tbuckley/cabot-search huggingface dataset:
Efficacy and safety of the combination of cisplatin plus nab-paclitaxel and nivolumab with radiotherapy after maximal tumor resection in non-metastatic muscle invasive bladder cancer (CNN-BC trial).
Authors: Chiara Ciccarese, Roberto Iacovelli, Anna Rita Alitto, Annunziato Anghelone, Ileana Sparagna, Luca Tagliaferri, Giuseppe Palermo, Marco Racioppi, Giampaolo Tortora
Journal: Journal of Clinical Oncology (2024)

TPS723 Background: The therapeutic gold standard for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) preceded by neoadjuvant chemotherapy when appropriate. However, RC is a major surgery procedure with 13% rate of severe complication and a perioperative mortality rate of about 1.5 - 5 %. Trimodal therapy (TMT) is a “bladder sparing” option alternative to RC. TMT consists of complete transurethral bladder tumor resection (TURBT) followed by a combination of systemic chemotherapy and locoregional radiotherapy (RT), with the option of “salvage” cystectomy in case of local treatment failure. Immunotherapy with anti-PD1/PD-L1 monoclonal antibody significantly improves survival of metastatic BC patients, and it seems to potentiate the activity of RT without increased toxicity. Therefore, we investigate the role of a multimodal TMT strategy to increase the disease-free survival (DFS) and avoid or delay RC in non-metastatic MIBC pts. Methods: CNN-BC trial (NCT05203913) is a phase 2, open-label, mono-institutional study evaluating the activity and safety of TMT with cisplatin, nab-paclitaxel and nivolumab as systemic therapy in non-metastatic MIBC pts. Eligible pts should have undergone complete TURBT with diagnosis of T2-T3 N0M0 urothelial carcinoma, and no evidence of lymph nodes or metastatic disease at FDG-PET within 6 weeks from the start of treatments. TMT consists of nivolumab (480 mg IV every 4 weeks for a total of 13 doses), weekly nab-paclitaxel (60mg/m2) plus cisplatin (20mg/m2) administered concurrently with RT (60Gy in 25 fractions over 5 weeks on original bladder tumor, plus a concomitant boost of 50Gy in 25 fractions on whole bladder and pelvic nodes). The primary endpoint is the 1-year DFS rate, defined as the rate of survival free of recurrence in pelvic nodes or bladder, or appearance of distant metastases. Secondary endpoints include: the rate of pts who require salvage cystectomy, the rate of locoregional complete response (CR) and of locoregional DFS, median DFS, safety, and quality of life. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05203913 .
Rethinking the definition of stage IV disease in adrenocortical carcinoma: Assessing the impact of clinical lymph node positive disease.
Authors: Helen Gao, Benjamin Lichtbroun, Kevin J. Chua, Arnav Srivastava, John Pfail, David Golombos, Thomas L. Jang, Saum Ghodoussipour
Journal: Journal of Clinical Oncology (2024)

5 Background: Stage III (pT3N0M0 or pT1-3N1M0) adrenocortical carcinoma (ACC) encompasses both lymph node positive (LN+) and lymph node negative (LN-) disease. However, in other malignancies, prior data demonstrates that LN+ disease portends outcomes similar to metastatic, stage IV disease. We similarly wanted to examine the impact of clinical LN+ disease on oncologic outcomes in ACC. Methods: Patients with clinical stage III and stage IV (M1) disease were identified using the National Cancer Database (NCDB). Stage III patients were stratified as having either LN+ or LN- disease. Kaplan-Meier curves illustrated overall survival of the three groups – stage III LN-, stage III LN+, and stage IV. Further analysis stratified stage III LN+ and stage IV patients by whether or not patients received treatment (systemic therapy, surgery, or both). Results: A total of 917 patients were included in the analysis – 322 stage III LN-, 67 stage III LN+, and 528 stage IV. 3-year OS for patients with stage IV, stage III LN+, and stage III LN – was 15.6% (95% CI, 12.5%-19.4%), 29.4% (95% CI, 19.8%-43.6%), and 48.6% (95% CI, 43.2%-54.6%), respectively. Within the stage III LN+ group 3-year OS was 33.0% (95% CI, 18.5%-58.8%) for those who received treatment and was 27.4% (95% CI, 16.1% - 46.6%) for those who did not. Within the stage IV group 3-year OS was 29.8% (95% CI, 22.7%-39.3%) for those who received treatment and was 10.2% (95% CI, 7.4% - 14.2%) for those who did not. Conclusions: The current staging paradigm of ACC includes LN+ disease as part of the stage III classification. Herein, we see that clinical stage III LN+ disease had a 3-year OS that was more similar to clinical stage IV disease than clinical stage III LN- disease. While the survival curves appear distinct, due to the rarity of the disease and therefore small sample size there was overlapping confidence intervals. In stage IV patients there was a significant difference in OS at 3 years between those who did and did not receive treatment. This same finding was not found in stage III LN + patients.
