Retrospective Analysis of All Types of Adjuvant Radiotherapy in Endometrial Cancer: Single-Center Experiences in a Middle-Income Country.

OBJECTIVE: We retrospectively analyzed the efficacy, focusing on overall survival (OS) and the patterns of failure, along with the toxicities of adjuvant radiotherapy (RT) in endometrial cancer patients. METHODS: Two-hundred and nineteen patients with endometrial cancer patients who received adjuvant radiotherapy ± adjuvant chemotherapy (ACT) from January 2014 to December 2018 were investigated for overall survival (OS), local recurrence-free survival rate (LRFS), regional recurrence-free survival rate (RRFS), and distant metastasis-free survival rate (DMFS). RESULT: Two-hundred and fourteen patients were evaluated. The numbers of VBT alone, EBRT plus VBT, and adjuvant chemotherapy (ACT) plus EBRT plus VBT were 65 (30.4%), 80 (37.4%), and 69 (32.2%) patients, respectively. Stage I (107 patients) was the most common followed by stage III (87 patients). With a median follow-up time of 67 months (IQR 56-78), the 5-year overall survival rates for VBT alone, EBRT plus VBT, and EBRT plus VBT plus ACT were 84.4%, 65%, and 57.4%, respectively. The most common severe (grade 3-4) acute toxicity was neutropenia (4.6%), followed by diarrhea (3.7%). Grade 3-4 late proctitis was found in only 1.9%. On multivariate analysis, advanced age (HR 6.15, p: 0.015), lymph node involvement (HR 6.66, p: 0.039), cervical involvement (HR 10.60, p: 0.029), and substantial LVSI (HR 21.46, p: 0.005) were associated with a higher risk of death. CONCLUSION: Advanced age (>65), substantial LVSI, lymph node involvement, and cervical stromal involvement were associated with poor overall survival. These findings here will help identifying high-risk patients and would make it possible to avoid unnecessary adjuvant treatment among patients with a good prognosis.

Head and Neck Cancer of Unknown Primary: A Multicenter Retrospective Cohort study in Northern Thailand, an Endemic Nasopharyngeal Cancer Area.

OBJECTIVE: This study aimed to evaluate the characteristics and oncological outcomes of head and neck carcinoma of unknown primary (HNCUP) patients in an endemic nasopharyngeal cancer (NPC) area. METHODS: One hundred and forty-four HNCUP patients curatively treated between January 1995 and December 2022 from 5 centers were retrospectively recruited onto the study to analyze the clinicopathological characteristics and oncological outcomes and compare them with historical data. A multivariate Cox proportional hazards model analysis was performed to evaluate factors affecting survival outcomes. A propensity-matched pair analysis of the patients with positive and negative EBV-encoded small RNA (EBER) staining was applied to compare the characteristics and outcomes between the two groups. RESULTS: The median follow-up time was 45 months. Most patients (88.2%) received total mucosal irradiation (TMI). Primary tumor emergence (PTE) was detected in 6 patients (4.2%) who did not have TMI. The 5-year overall survival (OS), disease-free survival, and locoregional recurrence-free survival were 51.3%, 64.9%, and 72.7%, respectively. Extranodal extension and N3 compared with the N1 stage were the significant independent predictors for OS (HR 2.90, 95% CI 1.12-7.51, p = 0.028 and HR 3.66, 95%CI 1.23-11.89, p = 0.031, respectively). The matched-pair analysis demonstrated comparable all survival outcomes between the EBER-positive and -negative groups. All patients in the matched pair analysis received TMI, and no PTE was detected. CONCLUSION: Our survival outcomes were comparable to previous studies with a low rate of PTE. The matched pair analysis of EBER-positive and -negative groups revealed similar oncological outcomes and no primary tumor emergence when total mucosal irradiation was administered.

Longitudinal measurements of neutrophil-to-lymphocyte ratio in nasopharyngeal cancer treated with concurrent chemoradiotherapy.

