Camelia Herdini

Primary Treatment Results of Nasopharyngeal Carcinoma (NPC) in Yogyakarta, Indonesia

Introduction Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia. Methods All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment. Results In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18–35) from day of diagnosis. Conclusion The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.

Can an online clinical data management service help in improving data collection and data quality in a developing country setting

BackgroundData collection by Electronic Medical Record (EMR) systems have been proven to be helpful in data collection for scientific research and in improving healthcare. For a multi-centre trial in Indonesia and the Netherlands a web based system was selected to enable all participating centres to easily access data. This study assesses whether the introduction of a Clinical Trial Data Management service (CTDMS) composed of electronic Case Report Forms (eCRF) can result in effective data collection and treatment monitoring.MethodsData items entered were checked for inconsistencies automatically when submitted online. The data were divided into primary and secondary data items. We analysed both the total number of errors and the change in error rate, for both Primary and Secondary items, over the first five month of the trial.ResultsIn the first five months 51 patients were entered. The Primary data error rate was 1.6%, whilst that for Secondary data was 2.7% against acceptable error rates for analysis of 1% and 2.5% respectively.ConclusionThe presented analysis shows that after five months since the introduction of the CTDMS the Primary and Secondary data error rates reflect acceptable levels of data quality. Furthermore, these error rates were decreasing over time. The digital nature of the CTDMS, as well as the online availability of that data, gives fast and easy insight in adherence to treatment protocols. As such, the CTDMS can serve as a tool to train and educate medical doctors and can improve treatment protocols.

A Prospective Study: Current Problems in Radiotherapy for Nasopharyngeal Carcinoma in Yogyakarta, Indonesia

Introduction Nasopharyngeal carcinoma (NPC) has a high incidence in Indonesia. Previous study in Yogyakarta revealed a complete response of 29% and a median overall survival of less than 2 years. These poor treatment outcome are influenced by the long diagnose-to-treatment interval to radiotherapy (DTI) and the extended overall treatment time of radiotherapy (OTT). This study reveals insight why the OTT and DTI are prolonged. Method All patients treated with curative intent radiotherapy for NPC between July 2011 until October 2012 were included. During radiotherapy a daily diary was kept, containing information on DTI, missed radiotherapy days, the reason for missing and length of OTT. Results Sixty-eight patients were included. The median DTI was 106 days (95% CI: 98−170). Fifty-nine patients (87%) finished the treatment. The median OTT for radiotherapy was 57 days (95% CI: 57–65). The main reason for missing days was an inoperative radiotherapy machine (36%). Other reasons were patient’s poor condition (21%), public holidays (14%), adjustment of the radiation field (7%), power blackout (3%), inoperative treatment planning system (2%) and patient related reasons (9%). Patient’s insurance type was correlated to DTI in disadvantage for poor people. Conclusion Yogyakarta has a lack of sufficient radiotherapy units which causes a delay of 3–4 months, besides the OTT is extended by 10–12 days. This influences treatment outcome to a great extend. The best solution would be creating sufficient radiotherapy units and better management in health care for poor patients. The growing economy in Indonesia will expectantly in time enable these solutions, but in the meantime solutions are needed. Solutions can consist of radiation outside office hours, better maintenance of the facilities and more effort from patient, doctor and nurse to finish treatment in time. These results are valuable when improving cancer care in low and middle income countries.

Photodynamic therapy as salvage therapy for patients with nasopharyngeal carcinoma experiencing local failures following definitive radiotherapy

BACKGROUND Treating local failures of nasopharyngeal carcinoma (NPC) is a challenge. This study evaluates photodynamic therapy (PDT) in the treatment of residual and recurrent NPC. METHOD In this phase II study, patients with local recurrent or residual NPC after curative intent (chemo-) radiation could be included. Exclusion criterion was a tumour depth more than 10mm. Foscan® 0.15mg/kg was administered intravenously. After 96h, the illumination was performed under local anaesthesia with a nasopharyngeal light applicator. Tumour response was measured 10 weeks after illumination by endoscopy, biopsy and CT-scan. Kaplan-Meier method was used for survival analysis. RESULTS Twenty-one patients were included. Fourteen patients were treated for residual disease (67%), and two for recurrent (10%). For five patients this distinction could not be made, due to uncertainty about complete response after initial treatment. The median follow-up time was 32 months. Twenty patients (95%) had a complete response 10 weeks post-treatment. Two patients had recurrent local disease at 5 and 7 months post-PDT. They received another course of PDT, one with success. The 2-year local control rate was 75%, progression free survival was 49% and overall survival was 65%. Nine patients (43%) had no evidence of disease and were in a good clinical condition (ECOG Performance Scale 0) at the end of the study period. No serious adverse events were observed. CONCLUSION This study showed that PDT is effective in treating local failures of NPC with a depth of less than 10mm. The treatment was easy to perform under local anaesthesia. Especially in regions were other modalities like radiation and surgery are limited PDT can be a good alternative treatment.

Remarkable response to photodynamic therapy in residual T4N0M0 nasopharyngeal carcinoma: A case report

Local treatment of residual or recurrent nasopharyngeal carcinoma (NPC) is a challenge. Photodynamic therapy (PDT) is an established treatment modality for incurable head and neck carcinoma. Several studies reported induction of an immune response after PDT. We present a patient with residual T4N0M0 NPC who was treated with PDT for residual disease after initial treatment with neo-adjuvant chemotherapy and radiotherapy. Five years after PDT, the tumor did not progress and the patient is still in good condition. We discuss this remarkable long-term response to PDT and speculate on possible mechanisms.

