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Objective Predicting the treatment response in patients with nasopharyngeal carcinoma (NPC) is challenging. This study evaluated the utility of diffusion-weighted imaging (DWI) in predicting the treatment response in patients with NPC. Methods We prospectively enrolled 33 patients with newly diagnosed NPC who underwent magnetic resonance imaging with the propeller DWI and apparent diffusion coefficient (ADC) map before and at 5 weeks after chemoradiation. The following ADC values of the primary tumor were calculated: pre-treatment ADC (pre-ADC), pre-treatment ADC ratio (pre-ADC ratio), ADC change (▵ADC), ADC change ratio (▵ADC ratio), and percentage of ADC change (▵%ADC). The correlations between these parameters and treatment outcomes were explored, and the patients were classified as good responders (complete response) and poor responders (stable disease, partial response, or progressive disease) based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Results The ▵ADC, ▵ADC ratio, and ▵%ADC were significantly lower in the poor-responder group ( n = 12) than in the good-responder group ( n = 21; p = 0.001, p = 0.002, and p = 0.004, respectively). There was no significant difference between groups in the pre-ADC and pre-ADC ratios ( p = 0.602 and p = 0.685, respectively). The optimal ▵ADC, ▵ADC ratio, and ▵%ADC cutoff values for predicting poor response were >0.65 mm2/sec, 0.28, and 60%, respectively (sensitivity: 83.3%, 75%, and 83.3%; specificity: 71.4%, 85.7%, and 71.4%, respectively). Conclusion The ▵ADC, ▵ADC ratio, and ▵%ADC obtained during the pre-treatment and mid-treatment periods could be potential biomarkers for predicting treatment response in patients with NPC.

Diminished immune response after vaccination occurs in cancer patients. This observational study evaluated the immune response and safety profile after COVID-19 vaccination in radiotherapy patients. The study comprised 53 cancer patients undergoing radiotherapy and voluntarily received the COVID-19 vaccine. The two regimens were homologous ChAdOx1-S recombinant (AstraZeneca, AZ), “AZ-AZ” and heterologous “AZ-mRNA”. The seroconversion rate and anti-RBD immunoglobulin geometric mean titers (GMT) were assessed and compared with healthy controls. Adverse effects were assessed using a questionnaire. The seroconversion rate was 52.4% 1 month after the first dose with GMT 4.3 U/mL (95%CI 1.4–13). Following the second dose, the AZ-AZ group achieved 95% seroconversion rate with GMT = 188.4 U/mL (95%CI 67.1–529), which was significantly lower than the healthy cohort, GMT = 945 U/mL (95%CI 708–1261). Cancer patients in AZ-mRNA group achieved a 100% seroconversion rate with a high GMT = 1400.8 U/mL (95%CI 429.5–4566), which was significantly lower than the healthy cohort, GMT = 5169.9 U/mL (95%CI 3582.2–7461.5). Most adverse effects were mild. Our findings suggest that radiotherapy patients had fair immunogenicity after the first dose, but achieved a high seroconversion rate after the second dose with manageable adverse effects. However, their immunologic response was lower than in healthy individuals, indicating that other preventive strategies are needed.

Purpose: For patients with early breast cancer who undergo breast-conserving surgery, adjuvant whole breast irradiation (WBI) with simultaneous integrated boost (SIB) results in lower radiotherapy fractions. Published studies have shown that both conventional fraction with SIB (C-SIB) and hypofractionation with SIB (H-SIB) seem to be safe and feasible. In this study, we sought to compare the oncologic outcomes between C-SIB and H-SIB in early-stage breast cancer.Materials and Methods: Stage I–II breast cancer patients who received adjuvant WBI with SIB between January 2008 and December 2017 were retrospectively reviewed. The radiation dose in the C-SIB group was 50 Gy and 65 Gy in 25 daily fractions, while in the H-SIB group, it was 43.2 Gy and 52.8 Gy in 16 daily fractions to the whole breast and tumor bed, respectively.Results: A total of 188 patients, 103 in the C-SIB group and 85 in the H-SIB group, were included. With a median follow-up time of 87 months, 7-year locoregional control of C-SIB was comparable to H-SIB (95.8% vs. 97.4%, p = 0.964). The 7-year distant metastasis-free survival rates of C-SIB and H-SIB were 89.9% and 95.9% (p = 0.111), while the 7-year disease-free survival rates were 84.2% and 95.4%, respectively (p = 0.176). In multivariate analysis, there was no significant prognostic factor associated with better overall survival. Conclusion: H-SIB provided comparable locoregional control to C-SIB. With the advantage of a shorter radiotherapy course, H-SIB could be a favorable option for WBI in early-stage breast cancer.

