bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome in terms of survival and treatment response of patients with metastatic urothelial carcinoma harboring FGFR alterations compared to wild-type tumors.
Authors: Sevillano Elena , Rodriguez-Moreno Juan Francisco , Barquin Arantzazu , Yagüe Monica , Ruiz Sergio , Navarro Paloma , Amarilla Sandra , Polo Ojea Patricia , García-Donas Jesús 
Published: May 2020

e17042 Background: FGFR gene alterations are a new target in metastatic urothelial carcinoma (mUC). However, controversial data have been published regarding the outcome of these tumors.In order to assess the prognostic value of this gene, we aimed to compare survival and response to treatment of patients harboring FGFR alterations vs wild type (WT) tumors. Methods: Medical records of patients with advanced urothelial cancer screened for FGFR mutations or fusions at our center were reviewed. Results: Between May 2011 and December 2019 up to 149 patients completed any screening test for FGFR alterations. 30 cases (20,1%) were deemed as positive (mutations: 12, amplifications: 9, rearragements /fusions: 4 and not specified in 5). 30% of the cases were Upper Tract Urothelial carcinoma (UTUC) versus 70% bladder UC. 8% patients had liver metastases and 100% PS ≤ 1 at first line.. 73% (22/30) received chemotherapy (1st line:15, 2nd line; 4, 3rd line: 4) with 1CR, 9 PR, 2SD in first line. 50% (15/30) received a checkpoint inhibitor (1st line:5, 2nd line:5, 3rd line:5). Of these, 2 cases responded, 2 remained stable and 8 progressed. Overall, 40% (12/30) received an FGFR inhibitor (1st line: 7, 2nd line: 4, 3rd line: 1). 54% (6/11) experimented tumor response (complete:1, partial:5). Median overall survival for the whole FGFR population was 24,6 month. Median progresion free survival was:1st line: 4,1 mo, 2nd line: 4,1, 3rd line: 7,1 respectively. Among the 119 cases deemed as FGFR WT. 95% of primary tumors were located at the bladder. 64% had liver metastases and PS ≥2: 34% at first line treatment. 43%(52/119) received chemotherapy: 1st line:33, 2nd line:13, 3rd line: with 4CR, 11PR, 4SD, 9PD. And 40% (48/119 ) CPI: 1st line: 30, 2nd line: 15, 3rd line:3 with 1CR, 3 PR, 4SD, 19PD. The median OS was 9,9 months for patients with wild-type patients. Median progresion free survival was: 1st line: 4,5 mo, 2nd line: 2,3, 3rd line: 0.8 month. Conclusions: FGFR is a relatively common molecular alteration in UC. Patients harboring a FGFR alteration present a better prognosis than wild type tumors. Clinical benefit with chemotherapy and CPIs was similar in both populations.
Oncotherad immunotherapy elicits promising responses in Bacillus Calmette-Guérin-unresponsive non–muscle invasive bladder cancer: Results from phase I/ II study.
Authors: Alonso João Carlos Cardoso , Reis Ianny Brum , Gonçalves Juliana Mattoso , Sasaki Bianca Ribeiro de Souza , Cintra Adriano Angelo , Duran Nelson , Billis Athanase , Fávaro Wagner José 
Published: May 2020

e17048 Background: Standard treatment for high-grade non-muscle-invasive bladder cancer (HGNMIBC) is transurethral resection of the bladder tumor followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. Up to 40% of patients with HGNMIBC will fail intravesical BCG therapy. A promising therapeutic perspective is represented by OncoTherad immunotherapy. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein developed by University of Campinas/Brazil that exhibits antitumor properties. The aims of this study were to evaluate the efficacy and safety of OncoTherad immunotherapy for BCG-refractory or relapsed HGNMIBC. Methods: We conducted a prospective, single-center (Municipal Hospital of Paulinia, São Paulo, Brazil), single-arm phase I/ II study of OncoTherad immunotherapy in 29 (18 male, 11 female) patients with BCG-unresponsive HGNMIBC (≥ 1 previous course of BCG intravesical therapy). The schedule was initiated with weekly intravesical (120 mg/mL) and intramuscular (25 mg/mL) OncoTherad treatment for 6 weeks, followed by one every other week application for 3 months and, one monthly application until the end of the treatment (24 months). Follow-up was performed with systematic mapping biopsies of the bladder, cystoscopy and ultrasound. The primary endpoint was pathological complete response (pCR) and recurrence-free survival (RFS). The recurrence was defined as histology proven tumor recurrence (any grade) and monitored at 3-month intervals. Secondary endpoints were time to disease recurrence and safety response. Results: The median age of the 29 patients was 64 years (range 34-94). At baseline pTis, pTaG2-3, pT1G2-3 occurred in 10%, 59% and 31% of patients respectively. OncoTherad treatment showed pCR rates (95% CI) of 100% at 3, 6 and 9 months, 89,6% (26/29) at 12 months and, 89,6% (26/29) at 24 months. A 24-months RFS rate in all patients was 79,3%. Also, the median time to disease recurrence for patients was 459 days (15,3 months; 95% CI) at 24-months follow-up. 95% of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria (51,7%), cystitis (34,5%), pruritus (44,8%), rash (27,6%), arthralgia (27,6%) and fatigue (27,6%). Conclusions: In conclusion, OncoTherad seems a safe and effective treatment option for BCG-unresponsive HGNMIBC patients and may provide benefit for preventing tumor recurrence. Clinical trial information: RBR-6swqd2.
Chemotherapy-induced peripheral neuropathy (CIPN) as a predictor of decreased quality of life and cognitive impairment in testicular germ cell tumor survivors.
Authors: Chovanec Michal , Galikova Dominika , Vasilkova Lucia , De Angelis Valentina , Rejlekova Katarina , Obertova Jana , Sycova-Mila Zuzana , Palacka Patrik , Kalavska Katarina , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Mego Michal 
Published: May 2020

