tbuckley/cabot-search huggingface dataset:
Unraveling the dietary impact: Associations between ultra-processed foods and prostate cancer in a two-decade study.
Authors: Elise Katsnelson, Derek Isrow, Crystal Taswell, Benjamin James Rich, William Jin
Journal: Journal of Clinical Oncology (2025)

135 Background: Prostate cancer is a leading cause of cancer-related morbidity in men, and emerging research suggests that dietary patterns, particularly involving processed foods, may play a role in its development. This study aims to explore the association between NOVA-classified food consumption and prostate cancer. Methods: Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) was analyzed. A sensitivity analysis was performed. Men aged 20 and older with a diagnosis of prostate cancer (n=731) and without any cancer (n=20,972) were contrasted. The mean daily caloric intake from various NOVA food categories was analyzed using independent t-tests, then corrected using Benjamini-Hochberg (p&lt;0.05). Subgroup analyses were conducted via Welch two-sample t-tests for age and BMI, while Chi-Square tests were used for race, education level, birth country, and military status. Results: Men with prostate cancer had a higher intake of the following NOVA group 4 ultra-processed foods: “cakes, cookies pies, pancakes” (p=0.031), “ice cream, ice pops, and frozen yogurts” (p&lt;0.001), “sugared breakfast cereals” (p&lt;0.001). They also had a higher intake of certain group 1 unprocessed or minimally processed foods: “roots and tubers” (p=0.019) and “fruits including juices” (p&lt;0.001). Men without cancer had a higher intake of certain NOVA 1 unprocessed or minimally processed foods: meat/poultry (p&lt;0.001), grains (p=0.002), pasta (p=0.025). They also ate more oils (NOVA 2 processed culinary ingredients, p=0.003), NOVA 3 processed foods like cheese (p&lt;0.001), and many NOVA 4 foods like salty snacks (p=0.002), pizza (p&lt;0.001), sandwiches/hamburgers (p=0.030), potato products (p&lt;0.001), sauces/dressing/gravies (p=0.001), soft drinks (p&lt;0.001), and sweetened beverages (p&lt;0.001). Subgroups analyses revealed a greater association with prostate cancer for people with older age, Non-Hispanic Black and Non-Hispanic White races, being US-born, having a higher education, and serving in the military. Conclusions: To our knowledge, this is the largest study evaluating dietary behavior in the context of food processing and prostate cancer prevalence. We identified a high risk dietary pattern associated with industrially processed, calorically dense, and high glycemic index foods; conversely, a low risk dietary pattern was associated with minimally processed Mediterranean diets and, interestingly, highly processed Western diets.
Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic papillary renal cell carcinoma: A GUARDIANS project.
Authors: Thomas Hilser, Can Aydogdu, Stefanie Zschaebitz, Emily Rinderknecht, Angelika Mattigk, Anna-Lisa Volk, Philipp Ivanyi, Jonas Wiegmann, Christopher Darr, Subhajit Mandal, Katrin Schlack, Daniel Seidl, Analena Handke, Melanie Klee, Tim Nestler, Marc Rehlinghaus, Sameh Hijazi, Axel Heidenreich, Viktor Grünwald, Pia Paffenholz
Journal: Journal of Clinical Oncology (2025)

496 Background: Papillary (pRCC) renal cell carcinoma is a rare cancer. We evaluated real-world treatment outcomes of 1st line treatment in these cohorts in Germany. Methods: Data were collected retrospectively from 13 GU cancer centres in Germany. Patients (pts) with advanced or metastatic pRCC were eligible. Adverse events (AEs) were reported according to CTCAE 5.0. ORR was accessed according to local standard. Progression Free Survival (PFS) were calculated from start of treatment to progression or death. Descriptive statistics and KM-plots were utilized, where appropriate. Results: 131 suitable pts (82% male) with median age of 63 years (range 22-86) were included. ECOG 0-1 was 70%, nephrectomy was performed in 78%. IMDC scores were: 0 in 18%, ≥ 1 in 53%, missing in 29%. The most common sites of metastasis were lymphatic (66%) and pulmonary (41%) metastases. 