OBJECTIVES Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. MATERIALS AND METHODS Case records of consecutive T4 NPC patients who received definitive IMRT in two tertiary oncology centers in 2004-2019 were reviewed. Patterns of cranial neuropathies at disease presentation were recorded. Time to neurological recovery and the rate of subsequent re-palsy were estimated by the Kaplan-Meier method. Clinical predictors were analyzed using multivariable Cox regression. RESULTS During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was two months (IQR, 1-4 months). Cranial nerves (CN) VI (56.4%), V2 (47.9%), and V3 (29.2%) were most frequently involved. At a median follow-up of 6.4 years, the crude partial and full recovery rates of neuropathies were 111 (22%) and 289 (57.3%), respectively. CN III, IV, and VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), XII (48.6%), and II (18.2%) (p

Radiation-induced hypothyroidism (RHT) is a common long-term complication for nasopharyngeal carcinoma (NPC) survivors. A model using clinical and dosimetric factors for predicting risk of RHT could suggest a proper dose-volume parameters for the treatment planning in an individual level. We aim to develop a multivariable normal tissue complication probability (NTCP) model for RHT in NPC patients after intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). The model was developed using clinical data and dose-volume data of thyroid and pituitary gland based on a standard backwards stepwise multivariable logistic regression analysis, then internally validated using 10-fold cross validation. The final NTCP model consisted of age, pre-treatment thyroid stimulating hormone (TSH) and mean thyroid dose. The model performance was good with an area under the receiver operating characteristic curve of 0.749 on an internal (200 patients) and 0.812 on an external (25 patients) validation. The mean thyroid dose at ≤ 45Gy was suggested for treatment plan owing to an RHT incidence of 2% versus 61% in the > 45Gy group.

In locoregional esophageal carcinoma (EC), airway involvement is the most common route of extraesophageal metastasis. The prognosis remains poor even with a multimodality approach. Although airway stenting is well known for restoration of the airway, the survival benefit is still lacking.A total of 37 of patients with airway involvement from EC who underwent airway stenting at a single institution from 2015 to 2020 were retrospectively reviewed. Survival curves after stent placement among different groups were analyzed using Kaplan-Meier method.Of 37 patients, 34 were male, and the mean age was 58.9 years (42 to 80). EC was commonly located at midesophagus (51.4%). The site of airway involvement was left main bronchus (48.6%), trachea (32.4%), multiple sites (16.2%), and right main bronchus (2.7%). The nature of airway involvement was tumor invasion (91.9%), compression (62.2%), and fistula (37.8%). Twenty-three patients (62.2%) had airway involvement at the time of esophageal cancer diagnosis. Only 4 patients underwent esophageal stenting. The median survival time after stent placement was 97 days (5 to 539). Chemotherapy and/or radiotherapy were given before stent placement in 18 patients (48.6%). Treatment-naive before airway stenting and diagnosis of airway involvement at the same time of EC diagnosis were independent predictors for the increased survival after stent placement (P0.05). Poststent treatment was associated with improved survival (P=0.002).In patients with malignant airway involvement from EC who underwent airway stenting, the prognostic predictors for improved survival were treatment-naive status, receiving treatment after airway stenting, and early-onset of airway involvement.

Aim To determine the associations between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters and plasma Epstein-Barr virus (EBV) DNA status and nasopharyngeal carcinoma (NPC) stages. Methods We prospectively studied the DCE-MRI results of 47 patients with newly diagnosed NPC and their pre-treatment plasma EBV DNA levels. We recruited all patients who had undergone MRI (1.5 T) simulation at the radiation therapy department of our institute between January 2018–2019. Regions of interest were drawn at primary tumors, and DCE-MRI parameters, including mean values of Ktrans, Kep, Ve, and Vp, were recorded. Spearman's rank correlation was used to identify significant associations between the DCE-MRI parameters and the plasma EBV DNA level and NPC stages. Mann-Whitney U tests and unpaired t-test were performed to compare the DCE-MRI parameters among different groups and to identify optimal cut-off values using receiver operating characteristic curves. Results We found that the DCE-MRI parameters correlated with the plasma EBV DNA levels and NPC stages. Positive plasma EBV DNA was correlated with lower Kep (optimal cut-off value, 2.1 min−1; area under the curve [AUC], 0.714) and higher Ve (optimal cut-off value, 0.675; AUC, 0.706). Ve higher than 0.765 (AUC, 0.678) was correlated with plasma EBV DNA (≥2300 copies mL−1). Higher Ktrans (cut-off value, 1.495 min−1) was correlated with high-T stage (AUC, 0.767) and high-stage group (AUC, 0.711). Conclusions The DCE-MRI parameters are correlated with the plasma EBV DNA status and NPC stages. Therefore, DCE-MRI findings may be used as imaging biomarkers for patients with NPC.

