Chawalit Lertbutsayanukul

Management of endometrial cancer in Asia: consensus statement from the Asian Oncology Summit 2009

Endometrial cancer is one of the gynaecological cancers that carries good overall prognosis because it is often detected at early stages of disease. The International Federation of Gynecology and Obstetrics replaced clinical staging with surgical staging in 1988 and updated the system in 2009. Controversies remain regarding the recommended screening protocol for women with a high risk of endometrial cancer, the role and benefit of retroperitoneal lymph-node dissection, the necessity of ovarian resection, the benefit and type of adjuvant radiation therapy, and the safety of hormone-replacement therapy after treatment. This article reviews the available evidence for optimum management of endometrial cancer and how management strategies can be applied in Asian countries with different levels of health-care resource availability and economic development. An overview of the literature for endometrial-cancer screening, diagnosis, and management is discussed. Consensus statements are formulated on the basis of basic, limited, enhanced, and maximum health-care resource availability, using the framework provided by the Breast Health Global Initiative.

Capecitabine-Based Chemoradiotherapy with Adjuvant Capecitabine for Locally Advanced Squamous Carcinoma of the Uterine Cervix: Phase II Results

OBJECTIVES Cisplatin-based chemoradiotherapy is the standard treatment for locally advanced cervical cancer but causes considerable toxicity. Capecitabine and radiotherapy show preclinical synergy and clinical activity. The activity, tolerability, and oral administration of capecitabine make it an attractive adjunctive therapy. METHODS In this phase II study, patients with untreated International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer received capecitabine, 825 mg/m(2) twice daily (Monday-Friday), during radiation (45 Gy per 25 fractions external-beam radiotherapy and 26 Gy high-dose rate brachytherapy to point A, maximum 8 weeks), followed by six cycles of capecitabine, 1,000 mg/m(2) twice daily (days 1-14 every 21 days). RESULTS The overall response rate in 60 patients was 88% (95% confidence interval [CI], 77.4%-95.2%), including complete responses (CRs) in 80% of patients. The 1-year progression-free and overall survival rates were 86% (95% CI, 77%-95%) and 95% (95% CI, 89%-100%), respectively. At 23 months, 76% of patients were progression free (95% CI, 65%-88%) and CR was maintained in 90% (95% CI, 81%-99%) of the 48 patients achieving a CR. There were three grade 3 or 4 treatment-related events: reversible grade 4 hypokalemia, grade 3 diarrhea, and grade 3 hand-foot syndrome. CONCLUSIONS Capecitabine-based chemoradiotherapy with adjuvant capecitabine is a well-tolerated option with an early signal of efficacy meriting further evaluation.

Efficacy of intensity-modulated radiotherapy with concurrent carboplatin in nasopharyngeal carcinoma

Abstract Background. The aim of the prospective phase II study was to evaluate the efficacy and toxicities of concurrent carboplatin with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). Patients and methods. Between October 2005 and November 2011, 73 stage II‒IVB NPC patients received IMRT 70 Gy concurrently with three cycles of carboplatin (AUC 5) every three weeks, followed by three cycles of adjuvant carboplatin (AUC 5) and 5-FU (1,000 mg/m2/day for four days) every four weeks. All patients were evaluated for tumour response using response evaluation criteria in solid tumour (RECIST) criteria, survival analysis using Kaplan-Meier methods, and toxicities according to common terminology criteria for adverse events (CTCAE) version 4.0. Results. At three months after chemoradiation, 82.2% and 17.8% of patients achieved complete and partial response, respectively. With a median follow-up of 48.1 months (1.3‒97.8 months), 9.6% and 17.8% had local recurrence and distant metastasis, respectively. The median survival was not reached. A three-year overall survival was 83.6% and a progression-free survival was 65.3%. Regarding treatment compliance, 97.2%, 68.5% and 69.8% completed radiation treatment, concurrent carboplatin and adjuvant chemotherapy, respectively. Grade 3‒4 acute toxicities were oral mucositis (16.4%), dysphagia (16.4%), xerostomia (15.1%) and haematotoxicity (6.8%). Conclusions. Carboplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. This should be considered as an alternative treatment for NPC patients.

