Three NCCS Clinician-Scientist bag Merit Awards at prestigious American Society of Clinical Oncology (ASCO) Annual Meeting 

Ø First time NCCS wins three awards at same ASCO meeting

Ø Selection of work based on stringent review by the ASCO 2013 Scientific Program Committee

Ø Quality of abstracts recognised by Conquer Cancer Foundation

Ø Lastest achievements adds to the total tally of 10 ASCO awards conferred to NCCS clinician scientists

Singapore, 13 May 2013 – Three NCCS clinician-scientists have each won the prestigious ASCO Merit Awards this year. This is a first for NCCS where three of its staff won the awards at the same scientific meeting.

The three recipients from NCCS are:

1. Dr Joanne Ngeow, Cancer Genomics Medicine Fellow, Genomic Medicine Institute, Cleveland Clinic; Consultant, Department of Medical Oncology;

2. Dr Tira Tan, Registrar, Department of Medical Oncology ; and

3. Dr Melvin Chua, Registrar, Department of Radiation Oncology.

In addition, Dr David Tai, Associate Consultant, Department of Medical Oncology, will also give an oral presentation about his research on whether patients would benefit from Phase 1 clinical trials by evaluating the clinical characteristics and outcomes of elderly patients enrolled in phase 1 trials using the Royal Marsden Hospital (RMH) prognostic score.

The ASCO meeting is a gathering of the world’s leading oncologists and is held from 31 May- 4 June in Chicago, US. Each year scientists and oncologists will travel from across the globe to congregate at ASCO to learn from experts on cancer research.

ASCO was founded in 1964 by a small group of physician members of the American Association of Cancer Research (AACR) who recognised the need for the creation of a separate society dedicated to issues unique to clinical oncology.

At each gathering, award winners, whose research abstracts have been put under the stringent review by the scientific program committee that adjudge all submission to determine the top abstracts, will be given the opportunity to present their research.

Being chosen to present at the ASCO meeting is an affirmation on the quality of the work of the clinician scientist as it is an indication of acceptance by an international community of world-renowned experts. The chosen clinician scientist will also put NCCS on a world’s stage and this augurs well for the small nation as it demonstrated its finesse in scientific research that are parallel to world standards.

Since 2005 till to-date, NCCS has bagged two Young Investigator’s Awards and eight Merit Awards. Commending the efforts of winners who are increasingly coming from the junior ranks of the profession, Prof Soo Khee Chee, Director of NCCS said: "I am heartened that our young clinician scientists are already beginning to make contributions to research at a time when they are just embarking on their careers. Their achievements corroborate the high standards that we set for our research work. I am confident that our researchers will be striving even harder on their research projects to gain a deeper insight into cancer.

For this year, the NCCS projects are:

- Dr Joanne Ngeow: Second malignant neoplasms in Cowden syndrome patients which studied the likelihood of patients getting a second cancer with underlying germline PTEN mutations which increases their lifetime risks for breast, uterine, thyroid and renal cancers.

- Dr Melvin Chua: Comparison of in vivo skin and in vitro blood lymphocyte models for the prediction of late normal tissue responses in breast radiotherapy (RT) patients, which ascertained that DNA damage in irradiated blood lymphocytes of breast cancer patients can predict for late toxicities following breast radiotherapy.

- Dr Tira Tan: Identification of Comprehensive Geriatric Assessment (CGA) based risk factors for malnutrition in elderly Asian cancer patients. In this study, CGA based clinical factors which predict for malnutrition was identified. This allows for early interventions which could improve tolerability to treatment as well as alter cancer outcomes.

The awards are conferred by the Conquer Cancer Foundation of ASCO, which aims to recognise oncology fellows who are first authors of abstracts selected for presentation at the upcoming Annual ASCO meeting.

The methods and results of the above studies are detailed in Annex A.

Prof Soo noted that increasingly cancer research is beginning to have greater relevance in producing better clinical outcomes for our patients. "As we continue to invest in our research programmes and give good support to our scientists, the ultimate beneficiaries to all their discoveries will be the patients. As medical science gives us new insights on cancer, our doctors will be better equipped to provide better diagnosis and treatment to all our patients. The well-being of our patients is the key focus when we get our researchers and clinicians to work on the research projects. We are grateful to all who have given us donations to support our research projects. Funding will enable these young clinician scientists the resources necessary to bring their projects into fruition. Through these projects, the doctors will be able to hone in on their knowledge and expertise for the benefit of our patients."

