Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit.

Introduction: Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre. Methods: Patients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014-2017) prior to institutional change to FoundationOne CDx (FM1; 2017-2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022. Results: A total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN-altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75). Conclusions: Broad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS.

Management of gout in the primary care setting.

Gout is a commonly treated inflammatory arthritis that is often managed in the primary care setting. This disease is prevalent among the multi-ethnic Malaysian population. Unfortunately, gout is still frequently managed sub-optimally, even in the hospital and primary care settings. Gout should be considered a major disease since it can potentially lead to multiple disabilities from joint destruction, nephropathy and increased cardiovascular morbidity and mortality. The objectives of this review are to summarise the latest updated information and management of gout in the primary care setting.

A practical approach to chronic kidney disease in primary care.

Chronic kidney disease (CKD), a common clinical problem in primary care, can be defined as any abnormality of the kidney structure and/or function that has been present for at least 3 months. Over the past 20 years, the incidence and prevalence of CKD have been increasing in Malaysia in line with the rising number of non-communicable diseases. At present, CKD has no cure. The treatment of CKD is very much dependent on early diagnosis and prevention of CKD progression. In this article, we aim to illustrate a practical approach to CKD in primary care, including diagnosis, evaluation, and management of CKD.

A case of atrial septal defect presenting with recurrent syncope.

Atrial septal defect (ASD) is a congenital heart disease often encountered in the adult population, as it is frequently asymptomatic in childhood. In untreated patients with ASD, some may go on to develop complications such as atrial arrythmias, pulmonary hypertension and Eisenmenger syndrome. Pulmonary hypertension is seen in 6 - 35% of this group of untreated patients in adulthood as a result of left-to-right shunting. Symptoms of pulmonary hypertension include progressive dyspnoea, ascites and syncope. Here, we would like to illustrate a case of ASD presenting with recurrent syncopal attack.

A young lady with dysphagia.

Chest radiograph is one of the most commonly employed imaging modalities in primary care. It may be done for symptomatic patients or routine health screening. Hence, it is important for a primary care physician to be able to interpret chest radiograph systematically in relation to patient's clinical history. Here, we would like to illustrate a case of abnormal chest radiograph detected during health screening.

Erythematous plaques of the vulvo-perineal region.

Skin conditions are a common reason for consulting primary health care. The public frequently expects their primary health care providers to be able to recognise and treat common skin conditions with confidence. Primary care providers must be able to identify 'red flag' skin conditions that require dermatology referral. However, diagnosis is often delayed due to the non-specific clinical presentation, low incidence, slow evolution and long-term history of such lesions. We report the case of a patient with extramammary Paget's disease that presented to her primary care provider and subsequently underwent a wide local excision.

Images of the month: Intractable vomiting and neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disorder of the nervous system which can be potentially debilitating. Its prevalence is estimated to be around 0.5-10 per 100,000 population with predilection towards Asians and females. It can be diagnosed based on core clinical characteristics, serum aquaporin antibodies and neuroimaging features. It is important to pick up the diagnosis of NMOSD as the treatment is different from other demyelinating disease. Here, we illustrate a case of NMOSD presented with intractable vomiting.

Interstitial pneumonia with autoimmune features.

BACKGROUND: Cardiac tamponade is a medical emergency. This study was carried out to determine the etiologies of cardiac tamponade and review the management and outcomes. METHODS: We retrospectively analysed case records of patients who underwent pericardiocentesis for cardiac tamponade during the two consecutive years (1 January 2018 to 31 December 2019) at Hospital Sultanah Nora Ismail, Batu Pahat, in Johor, Malaysia. RESULTS: There were ten patients (eight males, two females; age range 20 to 70 years old, mean age 36 years old) who underwent pericardiocentesis for cardiac tamponade during the said period. Malignancy (40%), tuberculosis (30%), idiopathic (20%), and bacterial (10%) were among the common causes of the pericardial effusion in this center. The commonest symptoms were breathlessness (90%), chest pain (60%), cough (50%), and unexplained fever (20%). Pulsus paradoxus was the most speciÿ c sign (100%) for the presence of echocardiographic feature of cardiac tamponade. Two of the patients with tuberculous pericarditis had retroviral disease; one patient had bacterial pericarditis due to salmonella typhi. CONCLUSION: This study has conÿ rmed that there are many etiologies and presentation of cardiac tamponade; clinicians should be alert as urgent pericardiocentesis is lifesaving.

A case of dapsone-induced methaemoglobinaemia.

Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest cause of acquired methaemoglobinaemia. The clinical signs and symptoms of methaemoglobinaemia include dyspnoea, desaturation, presence of saturation gap, headache, nausea and seizures depending on level of serum methaemoglobinaemia. We illustrate a case of dapsone-induced methaemoglobinaemia and its successful treatment by intravenous methylene blue.