OBJECTIVE: We study factors affecting neutrophil-to-lymphocyte ratio (NLR) and its changes throughout the treatment (ΔNLR) of nasopharyngeal carcinoma (NPC) underwent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy (AC) and oncological outcomes including overall survival (OS) and disease-free survival (DFS). METHODS: Data from 81 NPC patients was retrospectively evaluated. NLRs were obtained from first week of CCRT (pre-CCRT), last week of CCRT (end-CCRT), and at last cycle of AC (end-AC). Pre-CCRT NLR was categorized into "low" and "high". End-CCRT and end-AC ΔNLRs were divided into "increased" and "decreased" based on NLR at these two timepoints relative to the value at pre-CCRT. Associations between sex, age, cancer stage and NLR, ΔNLRs were investigated. OS and DFS were reported. RESULTS: Median NLR at pre-CCRT (2.47) was lower than NLR at end-CCRT (6.29) and end-AC (3.77) (P-value = 0.043). Advanced cancer stage associated with high pre-CCRT NLR (P-value = 0.047). Male gender was associated with "increased" end-CCRT ΔNLR, whereas male gender and age ≤51 were associated with "increased" end-AC ΔNLR. Three-year OS and DFS rates were 85.25% and 76.39%, respectively. There were no statistically significant differences observed in OS and DFS among groups categorized by pre-CCRT NLR, ΔNLRs, gender, age, and cancer stage. CONCLUSIONS: NLR increases during NPC treatment. Advanced staging is associated with higher baseline NLR. Increased ΔNLR is associated with male gender at end-CCRT and male gender with age ≤51 years at end-AC. No relation between NLR and its dynamic change with either OS or DFS was demonstrated.

Development of a quality assurance system in radiation oncology: A 12-year experience in a University Hospital.

PURPOSE: This study aimed to report 12 years of experience in the development of a quality assurance system in radiation oncology in a university hospital. MATERIAL AND METHODS: We developed the Quality Assurance Program in Radiation Oncology (QUAPRO) in 2008 to detect treatment deviation in the radiotherapy (RT) process with three steps of near-miss detection: simulation and prescription (primary check, PC), treatment planning (secondary check, SC), and treatment delivery process (tertiary check, TC). We transferred our paper-based medical records to electronic-based radiotherapy information systems (RTISs) in 2013. QUAPRO was completely integrated into RTIS in 2017. Since then, electronic-based incident reporting has been conducted. The program is called the Radiation Incident Learning System (RILS). The near-miss rates were compared during the three time periods: 2008-2012, 2013-2017, and 2017-2020. RESULTS: Five years of paper-based QUAPRO for 2008-2012 demonstrated a fluctuation in the checking ratio, with a gradually increasing rate of near misses of 3.5-19.7%. After electronic-based medical records were developed in 2013, the results revealed a dramatic increase from a rate of 2.7 to 4.2 in the number of checks per patient and achieved an increased rate of near misses of 24.7% for PC, SC, and TC. The rate of near misses gradually decreased to 5.3% after 2017 because of RT workflow improvement. CONCLUSION: The analysis of 12 years in near-miss data reflected the effectiveness of our quality assurance program. The QUAPRO system can detect near-miss incidents in the whole RT workflow and illustrate the detection improvement when integrated into electronic-based medical records. Regular feedback and exploration of near-miss reporting are recommended for proper RT workflow improvement.

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.

Brachytherapy dose changes: comparing in-room and out-room image-guided brachytherapy. A randomized study.

