tbuckley/cabot-search huggingface dataset:
Thromboembolic events associated with neoadjuvant chemotherapy for muscle invasive cancer of the bladder.
Authors: Muneeb Qureshi, Ahmed Rehan, Wai Kit Mok, Abdulazeez Salawu, Sabin Goktas Aydin, Jessica Tay, Rachel Hubbard, James W.F. Catto, Syed A. Hussain
Journal: Journal of Clinical Oncology (2024)

586 Background: Patients with muscle invasive bladder cancer who undergo platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy or radiotherapy are at high risk of venous and arterial thromboembolic events (TEE). TEE is associated with delay to radical cancer treatment, significant morbidity and even mortality. This study aimed to document the incidence and characteristics of TEE during NAC and prior to radical treatment. Methods: Retrospective data was collected on all patients in our centre who underwent NAC prior to radical treatment. TEE events were identified based on routine imaging to assess for response to NAC; or imaging based on clinical symptoms developed during (or within 28 days) of NAC but prior to radical treatment. Results: Data was collected on 148 patients between January 2015 and September 2023. Age range: 44 - 82 years, the majority (73.6%) of whom were male. All patients received platinum-based chemotherapy (median 4 cycles). A total of 31 patients (20.9%) developed 35 TEE, including 27 venous events (24 pulmonary emboli and 3 deep venous thromboses), and 8 arterial events (3 aortic thrombus, 4 limb ischaemia, 1 ischemic stroke). Four patients had a venous and arterial TEE. The majority of pulmonary venous TEE were subclinical. Conclusions: Our single-centre study demonstrates that the incidence of TEE during NAC prior to radical treatment for bladder cancer is high. Improved imaging techniques and routine scans post-NAC led to identification of subclinical TEE that require treatment as they are likely to become clinically significant. The high rate of TEE in this patient population is likely to benefit from prophylactic anticoagulation during NAC and should be investigated in future prospective clinical trials.
The immune characteristic analysis of BAP1 mutated clear cell renal cell carcinoma.
Authors: Zilin Wang, Jiayu Liang, Hao Zeng
Journal: Journal of Clinical Oncology (2024)

466 Background: Commonly mutated genes in clear cell renal cell carcinoma include VHL, PBRM1, and BAP1. Although the detection rate of BAP1 mutations in RCC is not high, from an evolutionary perspective. BAP1 mutated renal cell carcinoma tends to have clinical features of higher malignancy, faster disease progression, and poor efficacy of classic drug treatments. Therefore, this study uses our center and TCGA database to analyze the correlation between transcriptome, immune cell infiltration, immune checkpoint expression and other characteristics and the efficacy of immune checkpoint inhibitor-based treatment in patients with BAP1 mutated renal cell carcinoma. Methods: 1. The correlation between the expression of immune-related factors CD4, CD8 and immune checkpoints PD-L1, LAG3 and BAP1 RNA and the expression difference between wild and mutant groups were analyzed through the TCGA database. 2. Collect BAP1 mutant and wild-type patients retrospectively, and verify the expression of CD4, CD8, PD-L1 and LAG3 by immunohistochemistry. 3. The enrichment analysis of the signaling pathway was carried out after the intersection of TCGA and the differential genes of the center. 4. To analyze the clinical curative effect difference between BAP1 wild-type and mutant advanced RCC patients receiving target immunotherapy. Results: The TCGA data confirmed that there was no difference in the expression of PD-L1 RNA between the two groups (P=0.5); while there was a significant difference in the expression of LAG-3 RNA, which was higher in the BAP1 mutant type than in the wild type (P=0.023); 24 cases of BAP1 wild-type ccRCC specimens available in the gene detection database of our center were selected, and the results of immunohistochemistry suggested that there were differences in the expression of LAG3 (p=0.009) between the BAP1 wild-type and mutant types, while PD There was no significant difference in the expression of -L1 (p=0.157). The transcriptome data enrichment analysis results of TCGA and our center database showed that BAP1 was closely related to cytokine signaling, cAMP signaling pathway and immune response signals in the tumor immune microenvironment. In terms of clinical efficacy, the PFS time of BAP1 wild-type RCC patients receiving ICI combined with TKI therapy was significantly longer than that of BAP1 mutant patients (median follow-up time: 23.93 months; median PFS: 24.63 vs. 11.73 months, HR: 0.304, 95%CI: 0.070-1.324, p=0.025). Conclusions: This study found that BAP1 and cytokines, cAMP pathway and immune inflammation-related pathways were significantly enriched at the transcriptome level. IHC results suggested that LAG3 was more highly expressed in patients with BAP1 mutation. Clinical treatment analysis found that PD-1 inhibitor-based immune combination therapy is not effective for patients with BAP1 mutations. In summary, LAG3 may be a potential therapeutic target in the future for patients with BAP1-mutated RCC.