For further information, please contact:

Ms Veronica Lee 
Senior Executive, Corporate Communications
Tel: 6236 9429
Email: Veronica.Lee.H.E@nccs.com.sg 

Ms Rachel Tan 
Assistant Manager, Corporate Communications
Tel: 6236 9535
Email: Rachel.Tan.C.H@nccs.com.sg

About National Cancer Centre Singapore 
The National Cancer Centre Singapore (NCCS) is dedicated to providing a holistic and multidisciplinary approach to cancer treatment and patient care. We treat almost 70 per cent of the public sector oncology cases. Through developing sub-specialisation among its clinical oncologist, NCC patients receive the best in treatment and care. NCCS is simultaneously engaged in cutting-edge clinical and translational research which has received international recognition. NCCS was accredited by the Joint Commission International in 2010 for quality patient care and safety. NCCS, which is set to be a global leading institution, offers specialist training programmes and research training to local and international applicants. 

Annex A
Second malignant neoplasm (SMN) in Cowden syndrome patients with underlying germline
PTEN mutations 
Joanne Ngeow1,2, Jessica Mester1,2, Haider Mahdi1,2, Lamis Yehia1,2, Jill Barnholtz-Sloan5,6 and Charis Eng1-4,6,7

Background
Cowden syndrome (CS) patients with underlying germline PTEN mutations are at significantly increased risk of breast, thyroid, endometrial and renal cancers. Current estimates of lifetime cancer risks do not provide the majority of patients who present after their first cancer a meaningful gauge of their risk of a second malignant neoplasm (SMN). Quantification of the risk of a SMN will allow patients to be better informed and provide clinicians a much needed guide to finally address patients’ question of "so, how likely am I to have a second cancer and is it likely to be the same primary?"

Methods
We conducted a 5-year, multi-center prospective study of CS and CS-like patients, all of whom had comprehensive PTEN analysis done. Patients’ records were reviewed for prior history of invasive cancers. Invasive SMNs were confirmed by pathology reports or physician reports where possible. All metastatic disease, synchronous primary cancer at the same site and non-melanoma skin cancers were excluded. Incidences of SMNs were compared between patients with pathogenic PTEN mutations (PTENmut+) and wildtype PTEN (PTENwt). Standardised incidence ratios (SIR), cumulative incidences and excess absolute risks for SMNs were calculated comparing against SEER-derived data.

Results
Of 2792 CS/CS-like patients who present with 1 or more cancers, there were 100 (4%) PTENmut+ patients, of which 42% (42/100) had SMNs. Compared with PTENwt CS/CS-like patients with SMNs (223/2039; 11%), PTENmut+ cases were younger at median age of SMN diagnosis (48yrs vs 54 yrs; p=0.30). For PTENmut+ patients having had one cancer were 56-fold more likely to develop any SMN compared with the general population (95%CI 41-55); corresponding to an excess absolute risk of 731-fold. Breast cancer was the most common SMN encountered in PTENmut+ CS/CS-like patients (SIR 73; 95%CI 45-122) followed by endometrial (SIR 44; 95% CI 18-92), renal (SIR 47; 95% CI 15-113) and thyroid cancers (SIR 222; 95% CI37-734). 

Conclusion
Our study shows that PTENmut+ CS/CS-like patients are significantly more likely to present with a SMN compared to PTENwt CS/CS-like patients and the general population, and should be advised and surveillance accordingly.

Comparison of in vivo skin and in vitro blood lymphocyte models for the prediction of late normal tissue responses in breast radiotherapy (RT) patients. 
Melvin Chua, Navita Somaiah, Sue Davies, Lone Gothard, Kai Rothkamm, John Yarnold

Background
Critical opinions for the lack of success of DNA double-strand break (DSB) repair as a predictive marker of normal tissue radiosensitivity include the argument that in vitro cellular responses correlate poorly with in vivo responses due to the modifying influence of tissue environment. In this study, we test the hypothesis that a DNA damage assay based on in vivo irradiated skin tissues better predicts clinical responses in human skin, as opposed to the same assay performed in ex vivo irradiated lymphocytes.

Methods
DSB levels (24 h post-4 Gy) were quantified using ãH2AX/53BP1 immunostaining in irradiated skin tissues and G0 lymphocytes of 35 breast RT patients. Patients were selected on the basis of late RT effects in their breast and individuals with marked or minimal effects were classified as cases and controls, respectively. Risk factors of late effects established from multivariate analyses of outcomes of two breast RT trials were also considered in patient selection. They were 1) total RT dose, 2) RT dosimetry, 3) tumour bed boost, 4) breast size, 5) surgical cavity, and 6) axillary treatment.

Results
Clinical parameters were balanced in both patient groups. Residual foci levels in skin epidermis and dermis were comparable between cases (n = 20) and controls (n = 15). Mean foci per cell were 3.29 in cases, 2.80 in controls for dermal fibroblasts (p = 0.07); 3.28 in cases, 2.60 in controls for endothelial cells (p = 0.08); 2.87 in cases, 2.41 in controls for superficial keratinocytes (p = 0.45); 2.32 in cases, 2.35 in controls for basal keratinocytes (p = 0.27). Residual foci levels in lymphocytes were however significantly higher among cases (foci per cell = 12.1) compared to controls (foci per cell = 10.3, p = 0.01). Of the different cell types, only residual foci levels of dermal fibroblasts and lymphocytes correlated with clinical severity (R = 0.722, p < 0.001; 0.593, p = 0.01, respectively). Interestingly, foci levels were not correlated between skin cells and lymphocytes of the same patients.

