tbuckley/cabot-search huggingface dataset:
Evaluating prognostic models for stage I seminoma within the randomised trial of imaging and surveillance in seminoma testis (TRISST).
Authors: Robert A Huddart, Fay Helen Cafferty, Laura Murphy, Elizabeth James, Francesca Schiavone, Gordon J. S. Rustin, Syed A Sohaib, Johnathan K. Joffe
Journal: Journal of Clinical Oncology (2024)

501 Background: Prognosis in stage I seminoma is excellent. Most patients are cured by orchiectomy and, for the 15%-20% that relapse, salvage treatment is generally successful (survival approaching 100%). Relapse risk is reduced with adjuvant carboplatin but may unnecessarily expose young patients to long-term health risks. Effective and reliable risk stratification could guide use of adjuvant treatment and potentially reduce intensity of surveillance for the lowest risk patients. We used data from a UK multicentre, phase III trial to evaluate prognostic factors for relapse in stage I seminoma, including validation of a recently proposed model from the European Association of Urology (EAU)(1). Methods: TRISST used a randomised, factorial design to evaluate imaging schedules (3 vs 7 scans) and modality (MRI vs CT) in surveillance for men who had undergone orchidectomy for stage I seminoma (n=669). In this secondary analysis, model selection was used to fit a multivariable Cox regression to TRISST data to investigate factors predicting time to relapse, including: age, tumour mass size, rete testis invasion (RTI), T stage, lymphovascular invasion (LVI), side of tumour, and tumour markers (LDH, β-HCG). The final model was used to divide the cohort into risk groups. Relapse risk was also estimated according to EAU prognostic groups. Harrell’s C-index was used to measure model fit. Results: Based on TRISST data, tumour size ≥4cm and pT3 disease were associated with the highest risk (multivariable hazard ratio for ≥4cm vs &lt;2cm: HR=4.00, 95% confidence interval 2.00-8.01; pT3 vs pT1: HR=3.89, 1.77-8.57). Patients with one or both of these features (24% of the cohort) had 5-year relapse rate of 22.0%. Medium risk (age&lt;30 years and/or 2-4cm and/or pT2) and low risk (age≥30 years, &lt;2cm and pT1) groups had 5-year relapse rates 12.0% and 2.3% respectively. The EAU model was a good fit to the TRISST data (C-index=0.62); 66%, 33% and 2% fell into the very low, low and high-risk EAU groups respectively with 5-year relapse rates of 10.1%, 16.1% and 45.5%. Conclusions: In stage I seminoma, relapse risk in patients managed with surveillance following orchiectomy is low for the majority of patients. Tumour size is consistently shown to be the best predictor of relapse. The EAU prognostic model, validated here, identifies a small group (&gt;5cm, with RTI and LVI) with particularly high risk who may benefit from adjuvant therapy. Reference: 1. Boormans J, et al. Journal of Clinical Oncology 2023; 41 (6_suppl): 410. Clinical trial information: ISRCTN65987321 .
UNICAB: Cabozantinib in locally advanced or metastatic non‐clear cell renal cell carcinoma post immunotherapy or in those unsuitable for immunotherapy (ANZUP 1802).
Authors: David William Pook, Carole A. Harris, Emma Link, Jeffrey C. Goh, Francis Parnis, Howard Gurney, Ganessan Kichenadasse, Craig Underhill, Javier Torres, Felicia Roncolato, Andrisha Jade Inderjeeth, Ciara Conduit, Margaret Mary McJannett, Ian D. Davis, Craig Gedye
Journal: Journal of Clinical Oncology (2024)