52% patients received first-line IO-combinations (IO-IO: 18%, TKI-IO: 34%) and 40% patients TKI-monotherapy, predominantly sunitinib. AEs (all grades) with IO‐based or TKI mono therapy, were reported in 86% and 74%, CTCAE grade ≥ 3 in 46% and 22%, dose modifications were required in 35% and 26.0%. ORR and survival outcomes with median follow-up of 19 months (IQR 9-35) are described in the table. Conclusions: TKI-based therapy are frequently applied in pRCC. Our data support the use of IO+ TKI as a first-line standard for patients with pRCC. Major limitations were the retrospective data capture and short follow-up of our study. Additional analyses to tailor treatment strategies in patients with metastatic pRCC is warranted. ORR and survival outcomes of study population. Parameter All therapiesN=131 IO-ION=23 IO-TKIN=45 TKI monoN=51 OtherN=12 ORR (CR+PR) 34% 35 % 40 % 31 % 8% SD 29% 17 % 33 % 29 % 17% PD 23% 35 % 13 % 29 % 17% unknown 14% 13% 13 % 10 % 58 % mOS, months,95%-CI 32 .1 (24.4-39.9) 15.6(7.5-23.7) Not reached 27.6(19.7-35.7) 32.1(21.15-42.7) mPFS, months,95%-CI 8.5(6.5-10.4) 4.9(0.5-9.4) 9.2(3.5-15.0) 9.0(6.9-11.1) 8.5(0.0-22.8)
Checkpoint blockade as neoadjuvant strategy: A single-arm meta-analysis of dual PD-1/PD-L1 and CTLA-4 inhibition in urothelial cancer.
Authors: Gabriela Gazzoni, Isadora Mamede, Guilherme Melchior Maia Lopes, Carlos Stecca
Journal: Journal of Clinical Oncology (2025)

783 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard treatment for muscle-invasive urothelial cancer (MIUC). In patients who are ineligible or deny chemotherapy, upfront surgery is typically preferred. Immune checkpoint inhibitors, such as anti-PD-1/PD-L1 and anti-CTLA-4 antibodies, have emerged as potential neoadjuvant alternatives for these patients. This single-arm meta-analysis evaluates the efficacy and safety of combining anti-PD-1/PD-L1 with anti-CTLA-4 in MIUC. Methods: A systematic review of PubMed, Cochrane, ClinicalTrials.gov, and EMBASE identified clinical trials assessing neoadjuvant anti-PD-1/PD-L1 plus anti-CTLA-4 therapy in resectable, non-metastatic high-risk or muscle-invasive urothelial cancer. Outcomes included pathological complete response (pCR), pathological downstaging (&lt;ypT2N0), recurrence-free survival (RFS), mortality, progressive disease (PD), and treatment-related adverse events (TRAEs). Pooled proportions and 95% confidence intervals (CI) were calculated using a random-effects model. Heterogeneity was assessed using I² statistics. Results: 137 patients were included from 4 clinical trials, encompassing 6 cohorts. Two cohorts received Durvalumab plus Tremelimumab (D+T), and four cohorts received Nivolumab plus Ipilimumab (N+I). Of these, 73.7% were cisplatin-ineligible, and 15.3% had upper tract urothelial carcinoma (UTUC). The overall pooled pCR rate was 35% (CI: 27–44%, I² = 11%), with no significant subgroup difference between in muscle-invasive bladder cancer (MIBC)-only studies compared to studies that included patients with UTUC (p-interaction = 0.33). The downstaging rate was 47% (CI: 36–58%, I² = 41%). One-year RFS was 81% (CI: 64–92%, I² = 44%), while PD occurred in 19% of patients (CI: 9–36%, I² = 44%). The mortality rate was 16% (CI: 10–26%, I² = 11%). Grade ≥3 TRAEs were reported in 29% of patients (CI: 18–44%, I² = 61%). Additionally, TRAEs grade ≥ 3 were numerically less common in the D+T group (22%, 95% CI: 12–35%, I² = 0%) compared to the N+I group (33%, 95% CI: 16–56%, I² = 68%), although this difference was not statistically significant (p-interaction = 0.33). Conclusions: Neoadjuvant anti-PD-1/PD-L1 combined with anti-CTLA-4 therapy demonstrates promising pCR, pathological downstaging rates and 1-year RFS in patients with MIUC. Despite Grade ≥3 TRAEs occurring in nearly one-third of patients, the majority were manageable. While these results highlight the potential of this combination for patients who are ineligible or deny NAC, randomized controlled trials are needed to refine patient selection and validate these findings.
