individuals. Immune responses are less well characterised in cancer patient groups, especially those receiving anticancer therapy (e.g. immune therapy, chemotherapy and targeted therapies. We aim to assess the immune response to the SARS-COV-2 vaccination in patients with solid organ cancer on different systemic anti-cancer therapies. Methods: All patients received 2 doses of COVID-19 mRNA vaccination as part of the UK National vaccination programme; with the second booster dose administered within 12 weeks of the first dose. All patients received either BNT162b2 (Pfizer/BioNTech) or ChAdOx1 S (AstraZeneca) vaccines. Sequential serum samples were collected pre-booster dose vaccination (baseline/within -30 days) and after second dose SARS-COV-2 vaccination, at 14-35 days and 36-63 days. Presence and titres of serum Anti-SARS-CoV-2 Spike protein (S) antibody titres were measured. Seroconversion is defined as a response ≥0.8 U/ml, and maximum response to Anti-S is defined as ≥250 U/ml. Responses were measured in 3 patient groups according to the type of anti-cancer therapy: chemotherapy (CHT group), immune therapy (IO group) and targeted therapies, mainly VEGF TKI (TT group). Results: Overall, 61 patients were recruited: 45.9%(28/61) in CHT group, 32.8% (20/61) in IO group and 21.3% (13/61) in the TT group. Baseline characteristics were comparable between patient groups. In response to the booster dose vaccination at 14-35 days, the number of patients who seroconverted was 79.3% (23/29), 94.7% (18/19) and 84.6% (11/13) in the CHT, IO and TT groups, respectively. At this same time point, 51.7% (15/29) in the CHT group achieved maximum anti-S titre levels (≥250 U/ml), compared with 78.9% (15/19) of patients in IO group and 69.2% (9/13) of patients in TT group. All 3 groups demonstrated a significant increase in Anti-S antibodies at 14-35 days after second dose vaccine when compared to pre-booster serum levels, with the largest increase seen in the IO group with a mean Anti-S increase of 149.1 U/ml (SD±105.0, p < 0.0001) followed by the TT group mean increase 120.2 U/ml (SD ±110.8, p < 0.01) and the CHT group, mean increase 83.0 U/ml (SD ±108.4, p < 0.001). Anti-S antibody levels were sustained at 36-63 days post-booster across all groups. However only IO patients had a sustained immune response to vaccination, with median Anti-S titres level of ≥250 U/ml and a significant drop was seen in the CHT group (median Anti-S level 138, p < 0.05). Conclusions: Anti-S titres increase following vaccination in all 3 groups but remain most sustained in the IO group at 36-63 days post-vaccination. Chemotherapy and other targeted therapy treated patients may benefit from early COVID-19 vaccine boosters, compared to patients receiving immune therapy.
Using tele-mentoring to optimize quality of care and quality of life for patients with renal cell carcinoma (TOQQ-RCC).
Authors: Wulff-Burchfield Elizabeth Marie , Potts Maryellen , Knight Catherine , Klemp Jennifer R. 
Published: February 2022

326 Background: Overall survival from metastatic renal cell carcinoma (RCC) has risen in recent years due in part due to therapies such as immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI). TKI and ICI have unique and high-impact side effect profiles, and deficits persist in clinicians’ understanding of patient tolerance of and response to treatment, particularly in rural and community practices. We developed a tele-mentoring series to improve knowledge and clinical care gaps in ICI and TKI toxicity assessment and management for persons treated for RCC. Methods: Rural and community cancer care teams were invited by the Masonic Cancer Alliance, the outreach network of The University of Kansas Cancer Center, to participate in a five session Project ECHO (Extension for Community Health Outcomes) didactic and case-based educational series. Topics included distress screening, shared decision-making for RCC treatment, ICI and TKI toxicity assessment and management, at-home ICI administration, and implementing toxicity monitoring protocols. A mixed-methods approach collected data from participants pre- and post-TOQQ-RCC series. Clinician interviews assessed current practice protocols and were transcribed and analyzed thematically. Organizational Readiness for Implementing Change (ORIC) was administered pre- and post-TOQQ-RCC intervention; mean scores were calculated to determine readiness for change in toxicity monitoring and management protocols. Participant engagement and satisfaction were assessed; satisfaction measure included a Likert-like scale of poor, fair, average, good, and outstanding. Results: Fifty-two attendees from 11 cancer care institutions across Kansas and Missouri registered for the TOQQ-RCC sessions. An average of 15 participants attended each session including physicians, advanced practice providers, nurses, and other disciplines. Session evaluations rated content/delivery as good or outstanding. Themes from qualitative analysis revealed patient education as a primary barrier to effective toxicity identification and management. One-third of participants completed ORIC post-assessment; mean ORIC scores dropped by a mean 0.4 (10%) post-TOQQ-RCC series, indicating decreased readiness to implement changes to toxicity monitoring and management protocols. Conclusions: Rural and community oncology clinicians are willing to engage in tele-mentoring to improve knowledge and clinical care gaps regarding ICI and TKI toxicity assessment and management. Decrease in ORIC scores post-TOQQ-RCC series may indicate increased understanding of the complex processes and resources required to institute meaningful improvement to toxicity monitoring and management protocols for patients treated in rural and community settings. Future directions will include formal organizational needs assessments.