Adverse effects and discontinuation of pembrolizumab in BCG refractory non-muscle invasive bladder cancer.
Authors: Borivoj Golijanin, Kamil Malshy, Vikas Bhatt, Galina Lagos, Ali Amin, Andre Luiz De Souza, Liang Cheng, Anthony E. Mega, Dragan Golijanin
Journal: Journal of Clinical Oncology (2024)

588 Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression despite adequate intravesical treatment with Bacillus Calmette-Guerin (BCG). Pembrolizumab was found to be effective in treating BCG-refractory NMIBC in the KEYNOTE-057 trial with a 41% complete response after 3 months and minimal adverse effects. As a result it was approved by the FDA on January, 2020, for the treatment of high risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors in patients ineligible for or unwilling to undergo cystectomy. This study reports a single institution’s experience using pembrolizumab in BCG refractory patients with high-risk NMIBC. Methods: Records of NMIBC patients who commenced treatment with pembrolizumab between January 2020 and January 2023 at a single institution were retrospectively reviewed. Demographic and clinicopathologic information was collected. Kaplan-Meier curves were generated to calculate progression-free survival (PFS), and treatment-specific survival (TSS). The combined positive score (CPS) of PD-L1 was assessed for each case treated by pembrolizumab. Results: Out of 250 patients with NMIBC who were screened for the study, 18 met the inclusion criteria. The median age was 74.1 years (IQR=67.8 – 81.4), male to female ratio of 3.5:1. The median follow-up time was 17.5 months (IQR= 8.1–22.5). A previous history of CIS was present in all patients as well as second-line chemotherapy for BCG refractory disease. At the start of pembrolizumab, stage distribution was as follows: 1 (5.6%) cTa, 6 (33.3%) had CIS, and 11 (61.1%) cT1. After an average of 8.9 cycles, 72.2% (13/18) stopped treatment. 27.8% (5/18) are still undergoing treatment, with an average of 12.6 cycles (SD=10.4). 1 out of the 13 patients who stopped treatment had a complete response. The remaining reasons for termination of treatment are Grade 2 or higher immune-related adverse events in 53.8% (7/13), progression in 30.8% (4/13), and recurrence in 7.7% (1/13). Four patients ultimately required radical cystectomy which revealed 1 pTa, 1 pTis, 1 pT1, and 1 pT4. Only 1 patient had CPS of PD-L1 &gt; 10. Conclusions: There were higher rates of toxicity from pembrolizumab for the treatment of BCG-refractory NMIBC than expected. More research is needed to better define the patients who are likely to benefit from this treatment. Pembrolizumab for BCG refractory NMIBC can have high rates of Grade 2 or higher adverse events leading to early withdrawal from treatment. Early discussion about radical surgery remains an important part of the treatment guidelines for BCG refractory NMIBC.
Safety outcomes in patients with metastatic castration-resistant prostate cancer treated with radium-223 following external beam radiation therapy: REASSURE US subset.
