tbuckley/cabot-search huggingface dataset:
Improved overall survival with immune checkpoint inhibitors in the treatment of metastatic urothelial carcinoma: A national retrospective comparative study.
Authors: Chih-Chin Yu, Po-Jung Su, Yao-Chou Tsai
Journal: Journal of Clinical Oncology (2024)

e16550 Background: Numerous randomized trials have illustrated the survival advantages of immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma. However, the application of ICI varies in different trials, encompassing first-line, second-line, monotherapy, combination with chemotherapy, or maintenance therapy. Real-world clinical practices often diverge from trial criteria. This study aims to evaluate the effectiveness of any ICI regimen in treating metastatic urothelial carcinoma using real-world data. Methods: This retrospective comparative study included patients diagnosed with locally advanced or metastatic urothelial carcinoma between January 2015 and July 2023, sourced from the Taiwan Upper Tract Urothelial Cancer and Bladder Cancer Collaboration Database. Patients with prior neo-adjuvant or adjuvant systemic therapy were excluded. Results: Among 427 patients, 152 (35.6%) who received any ICI as the first-line or second-line regimen constituted the ICI group, while the remaining 275 (64.4%) patients receiving only chemotherapy formed the chemotherapy group. Within the ICI group, 55 (36.2%) patients received monotherapy, 49 (32.2%) received combination therapy with chemotherapy, and 4 (2.6%) received maintenance therapy as the first-line regimen. The remaining 44 (28.9%) patients received ICI as the second-line regimen. No significant differences were observed in age, sex, performance status, renal function, tumor site, ratio of locally advanced disease, ratio of visceral metastasis, and ratio of previous radical surgery between the two groups. Median overall survival (OS) from the start of the first-line therapy was 15.8 months in the ICI group and 10.2 months in the chemotherapy group. Kaplan-Meier curves demonstrated that the ICI group exhibited superior OS and cancer-specific survival compared to the chemotherapy group (log-rank p= 0.009 and 0.004, respectively). In the multivariable analysis, the ICI group also demonstrated favorable outcomes in OS [hazard ratio (HR) 0.726, p=0.011] and cancer-specific survival (HR 0.67, p=0.004). Conclusions: Our study confirms the clinical efficacy of ICI in metastatic urothelial carcinoma. The use of ICI monotherapy or combination in the first-line or second-line regimen for metastatic urothelial carcinoma improves patient survival. [Table: see text]
How febrile neutropenia affects hospitalization in patients with bladder cancer: Nationwide insights.
Authors: Evadne Rodriguez, Saad Javaid, Kelly Frasier, Vivian Li, Julia Vinagolu-Baur, Nataly Ortega Yaguachi, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

e16625 Background: Bladder cancer is the most prevalent form of malignancy in the urinary tract and is a leading global health concern. Febrile neutropenia is a severe and potentially life-threatening complication of cancer treatment, and limited research exists on the impact of Febrile Neutropenia in bladder cancer. Our study examined its effects on adverse outcomes for hospitalized bladder cancer patients. Methods: The National Inpatient Sample (2017-2020) was employed to identify Bladder cancer patients with regional and advanced metastatic disease as the primary diagnosis and were stratified based on the presence or absence of a secondary diagnosis of Febrile neutropenia (FN). The primary outcome measure was mortality, while the secondary outcomes included length of stay, total cost of hospitalization, and other