Background Stereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT). Methods Patients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT. Results From February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29–48.95, P=0.003) and gross tumor volume (GTV) mean BED10 ≤147 Gy (HR 5.16, 95% CI: 1.13–23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1–2 toxicities were radiation pneumonitis (26.5%). No grade 3–5 event was observed. Conclusions This study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC.

Magnetic resonance imaging (MRI) parameters that reflect the tumor microenvironment of nasopharyngeal carcinoma (NPC) may predict treatment response and facilitate treatment planning. This study aimed to evaluate the diffusion-weighted imaging and dynamic contrast-enhanced MRI (DCE-MRI) values for predicting the treatment outcomes in NPC patients.Eighty-three patients with NPC underwent pretreatment MRI simulation with diffusion-weighted imaging and dynamic contrast-enhanced MRI. Average values of the apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, Vp, and tumor volume of the primary tumors were measured. Other potential clinical characteristics (age, sex, staging, pathology, pretreatment Epstein-Barr virus level, and treatment type) were analyzed. Patients underwent follow-up imaging 6 months after treatment initiation. Treatment responses were assigned according to the Response Evaluation Criteria in Solid Tumors guideline (version 1.1).Fifty-one patients showed complete response (CR), whereas 32 patients did not (non-CR). Univariable logistic regression with variables dichotomized by optimal cutoff values showed that ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, tumor volume of ≥14.05 mL, high stage (stages III and IV), and Epstein-Barr virus level of ≥2300 copies/mL were predictors of non-CR ( P = 0.008, 0.05, 0.01, 0.009, and 0.04, respectively). The final multivariable model, consisting of a combination of ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, and high stage, could predict non-CR with a good discrimination ability (area under the receiver operating characteristic curve, 0.76 [95% confidence interval, 0.66-0.87]; sensitivity, 62.50%; specificity, 80.39%; and accuracy 73.49%).A multivariable prediction model using a combination of ADC ≥1.45 × 10 -3 mm 2 /s, Vp ≥0.14, and high stage can be effective for treatment response prediction in NPC patients.

To compare patient-rated cosmetic and satisfactory outcomes between conventional fractionation with simultaneously integrated boost (C-SIB) vs hypofractionation with SIB (H-SIB) in early breast cancer. Patients with stage I and II breast cancer who received breast-conserving surgery followed by radiation with SIB to tumor bed and completed questionnaire were included in this study. Radiotherapy was as follows: C-SIB arm = 50 Gy and 65 Gy in 25 fractions and H-SIB arm = 43.2 Gy and 52.8 Gy in 16 fractions to the whole breast and tumor bed, respectively. Single cross-sectional assessment of the breast cosmesis was done by patients and radiation oncologist at a follow-up visit. Breast cosmetic and satisfaction scores were collected using a four-point Harvard/NSABP/RTOG cosmesis criteria scale and a four-point Likert-type scale, respectively. Of a total of 114 patients (C-SIB = 57) and (H-SIB = 57) arms, a median time from radiotherapy completion to questionnaire response was 7.2 years. Patient-rated cosmetic outcome in C-SIB vs H-SIB was "excellent" in 40.3% vs 45.6%, "good" in 33.3% vs 42.1%, "fair" in 21.1% vs 10.5%, and "poor" in 5.3% vs 1.8% (P = .288). Corresponding satisfaction was "very satisfied" in 52.6% vs 57.9%, "satisfied" in 40.4% vs 35.1%, "neutral" in 7.0% vs 5.2%, and "unsatisfied" in 0% vs 1.8% (P = .683). Stage I and older age at radiotherapy were predictors for favorable (good or excellent) cosmesis and satisfaction, respectively. In early-stage breast cancer, H-SIB provided a trend for better cosmesis than C-SIB while maintaining satisfaction. The reduction in treatment duration and cost as well as favorable cosmesis outcomes encourages the use of H-SIB.