e17063 Background: Chemotherapy-induced peripheral neuropathy (CIPN20) after curative treatment for testicular germ cell tumors (GCTs) has been previously reported. The impact of CIPN on long-term quality of life (QOL) in GCT survivors remains unclear. Herein, we aimed to evaluate chemotherapy-induced peripheral neuropathy (CIPN20) in association with QOL in GCT survivors. Methods: European Organisation for Research and Treatment of Cancer (EORTC) CIPN20, QLQ-C30 and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaires were prospectively completed by GCT survivors (N = 153) at National Cancer Institute in Slovakia during their annual follow-up. The median follow-up was 10 years (range 4-25). Upon obtaining the scores from each questionnaire per recommended guidelines, each score from QLQ-C30 and FACT-Cog was correlated with CIPN defined as high or low (above and below median) as obtained from CIPN20. Results: GCT survivors with CIPN high reported impairment in quality of life in QLQ-C30. The global health status was lower in survivors with high vs low CIPN (mean score ± SEM: 66.5 ± 1.9 vs. 86.2 ± 1.8, P < 0.00001). Survivors with CIPN high reported substantially worse physical, role, emotional, cognitive and social functioning compared to CIPN low (all P < 0.00001). CIPN high survivors perceived more fatigue, nausea, pain, dyspnoea, appetite loss and more sleeping disorders compared to CIPN low (all P < 0.0001). Higher burden of CIPN was associated with more financial problems vs CIPN low (mean score ± SEM: 19.6 ± 2.6 vs. 6.67 ± 2.3, P = 0.0002). Cognitive impairment was higher in all FACT-Cog domains including the overall cognitive function score (all P < 0.001) for CIPN high. Spearman analysis has confirmed negative correlations of CIPN20 overall score with QLQ-C30 global health status (R = -0.54, P < 0.0001) and with FACT-Cog overall cognitive function score (R = -0.52, P < 0.0001). Conclusions: CIPN is a powerful predictor of disturbances in QOL and cognitive functioning among GCT survivors. Physicians should never over-treat patients unnecessarily and novel therapies with lower burden of late toxicity should be researched
Risk of hypocalcemia in cancer patients treated with cabozantinib: A meta-analysis.
Authors: Khorasanchi Adam , Wu Shenhong 
Published: May 2020