Tumor suppressor genes (TSG), treatment, and survival in de novo metastatic hormone-sensitive prostate cancer.
Authors: Martin W. Schoen, Robert Bruce Montgomery, Eric Marshall Knoche
Journal: Journal of Clinical Oncology (2024)

187 Background: The standard of care for metastatic hormone sensitive prostate cancer (mHSPC) has changed substantially in less than a decade. For patients with suitable functional status, combination therapy is recommended. A diverse molecular landscape of mHSPC exists, however molecular findings have yet to inform treatment in mHSPC. Outcomes for patients vary according to baseline molecular features and patients with mutations of tumor suppressor genes (TSG) have worse survival. We sought to examine the impact of TSG alterations on overall survival (OS) for men with de novo mHSPC. Methods: We identified patients diagnosed with de-novo mHSPC from July 2017-December 2021 within the Veterans Health Affairs. Alterations in TSG including TP53, PTEN, and RB1 were determined from National Precision Oncology Program (NPOP) testing collected at any time and all alterations were included. Only patients who survived 4 months and treated within 4 months of diagnosis were included. Treatments included androgen deprivation therapy (ADT) alone, docetaxel, or androgen receptor pathway inhibitors (ARPI). Kaplan-Meier and Cox proportional hazard models to assess the association between TSG and age, BMI, weight change in the year prior to mHSPC, Charlson comorbidity index, PSA at diagnosis, Black race, treatments for mHSPC, and OS. Results: We identified 2808 veterans with de novo mHSPC and 915 (32.6%) had NPOP data available. Patients with NPOP data were younger (mean age 71.4 vs. 75.2 years, p&lt;0.001) and had longer OS than veterans without testing (43.7 months vs. 31.0, p&lt;0.001). TSG alterations were found in 475 of 915 veterans (51.9%) and included 344 TP53 (37.6%), 206 PTEN (22.5%) and 50 RB1 (5.5%). Veterans with TSG had shorter OS compared to no TSG, median OS 48.5 months without TSG vs 37.7 with 1 or more TSG (p&lt;0.001). Each TSG alteration was associated with mortality, TP53 adjusted Hazard Ratio (aHR) and 95% confidence interval 1.68 (1.35-2.09), PTEN aHR 1.33 (1.02-1.73), RB1 aHR 1.51 (1.01-2.26). ADT alone was given in 354 veterans (38.7%), docetaxel in 139 (15.2%), and ARPI in 422 (46.1%). In veterans with one or more TSG neither docetaxel nor ARPI therapy was associated with OS in unadjusted or adjusted analyses compared to ADT alone (Table). Conclusions: TSG alterations were associated with shorter survival in de novo mHSPC in veterans with molecular testing. In this real-world observational study, treatment intensification with docetaxel or ARPI in veterans with TSG was not associated with improved overall survival. [Table: see text]
Preliminary reliability of the FACT-RNT in standard-of-care Lu-PSMA therapy of metastatic castration-resistant prostate cancer.
