Adlinda Alip

Treatment outcome for head and neck squamous cell carcinoma in a developing country: University Malaya Medical Centre, Malaysia from 2003-2010.

BACKGROUND Head and neck cancer (HNC) is the eighth most common cancer as estimated from worldwide data. The incidence of HNC in Peninsular Malaysia was reported as 8.5 per 100,000 population. This study was aimed to determine the treatment outcomes for HNC patients treated in the Oncology Unit of University Malaya Medical Centre (UMMC). MATERIALS AND METHODS All newly diagnosed patients with squamous cell carcinoma of head and neck (HNSCC) referred for treatment to the Oncology Unit at UMMC from 2003-2010 were retrospectively analyzed. Treatment outcomes were 5-year overall survival (OS), cause specific survival (CSS), loco-regional control (LRC) and radiotherapy (RT) related side effects. Kaplan-Meier and log rank analyses were used to determine survival outcomes, stratified according to American Joint Committee on Cancer (AJCC) stage. RESULTS A total of 130 cases were analysed. Most cases (81.5%) were at late stage (AJCC III-IVB) at presentation. The 5-year OS for the whole study population was 34.4% with a median follow up of 24 months. The 5-year OS according to AJCC stage was 100%, 48.2%, 41.4% and 22.0% for stage I, II, III and IVA-B, respectively. The 5-year overall CSS and LCR were 45.4% and 55.4%, respectively. Late effects of RT were documented in 41.4% of patients. The most common late effect was xerostomia. CONCLUSIONS The treatment outcome of HNSCC at our centre is lagging behind those of developed nations. Efforts to increase the number of patients presenting in earlier stages, increase in the use of combined modality treatment, especially concurrent chemoradiotherapy and implementation of intensity modulated radiotherapy, may lead to better outcomes for our HNC patients.

Prognostic Factors in Patients with Non-small Cell Lung Carcinoma and Brain Metastases: a Malaysian Perspective

BACKGROUND Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma (NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used but increasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomes in NSCLC patients receiving local therapy for brain metastases. MATERIALS AND METHODS The case records of 125 patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres from January 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patients receiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariate testing. RESULTS Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients with multiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3 metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure (yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgery or SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use of post-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All four factors remained statistically significant on multivariate analysis. CONCLUSIONS ECOG ≤2, presence of seizures, oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapy systemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.

Efficacy, safety, and prognostic indicators of first-line sunitinib in patients with metastatic renal cell carcinoma: A single center experience

Background: We assessed the efficacy and safety of sunitinib as the first-line treatment in metastatic renal cell carcinoma (mRCC) patients. The predictors of survival and efficacy in mRCC as identified from previous studies, including the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic RCC Database Consortium (IMDC) factors, were also evaluated. Patients and Methods: Data from 56 patients with mRCC, treated with sunitinib at our institute (2006–2014), were analyzed retrospectively. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated using univariate and multivariate analyses performed by log-rank test and Cox regression. Results: Fifty-one (91.1%) patients received starting dose of sunitinib of 50 mg/day in 4/2 schedule. The median PFS was 12.7 months (95% confidence interval [CI], 4.5–20.9 months) and the median OS was 16.9 months (95% CI, 3.8–29.9 months). The objective response rate was 27.5%. Dose interruption and reduction due to toxicities were required in 37.5% and 60.7% of patients, respectively. The most common Grades 3–4 toxicities were hand-foot syndrome (HFS) (23.2%), thrombocytopenia (16.1%), and hypertension (14.3%). The Eastern Cooperative Oncology Group performance status ≥2, hemoglobin < lower limit of normal, neutrophil > upper limit of normal (ULN), platelet > ULN, no prior nephrectomy, metastatic sites >:1, liver metastases, lymph node metastases, and development of HFS were independent prognostic factors. Conclusions: Sunitinib treatment has acceptable efficacy and safety profile in Malaysian mRCC patients. The MSKCC and IMDC factors are relevant for predicting survival in our patient cohort while HFS is a promising prognostic predictor which warrants further investigation.

Single vs multiple fraction palliative radiotherapy for uncomplicated painful bone metastases treated at University of Malaya Medical Centre: A single institutional Malaysian experience

This study was conducted to compare pain response between single and multiple fraction palliative radiotherapy and to describe prognostic factors affecting treatment response in University of Malaya Medical Centre (UMMC).