adverse in-hospital outcomes. Multivariate regression analysis was used to adjust for the confounding variables. Results: A total of 102,485 patients were hospitalized for Bladder cancer, among whom 865 had concurrent FN. The mean age of patients with FN was 67.31±17.44, while that of patients without FN was 72.19±11.48, p&lt;0.001. As compared to Patients without FN, those with FN had a greater percentage of patients with Medicaid (8.77% vs. 6.15%) and private insurance (30.41% vs. 19.74%), while fewer patients with Medicare (58.48% vs. 72.17%), p=0.001. After multivariate regression analysis, patients with FN had increased odds of mortality (OR=4.33,(2.52-7.45); p&lt;0.001). FN patients had a longer length of stay (+2.69 days (1.32-4.05); p&lt;0.001) and higher total cost of hospitalization (+$23,229(3,907-4,255); p&lt;0.001). Patients with FN were more likely to have fluid and electrolyte disorders (OR=1.57(1.11-2.20); p=0.009). However, no significant differences were observed in the odds of Sepsis (OR=1.34(0.62-2.85); p=0.45), Acute kidney injury (OR=1.10 (0.74-1.63); p=0.61), Acute respiratory failure (OR=1.11(0.50-2.50); p=0.78) and ICU admission (OR=0.56(0.20-1.57); p=0.27) between the two groups. Conclusions: In patients with bladder cancer, febrile neutropenia has been identified as an independent predictor of mortality. It is associated with increased healthcare resource utilization and fluid and electrolyte disorders. Proactive management of risk factors can help control febrile neutropenia and reduce the occurrence of adverse events in patients hospitalized with bladder cancer. [Table: see text]
Effect of body mass index (BMI) on efficacy of immune checkpoint inhibitors (ICIs) in patients with metastatic urothelial carcinoma (mUC) in real-world setting.
Authors: David Lynn, Scott Dawsey, Charbel Hobeika, Ubenthira Patgunarajah, Nikhil Pramod, Wei Wei, Monica Nair, Kimberly Maroli, Allison Martin, Moshe Chaim Ornstein, Christopher Eing Wee, Timothy D. Gilligan, Amanda Nizam, Amanda Bonham, Omar Y. Mian, Paul G. Pavicic, C. Marcela Diaz-Montero, Shilpa Gupta
Journal: Journal of Clinical Oncology (2024)

e16577 Background: There is emerging data on the role of BMI and outcomes of ICIs in various solid tumors, with underweight pts having worse outcomes to ICIs. The effect of BMI on efficacy of ICIs in pts with mUC is not clear. Methods: We identified 455 adult pts with mUC at the Cleveland Clinic treated who received &gt;/= 2 cycles of ICI with pembrolizumab (P), atezolizumab (A), or avelumab (Av) between 2015 and 2023. Patient characteristics including age, sex, race, primary site (bladder vs upper tract UC (UTUC)), tumor histology and pre ICI treatment NLR values were collected. BMI was calculated and values were collected and compared to assess impact on overall (OS) and progression free survival (PFS) after ICI start date. BMI was broken down into four categories: underweight (BMI less than 18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25 and 29.9 kg/m2) and obese (BMI 30 kg/m2 or greater). OS and PFS were estimated by Kaplan Meier method and compared using log rank test. Results: Median age of pts was 73 yrs (35-95) and 341 (75%) pts were males. 269 (59%) received P, 90 (20%) received A, and 96 (21%) received Av. We found that underweight pts had significantly worse OS compared to normal or higher BMI (p=0.001). BMI did not impact PFS (p=0.1) (Table). Conclusions: In our large real-world cohort of mUC pts receiving ICI, we report for the first time the effect of BMI on outcomes with ICI with underweight pts having better outcomes. Further prospective studies are warranted. [Table: see text]
Treatment and outcomes of bladder cancer in Armenia.
Authors: Samvel Bardakhchyan, Hovsep Gharadaghyan, Davit Zohrabyan, Liana Safaryan, Armen Avagyan, Lilit Harutyunyan, Amalya Sargsyan, Mariam Mailyan, Martin Harutyunyan, Marine Rushanyan, Gohar Mkrtchyan, Nune Karapetyan, Sergo Mkhitaryan, Jemma Arakelyan
Journal: Journal of Clinical Oncology (2024)

e16574 Background: Bladder cancer is the fifth most common cancer by incidence in Armenia with around 450 new cases diagnosed every year. Methods: For this retrospective hospital-based study we have collected data from three main oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. Data of patients with bladder cancer who were treated at these three centers during 01/Jan/2010 - 01/Jan/2023 period was collected from the medical records. Statistical analysis was conducted by 01/Nov/2023. Results: Eighty-seven patients with bladder cancer treated during mentioned period in these three hospitals were included in the final analysis. Male to female ratio was 8.6:1. 70% of patients were smokers. Median age at diagnosis was 65 years (range 37-82 years). 5.7% of patients had stage I, 17.2% stage II, 47.1% stage III, 25.3% stage IV bladder cancer, and for 4.6% of patients' stage was unknown. 9.2% of patients had grade 1, 18.4% grade 2 and 60.9% grade 3 tumors. Among stage IV patients the most common metastasis sites were lungs (36.4%), followed by non-regional lymph nodes (31.8%). Median overall survival (OS) was 31 months for the entire cohort. Median OS was 31 months for stage I, 62 months for stage II, 40 months for stage III and 14 months for stage IV patients. While OS for non-metastatic bladder cancer was higher than for metastatic stage, this difference was not statistically significant (39 vs 14 months; p=0,088). About 61% of patients received 1 st line chemotherapy with Cisplatin and 33.3% with Carboplatin. Only 9% of patients received immunotherapy during their course of treatment. In non-metastatic setting median OS was significantly better for those treated with Cisplatin containing regimens, compared with those treated with Carboplatin containing regimens (40 vs 23 months; p=0,021), while in stage IV this difference was not statistically significant (30 vs 14 months; p=0,269). Conclusions: Bladder cancer is one of the most common cancers in Armenia. Treatment with Cisplatin in non-metastatic patients was associated with better OS compared with Carboplatin. Patients diagnosed in metastatic setting have really poor prognosis with median OS slightly surpassing 1 year. While new treatment modalities with immunotherapy and targeted therapy are showing promising results worldwide, they are not widely available in Armenia.
Clinical and pathological characteristics of cancer of unknown primary with renal profile using gene expression profiling (GEP)–based cancer classification.
Authors: Joelle Allam, Li Ma, Jianping Zhao, Jeannelyn Estrella, Victoria Higbie, Anneleis Willett, Aurelio Matamoros, Elizabeth A Lano, Kai Treuner, Kanwal Pratap Singh Raghav, Ryan W Huey
Journal: Journal of Clinical Oncology (2024)

e16627 Background: Cancers of unknown primary (CUP) are rare and heterogeneous tumors with clinically unidentifiable origin at time of diagnosis, accounting for approximately 1-3% of all malignant neoplasms. CUP with Renal Profile (CUP-RP) appears to be a clinically distinct subset, based on immunophenotyping, specifically PAX8 staining. Precision in diagnosis is critical, as cytotoxic chemotherapy options for CUP do not overlap with tyrosine kinase inhibitors or checkpoint inhibitors used for renal cell carcinoma. Gene expression-based cancer classification in patients with CUP offers an objective molecular assessment in the search for CUP origin and further categorization. Methods: We retrospectively evaluated 300 patients with CUP composed of cases classified as renal profile (N=100, clear cell or papillary) or controls (N=200, non-renal cases) using the 92-gene assay (CancerTYPE ID), a validated classifier for predicting tissue of origin, between January 2018 and December 2022. Clinicopathologic data including immunohistochemistry (IHC) and molecular profiling (NeoTYPE) results were collected using