e17067 Background: Cabozantinib as a multiple tyrosine kinase inhibitor has been used extensively in cancer treatment and clinical trials, and is associated with the development of hypocalcemia. Its impact on calcium metabolism is not clear. We have performed a meta-analysis to determine the overall risk of hypocalcemia with cabozantinib in cancer patients. Methods: Databases including PubMed and Google Scholar until January 2020 were used to identify relevant studies. Studies of patients assigned to cabozantinib with available data on hypocalcemia were included. Incidence and relative risk (RR) of hypocalcemia were calculated using a random-effects or fixed effects model, depending on the heterogeneity of the included studies. Results: 88 articles were screened with a total of eight studies including 1,460 cancer patients were selected for analysis. For patients receiving cabozantinib, the overall incidences of all-grade and high-grade (grade 3 or 4) hypocalcemia were 15.5% (95% CI: 12.1-42.5%) and 3.5% (95% CI: 1.1-6.8%), respectively. The incidences of all-grade and high-grade hypocalcemia varied significantly with tumor types and cabozantinib dose. Cabozantinib was associated with a significantly increased risk of all-grade and high-grade hypocalcemia with RR of 6.2 (95% CI: 2.6-14.5, p < 0.001) and 10.7 (95% CI: 2.0-56.2, p = 0.005) in comparison with controls including placebo or sunitinib. Conclusions: Cabozantinib was associated with a significantly increased risk of developing all-grade and high-grade hypocalcemia in cancer patients. Further studies are needed to understand the effect of cabozantinib on calcium metabolism and patient outcome.
The serum level of the components of the renin-angiotensin system correlates with its tumor tissue expression in kidney cancer patients.
Authors: Osokin Roman , Komarova Ekaterina , Aboyan Igor , Maksimov Aleksey Yu. , Ushakova Natalya D. , Ischenko Roman , Shatova Olga , Komarova Elizaveta 
Published: May 2020

e17068 Background: To date, it has not been decided whether the locally-generated components of the renin-angiotensin system (RAS) involved in the pathogenesis of kidney cancer and arterial hypertension, and are local and systemic RAS related? The aim was to assess the relationship of the level of RAS in the tumor tissue and peripheral blood in patients with localized kidney cancer with arterial hypertension. Methods: In patients with localized kidney cancer T1N0M0 (KС) and arterial hypertension of the I-II stage (AH), tissue and serum levels of angiotensin I, angiotensin II, angiotensin (1-7), as well as angiotensin converting enzymes (ACE and ACE2) were determined in the following groups: patients with KC without AH (n = 35, KC) and with concomitant AH (n = 30; KC+ AH). The normative values of peripheral blood indices were revealed in healthy donors (n = 30). Results: The level of all studied RAS peptides in the serum of patients with KC was increased in comparison with healthy donors regardless of concomitant hypertension, and the activity of both circulating angiotensin-converting enzymes, on the contrary, was increased only in patients with hypertension. The level of AT1 exceeds the control indicators by 1.7 times (KC) and 2.8 times (KC + AH). The formation of AT2 is higher in the KC + AH compared to KC (2.2 times versus 1.7 times, at p < 0.05). The content of AT (1-7) significantly exceeds the control (1.3 times on average, p < 0.05) and higher in the KC + AH. Increased enzyme activity was detected in KC + AG: increased by 1.5 times (p < 0.05) and 1.7 (p < 0.05) compared with the control for ACE and ACE2, respectively. The pair correlation coefficients between the serum RAS and the studied tissues in the KC were: for AT1 -0.78/0.65; АТ2-0.64/0.59 and АТ (1-7) - 0.56/0.51; ACE2 0.55/0.65 (for tumor/peritumoral tissue: in all cases at p < 0.05). In the KC+AH, these ratios were: for AT1 -0.85/0.81; АТ2-0.72/0.74 and АТ (1-7) - 0.65/0.59; ACE2 0.61/0.52 (for tumor / peritumoral tissue: in all cases at p < 0.05). Conclusions: The serum content of RAS peptides had positive statistical relationships with the corresponding parameters in tumor and peritumoral tissues of kidney cancer pts. However, in hypertensive patients with kidney cancer the correlations found had a tightness of higher strength. Positive correlations of the level of locally generated tumor parameters of RAS with their circulating analogues indicate the possibility of their use as diagnostic markers of the development of kidney cancer.
Sequential treatment with pazopanib followed by nivolumab in patients with renal cell carcinoma: Updated interim results of the non-interventional study PAZOREAL.
Authors: Bedke Jens , Boegemann Martin , Schostak Martin , Hering-Schubert Christiane , Welslau Manfred , Schleicher Jan , Petzoldt Alexander , Doehn Christian , Gruellich Carsten , Goebell Peter-Juergen , Steiner Thomas , Degenkolbe Elisa , Hanson Sven , Grünwald Viktor 
Published: May 2020