Background: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) is a multidimensional tool to assess malnutrition and risk factors. The objectives of this study are to determine the validity of the Thai version of the Scored PG-SGA (Thai PG-SGA) and examine the correlations with selected nutritional parameters. Methods: This observational analytic study included 195 cancer patients aged greater than 18 years at a university-affiliated hospital in Bangkok, Thailand. All patients were assessed for nutritional status by Thai PG-SGA in comparison to subjective global assessment (SGA). Anthropometry, body composition, and hand grip strength were evaluated. Results: According to PG-SGA global assessment categories, 39% (75) of 195 cancer patients were well nourished, 27% (53) were moderately malnourished and 34% (67) of patients were severely malnourished. Thai PG-SGA had a sensitivity of 99.1% and a specificity of 86.0% at predicting SGA classification. PG-SGA numerical scores were significantly different between well-nourished and malnourished groups (4.2 ± 2.4 Vs 16.3 ± 4.9; p < 0.001). The PG-SGA scores, nutritional status assessed by PG-SGA, and nutritional status assessed by SGA were correlated with weight, % weight loss in one month, body mass index, body fat, and hand grip strength (p < 0.001) respectively. Conclusions: Thai PG-SGA showed high sensitivity and good specificity in predicting malnutrition in Thai cancer patients. This tool demonstrated the correlations with anthropometric parameters, body composition, and muscle strength.

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.

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.

This study was performed to compare the acute and late toxicities between sequential (SEQ) and simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT. SEQ-IMRT consisted of two plans: 2 Gy × 25 fractions to low-risk planning target volume (PTV) followed by a sequential boost (2 Gy × 10 fractions) to high-risk PTV, while SIB-IMRT treated low- and high-risk PTVs with doses of 56 and 70 Gy in 33 fractions. Toxicities and survival outcomes were analyzed. Between October 2010 and September 2015, of the 209 patients who completed treatment, 102 in the SEQ and 107 in the SIB arm were analyzed. The majority had undifferentiated squamous cell carcinoma (82%). Mucositis and dysphagia were the most common grade 3–5 acute toxicities. There were no statistically significant differences in the cumulative incidence of grade 3–4 acute toxicities between the two arms (59.8% in SEQ vs. 58.9% in SIB; P = 0.892). Common grade 3–4 late toxicities for SEQ and SIB included hearing loss (2.9 vs. 8.4%), temporal lobe injury (2.9 vs. 0.9%), cranial nerve injury (0 vs. 2.8%), and xerostomia (2 vs. 0.9%). With the median follow-up of 41 months, 3‑year progression-free and overall survival rates were 72.7 vs. 73.4% (P = 0.488) and 86.3 vs. 83.6% (P = 0.938), respectively. SEQ and SIB provide excellent survival outcomes with few late toxicities. According to our study, SIB with a satisfactory dose–volume constraint to nearby critical organs is the technique of choice for NPC treatment due to its convenience.

PURPOSE/OBJECTIVE(S) Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. This study sets to evaluate the prognostic factors and recovery pattern of cranial neuropathies, using longitudinal clinical data from two tertiary oncology centers in endemic areas. MATERIALS/METHODS Case records of consecutive T4 NPC patients who received definitive IMRT in 2004-2019 were reviewed. Distribution of cranial neuropathies at disease presentation were recorded. Time to partial and full neurological recovery, time from neurological recovery to re-palsy, relapse-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors for neurological recovery were analyzed using multivariable Cox regression. RESULTS During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was 2 months (IQR, 1-4 months). All patients completed definitive IMRT, and 94% of patients received chemotherapy. The 5-year RFS and OS of the combined cohort were 50.8% and 60.1% respectively. Median RFS of patients with single versus multiple neuropathies were 5.8 years and 4.2 years (P = 0.62). Cranial nerves (CN) VI (56.4%), V2 (47.9%) and V3 (29.2%) were most frequently involved. Over a median follow-up of 6.4 years, 111 (22%) and 289 (57.3%) neuropathies attained partial and full recovery respectively, and 86% of the recoveries occurred within the first year after definitive radiotherapy. CN III, IV, VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), CN XII (48.6%), and CN II (18.2%) (P < 0.001). Positive smoking history, optic nerve involvement, and long duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences at the base of skull. CONCLUSION Rate and durability of cranial neuropathy recovery in this contemporary NPC cohort compared favorably with data from the 2D radiotherapy era. Both patient and disease factors affected the chance of nerve recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

Background 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. Methods Data of patients with cT2-cT4 or node positive squamous cell carcinoma of the esophagus who received trimodality treatment between February 2006 and June 2015 were reviewed. Results Forty-four patients were treated with intensity-modulated radiation therapy, volumetric-modulated arc therapy or three-dimensional radiation therapy. The median radiation dose was 60 Gy. The average volume of the lungs receiving 10 Gy was 48.1%, 20 Gy was 24.5%, and the average mean lung dose was 14 Gy. After chemoradiation, R0 resection was achieved in 31 patients (71%). Patients who received >60 Gy had a higher pathologic complete remission rate than those in the lower dose group (59.1% vs. 36.4%). R0 resection and radiation dose >60 Gy were associated with better overall survival in Cox proportional hazards regression analysis. The median follow-up duration was 22.4 months and median survival was 25.6 months. Two-year overall, progression-free survival and locoregional control rates were 55.9%, 28.6%, and 56%, respectively. The most common grade 3–4 toxicities were esophagitis (63.6%) and neutropenia (25%). Grade 3–4 postoperative morbidities included surgical wound infection (2.3%), acute renal failure (2.3%), and anastomosis stricture (2.3%). Conclusion Trimodality treatment with a high preoperative radiation dose and chemotherapy yielded a good pathologic complete response rate, and long-term survival with low toxicities.