pathology specimens and reports. Results: At baseline, median age at diagnosis was 69 years (range 31-89). Most patients were male (63%). For CUP-RP patients, pathology was reported as poorly differentiated in 47% of tumors. Tumors were described as adenocarcinoma in 27%, carcinoma in 63%, and malignant neoplasm in 10%. Median number of IHC stains performed was 11 (range 0-33). PAX8 staining was found to be strongly or focally positive in 88%. PAX8 was not tested in 36% of cases. Compared to non-renal profile CUP, CUP-RP patients were more likely to have bone biopsies (28% vs 16.5%, OR 1.97, p=0.02). CUP-RP were much less likely to have high-TMB (2% vs 28.2%, OR 0.07, p=.001). CUP-RP had a lower proportion of TP53 mutations (18.8% vs 81.2%, OR 0.028, p&lt;0.0001) and KRAS mutations (13.3% vs 86.7%, OR 0.045, p&lt;0.0001). Detailed IHC from 30 CUP-RP cases is shown in the table. CA IX was tested in 2/30 (6.7%) of cases. Conclusions: In this cohort of CUP with a molecular classification of renal cell carcinoma, we found a wide range in diagnostic work-up. The 92-gene assay can serve as an adjunct to IHC, to improve diagnostic accuracy for CUP. Critical immune stains necessary in diagnosis are performed infrequently. While PAX8 was often positive in CUP-RP, it was omitted in over 1/3 of cases. CUP-RP cases had lower TMB and less often mutations in TP53 and KRAS. Gene expression profiling presents an opportunity to complement standard pathology in the workup of this subset of CUP to guide treatment selection and improve clinical outcomes. [Table: see text]
Tislelizumab combined with gemcitabine and cisplatin (GC) as adjuvant therapy in patients with high-risk upper urothelial carcinoma (UTUC) after surgery: A 2-year follow-up, real-world study.
Authors: Penghe Quan, Haozhong Hou, Xiaojian Yang
Journal: Journal of Clinical Oncology (2024)

e16548 Background: In China, the prevalence of upper tract urothelial carcinoma (UTUC) among patients (pts) with urothelial carcinoma (UC) ranges from 9.3% to 19.9%, which is higher compared to the 5%-10% observed in Caucasoid populations. Following radical nephroureterectomy (RNU), UTUC pts with high-risk factors (e.g., local , pT3-4a, ypT2-4a, or N+) still have a poor prognosis and require adjuvant therapy. Immune checkpoint inhibitor as adjuvant therapy has been previously demonstrated improved disease-free survival (DFS) for UC pts, but the data from UTUC studies is limited.This real-world study aimed to evaluate the efficacy and safety of tislelizumab (Tisle) plus gemcitabine and cisplatin (GC) in high-risk UTUC pts. Methods: Pts who were diagnosed with T1N1 or T2-T4aN0-1M0 UTUC, tolerated surgery, and had adequate renal function reserve after surgery and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 were retrospectively enrolled from the Department of Urology, Xijing Hospital of Air Force Military Medical University between January 2020 and March 2023. Within 90 days following the RNU surgery, pts received adjuvant therapy of 200 mg Tisle on day 1 every 3 weeks plus 0-6 cycle GC chemotherapy (1000 mg/m 2 gemcitabine on days 1 and 8; 70 mg/m 2 cisplatin on day 2). Tisle was continued until disease progression or intolerable toxicity. The primary endpoint was 3-year DFS rate. Secondary endpoints were 5-year DFS rate, overall survival (OS), cancer-specific survival (CSS), and safety. Results: A total of 53 pts were enrolled in this study for efficacy evaluation. As of the cut-off date , median follow-up time was 26 (5-46) months, and of the pts were followed up for &gt;24 months. The 2-year DFS rate was 75.56% (95% confidence intervals [CI], 57.87%-86.63%), and the 2-year OS rate was 79.63% (95% CI, 61.50%-89.88%). Compared to GC &lt; 3 cycles, GC ≥ 3 cycles significantly improved DFS (hazard ratio [HR], 0.125; 95% CI, 0.034-0.461; p=0.019) and OS (HR, 0.147; 95% CI, 0.037-0.589; p=0.037), indicating a long tail in survival with the addition of Tisle to GC. Conclusions: In this real-world setting, adjuvant therapy with Tisle plus GC demonstrated encouraging efficacy and well-tolerated safety among high-risk UTUC pts. The final results will reported in further studies.
