On the Use of Optically Stimulated Luminescent Dosimeter for Surface Dose Measurement during Radiotherapy.

This study was carried out to investigate the suitability of using the optically stimulated luminescence dosimeter (OSLD) in measuring surface dose during radiotherapy. The water equivalent depth (WED) of the OSLD was first determined by comparing the surface dose measured using the OSLD with the percentage depth dose at the buildup region measured using a Markus ionization chamber. Surface doses were measured on a solid water phantom using the OSLD and compared against the Markus ionization chamber and Gafchromic EBT3 film measurements. The effect of incident beam angles on surface dose was also studied. The OSLD was subsequently used to measure surface dose during tangential breast radiotherapy treatments in a phantom study and in the clinical measurement of 10 patients. Surface dose to the treated breast or chest wall, and on the contralateral breast were measured. The WED of the OSLD was found to be at 0.4 mm. For surface dose measurement on a solid water phantom, the Markus ionization chamber measured 15.95% for 6 MV photon beam and 12.64% for 10 MV photon beam followed by EBT3 film (23.79% and 17.14%) and OSLD (37.77% and 25.38%). Surface dose increased with the increase of the incident beam angle. For phantom and patient breast surface dose measurement, the response of the OSLD was higher than EBT3 film. The in-vivo measurements were also compared with the treatment planning system predicted dose. The OSLD measured higher dose values compared to dose at the surface (Hp(0.0)) by a factor of 2.37 for 6 MV and 2.01 for 10 MV photon beams, respectively. The measurement of absorbed dose at the skin depth of 0.4 mm by the OSLD can still be a useful tool to assess radiation effects on the skin dermis layer. This knowledge can be used to prevent and manage potential acute skin reaction and late skin toxicity from radiotherapy treatments.

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.

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.

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.

CT based 3-dimensional treatment planning of intracavitary brachytherapy for cancer of the cervix: comparison between dose-volume histograms and ICRU point doses to the rectum and bladder.

BACKGROUND: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT). MATERIALS AND METHODS: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6 Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose (DMax) to rectum was the highest recorded dose at one of these five points. Using the HDR plus 2.6 brachytherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded (D2cc) for all individual fractions. The mean D2cc of rectum was compared to the means of ICRU rectal point and rectal DMax using the Student's t-test. The mean D2cc of bladder was compared with the mean ICRU bladder point using the same statistical test .The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (α/ß value of 10 Gy for target, 3 Gy for organs at risk). RESULTS: The total prescribed dose was 77.5 Gy α/ß10. The mean dose to the rectum was 4.58 ± 1.22 Gy for D 2cc, 3.76 ± 0.65 Gy at D ICRU and 4.75 ± 1.01 Gy at DMax. The mean rectal D 2cc dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48 -1.19 Gy). The mean EQD2 was 68.52 ± 7.24 Gy α/ß3 for D 2cc, 61.71 ± 2.77 Gy α/ß3 at D ICRU and 69.24 ± 6.02 Gy α/ß3 at DMax. The mean ratio of D 2cc rectum to D ICRU rectum was 1.25 and the mean ratio of D 2cc rectum to DMax rectum was 0.98 for all individual fractions. The mean dose to the bladder was 6.00 ± 1.90 Gy for D 2cc and 5.10 ± 2.03 Gy at D ICRU. However, the mean D 2cc dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25 Gy). The mean EQD2 was 81.85 ± 13.03 Gy α/ß3 for D 2cc and 74.11 ± 19.39 Gy α/ß3 at D ICRU. The mean ratio of D 2cc bladder to D ICRU bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose. CONCLUSIONS: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder point may be a reasonable surrogate for the D 2cc and rectal DMax for D 2cc. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the D 2cc.

Treatment outcome with brachytherapy for recurrent nasopharyngeal carcinoma.