Seroreactivity against Epstein-Barr virus (EBV) among first-degree relatives of sporadic EBV-associated nasopharyngeal carcinoma in Indonesia

Epstein–Barr virus (EBV) infection and family history are significant risk factors associated with undifferentiated nasopharyngeal carcinoma. The presence of aberrant immunoglobulin A (IgA) antibodies against specific EBV antigens in healthy individuals can be predictive of the disease. Very limited reports explored the EBV IgA antibody presence within families of sporadic cases of nasopharyngeal carcinoma. This study aimed to determine whether EBV IgA was observed more frequently among family members of sporadic cases of nasopharyngeal carcinoma compared to community controls and evaluated the non‐viral factors as determinants of antibody level. First‐degree relatives of nasopharyngeal carcinoma patients (n = 520) and case‐matched community controls (n = 86) were recruited. Sera from all individuals were tested in standardized peptide‐based EBV IgA ELISA. Data on demographic variables and other exogenous factors were collected using a questionnaire through face‐to‐face interviews. A similar frequency of EBV IgA (cut‐off value/CoV 0.354) was observed in the first‐degree relatives of cases and in community controls (41.2% vs. 39.5%, P = 0.770). However, with a higher antibody level (OD450 = 1.000; about three times standard CoV), the relatives showed significantly higher frequency (36.9% vs. 14.7%, P = 0.011). When adjusted for all exogenous factors, the strongest factors associated with seropositivity are being a father (odds ratio/OR = 4.36; 95% confidence interval/CI = 1.56–12.21) or a sibling (OR = 1.89; 95% CI = 1.06–3.38) of a case of nasopharyngeal carcinoma. The higher level of EBV IgA seroreactivity in first‐degree relatives of sporadic cases of nasopharyngeal carcinoma compared to the general population supports the use of EBV IgA ELISA for screening among family members. J. Med. Virol. 84:768–776, 2012.

The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with Nasopharyngeal Carcinoma; A Retrospective Study

Purpose In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored. Methods In this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS). Results The median WT was 117 days (range 12–581) and OTT was 58 days (43–142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log- WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09–2.61), LRC (HR 1.66; 95% ci: 1.15–2.39), and DFS (HR 1.4; 95% ci: 1.09–1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn’t received concurrent chemotherapy. Conclusion Not receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient’s physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors.

Effectiveness of a multicentre nasopharyngeal carcinoma awareness programme in Indonesia

Objective To evaluate the effectiveness of a nasopharyngeal carcinoma (NPC) awareness programme on the short-term and long-term improvement of knowledge and referral of patients with NPC by primary healthcare centres (PHCCs) staff in Indonesia. Design The NPC awareness programme consisted of 12 symposia including a Train-The-Trainer component, containing lectures about early symptoms and risk factors of NPC, practical examination and the referral system for NPC suspects. Before and after training participants completed a questionnaire. The Indonesian Doctors Association accredited all activities. Participants 1 representative general practitioner (GP) from each PHCC attended an NPC awareness symposium. On the basis of the Train-The-Trainer principle, GPs received training material and were obligated to train their colleagues in the PHCC. Results 703 GPs attended the symposia and trained 1349 staff members: 314 other GPs, 685 nurses and 350 midwives. After the training, respondents’ average score regarding the knowledge of NPC symptoms increased from 47 points (of the 100) to 74 points (p<0.001); this increase was similar between symposium and Train-The-Trainer component (p=0.88). At 1½ years after the training, this knowledge remained significantly increased at 59 points (p<0.001). Conclusions The initial results of this NPC awareness programme indicate that the programme effectively increases NPC knowledge in the short and long term and therefore should be continued. Effects of the improved knowledge on the stage at diagnoses of the patients with NPC will still need to be scrutinised. This awareness programme can serve as a blueprint for other cancer types in Indonesia and for other developing countries.

1368PSEROREACTIVITY AGAINST EPSTEIN-BARR VIRUS (EBV) IN FAMILY MEMBERS OF EBV-ASSOCIATED NASOPHARYNGEAL CARCINOMA AND NON-FAMILY INDIVIDUALS

ABSTRACT Aim: Epstein-Barr virus (EBV) infection and family history are strong risk factors associated with undifferentiated nasopharyngeal carcinoma (NPC). The presence of aberrant immunoglobulin A (IgA) antibodies against specific EBV antigens in healthy individuals can be predictive of the disease. Unlike in familial NPC, very limited reports have explored the EBV IgA antibody presence within families of sporadic cases of NPC.The aim of this study is to determine whether EBV IgA was more frequently observed among healthy family members of sporadic cases of NPC compared to healthy non-family individuals. Methods: First-degree relatives of NPC patients (n = 508) were recruited in a home visite program. Non-family individuals (n= 284) were recruited from Yogyakarta blood bank. Sera from all individuals were tested in standardized peptide-based EBV IgA ELISA and a positive result of seroreactivity was defined as OD450 >0.354, being the cutt-of value (CoV). Data on demographic variables were collected using a questionnaire through face-to-face interviews. Results: A total of 280 (35.4%) individuals showed seroreactivity of EBV IgA. A significant higher frequency was observed in the first-degree relatives of NPC cases than in non-family individuals (41.9% versus 21.2%, p Conclusions: Family members of NPC cases demonstrated higher level of EBV IgA seroreactivity compared to non-family individuals, implicating a suitability of screening program among this group. Disclosure: All authors have declared no conflicts of interest.