Sacituzumab govitecan (SG) plus enfortumab vedotin (EV) for metastatic urothelial carcinoma (mUC) treatment-experienced (DAD) and with pembrolizumab (P) in treatment naïve UC (DAD-IO).
Authors: Bradley Alexander McGregor, Lucia Kwak, Guru P. Sonpavde, Stephanie A. Berg, Toni K. CHOUEIRI, Joaquim Bellmunt, Charlene Mantia
Journal: Journal of Clinical Oncology (2024)

TPS4618 Background: In the DAD study (NCT04724018) the combination of SG+EV demonstrated favorable safety determining a maximum tolerated dose of 10 mg/kg and 1.25 mg/kg IV D1,8 every 21 days along with encouraging efficacy in treatment resistant mUC as evidenced by an objective response rate (ORR) of 70% in 23 evaluable patients. Given cumulative toxicities and efficacy across dose levels, the recommended phase 2 dose was SG 7.5 mg/kg and EV 1.25 mg/kg D1,8 of 21-day cycle. As EV+P is now a standard of care for front line urothelial carcinoma, NCT04724018 was amended to include 2 cohorts of distinct patient populations; one expanding SG+EV (DAD) and a second exploring the SG+EV+P (DAD-IO) combination. Methods: In DAD cohort, patients with mUC progressing on platinum and immunotherapy or on one line of therapy receive SG 7.5 mg/kg + EV 1.25 mg/kg intravenously (IV) on day(D)s 1 and 8 every 3 weeks (1 cycle) until progression or intolerable toxicities. In DAD-IO cohort, patients with treatment naïve mUC are given SG 7.5 mg/kg+EV 1.25 mg/kg IV D1, 8 of a 21-day cycle with P 200 mg every 3 weeks or 400 mg every 6 weeks per investigator discretion. In both cohorts, prophylactic granulocyte colony stimulating factor (GCSF) support is given per supportive care guidelines with cycle 1. Following first dose on trial, SG and EV can be reduced and held independently for toxicity with reductions of SG to 5 mg/kg, and EV to 1, 0.75 and 0.5 mg/kg. P dose reductions are not allowed but can be held as needed for immune related adverse events. Laboratory evaluation is performed on days 1 and 8 every cycle. Imaging is performed at baseline and every 6 weeks for the first 4 cycles followed by every 9 weeks thereafter. In both cohorts, the primary endpoint is RECIST 1.1 ORR with secondary endpoints being progression free survival, overall survival, and safety. DAD aims to enroll 41 eligible patients, assuming an ORR of 65% for EV+SG, to detect a 25% improvement with over 90% power at a one-sided type I error rate of 0.05 using a single-stage exact one-sample binomial design; ³ 23 responses would rule out a null of 40% ORR. DAD-IO plans to enroll 41 eligible patients, assuming an ORR of 75% for SG+EV+P to detect a 20% improvement with 90% power at a one-sided type I error rate 0.09 based on a Simon optimal two-stage design. If ³ 11 responses are observed in the first 18 patients, an additional 23 patients will be enrolled. At least 27 responses among a total of 41 will be needed to confirm its efficacy. The study includes a 12-patient safety lead in using a Bayesian toxicity monitoring. If ≤2 dose limiting toxicities (DLTs) occur in the first 6 patients, the next 6 are enrolled. The study halts if ≥5 DLTs occur among 12 evaluable patients. Clinical trial information: NCT04724018 . [Table: see text]
Feasability of single-port gasless retroperitoneal laparoscopic adrenalectomy for patients with adrenal tumor: A prospective control study.