428 Background: Rare variant non-clear cell renal cell cancer (nccRCC) have diverse biology and therapeutic response. Immune checkpoint immunotherapy (ICI) can benefit some people with nccRCC, but many experience progression. We sought to test cabozantinib (C) in people with nccRCC refractory to, or unsuitable for ICI. Methods: Eligible participants (pts) had advanced/metastatic nccRCC with good ECOG PS (&lt;2) and either prior treatment with ICI or were unsuitable for ICI due to a contraindicating autoimmune disorder. Pts with urothelial or collecting duct tumour were excluded. Eligible pts started C at 60mg per day with dose modifications as required. Clinical cycles were 28 days and radiological assessment occurred 8-weekly for 12 months. Pts could then continue C via an access program. Results: 33 pts with nccRCC were recruited from Mar 2019 to Dec 2022. Recruitment was influenced by the COVID19 pandemic. Two pts were found ineligible (brain metastasis, concurrent CYP3A4 inducer). Pts tumour histology included papillary type 1 (10), chromophobe (7), papillary type 2 (4), Xp11 translocation (3) and other histologies (7). 24 pts had received prior ICI, mostly nivolumab alone (17) or anti-PD1-antibodies in combination with other agents (anti-CTLA4, anti-TIGIT). Median duration of therapy was 9 cycles. 17 pts ceased for unacceptable toxicity or disease progression and 12 pts completed the 12 months of treatment, with 2 remaining on trial treatment at time of analysis. A partial response was seen 7/31 (22%) pts overall, including 7/24 pts with prior ICI and 0/7 pts unsuitable for ICI. Median treatment duration was 7.5 cycles (range 2-12) in pts with prior ICI treatment, and 11 cycles (range 2-12) in pts unsuitable for ICI. 90% of pts required dose reduction, most often due to fatigue, hypertension, diarrhoea and hand-foot syndrome, with a mean C dose of 46mg/day. No new safety signals were observed. Conclusions: C is an active treatment for people with nccRCC previously treated with ICI, with similar toxicity to previous reports in other cancers. Pts unsuitable for ICI may have poorer outcomes for C therapy in nccRCC. Further follow-up will determine duration of response and overall survival. Clinical trial information: NCT03685448 .
Single-stage retrocrural and retroperitoneal lymph node dissection for metastatic germ cell tumor: The University of Southern California experience.
Authors: Alireza Ghoreifi, Muhannad Alsyouf, Hooman Djaladat, Anne K. Schuckman, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2024)

515 Background: Resection of retrocrural disease in patients with metastatic germ cell tumors is a surgical challenge, especially in the post-chemotherapy setting. Herein, we present our experience with single-stage retrocrural metastasectomy and retroperitoneal lymph node dissection (RPLND). Methods: Using our IRB-approved testicular cancer database we identified patients who underwent one-stage retrocrural and retroperitoneal mass resection between September 1997 and December 2022. Clinical characteristics, surgical approach, peri-operative complications, and oncological outcomes of these patients were reviewed. Results: Among 400 patients who underwent RPLND for testicular cancer over the study interval, concurrent retrocrural resection was performed in 23 cases. Demographics and clinical features of the patients are shown in the table. All surgeries were performed in the post-chemotherapy setting, except one who underwent primary RPLND for seminoma. Surgical approach has evolved over time, including thoracoabdominal (TA) in 6 (all before 2010) and midline transabdominal (MA) in 17, including 3 midline extraperitoneal. There were 9 (39%) patients who required adjunctive procedures. Histology of retrocrural masses revealed viable tumor in 2 (embryonal carcinoma and seminoma), teratoma in 18 (including one with malignant transformation), and necrosis/fibrosis in 3. Pathologic concordance rate between retrocrural and retroperitoneal pathology was 83%. Median length of hospital stay was 5 days (9 vs. 3.5 for TA and MA, respectively). The 90-day complication rate was 43% (Clavien 3=17%), with a lower rate in patients undergoing MA vs. TA incisions (35% vs. 67%). With a median (IQR) follow-up of 24 (6-90) months, only one patient had retrocrural recurrence requiring re-resection, and no mortality was reported. Conclusions: The midline transabdominal is an effective approach for the concurrent retrocrural and retroperitoneal lymph node dissection in select patients with metastatic germ cell tumors. It is associated with a lower perioperative complication rate compared to the traditional thoracoabdominal approach.[Table: see text]
Survivorship issues beyond 2 years after treatment in testicular germ cell tumors: Experience from a large centre in the United Kingdom.
Authors: Lucy Flanders, Wendy Ansell, Daniel Richardson, Peter Wilson, Kenrick Ng, Jonathan Shamash
Journal: Journal of Clinical Oncology (2024)

