bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of combination of PD-1 immune checkpoint inhibition with all-lesion stereotactic radiation (SBRT) in oligometastatic renal cell carcinoma (omRCC).
Authors: Liu Jing , Zou Benkui , Zhang Chao , Zhu Kunli , Feng Rui , Xu Lei , Dou Xue , Shi Pengyue , Zhang Yun , Yue Jinbo 
Published: March 2023

677 Background: Although systemic therapy has recently made strides, the 5-year survival rate of mRCC patients is still low — around 10%. Through the abscopal effect, SBRT can improve the antitumor immunity of PD-1 immune checkpoint inhibition (ICI) in metastatic RCC. OmRCC patients have a low tumor load and a favorable prognosis, so more active treatment strategies are needed. It might work even better when all lesions of omRCC are controlled by SBRT. The study aims to evaluate whether the antitumour immunity can be enhanced by combination of ICI and all-lesion SBRT for omRCC. Methods: Patients with progression disease after ≤ 2 prior anti-angiogenic therapies and with ≤ 5 lesions located in ≤ 3 non-brain metastatic sites may all suitable for SBRT are included. Tislelizumab was given as 200 mg in intravenously on day 1, Q3W, until PD or unacceptable toxicity. Hypofractionated radiation at a dose and schedule of 5-8 Gy×3-10 fractions were performed according to lesion site, size and organs at risk individually. SBRT of first lesion were applied after 7 days from the first infusion of Tislelizumab. SBRT of other lesions were performed sequentially during the intervals of Tislelizumab. The primary objective is Objective Response Rate (ORR) according to RECIST v1.1. Secondary endpoints are progression free survival (PFS), overall survival (OS) and safety profile. An exploratory project also identifies molecular basis of synergistic effect of SBRT and immunotherapy, potential mechanisms of ICI resistance. Results: Fifteen patients were enrolled from May 2021 to May 2022. Totally 36 lesions were radiated, including 10 lung lesions (63 Gy/9 fractions), 10 bone lesions (24-40 Gy/5-8 fractions), 7 lymph nodes (30-50 Gy/6-10 fractions), 4 kidney lesions (40 Gy/5 fractions), and 5 other lesions. ORR were 33.3% for patients (CR=0, PR=5, SD=7, PD=2, not evaluable=1) and 27.8% for lesions (CR=2, PR=8, SD=11, PD=3, not evaluable=12). The most common treatment-related toxicities include fatigue (20%), hypothyroidism (20%), and pneumonia (13.3%), all with G1-2. One patient suffered G3 treatment-related hematologic toxicity. There were no treatment related deaths. Median PFS and OS were not reached. Conclusions: The combination of all-lesion SBRT with ICI is feasible and associated with an accepted safety profile. Encouraging antitumor activity was observed warranting further investigations. Clinical trial information: ChiECRCT20210046 .
Barriers to guideline-concordant use of bone modifying agents for prostate cancer.
Authors: Mitchell Aaron Philip , Persaud Sonia , Chimonas Susan , Salner Andrew L. , Palyca Paul , Farooki Azeez , Ostroff Jamie S. , Morris Michael J. 
Published: March 2023

68 Background: NCCN Guidelines recommend the use of bone-modifying agents (BMAs) to prevent skeletal-related events (SRE) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Prior studies have identified both underuse of BMAs for CRPC and overuse for CSPC, but the clinical circumstances underlying these apparent gaps in care are unknown. Methods: Qualitative interview study, with physicians who treat prostate cancer within an academic cancer center and an affiliated network of community-based practices. Using a semi-structured interview guide, an experienced moderator probed participants’ experiences and perceptions around NCCN Guidelines recommendations, guideline adherence and non-adherence, and barriers to adherence. Interviews also probed participants’ views of potential interventions to promote guideline-concordant BMA use. Participants used Likert-scale items to rate the likely effectiveness of each intervention in influencing BMA practice patterns. They also identified the 3 most helpful interventions for reducing BMA underuse and overuse separately. Results: 19 physicians were invited, of whom 15 agreed to participate; 1 physician did not respond to some questions as outside scope of practice. All were aware of the recommendation for use of BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the burden of bony metastatic disease. 36% (5/14) were unaware of recommendations for baseline DEXA scan and BMA for patients with low bone mineral density. The most commonly reported barriers (occurring “often” or “sometimes”) to BMA use for CRPC were obtaining dental clearance (11/15) and insufficient time in clinic (6/15). The interventions perceived as most helpful to reduce underuse for CRPC were dental navigation (11/15) and EMR-based guidance (9/15). The interventions identified as most helpful to reduce overuse for CSPC were peer-to-peer education (14/15) and EMR-based guidance (13/15). Conclusions: Among physicians treating prostate cancer in our study, there was incomplete awareness of guideline recommendations for screening and treatment of low bone mineral density, and against BMA use for SRE prevention in CSPC. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred implementation strategies to reduce underuse and overuse of BMAs.
