A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

AIMS: To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). METHODS: Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. RESULTS: Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. CONCLUSIONS: Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

Prediction of survival and analysis of prognostic factors for hepatocellular carcinoma: a 20-year of imaging diagnosis in Upper Northern Thailand.

BACKGROUND: To evaluate survival rates of hepatocellular carcinoma (HCC), the Chiang Mai Cancer Registry provided characteristics data of 6276 HCC patients diagnosed between 1998-2020 based on evolution of imaging diagnosis. Evolution can be separated into four cohorts, namely, cohort 1 (1990-2005) when we had ultrasound (US) and single-phase computed tomography (CT), cohort 2 (2006-2009) when one multi-phase CT and one magnetic resonance imaging (MRI) were added, cohort 3 (2010-2015) when MRI with LI-RADS was added, and finally, cohort 4 (2016-2020) when two upgraded MRIs with LI-RADS were added. METHODS: Cox proportional hazard models were used to determine the relation between death and risk factors including methods of imagining diagnosis, gender, age of diagnosis, tumor stages, history of smoking and alcohol-use, while Kaplan-Meier curves were used to calculate survival rates. RESULTS: The median age of diagnosis was 57.0 years (IQR: 50.0-65.0) and the median survival time was 5.8 months (IQR: 1.9-26.8) during the follow-up period. In the univariable analysis, all factors were all associated with a higher risk of death in HCC patients except age of diagnosis. In a multivariable analysis, elderly age at diagnosis, regional and metastatic stages and advanced methods of imagining diagnosis during cohorts 2 and 3 were independently associated with the risk of death in HCC patients. The survival rate of patients diagnosed during cohort 4 was significantly higher than the other cohorts. CONCLUSION: As a significantly increasing survival rate of HCC patients in cohort 4, advanced methods of diagnostic imaging can be a part of the recommendation to diagnose HCC.

Plan quality analysis of stereotactic ablative body radiotherapy treatment planning in liver tumor.

PURPOSE: Stereotactic ablative body radiotherapy (SABR) in the liver, RTOG-1112 guides the treatment modalities including the dose constraints for this technique but not the plan parameters. This study is not only analyzing the plan quality by utilizing the plan parameters and indexes but also compares treatment modalities from the protocol implementation. METHOD AND MATERIAL: Twenty-five patients treated in the period from February 2020 to September 2022 were recruited in this analysis. Two planners randomly selected the patients and modalities. The modalities employed were Volumetric-Modulated Arc Therapy (VMAT) and Helical Tomotherapy (HT). Various parameters and indexes were used to access not only the plan quality but also to compare each modality. The parameters and indexes studied were the homogeneity index (HI), conformity index (CI), gradient distance (GD), and the dose received by the organs at risk. RESULT: The data reveals that the mean volume of PTV is 60.8 ± 53.9 cc where these targets exhibit no significant difference between each modality. The HI shows a consistent value for both modalities. Between each modality, the CI value shows less deviation, but the HT shows slightly higher performance than VMAT. The value of GD is 1.5 ± 0.3 cm where the HT provides a shorter distance compared to VMAT as well. CONCLUSION: The parameters and indexes should be utilized for the plan evaluation although in the guidelines this was not required. Various modalities were employed for treatment. Both can achieve the treatment criteria with slightly low performance of VMAT.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Breast Cancer Subtypes in Northern Thailand and Barriers to satisfactory survival outcomes.

BACKGROUND: The incidence of breast cancer (BC) in Thailand has been rising at an alarming rate. The annual incidence of BC in Thailand has doubled over a span of 15 years. A retrospective study was conducted with the primary objective of assessing and comparing survival rates of patients with BC, stratified by subtype of BC. METHODS: A retrospective study was implemented for a cohort of women receiving a diagnosis of invasive BC with the objective of assessing and comparing their overall survival, stratified by BC subtype. Thai women receiving a diagnosis of their first primary invasive BC between January 2006 and December 2015 at Chiang Mai University Hospital were studied with 3,150 cases meeting the eligible criteria. RESULTS: The median follow-up time was 4.9 years (Inter Quartile Range: 2.8-7.7). The most common diagnosed subtype was luminal B-like (n = 1,147, 36.4%). It was still the most prevalent subtype (35.8%) in women younger than 40 years and the 40-60 age-group, The proportion of patients with TNBC is the highest in women aged less than 40 years with 19.3% compared to the other age categories. Finally, among women older than 60 years, the proportion of each subtype was relatively uniform. Most women received a diagnosis of stage II disease. Triple negative subtype increased overall mortality in advanced staging (stages III and IV) (aHR:1.42, 95% CI: 0.96-2.11). The 5-year overall survival rate was found in luminal A-like at 82.8%, luminal B-like at 77.6%, HER-2 enriched at 66.4% and triple negative subtype at 64.2%. CONCLUSION: The histologic subtype, correlated with age and staging influenced the OS. Our results confirmed the association of triple negative BC with poor prognosis especially in advanced stage. The adjuvant medical treatment in our country could not be accessible in some group of patients, so the results of treatment and survival especially HER-2 enriched are lower than other countries without treatment barrier.

