Diagnostic work-up and systemic treatment for advanced non-squamous non-small-cell lung cancer in four Southeast Asian countries.

BACKGROUND: Lung cancer is the second most common cancer and leading cause of cancer mortality worldwide. Recent advances in molecular testing and targeted therapy have improved survival among patients with metastatic non-small-cell lung cancer (NSCLC). We sought to quantify and describe molecular testing among metastatic non-squamous NSCLC cases in selected Southeast Asian countries and describe first-line therapy chosen. PATIENTS AND METHODS: A retrospective study was conducted based on incident lung cancer cases diagnosed between 2017 and 2019 in Lampang (Thailand), Penang (Malaysia), Singapore and Yogyakarta (Indonesia). Cases (n = 3413) were defined using the International Classification of Diseases for Oncology third edition. In Singapore, a clinical series obtained from the National Cancer Centre was used to identify patients, while corresponding population-based cancer registries were used elsewhere. Tumor and clinical information were abstracted by chart review according to a predefined study protocol. Molecular testing of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangement, ROS1 gene rearrangement and BRAF V600 mutation was recorded. RESULTS: Among 2962 cases with a specified pathological diagnosis (86.8%), most patients had non-squamous NSCLC (75.8%). For cases with staging information (92.1%), the majority presented with metastatic disease (71.3%). Overall, molecular testing rates in the 1528 patients with stage IV non-squamous NSCLC were 67.0% for EGFR, 42.3% for ALK, 39.1% for ROS1, 7.8% for BRAF and 36.1% for PD-L1. Among these patients, first-line systemic treatment included chemotherapy (25.9%), targeted therapy (35.6%) and immunotherapy (5.9%), with 31% of patients having no record of antitumor treatment. Molecular testing and the proportion of patients receiving treatment were highly heterogenous between the regions. CONCLUSIONS: This first analysis of data from a clinically annotated registry for lung cancer from four settings in Southeast Asia has demonstrated the feasibility of integrating clinical data within population-based cancer registries. Our study results identify areas where further development could improve patient access to optimal treatment.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

Current standards and practice changing studies in genitourinary (GU) cancers-a review of studies in localized/early GU cancers.

Optimizing treatment of genitourinary cancers in the early-stage setting continues to remain an area of need, given that the development of distant metastases is often the life-limiting factor in the natural history of these cancers. The use of perioperative therapies in the treatment of these cancers deemed to be at high risk of recurrence has shown considerable benefits in outcomes in recent studies. In this article, we review the recently published studies in early-stage genitourinary cancers (renal cell, urothelial and prostate carcinomas), and their impact on disease outcomes and treatment practices. The results of subgroup analysis from some of these trials, with Asian patients enrolled, give assurance of the clinical efficacy and safety of these therapies in early-stage urological malignancies in the Asian setting.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.

Linguistic validation of the simplified Chinese version of the US National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™).

BACKGROUND: The aim of this study was to translate and linguistically validate the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) into Simplified Chinese for use in Singapore. METHODS: All 124 items of the English source PRO-CTCAE item library were translated into Simplified Chinese using internationally established translation procedures. Two rounds of cognitive interviews were conducted with 96 cancer patients undergoing adjuvant treatment to determine if the translations adequately captured the PRO-CTCAE source concepts, and to evaluate comprehension, clarity and ease of judgement. Interview probes addressed the 78 PRO-CTCAE symptom terms (e.g. fatigue), as well as the attributes (e.g. severity), response choices, and phrasing of 'at its worst'. Items that met the a priori threshold of ≥20% of participants with comprehension difficulties were considered for rephrasing and retesting. Items where < 20% of the sample experienced comprehension difficulties were also considered for rephrasing if better phrasing options were available. RESULTS: A majority of PRO-CTCAE-Simplified Chinese items were well comprehended by participants in Round 1. One item posed difficulties in ≥20% and was revised. Two items presented difficulties in < 20% but were revised as there were preferred alternative phrasings. Twenty-four items presented difficulties in < 10% of respondents. Of these, eleven items were revised to an alternative preferred phrasing, four items were revised to include synonyms. Revised items were tested in Round 2 and demonstrated satisfactory comprehension. CONCLUSIONS: PRO-CTCAE-Simplified Chinese has been successfully developed and linguistically validated in a sample of cancer patients residing in Singapore.

Real-world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Objectives: In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (mrcc) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (vegfr) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (os) and time to treatment failure (ttf) were calculated using Kaplan-Meier curves. Overall response rates (orrs) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results: The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median os was observed: 22.10 months [95% confidence interval (ci): 17.18 months to not reached] with nivolumab and 23.70 months (95% ci: 15.52 months to not reached) with cabozantinib (p = 0.61). The ttf was also similar at 6.90 months (95% ci: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% ci: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (hr) for nivolumab compared with cabozantinib was 1.30 (95% ci: 0.73 to 2.3), p = 0.38. When adjusted by imdc criteria and age, the hr was 1.32 (95% ci: 0.74 to 2.38), p = 0.35. Conclusions: Real-world imdc data indicate comparable os and ttf for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line vegfr-targeted therapy.

Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and manifestation of toxicities from sunitinib in Asian patients.

The objective of this study was to determine the effect of the CYP3A5 and ATP binding cassette subfamily B member 1 (ABCB1) single-nucleotide polymorphisms on the disposition of sunitinib and SU12662, on clinical response, and on the manifestation of toxicities in Asian metastatic renal cell carcinoma patients. At week 4 of each treatment cycle, toxicities and plasma steady-state levels were assessed. Clinical response was assessed after two cycles. Genotyping was performed by using the PCR restriction fragment length polymorphism method. The CC genotype for ABCB1 was associated with a higher sunitinib exposure (76.81 vs 56.55 ng ml(-1), P=0.03), higher risk of all-grade rash (RR 3.00, 95% CI 1.17-7.67) and mucositis (RR 1.60, 95% CI 1.10-2.34) and disease progression than compared with the CT/TT genotype. There was a lack of association observed between the CYP3A5 polymorphism and exposure, response and toxicities. The polymorphism of ABCB1 (C3435T) has an important role in the manifestation of toxicities and drug exposure, but not polymorphism of CYP3A5.

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†.

BACKGROUND: Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS: SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS: Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS: Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

A prospective cohort study on the effect of various risk factors on hypoglycaemia in diabetics who fast during Ramadan.

Muslim diabetics who fast during Ramadan are at risk of hypoglycaemia, and previous consensus guidelines have highlighted certain risk factors. This prospective cohort study aims to determine the relative risk (RR) of hypoglycaemia during Ramadan fasting compared with a non-fasting period of equivalent length, and to ascertain which risk factors are clinically significant. From the results, Ramadan fasting carries a RR of hypoglycaemia of 1.60 (95% CI 1.05 to 2.43). Good metabolic control (HbAlc < 8%) and old age (> 60 years) increased RR more than twice, while taking breakfast prior to fasting reduces RR to less than half.