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

OBJECTIVE To validate the eighth edition of the AJCC/UICC staging system in nasopharyngeal cancer (NPC) patients who were uniformly treated in a prospective randomized study using intensity-modulated radiation therapy and to investigate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level when incorporated into the TNM staging. METHODS Between October 2010 and September 2015, non-metastatic NPC patients were treated with concurrent chemoradiation followed by adjuvant chemotherapy. Pretreatment images of 205 patients were reviewed by two radiologists to determine the TNM classification according to the seventh and eighth editions of the AJCC/UICC staging system. Overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated. Harrell's C concordance index (C-index) and Akaike information criterion (AIC) were used to compare the staging models. Recursive partitioning analysis (RPA) was conducted and incorporated with plasma EBV DNA. RESULTS Overall, the eighth edition showed higher C-indexes and lower AIC values in nodal classification and stage groups, indicating a better discrimination performance and better goodness of fit, but showed similar separation for T classification compared with the seventh edition. The integration of pretreatment EBV values (

Diffusion-weighted imaging (DWI) is an MRI technique which provides functional information of tissue by detecting microscopic motion of water molecules. The change of apparent diffusion coefficient (ADC) derived from DWI was used as an imaging biomarker for treatment response prediction in cancers [1]. However, it was based on whole-tumor analysis which did not reflect heterogeneity within the tumor. To overcome this limitation, a new method called parametric response map (PRM) analysis was proposed to evaluate response by quantifying voxel-wise changes in ADC [2]. Here we investigated the use of PRM analysis on ADC from DWI as an imaging biomarker for treatment response prediction in nasopharyngeal cancer (NPC) patients. We collected thirteen patient datasets including ten complete response (CR) patients and three partial response (PR) patients at King Chulalongkorn Memorial Hospital where one patient dataset consisted of DWI and ADC data acquired before (i.e. pre-treatment) and at five weeks after (i.e. mid-treatment) initiation of chemoradiation therapy. For each dataset, we compared pre-treatment ADC image with co-registered mid-treatment ADC image, and calculated the percentage of voxels with increased ADC values with respect to total voxels within the tumor ROI, defined as PRM+. To validate the feasibility of the PRM biomarker, we computed the mean and standard deviation (SD) of percentage change in tumor volume (%AVol ) and in ADC (%AADC) and PRM+ across CR and PR patients, where tumor response was from 6-month follow-up data using RECIST1.1 guideline. The results showed that %AVol as well as %AADC between both groups was not significantly different. In contrast, PRM+ was significantly different between both groups (p < 0.05, 82.7±7.8% in CR vs 66.7±6.5% in PR). Our results implied that the proposed PRM+ biomarker could be a potential biomarker for early treatment response prediction in NPC patients.

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.

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

Background 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. Methods Data of patients with cT2‐cT4 or node positive squamous cell carcinoma of the esophagus who received trimodality treatment between February 2006 and June 2015 were reviewed. Results Forty‐four patients were treated with intensity‐modulated radiation therapy, volumetric‐modulated arc therapy or three‐dimensional radiation therapy. The median radiation dose was 60 Gy. The average volume of the lungs receiving 10 Gy was 48.1%, 20 Gy was 24.5%, and the average mean lung dose was 14 Gy. After chemoradiation, R0 resection was achieved in 31 patients (71%). Patients who received >60 Gy had a higher pathologic complete remission rate than those in the lower dose group (59.1% vs. 36.4%). R0 resection and radiation dose >60 Gy were associated with better overall survival in Cox proportional hazards regression analysis. The median follow‐up duration was 22.4 months and median survival was 25.6 months. Two‐year overall, progression‐free survival and locoregional control rates were 55.9%, 28.6%, and 56%, respectively. The most common grade 3–4 toxicities were esophagitis (63.6%) and neutropenia (25%). Grade 3–4 postoperative morbidities included surgical wound infection (2.3%), acute renal failure (2.3%), and anastomosis stricture (2.3%). Conclusion Trimodality treatment with a high preoperative radiation dose and chemotherapy yielded a good pathologic complete response rate, and long‐term survival with low toxicities.