512 Background: Testicular germ cell tumors (tGCTs) are rare but are highly curable, resulting in a large cohort of long-term survivors. The primary aim of most follow-up programs after initial treatment is to detect recurrence, which emphasizes regular imaging and measurement of serum tumor markers. Most relapses occur in the first two years after treatment. However, many of these patients also experience survivorship issues beyond the two-year timepoint which are underrecognized in the clinical setting and underreported in clinical literature. Methods: We retrospectively reviewed clinical documentation across a cohort of tGCT patients in St Bartholomew’s Hospital who received adjuvant treatment (n=171), treatment for metastatic cancer (n=325) and those who underwent surveillance only (n=225) from 2011 and 2021. Only patients with a minimum follow-up of 5 years were included. Data was collected between Year 3 to Year 10 after initial treatment, ie only after two years of surveillance were completed. The frequency in which the following terminology/symptoms appeared in clinical documentation was recorded: relapse, endocrinology (a hormone problem including, but not included to hypogonadism/diabetes/thyroid dysfunction), lifestyle advice (eg weight management), blood pressure, cholesterol, psychology, fertility and other problems. Each reported issue was only recorded once per patient for this study. Results: Relapse rates were 0-0.75% annually (0% adjuvant, 0.7% metastatic, 0.75% surveillance). Total relapse rates beyond the two year time point, per group, were 0% in the adjuvant group, 5.8% in the metastatic group, and 6.0% in the surveillance group. Of the patient group who received treatment, significantly more reported endocrinological issues (7.0% average annually in the adjuvant group vs 4.2% metastatic vs 0.1% surveillance). Issues relating to blood pressure were equally reported (5.5% average annually in adjuvant vs 2.95% in metastatic vs 2.60% in surveillance) as were cholesterol (4.7% average annually in adjuvant vs 2.2% in metastatic vs 2.2% in surveillance). Fertility issues were more commonly reported in the group of patients who received treatment for metastatic cancer (2.4%) as opposed to those who received adjuvant treatment(0.5%) and surveillance only (0.7%). Conclusions: Relapse rates in our cohort of patients are low and consistent with previous studies. However, we highlight multiple survivorship issues for patients who have received treatment – particularly issues pertaining to endocrinological issues and fertility. These results suggest the need to incorporate monitoring of survivorship issues into our routine follow-up to improve patient experiences and outcomes. We suggest that a specialist clinic focused on long-term survivorship issues be established to better address the needs of this patient population.
Outcomes and prognostic factors of first-line combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in <i>TFE3</i>-rearranged renal cell carcinoma.
Authors: Junjie Zhao, Yanfeng Tang, Xu Hu, Junru Chen, Haoyang Liu, Haolin Liu, Jiayu Liang, Xingming Zhang, Jinge Zhao, Pengfei Shen, Zhenhua Liu, Guangxi Sun, Hao Zeng
Journal: Journal of Clinical Oncology (2024)

429 Background: Due to the rarity of TFE3-rearranged renal cell carcinoma ( TFE3-rRCC) and the poor understanding of its underlying mechanisms, the clinical treatment landscape in TFE3-rRCC is largely undefined. Hence, the optimal therapy for TFE3-rRCC remains to be determined. The diversity of fusion partners leads to the high heterogeneity of TFE3-rRCC, yet no studies have compared responses of patients with different fusion partners to systemic treatment. Methods: Data were collected retrospectively from our institution. Patients with metastatic TFE3-rRCC were eligible. Kaplan-Meier survival analysis and univariate and multivariate analysis were performed to compare survival outcomes. RNA-seq was performed to determine fusion partners and explore the transcriptomic features. Results: A total of 38 patients with metastatic TFE3-rRCC were enrolled in this study. The fusion partners were identified in 33 (87%) patients. Patients receiving first-line ICI plus TKI had longer PFS than those not receiving first-line ICI plus TKI (median PFS: 11.5 vs. 5.1 months, P=0.098). Subgroup analysis demonstrated that patients with ASPSCR1-TFE3 fusion significantly benefited from ICI plus TKI (PFS HR: 0.068, 95% CI: 0.008-0.609, P=0.016), whereas no improvement in PFS was observed in patients with other fusions. Univariate and multivariate cox regression analysis further demonstrated that besides IMDC risk score, ASPSCR1-TFE3 fusion could also serve as an independent prognostic factor for PFS in patients receiving first-line ICI plus TKI. Among patients receiving ICI plus TKI, those with ASPSCR1-TFE3 fusion had longer PFS than those with other fusions (median PFS: not reached vs. 6.5 months, P=0.01). Transcriptomic data revealed that ASPSCR1-TFE3 fusion rearranged RCC harbored higher angiogenesis activity. Additionally, decreased infiltration of immunosuppressive M2-phenotype macrophages and Tregs was observed in tumors with ASPSCR1-TFE3 fusion. Conclusions: Metastatic TFE3-rearranged RCC patients with ASPSCR1-TFE3 fusion could benefit from ICI plus TKI. Higher angiogenesis activity and decreased infiltration of immunosuppressive cells were observed in tumors with ASPSCR1-TFE3 fusions, which may explain the clinical outcome.
Tislelizumab in combination with gemcitabine plus cisplatin as neoadjuvant therapy for lymph node‐positive bladder cancer: Results of a prospective study.
Authors: Xiao Yang, Juntao Zhuang, Qiang Cao, Lingkai Cai, Qikai Wu, Qiang Lu
Journal: Journal of Clinical Oncology (2024)

