Tam Cam Ha

Meta-analysis of clodronate and breast cancer survival.

Clinical trials have reported conflicting results on whether oral clodronate therapy improves survival in breast cancer patients. This study was undertaken to evaluate further the effect of oral clodronate therapy on overall survival, bone metastasis-free survival and nonskeletal metastasis-free survival among breast cancer patients. An extensive literature search was undertaken for the period 1966 to July 2006 to identify clinical trials examining survival in breast cancer patients who received 2 or 3 years of oral clodronate therapy at 1600 mg day−1 compared with those without therapy. Meta-analyses were carried out separately for patients diagnosed with advanced breast cancer and early breast cancer. Our meta-analysis found no evidence of any statistically significant difference in overall survival, bone metastasis-free survival or nonskeletal metastasis-free survival in advanced breast cancer patients receiving clodronate therapy or early breast cancer patients receiving adjuvant clodronate treatment compared with those who did not receive any active treatment.

Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE We sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone. METHODS AND MATERIALS Seven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria. RESULTS Median follow-up was 7.2 years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3 months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermittes syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%). CONCLUSIONS While radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques.

Twelve Tips for Facilitating Team-Based Learning.

Abstract Background: Team-based learning (TBL) has become a more commonly recognized and implemented pedagogical approach in curricula of numerous disciplines. The desire to place more autonomy on the student and spend less in-class time delivering content has resulted in complete or partial adoption of this style of learning in many educational settings. Aim: Provide faculty with tools that foster a well facilitated and interactive TBL learning environment. Methods: We examined the published literature in the area of facilitation – specifically in TBL environments, and explored learning theories associated with team learning and our own experiences to create these facilitation tips. Results: We created 12 tips for TBL facilitation designed to assist faculty to achieve an effective and engaging TBL learning environment. Conclusions: Applying these twelve tips while facilitating a TBL classroom session will help to ensure maximal participation and optimal learning in a safe yet stimulating environment.

Effect of concomitant statin, metformin, or aspirin on rituximab treatment for diffuse large B-cell lymphoma

Several pre-clinical studies report that statins interfere with the surface binding of rituximab to CD20. This study investigated the effects of statins in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-based chemoimmunotherapy, and the impact of commonly used drugs, metformin and aspirin, on the clinical outcomes of patients receiving chemoimmunotherapy. We included 213 patients with DLBCL who received rituximab-based chemoimmunotherapy. Details of statin, metformin, and aspirin use and initiation of chemoimmunotherapy were abstracted from medical records. All patients received rituximab, and 47 (22.1%) were taking statins. The median age of patients receiving statins was significantly higher compared to those who did not (p <0.001). Response rates between patients receiving and not receiving statins were not significantly different (85.1% vs. 87.3%; p = 0.688). Event-free survival (EFS) was not significantly different (p = 0.352). Overall survival was lower in patients receiving statins compared to those who did not (p = 0.036). However, it was no longer significant after adjustment for age (p = 0.140). Metformin had no impact on the response rate (p = 0.268), EFS (p = 0.574), and overall survival (p = 0.141). Aspirin had no impact on the response rate (p = 0.784), EFS (p = 0.836), and overall survival (p = 0.779). Statins do not interfere with rituximab, and need not be withheld during rituximab administration. Larger studies are needed to confirm the impact of metformin and aspirin on patients with DLBCL receiving chemoimmunotherapy.