Integration of breast cancer care in a middle-income country: learning from Suandok Breast Cancer Network (SBCN).

BACKGROUND: Breast cancer incidence in Northern Thailand has shown a continuous increase since records began in 1983. In 2002 the urgency of the situation prompted Maharaj Nakorn Chiang Mai Hospital to initiate the Suandok Breast Cancer Network (SBCN). METHODS: The SBCN is a not-for-profit organization in the university hospital which serves as a training and education center and provides highly specialized medical care for patients in Chiang Mai and in 5 provinces of northern Thailand, with the key mission of improving breast cancer care. The short-term goal was to overcome the barriers to engagement with breast cancer and its treatment and the long-term goal was to increase the overall survival rate of breast cancer patients in our region. RESULTS: We enrolled breast cancer patients treated at Maharaj Nakorn Chiang Mai Hospital between January 2006 and December 2015 and divided into 2 cohorts: 1485 patients who were diagnosed from 2006 to 2009 (cohort 1: early implementation of SBCN) and 2383 patients who were diagnosed from 2010 to 2015 (cohort 2: full implementation of SBCN). Criteria to measure improved cancer waiting time (CWT) would include: time to diagnosis, time to surgery, and time to radiotherapy. The 5-year overall survival (OS) of the cohort 2 was higher than that in cohort 1, at 73.8 (72.0-75.5) compared to 71.5 (69.2-73.7) (p-value = 0.03). CONCLUSIONS: Reasons behind the success of project include the uniformity of care encouragement, service network development and timely access to each step of breast cancer management. The model used in SBCN could be adopted as a learning guide to improve healthcare access and outcome for breast cancer patients in low- to middle-income countries.

Incidence of radiation-induced hypothyroidism following head and neck irradiation: a single-center analysis.

Background: The purpose of this study was to investigate the incidence of primary hypothyroidism (HT), as well as any correlation between dosimetric parameters and thyroid dysfunctions after neck radiotherapy (RT) in head and neck cancer (HNC) patients. Materials and methods: This study retrospectively reviewed HNC patients who finished neck RT for at least 12 months and who had available back-up treatment information. Eligible patients further received a single thyroid function test (TFT). Dosimetric parameters of the thyroid glands were retrospectively evaluated in order to detect any correlation between dose-volume parameters and primary HT. Results: We reviewed 1,102 HNC patients. Accordingly, 64 patients were deemed eligible and were included in this study. The median time interval between RT completion and TFT was 21 months (interquartile range, 14-34 months), while 26 patients (40.6%) were diagnosed with HT. The thyroid volume spared from a dose of 50 Gy (VS50Gy) was found to be statistically significant and considered an associated factor for developing HT (p = 0.047). Furthermore, there was an observable trend indicating a reduction in the risk of HT when VS50Gy was more than 5 cm3 (p = 0.052). Conclusion: In our study, VS50Gy was determined to be a significant predictive parameter of radiation-induced HT.

Disparities in the change of cervical cancer mortality rate between urban and rural Chiang Mai in the era of universal health care and the Thai national screening program.

