IDENTIFICATION OF NOVEL BIOMARKERS FOR LUNG CANCER RISK IN HIGH LEVELS OF RADON BY PROTEOMICS: A PILOT STUDY.

Radon is the second most important risk factor for lung cancer after tobacco smoking. In Chiang Mai, Thailand, the values of indoor radon activity concentrations are considerably higher than global average values and it is a highest level among East Asian countries. The aim of our study is to identify novel biomarkers for lung cancer risk in high radon areas using a proteomic approach. In our transitional study, a total of 81 participants of non-smokers were examined, consist of 25 lung cancer patients (LC), 16 healthy controls from low levels of natural radiation areas (LLNRA) and 40 healthy controls from high levels of natural radiation areas (HLNRA). The results showed that a total of 799 differentially expressed proteins were identified. Among these, a total of 25 proteins were observed in both LC and HLNRA, but not in LINRA. Owing to the results obtained from this study, we also point out the research direction regarding the validation of some new candidate protein as a biomarker to screen population with high risk for lung cancer in the area with high levels of radon.

Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines.

Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.

A phase II study of oxaliplatin with 5-FU/folinic acid and concomitant radiotherapy as a preoperative treatment in patients with locally advanced rectal cancer.

OBJECTIVE: To evaluate the activity and safety of adding oxaliplatin to a standard chemoradiotherapy schema, including 5-fluorouracil (5-FU)/folinic acid (FA), in locally-advanced rectal cancer (LARC). METHODS: Two cycles of oxaliplatin 130 mg/m(2) plus FA 20 mg/m(2) bolus for 5 days and 5-FU 350 mg/m(2) continuous infusion for 5 days were given during week 1 and 4 of pelvic radiotherapy 46 Gy. Patients with a T3/4 and/or node-positive rectal tumour were eligible. Surgery was performed 4-6 weeks after radiotherapy. The primary endpoint was to determine the rate of pathological response. Secondary endpoints were to assess the rate of clinical response and the safety profile. RESULTS: Between March 2005 and January 2009, a total of 35 patients were enrolled. The pathological down-staging rate was 79% with a pathological complete response rate of 17%. The overall clinical response rate (assessed by computed tomography or transrectal ultrasound) was 77%. Grade 3 diarrhoea and Grade 3 neutropaenia were reported in 14% and 11% of the patients, respectively. Eleven patients did not undergo surgery: four of them refused the operation, and seven patients were inoperable due to disease progression. In 24 patients who had surgery, a sphincter-preserving procedure could be performed in 29%. At the median follow-up time of 28.1 months, 25 patients (71%) survived with no evidence of disease. CONCLUSION: The promising results in terms of pathological response, and the associated good safety profile of a regimen of oxaliplatin plus 5-FU/FA with concomitant radiotherapy, suggest that the regimen could be used in LARC.

A phase II study of oxaliplatin with 5-FU/folinic acid and concomitant radiotherapy as a preoperative treatment in patients with locally advanced rectal cancer

Objective: To evaluate the activity and safety of adding oxaliplatin to a standard chemoradiotherapy schema, including 5-fluorouracil (5-FU)/folinic acid (FA), in locally-advanced rectal cancer (LARC). Methods: Two cycles of oxaliplatin 130 mg/m2 plus FA 20 mg/m2 bolus for 5 days and 5-FU 350 mg/m2 continuous infusion for 5 days were given during week 1 and 4 of pelvic radiotherapy 46 Gy. Patients with a T3/4 and/or node-positive rectal tumour were eligible. Surgery was performed 4–6 weeks after radiotherapy. The primary endpoint was to determine the rate of pathological response. Secondary endpoints were to assess the rate of clinical response and the safety profile. Results: Between March 2005 and January 2009, a total of 35 patients were enrolled. The pathological downstaging rate was 79% with a pathological complete response rate of 17%. The overall clinical response rate (assessed by computed tomography or transrectal ultrasound) was 77%. Grade 3 diarrhoea and Grade 3 neutropaenia were reported in 14% and 11% of the patients, respectively. Eleven patients did not undergo surgery: four of them refused the operation, and seven patients were inoperable due to disease progression. In 24 patients who had surgery, a sphincter-preserving procedure could be performed in 29%. At the median follow-up time of 28.1 months, 25 patients (71%) survived with no evidence of disease. Conclusion: The promising results in terms of pathological response, and the associated good safety profile of a regimen of oxaliplatin plus 5-FU/FA with concomitant radiotherapy, suggest that the regimen could be used in LARC.

Induction chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by concurrent chemoradiotherapy for unresectable locally advanced head and neck cancer.

OBJECTIVE: Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) for locally advanced head and neck cancer has been studied in many clinical trials. This study was conducted to determine the response rate of IC with paclitaxel, ifosfamide, and cisplatin followed by CCRT with cisplatin for this group of patients, and the effect of the entire treatment on survival and time to disease progression. METHODS: Thirty patients with advanced and unresectable head and neck cancer were treated with 2 cycles of induction paclitaxel/ ifosfamide/ cisplatin. If the primary tumor had a complete or partial response, patients were treated with 2 more cycles of IC followed by radiotherapy 70 Gy plus 3 cycles of cisplatin. For those with less than partial response or disease progression were treated according to the discretion of the physicians. RESULTS: Ninety percent of patients had stage IV disease and 40% of them had primary tumor at maxillary sinus and nasal cavity. One patient (3%) achieved complete response (CR) and 18 patients had partial responses (PR) to IC. CCRT enhanced the response rate, resulting in a total of 3 CR (10%) and 16 PR (53%) to treatment. The median time to progression was 11.5 months. The median overall survival was 27 months. The most severe hematologic toxicity occurred during IC was grade3-4 neutropenia (40%). Grade 3-4 mucositis occurred in 68% of patients during CCRT. CONCLUSION: This novel combined-modality treatment program, is toxic but feasible, and can be administered for selected patients with advanced and unresectable head and neck cancer. © 2010 Biomedical Imaging and Intervention Journal. All rights reserved.