BACKGROUND: To evaluate the treatment outcome and major late complications of all patients with recurrent nasopharyngeal carcinoma (NPC) treated with intracavitary brachytherapy (ICBT) in Hospital Kuala Lumpur. MATERIALS AND METHODS: This retrospective study was conducted at the Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Malaysia. All patients with histologically confirmed recurrent NPC in the absence of distant metastasis treated in the period 1997-2010 were included in this study. These patients were treated with ICBT alone or in combination with external beam radiotherapy (EBRT). Treatment outcomes measured were local recurrence free survival (LRFS), disease free survival (DFS) and overall survival (OS). RESULTS: Thirty three patients were eligible for this study. The median age at recurrence was 56 years with a median time to initial local recurrence of 27 months. Majority of patients were staged as rT1-2 (94%) or rN0 (82%). The proportion of patients categorised as stage III-IV at first local recurrence was only 9%. Twenty one patients received a combination of ICBT and external beam radiotherapy while 12 patients were treated with ICBT alone. Median interval of recurrence post re-irradiation was 32 months (range: 4-110 months). The median LRFS, DFS and OS were 30 months, 29 months and 36 months respectively. The 5 year LRFS, DFS and OS were 44.7%, 38.8% and 28.1% respectively. The N stage at recurrence was found to be a significant prognostic factor for LRFS and DFS after multivariate analysis. Major late complications occurred in 34.9% of our patients. CONCLUSIONS: Our study shows ICBT was associated with a reasonable long term outcome in salvaging recurrent NPC although major complications remained a significant problem. The N stage at recurrence was a significant prognostic factor for both LRFS and DFS.

Preoperative long course chemoirradiation in a developing country for rectal carcinoma: Kuala Lumpur hospital experience.

BACKGROUND: The use of preoperative chemoirradiation is the commonest treatment strategy employed in Malaysia for locally advanced rectal cancer. We need to determine the local control and survival rates for comparison with established rates in the literature. MATERIALS AND METHODS: This retrospective study analyzed all newly diagnosed patients with rectal adenocarcinoma who underwent long course preoperative radiotherapy (RT) at the Department of Radiotherapy and Oncology, Kuala Lumpur Hospital (HKL) between 1st January 2004 and 31st December 2010. The aim of the study was to determine the radiological response post radiotherapy, pathological response including circumferential resection margin (CRM) status, 3 years local control, 3 years overall survival (OS) and 3 years disease free survival (DFS). Statistical analysis was performed using the SPSS software. Kaplan-Meier and log rank analysis were used to determine survival outcomes. RESULTS: A total of 507 patients with rectal cancer underwent RT at HKL. Sixty seven who underwent long course preoperative RT were eligible for this study. The median age at diagnosis was 60 years old with a range of 26-78 years. The median tumour location was 6 cm from the anal verge. Most patients had suspicion of mesorectum involvement (95.5%) while 28.4% of patients had enlarged pelvic nodes on staging CT scan. All patients underwent preoperative chemo-irradiation except for five who had preoperative RT alone. Only 38 patients underwent definitive surgery (56.7%). Five patients were deemed to be inoperable radiologically and 3 patients were found to have unresectable disease intraoperatively. The remaining 21 patients defaulted surgery (31.3%). The median time from completion of RT to surgery was 8 weeks (range 5.6 to 29.4 weeks). Fifteen patients (39.5%) had surgery more than 8 weeks after completion of RT. Complete pathological response was noted in 4 patients (10.5%). The pathological CRM positive rate after RT was 18.4%. With a median follow-up of 38.8 months, the 3 year local control rate was 67%. The 3 years rate for CRM positive (<2 mm), CRM clear (>2 mm) and pCR groups were 0%, 88.1% and 100% respectively (p-value of 0.007). The 3 year OS and DFS were 57.3% and 44.8% respectively. CONCLUSIONS: In conclusion, the approach of long course preoperative chemoirradiation for rectal cancer needs to be re-examined in our local setting. The high rate of local recurrence is worrying and is mainly due to patient defaulting post-preoperative chemoirradiation or delayed definitive surgery.