BACKGROUND: The Ministry of Public Health of Thailand established universal health coverage (UHC) in 2002, which also included national-level screening for cervical cancer in 2005. This study examined the changes in mortality of cervical cancer in rural and urban areas in Chiang Mai Province of northern Thailand during the era of UHC and the immediately preceding period. METHODS: Data of cervical cancer patients in Chiang Mai in northern Thailand, who died from 1998 through 2012, were used to calculate the change in age-standardized rates of mortality (ASMR) using a joinpoint regression model and to calculate estimated annual percent changes (APC). The change in mortality rate by age groups along with changes by geographic area of residence were determined. RESULTS: Among the 1177 patients who died from cervical cancer, 13(1%), 713 (61%) and 451 (38%) were in the young age group (aged < 30), the screening target group (aged 30-59) and the elderly group (aged ≥60), respectively. The mortality rate among women aged 30-59 significantly declined by 3% per year from 2003 through 2012 (p < 0.001). By area of residence, the mortality rate in women targeted by the screening program significantly decreased in urban areas but remained stable in more rural areas, APC of - 7.6 (95% CI: - 12.1 to - 2.8) and APC of 3.7 (95% CI: - 2.1 to 9.9), respectively. CONCLUSION: The UHC and national cervical cancer screening program in Thai women may have contributed to the reduction of the mortality rate of cervical cancer in the screening target age group. However, this reduction was primarily in urban areas of Chiang Mai, and there was no significant impact on mortality in more rural areas. These results suggest that the reasons for this disparity need to be further explored to equitably increase access to cervical cancer services of the UHC.

Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer.

Cancer stem cells (CSCs) play a critical role in radiation resistance and recurrence. Thus, drugs targeting CSCs can be combined with radiotherapy to improve its antitumor efficacy. Here, we investigated whether a gallotannin extract from Bouea macrophylla seed (MPSE) and its main bioactive compound, pentagalloyl glucose (PGG), could suppress the stemness trait and further confer the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, we evaluate the effect of MPSE or PGG to suppress CSC-like phenotypes and radiosensitization of HNSCC cell lines using a series of in vitro experiments, tumorsphere formation assay, colony formation assay, apoptosis assay, and Western blotting analysis. We demonstrate that MPSE or PGG is able to suppress tumorsphere formation and decrease protein expression of cancer stem cell markers. MPSE or PGG also enhanced the radiosensitivity in HNSCC cells. Pretreatment of cells with MPSE or PGG increased IR-induced DNA damage (γ-H2Ax) and enhanced radiation-induced cell death. Notably, we observed that pretreatment with MPSE or PGG attenuated the IR-induced stemness-like properties characterized by tumorsphere formation and the CD44 CSC marker. Our findings describe a novel strategy for increasing therapeutic efficacy for head and neck cancer patients using the natural products MPSE and PGG.

An underestimated pitfall of oral candidiasis in head and neck cancer patients undergoing radiotherapy: an observation study.

BACKGROUND: Oral candidiasis is a common problem associated with head and neck radiation therapy (RT) consequences being pain, burning sensation, taste change, and systemic infection. There are difficulties in differentiating between oral candidiasis and radiation induced oral mucositis. We conducted a prospective study to explore the incidence of clinical oral candidiasis and evaluate the accuracy of diagnosis among head and neck cancer (HNC) patients receiving RT or concurrent chemoradiotherapy (CCRT). METHODS: This study included 86 HNC patients who had no clinical signs or symptoms of oral candidiasis. Oral mucosa and tongue swabs were carried out and analyzed three times by fungal cultures at the following time points: (1) before RT, (2) at the time of clinically diagnosed candidiasis or during RT at between the 15th-17th fraction (whichever occurred first), and (3) at the end of RT. The accuracy of clinical oral candidiasis was explored and confirmed by fungal colonization techniques. The incidence and risk factors associated with fungal colonization before and throughout the treatment were analyzed. RESULTS: The overall incidence of clinical oral candidiasis was 53.5% throughout the course of RT. Confirmation of fungal colonization was found in 39.5%, 65.9%, and 57.7% of cases before RT, during RT, and end of RT, respectively. The accuracy of the diagnosis using only clinical presentation was demonstrated in 60%, 50%, and 52% before RT, during RT, and end of RT, respectively. Logistic regression analysis showed that age, CCRT, and using 2% viscous lidocaine solution were independent risk factors for fungal colonization. CONCLUSIONS: The results of this study demonstrated an underestimation of clinical oral candidiasis before and throughout the course of radiotherapy from using only clinical sign and symptoms. Crucial attention to detail and testing in the oral examination could improve decision making for detection of oral candidiasis in HNC patients receiving RT or CCRT.

Analysis of the planned, delivered dose distributions and quality assurance for helical tomotherapy and volumetric modulated arc therapy in locally advanced non-small cell lung cancer.