Changes in perception of immunotherapy over time among patients with advanced genitourinary cancers.
Authors: Malhotra Jasnoor , Philip Errol James , Govindarajan Ameish , Meza Luis A , Zengin Zeynep Busra , Salgia Sabrina , Muddasani Ramya , Chawla Neal Shiv , Castro Daniela , Chehrazi-Raffle Alex , Dizman Nazli , Bergerot Paulo Gustavo , Hsu Joann , Dorff Tanya B. , Pal Sumanta K. , Bergerot Cristiane Decat 
Published: February 2022

328 Background: Previous studies have shown that a significant proportion of patients with metastatic genitourinary cancers harbor inaccurate expectations of cure prior to starting treatment with immunotherapy. This study sought to compare changes in perceptions of immunotherapy reported before, and three months after, the start of therapy, as well as treatment side-effects and quality of life. Methods: This longitudinal study enrolled patients diagnosed with advanced genitourinary cancers (bladder, renal, and prostate cancers) prior to commencing immunotherapy. Patients’ perceptions were assessed prior to starting treatment (T0) and three months later (T1). Patients responded to the same survey at both time points assessing expectations of side effects, clinical outcomes (expectation of cure) and quality of life (Functional Assessment of Chronic Illness Therapy-General). Results: Among the 30 patients enrolled, the median age was 67 years old (range, 44-91); most were male (70%), married (80%), and well-educated (70%). Renal cell carcinoma (70%) was the most common form of cancer. Before starting immunotherapy (T0), patients expected (1) fewer side effects (83%) compared with other types of cancer treatment, (2) great efficacy in preventing tumor progression (90%). and (3) increased survival (90%). Notably, the expectation of cure with immunotherapy treatment had changed over time (T0 = 24% vs T1 = 7%; P = 0.001) and overall quality of life had increased (median at T0 = 90 vs T1 = 98; P = 0.01). Three months into treatment (T1), patients perceived themselves as less active (T0 = 70% vs T1 = 63%; P = 0.02), however just 16% reported severe side effects, including fatigue (10%) and diarrhea (10%). In general, patients were satisfied with the management of these side effects (60%). The majority of patients perceived improvement in their condition (50%) and were satisfied with their treatment (60%). Conclusions: This longitudinal study suggests that inaccurate perceptions of cure with immunotherapy may recede over time, with an increased proportion of patients estimating a more accurate (and lower) chance of cure after 3 months of treatment. Patients also reported improved quality of life despite these adjusted expectations of cure.
Variance of mean baseline health-related quality of life across phase III clinical trials in metastatic renal cell carcinoma.