Prevalence and significance of plasma Epstein-Barr Virus DNA level in nasopharyngeal carcinoma

Abstract Epstein-Barr virus (EBV) DNA has been recognized as a promising tumor marker for nasopharyngeal carcinoma (NPC). This study aims to demonstrate the prevalence of plasma EBV DNA and its temporal correlation with treatment outcomes in the modern era. A total of 204 patients with Stage I–IVB NPC treated with intensity-modulated radiotherapy (IMRT) were enrolled. Quantitative plasma EBV DNA measurement was performed before treatment (pre-IMRT), on the fifth week of radiation (mid-IMRT), at 3 months after radiation (post-IMRT), then every 6 months until disease relapse. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Plasma EBV DNA was detected in 110 patients (53.9%), with a median pre-IMRT EBV DNA level of 8005 copies/ml. Significant correlation was noted between pre-IMRT EBV DNA level and disease stage, but not between pre-IMRT EBV DNA level and World Health Organization classification. With a median follow-up time of 35.1 months, the 3-year PFS and OS rates were higher in the group with undetectable pre-IMRT EBV DNA level compared with in the group in which it was detectable. When classified according to disease stage and pre-IMRT EBV DNA, patients with early disease and detectable pre-IMRT EBV DNA experienced poorer survival than those with locally advanced disease and undetectable pre-IMRT EBV DNA. According to the dynamic changes in EBV DNA level between pre-IMRT and mid/post IMRT, survival was significantly higher in patients who achieved an undetectable level following treatment. On multivariate analysis, post-IMRT EBV DNA level was the strongest predictor of all treatment outcomes (P < 0.001). Our study demonstrated the clinical significance of the plasma EBV DNA level at specific time points, as well as of the dynamic changes in the EBV DNA level. Disappearance of plasma EBV DNA after treatment was associated with better survival.

High dose radiation with chemotherapy followed by salvage esophagectomy among patients with locally advanced esophageal squamous cell carcinoma

Locoregional failure is a major problem associated with chemoradiation treatment for squamous cell esophageal carcinoma. The aim of this study was to assess the feasibility, efficacy, and toxicity of preoperative radiation (dose > 50 Gy) with platinum‐based chemotherapy followed by esophagectomy in locally advanced squamous cell carcinoma.

Prognostic value of plasma EBV DNA for nasopharyngeal cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy

Abstract Background Plasma EBV DNA concentrations at the time of diagnosis (pre-EBV) and post treatment (post-EBV) have significant value for predicting the clinical outcome of nasopharyngeal cancer (NPC) patients. However, the prognostic value of the EBV concentration during radiation therapy (mid-EBV) has not been vigorously studied. Patients and methods This was a post hoc analysis of 105 detectable pre-EBV NPC patients from a phase II/III study comparing sequential (SEQ) versus simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT). Plasma EBV DNA concentrations were measured by PCR before commencement of IMRT, at the 5th week of radiation therapy and 3 months after the completion of IMRT. The objective was to identify the prognostic value of mid-EBV to predict overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). Results A median pre-EBV was 6880 copies/ml. Mid-EBV and post-EBV were detectable in 14.3% and 6.7% of the patients, respectively. The median follow-up time was 45.3 months. The 3-year OS, PFS and DMFS rates were 86.0% vs. 66.7% (p = 0.043), 81.5% vs. 52.5% (p = 0.006), 86.1% vs. 76.6% (p = 0.150), respectively, for those with undetectable mid-EBV vs. persistently detectable mid-EBV. However, in the multivariate analysis, only persistently detectable post-EBV was significantly associated with a worse OS (hazard ratio (HR) = 6.881, 95% confident interval (CI) 1.699-27.867, p = 0.007), PFS (HR = 5.117, 95% CI 1.562–16.768, p = 0.007) and DMFS (HR = 129.071, 95%CI 19.031–875.364, p < 0.001). Conclusions Detectable post-EBV was the most powerful adverse prognostic factor for OS, PFS and DMFS; however, detectable mid-EBV was associated with worse OS, PFS especially Local-PFS (LPFS) and may facilitate adaptive treatment during the radiation treatment period.