Authors: Lisa Marie Gudenkauf, Vishnu Murthy, Ethan C. Lam, Xiaoyin Li, Linda Gardner, Scott T. Tagawa, Adam P. Dicker, David Cella, Johannes Czernin, Jeremie Calais, Brian D. Gonzalez
Journal: Journal of Clinical Oncology (2024)

99 Background: The Functional Assessment of Cancer Therapy-Radionuclide Therapy (FACT-RNT) was recently developed as the first patient-reported outcome (PRO) measure designed to monitor RNT-relevant symptoms and toxicities for patients with advanced metastatic castrate-resistant prostate cancer (mCRPC). This study aimed to examine preliminary reliability of the FACT-RNT in patients receiving RNT as part of standard of care. Methods: Patients scheduled to start 177Lu-PSMA-617 for advanced mCRPC December 2022 – August 2023 who were fluent in English or Spanish completed the FACT-RNT on day 1 of each RNT cycle administered at UCLA. The FACT-RNT is a 15-item measure assessing symptoms and toxicities on a 0-4 scale; total scores range from 0-60, with higher scores indicating better quality of life. Reliability was assessed in R using data from cycles 1-4 with Cronbach’s alpha test of internal consistency, Guttman’s Lamba 6 test of split-half reliability, inter-item correlations, and test-retest reliability. Results: Patients (N=43) were, on average, 69 years old (SD = 9, range = 51-91) at RNT cycle 1, were mostly non-Hispanic (79%) and White (58%) with Gleason score ≥ 7 (67%) at diagnosis. Patients had undergone surgery (35%), chemotherapy (98%), radiation (65%), hormone therapy (100%), and/or immunotherapy (28%). Some patients who recently began therapy were not yet due for follow-up cycles, and 9 (21%) died during the study period. Completion of the FACT-RNT ranged from n=43 (Cycle 1) to n=19 (Cycle 4). The FACT-RNT total score ranged from 18-60 across cycles. Internal consistency reliability ranged from 0.82 (good) to 0.91 (excellent), and split-half reliability ranged from 0.92 to 0.99 (excellent). Average inter-item correlations were acceptable for scaling purposes (all exceeding 0.20). Within-subject correlations between scores were r=0.75 for cycles 2 vs. 3 and r=0.94 for cycles 3 vs. 4, indicating good measurement stability across cycles. Conclusions: In preliminary analyses, the FACT-RNT demonstrates good to excellent internal consistency across the first four cycles, moderate to strong consistency of measuring a common underlying construct, and good measurement stability. Findings support reliability of the FACT-RNT and its use in future research.
Real-world clinical outcomes of patients treated with Lu-177-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC): A single-institution experience.
Authors: Valeria Maldonado Grijalva, John Wang, Marybeth Nedrud, Colm Kelleher, Terence Z. Wong, Matthew Labriola, Hannah Dzimitrowicz McManus
Journal: Journal of Clinical Oncology (2024)

83 Background: The radiopharmaceutical Lu177-PSMA-617 (LuPSMA) was FDA approved in March 2022 for patients with mCRPC previously treated with both an androgen receptor signaling inhibitor (ARSI) and a taxane, if eligible based on PSMA PET. However, data regarding real world LuPSMA treatment outcomes are limited. Methods: This is a retrospective analysis of the first 100 mCRPC patients who received at least 1 cycle of LuPSMA at a single institution from June 2022 to August 2023. Demographic and clinical characteristics as well as laboratory values were collected. Central review of qualifying PSMA PET/CT was performed to assess disease distribution. A PSA decrease of 30%, 50%, or 90% from baseline at any point during treatment was the primary measure of response (PSA30, PSA50, and PSA90 respectively). Results: Of the 100 patients identified, 2 were excluded from analysis due to prior receipt of LuPSMA on clinical trial. Three patients were still receiving LuPSMA at the time of data collection. Median age was 72 (range, 50 - 93) and median number of treatments received was 4.0. On baseline PET/CT, 43 patients (44%) had bone + nodal metastases only, 19 (19%) had bone metastases