Clinical characteristics and outcomes of SARS-CoV-2 infection in patients with genitourinary cancer.
Authors: Kenny Dorothy , Wang Jue 
Published: March 2023

7 Background: Cancer patients have increased risk for severe outcomes related to SARS-CoV-2 infection (COVID-19), due to their increased vulnerability to infection, older age, and comorbidities in comparison to the general population. While multiple studies have been completed examining outcomes of COVID-19 infection in cancer patients overall, there has been limited investigation into the outcomes of COVID-19 infection in patients with genitourinary (GU) cancers. Methods: We completed a single institution retrospective study to examine the outcomes of adults with GU cancers and COVID-19 infection from March 10, 2020 to June 15, 2022. Baseline data included age, sex, BMI, type of malignancy, cancer status (stable or progressive disease, in remission), current and previous anticancer therapy received, and comorbidities. Results: Eighty-four patients with a GU cancer diagnosis and laboratory-confirmed SARS-CoV-2 infection were identified. Seventy-nine (94%) were male and the median age was 64 years (range 24-91). Forty-four (52%) were non-Hispanic white, 28 (33%) were Hispanic, and 11 (13%) were African-American. Prostate cancer was the most common (n = 45), followed by renal cell carcinoma (n = 20), testicular (n = 9), bladder (n = 6), and penile cancer (n = 3). Eight patients had ≥2 episodes of COVID-19 infection. Sixty-three percent of patients were unvaccinated at the time of infection, while 37% of patients had breakthrough infection. Hospitalization was required for 39.3% (n = 33), with 4.8% (n = 4) requiring ICU admission. Of the patients requiring hospitalization, 26.2% (n = 22) died. Hospitalization was associated with having ≥2 comorbidities (OR 18.6 [95% CI, 3.1-111.8], p<0.01) and receiving active cancer treatment (OR 12.4 [95% CI, 1.92-79.7], p< 0.01). Mortality was associated with advanced age (OR 21.7 [95% CI, 1.40-341.7], p=0.03) and ≥2 comorbidities (OR 19.2 [95% CI, 3.02-122.5], p=0.02). Vaccination was negatively associated with both hospitalization (OR 0.04 [95% CI, 0.02-0.91], p=0.04) and mortality (OR 0.14 [95% CI, 0.02-0.84], p=0.03). Conclusions: Among patients with GU cancer, advanced age and comorbidities are associated with adverse outcomes of COVID-19 infection; vaccination is protective. With the emergence of variants and waning immunity of vaccines, our findings highlight the importance of development and implementation of enhanced mitigation strategies in cancer patients, especially those undergoing active cancer treatment.
Dynamic and immunocytochemistry analysis of circulation tumor cells (CTCs) in blood samples from patients with advanced ccRCC starting first-line treatment in a Brazilian Cancer Center.
Authors: Tariki Milena Shizue , Carreta Ruano Anna Paula , Torres Jacqueline Aparecida , Braun Alexcia Camila , Costa Daniela JF , Torrezan Giovana Tardin , Carraro Dirce Maria , da Costa Walter Henriques , Chinen Ludmilla T.D. 
Published: March 2023

704 Background: Treatment of advanced clear cell renal carcinoma (ccRCC) improved dramatically in the last 20 years, but biomarkers development lagged behind. Circulating tumor cell (CTC) is used as a prognostic and predictive tool in many solid tumors but is poorly studied in ccRCC. Objective: Our aim was to evaluate CTC counts in serial blood samples from patients with advanced ccRCC that started first-line treatment and analyze the protein expression of PBRM1, BAP1, PD-L1 and CD133 in these cells. Methods: Blood samples (10mL) were collected in EDTA tubes at three different timepoints, 30 days apart, after treatment start. We used a filtration technique (ISET system, Rarecells/France) to isolate and collect CTCs. Protein expression was evaluated by immunocytochemistry. Results: Twelve patients were included. All had detectable CTCs at baseline (1st blood draw), with a median of 1.5 CTCs/mL. Patients with CTCs above the median had ≥2 metastatic sites (p=0.015) and worse progression free survival (PFS) (19.7 vs 31.1 months, p=0.35), although the difference was not statistically different. Favorable CTCs kinetics at the time of first follow-up (2nd blood draw) indicated better PFS (24.76 months) versus unfavorable (6.65 months; p=0.014). PBRM-1, BAP-1 and PD-L1 expression in CTCs was associated with better overall survival (OS), although without statistical significance. CD133 expression in CTCs at baseline was associated with worse OS (p=0.08). Conclusions: CTCs isolation was feasible in advanced ccRCC patients starting first-line treatment and were frequently detected by ISET method. CTC counts at baseline and at 30 days after treatment initiation had prognostic implication, as well as its dynamic evaluation after 30 days of treatment with a favorable kinetics associated with better outcome.
Molecular characteristics of advanced clear cell renal cell carcinoma (ccRCC) harboring TERTmutations.
Authors: Mar Nataliya , Jaeger Ellen B. , Ashok Arya , Rezazadeh Arash 
Published: March 2023

706 Background: There is a large unmet need for identifying prognostic and predictive biomarkers in advanced RCC. TERT is a catalytic subunit of the telomerase enzyme and TERT promoter mutations lead to increased telomerase activity, which promotes tumorigenesis by preventing telomere shortening. Emerging data suggests a correlation between TERT promoter mutations (pTERTmut) and improved responses to immune checkpoint inhibitors in urothelial carcinoma (UC), while there is paucity of such data in RCC. This study aims to analyze the immune biomarker environment and co-mutational landscape in TERT mutated versus wild-type RCC. Methods: A retrospective analysis of patients with advanced ccRCC who completed sequencing with the Tempus xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq) was performed. De-identified data was analyzed for presence of pTERTmut, all other TERT mutations (otherTERT), and TERT wildtype (wtTERT). Companion alterations and immune biomarkers were compared between these three groups. Results: A total of 866 samples was analyzed, with 58% from primary renal lesions and 42% from a metastatic site. The frequency of all TERT mutations was 8.2% (71/866). pTERTmut was present in 5.6% (28/502) of primary and 5.5% (20/364) of metastatic sites, while otherTERT was present in 3.0% (15/502) of primary and 2.2% (8/364) of metastatic sites. Tumor mutational burden (TMB) was performed in 764 samples and only 0.4% had TMB greater than 10 m/MB, all of which were wtTERT. Median TMB was 2.08 m/MB across all samples, with 1.91 m/MB in pTERTmut, 1.72 m/MB in otherTERT, and 2.31 m/MB in wtTERT. Only 0.2% of 834 samples harbored MSI-high and 1.4% of 295 samples were mismatch repair deficient (dMMR), all of which were wtTERT. PD-L1 status was available in 439 samples, with 14% scored as positive (PD-L1+) with a combined positive score >10. Of PD-L1+, 4.8% was in pTERTmut, 3.2% in otherTERT, and 92.1% in wtTERT. Neoantigen tumor burden of all non-silent mutations was evaluated in 698 samples, with a median value of 2.11 in pTERTmut, 1.58 in otherTERT, and 2.11 in wtTERT. PBRM1 co-mutations were noted in 22.9% of samples with pTERTmut, 21.7% in otherTERT, and 33.2% in wtTERT. Additional RCC co-mutations are listed in the table. RCC mRNA and UC cohort data analysis is in progress. Conclusions: This is the largest analysis of the molecular and immune landscape of TERT mutated ccRCC. Interestingly, this dataset showcases that traditional immune biomarkers (TMB, MSI, dMMR, and PD-L1) do not appear to be highly prevalent in RCC and their use in clinical practice may be limited. Further investigation into the TERT biomarker candidate is warranted. [Table: see text]
Characteristics and outcomes of T1a renal cell carcinoma presenting with metastasis.