BACKGROUND: With full access to both helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT), we compared locally advanced non-small cell lung cancer (LA-NSCLC) treatment plans and verified the plans using patient-specific pretreatment quality assurance (PSQA). MATERIALS AND METHODS: For each of the seventeen patients included in the study, two treatment plans (i.e. HT and VMAT) were created. Optimized plans were evaluated following the ICRU 83 criteria. Planned quality indexes and dosimetric parameters were compared. Lastly, all plans were subjected to PSQA assessment by determining the gamma passing rate (GPR). RESULTS: All dosimetry results obtained from the planning target volume passed the ICRU 83 criteria. With regard to similar homogeneity indices, VMAT produced better conformity number values than HT (0.78 vs. 0.64), but differences in the values were insignificant. Furthermore, VMAT was associated with a significantly shorter mean treatment time (1.91 minutes vs. 6.66 minutes). For PSQA assessment, both techniques resulted in adequate GPR values (> 90% at the 3%/3 mm criteria). CONCLUSION: Both HT and VMAT techniques led to the generation of clinically satisfactory and reliable radiotherapy plans. However, the VMAT plan was associated with a non-significantly better degree of conformity and a significantly shorter treatment time. Thus, VMAT was determined to be a better choice for LA-NSCLC.

Dosimetric comparison of TomoDirect, helical tomotherapy, and volumetric modulated arc therapy for postmastectomy treatment.

PURPOSE: To compare dose to the targets and organs at risk (OARs) in different situations for postmastectomy patients who require radiation to the chest wall with or without regional nodal irradiation when using three treatment techniques. METHODS AND MATERIALS: Thirty postmastectomy radiotherapy (PMRT) patients previously treated by helical tomotherapy (HT) at our institution were identified for the study. The treatment targets were classified in three situations which consisted of, the chest wall (CW) only, the chest wall plus supraclavicular lymph nodes (CW + SPC), and the chest wall plus supraclavicular and whole axillary lymph nodes irradiation (CW + SPC+AXLN). The volumetric modulated arc therapy (VMAT) plans and Tomodirect (TD) plans were created for each patient and compared with HT treatment plans which had been treated. The target coverage, dose homogeneity index (HI), conformity index (CI), and dose to OARs were analyzed. The quality scores were used to evaluate the appropriate technique for each situation from multiparameter results. RESULTS: The HT and VMAT plans showed the advantage of target coverage and OARs sparing for the chest wall with regional nodal irradiation with the higher plan quality scores when compared with TD plans. However, TD plans demonstrated superiority to contralateral breast sparing for the chest wall without regional nodal situation reaching the highest of planned quality scores. HT plans showed better HI, CI, and target coverage (P < 0.01) than TD and VMAT plans for all patient situations. Volumetric modulated arc therapy plans generated better contralateral breast and heart sparing at a lower dose than HT. CONCLUSION: The arc-based techniques, HT and VMAT plans, provided an advantage for complex targets in terms of target coverage and OARs sparing. However, the static beam TD plan was superior for contralateral organ sparing meanwhile achieving good target coverage for the chest wall without regional node situations.

The prognostic value of excision repair cross-complementing Group 1 expression in nasopharyngeal cancer patients.

BACKGROUND: Overexpression of excision repair cross-complementing Group 1 (ERCC-1) is related to cisplatin resistance and defective repair of radiation damage. The purpose of this study was to evaluate the clinical significance of excision (ERCC-1) expression in nasopharyngeal cancer (NPC). MATERIALS AND METHODS: We conducted a retrospective review of patients diagnosed with NPC between 2000 and 2013. The archived tissues were analyzed using immunohistochemistry to determine ERCC-1 expression. The ERCC-1 expression level along with other clinical factors and overall survival (OS) were analyzed. Hazard ratio (HR) with a 95% confidence interval was calculated to assess the risk. RESULTS: The analysis of ERCC-1 expression was available in 262 NPC patients who had medical records at our hospital. Among those patients, 221 (84%) were treated with curative radiotherapy (RT)/concurrent chemoradiotherapy, 22 (7%) were treated with palliative RT alone, and 19 (9%) were given best supportive care. There was no correlation between ERCC-1 expression and stage of cancer or OS. No difference in 5-year OS was found between patients with low ERCC-1 expression and high ERCC-1 expression (38% vs. 36%; P = 0.981). The adjusted HR (aHR) of cancer death increased with cancer stage (aHR = 2.93 for advanced Stages III-IV; P = 0.001) and age (aHR = 2.11 for age >55; P ≤ 0.001). ERCC-1 expression exhibited no prognostic significance in our study (aHR = 1). CONCLUSION: In this study, ERCC-1 expression has no statistical significance to be considered a prognostic factor for OS among NPC patients. On the other hand, cancer stage, age, and types of treatment can be prognostic factors in NPC patients.