Can radiographic plain film be used to determine the depth of the tumour bed in the absence of surgical clips for breast boost planning.

PURPOSE: A number of studies have demonstrated the importance of using surgical clips to define the tumour bed in breast boost radiotherapy. In the absence of such clips, other techniques suggested to improve boost location have included CT and ultrasound (US). Determination of the depth of the tumour bed is important in the selection of electron energy. This study was conducted to prospectively compare the depth of the lumpectomy cavity as defined by ultrasound to radiographic plain film evaluation of the anterior border of the pectoralis muscle. MATERIALS AND METHODS: Forty-one breast-cancer patients treated at the Division of Therapeutic Radiology and Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University between December 2004 and December 2006 were prospectively identified as having no surgical clips within the lumpectomy cavity. All patients underwent both US evaluation of the depth of tumour bed (D1) and radiographic evaluation of the depth of the anterior border of the pectoralis muscle (D2). These depth dimensions (D1 and D2) were compared using a paired t-test. The correlation of both methods was analyzed by Pearson correlation test. RESULTS: Depth dimensions by US were shorter than the radiographic film method in 85% of patients. The absolute mean difference of the depth (radiographic films minus US) was 0.129 cm. A paired t-test demonstrated that the difference between these two methods to be not statistically significant (p= 0.27). The absolute difference of depth between the two methods ranged from 0 to 0.5 cm. A significant correlation was found between US and radiographic film measurements (p<0.01). CONCLUSION: Plane radiographic film evaluation of the anterior border of the pectoralis muscle can be used to define the depth of the tumour bed in patients who have no surgical clips. However, the plane radiographic film method determines only the depth, not the transverse and longitudinal dimensions of the tumour bed. Additional information from US is needed to delineate the target volume for the tumour bed boost. In the absence of surgical clips, the authors recommend integration of both methods in breast boost planning process.

Analysis of 587 cases of oral squamous cell carcinoma in northern Thailand with a focus on young people.

The increasing incidence of oral squamous cell carcinoma (SCC) especially among younger people has been observed in many parts of the world. The objective of this study was to delineate the profile of patients with oral SCC with an emphasis on younger people in northern Thailand between 1991-2000. The medical records of 587 (median age 65, male-to-female ratio 1:3:1) patients presenting oral SCC were reviewed, with details of demographic data, staging, histological grading, treatment modality and risk factor profile being collated in detail. Seventy-five patients (12.8%) were 45 years of age or below (median age, 39 years). Most patients regardless of age had stage IV disease (56.2%). The most common histological gradings were well or moderately differentiated SCC (79.4%). The most common site regardless was tongue (42.8%). Most patients (79.4%) received treatments with either radiotherapy alone or a combination of surgery and radiotherapy. 64.4% of patients (87.2%) did not have a familial history of cancer. Collectively this data indicates that oral SCC remains a constant problem to the northern Thai population. In addition, the occurrence of oral SCC in young people is relatively high. Therefore, it is recommended that prevention of oral SCC with early detection, early treatment intervention, and withdrawal from risk habits are important factors for improving the wellbeing of these people.

High-dose-rate afterloading brachytherapy in carcinoma of the cervix: an experience of 1992 patients.

PURPOSE: To report the results of radiation therapy in carcinoma of the cervix treated by external irradiation and high-dose-rate (HDR) intracavitary brachytherapy. METHODS AND MATERIALS: This is a retrospective analysis of 2,063 patients with histologically proven carcinoma of the cervix treated by external irradiation and HDR intracavitary brachytherapy between March 1985-December 1991. The Kaplan-Meier method was used for survival and disease-free survival analysis. Late complications in the bowel and bladder were calculated actuarially. RESULTS: There were 71 patients who did not complete the course of irradiation so only 1992 patients were retrospectively analyzed for survival. There were 2 patients (0.1%) in Stage IA, 211 (10.2%) Stage IB, 225 (10.9%) in Stage IIA, 902 (43. 7%) in Stage IIB, 14 (0.7%) in Stage IIIA, 675 (32.7%) in Stage IIIB, 16 (0.8%) in Stage IVA, and 16 (0.8%) in Stage IVB. The median follow-up time was 96 months. The actuarial 5-year disease-free survival rate was 79.5%, 70.0%, 59.4%, 46.1%, 32.3%, 7.8%, and 23.1% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. The actuarial 5-year disease-free survival rate for Stage IB(1) and IB(2) squamous cell carcinoma was 88.7% and 67.0%. The actuarial 5-year overall survival rate was 86.3%, 81.1%, 73.0%, 50.3%, 47.8%, 7.8%, and 30.8% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. Pattern of failure revealed 20.8% local recurrence, 18. 7% distant metastases, and 4% in both. The late complication rate Grade 3 and 4 (RTOG) for bowel and bladder combined was 7.0% with 1. 9% Grade 4. CONCLUSION: HDR brachytherapy used in this series produced pelvic control and survival rates comparable to other LDR series.