only, 8 (8%) had nodal metastases only, and 11 (11%) had liver metastases. As for prior therapies, 47% had received ≥2 ARSIs (n=47/98), 48% had received 2 prior taxanes (n= 47/98), 42% had received 1 prior taxane (n=41/98), 17% received radium-223 (n=17/98), and 10% were treated off-label with no prior chemotherapy (n=10/98). Median follow up from the start of LuPSMA treatment was 7.6 months (range= 0.6-14.1 months, n=98). During treatment, 21 (21%) patients achieved a PSA90 response, 51 (52%) patients achieved a PSA50 response and 60 (61%) patients achieved a PSA30 response. An increase or no change in baseline PSA was seen in 28% (n=26/94 evaluable patients). Among patients with an initial rise in PSA after the first treatment, 10% had a subsequent reduction from baseline PSA (n=3/29). Conclusions: In this cohort of heavily pretreated mCRPC patients, we observed a PSA50 response of 54% and 21% of patients experiencing a PSA reduction ≥90%. This data supports the clinical benefit of LuPSMA in real-world clinical practice. Characterization of response rates within subgroups by prior treatment and disease characteristics are ongoing.
What criteria do clinicians use to classify men as “high risk” among patients with biochemically recurrent nonmetastatic castration-sensitive prostate cancer?
Authors: Stephen J. Freedland, Amanda Ribbands, Jake Butcher, Maria Walley, Sophie Barlow, David Russell, Christopher S Bland, Maelys Touya, Jasmina I. Ivanova
Journal: Journal of Clinical Oncology (2024)

300 Background: In patients with biochemically recurrent (BCR) nonmetastatic castration-sensitive prostate cancer (nmCSPC), guidelines support the use of clinical factors such as prostate-specific antigen doubling time (PSADT) and Gleason score to identify high-risk patients who are more likely to develop metastases and could benefit from earlier intervention. The current study aimed to understand criteria used by physicians in the real-world to categorize patients with BCR nmCSPC as high-risk. Methods: This analysis used data from the Adelphi Real World nmCSPC retrospective survey, completed by urologists and radiation oncologists in the US. Physicians extracted data from medical charts for their last 6–8 patients diagnosed with high-risk BCR nmCSPC since January 2021 (until July 2023). A physician attitudinal survey was also completed. Data were analyzed descriptively. Results: Overall, 84 physicians provided data (68 urologists; 16 radiation oncologists). When asked in general (not patient specific) to name clinical factors used to determine level of risk, physicians cited using multiple factors, most frequently PSADT (93%), Gleason score (88%), absolute PSA rise following definitive therapy (86%), and clinical stage (85%). PSADT was cited as the single most important clinical factor by nearly 50%, followed by Gleason score, clinical stage, and absolute PSA rise following definitive therapy (Table). For physicians who used PSADT to risk stratify, the median (IQR) threshold for high-risk was 6 (6–9) months. Aggregated patient-level data were analyzed for 352 patients with high-risk BCR nmCSPC, as defined by the physicians. Clinical factors used to classify patients as having high-risk BCR in this study included PSADT (58%), Gleason score (44%), absolute PSA rise after definitive therapy (42%), clinical stage (21%), and pathological findings at radical prostatectomy (15%). Overall, 65% of patients had a PSADT ≤9 months after BCR, and 68% had a PSADT &lt; 12 months (high-risk per the AUA guidelines). Conclusions: Physicians reported using multiple clinical factors to classify patients as having high-risk BCR nmCSPC, with PSADT considered the most important for risk stratification. Appropriate and timely identification of patients as high-risk may help to identify patients for whom earlier intervention could be beneficial.[Table: see text]
The Capio Prostate Cancer Center model for prostate cancer diagnostics using Stockholm3, MRI, and targeted biopsies: Real-world evidence from 2018 to 2022.