Personalised medicine in nasopharyngeal cancer

568 www.thelancet.com/oncology Vol 13 June 2012 The main principle of traditional Chinese medicine— which began more than 4000 years ago and is summarised in The Yellow Emperor’s Canon of Medicine—is the notion of syndrome diff erentiation and treatment. This notion aims to analyse, induce, synthesise, judge, and summarise the clinical data of symptoms and signs collected with four diagnostic methods (inspection, listening and smelling, inquiry, and pulse reading and palpation) into a diagnosis of one syndrome. Therapeutic strategies are then decided according to the result of syndrome diff erentiation. Thus, although people living hundreds or thousands of years ago did not have access to next-generation sequencers, they were nevertheless very astute observers of nature and human beings. A study published in 2010 showed that diff erent radiological signs of nasopharyngeal carcinoma (eg, cervical lymph node metastases, skull-base erosions, and radiosensitivity) could be correlated with diff erent syndrome types from traditional Chinese medicine. In another study of 706 individuals, Chen and colleagues showed a possible genetic basis for the classifi cation of physical constitution in traditional Chinese medicine. Therefore, syndrome diff erentiation as per traditional Chinese medicine might provide a subtle phenotypic subclassifi cation within an allopathic disease diagnosis, suggesting an underlying genotypic diff erence. Fast forward to modern allopathic medicine and the TNM system, which has been in existence since the 1940s, and use of classifi cation from anatomical prognostic factors has withstood the test of time. Such anatomical assessment remains the basis of personalised medicine. In nasopharyngeal carcinoma, a group from Hong Kong successfully tailored therapy by reducing the radiotherapy dose to the pituitary fossa and neck for patients without cancer involvement of those structures. This group’s next attempt at personalised medicine was confi rmation of the usefulness of addition of concurrent chemotherapy to radiotherapy in two trials. The fi rst trial (NCT00563927) tested the addition of chemotherapy for patients at highest risk of development of distant metastases and the second (NCT00563862) had a component of accelerated radiation in a subset of patients at increased risk for local failure. The same group is presently assessing the use of Epstein-Barr virus (EBV) DNA levels after radiotherapy to identify patients who would benefi t from additional adjuvant treatment (NCT00370890). Use of molecular signatures has proven to be important for the prediction of outcomes of many cancers. A group from Guangzhou (Guangdong, China) led an international consortium to identify an eight signature classifi er for prediction of survival in nasopharyngeal carcinoma. MicroRNAs (miRNAs) make up a large class of small non-protein-coding RNAs that are very infl uential in gene regulation and cellular function. Complex interactions between miRNAs, and their dysregulation, can amplify diverse pathogenic processes that contribute to initiation of tumour growth, proliferation, and metastases. Ri cc ar do C as sia ni -In go ni /S PL

Outcomes and Prognostic Factors of Radiation-Induced and De Novo Head and Neck Squamous Cell Carcinomas.

Objective We sought to compare clinical outcomes, pathological features, treatment patterns, and survival outcomes between radiation-induced squamous cell carcinoma (RISCC) and de novo SCC (DNSCC) of the head and neck, as well as identify prognostic factors in these patients. Study Design Case-control study. Setting Tertiary medical center. Subjects and Methods Retrospective case-control analysis of 34 RISCCs and 136 DNSCCs matched by age at diagnosis, sex, smoking status, and primary tumor site. Results Median latency of RISCC development was 13 years. Radiation-induced squamous cell carcinomas were more likely to present with node-negative disease than DNSCCs (70.6% vs 42.9%; P = .024). A greater proportion of DNSCCs was treated with curative intent (92.6% vs 79.4%; P = .048) and achieved no residual disease posttreatment (82.2% vs 41.2%; P < .001) compared with RISCCs. Patients with RISCC had poorer overall survival (OS) (median, 1.67 vs 5.03 years; P = .018) and disease-specific survival (DSS) (median, 1.67 vs 8.65 years; P = .001) than those with DNSCC. Among patients who underwent curative treatment with no residual disease after treatment, there were, however, no survival differences between RISCC and DNSCC. Conclusion In our cohort, RISCCs have a poorer prognosis than DNSCCs. However, those able to undergo curative treatment and have no residual disease after treatment have comparable survival outcomes. Locoregional control of these tumors appears paramount in achieving the best outcomes for patients with RISCC.

High incidence of nasopharyngeal cancer： similarity for 60% of mitochondrial DNA signatures between the Bidayuhs of Borneo and the Bai-yue of Southern China

Populations in Southern China (Bai-yue) and Borneo (Bidayuh) with high incidence of nasopharyngeal cancer (NPC) share similar mitochondrial DNA signatures, supporting the hypothesis that these two populations may share the same genetic predisposition for NPC, which may have first appeared in a common ancestral reference population before the sea levels rose after the last ice age.

