Kok Hoe Chan

Bladder preservation remains a highly desirable therapeutic goal in urothelial carcinoma, particularly when durable survival can be achieved. Radical cystectomy is the standard treatment for muscle-invasive disease; however, it results in irreversible bladder loss and significant morbidity. Among patients with locally advanced or metastatic urothelial carcinoma, recurrence rates after standard therapy remain high. Consolidation therapy with enfortumab vedotin and pembrolizumab following cisplatin-based induction chemotherapy has demonstrated promising efficacy, with substantial complete response rates and improved bladder preservation. This single-center retrospective analysis evaluated the efficacy and safety of enfortumab vedotin plus pembrolizumab as consolidation therapy in 11 patients with metastatic urothelial carcinoma who completed cisplatin-based induction chemotherapy. More than 90% of patients achieved a radiographic or clinical complete response, and several maintained prolonged treatment-free remission. Treatment-related adverse events, including dermatologic toxicity, reversible peripheral neuropathy, and hyperglycemia, were observed but were predominantly manageable, allowing treatment continuation in most cases. Notably, the regimen demonstrated clinical activity in cisplatin-intolerant patients and in those who did not achieve an initial complete response after cisplatin therapy. Compared with conventional cisplatin-based therapy alone, consolidation with enfortumab vedotin plus pembrolizumab was associated with favorable tolerability, durable responses, and a high rate of bladder preservation. These findings support further investigation of enfortumab vedotin and pembrolizumab as a potential bladder-sparing strategy in advanced urothelial carcinoma.

Introduction: Despite the growing use of CAR‐T therapy, adults over 65 still receive this treatment less frequently than younger patients. Methods: Using the Nationwide Readmissions Database (2018–2020), we analyzed 2928 CAR‐T recipients, dividing them into young (18–40), middle‐aged (41–65), and older adults (≥ 66). Propensity score matching (caliper of 0.2, 1:1:1 ratio) was performed. We adjusted for the following confounding variables: gender, comorbidities, and social factors including smoking, alcohol use, and illicit drug use. Results: Older adults had the highest rates of acute kidney injury (11.7% vs. 13.0% vs. 18.1%, p = 0.02) and cardiac complications (2.0% vs. 3.6% vs. 5.4%, p = 0.03). These three different age groups had comparable rates of leukopenia (45.0% vs. 42.7% vs. 39.1%, p = 0.10), infection (41.0% vs. 43.6% vs. 42.1%, p = 0.74), neurotoxicity (6.2% vs. 6.5% vs. 7.7%, p = 0.52), and pulmonary embolism (1.0% vs. 2.9% vs. 2.3%; p = 0.2). Despite the highest rates of non‐home discharge among the older patients (14.0% vs. 7.5% vs. 8.8%), there were no significant differences in early mortality (5.2% vs. 6.2% vs. 6.7%, p = 0.34), 30‐day readmission (23.1% vs. 23.8% vs. 24.4%, p = 0.48), prolonged index hospitalization (96.1% vs. 94.8% vs. 93.6%, p = 0.14), and total length of stay (21.2 days vs. 18.2 days vs. 21.3 days, p = 0.58). Conclusion: CAR‐T therapy is safe among older adults with close monitoring for cardiac and renal complications.

Purpose: Our study aims to describe the mortality trends and disparities among individuals with thalassemia in the United States (US). Patients and Methods: We used CDC WONDER database to calculate the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and used the Joinpoint Regression Program to measure the average annual percent change (AAPC). Subgroup evaluations were performed by sex, age, race, census region, and urbanization level. Results: From 1999 to 2020, there were 2797 deaths relatd to thalassemia in the US. The AAMR of thalassemia-related death showed a decreasing trend from 0.50 (95% CI, 0.41– 0.58) in 1999 to 0.48 (95% CI, 0.41– 0.55) in 2020 with the AAPC of − 1.42 (95% CI, − 2.42, − 0.42). Asians have the highest AAMR (1.34 [95% CI, 1.20– 1.47]), followed by non-Hispanic Blacks (0.65 [95% CI, 0.59– 0.71]), non-Hispanic Whites (0.32 [95% CI, 0.30– 0.33]), and Hispanics (0.11 [95% CI, 0.08– 0.14]). Cardiovascular disease remains the leading cause of death among individuals with thalassemia. The urban population has a higher AAMR than the rural population (0.43 [95% CI, 0.41– 0.45] vs 0.29 [95% CI, 0.26– 0.32]). Conclusion: Our study calls for targeted interventions to address the racial and geographic disparities existed among individuals of thalassemia in the US.

Introduction: Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors. Data sources: Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry ( http://www . Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms “bisphosphonates/diphosphosphonates and mechanism,” “bisphosphonates and breast cancer,” “bisphosphonates and prostate cancer,” “bisphosphonates and lung cancer,” “bisphosphonates and cancer risk,” and “bisphosphonates and adverse events.” Manual searches of some major oncology journals were also conducted. Discussion: This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

The therapeutic landscape of the management of stage III non-small cell lung cancer (NSCLC) has drastically evolved with the incorporation of immunotherapy and targeted therapy. Stage III NSCLC accounts for one-third of the cases and the treatment strategy of these locally advanced presentations are diverse, ranging from surgical to non-surgical options; with the incorporation of chemo-immunotherapy, radiation, and targeted therapies wherever applicable. The staging of this disease has also changed, and it is essential to have a strong multidisciplinary approach to do justice to patient care. In this article, we aim to navigate the nuanced approaches in the diagnosis and treatment of stage III NSCLC and expand on the evolution of the management of this disease.