Authors: Wang Luke , Puri Dhruv , Liu Franklin , Dhanji Sohail , Meagher Margaret F , Shah Aastha , Ghassemzadeh Saeed , Javier-Desloges Juan , Bagrodia Aditya , Rose Brent Shane , Murphy James Don , Derweesh Ithaar H , McKay Rana R. 
Published: March 2023

734 Background: T1a renal cell carcinoma (RCC) is associated with excellent cure rates. However, a small fraction present with metastasis. We sought to determine the clinical characteristics, variables associated with synchronous metastasis, and survival outcomes in patients with pT1a and cT1a RCC using the National Cancer Database (NCDB). We secondarily evaluated whether surgery impacted risk of all cause mortality in cT1a RCC with synchronous lung and bone metastasis. Methods: From 2004 to 2019, all cases of RCC in patients age ≥18 were extracted from NCDB. pT1a and cT1a RCC were characterized as those 1) with no metastasis at diagnosis, 2) with synchronous metastasis [pT1aNxM1 at diagnosis]. Impact of surgery on all cause mortality was not evaluated for cT1a with synchronous metastasis to liver and brain due to low sample sizes. Results: The table describes selected characteristics of the cohorts. On multivariable logistic regression, diagnosis of pT1a with synchronous metastasis was associated with age (OR 1.02), male sex (OR 1.64), tumor size (OR 1.84), cN1 (OR 1.08), sarcomatoid (OR 5.50), tumor grade (OR 2.84) (p<0.005 for these variables); and inversely with diagnosis in 2016-2019 (OR 0.66, p=0.044) and papillary histology (OR 0.45, p<0.001). On multivariable Cox regression of the cT1a cohort, ACM was associated with Charlson score (HR 1.50, p<0.001), metastasis to >1 site (HR 2.48, p=0.032), and inversely with radical (HR 0.42, p<0.001) and partial nephrectomy (HR 0.31, p<0.001). In cT1a with lung metastasis, partial (HR 0.06, p=0.049) and radical nephrectomy (HR 0.17, p=0.006) was inversely associated with ACM, while surgery of distant site was not. In cT1a with bone metastasis, partial (HR 0.21, p<0.001) and radical nephrectomy (HR 0.32, p<0.001) were the only variables inversely associated with ACM. 5-year overall survival for pT1a with synchronous metastasis is 39.4%; for cT1a with synchronous metastasis is 20.9%. Conclusions: Known prognostic features were associated with synchronous metastasis in T1a RCC. Surgical resection of primary site may impact risk of all cause mortality in select cases of synchronous metastatic disease. [Table: see text]
Predicting perioperative complications for partial versus radical nephrectomy in T1b-T2 renal cell carcinoma.
Authors: Shah Yash , Wang Kerith Ruoyao , Simhal Rishabh Kumar , Goldberg Hanan , Mark James Ryan , Shah Mihir S , Gomella Leonard G. , Lallas Costas D. , Chandrasekar Thenappan 
Published: March 2023

737 Background: The standard of care for larger localized RCC lesions is radical (RN) or partial (PN) nephrectomy. RN is increasingly utilized to maximize oncologic benefit in complex tumors. Although PN is a more technically complex procedure, its nephron-sparing nature confers lasting renal and cardiovascular benefits. We utilized the National Surgical Quality Improvement Program (NSQIP) database to elucidate predictors of perioperative morbidity in T1b-T2 RCC patients. Methods: Using the NSQIP Nephrectomy-Targeted PUF, 2,094 patients undergoing nephrectomy between 2019-2020 for localized T1b-T2 RCC were identified. Variables of interest included surgical procedure and approach, tumor stage, demographics, pre-operative laboratory values, comorbidities, infection and venothromboembolism (VTE) prophylaxis techniques, peri-operative complications, operative time, length of hospital stay, 30-day reoperations, and 30-day readmissions. Chi square test was used to analyze univariate associations between certain comorbidities and complications. Multivariate regression analysis was utilized to compare complication rates between PN and RN after adjusting for baseline characteristics and surgical approach. p<0.05 was considered statistically significant. Results: 816 patients received PN while 1,278 