Childhood cancer incidence and survival in Thailand: A comprehensive population-based registry analysis, 1990-2011.

BACKGROUND: Southeast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20-year period. METHODS: Cancer cases diagnosed in children ages 0-19 years (n = 3574) from 1990 to 2011 were extracted from five provincial population-based Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Age-standardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the Kaplan-Meier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC). RESULTS: The ASR of all childhood cancers during the study period was 98.5 per million person-years with 91.0 per million person-years in 1990-2000 and 106.2 per million person-years in 2001-2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P < 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5-year survival for all childhood cancers significantly improved from 39.4% in 1990-2000 to 47.2% in 2001-2011 (P < 0.01). CONCLUSIONS: Both childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in low- and middle-income countries can improve understanding of cancer etiology and pediatric health care disparities.

Intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer.

OBJECTIVES: To report the intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer. MATERIALS AND METHODS: Ninety-two patients with cervical cancer (stage IB-IVA, according to FIGO staging), were treated by curative radiotherapy from February 2012 to June 2015. All patients were treated with whole pelvic radiotherapy to 50 Gy in 25 fractions and central shielding after 44 Gy, in combination with TAUS-guided brachytherapy, in order to escalate the total dose (EQD2) to the minimal dose at cervical points (in EQD2 concepts) defined by TAUS, while maintaining low doses to ICRU bladder and rectal points. The treatment results and toxicity profiles were reported. RESULTS: At median follow-up time of 41.2 months (range 8 to 61 months) the pelvic control, disease-free survival, and overall survival rates were 84.8%, 75%, and 88%, respectively. The mean applied doses to cervix, bladder, and rectal points were 83.5, 72.3, and 76.5 Gy, respectively. Eight patients developed grade 2 Gastrointestinal toxicity. CONCLUSION: The 3-year results demonstrated that TAUS-guided brachytherapy is feasible and associated with excellent tumor control/toxicity rates in cervical cancer.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

PURPOSE: The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. METHODS: Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. RESULTS: The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. CONCLUSIONS: For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Risk patterns of lung cancer mortality in northern Thailand.

BACKGROUND: Over the past decade, lung cancers have exhibited a disproportionately high mortality and increasing mortality trend in Thailand, especially in the northern region, and prevention strategies have consequently become more important in this region. Spatial analysis studies may be helpful in guiding any strategy put in place to respond to the risk of lung cancer mortality in specific areas. The aim of our study was to identify risk patterns for lung cancer mortality within the northern region of Thailand. METHODS: In the spatial analysis, the relative risk (RR) was used as a measure of the risk of lung cancer mortality in 81 districts of northern Thailand between 2008 and 2017. The RR was estimated according to the Besag-York-Mollié autoregressive spatial model performed using the OpenBUGS routine in the R statistical software package. We presented the overall and gender specific lung cancer mortality risk patterns of the region using the Quantum Geographic Information System. RESULTS: The overall risk of lung cancer mortality was the highest in the west of northern Thailand, especially in the Hang Dong, Doi Lo, and San Pa Tong districts. For both genders, the risk patterns of lung cancer mortality indicated a high risk in the west of northern Thailand, with females being at a higher risk than males. CONCLUSIONS: There was distinct geographical variation in risk patterns of lung cancer mortality in Thailand. Differences could be related to differences in risk factors such as ground-based radon and air pollution. This study provides a starting point for estimating the spatial pattern of the risk of lung cancer mortality and for examining associations between geographic risk factors and lung mortality for further studies.

Evaluation of Deformable Image Registration (DIR) Methods for Dose Accumulation in Nasopharyngeal Cancer Patients during Radiotherapy.