Most patients with endometrial cancer (EMC) present their symptoms early in their course, leading to an overall favorable outcome. However, some patients who are in early-stage diseases may carry some risk features that would hamper their prognoses. For these early-stage diseases with high risk of recurrences, radiation therapy certainly plays a major role as an adjuvant treatment. Despite an excellent local diseases control by radiation, systemic failures are still encountered. To improve the prognoses, other types of adjuvant therapy have been attempted. In this review, various options of adjuvant treatment for this early-stage EMC including radiation therapy, chemotherapy, and hormonal therapy are discussed.

Purpose Intracavitary brachytherapy plays an important role in the treatment of cervical carcinoma. Previous results have shown controversy between the effect of dose rate on tumor control and the occurrence of complications. We performed a prospective randomized clinical trial to compare the clinical outcomes between low-dose-rate (LDR) and high-dose-rate (HDR) intracavitary brachytherapy for treatment of invasive uterine cervical carcinoma. Methods and materials A total of 237 patients with previously untreated invasive carcinoma of the uterine cervix treated at King Chulalongkorn Memorial Hospital were randomized between June 1995 and December 2001. Excluding ineligible, incomplete treatment, and incomplete data patients, 109 and 112 patients were in the LDR and HDR groups, respectively. All patients were treated with external beam radiotherapy and LDR or HDR intracavitary brachytherapy using the Chulalongkorn treatment schedule. Results The median follow-up for the LDR and HDR groups was 40.2 and 37.2 months, respectively. The actuarial 3-year overall and relapse-free survival rate for all patients was 69.6% and 70%, respectively. The 3-year overall survival rate in the LDR and HDR groups was 70.9% and 68.4% ( p = 0.75) and the 3-year pelvic control rate was 89.1% and 86.4% ( p = 0.51), respectively. The 3-year relapse-free survival rate in both groups was 69.9% ( p = 0.35). Most recurrences were distant metastases, especially in Stage IIB and IIIB patients. Grade 3 and 4 complications were found in 2.8% and 7.1% of the LDR and HDR groups ( p = 0.23). Conclusion Comparable outcomes were demonstrated between LDR and HDR intracavitary brachytherapy. Concerning patient convenience, the lower number of medical personel needed, and decreased radiation to health care workers, HDR intracavitary brachytherapy is an alternative to conventional LDR brachytherapy. The high number of distant failure suggests that other modalities such as systemic concurrent or adjuvant chemotherapy might lower this high recurrence, especially in Stage IIB and IIIB.

To study the outcome of less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication in the treatment of intracranial germ cell tumor (ICGCT) at the King Chulalongkorn Memorial Hospital.A descriptive study was established by reviewing patients' records from the Division of Therapeutic Radiology and Oncology admitted between 2001 and 2008. Median follow-up time was 65 months. Patient characteristics, investigations, and treatment modalities were presented in proportion. Survival analysis was evaluated by Kaplan-Meier method. The results were compared with the previous study in done in 1990 to 2000.Forty-two records were reviewed and 71% were male. The median age was 16 years. Pineal region was the most common site in 55%. Interestingly, 12% had synchronous lesions at both pineal and suprasellar regions. Out of 41 patients who had histopathological confirmation, 71% were germinoma. Out of 37 patients who had MRI spine or CSF cytology, 43% had CNS dissemination. Less aggressive radiotherapy combined with surgery and chemotherapy was increasingly utilized; however five-year overall survival rate in all patients was 83%, comparable to 82% from the previous study. Survival rates of patients without CNS dissemination were 88% in the present study and 83% in the previous study. Survival rates adjusted for histopathology were 86% for germinoma and 76% for non-germinoma.Less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication is an effective treatment for ICGCT.

To assess and compare the impact on skin reactions and cosmesis between hypofractionated whole breast and conventional irradiation for early breast cancer.Seventy-three patients with operable breast cancer (pT1-3pN0-1M0) who underwent breast-conserving surgery were assigned for irradiation to either conventional arm (50 Gy in 25 fractions) with a sequential electron boost of 15-16 Gy over five weeks or hypofractionated arm (43.2 Gy in 16 fractions) with a concomitant electron boost of 0.6 Gy over three weeks.At 3-week follow-up, skin toxicities in the hypofractionated arm were significantly worse than that seen in the conventional arm, while at 6-week follow-up, the percentages of skin toxicities in the conventional arm were higher After a median follow-up of six months, there was no significant difference in skin toxicities between the two treatment groups. In addition, there were no significant differences in the mean scores of cosmetic outcome for patients between two regimens.This hypofractionated radiotherapy regimen of 43.2 Gy in 16 fractions with a concomitant electron boost showed good results in terms of normal tissue effects and cosmesis. A long-term follow-up is needed to confirm these favorable results.