Authors: A. Oliver Sartor, Peter Conti, Mary-Ellen Taplin, Daniel Song, Saby George, Jeffrey John Tomaszewski, John Sylvester, Constantine Anastasios Mantz, Robert Given, Robert K. Brookland, Jeffrey Meltzer, Matthew J. Korn, Jacqueline Parkin, Svetlana Babajanyan, Celestia S. Higano
Journal: Journal of Clinical Oncology (2024)

106 Background: In the Phase 3 ALSYMPCA trial, radium-223 (Ra-223) demonstrated an overall survival (OS) benefit and a favorable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC). REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of Ra-223 use in patients with mCRPC with bone metastases within routine clinical settings. Utilizing data from the second planned interim analysis, we evaluated safety outcomes in patients with mCRPC treated with Ra-223 following external beam radiation therapy (EBRT) in the US. Methods: In this descriptive analysis (data cutoff 3-20-2019), we included patients who received EBRT to bone prior to Ra-223 (≤2 years prior to Ra-223 first dose); results are presented relative to the overall US subset of patients enrolled into REASSURE. The focus of this abstract is on incidence of hematological toxicities, bone fractures, and second primary malignancies (SPM). Results: Of N=498 patients in the US subset, 118 patients received prior EBRT to bone. Median duration of observation was 11.7 months among patients who received EBRT and 11.9 months for the overall US subset. Any-grade drug-related hematological treatment-emergent adverse events (TEAEs) occurred in 8% (10/118) and 9% (47/498) of patients who received EBRT and the overall subset, respectively (Table). Grade ≥3 drug-related hematological TEAEs occurred in 5% (6/118) and 6% (32/498) of patients who received EBRT and the overall subset, respectively. Bone fractures occurred in 7% (8/118) and 4% (19/498) of patients who received EBRT and the overall subset, respectively. Six SPMs occurred in 5/118 patients who received EBRT (4%), and 11 SPMs occurred in 10/498 patients in the overall subset (2%). Results of bone fracture events by bone health agent use will be included in the full presentation. Conclusions: In this descriptive analysis of real-world data, patients who received EBRT prior to Ra-223 did not demonstrate an increased incidence of hematological toxicities relative to the overall US subset. Although percent of SPMs and bone fractures seems higher among patients treated with EBRT relative to the overall US subset, the real-world incidence of these events remains low. [Table: see text]
Rate of hospitalization and length of hospital stay during and post docetaxel for darolutamide in metastatic hormone-sensitive prostate cancer using ARASENS.
Authors: Alicia K. Morgans, Martin Boegemann, Noman Paracha, Jamie Grossman, Fernando Rodriguez Santamaria, Emma Tyas, Jane Candish, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

228 Background: ARASENS was a randomized, double-blind, Phase III trial of darolutamide (daro) + docetaxel + androgen deprivation therapy (ADT) vs. placebo (pbo) + docetaxel + ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC). We sought to compare rates of hospitalizations and length of hospital stay (LoS) per patient due to any reason, and due to adverse events (AE) during or post docetaxel using data from ARASENS. Methods: We used mixed effects negative binomial regression to estimate time-varying rate of hospitalization and LoS by patient. Patients with records that began on the same start date were considered duplicates and were condensed into one visit, using the latest end date. Patients with multiple records with overlapping time periods were combined into one visit. A constant hospitalization rate assumption was considered inappropriate since docetaxel is administered for 6-cycles (~4.14 months). Hospitalizations that began within and after first 4 months of treatment were grouped together. Conversely, LoS was assumed to be time invariant. Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalization both due to any reason and to AE (Table 1). Daro was associated with a numerical reduction in rate of hospitalization (per year) due to any reason during docetaxel (0.75 days [95% CI: 0.61, 0.88]) vs. pbo (0.91 days [95% CI: 0.75, 1.07]) and after docetaxel (0.31 days [95% CI: 0.26, 0.37]) vs. pbo (0.38 days [95% CI: 0.31, 0.45]). A similar trend was observed for hospitalizations due to AE. Daro was associated with a marginally longer LoS per hospitalization compared with pbo (+1.90 days). Similar results were seen for LoS due to AE (+1.67 days). Conclusions: Daro was associated with a numerically lower rate of hospitalization, but marginally longer LoS compared to pbo. A lower rate of hospitalization was observed post docetaxel as opposed to during docetaxel. Clinical trial information: NCT102799602 . [Table: see text]
Comparative effectiveness of ChatGPT 4.0 and medical oncologists in telemedicine-based management of metastatic prostate carcinoma (mPC).