Authors: Henegan John Clark , Bell Francis Garner 
Published: February 2022

329 Background: Health-related quality of life (HRQoL) instruments in clinic trials provide insight into the impacts a disease and therapy have on a person’s well-being. Baseline measurements of global HRQoL reflect a trial population’s quality of life at the start of a trial. It is unknown how baseline mean HRQoL values vary across trials. Our hypothesis: The HRQoL for trials populations would decrease with later lines of therapy but would not be affected by chronological time. Methods: The year the first patient was enrolled in a trial, the number of prior lines of therapy, the HRQoL instrument(s) used, and the trial’s name was recorded along with the intervention arm’s global HRQoL summary statistics (i.e., mean value, standard deviation, and number of respondents). The intervention arm (as opposed to a combination of both arms of the study) was analyzed since the HRQoL at baseline was often balanced between the two arms but baseline HRQoL summary statistics for the entire trial population was not typically available. The baseline HRQoL means were compared across trials using common HRQoL instruments via one-way ANOVA (https://statpages.info/anova1sm.html). A p-value of less than 0.05 indicated there was a significant difference in mean HRQoL values somewhere among the various groups. The Tukey honestly significantly different post-hoc test was used to evaluate which groups were significantly different from others. Results: Mean baseline HRQoL varied significantly across trials for the FKSI-19 (p < 0.001) and the EQ-5D (p = 0.004) instruments. Conclusions: While HRQoL varied across trials for the FKSI-19 and the EQ-5D instruments, post-hoc tests indicated that only the FKDI-19 varied as hypothesized by line of therapy. The EQ-5D baseline HRQoL values variation correlated more by year of first participant. Future research should focus on the applicability of the EQ-5D and EQ-VAS HRQoL instruments in a modern population of patients with metastatic RCC.[Table: see text]
Real-world clinical outcomes of patients (pts) with metastatic renal cell carcinoma (mRCC) in current immune-oncology (IO) and tyrosine kinase inhibitors (TKIs) era.
Authors: Shah Neil J. , Sura Sneha , Shinde Reshma , Shi Junxin , Perini Rodolfo F. , Puneet Singhal , Robert Nicholas J. , Vogelzang Nicholas J. , Motzer Robert J. 
Published: February 2022

331 Background: IO agents and TKIs have revolutionized treatment landscape of mRCC pts. Despite robust clinical trials’ data for these agents, real-world (rw) clinical outcomes data, especially from community setting in the US is limited. Methods: This retrospective cohort study included mRCC pts who received 1L treatment with either, pembrolizumab + axitinib (P+A) (IO+TKI), ipilimumab + nivolumab (I+P) (IO+IO) or cabozantinib, sunitinib, pazopanib and axitinib (TKI monotherapy (mono)) between 1/1/2018 and 9/30/2020 from The US Oncology Network of 480 sites. Patients were followed until 12/31/2020 to collect data on rw-time on treatment (rwToT), rw-time to next treatment (rwTTNT) and overall survival (OS). Kaplan-Meier analyses were performed to examine clinical outcomes. Results: We identified 1,538 eligible pts, of which 18% (n = 279) received P+A, 42% (n = 641) I+N and 40% (n = 618) TKI mono. The median follow-up duration for P+A, I+N and TKI mono cohort was 7.2 (range 0.0 - 20.5), 8.5 (range 0.0 - 32.3) and 7.8 (range 0.0 - 35.3) months, respectively. Majority of pts had clear cell histology (P+A - 82%, I+N - 86%, and TKI mono - 72%) and intermediate/poor IMDC risk score (P+A - 87%, I+N - 94%, and TKI mono - 81%). Median OS was not reached for P+A and was similar for I+N and TKI mono cohort (NR, 27.6, and 26.9 months, p=0.237, respectively). The median rwToT (13.6 vs. 5.8 vs. 3.4 months, p<0.0001) and rwTTNT (16.4 vs. 8.3 vs. 8.4 months, p<0.0001) was higher for P+A cohort compared to I+N and TKI mono cohort, respectively. Similar clinical outcomes results were noted for subgroup of pts with intermediate and/or poor IMDC risk score (Table). Conclusions: In this rw US community oncology-based study, longer treatment exposure (rwToT, rwTTNT) was noted in P+A compared to I+N or TKI mono. These rw endpoints may reflect treatment exposure, tolerability and/or compliance.[Table: see text]
Systemic therapy in patients with metastatic Xp11.2 translocation renal cell carcinoma.