INTRODUCTION: Deformable image registration (DIR) is used to modify structures according to anatomical changes for observing the dosimetric effect. In this study, megavoltage computed tomography (MVCT) images were used to generate cumulative doses for nasopharyngeal cancer (NPC) patients by various DIR methods. The performance of the multiple DIR methods was analysed, and the impact of dose accumulation was assessed. PATIENTS AND METHODS: The study consisted of five NPC patients treated with a helical tomotherapy unit. The weekly MVCT images at the 1st, 6th, 11th, 16th, 21st, 26th, and 31st fractions were used to assess the dose accumulation by the four DIR methods. The cumulative dose deviations from the initial treatment plan were analysed, and correlations of these variations with the anatomic changes and DIR methods were explored. RESULTS: The target dose received a slightly different result from the initial plan at the end of the treatment. The organ dose differences increased as the treatment progressed to 6.8% (range: 2.2 to 10.9%), 15.2% (range: -1.7 to 36.3%), and 6.4% (range: -1.6 to 13.2%) for the right parotid, the left parotid, and the spinal cord, respectively. The mean uncertainty values to estimate the accumulated doses for all the DIR methods were 0.21 ± 0.11 Gy (target dose), 1.99 ± 0.76 Gy (right parotid), 1.19 ± 0.24 Gy (left parotid), and 0.41 ± 0.04 Gy (spinal cord). CONCLUSIONS: Accuracy of the DIR methods affects the estimation of dose accumulation on both the target dose and the organ dose. The DIR methods provide an adequate dose estimation technique for observation as a result of inter-fractional anatomic changes and are beneficial for adaptive treatment strategies.

The Outcome of the First 100 Nasopharyngeal Cancer Patients in Thailand Treated by Helical Tomotherapy.

BACKGROUND: The aim of the study was to analyse of two-year loco-regional failure free survival (LRFFS), distant metastasis free survival (DMFS), overall survival (OS), and toxicity outcomes of the first 100 nasopharyngeal carcinoma patients in Thailand treated by helical tomotherapy. PATIENTS AND METHODS: Between March 2012 and December 2015, 100 patients with non-metastatic nasopharyngeal carcinoma were treated by helical tomotherapy. All patients were treated by platinum-based concurrent chemoradiotherapy and adjuvant or neo-adjuvant chemotherapy. RESULTS: The median age was 51 years (interquartile ranges [IQR]: 42.5-57.0). The mean ± SD of D95% of planning target volume (PTV) 70, 59.4 and 54 were 70.2 ± 0.5, 59.8 ± 0.6, and 54.3 ± 0.8 Gy, respectively. The mean ± SD of conformity index, and homogeneity index were 0.89 ± 0.13 and 0.06 ± 0.07. Mean ± SD of D2 % of spinal cord and brainstem were 34.1 ± 4.4 and 53.3 ±6.3 Gy. Mean ± SD of D50 of contralateral and ipsilateral parotid gland were 28.4 ± 6.7 and 38.5 ± 11.2 Gy. At a median follow-up of 33 months (IQR: 25-41), the 2-year LRFFS, DMFS, OS were 94% (95%CI: 87-98%), 96% (95% CI: 89-98%), and 99% (95% CI: 93-100%), respectively. Acute grade 3 dermatitis, pharyngoesophagitis, and mucositis occurred in 5%, 51%, and 37%, respectively. Late pharyngoesophagitis grade 0 and 1 were found in 98% and 2% of patients. Late xerostomia grade 0, 1 and 2 were found in 17%, 78% and 5%, respectively. CONCLUSIONS: Helical tomotherapy offers good dosimetric performance and achieves excellent treatment outcome in nasopharyngeal carcinoma patients.

Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy. METHODS AND FINDINGS: HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naïve patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naïve patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naïve patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p = 0.03). High genomic concordance between biopsies taken before and following afatinib resistance was observed with stable clonal structures in non-responding tumours, and evidence of branched evolution in 8 of 9 tumours analysed. Recruitment to the trial was terminated early following the LUX-Breast 1 trial, which showed that afatinib combined with vinorelbine had similar PFS and OR rates to trastuzumab plus vinorelbine but shorter overall survival (OS), and was less tolerable. The main limitations of this study are that the results should be interpreted with caution given the relatively small patient cohort and the potential for tumour sampling bias between pre- and post-treatment tumour biopsies. CONCLUSIONS: Afatinib, with or without vinorelbine, showed activity in trastuzumab-naïve HER2-positive IBC patients in a planned subgroup analysis. HER2-positive IBC is characterized by frequent TP53 gain-of-function mutations and a high mutational burden. The high mutational load associated with HER2-positive IBC suggests a potential role for checkpoint inhibitor therapy in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325428.