Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes.

BACKGROUND: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming. METHODS: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer. RESULTS: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms. CONCLUSION: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

The Clinical Features and Expression of bcl-2, Cyclin D1, p53, and Proliferating Cell Nuclear Antigen in Syndromic and Nonsyndromic Keratocystic Odontogenic Tumor.

UNLABELLED: The aim of this study was to describe the clinical features and expression of bcl-2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT). METHODS: This descriptive study comprised 5 patients of KCOT associated with NBCCS and 8 patients of nonsyndromic type treated in the Department of Oral Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre between years 1998 and 2011. The clinical features (site, size, treatment, and recurrence), demographic characteristics, and immunohistochemistry results using antibodies of bcl-2, cyclin D1, p53, and PCNA were examined. The association of the antibody expression and the type of KCOT was analyzed using Fisher exact test. RESULTS: Altogether there were 13 patients, 5 with syndromic KCOT (1 patient met 3 major criteria of NBCCS) and 8 with sporadic KCOT. The age range for syndromic KCT was 11 to 21 years (mean 16.00 years, SD 4.36) and 10 to 54 years (median 24.50 years, interquartile range 19.00) for the nonsyndromic KCOT. Tumor recurrence occurred in 3 patients (7.7%); 1 patient from the syndromic and 2 patients from the nonsyndromic. The most positive expression was observed in PCNA for both the syndromic and nonsyndromic samples and the least positive expression involved the p53. CONCLUSION: PCNA, bcl-2 protein, and cyclin D1 expressions could be useful in evaluating the proliferative activity of the tumor and the aggressiveness of the clinical presentation; however, the authors would propose for larger sample size research for more definitive results.

Information needs of Malaysian parents of children with cancer: A qualitative study.

Objective: Informational support is an important pillar of psychosocial care for parents of children with cancer. Understanding the information needs of these parents may improve the provision of family-centered informational support. This paper aims to explore the information needs of Malaysian parents whose children have cancer. Methods: This qualitative study was conducted among 14 parents of children with cancer and 8 healthcare providers. The parents were recruited from two urban pediatric oncology centers in Malaysia. Healthcare providers were recruited from these centers, as well as from community-based palliative care providers. In-depth interviews were conducted based on semi-structured topic guides, audio-recorded, and transcribed for thematic analysis using elements of the grounded theory approach. Results: Analysis revealed three themes of information needs, which were: "interaction with the healthcare system," "care for the child at home" and "psychosocial support for parents". Information needs on parents' interaction with the healthcare system consisted of disease and treatment-related information, as well as health system navigation. Information needs on care for the child at home were represented by their caregiving for basic activities of daily living, medical caregiving, and psychosocial caregiving. Psychosocial support for parents included information on practical support and self-care. There were differences in priorities for information needs between parents and healthcare providers. Conclusions: Meeting the information needs of parents is an important part of psychosocial care in pediatric cancer care. Informational support may empower parents in caregiving for their child. The development of suitable information resources will be invaluable for healthcare providers in supporting parents' needs.

Development and Validation of a Caregiving Knowledge Questionnaire for Parents of Pediatric Leukemia and Lymphoma Patients in Malaysia.

Introduction Validated tools to measure caregiving knowledge among parents of children with hematological cancers are needed to measure the clinical outcome of caregiver interventions. This study reports the development and validation of the Hematological Oncology Parents Education Caregiving Knowledge Questionnaire (HOPE-CKQ) among Malaysian parents of pediatric leukemia and lymphoma patients. Methods Initially, 60 items on caregiving knowledge were developed based on a qualitative needs assessment study. Content validity was evaluated using item content validity index (I-CVI) and scale content validity index (S-CVI/Ave). Parents of pediatric leukemia and lymphoma patients were invited to complete the 60-item version of the HOPE-CKQ. Exploratory factor analysis (EFA) using polychoric correlation resulted in an 18-item version of HOPE-CKQ. Confirmatory factor analysis (CFA) was used to verify the factor structure. Known-group validity was tested by comparing the scores among different levels of parent education. Results The I-CVI ranged from 0.83 to 1.00 whereas the S-CVI/Ave was 0.99, indicating good content validity. A total of 167 complete responses were analyzed for factor analysis. EFA using polychoric correlations resulted in a single-factor structure consisting of 18 items. CFA confirmed that the 18-item single-factor HOPE-CKQ model had a good fit for the data. The internal consistency reliability was good (α=0.80). Parents with tertiary education level had higher caregiving knowledge (M=12.61, SD=3.37) compared to parents with secondary education and below (M=10.33, SD=3.80) (t=3.58, p<0.001). Conclusions The 18-item HOPE-CKQ is valid and reliable for use to measure caregiving knowledge among pediatric leukemia and lymphoma parents. This tool may be considered to measure caregiving knowledge in future preventive and intervention programs.

Molecular diagnosis of severe combined immunodeficiency--identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children.

Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient's gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n = 19), IL7R (n = 2), JAK3 (n = 2), RAG1 (n = 1), RAG2 (n = 1), and DCLRE1C (n = 1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette-Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed.

Vincristine-induced vocal cord palsy: case report and review of the literature.

Vincristine-induced vocal cord paralysis is a rare but serious complication. We report 2 patients with acute lymphoblastic leukemia who developed progressive stridor during induction chemotherapy. There were no clinical features of peripheral or autonomic neuropathy. Flexible laryngoscopy confirmed the diagnosis of bilateral vocal cord palsy; interestingly, the nerve conduction test revealed axonal motor neuropathy involving the median and common peroneal nerves in both patients. The first patient required prolonged ventilatory support necessitating unilateral cordectomy before extubation, whereas the second only required supplemental oxygen therapy. There was resolution of stridor in the first patient after cordectomy and gradual clinical improvement in the second. These cases illustrate that a high index of suspicion of vincristine-induced vocal cord palsy with prompt otolaryngology consultation for laryngoscopy is required in the diagnostic evaluation of a patient who has received vincristine.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.