received RN. PN patients had an increase in the following events: 30-day readmissions (7.0% vs. 4.7%, p=0.026), major bleeds (9.19% vs. 5.56%, p=0.001), renal failure requiring dialysis (1.23% vs. 0.31%, p=0.013), and urine leak or ureteric fistulae (1.10% vs. 0.31%, p=0.025). Open surgery was associated with increased VTE, renal failure, bleeds, urine leaks or ureteric fistulae, readmissions, and reoperations. Multivariate analysis revealed that PN remained predictive of all four aforementioned events, although further adjustment for robotic approach led to a loss of significance for renal failure and ureteric fistulae. Additional patient-specific predictors of relevant complications across procedure type included bleeding disorder and dialysis for bleeds, and renal failure, steroid use, and COPD for readmissions. Conclusions: This is the first study to evaluate the new NSQIP Nephrectomy-Targeted PUF. This population-based cohort provides unique insights into nephrectomy for pT1b-T2 localized RCC. We demonstrate significant associations between PN and specific complications, modulated by particular comorbidities, although both PN and RN were exceedingly safe. This analysis supports the development of novel risk stratification tools which account for specific patient comorbidities in predicting near term risk. Improved understanding of case-specific determinants of morbidity following PN or RN may facilitate shared decision making in localized RCC management.
Survival and hemoglobin A1c in metastatic castrate resistant prostate cancer.
Authors: Govindan Srinivas , Cheranda Nina , Luo Suhong , Riekhof Forest , Schoen Martin W. 
Published: March 2023

75 Background: The two common therapies for metastatic castrate resistant prostate cancer (mCRPC), enzalutamide (ENZ) and abiraterone (AA), have different effectiveness in patients with diabetes mellitus and obesity due to different mechanisms of action, along with AA requiring the co-administration of prednisone. However, no prior study has assessed responses to treatment based on glycated hemoglobin (HbA1c) while accounting for body-mass index (BMI). Methods: Patients treated with AA or ENZ from September 10, 2014 to June 2, 2017 were identified within the Veterans Health Administration. The patients were classified by most recent HbA1c values (<5.6%, 5.6%-6.4%, 6.5%-7.1%, ≥7.2%) collected prior to the start of AA or ENZ. Kaplan Meier and Cox proportional hazards modeling was performed to assess the association between overall survival and covariates including age, Charlson Comorbidity Index, BMI, baseline PSA, and HbA1c. Results: 3421 veterans treated with AA or ENZ had HbA1c data available. 658 patients with HbA1c <5.6%, 1430 with 5.6-6.4%, 667 with 6.5%-7.1%, and 666 with HbA1c ≥7.2. Kaplan Meier analysis showed the following median survival in months with ENZ vs AA: <5.6% = 22.1 vs 24.5 (p = 0.04 by log-rank), 5.6%-6.4% = 27.7 vs 22.6 (p = 0.01), 6.5%-7.1% = 23.0 vs 19.8 (p = 0.005), ≥7.2% = 26.0 vs 21.0 (p = 0.04). Cox models showed no difference in median survival between ENZ vs AA in patients with HbA1c <5.6%, adjusted hazard ratio (aHR) 1.15 (95% CI, 0.960-1.370). However, there was significantly longer survival in patients who received ENZ compared to AA in all other groups as follows: 5.6%-6.4% aHR 0.86 (95% CI, 0.759-0.965), 6.5%-7.1% aHR 0.74 (0.623-0.879) and ≥7.2% aHR 0.80 (0.669-0.948). Additionally, in patients treated with AA, higher HbA1c values were associated with inferior survival compared to HbA1c <5.6%, aHR 1.40 (1.19-1.65) for 6.5-7.1% and aHR 1.25 (1.05-1.48) for ≥7.2%. Conclusions: In patients with HbA1c ≥5.6%, ENZ was associated with longer overall survival compared to AA, even when including baseline BMI. Additionally, in patients treated with AA, higher HbA1c values had inferior survivals compared to patients with HbA1c <5.6%. No difference in survival was observed across the HbA1c strata with ENZ. Further studies of interactions between patient factors and treatments are warranted to guide treatment selection for prostate cancer therapy.