Conclusions
DSB repair of ex vivo irradiated lymphocytes appears to be a better predictive marker of late effects to breast RT than DSB repair of in vivo irradiated skin.

Identification of Comprehensive Geriatric Assessment based risk factors for malnutrition in elderly Asian cancer patients
Tan TJ1, Ong WS2, Koo KN3, Tan IB1, Poon D4,5, Kanesvaran R1

Background 
Elderly patients with cancer are at increased risk for poor nutrition. Malnutrition is associated with increased morbidity and mortality. There is limited information on the clinical risk factors for malnutrition in elderly Asian cancer patients. We aim to identify comprehensive geriatrics assessment (CGA) based clinical factors in elderly Asian cancer patients associated with an increase in malnutrition risk.

Methods
CGA data was collected from 249 Asian patients aged 70 years or older who attended the outpatient oncology clinics at the National Cancer Centre Singapore. Nutritional status, one of the seven domains of CGA, was assessed based on the DETERMINE nutritional risk index. Univariate and multivariate logistic regression analyses were applied to assess the association between patient clinical factors together with domains within the CGA and moderate to high nutritional risk. Goodness of fit was assessed using Hosmer-Lemeshow test and discrimination ability assessed based on the area under the receiver operating characteristics curve (AUC). Internal validation was performed using simulated datasets via bootstrapping.

Results
Among the 249 patients, 184 (74%) had moderate to high nutritional risk. Multivariate logistic regression analysis identified stage 3–4 disease (Odds Ratio [OR] 2.54; 95% CI, 1.14-5.69), ECOG performance status of 2-4 (OR 3.04; 95% CI, 1.57–5.88), presence of depression as measured by geriatric depression scale (OR 5.99; 95% CI, 1.99-18.02) and haemoglobin levels <12 g/dL (OR 3; 95% CI 1.54-5.84) as significant independent factors associated with moderate to high nutritional risk. The model achieved good calibration (Hosmer-Lemeshow test’s p = 0.17) and discrimination (AUC = 0.80). It retained good calibration and discrimination (bias-corrected AUC = 0.79) under internal validation.

Conclusion
Having advanced stage of cancer, poor performance status, depression and anaemia were found to be independent predictors of moderate to high nutritional risk. Early identification of patients with these risk factors will allow for nutritional interventions which may improve treatment tolerance, quality of life and survival outcomes.

Do elderly patients benefit from enrollment into Phase 1 Trials
Tai WM, Lim C, Ahmad A, Ong WS, Choo SP, Lim WT, Tan EH, Tan DS 

Background
Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. We evaluated the clinical characteristics and outcomes of elderly patients enrolled in phase 1 clinical trials in our centre and evaluated the performance of Royal Marsden Hospital (RMH) prognostic score (albumin, LDH, no of met sites) in this patient population. 

Methods
296 consecutive patients who were treated in 20 phase 1 trials from 2005-2012 in our unit were analysed. Clinical characteristics and outcomes between young pts (<65, n=202) and older patients (≥65, n=94) were compared.

Results
The median age of the older patients was 69 (65-84), 71% were males. 51% of the patients received chemotherapy based treatment with or without biological agents. 65% of the patients had lung cancers and 34% had gastrointestinal cancers. 52% of patients had ≥2 co-morbidities. After median follow up of 7.1 months (0.36-50.6 mths), the median progression free survival (PFS) and overall survival (OS) were 5.8 and 8.8 months respectively. Although elderly patients had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 mths vs 9.9 mths, p=0.68) and clinical benefit rate (69% versus 56%, p=0.07) compared to younger patients. The prognostic factors for OS identified in multivariate analysis were prior lines of chemotherapy (0-2 vs ≥3), baseline sodium levels (≥135 vs <135mmol/L) and platelet levels (≤400 vs >400×10). We developed a risk normogram based on the factors identified prognostic of survival with concordance (c)-index of 0.65. RMH score (2-3 vs 0-1) predicted for survival with hazard ratio of 2.1 (1.1-3.9), p=0.03 and c- index of 0.63. 26% of elderly patients experienced grade 3/4 toxicities. Common grade 3/4 toxicities were dermatological (25%), 17% haematological (17%) and gastrointestinal (13%). There was no treatment related deaths. Both age of patients (p=0.23) and dose levels (p=0.05) did not have any bearing on occurrence of grade 3/4 toxicities.

Conclusion
Elderly patients (>65) enrolled into phase 1 clinical trials had similar survival outcomes and toxicity profiles compared to younger patients. Risk scoring models to aid patient selection need further clarification.