Summary 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.

To compare simultaneous integrated boost and sequential boost after conventional irradiation in breast-conserving therapy in aspect of late effects and cosmetic results.Between August 2006 and June 2007, 60 breasts were treated in this prospective nonrandomized study, designed to compare simultaneous integrated boost (additional 10 Gy/25F) and sequential boost (15 Gy/5F) to the tumor bed in terms of late effects and cosmetic results at 7-month and 3-year follow-up. Pearson Chi-square test was used, with an a-value of 0.05.Hyper/hypopigmentation and induration/fibrosis were commonly seen at 7-months follow-up (p = 0.84 and 0.83, respectively). The cosmetic results were good or excellent.Although the present study included a small number of patients and short follow-up time, the preliminary results were comparable between the study groups.

The authors present the result of a dosimetric comparison of inverse-planed intensity modulated, forward-planned intensity modulated, and conventional tangential technique in breast conserving radiotherapy.The breasts (Right side: Left side = 1:1), heart, and lungs of 28 patients were contoured on all the computed tomography (CT)-slice. Three different treatment plans were created: (1) inverse IMRT (iIMRT), (2) forward IMRT (fIMRT), and (3) conventional tangential technique (CVT). The total prescribed dose for all plans was 50 Gy/25 fractions. All treatment plans were normalized at 95% of the prescribed dose covered the entire PTV and used inhomogeneity corrections.For the entire group, the mean breast volume was 517 cc. The V105% for iIMRT, fIMRT and conventional plans was 1.12%, 2.36% and 16.81%, which iIMRT better than fIMRT and CVT (p0.001) and fIMRT better than CVT (p0.05). The Dmax for the iIMRT plan received 105.03%, which was significantly less than those from the fIMRT(106.6%, p0.001) and the conventional (110.68%, p0.001) plan. The PTV coverage (V95-105%) for the iIMRT, fIMRTand conventional was 96%, 91% and 87%, which iIMRT better than fIMRT and CVT (p0.05) and fIMRT better than CVT (p0.05). The PTV CI for the iIMRT technique was 0.704, which was significantly more conformity than those from the fIMRT (0.639, p0.001) and the conventional (0.539, p0.001) techniques. The PTV CI of fIMRT is significantly better than CVT (p0.005). Mean ipsilateral lung dose was 642.7 cGy, 747.6 cGy and 882.25 cGy for iIMRT fIMRT and CVT respectively (p0.05) The V20Gy reduced from 14.87% for conventional plan to 12.82% for the fIMRT plan, while 0.88% was obtained for the iIMRT plan (P0.05). The heart V30 Gy value was 3.124%, 4.65%, and 5.84% for iIMRT, fIMRT and conventional plans, respectively (p0.05). The mean dose of contralateral breast was 55.86 cGy, 60.33 cGy, 68.57 cGy for iIMRT, fIMRT and conventional plans, respectively (p0.05 both). The mean contralateral lung dose was 57.8 cGy, 43.87 cGy, and 32.28 cGy for iIMRT, fIMRT and conventional plans, respectively (p0.005 both).The iIMRT technique provides significantly improved PTV Dmax, PTV V105%, PTV V110%, target volume coverage, dose homogeneity and dose conformity throughout the target volume of breast and reduced doses to all critical structures, compared to the fIMRT and conventional techniques. In view of fIMRT technique, it significantly improved the dose distribution and reduced dose to OARs compared to conventional technique, although not better than iIMRT technique.

Three dimensional conformal radiation therapy (3D CRT) and intensity-modulated radiation therapy (IMRT) have been implemented at Department of Therapeutic Radiation and Oncology, King Chulalongkorn Memorial Hospital (KCMH) since July 2005. This is the first study in Thailand to evaluate the pattern of care and utilization of 3D CRT and IMRT for treatment in each individual cancer.Between July 2005 and July 2007, 925 newly diagnosed cancer patients underwent IMRT or 3D CRT at KCMH. The authors retrospectively reviewed the experience and utilization of 3D CRT and IMRT for each disease site and region.There were 471 males and 454 females. There were 332 patients (35.9%) treated with IMRT. Among the 332 IMRT patients, there were 100, 32 and 27 nasopharyngeal, lung and prostate cancers, respectively. On the contrary, 593 patients (64.1%) were treated with 3D CRT. Among these, breast, cervix and lung cancers were the most common diseases. Except for head and neck as well as genitourinary cancer 3D CRT was still the main technique used in more than 60% of the patients at KCMH.3D CRT and IMRT have been successfully implemented at KCMH for 2 years. Three dimensional conformal radiation therapy was still the main technique used in more than 60% of the patients at KCMH. Prospective studies evaluating tumor control and treatment sequelae are expected.