Authors: Yan Xieqiao , Li Siming , Chi Zhihong , Si Lu , Cui Chuanliang , Kong Yan , Zhou Li , Tang Bixia , Wu Xiaowen , Mao Lili , Wang Xuan , Lian Bin , Bai Xue , Dai Jie , Guo Jun , Sheng Xinan 
Published: February 2022

341 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5 - 8.8) and 17.9 months (12.4 - 24.4), respectively. First-line treatment mainly included sunitinib (n = 14), sorafenib (n = 15), axitinib (n = 6), and pazopanib (n = 5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, axitinib and mTOR inhibitor, the median PFS for these regimens was 8.5, 7.2 and 2.0 months, respectively. Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Conclusions: Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI/ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC.
Treatment outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC) with sarcomatoid and/or rhabdoid (S/R) features after progressive disease (PD) on immune checkpoint therapy (ICT): The MD Anderson Cancer Center experience.
Authors: Hahn Andrew Warren , Viscuse Paul Vincent , Surasi Devaki Shilpa , Bathala Tharakeswara , Wiele Andrew James , Starbuck Michael W , Campbell Matthew T , Shah Amishi Yogesh , Jonasch Eric , Gao Jianjun , Alhalabi Omar , Sircar Kanishka , Tannir Nizar M. , Msaouel Pavlos 
Published: February 2022

351 Background: S/R mRCC is an aggressive disease that is associated with improved response to ICT. Studies performed prior to the approval of ICT demonstrated poor outcomes of S/R RCC with VEGF targeted therapies (TT). Here, we report outcomes of pts with S/R mRCC treated with VEGF TT after PD on ICT. Methods: We retrospectively reviewed the records of pts with mRCC with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S+R) features who received VEGF TT after PD on ICT. Clinical endpoints of interest were time on VEGF TT and OS from treatment initiation. Directed acyclic graphs were used to identify confounders for adjustment in regression models. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using multivariable Cox regression. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGF TT, and inclusion of cabozantinib in the post-ICT VEGF TT regimen. Results: 57 pts with metastatic S/R RCC (52 with clear cell and 5 with non-clear cell histology) received a VEGF TT after PD on ICT. 46% of pts received a VEGF TT prior to ICT. After PD on ICT, 67% of pts had IMDC intermediate-risk disease; the most commonly used VEGF TT were cabozantinib (44%), either sunitinib, pazopanib, or axitinib (24%), and a VEGF TT in combination with an ICT (21%). Pts with R RCC had significantly longer time on VEGF TT compared with S RCC (adjusted HR = 0.45, 95% CI 0.21-0.94, p = 0.034), whereas the OS comparison was inconclusive (adjusted HR = 0.77, 95% CI 0.36-1.62, p = 0.486). IMDC risk classification following ICT progression was predictive of OS (adjusted HR = 2.22, 95% CI 1.07-4.61, p = 0.032), whereas, its association with time on VEGF TT was less conclusive (adjusted HR = 1.78, 95% CI 0.88-3.60, p = 0.107). Conclusions: Patients with S/R mRCC derive clinical benefit from VEGF TT after progression on ICT, and it is similar to the benefit previously described for patients without S/R features. Our findings suggest that the type of S/R features present and IMDC risk score inform the clinical benefit that VEGF TT will produce in this setting.[Table: see text]
Efficacy and safety of nivolumab plus ipilimumab (N+I) versus sunitinib (S) for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (sRCC) in the phase 3 CheckMate 214 trial with extended 5-year minimum follow-up.
Authors: Tannir Nizar M. , Signoretti Sabina , Choueiri Toni K. , McDermott David F. , Motzer Robert J. , George Saby , Powles Thomas , Donskov Frede , Tykodi Scott S. , Pal Sumanta K. , Gupta Saurabh , Lee Chung-Wei , McHenry M. Brent , Rini Brian I. 
