PRINCIPAL FINDINGS: The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h), terminal phase half-life (13.6 h) and systemic bioavailability (41.9%) of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively). Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5%) compared to that of the phospholipase A2 (Fi.m.=68.6%) or cardiotoxin (Fi.m.=45.6%). The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.
CONCLUSION/SIGNIFICANCE: Our results suggest that the venom neurotoxin is absorbed very rapidly and has the highest bioavailability following intramuscular injection, supporting its role as the principal toxin in systemic envenoming.
MATERIALS AND METHODS: Data from 10 consecutive patients treated with IMRT from June-October 2011 in Penang General Hospital were collected retrospectively for analysis. For each patient, dose volume histograms were generated for both the IMRT and 3DCRT plans using a total dose of 70Gy. Comparison of the plans was accomplished by comparing the target volume coverage (5 measures) and sparing of organs at risk (17 organs) for each patient using both IMRT and 3DCRT. The means of each comparison target volume coverage measures and organs at risk measures were obtained and tested for statistical significance using the paired Student t-test.
RESULTS: All 5 measures for target volume coverage showed marked dosimetric superiority of IMRT over 3DCRT. V70 and V66.5 for PTV70 showed an absolute improvement of 39.3% and 24.1% respectively. V59.4 and V56.4 for PTV59.4 showed advantages of 18.4% and 16.4%. Moreover, the mean PTV70 dose revealed a 5.1 Gy higher dose with IMRT. Only 4 out of 17 organs at risk showed statistically significant difference in their means which were clinically meaningful between the IMRT and 3DCRT techniques. IMRT was superior in sparing the spinal cord (less 5.8Gy), V30 of right parotid (less 14.3%) and V30 of the left parotid (less 13.1%). The V55 of the left cochlea was lower with 3DCRT (less 44.3%).
CONCLUSIONS: IMRT is superior to 3DCRT due to its dosimetric advantage in target volume coverage while delivering acceptable doses to organs at risk. A total dose of 70Gy with IMRT should be considered as a standard of care for radical treatment of NPC.
METHODS: This retrospective study covered all NPC patients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February 2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Information was collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/or concurrent chemotherapy, acute toxity and completion of IMRT within the OTT.
RESULTS: A total of 26 NPC patients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% received neo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed the treatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade 2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis (57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in 19.2%. However, haematological toxicity was mild with only one patient having leucopaenia.
CONCLUSION: IMRT treatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT in the majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional and analgesic support is required throughout the treatment.