Authors: Thorgerdur Palsdottir, Harold Söderbäck, Fredrik Jäderling, Martin Bergman, Hari Thambiah Vigneswaran, Henrik Gronberg
Journal: Journal of Clinical Oncology (2024)

295 Background: The Capio Prostate Cancer Center (Capio PCC) handles approximately 25% of prostate cancer care in Stockholm, Sweden. The Capio PCC Model utilizes Stockholm3 and MRI scans to assess prostate cancer risk, followed by targeted and systematic biopsies for those at increased risk. This study describes the clinical process and real-world evidence of the Capio PCC Model. Methods: If eligible for prostate cancer testing, men undergo a blood test for PSA. Men with PSA ≥1.5 ng/ml are additionally tested with Stockholm3 and men with a Stockholm3 ≥15, undergo MRI. Men with elevated risk on MRI undergo targeted and systematic biopsies. Men were included from 2018-2022 at the Capio PCC, if they underwent PSA and Stockholm3 (for PSA ≥1.5 ng/ml). The results on PSA, Stockholm3, MRI, and biopsies are presented, including the number of clinically significant prostate cancer as defined as ISUP grade ≥2. We compare the biopsy results from Capio PCC to other hospital regions in Sweden and evaluate health economics of the diagnostic pathway. Results: A total of 12,406 men aged 45-75 underwent testing for prostate cancer. Median age was 61 years (IQR: 55-67), median PSA was 1.6 ng/ml (IQR: 0.8 – 3.3), median Stockholm3 was 4 (IQR: 3-11) and 1,064 (8.6%) men were biopsied. A total of 611 (57% of biopsied) men were diagnosed with clinically significant prostate cancer. Of the tested men, 3,496 had PSA ≥3 ng/ml and 2,002 had Stockholm3 ≥15, decreasing the number MRIs by 43%. In total, 2,980 men had PSA between 1.5-2.99 ng/ml and of those, 360 (12%) had Stockholm3 ≥15 with 72 (56% of biopsied) men having clinically significant prostate cancer. In total, 330 men had PSA ≥10 ng/ml and of those, 87 men (26%) had Stockholm3 &lt;15, reducing MRI and biopsy in this higher risk group. Comparing national Swedish prostate cancer data, the Capio PCC Model showed fewer diagnoses of low-risk cancers (14% vs. 25%), more intermediate risk cancers (59% vs. 42%), and less high-risk and advanced cancers (26% vs. 30%). Conclusions: The study demonstrates that the protocol-driven and diagnostic process at Capio PCC leads to an effective care, enabling earlier diagnosis of intermediate risk cancer and reducing the number of MRIs as well as incidence of overdiagnosis of low-risk cancers compared to the prostate cancer care in Sweden.[Table: see text]
Identification of patients with metastatic urothelial cancer not able to receive maintenance avelumab.