Authors: Emre Dal, Ayana Srivastava, Beverly Chigarira, Chadi Hage Chehade, Arshit Narang, Georges Gebrael, Richard Ji, Neeraj Agarwal, Umang Swami, Haoran Li
Journal: Journal of Clinical Oncology (2024)

226 Background: The advent of telemedicine, accentuated during the COVID-19 pandemic, offers a prospective modality, especially when synergized with artificial intelligence (AI) tools such as ChatGPT 4.0. In this investigation, we sought to investigate the proficiency of ChatGPT vs. medical oncologists in the telemedicine-centric management of mPC. Methods: This IRB-approved retrospective study compared the competencies of ChatGPT and oncologists in conducting telemedicine consultations for patients with mPC. Out of 975 patients screened between April 1, 2022, and March 30, 2023, 102 met the inclusion criteria of having a diagnosis of mPC, attending at least one telemedicine consultation during the specified period, and having documentation available for two consecutive visits to enable the analysis of treatment decisions and outcomes. ChatGPT was asked to pre-chart and determine if a face-to-face consultation is needed. Its clinical competence was assessed using miniCEX, and medical decision-making (MDM). The Cohen's kappa test was used to measure the level of agreement between ChatGPT and oncologists in treatment decisions, and the Mann-Whitney U test was used to compare miniCEX and MDM. Results: The majority of patients were White (97.06%), with a median age of 75 years (range:53 to 99). Nearly all patients were diagnosed with adenocarcinoma (96.08%), with a median Gleason score of 7 (range: 6 to 10). The prevalent metastatic sites were bone (47.4%) and lymph nodes (44.16%). 26.88% had an ECOG score of 0, 54.84% had a score of 1, and 18.28% had a score greater than 1. Common coexisting conditions included diabetes mellitus (11.11%), hypertension (29.82%), hyperlipidemia (24.56%), and depression (7.6%). The primary outcome measured the concordance between ChatGPT and oncologists on whether to continue or cease the current treatment There was a statistical significance in sensitivity and specificity between clinicians and ChatGPT (Chi-squared=5.1, p=0.02). Cohen's Kappa showed a moderate concordance (Kappa = 0.43, p&lt;0.001). There was no difference in the number of diagnoses made by the two parties (p=0.13 and 0.06, respectively). ChatGPT's median miniCEX score was 8 (SD=0.59), and its median MDM length was 41 words (SD=6.06). The average time saved by ChatGPT in pre-charting was 41 minutes (SD=6). Conclusions: ChatGPT showed moderate concordance with oncologists for the management of mPC in telemedicine. Subsequent investigations are needed to explore its potential in healthcare.
A study to evaluate patient benefit/risk preferences for treatment of metastatic prostate cancer (mPC) in Hong Kong: A discrete choice experiment.
