Upright epiglottis prevents aspiration in patients with nasopharyngeal carcinoma post-chemoradiation.

NPC is the most widely found malignant tumor in the head and neck region in Indonesia. Chemoradiation therapy for NPC can induce swallowing disorders (dysphagia) that adversely affects a patients quality of life. This study aimed to assess the swallowing process by flexible endoscopic evaluation of swallowing in patients with nasopharyngeal carcinoma after chemoradiation. Thirty-nine patients with NPC who had chemoradiation therapy more than one month previously underwent flexible endoscopic evaluation of swallowing and were assessed for oral transport time, sensation, standing-secretion, pre-swallowing leakage, residue, penetration, aspiration, and silent aspiration. The most common structural abnormalities were an upright and swollen epiglottis (89.4%), poor oral hygiene, and velopharyngeal closure defects (56.4%). This examination also revealed a mild degree of standing secretion (38.5%) and aspiration (10.3%). No penetration was observed in 64.1% of the patients, and no silent aspiration was observed in any of the patients. A severe degree of residue (45.7%) was observed when administering oatmeal, while the residue was mild to moderate when administering gastric rice, crackers, and milk. The residue changed to a mild degree (32.3%-51.4%) in all food administrations after the watering maneuver. The highest penetration was noted after oatmeal administration (42.8%), and the highest aspiration was found after milk administration (8.6%). Standing secretion in almost all patients was caused by hyposensitivity of the hypopharynx. Persistent residue and hyposensitivity of the hypopharynx led to aspiration. The low percentage of aspiration and silent aspiration might have been caused by the upright and swollen epiglottis that prevented aspiration. Poor oral hygiene and a dry mouth led to prolonged oral transport. Therefore, most patients had hypopharyngeal abnormalities in the form of a swollen and upright epiglottis. Secretion and food residue were also detected. Drinking helps to expedite the swallowing process by facilitating oral phase transport and reducing residues.

Multi-institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiation Therapy Using Weekly Cisplatin for Patients With Pelvic Node-Positive Cervical Cancer in East and Southeast Asia.

PURPOSE: This multi-institutional observational study conducted among 11 countries in East and Southeast Asia aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with locally advanced cervical cancer. METHODS AND MATERIALS: Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course. RESULTS: A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. CONCLUSIONS: The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Multicentre dose audit for clinical trials of radiation therapy in Asia.

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.

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/m(2)). 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.

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.

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/m(2) on Day 1) and fluorouracil (800 mg/m(2) 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.

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.

Accelerated hyperfractionated radiotherapy for cervical cancer: multi-institutional prospective study of forum for nuclear cooperation in Asia among eight Asian countries.

PURPOSE: To evaluate the toxicity and efficacy of accelerated hyperfractionated radiotherapy (RT) for locally advanced cervical cancer. METHODS AND MATERIALS: A multi-institutional prospective single-arm study was conducted among eight Asian countries. Between 1999 and 2002, 120 patients (64 with Stage IIB and 56 with Stage IIIB) with squamous cell carcinoma of the cervix were treated with accelerated hyperfractionated RT. External beam RT consisted of 30 Gy to the whole pelvis, 1.5 Gy/fraction twice daily, followed by 20 Gy of pelvic RT with central shielding at a dose of 2-Gy fractions daily. A small bowel displacement device was used with the patient in the prone position. In addition to central shielding RT, intracavitary brachytherapy was started. Acute and late morbidities were graded according to the Radiation Therapy Oncology Group and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: The median overall treatment time was 35 days. The median follow-up time for surviving patients was 4.7 years. The 5-year pelvic control and overall survival rate for all patients was 84% and 70%, respectively. The 5-year pelvic control and overall survival rate was 78% and 69% for tumors > or = 6 cm in diameter, respectively. No treatment-related death occurred. Grade 3-4 late toxicities of the small intestine, large intestine, and bladder were observed in 1, 1, and 2 patients, respectively. The 5-year actuarial rate of Grade 3-4 late toxicity at any site was 5%. CONCLUSION: The results of our study have shown that accelerated hyperfractionated RT achieved sufficient pelvic control and survival without increasing severe toxicity. This treatment could be feasible in those Asian countries where chemoradiotherapy is not available.

A regional cooperative clinical study of radiotherapy for cervical cancer in east and south-east Asian countries.

PURPOSE: Radiotherapy differed widely in east and south-east Asia because of technical, cultural, and socio-economic differences. With the purpose of standardizing radiotherapy for cervical cancer in the region, an international clinical study was conducted. MATERIALS AND METHODS: Eleven institutions in eight Asian countries participated in the study. Between 1996 and 1998, 210 patients with stage IIIB cervical cancer were enrolled. Patients were treated with a combination of external beam radiotherapy (total dose, 50Gy) and either high-dose-rate (HDR) or low-dose-rate (LDR) intracavitary brachytherapy (ICBT) according to the institutional practice. The planned point A dose was 20-28Gy/4 fractions for HDR-ICBT and 30-40Gy/1-2 fractions for LDR-ICBT. RESULTS: Hundred patients were treated with HDR-ICBT and 110 were treated with LDR-ICBT. The ICBT doses actually delivered to point A ranged widely: 12-32Gy in the HDR group and 26-52.7Gy in the LDR group. The 5-year follow-up rate among the countries differed greatly, from 29% to 100%. The 5-year major complication rates were 6% in the HDR group and 10% in the LDR group. The 5-year overall survival rates were 51.1% in the HDR group and 57.5% in the LDR group. CONCLUSIONS: Although there were several problems with treatment compliance and patients' follow-up, the study suggests that the protocols provided favorable outcomes with acceptable rates of late complications in the treatment of advanced cervical cancer in east and south-east Asia.

HDR interstitial perineal implant for locally advanced or recurrent uterine cervix cancer.

PURPOSE: To evaluate whether high-dose-rate (HDR) interstitial perineal implants can effectively eradicate residual tumor or recurrent tumor in uterine cervix cancer after complete radiation treatment. MATERIALS AND METHODS: This method of treatment was commenced in January 2002, and four advanced stage and four uterine cervix cancer (UCC) recurrences were admitted for this study. All untreated stage II bulky mass and IIIB patients received 50 Gy external beam radiotherapy (EBR) to the whole pelvis prior to the interstitial perineal implant. No EBR was given to recurrent UCC. Brachytherapy was delivered using Martinez Universal Perineal Interstitial Template (MUPIT) and 192Ir HDR. This implant will only be done if residual disease on the parametria was bimanually palpable or was proven by CT scan or MRI. The dose of interstitial brachytherapy boost to the parametria was 17 to 30 Gy, and treatment days ranged from 42 to 64 days. Uterine recurrences were found on the uterine cervix and/or parametria. The dose delivered by this implant ranged from 6 to 16 Gy and encompassed either uterus or vaginal stump and both parametria. Total treatment days ranged from 1 to 2 days. RESULTS: This short-term study showed that almost all tumors were locally controlled when the study was closed (1 to 15 months). One distant metastasis was found. No significant morbidity has been identified until now. CONCLUSION: HDR 192Ir interstitial perineal implants were proven to be effective in eradicating tumor cells in advanced stage UCC and recurrent disease with no significant morbidity.