Extensive necrosis as a prognostic indicator in metastatic RCC patients undergoing deferred cytoreductive nephrectomy after immunologic checkpoint inhibitor treatment.
Authors: Paulo Siqueira do Amaral, Katy Beckermann, Gabriel Berlingieri Polho, Kelvin A. Moses, Jennifer B. Gordetsky, Sam S. Chang, Amy Luckenbaugh, Kristin Kathleen Ancell, Morgan Lambrecht, Kerry Roe Schaffer, Elizabeth Kaiser, Daniel D. Joyce, Brian I. Rini
Journal: Journal of Clinical Oncology (2025)

468 Background: The role of cytoreductive nephrectomy (CN) in patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitor (ICI)-based therapies remains under debate. Retrospective cohorts have reported shrinkage in the primary tumors and no residual tumor in primary specimens (pT0), however, the clinical relevance has not been explored. Assessing the pathological outcomes of CN following ICI may provide valuable information. Methods: This is a single-center retrospective analysis of metastatic/locally advanced RCC who underwent CN between May 2017 and September 2024 after ICI-based treatment. Demographic and clinicopathological were collected. The primary endpoint was the rate of patients with extensive necrosis (EN), defined as ≥ 95% of necrosis in the resected primary tumor. Progression-free survival (PFS) was calculated at two timepoints: from the date of ICI initiation (PFS1) and from the date of surgery (PFS2) until event (progression or death) or last follow-up, using the Kaplan-Meier method. Differences between groups (pts with EN in resected kidney vs not) were assed with the log-rank test and hazard ratios were calculated with Cox regression model. Correlations were made with the Fisher test between presence of EN and other categorical variables. Results: Twenty-five pts were identified, with a median age of 62 years (range, 40–83), and median follow-up of 31.5 months after initiating ICI. 84% were metastatic, with 84% receiving first-line ICI-based combinations (5 Ipi/Nivo;16 ICI-TKI), while the remaining 16% had second-line nivolumab. The median ICI exposure before surgery was 10.5 m (range, 2.1–42.7) in the entire cohort, 12.7 m (range, 2.1–28.8) in the EN subgroup and 10.3 m (range, 3.1–42.7) in the non-EN. Best overall radiological response prior to surgery included 4% CR, 68% PR and 28% SD. Pathological assessment revealed 76% clear cell, 16% unclassified and 8% papillary RCC and 16% had a sarcomatoid component. 40% of pts had ≥ 95 % necrosis, with half of these pts (20%) achieving pT0. The median PFS1 was numerically longer in pts with EN, not reached (NR) vs 27.7 m, (HR 0.33; 95% CI, 0.09 -1.26; p = 0.09). The median follow-up after surgery was 10 months, and the median PFS2 was longer in the EN subgroup, NR vs 9.7 m, (HR 0.2; 95% CI, 0.04–0.96; p &lt; 0.05). No significant correlations were found between EN and Fuhrman grade, presence of sarcomatoid differentiation, treatment duration, or radiological response. Conclusions: ICI-based regimens showed activity in primary RCC tumors, leading to EN (≥ 95% of necrosis) in a subset of pts. Those who achieved EN appear to have reduced risk of disease progression.