Inclination towards research and the pursuit of a research career among medical students: an international cohort study

BackgroundInvolvement of clinicians in biomedical research is imperative for the future of healthcare. Several factors influence clinicians’ inclination towards research: the medical school experience, exposure to research article reading and writing, and knowledge of research. This cohort study follows up medical students at time of graduation to explore changes in their inclination towards research and pursuing a research career compared to their inclination at time of entry into medical school.MethodsStudents from medical schools in six different countries were enrolled in their first year of school and followed-up upon graduation in their final year. Students answered the same self-administered questionnaire at both time points. Changes in inclination towards research and pursuing a research career were assessed. Factors correlated with these changes were analysed.ResultsOf the 777 medical students who responded to the study questionnaire at entry into medical school, 332 (42.7%) completed the follow-up survey. Among these 332 students, there was no significant increase in inclination towards research or pursuing a research career over the course of their medical schooling. Students from a United States based school, in contrast to those from schools other countries, were more likely to report having research role models to guide them (51.5% vs. 0%–26.4%) and to have published in a peer-reviewed journal (75.7% vs. 8.9%–45%). Absence of a role model was significantly associated with a decrease in inclination towards research, while an increased desire to learn more about statistics was significantly associated with an increase in inclination towards pursuing a research career.ConclusionMost medical students did not experience changes in their inclination towards research or pursuing a research career over the course of their medical schooling. Factors that increased their inclination to undertaking research or pursuing a research career were availability of a good role model, and a good knowledge of both the research process and the analytical tools required.

The predominant learning approaches of medical students

BackgroundBy identifying medical students’ learning approaches and the factors that influence students’ learning approaches, medical schools and health care institutions are better equipped to intervene and optimize their learning experience. The aims of our study is to determine the predominant learning approach amongst medical students on a clinical posting in a hospital in Singapore and to examine the demographic factors that affect their learning approach.MethodsThe Approaches and Study Skills Inventory for Students (ASSIST) questionnaire was administered to 250 medical students from various medical schools on clinical attachment to the Obstetrics and Gynaecology (O&G) department of KK Women’s and Children’s Hospital (KKH) Singapore between March 2013 and May 2015 to determine students’ predominant learning approaches. Multinomial logistic regression was used to examine the association between demographic factors (age, gender and highest education qualification) and predominant learning approach. A cut-off of p < 0.05 was used for statistical significance.ResultsAmongst 238 students with one predominant learning approach, 96 (40.3%) and 121 students (50.8%) adopted the deep and strategic approach respectively, whilst only 21 (8.8%) adopted the surface approach. Male students appeared less likely to adopt the strategic learning approach than female students (p value = 0.06). Predominant learning approaches were not influenced by demographic characteristics such as age, gender and highest educational qualifications.ConclusionsThis study provided insight into the learning approaches of a heterogeneous group of medical students in Singapore. While it is encouraging that the majority of students predominantly utilised the deep and strategic learning approach, there was a significant proportion of students who utilised the surface approach. Interventions can be explored to promote deeper learning amongst these students.

Retention in Enhanced Team Based Learning Course: retain or refrain?

Students’ ability to retain content in medical school has always been a concern. At Duke-NUS Medical School, we modified our Team-Based Learning (TBL) classes known as TeamLEAD, a learning strategy for first year basic science content, to include an open/closed-book option in the readiness assurance phase to engage teams in deeper discussion. We hypothesize that the open-book option allows students to engage in deeper learning in their teams, which leads to an improvement in retention ability for each individual student at the end of their first year basic science curriculum. Methods: A total of 115 MCQs used throughout first year basic science courses from 2011 to 2013 were repeated during a two-week end-of-year review. We analysed the extent of students’ retention by examining the influence of team’s choice for open/closed-book on initial and repeated individual performance score. Results: Student’s individual scores increased from 56.2% correct the first time encountering the questions to 68.7% for the second time (p<0.01). For teams that chose open-book option for group readiness assurance (GRA) test, individual students’ second encounter score increased by 11.8% (p<0.01) compared to 10.3% (p<0.01) for teams that chose closed-book option. Students’ retention was higher for those questions from second half of the year compared to questions from first half (p<0.01). Conclusion: Implementation of open-book component enables students to drive challenging discussion in teams. This helps individual students to consolidate, recall and retain more information over time, which results in an improved individual performance at the end-of-year review.