Validation of previously reported predictors for radiation-induced hypothyroidism in nasopharyngeal cancer patients treated with intensity-modulated radiation therapy, a post hoc analysis from a Phase III randomized trial

Abstract This study aimed to validate previously reported dosimetric parameters, including thyroid volume, mean dose, and percentage thyroid volume, receiving at least 40, 45 and 50 Gy (V40, V45 and V50), absolute thyroid volume spared (VS) from 45, 50 and 60 Gy (VS45, VS50 and VS60), and clinical factors affecting the development of radiation-induced hypothyroidism (RHT). A post hoc analysis was performed in 178 euthyroid nasopharyngeal cancer (NPC) patients from a Phase III study comparing sequential versus simultaneous-integrated boost intensity-modulated radiation therapy. RHT was determined by increased thyroid-stimulating hormone (TSH) with or without reduced free thyroxin, regardless of symptoms. The median follow-up time was 42.5 months. The 1-, 2- and 3-year freedom from RHT rates were 78.4%, 56.4% and 43.4%, respectively. The median latency period was 21 months. The thyroid gland received a median mean dose of 53.5 Gy. Female gender, smaller thyroid volume, higher pretreatment TSH level (≥1.55 μU/ml) and VS60 < 10 cm3 were significantly associated with RHT in univariate analyses. Only pretreatment TSH ≥ 1.55 μU/ml and VS60 < 10 cm3 were significant predictors in multivariate analysis. Our results suggested that patients with pretreatment TSH ≥ 1.55 μU/ml should be cautious about the risk of RHT. The VS60 ≥ 10 cm3 is recommended for treatment planning.

Optimal plasma pretreatment EBV DNA cut-off point for nasopharyngeal cancer patients treated with intensity modulated radiation therapy

Objective Plasma Epstein-Barr virus (EBV) DNA concentration at the time of diagnosis (pre-EBV) can be used to stratify risk for nasopharyngeal cancer (NPC) patients. However, pre-EBV cut-off values vary among studies. Methods This was a post hoc analysis of 208 NPC patients from a phase II/III study comparing sequential (SEQ) vs. simultaneous integrated boost (SIB) intensity modulated radiation therapy. The objective was to identify the optimal pre-EBV cut-off value to predict overall survival (OS), progression free survival (PFS) and distant metastatic free survival (DMFS) rates. Results The pre-EBV and post-treatment EBV DNA (post-EBV) were detectable in 59.1% and 3.8% of the patients, respectively. A new pre-EBV cut-off value of 2300 copies/ml was identified by the receiver operating characteristics analysis. This cut-off value showed 82% sensitivity, 59% specificity and 31.7% positive and 93.5% negative predictive values in predicting OS. The 3-year OS, PFS and DMFS were 95.6 vs. 73.8%, 89.8 vs. 55.3% and 93 vs. 70.1% for pre-EBV < vs. ≥2300 copies/ml, respectively. Older age group (≥45 years), high pre-EBV and detectable post-EBV concentration were independent predictors for OS, PFS and DMFS in a multivariate analysis. When the stage grouping and pre-EBV value were combined, a subgroup of patients with stage II-III and pre-EBV values <2300 copies/ml. had the best survival outcomes, while the worst survival subgroup was the patients with stage III-IVb with pre-EBV values ≥2300 copies/ml. Conclusions Pre-EBV cut-off of 2300 copies/ml is an optimal value predicting OS, PFS and DMFS.

Clinical Outcomes of Stereotactic Body Radiation Therapy Using Flattening Filter Free (FFF) in Early Non–Small Cell Lung Cancers and Metastatic Lung Cancers

improved OS (HR 0.379; 95% CI 0.16-0.93; PZ.033). This was not observed in patients with higher GPA scores. Conclusion: Brain radiation therapy plus EGFR-TKI, whether upfront or delayed, may improve intracranial disease control compared with TKI alone in EGFR mutant NSCLC with BM. The addition of brain irradiation to EGFR-TKI did not appear to improve survival in unselected patients, but low GPA scores may be a useful clinical predictor for early brain irradiation. Further prospective studies are needed to determine the optimal timing and appropriate patient group who need upfront brain radiation therapy. Author Disclosure: Y. Liu: None. L. Deng: None. X. Zhou: None. L. Zhou: None. Y. Xu: None. Y. Gong: None. J. Wang: None. Y. Lu: None.