Feasibility of surgical orchiectomy in prostate cancer patients on long term luteinizing hormone-releasing hormone (LHRH) agonist therapy.
Authors: Alon Ya'aqov Lazarovich, Walter Michael Stadler, Scott Eggener, Ashley Page, Brian Heiss, Daniel M. Geynisman, Natalie Marie Reizine
Journal: Journal of Clinical Oncology (2025)

265 Background: Androgen deprivation, achieved through surgical or medical castration, is central to metastatic prostate cancer (PCa) treatment. Life-long castration is thought to be critical to the management of patients with metastatic disease. Orchiectomy offers an alternative, more convenient, and cheaper alternative for permanent castration, but is under-utilized, in part due to patient reluctance. We hypothesized that patients on long term medical castration therapy would be willing to accept surgical castration as an alternative to repeated LHRH agonist injections. Methods: Men ≥18 years with metastatic PCa, on LHRH agonists for ≥1 year and ≤2 prior systemic therapies, were eligible. Participants first provided consent for an educational session on orchiectomy, followed by the collection of demographic and disease characteristics. Those providing further consent completed the PROMIS sexual function and satisfaction measures v2.0 and the Hopwood body image surveys, with a urology consult offered. At 6 months, patients completed the same surveys, and those undergoing orchiectomy also completed the decision regret scale. 100 patients agreeing to the educational session were required to provide a 10% confidence interval on an estimated 30-50% of patients undergoing an orchiectomy. Results: Of the 130 patients approached, 101 signed the first consent form (education), 58 signed the second (surveys), and 27 agreed to meet with the urology team. Patients agreeing to the educational session had a median age of 71 years (IQR 65-75), 46% were Black and 48% White, 48% completed college or an advanced degree, 36% had annual income &gt; $80K, 58% were married and 64% received systemic therapy other than LHRH agonists. Fourteen patients underwent bilateral orchiectomy (one subcapsular). No association was found between orchiectomy and race, education, annual income, or marital status. While ~75% of all patients were dissatisfied with their sexual life, the vast majority had no body image concerns. Decision regret was low, with 13/14 patients satisfied with their choice of orchiectomy. Pathology revealed testicular atrophy in all cases. Conclusions: Only 11% of patients approached, and 14% of patients who participated in an educational session on orchiectomy proceeded with the procedure, suggesting limited feasibility for surgical castration in patients on long-term LHRH agonists. Testicular atrophy suggests that discontinuing medical castration may be an alternative cost-effective strategy to maintain castration in prostate cancer patients with metastatic disease. Clinical trial information: NCT04705038 .
Grade and volume progression and its association with the Decipher genomic classifier using patients enrolled in a prospective active surveillance protocol.