This is the first report in Thailand to evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of head-and-neck cancer.From July 2005 to March 2006, eighteen patients with head and neck cancer were treated with IMRT, fourteen of which were nasopharyngeal cancer. The median age at diagnosis was 52 years (range 23-58 years). The treatment plan composed of two sequential plans for PTV-low risk (50Gy in 25 fractions) and PTV-high risk (20Gy in 10 fractions). Chemotherapy was given to 13 patients with locoregionally advanced disease (stage T3/T4 and N2/3) using cisplatin (n = 3) or carboplatin (n = 10) every 3 weeks during the course of radiation therapy.The median overall treatment time was 49 days (range, 43-57 days), and 77.8 percent of the patients completed 35 fractions within 50 days. The clinical complete response and partial response rates at 3 months after complete radiation were 71.4% and 28.6%, respectively. However at the median follow-up of 5.6 months, the complete response rate increased to 89%. Treatment break during RT range from 3 to 7 days, was observed in three patients. All of them received concurrent chemoradiation. No distant metastasis was noted.The authors' experience of using concurrent chemotherapy with IMRT for a cohort of patients with head and neck carcinoma showed a very high rate response rate at early follow-up. Long-term clinical outcome is expected.

Phase I multicenter study defined the maximal tolerated dose (MTD), dose-limiting toxicity (DLT) and safety profile of capecitabine in combination with preoperative radiation for patients with locally advanced rectal cancer (LARC).Patients were treated with oral capecitabine (700, 800, 900, 1000, 1100 and 1200 mg/m2 twice daily continuously) plus preoperative whole pelvic irradiation (45-46 Gy in 23-25 fractions over 5-6 weeks). Surgery was performed at the median of 42 days after chemoradiation treatment.Twenty-seven patients were in this trial. Eighteen patients (3 per dose level) had received capecitabine from 700 mg/m2 twice daily to the highest dose level of 1200 mg/m2 twice daily. There were no grade 3/4 DLTs during dose escalation, a further nine patients were included at the highest capecitabine dose. Two of the twelve patients (16%) receiving capecitabine 1200 mg/m2 twice daily developed grade 3 diarrhea and discontinued treatment. There were no other grade 3/4 adverse events. After capecitabine chemoradiation, 24 of 27 patients (89%) received definite surgery. Primary and lymph node down staging occurred in ten patients (42%). Sphincter-sparing surgery was performed in seven patients (26%) and abdominal-perineal resection was performed in 17 patients (63%).Preoperative capecitabine chemoradiation based on continuous daily capecitabine is very well tolerated in patients with LARC. The authors did not reach the MTD in the present study.

Purpose: To measure the interfraction setup variation of patient undergoing intensity-modulated radiation therapy (IMRT) of head and neck cancer. The data was used to define adequate treatment CTV-to-PTV margin. Materials and methods: During March to September 2006, data was collected from 9 head and neck cancer patients treated with dynamic IMRT using 6 MV X-ray beam from Varian Clinac 23EX. Weekly portal images of setup fields which were anterior-posterior and lateral portal images were acquired for each patient with an amorphous silicon EPID, Varian aS500. These images were matched with the reference image from Varian Acuity simulator using the Varis vision software (Version 7.3.10). Six anatomical landmarks were selected for comparison. The displacement of portal image from the reference image was recorded in X (Left-Right, L-R), Y (Superior-Inferior, S-I) direction for anterior field and Z (Anterior-Posterior, A-P), Y (S-I) direction for lateral field. The systematic and random error for individual and population were calculated. Then the population-based margins were obtained. Results: A total of 135 images (27 simulation images and 108 portal images) and 405 match points was evaluated. The systematic error ranged from 0 to 7.5 mm and the random error ranged from 0.3 to 4.8 mm for all directions. The population-based margin ranged from 2.3 to 4.5 mm (L-R), 3.5 to 4.9 mm (S-I) for anterior field and 3.4 to 4.7 mm (A-P), 2.6 to 3.7 mm (S-I) for the lateral field. These margins were comparable to the margin that was prescribed at the King Chulalongkorn Memorial Hospital (5-10 mm) for head and neck cancer. Conclusion: The population-based margin is less than 5 mm, thus the margin provides sufficient coverage for all of the patients.