Authors: Chi-Fai Ng, Yeuk-Lam Hong, Kenneth C.W. Wong, Wing-Yan Kong, Chi-ho Leung, Pui-Tak Lai
Journal: Journal of Clinical Oncology (2024)

104 Background: The patient’s preference for treatment is dynamic across different cultures and at various stages of cancer. Yet little is known regarding their priorities in making treatment decisions. The study's primary objective is to examine the preference weightings in terms of risk/ benefit attributes of therapy in metastatic prostate cancer (mPC) patients in both the hormone-sensitive (mHSPC) and castration-resistant (mCRPC) settings. Methods: This is a non-interventional cross-sectional survey study. A discrete choice experiment was used to assess their priorities on treatment options. 300 consecutive patients with mPC (200 mHSPC and 100 mCRPC) diagnosed within 5 years were recruited from the specialty clinics of our hospital from Feb 2023 to Jul 2023. A facilitated group interview session of 5 patients was conducted to evaluate the importance and relevance of potential attributes selected from the literature search. Five attributes were adopted, and each has 3 levels compromised between real-life rates and expectations of patients from the interview session. Patients were randomized into 2 blocks by recruitment sequence and chose 1 medication profile out of 2 throughout the 9 questions in each block of the questionnaire. A mixed logit model was used for data analysis. Results: Median age was 75 (IQR:71-81). One hundred and seventy (56.7%) had no income, and 245 (81.7%) claimed to take care of themselves. The mean maximum amount affordable for treatment was US$20,456 (SD:43,568), and 160 (53.3%) said they would not consider further treatment if the cost exceeded their affordability. Compared to intravenous formulation, oral medication once/day had a non-statistically significant favorable preference (0.06 p:0.272), and oral medication twice/day had a negative statistically significant preference (-0.20 p:0.040). The percentage of retained self-care ability (4.37 p&lt;0.001) and percentage of extension in life expectancy (2.83 p&lt;0.001) had a statistically significant favorable preference. In contrast, the chance of adverse effects leading to complicated medication treatment or hospitalization (-6.97, p&lt;0.001) and treatment cost (in HK$ million) (-3.14 p&lt;0.001) had a negative statistically significant preference. The mCPRC group was more sensitive to changes in treatment cost (-3.61 vs. -2.97), percentage of extension in life expectancy (3.47 vs. 2.55) and the chance of adverse effects (-7.55 vs -6.80) than the mHSPC group. Those who could afford treatment were more sensitive to the percentage of retained self-care ability (4.89 vs. 4.02) and the chance of adverse effects (-7.57 vs -6.70) than those who could not. Conclusions: The chance of adverse effects took the largest weighting in treatment decisions, followed by the percentage of retained self-care ability.
Barriers and facilitators to first-line (1L) treatment intensification (TI) in metastatic castration-sensitive prostate cancer (mCSPC): The IMPLEMENT study.
Authors: Stacy Loeb, Neeraj Agarwal, Nader N. El-Chaar, Laura de Ruiter, Janet Kim, Jessica Mack, Christopher S Bland, Sarah Rich-Zendel, Jin Su Joo, Judith Dyson
Journal: Journal of Clinical Oncology (2024)

224 Background: Despite evidence of benefits and guideline recommendations for first-line treatment intensification (ie, androgen-deprivation therapy with chemotherapy, novel hormonal therapies, or both) in mCSPC, it is underutilized. We examined barriers and facilitators that US urologists and oncologists face with treatment intensification for mCSPC and identified behavior change techniques to address these through an implementation science approach. Methods: We conducted 36 double-blind, semi-structured, virtual interviews with practicing US urologists and oncologists who manage mCSPC using an interview guide based on the theoretical domains framework. Saturation was met when no new themes emerged. Physician statements were coded into 11 domains and themes to identify barriers and facilitators. To confirm codebook reliability, 10% of transcripts were double coded independently (k=0.77). Key domains and the associated barriers and facilitators were analyzed for frequency, perceived potential to impact behavior, and presence of disagreement. Top domains were cross-referenced with a taxonomy of validated behavior change techniques. Results: 36 interviewed physicians (20 low intensifiers[≤50% of patients get treatment intensification]; 16 high intensifiers [&gt;50% of patients get treatment intensification]), 14 (39%) were from academic centers. Five impactful domains and the associated barriers and facilitators were identified along with behavior change techniques to overcome them (Table). Conclusions: Underutilization of treatment intensification in US is multifactorial. Poor knowledge, habit, anticipated regret, costs, and reserving treatment intensification for later use were prominent barriers. These can be addressed through behavior change techniques to improve mCSPC care. [Table: see text]