619 Background: Although multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs combined with gemcitabine plus cisplatin in MIBC, lymph node‐positive bladder cancer is generally excluded. In this study, our specific aim was to compare the efficacy and prognosis of neoadjuvant tislelizumab combined with gemcitabine plus cisplatin in patients with lymph node‐positive bladder cancer. Methods: In this investigator-initiated study, eligible patients had cT2-T4 N+ M0 MIBC, cisplatin-eligible, and to be planned radical cystectomy (RC). Patients received tislelizumab 200 mg in day 8 (D8), cisplatin 70 mg/m2 D2-4, and gemcitabine 1000 mg/m2 D1 and D8 every 21 days for 3 or 4 cycles. RC was performed within 6 weeks after last dose treatment. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (&lt;ypT2), EFS, OS and safety. Results: A total of 15 pts were enrolled,14 pts (2 cT2, 7 cT3, 5 cT4) have completed neoadjuvant therapy and underwent RC. One patient declined surgery for personal reasons and received further systemic therapy. In 14 pts evaluable for efficacy, the investigator-assessed confirmed clinical complete response was 21.4% (3/14). Final pathologic results showed that 5 pts (50%) achieved pCR (ypT0N0), 4 ypT1, and 5 ypT2/T3, and 9 patients (&lt;ypT2N0,64.2%) had staging downgrades, with no patients experiencing progression. A complete nodal response (pN0) occurred in 11 (78.5%) pts after tislelizumab +chemotherapy. The median follow-up was 8.9 months, with one death due to multiple metastases and the remaining patients showing no signs of recurrence or metastasis. Median EFS and OS was not reached. Most common neoadjuvant therapy-related AEs of any grade were hematologic toxicities (11/14,78.5%), nausea (9/14,64.2%), vomiting (8/14,57.1%). Grade ≥3 neoadjuvant therapy-related AEs were neutropenia (n = 3), thrombocytopenia (n = 2), anemia (n = 2). One patient discontinued tislelizumab due to AEs. Conclusions: The combination of tislelizumab and gemcitabine/cisplatin is clinically active with a manageable safety profile as a neoadjuvant therapy for lymph node‐positive bladder cancer. Clinical trial information: NCT04570410 .
Daro-PET: A phase 2 trial of darolutamide as a prostate-specific membrane antigen (PSMA) expression enhancer in patients with localized prostate cancer.
Authors: Jose Mauricio Mota, Camila Mosci, Jéssica Vasconcellos, Thiago Souto Hemerly, Deusdedit Cortêz Vieira Silva Neto, Luis Felipe Brandao, Victor Srougi, Rodrigo Nalio Ramos, Isabela Werneck Cunha
Journal: Journal of Clinical Oncology (2024)

TPS348 Background: Prostate specific membrane antigen (PSMA) has been explored as a target in imaging studies using positron emission tomography (PSMA-PET) to unveil occult prostate cancer metastasis, and as a target for radioligand therapy. Preclinical and retrospective clinical studies suggest that PSMA expression can be rapidly increased by androgen suppression, which might impact the accuracy of disease detection using PSMA-PET scans and radioligand treatment efficacy. Methods: Daro-PET (NCT05900973) is a single-arm phase 2 study to evaluate the efficacy of a limited course of darolutamide as a PSMA expression enhancer in men planned for radical prostatectomy due to high-risk localized prostate cancer as per conventional imaging. PSMA PET/CT scans will be acquired before (PSMA-PET 1) and after (PSMA-PET 2) a 7-day treatment with darolutamide 600 mg PO q12 h. The primary endpoint is the proportion of patients achieving an increase in SUVmax of 20% or greater from PSMA-PET 1 to PSMA-PET 2. Key secondary endpoints include other PSMA PET parameters (e.g. SUVmean, Total lesion PSMA), proportion of planned management changes, detection of pelvic or extrapelvic metastatic disease, and safety. Correlative exploratory studies will include PSMA expression by immunohistochemistry, gene expression, and methylation patterns between tissue samples from prostate biopsy and prostatectomy. The trial will enroll up to 16 patients using a Simon’s two-stage design, with a power of 0.80 and a one-sided alpha error of 0.05. As of September 20 th , 1 patient was included in the study. Clinical trial information: NCT05900973 .
Value-based payment models and management of newly diagnosed prostate cancer.
Authors: Avinash Maganty, Samuel Kaufman, Mary Oerline, Kassem S Faraj, Megan Veresh Caram, Vahakn B. Shahinian, Brent K. Hollenbeck
Journal: Journal of Clinical Oncology (2024)