Published: February 2022

352 Background: sRCC is an aggressive histologic growth pattern in RCC with a poor prognosis and limited therapeutic options. First-line N+I provided efficacy benefits over S in patients (pts) with sRCC and intermediate/poor (I/P)-risk disease at 42 months follow-up. Here, we report an exploratory post hoc analysis of N+I vs S in pts with I/P-risk and sRCC with long-term follow-up of 5 years. Methods: Pts with clear cell advanced RCC were randomized 1:1 to N 3 mg/kg plus I 1 mg/kg every 3 weeks × 4, then N 3 mg/kg every 2 weeks vs S 50 mg once daily (4 weeks; 6-week cycles). Pts with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology. Outcomes in pts with sRCC were not prespecified. Endpoints in pts with sRCC and IMDC I/P risk included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Outcomes were also assessed per baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes used descriptive statistics. Results: Of 1096 randomized pts in CheckMate 214, 139 I/P-risk pts with sRCC were identified (N+I, n = 74; S, n = 65). Of all treated pts, 9 of 73 (12%) in the N+I arm vs zero of 65 in the S arm remained on treatment. The primary reason for discontinuation was disease progression (N+I, 37%; S, 71%). OS continued to favor N+I vs S (HR 0.46 [95% CI 0.29–0.71]; P = 0.0004; table). PFS benefit with N+I vs S was similarly maintained (HR 0.50 [95% CI 0.32–0.80; P = 0.0036]). Additionally, ORR was higher (61% vs 23%; P < 0.0001), median duration of response was longer (NR vs 25 months), and more pts had complete responses (23% vs 6%) with N+I vs S, respectively. Efficacy was better with N+I vs S regardless of PD-L1 expression, yet the degree of OS, PFS, and ORR benefits with N+I was greater for pts with PD-L1 ≥ 1% (Table). No new safety signals emerged in either arm. Conclusions: N+I showed clinically meaningful benefits in long-term OS, PFS, and the frequency and depth of response vs S in previously untreated pts with sRCC and I/P-risk disease, supporting N+I as a preferred first-line therapy in this population. Clinical trial information: NCT02231749. [Table: see text]
Comparison of patients with high-risk nonmetastatic clear cell renal carcinoma in adjuvant therapy trials versus nonclinical trial patients.
Authors: Hoogenes Jen , Breau Rodney H. , Bhindi Bimal , Rendon Ricardo A. , Tanguay Simon , Finelli Antonio , So Alan , Lavallee Luke , Pouliot Frederic , Lattouf Jean-Baptiste , Dean Lucas W. , Drachenberg Darrel E , Wood Lori , Basappa Naveen S. , Heng Daniel Yick Chin , Hansen Aaron Richard , Soulieres Denis , Bjarnason Georg A. , Mallick Ranjeeta , Kapoor Anil 
Published: February 2022

361 Background: Characteristics of patients with high risk for recurrence non-metastatic renal cell carcinoma (nmRCC) participating in adjuvant therapy clinical trials post-nephrectomy have not been well described. We evaluated high risk nmRCC patients in the CKCis database to explore differences between trial and non-trial patients. Methods: Adult patients undergoing partial or radical nephrectomy for clear cell nmRCC between January 1, 2011 and March 31, 2021 were included. CKCis is a prospective cohort of patients from 14 Canadian academic institutions. Patients with high risk nmRCC (using modified UCLA Integrated Staging System) were included. Demographic, clinical, and survival statistics were analyzed for all patients and comparatively for the trial and non-trial groups. Results: 1459 patients, including 63 in adjuvant trials, were evaluated. 71% were male, 91% had pT3N0M0 disease. Disease characteristics including tumor size, stage, grade, location, necrosis, and margin status were similar between groups. Trial patients were younger (mean age 58.1 vs. 63.6; p < 0.0001) and had lower Charlson Comorbidity Index scores (median 4 [3,6) vs. 5 [4,6] p < 0.001). Estimated overall survival (OS) at 5 years was 80.8% (95% CI, 65,90) for trial patients and 74.8% (95% CI, 71,78.2) for non-trial patients. Recurrence-free survival at 5 years for trial patients was 48.6% (95% CI, 34,61.7) and 39.2% (95% CI, 35.2,43.1) for non-trial patients. Conclusions: Patients in adjuvant trials were younger and healthier at baseline than the average high risk nmRCC CKCis patient. Trial patients appear to have had longer time to recurrence and longer survival compared to non-trial patients, although not reaching statistical significance. Selection bias is common in clinical trials and evaluation of real-world population-based evidence of patients receiving adjuvant therapy will be important to ensure phase 3 trial results have external validity.