Yaowalak Chansilpa

Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients.

BackgroundSensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear.MethodsA retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as > 15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA.ResultsMedian audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of > 50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p = 0.047).ConclusionIMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.

Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: A prospective randomized trial of the International Atomic Energy Agency

AbstactBackgroundThe purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy.MethodsPatients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR – 11 Gy) or high dose-rate (HDR – 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3–4 adverse events.Results274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67 patients) (p = 0.343). The grade 3–4 toxicity rate was 21.6% (30/139) and 24.4% (33/135) respectively (p = 0.687).ConclusionsThe addition of a brachytherapy boost to external beam radiotherapy and chemotherapy did not improve outcome in loco-regionally advanced nasopharyngeal carcinoma.

Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

PURPOSE To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. METHODS AND MATERIALS Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m(2)) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. RESULTS Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. CONCLUSIONS The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

Multi-Institutional Phase II Clinical Study of Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer in East and Southeast Asia

PURPOSE To evaluate the toxicity and efficacy of concurrent chemoradiotherapy using weekly cisplatin for patients with locally advanced cervical cancer in East and Southeast Asia, a multi-institutional Phase II clinical study was conducted among eight Asian countries. METHODS AND MATERIALS Between April 2003 and March 2006, 120 patients (60 with bulky Stage IIB and 60 with Stage IIIB) with previously untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiotherapy consisted of pelvic external beam radiotherapy (total dose, 50 Gy) and either high-dose-rate or low-dose-rate intracavitary brachytherapy according to institutional practice. The planned Point A dose was 24-28 Gy in four fractions for high-dose-rate-intracavitary brachytherapy and 40-45 Gy in one to two fractions for low-dose-rate-intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m(2)) were administered during the radiotherapy course. RESULTS All patients were eligible for the study. The median follow-up was 27.3 months. Of the 120 patients, 100 (83%) received four or five cycles of chemotherapy. Acute Grade 3 leukopenia was observed in 21% of the patients, and Grade 3 gastrointestinal toxicity was observed in 6%. No patient failed to complete the radiotherapy course because of toxicity. The 2-year local control and overall survival rate for all patients was 87.1% and 79.6%, respectively. The 2-year major late rectal and bladder complication rate was 2.5% and 0%, respectively. CONCLUSION The results have suggested that concurrent chemoradiotherapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Advanced imaging applications for locally advanced cervical cancer.

Advanced imaging approaches (computed tomography, CT; magnetic resonance imaging, MRI; 18F-fluorodeoxyglucose positron emission tomography, FDG PET) have increased roles in cervical cancer staging and management. The recent FIGO (International Federation of Gynecology and Obstetrics) recommendations encouraged applications to assess the clinical extension of tumors rather than relying on clinical examinations and traditional non-cross sectional investigations. MRI appears to be better than CT for primary tumors and adjacent soft tissue involvement in the pelvis. FDG-PET/CT has increased in usage with a particular benefit for whole body evaluation of tumor metabolic activity. The potential benefits of advanced imaging are assisting selection of treatment based upon actual disease extent, to adequately treat a tumor with minimal normal tissue complications, and to predict the treatment outcomes. Furthermore, sophisticated external radiation treatment and brachytherapy absolutely require advanced imaging for target localization and radiation dose calculation.

Multicentre dose audit for clinical trials of radiation therapy in Asia

Abstract A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy.

Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2–3 nasopharyngeal cancer: a multicenter trial of the Forum for Nuclear Cooperation in Asia

The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2–3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1–4 N2–3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m 2), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m2 on Day 1) and fluorouracil (800 mg/m2 on Days 1–5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3–4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities.

Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer

Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90-100% and 70-90%, respectively).

Concurrent chemoradiotherapy for T3–4 and N0–1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3–4 and N0–1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3–4 N0–1 M0, World Health Organization Type 2–3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m2). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3–4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis–free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.

Posterior cervical lymph node metastasis as the valuable prognostic factor for stage IVA/IVB nasopharyngeal carcinoma treated with induction chemotherapy followed by concurrent chemo-radiotherapy

Introduction/Aim To evaluate the prognostic properties of retropharyngeal lymph node (RP), posterior cervical lymph node (PCN), and supraclavicular lymph node (SPC), in stage IVA/IVB nasopharyngeal carcinoma (NPC) patients in setting of induction chemotherapy. Methods We performed a retrospective study including 43 patients with stage IVA/IVB NPC (7th AJCC) treated with induction chemotherapy followed by concurrent chemo-radiotherapy. We analyzed prognosis with the multivariate Cox regression model and p-value from the Walds test, using the backward elimination method (by likelihood ratio test and percent change of coefficient factors). Result Overall, 24 patients (55.8%) were in stage IVA and 19 (44.2%) in stage IVB. After a median follow-up time of 30 months, the 2-year overall survival (OS) was 79.1%, while the 2-year progression free survival (PFS) and distant metastasis free survival (DMFS) were 59.8% and 69.1%, respectively. In multivariate analysis for predicting DMFS, SPC involvement was not statistically significant (HR 3.39; 95% CI 0.76-15.07; p=0.1), whereas RP involvement was statistically significant (HR 5.81; 95% CI 1.08-31.16; p=0.04). Moreover, and more importantly, PCN involvement was the only nodal factor to predict all of DMFS, PFS, and OS (respectively HR 5.57, 95% CI 1.12-27.71, p=0.036; HR 16.05, 95% CI 1.93-133.65, p=0.01; and HR 28.02, 95% CI 2.74-286.22, p=0.005). Discussion PCN involvement is the only independent prognostic factor of stage IVA/IVB NPC patients treated by induction chemotherapy that predicts DMFS and turns this effect to PFS and OS. PCN involvement is a highly accurate predictor for failure of conventional chemo-radiotherapy. Therefore, patients with PCN involvement should be defined at high-risk, as to be investigated for a new staging system.