309 Background: To examine the effect of urologist participation in value-based payment models on the management of men with newly diagnosed prostate cancer. Methods: Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019 were assigned to their primary urologist, each of whom was then aligned to a value-based payment model (the Merit-based incentive payment system [MIPS], accountable care organization [ACO] without financial risk, and ACO with risk). Multivariable mixed-effects logistic regression was used to measure the association between payment model participation and treatment of prostate cancer. Additional models estimated the effects of payment model participation on use of treatment in men with very high risk (i.e.,&gt;75%) of non-cancer mortality within 10 years of diagnosis (i.e., a group of men for whom treatment is generally not recommended) and price-standardized prostate cancer spending in the 12 months after diagnosis. Results: Treatment did not vary by payment model, both overall (MIPS— 67% [95%CI 66 to 68%], ACOs without risk—66% [95%CI 66 to 68%], ACOs with risk— 66% [95%CI 64 to 68%]). Similarly, treatment did not vary among men with very high risk of non-cancer mortality by payment model (MIPS— 52% [95%CI 50 to 55%], ACOs without risk— 52% [95%CI 50 to 55%], ACOs with risk— 51% [95%CI 45% to 56%]). Adjusted spending was similar across payment models (MIPS— $16,501 [95%CI $16,222 to $16,780], ACOs without risk— $16,140 [95%CI $15,852 to $16,429], ACOs with risk— $16,117 [95%CI $15,585 to $16,649]. Conclusions: How urologists participate in value-based payment models is not associated with treatment, potential overtreatment and prostate cancer spending in men with newly diagnosed disease.
Efficacy and safety of disitamab vedotin combined with toripalimab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer.
Authors: Chenglong Li, Jiefu Zhu, Weimin Yu
Journal: Journal of Clinical Oncology (2024)

631 Background: For HER2 positive muscle-invasive bladder cancer (MIBC), the efficacy of cisplatin-based NAC is unsatisfied, and adverse reactions are inevitable or even intolerable. Disitamab vedotin is an antibody-drug conjugate composed of an anti-HER2 antibody disitamab and MMAE payload. Multiple clinical studies have confirmed that promising activity in HER2-positive locally advanced or mUC patients。This study aims to evaluate the safety and efficacy of disitamab vedotin, and toripalimab as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced MIBC. Methods: In this Study, Platinum intolerance and pathological andimaging diagnosed cT2-4bN0M0 MIBC patients with HER2 positive (HER2 IHC2+ or HER2 IHC3+) received 3 cycles toripalimab (200mg, iv, D1, Q2W) combined with disitamab vedotin (2mg/kg, iv, D1, Q2W). The primary endpoint was pCR, and the secondary endpoints included PFS, OS, and safety. Results: From July 2023 to Sep 2023, 12 patients were enrolled. The median age was 68 (55-82) years . By the data cut off in August 2023, the primary end point pCR was 80% (8/10). Median follow-up time was 4.2 (2.2-8.45) month. The median overall survival (OS) was not reached，ORR was100%. In terms of safety, the treatment-related adverse events (TRAEs) of any grade occurred in ten patients (83.3%), and the most common TRAEs were nausea (58.3%), followed by alopecia (33.3%), diarrhea (16.7%) and Cardiac tachycardia (8.3%). most of which are grade 1-2. Grade 3 TRAE is Cardiac tachycardia and occurred in one patient. No grade 4 and 5 TRAEs were observed. Conclusions: From July 2023 to Sep 2023, 12 patients were enrolled. The median age was 68 (55-82) years . By the data cut off in August 2023, the primary end point pCR was 80% (8/10). Median follow-up time was 4.2 (2.2-8.45) month. The median overall survival (OS) was not reached, ORR was100%. In terms of safety, the treatment-related adverse events (TRAEs) of any grade occurred in ten patients (83.3%), and the most common TRAEs were nausea (58.3%), followed by alopecia (33.3%), diarrhea (16.7%) and Cardiac tachycardia (8.3%). most of which are grade 1-2. Grade 3 TRAE is cardiac tachycardia and occurred in one patient. No grade 4 and 5 TRAEs were observed.