INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

Background/Aims: The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods: The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Humans ; Fibrosarcoma/surgery* ; Sarcoma ; Temporal Bone ; Soft Tissue Neoplasms/surgery*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins