Gaurav Prakash

From the 8th International Cancer Congress

From the 8th International Cancer Congress

Background: [ ¹⁷⁷ Lu]Lu‐PSMA‐617 has been an approved treatment modality for metastatic castration‐resistant prostate cancer (mCRPC). Recent studies have shown PSMA upregulation following enzalutamide, which may enhance the outcomes with [ ¹⁷⁷ Lu]Lu‐PSMA‐617. This study aims to evaluate the efficacy and safety of short‐course enzalutamide priming with [ ¹⁷⁷ Lu]Lu‐PSMA‐617 in mCRPC patients. Methods: This investigator‐initiated, single‐arm phase 2 trial recruited men with mCRPC, having progressed on ≥one line of taxane and androgen‐receptor pathway inhibitors (ARPIs), and fit for [ ¹⁷⁷ Lu]Lu‐PSMA‐617. Enzalutamide (160 mg/day) was administered orally for 7 days before and after [ ¹⁷⁷ Lu]Lu‐PSMA‐617 (7.4 GBq/cycle, up to 6 cycles, at 6–8 week intervals). The primary end‐point was proportion of patients achieving ≥ 50% decline in prostate‐specific antigen (PSA50‐response rate, PSA50‐RR). A sample size of 20 patients was calculated using Simon's two‐stage design with at least 12/20 PSA50‐responses required for rejection of null hypothesis. Secondary end‐points included objective radiographic response rate (ORR), PSA progression‐free survival (PSA‐PFS), radiographic PFS (rPFS), overall survival (OS), and adverse events (AEs). Results: Between May 2023 and January 2025, 20 mCRPC patients (median age 67 years) were enrolled. The PSA50‐RR was 40% (8/20, 95% CI: 19–64), thus the null hypothesis was not rejected. The ORR was 25% (5/20, 95% CI: 10–49). Over a median follow‐up of 24 months, median PSA‐PFS, rPFS, and OS were 4.0 months (95% CI: 3.0–7.5), 4.0 months (95% CI: 4.0–7.5), and 12.6 months (95% CI: 6.2–17.0), respectively. Grade 3 AEs were observed in four patients (20%, 95% CI: 6–44). Conclusion: The addition of short‐course enzalutamide to [ ¹⁷⁷ Lu]Lu‐PSMA‐617 did not meaningfully improve treatment outcomes of taxane and ARPI‐exposed mCRPC patients in this trial. Trial Registration: Clinical Trials Registry‐India, CTRI/2023/05/053301. Registered 31 May 2023.

Accurate identification and segmentation of abdominal lymph nodes on computed tomography (CT) is crucial for cancer staging and treatment planning but remains a challenging and time-consuming radiologic task. We developed and validated ConLymphNet, a deep learning-based approach for automated abdominal lymph node segmentation using vertebral landmarks as anatomic reference points to standardize the region of interest. We implemented a novel preprocessing pipeline incorporating vertebral landmark-based region selection followed by a 3D nnUNet segmentation model. The model was trained on 481 contrast-enhanced CT scans from patients with gallbladder cancer (GBC) and validated on external data sets including GBC (n = 54), public lymph node (n = 81), and multicancer data sets (n = 606). Performance was compared with three radiologists of varying experience levels. Interobserver agreement among radiologists and the incremental value of artificial intelligence (AI)-assisted reading were also assessed. To support reproducibility and future research, we also contribute 45 expert-verified lymph node segmentations for cases from public multicancer data sets. ConLymphNet achieved mean Dice coefficients of 0.696 ± 0.179, 0.631 ± 0.187, and 0.639 ± 0.176 and low false-positive rates of 0.78 ± 0.35, 0.81 ± 0.33, 0.93 ± 0.47/volume on internal cross-validation, external GBC, and public lymph node data sets, respectively. Performance varied by lymph node location (P = .0080) and size (P = .0444), with larger nodes yielding better results. The model's detection rate (89.6%) was comparable with experienced residents (89.2%) but with reduced processing time (28.7 ± 12.4s v 165.3 ± 47.8 s). AI assistance improved radiologists' performance significantly, particularly for less experienced readers (detection rate +20.2%, segmentation accuracy +13.0%, P < .001), while reducing false positives by 33.3%. ConLymphNet demonstrates reasonable performance across diverse cancer types and imaging protocols, offering segmentation accuracy comparable with radiologists with substantially faster processing times.