e17075 Background: Real-world evidence is urgently needed to monitor the translation of new treatment approaches into routine clinical practice as well as to improve cancer treatment and survivorship care. Methods: PAZOREAL is a prospective, multicenter, non-interventional study to evaluate effectiveness, tolerability, safety, and quality of life (QoL) in patients (pts) with advanced or metastatic renal cell carcinoma (mRCC) treated with 1st-line pazopanib (PAZO) followed by 2nd-line nivolumab (NIVO). The primary variable was time on drug (TD) in the respective treatment (Tx) lines. Other endpoints include overall survival (OS), safety and QoL evaluated by EQ-5D-5L. Results: Between December 2015 and September 2017, 414 pts were enrolled and 388 pts started first-line PAZO Tx, 136 pts subsequently received NIVO as second-line Tx. At time of data-cut (30 Sep 2019) median TD was 6.5 months (95%CI 5.7-7.6) for 1st-line PAZO and 4.6 months (95%CI 3.3-6.0) for 2nd-line NIVO. 9.0% of 1st-line PAZO pts and 5.9% of 2nd-line NIVO pts achieved a complete response and disease control rate was 58.0% (95% CI 53.0-62.8) and 44.9% (95% CI 36.8-53.2) for PAZO or NIVO, respectively. Median OS was 32.6 months (95% CI 28.0-38.9) for all pts, 32.6 months (95%CI 28.2-NA) for pts with 2nd-line NIVO and 32.3 months (95%CI 18.8-NA) for pts with other 2nd-line Tx. The most commonly reported treatment emergent AEs were diarrhea (37.2%), nausea (21.7%) and fatigue (19.1%) for PAZO Tx and diarrhea (8.8%), peripheral edema (5.9%) and dyspnea, fatigue, nausea, rash, vomiting (5.1% each) for NIVO. 66 pts (17.1%) discontinued PAZO and 7 pts (5.1%) discontinued NIVO due to related TEAEs. During 1st-line PAZO Tx, mean EQ-5D-5L utility scores initially decreased slightly by time, returned to baseline level and remained stable afterwards. During 2nd-line NIVO Tx the utility scores initially increased by time and remained stable thereafter. Similar tendencies were reported for mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Conclusions: The interim results of the PAZOREAL study confirm favorable clinical trial outcomes, the good benefit-risk profile and the sustained QoL in pts with mRCC in a real-world setting. The sequential treatment with PAZO followed by NIVO is effective and well tolerated. Clinical trial information: NIS-Nr.: 6687.
Sorafenib as second-line treatment in metastatic renal cell carcinoma: A prospective cohort.
Authors: Martin Aguilar Ana Elena , Núñez-López Haidé Nayeli , Ramirez-Sandoval Juan C. Carlos 
Published: May 2020

e17077 Background: Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with advanced or metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a 2nd-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI). Methods: Prospective observational cohort in Mexico City (July 2012 to July 2019). We included 148 subjects with metastatic RCC, treated by nephrectomy and who had RCC progression despite treatment with sunitinib (n = 144) or pazopanib (n = 4). All patients received sorafenib 400 mg orally twice a day on a continuous dosing schedule until disease progression or intolerable toxicity. The primary endpoint was time to progression evaluated every 12-16 weeks. Risk factors were classified according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC-RF) prognostic model. Results: Mean age of cohort was 58±10 years, 104 (70%) were male, 51 (35%) had none of IMDC-risk factors, and the most common sites of metastasis before sorafenib treatment were lung (n = 79, 53%) and bone (n = 30, 20%). The median progression-free survival and survival after the introduction of sorafenib treatment was 8.5 months (95% IC 6.8-10.2) and 40.1 months (95% IC 35.2-45.0) respectively. Median overall survival from RCC diagnosis to death was 71 months (95% CI 63.9-79.4). Median progression-free survival was longer in advanced RCC with none IMDC-RF compared with subjects with ≥2 IMDC-RF (10.3 [95%CI 6.1-14.6] vs 7.9 [95%CI 5.8-9.9] mo. respectively, p = 0.035). Age > 65 decreased risk of progression after sorafenib therapy (OR 0.33, 95% CI 0.14-0.77, p = 0.010). Median progression-free survival in subjects > 65 yrs old was longer (14 months, 95% CI 9.2-17.9) compared to subjects ≤65 yrs (7.2 months, 95% CI 5.5-8.9, p = 0.018). Adverse events associated to sorafenib occurred in 118 (80%) subjects: hand-foot syndrome (n = 118, 80%), diarrhea (n = 113, 76%), hypothyroidism (41, 28%), and mucositis (84, 57%). Any adverse events corresponding to a grade > 2 occurred in 48 (32%) patients. Conclusions: Sequential inhibition of VEGF with sorafenib as a 2nd-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 yrs old. Further clinical trials are needed.
Predictors of first line systemic therapy for metastatic renal cell carcinoma in IMDC favorable risk patients.
Authors: Mizuno Ryuichi , Takamatsu Kimiharu , Tanaka Nobuyuki , Hayakawa Nozomi , Kosaka Takeo , Kikuchi Eiji , Oya Mototsugu 
Published: May 2020