Authors: Zhenhua Liu, Xiaobo He, Yuhui Long, Nan Ma, Renchun Lai, Shengjie Guo
Journal: Journal of Clinical Oncology (2024)

e16628 Background: The safety and efficacy of single-port-gasless retroperitoneal laparoscopic adrenalectomy (SPG-RLA) in the treatment of adrenal tumors have not been fully explored. We aimed to explore the safety and efficacy of SPG-RLA for adrenal tumors. Methods: Thirty patients with adrenal tumors &lt;4 cm undergoing SPG-RLA were prospectively enrolled from July 2022 to February 2023. Operative time, blood loss, conversion and complication rates, and postoperative data were compared to another 30 patients with the same characteristics treated with traditional single-port retroperitoneal laparoscopic adrenalectomy (RP-LESS-A). Results: Both 30 SPG-RLA operations and 30 RP-LESS-A operations were completed without any mortality, reoperation, blood transfusion, or conversion. The mean operative time and blood loss were 62.3 min and 94.1 ml, respectively. Compared with the traditional surgery group, SPG-RLA patients had 15% lower hospitalization costs ( p &lt; 0.001), lowerΔpCO 2 (2.52 mmHg vs 6.86 mmHg, p = 0.001) and ΔpH (−0.05 vs −0.08, p = 0.004) values, and similar operative and postoperative complications, the average time to first oral intake (21.2 h vs 19.7 h, p = 0.106), ventilation time ( p = 0.058), duration of drainage ( p = 0.568), postoperative narcotic use ( p = 0.958), and postoperative hospitalization ( p = 0.116). However, the SPG-RLA group had longer operative time (62.3 min vs 45.7 min, p &lt; 0.001), more blood loss ( p = 0.032), and longer incisional length ( p &lt; 0.001). No local tumor recurrence or hormonal relapse was observed in the 6-month follow-up. Conclusions: SPG-RLA is a safe, minimally invasive, and economically viable surgery, which may especially be suitable for low-resource regions and in patients with cardiopulmonary insufficiency due to adrenal tumors. Clinical trial information: ChiCTR220005735 . [Table: see text]
Nimotuzumab, a novel anti-EGFR with concurrent chemoradiotherapy in muscle invasive bladder cancer: A real-world experience from India.
Authors: Shyam Rawat, Rajesh Jain
Journal: Journal of Clinical Oncology (2024)

e16592 Background: Muscle invasive bladder cancer (MIBC) shows 55-75% EGFR overexpression. Radical cystectomy (RC) with/without neoadjuvant chemotherapy is mainstay of treatment. Targeting with anti-EGFR therapy would be potential treatment option to preserve the organ in MIBC. Methods: Evaluation of medical records of patients with transitional cell carcinoma of urinary bladder who received concurrent cisplatin (40 mg/m 2 ) and radiotherapy (60 Gy) (CRT) with Nimotuzumab (200 mg) between 2012 and 2020 was done with prior consent of patients. Results: Medical records of 21 patients were analyzed of which 86% of male with average age of 64.6 years. Tobacco addiction was reported in 76% patients. Eighty-six percent of patients had locally advanced disease, of which 71% with grade III lesions. Treatment with CRT + Nimotuzumab was completed by all patients. Objective response rate was 100% (complete response 95% and partial response 5%) at 6-months post treatment. At the of follow-up was 59 months median overall survival (OS) and disease-free survival (DFS) was not reached. OS and DFS rates at 3-years were 100% and 90.4% respectively. Only two RC were performed subjecting to 90% organ preservation rate. There were no grade 3 or 4 adverse events, however grade 1-2 AEs Included neutropenia (28%), loose motion (76%) and skin reactions (47%). Conclusions: Concurrent CRT with Nimotuzumab could be a possible treatment option for organ preservation with improved outcomes and tolerable safety profile in patients with MIBC, and it can be evaluated further. Keywords: bladder cancer, MIBC, organ preservation, nimotuzumab, chemoradiation. Acknowledgment: We thank you Dr. Amit Y Jadhav for editorial support for this research project.