Background: Adequate oxygen saturation (SpO ₂ ) is crucial for managing sickle cell disease (SCD). Children with SCD are at increased risk for occult hypoxemia; therefore, understanding SpO ₂ threshold practices would help identify barriers to oxygen optimization in a population sensitive to oxyhemoglobin imbalances. We investigated SpO ₂ cutoff levels used in clinical algorithms for management of acute SCD events at children's hospitals across the United States, and determined their consistency with recommended national guidelines (SpO ₂ > 95%). Methods: Clinical pathways and algorithms used for the management of vaso‐occlusive crisis (VOC) and acute chest syndrome (ACS) in SCD were obtained and reviewed from large children's hospitals in the United States. Results: Responses were obtained from 94% (140/149) of eligible children's hospitals. Of these, 63 (45%) had available clinical algorithms to manage VOC and ACS. SpO ₂ cutoff was provided in 71.4% (45/63) of clinical algorithms. Substantial variation in SpO ₂ cutoff levels was noted, ranging from ≥90% to more than 95%. Only seven hospitals (5% of total hospitals and 15.6% of hospitals with clinical algorithms available) specified oxygen cutoffs that were consistent with national guidelines. Hospitals geographically located in the South (46.8%; n = 29/62) and Midwest (54.8%; n = 17/31) were more likely to have VOC and ACS clinical algorithms, compared to the Northeast (26.5%; n = 9/34) and West (36.4%; n = 8/22). Conclusion: There is inconsistency in the use of clinical algorithms and oxygen thresholds for VOC and ACS across US children's hospitals. Children with SCD could be at risk for insufficient oxygen therapy during adverse acute events.

While renal cell carcinoma (RCC) is often linked to smoking, obesity, and hypertension, hereditary forms also account for about 3% of RCC cases. Notably, NCCN guidelines identify 7 major hereditary syndromes associated with an increased RCC risk. Inherited mutations in DNA repair genes, such as ATM, BRCA, and TP53, significantly increase the risk of various cancers. Biallelic pathogenic mutations in ATM cause Ataxia-Telangiectasia (A-T) syndrome, while heterozygous germline pathogenic ATM mutations, present in about 1% of the population, also elevate cancer risk. RCC has not traditionally been associated with germline pathogenic ATM mutations, only limited retrospective analyses have identified such mutations. This case report presents a 68-year-old woman with a germline pathogenic ATM mutation (c.8786+1 G>A) who developed high-risk clear cell RCC followed by an acquired somatic VHL mutation in RCC and a 3-cm serous cystadenoma, illustrating the double-hit phenomenon. Her brother, who shares the same germline pathogenic mutation, was diagnosed with pancreatic cancer and prostate cancer. This case highlights the potential use for enhanced screening protocols for RCC in patients who have germline pathogenic ATM mutations and the importance of research in targeted treatments for tumors driven by dual genetic mechanisms. Increased awareness and vigilant screening for RCC are crucial in managing hereditary cancer syndromes effectively.

Urothelial carcinoma of the upper urinary tract (UTUC) presents a significant clinical challenge, often requiring aggressive surgical intervention for optimal management. We present a case of an 84-year-old woman with recurrent high-grade papillary UTUC of the left renal pelvis, refractory to prior endourologic interventions, who underwent neoadjuvant treatment with pembrolizumab and enfortumab vedotin (Pembro/EV) due to contraindications to cisplatin therapy. Following a favorable response to neoadjuvant therapy, the patient underwent laparoscopic left radical nephroureterectomy, achieving a pathologic complete response. We discuss the utility of Pembro/EV in the perioperative management of patients with UTUC, particularly in those ineligible for cisplatin-based therapy. In addition, we highlight the potential role of somatic mutation testing and the integration of novel therapeutic agents such as olaparib in personalized treatment strategies for UTUC. This case underscores the importance of exploring innovative treatment approaches and optimizing patient selection for kidney preservation strategies in the management of UTUC. Further research and clinical trials are warranted to elucidate the full therapeutic potential of Pembro/EV and other emerging therapies in this setting.

Gastric cancer ranks as the fifth leading cause of global cancer incidences, exhibiting varied prevalence influenced by geographical, ethnic, and lifestyle factors, as well as Helicobacter pylori infection. The ATM gene on chromosome 11q22 is vital for genomic stability as an initiator of the DNA damage response, and mutations in this gene have been associated with various cancers. Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, have shown efficacy in cancers with homologous recombination repair deficiencies, notably in those with ATM mutations. Here, we present a case of a 66-year-old patient with germline ATM-mutated metastatic gastric cancer with very high CA 19-9 (48 000 units/mL) who demonstrated an exceptional response to the addition of olaparib to chemo-immunotherapy and subsequent olaparib maintenance monotherapy for 12 months. CA 19-9 was maintained at low level for 18 months. Despite the failure of a phase II clinical trial on olaparib in gastric cancer (NCT01063517) to meet its primary endpoint, intriguing findings emerged in the subset of ATM-mutated patients, who exhibited notable improvements in overall survival. Our case underscores the potential clinical utility of olaparib in germline ATM-mutated gastric cancer and emphasizes the need for further exploration through larger clinical trials. Ongoing research and clinical trials are essential for optimizing the use of PARP inhibitors, identifying biomarkers, and advancing personalized treatment strategies for gastric cancer.