e17086 Background: With the induction of molecular targeted agents, which interfere with proteins that play critical roles in tumor growth and progression, and immune checkpoint inhibitors (ICI), the scenario of systemic treatment of metastatic renal cell carcinoma (mRCC) have dramatically been changed with improved survival. Prognostic risk assessment is essential for choosing the most appropriate first line treatment option, with selection based on International Metastatic RCC Database Consortium (IMDC) Risk Category. This study was designed to evaluate the actual efficacy of systemic therapy in the IMDC favorable risk group patients with mRCC. Methods: A total of 218 patients with mRCC who received systemic therapy were retrospectively reviewed (Institutional review board approval No 2013-0425). Among them, 55 (25%) patients were classified as favorable risk group based on the IMDC Risk Category. These mRCC patients in the favorable risk were divided into 2 groups by following factors; gender (male or female), age (≥70, or not), baseline serum CRP levels (≥0.6, and < 0.6 mg/dl), metastatic sites (exclusive lung, or lung and others), BMI (≥22, or < 22), respectively. The overall survival (OS) of patients in the favorable risk group were compared between the two cohorts. Results: The median PFS for first line treatment and OS of patients in favorable risk group were 31.6 (95% CI 19.9–33.7)) and 85.8 (56.8-NE) months, respectively. The median OS in patients with BMI≥22 and < 22 was 65.6 (95% CI 56.8–NE) and 56.8 (95% CI 30.8–NE) months, respectively (p = 0.0497). The median OS in patients with exclusive lung metastasis, and lung and other metastases were 115.1 (95% CI NE) and 65.6 (95% CI 43.9–NE) months, respectively (p = 0.0073). No significant difference was found in OS between male and female, age≥70 and < 70, and baseline serum CRP levels ≥0.6 mg/dl and < 0.6, respectively. Conclusions: The first line systemic treatment for mRCC patients in IMDC favorable risk group was feasible and effective in patients with BMI≥22 or exclusive lung metastasis.
Safety of inactivated vaccines in patients with genitourinary (GU) malignancies receiving immune checkpoint inhibitors (ICI).
Authors: Wulff-Burchfield Elizabeth Marie , Kurkowski Austin , Grauer Dennis , Ralph Shelbie , Mahmoudjafari Zahra , Parikh Rahul Atul , Martin Grace 
Published: May 2020

e17108 Background: ICI therapy has become the standard of care for many advanced GU cancers, but immune-related adverse events (IRAE) may result in treatment delays or discontinuation. Concurrent vaccine use has been posited to increase the IRAE risk, but safety data is mixed. There are no published data regarding safety of concurrent inactivated vaccines other than influenza, including and especially in the GU cancer population. Methods: We performed a single-institution, retrospective, matched-cohort (1:2, cohort A:B, vaccinated to control) study of all GU cancer patients treated with an inactivated vaccine 30 days prior to or 60 days following ICI therapy from 2015-2019. Baseline clinical characteristics were abstracted from the electronic health record (EHR). Clinically significant IRAEs were defined as any event developing during or 30 days following ICI therapy requiring therapy with ≥ Prednisone 20 mg daily (or equivalent) or other immunosuppression. Delays were defined as ICI therapy given > 14 days past expected date for cycle 2 or beyond. Bivariate analysis with chi-squared statistics were used to describe incidence. Results: Sixty patients were included: 20 in cohort A (vaccinated) and 40 in cohort B (control). Thirty-seven (61.7%) patients had renal cell carcinoma, 17 (31.7%) had urothelial carcinoma, and 4 (6.7%) had prostate cancer. There was no difference in incidence of clinically significant IRAEs between cohorts A and B (15% vs 32.5%, p = 0.148), nor were differences observed in rates of treatment delays (10% vs 12.5%, p = 0.776) or discontinuation (10% vs 12.5%, p = 0.776) due to IRAEs. Most common vaccines were inactivated influenza (n = 18, 90%) and pneumococcal vaccine (n = 3, 15%). Among the 16 patients experiencing clinically-significant IRAEs, the most common were colitis (n = 3), dermatitis (n = 3), and pneumonitis (n = 3). All patients requiring immunosuppressive therapy received systemic corticosteroids. Conclusions: This retrospective cohort study demonstrates that GU cancer patients receiving inactivated vaccines during ICI therapy does not increase IRAE incidence, treatment delays, or discontinuation, suggesting that inactivated vaccines may be safely administered during ICI therapy in this population. Though influenza vaccines were still the most common, this is the first study to include other inactivated vaccines. Limitations include sample size, EHR accuracy and use of surrogate markers for determination of IRAE incidence. Next steps will include a multi-institutional retrospective study.