Authors: David J Lee, Tarek Ajami, Hui Yu, Nachiketh Soodana-Prakash, Joao Porto, Yuval Avda, Ankur Malpani, Dinno F Mendiola, Pedro F.S. Freitas, Archan Khandekar, Sanjaya Swain, Sandra M. Gaston, Brandon A. Mahal, Sanoj Punnen
Journal: Journal of Clinical Oncology (2025)

262 Background: The progression of prostate cancer through serial biopsies in patients on active surveillance is a multifaceted process, with grade and volume progression offering unique perspectives on disease advancement. The Decipher genomic classifier has been recognized as a valuable tool for predicting disease progression. This study examines the relationship between the Decipher score, and other GRID signatures and pathways, and grade and volume progression in prostate cancer patients, utilizing data collected prospectively from the Miami Active Surveillance Trial (MAST). Methods: We scrutinized 224 baseline samples from 124 unique patients participating in the MAST database. Progression was categorized into grade progression, volume progression, and no progression. For patients with multiple samples, the sample with the highest Decipher score was selected. We also evaluate the association between 11 prognostic signatures, including the Decipher score and an average genomic risk score combining the 11 signatures and 20 pathways available from the Decipher GRID. Results: Out of the baseline samples, 60 demonstrated grade progression, 51 volume progression, and 113 showed no progression. We found that the Decipher was not associated to our trial definition of progression, that combined grade and volume progression however we did find a statistically significant difference in Decipher scores from patients who experience grade progression (p=0.0005) as compared to volume progression (p=0.92) when comparing them with patients with no progression. A heat map evaluating prognostic signatures and pathways available on the Decipher grid found that the majority of prognostic signatures including the Decipher score and the average risk model were more associated with grade progression compared to volume or no progression. Conclusions: Our findings suggest that the Decipher score has a stronger correlation with grade progression than volume progression in prostate cancer patients. This highlights the potential of genomic classifiers like Decipher in enhancing our understanding of disease progression and in tailoring personalized treatment strategies. Further prospective studies are required to validate these findings. Clinical trial information: NCT02242773 .
Population-adjusted network meta-analyses (NMA) to evaluate the efficacy of treatment alternatives for metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Neal D. Shore, Alicia K. Morgans, Noman Paracha, Howard Thom, Edna Keeney, Philip Orishaba, David Phillippo, David Aceituno, Christopher J.D. Wallis, Martin Boegemann
Journal: Journal of Clinical Oncology (2025)

267 Background: Existing NMA in mHSPC compare treatments assuming homogeneity in treatment effect modifiers across study populations. However, evidence suggests that these effects vary in mHSPC. This study employs the recent methods of multilevel network meta-regression (ML-NMR) and network meta interpolation (NMI) to adjust for population differences and predict relative effect estimates for an ARASENS-like target population. Methods: We used a systematic literature review to identify studies for our NMA on overall survival (OS) in mHSPC. We applied ML-NMR to adjust for imbalances in treatment effect modifiers by integrating individual patient data (IPD) regression from the ARASENS trial across the covariate distributions of comparator studies. The IPD was reconstructed from Kaplan-Meier curves for aggregate data studies, incorporating covariates age, ECOG performance status, Gleason score, and disease volume. Utilizing the same set of variables, NMI was employed to analyze subgroup data from comparator studies using reported hazard ratios. Results: Twelve studies were identified for inclusion in our analyses. The ML-NMR demonstrated a significant benefit for the darolutamide (daro) triplet compared to enzalutamide + ADT, apalutamide + ADT, abiraterone + ADT, and the abiraterone triplet in the ARASENS-like population. However, in the NMI analysis, the daro triplet was significantly favored over abiraterone + ADT when compared to other commonly utilized alternatives (Table). A key strength of the ML-NMR over NMI is that it only requires baseline characteristics to be reported, rather than subgroups which were relatively poorly reported or not powered to detect statistically significant differences. The NMI method suffered due to incomplete subgroup data, with full data for effect modifiers available in 8/12 studies. Conclusions: Both ML-NMR and NMI analyses support triplet benefit with ADT + docetaxel + daro in improving OS for patients with mHSPC. The evidence from ML-NMR is particularly robust, benefiting from the better covariate data and the attendant decrease in uncertainty. Hazard ratio from ML-NMR and NMI. Daro + docetaxel + ADT versus ML-NMR: OSHR (95% CrI) NMI: OSHR (95% CrI) SNA+ADT 0.28 (0.17, 0.46)* 0.36 (0.23, 0.56)* ADT 0.43 (0.32, 0.60)* 0.51 (0.39, 0.65)* Docetaxel + ADT 0.57 (0.42, 0.77)* 0.68 (0.57, 0.80)* Enzalutamide + ADT 0.64 (0.44, 0.96)* 0.80 (0.57, 1.11) Apalutamide + ADT 0.68 (0.46, 1.00)** 0.75 (0.55, 1.03) Abiraterone + ADT 0.65 (0.45, 0.92)* 0.65 (0.52, 0.81)* Abiraterone acetate + docetaxel + ADT 0.66 (0.47, 0.93)* 0.89 (0.59, 1.34) CrI: credible interval, SNA: standard nonsteroidal antiandrogen, ADT: androgen deprivation therapy, *upper CrI did not cross the line of no effect, **rounding, upper CrI limit treated as below 1.00.
Rates of acute GI and GU toxicities with dose-escalated intensity modulated proton therapy (IMPT) for the treatment of node-positive prostate cancer.
Authors: Mehmet Murat Zerey, Omer Gal, Maria-Amelia M. Rodrigues, Adeel Kaiser, Alonso Gutierrez, Minesh P. Mehta, Jessica Wohl, Marcio Fagundes
Journal: Journal of Clinical Oncology (2025)

380 Background: Node-positive prostate cancer (PCa) poses a unique treatment challenge since bowel radiation tolerance often limits the delivery of doses of 60-70Gy or more required to control gross nodal disease. IMPT is a novel therapeutic option which utilizes beam stopping properties to achieve dose sparing of normal organs with the ability to dose escalate (DE) with potentially greater safety. However, the safety of DE-IMPT in node positive PCa has not been well described. Methods: Data were reviewed for consecutive patients treated between 9/2018-4/2024 with DE-IMPT for radiographically detected node-positive PCa. Treatment to the prostate and seminal vesicles consisted of 78Gy/39fractions; elective nodal regions received 46-48.6Gy in 1.8-2Gy/fraction, as part of whole pelvis treatment, while positive nodes were DE to a mean equivalent dose at 2 Gy/fraction (EQD2) dose of 66Gy (54-77.1Gy) in 1.8-2.5Gy/fraction, based on respecting predefined surrounding organs at risk (OAR) tolerances. Acute toxicities were assessed at baseline, weekly during treatment, and up to 3 months post-IMPT using Common Terminology Criteria for Adverse Events (CTCAE version 5). Results: The study included 58 patients presenting with a mean of 3 positive nodes (1-12). Median follow up was 19.5 months (3-67 months). Median age was 73 years (49-86). Majority were high-risk: Gleason 8-10 (67.2%), T3a-b (50%), PSA &gt; 20 (44.8%). Median prostate gland volume was 52cc (19-157). All pts received androgen deprivation therapy (ADT) with 97% completing at least 6 months; Androgen receptor pathway inhibitors were added in 26 pts (45%). Overall mean rectal V70, V60 and V50 were 6.7%, 11.2% and 16.5% while mean bladder V70, V60 and V50 were 12%, 17.3% and 24%, respectively. Mean small bowel dose to 1 cc volume D 1cc was 50.7Gy (45.6-57Gy), while mean Dmax point dose to 0.03cc was 52.2Gy (47.8-61.8). Worst acute Genitourinary (GU) toxicities Grade 0 and 1 were 1.7% and 12%, respectively. During treatment, 18/58 patients (31%) were started on Alpha-blockers for increased urinary frequency, retention and urgency, consistent with GU Grade 2 toxicity of which 7(39%) had discontinued medication by 3 months post-treatment. Before treatment, 32/58 (55.1%) were already on Alpha-blockers. There were no GU Grade ≥ 3 toxicities observed. Acute gastrointestinal (GI) Grade 0 and 1 were 43.1% and 53.5%, respectively. Grade 2 GI toxicities were observed in 2 (3.4%) patients consisting of diarrhea and proctitis. One patient (1.7%) developed transient Grade 3 enteritis. Conclusions: This contemporary series demonstrates that DE-IMPT is a safe treatment option for node-positive PCa with acceptable rates of acute grade 1 or 2 toxicity. Acute grade 3 toxicity was rare, occurring in only one patient in this cohort.