Efficacy and safety of pazopanib in advanced renal cell carcinoma treated at University Malaya Medical Centre (UMMC)

Background: Pazopanib is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) that was approved as first line treatment for advanced renal cell carcinoma (aRCC). The pivotal trial showed significant increase in median progression free survival (mPFS) of 9.2 months versus 4.0 months with placebo and objective response rate of 30%. Median overall survival (mOS) was 28.4 months with pazopanib. Local data on efficacy and safety of pazopanib is lacking. This study reviewed the efficacy and safety of pazopanib in aRCC in University Malaya Medical Centre (UMMC). Methods: We retrospectively reviewed outcome of patients with advanced renal cell carcinoma who received pazopanib from January 2012 to March 2017. Analysis was done in July 2017. Results: Twenty-one patients were enrolled – 16 (76.2%) were males and five (23.8%) were females. The mean age at diagnosis was 61.9 years old. Majority of the patients were of Chinese ethnicity, ( n = 13, 61.9%). Fourteen patients (67%) were diagnosed as metastatic disease at presentation and all had cytoreductive nephrectomy. Eighteen patients (86%) had clear cell histology. The most common metastatic site was lung (66.7%) followed by bone and liver. Except for one, all patients were treated with pazopanib in the first line setting. Majority of the patients (76.2%) was started on pazopanib within a year after diagnosis. Fourteen patients (66%) were started on 800 mg daily as the initial dose. From the analysis, the best tumour response is partial response ( n = 8, 38%) followed stable disease ( n = 4, 19%). Six patients (28.6%) had progressive disease while three other patients were not assessable. The mPFS was 9 months (95% CI: 7.2 – 10.8) and mOS was 24 months. For toxicity analysis, only 17 patients had side-effects documented in our database. The most common side effects were hypertension (19%) and hand-foot syndrome (19%) followed by diarrheoa (14.3%). Conclusions: In general, pazopanib is well tolerated and demonstrated good PFS and OS in our study population, comparable to previous studies and real-world data.

Determinants of adherence to therapies among Malaysian women with breast cancer: MyBCC Cohort

Background: Breast cancer therapies have been progressively advancing to improve the breast cancer survival over the last few decades. However, non-adherence to cancer treatments has shown to be associated with reduced treatment effectiveness, increased mortality, and increased health care costs. The aim of the study is to understand the determinants of adherence to therapies among Malaysian breast cancer patients. Methods: This was a secondary analysis of all newly diagnosed Malaysian breast cancer patients recruited into a prospective cohort study in Universiti Malaya Medical Centre, MyBCC cohort, from 1st February 2012 to 31st December 2015. The MyBCC cohort study has ethics approval, MEC number 896.150. The treatment options (surgery, chemotherapy, radiotherapy, and overall therapies), surgical options, socio-demographic characteristics, clinical signs and symptoms, traditional and complementary medicine, and psychosocial assessments were measured using Hospital Anxiety and Depression Scale (HADS) and Multidimensional Scale of Perceived Social Support (MSPSS). Results: In total, 467 patients were analysed. The adherence to surgery was 93.8%, chemotherapy 87.7%, radiotherapy 89.1%, and overall therapies 65.8% respectively. Breast conserving surgery was associated with adherence to surgery compared to mastectomy (adjusted OR 5.48 [95% CI 1.00, 30.09], p = 0.034), radiotherapy (adjusted OR 5.44 [95% CI 1.17, 25.16], p = 0.030) and overall therapies (adjusted OR 2.45 [95% CI 1.04, 5.78], p = 0.041). Time from diagnosis to surgery of less than 60 days was associated with adherence to surgery (adjusted OR 49.98 [95% CI 8.47, 289.05], p less than 0.0001) and overall therapies (adjusted OR 9.38 [95% CI 1.26, 69.73], p = 0.029). Adherence to chemotherapy associated with no surgery (adjusted OR 0.15 [95% CI 0.03, 0.70], p = 0.016). Adherence to radiotherapy was associated with financial reimbursement (adjusted OR 4.34 [95% CI 1.03, 18.26], p = 0.045) and adherence to chemotherapy (adjusted OR 0.01 [95% CI 0.00, 0.04], p less than 0.0001). Conclusion: The study demonstrated excellent adherence to breast cancer surgery management. Surgical options and time from diagnosis to surgery affect the adherence to surgery and the systemic treatments. Financial reimbursement and adherence to chemotherapy were predictors of adherence to radiotherapy. Timely surgery and financial resource remain major contributor to treatment adherence. CAM and psychosocial factors did not contribute to treatment adherence in this study. This study was supported by postgraduate research grant from University Malaya. MEC number 896.150.

Risk of Treatment Related Death and Febrile Neutropaenia with First Line Palliative Chemotherapy for De Novo Metastatic Breast Cancer in Clinical Practice in a Middle Resource Country

BACKGROUND The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). MATERIALS AND METHODS Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature >38.5° or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test. RESULTS Between 1st January 2002 and 31st December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319). CONCLUSIONS In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

Capecitabine Pattern of Usage, Rate of Febrile Neutropaenia and Treatment Related Death in Asian Cancer Patients in Clinical Practice

BACKGROUND Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). MATERIALS AND METHODS We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from 1st January 2009 till 31st June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature >38.5°or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. RESULTS Between 1st January 2009 and 30th June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. CONCLUSIONS Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.