Venetoclax is a first-in-class, orally bioavailable, and highly selective BCL-2 inhibitor. It has transformed the therapeutic landscape of hematologic malignancies by targeting the anti-apoptotic pathway in malignant cells. Its rational development followed the limitations of earlier BCL-2 inhibitors, such as navitoclax, which showed off-target BCL-XL inhibition and caused dose-limiting thrombocytopenia. Venetoclax demonstrates predictable pharmacokinetics, favourable tolerability, and efficacy across lymphoid and myeloid cancers. In chronic lymphocytic leukaemia (CLL), venetoclax-based regimens—particularly venetoclax-rituximab and venetoclax-obinutuzumab—have produced deep molecular remissions, high rates of undetectable minimal residual disease, and durable progression-free survival in both relapsed and frontline settings. Combination strategies of venetoclax with BTK inhibitors have enabled time-limited, chemotherapy‑free, and all oral treatment options Repurposing venetoclax for acute myeloid leukaemia (AML) has been a major therapeutic advancement. The VIALE‑A and VIALE‑C trials established venetoclax with hypomethylating agents or low‑dose cytarabine as the standard of care for older or unfit AML patients, with significant improvements in remission rates and overall survival. Emerging evidence supports its use in younger AML patients, with comparable or superior efficacy to intensive chemotherapy and markedly reduced early mortality. Dose-modification strategies, including low-dose venetoclax with azole prophylaxis or shortened treatment duration, offer practical solutions to reduce toxicity in real-world settings. Beyond CLL and AML, venetoclax has demonstrated clinically meaningful activity in multiple myeloma with t(11;14), mantle cell lymphoma, lymphoplasmacytic lymphoma, T‑ALL, and select high‑risk lymphomas. Its expanding role across hematologic malignancies reflects a strong mechanistic rationale, synergistic potential with partner drugs, and a favourable therapeutic index.

Venetoclax is a first-in-class, orally bioavailable, and highly selective BCL-2 inhibitor. It has transformed the therapeutic landscape of hematologic malignancies by targeting the anti-apoptotic pathway in malignant cells. Its rational development followed the limitations of earlier BCL-2 inhibitors, such as navitoclax, which showed off-target BCL-XL inhibition and caused dose-limiting thrombocytopenia. Venetoclax demonstrates predictable pharmacokinetics, favourable tolerability, and efficacy across lymphoid and myeloid cancers. In chronic lymphocytic leukaemia (CLL), venetoclax-based regimens—particularly venetoclax-rituximab and venetoclax-obinutuzumab—have produced deep molecular remissions, high rates of undetectable minimal residual disease, and durable progression-free survival in both relapsed and frontline settings. Combination strategies of venetoclax with BTK inhibitors have enabled time-limited, chemotherapy‑free, and all oral treatment options Repurposing venetoclax for acute myeloid leukaemia (AML) has been a major therapeutic advancement. The VIALE‑A and VIALE‑C trials established venetoclax with hypomethylating agents or low‑dose cytarabine as the standard of care for older or unfit AML patients, with significant improvements in remission rates and overall survival. Emerging evidence supports its use in younger AML patients, with comparable or superior efficacy to intensive chemotherapy and markedly reduced early mortality. Dose-modification strategies, including low-dose venetoclax with azole prophylaxis or shortened treatment duration, offer practical solutions to reduce toxicity in real-world settings. Beyond CLL and AML, venetoclax has demonstrated clinically meaningful activity in multiple myeloma with t(11;14), mantle cell lymphoma, lymphoplasmacytic lymphoma, T‑ALL, and select high‑risk lymphomas. Its expanding role across hematologic malignancies reflects a strong mechanistic rationale, synergistic potential with partner drugs, and a favourable therapeutic index.