Authors: Francesca Jackson-Spence, Vishwani Chauhan, Sofia Silva Diaz, Ayushma Gurung, Matthew Nicholas Young, Elizabeth Nally, Connor Wells, Bernadett Szabados, Thomas Powles
Journal: Journal of Clinical Oncology (2024)

702 Background: Maintenance avelumab following frontline platinum-based chemotherapy for metastatic urothelial cancer (mUC) is associated with survival benefit. Eligibility to receive avelumab maintenance requires receiving 4-6 cycles chemotherapy without disease progression. Not all patients complete 6 cycles of chemotherapy or meet eligibility to receive avelumab and these patients may need to have alternative therapies. Here we present real world data to assess whether baseline characteristics can be used to identify patients unable to complete 6 cycles of chemotherapy and whom may not be eligible for maintenance avelumab. Methods: This retrospective audit was performed at Barts Cancer Centre for consecutive patients from January 2010 until August 2023. Patients who received frontline gemcitabine and cisplatin/carboplatin chemotherapy for advanced mUC were included. Eligibility for avelumab is defined as completing 4-6 cycles of chemotherapy without disease progression (PD). Characteristics of patients completing 6 cycles of chemotherapy, versus those who do not were described. Chi-squared tests were conducted to compare characteristic between the two groups, using SPSS v28. Results: 265 patients receiving frontline systemic therapy were identified over a 13-year period. 242 (91%) received Gem/Cis or Gem/Carbo chemotherapy. 151 (63%) patients were eligible to receive maintenance avelumab. 91 (38%) patients were not eligible due to receiving less than 4 cycles chemotherapy (68%) or due to PD (75%), or both. 91 (38%) patients completed 6 cycles of chemotherapy. Having a low baseline Hb &lt;100g/dl was the only baseline characteristic associated with receiving less than 6 cycles chemotherapy (p=0.002). 33% of patients who completed less than 6 cycles chemotherapy had a Hb &lt;100g/dl, compared to 10% of the patients who completed chemotherapy (p=0.002). Any dose delays was associated with a lower likelihood of being eligible to receive avelumab (32% and 18% dose delays in avelumab eligible vs ineligible cohorts, respectively (p&lt;0.001). Patients with any dose delays had more frequently received carboplatin (65% vs 39%, p=0.012) and had visceral metastases including liver metastases (63% vs 39%, p=0.014), compared to those without dose delays. Conclusions: Specific baseline factors predispose to an inability to deliver 6 cycles of chemotherapy without complications or progression. These patients are less likely to receive maintenance avelumab. These data help the optimise number of cycles offered to patients in mUC.
Optimal timing of delayed cytoreductive nephrectomy in metastatic renal cell carcinoma during the immunotherapy era.
Authors: Insija Ilyas Selene, Feitong Lei, Bin Huang, Amina Dhahri, Patrick Heckman, Roshmita Bardhan, Jemin Jose, Zin Myint
Journal: Journal of Clinical Oncology (2024)

403 Background: The CARMENA study found no survival benefit from cytoreductive nephrectomy (CN) in poor-risk metastatic renal cell cancer (mRCC) patients treated with first line Sunitinib. Although retrospective studies have reported survival benefits with CN following immunotherapy (IO)-based therapy, the timing remains unclear. We aimed to investigate the ideal timing of CN following IO using the National Cancer Database. Methods: 783 patients with de novo mRCC were diagnosed between 2016 and 2020 who received upfront systemic therapy and underwent CN, 343 patients met our criteria. Patients were categorized into four groups based on the timing of nephrectomy: CN ≤3 months (Group A), 4 to 6 months (Group B), 7 to 9 months (Group C) and ≥ 10 months (Group D) following the initiation of IO-based therapy. Descriptive analysis was performed to examine the demographic and clinical characteristics. Follow up time was measured from the date of surgery to reduce bias. Kaplan-Meier plots were used to analyze survival curves, and a multivariable cox regression analysis was performed to explore associations between timing and survival. Results: 343 patients who received upfront IO -based therapy were divided into four groups: 104 (30%) in A, 114 (33%) in B, 74 (22%) in C and 51 (15%) in D. 71%were male, white (90%), age 40 – 64 (62%), comorbidity index 0 (70%), clear cell histology (69%), sarcomatoid (14%). 54% were treated in academia, 57% had bone metastasis, 50% had lung, 11% had liver, and 7% had brain metastases. 66% received only IO, and 34% received IO + TKI. No significant association between CN timing and survival observed in multivariate cox regression model. (HR 0.87, 95% CI: 0.5- 1.7, p = 0.84). Compared to group A, the HR were 0.96 (95% CI, 0.73 to 1.27; p=0.78), 0.77 (95% CI, 0.53 to 1.13; p=0.19), and 0.66 (95% CI, 0.37 to 1.20; p=0.17) respectively for groups B, C and D. Conclusions: Our study did not find significant survival improvement with an optimal timing of CN following IO-based therapy, while HRs were reduced after 6 months of delay, though insignificant. This could be due to the small sample size or other confounders.