Purpose: Image-based brachytherapy, involving an image machine and a brachytherapy unit in the same room (in-room brachytherapy [IRBT]), limits patient movements; however, this technique may not be feasible in high workload centers. In this study, we compared changes in the dose and volume of organs at risk (OARs) with out-room brachytherapy (ORBT) technique, in which patients musted be transferred to a waiting room and then transferred back for brachytherapy delivery. Material and methods: This was a randomized prospective study comparing changes in D2cc doses and volume of OARs during IRBT and ORBT. Patients underwent CT for treatment planning (CT1) installed in brachytherapy loading room, and another CT immediately before brachytherapy (CT2) during each fraction. While patients remained on CT table after CT1 during treatment planning and delivery in IRBT arm, they were transferred out to waiting room and back to CT table in ORBT arm. CT2 was analyzed with CT1 to evaluate any changes in volumes and doses. Results: A total of 294 fractions of brachytherapy were considered. The findings indicated no significant differences in the mean D2cc changes (Gy) (CT2 minus CT1) to the bladder, rectum, and sigmoid between IRBT and ORBT (mean ±SD: -0.07 ±0.36 vs. -0.01 ±0.39, p = 0.1426; -0.15 ±0.32 vs. -0.14 ±0.29, p = 0.8898; -0.17 ±0.38 vs. -0.19 ±0.31, p = 0.5221, respectively). Moreover, significant correlations were observed between D2cc changes and volume changes to each of OARs, p < 0.001. Conclusions: IRBT does not result in differences in dose changes between planning and pre-treatment imaging when compared with ORBT. Consequently, ORBT can be considered for routine practice in high workload centers. Correlations in volume change and dose change to OARs were also observed.

Survival outcome of cervical cancer patients treated by image-guided brachytherapy: a 'real world' single center experience in Thailand from 2008 to 2018.

The objective of our study was to evaluate the survival outcome of cervical cancer patients treated using image-guided brachytherapy (IGBT). From 2008 to 2018, 341 patients with cervical cancer were treated by radical radiotherapy. IGBT (by computed tomography [CT] or transabdominal ultrasound [TAUS]) was used to treat all of these patients. The characteristic data and patient status after treatment were recorded. All data were evaluated for survival outcome analysis. From a total of 341 patients, 295 patients were analyzed and 46 patients were excluded due to data missing in the survival outcomes. At the median follow-up time of 48 months (IQR 30-80 months), The 4-year local control, progression-free survival and overall survival rates were 89.5%, 74.9% and 69.1%, respectively. For overall survival, the size (> 5 cm), pathology (non-SCCA), stage (stage III-IV by FIGO 2009), lymph node (LN) (presented) and overall treatment time (OTT) (> 56 days) showed statistical significance in univariate analysis while non-SCCA pathology, advanced stage, presented LN and longer OTT showed statistical significance in multivariate analysis. In conclusion, our analysis reports a 4-year overall survival rate of 69.1%. Non-SCCA pathology, advanced stage disease, LN presence and longer OTT showed worse prognostic factors in multivariate analysis.

The association of vagina equivalent dose in 2Gy fraction (EQD2) to late vagina toxicity in patients of cervical cancer treated with WPRT plus IGABT.

AIM: To evaluate the associations of vaginal dose parameters and incidence of vaginal stenosis in patients with cervical cancer treated with image-guided brachytherapy (IGBT). MATERIALS AND METHODS: Fifty-four patients with cervical cancer treated with IGBT were included. The vagina contouring was done on previously treated CT images and the vaginal dose points were marked. The cumulative dose in EQD2 from EBRT and IGBT was calculated for both aspects and the vaginal toxicity was evaluated. RESULTS: At median follow-up time of 18.5 months, grade 2 or higher vaginal stenosis was observed in 24% of patients. On univariate analysis, parameters that were associated with ≥ grade 2 vaginal stenosis were age, mean dose of lateral 5 mm vagina, dose at PIBS-2 cm, mid vaginal D0 .03cc, mid vagina D1cc, lower vagina D0.03cc, lower vagina D0.1cc, lower vagina D1cc and lower vagina D2cc. On multivariate analysis, the significant parameters were age > 68.5 years old (P = 0.038), mean dose of lateral 5-mm (P = 0.034), and dose at PIBS-2 cm (P = 0.042). CONCLUSIONS: Age > 68.5 years old, mean dose of lateral 5 mm vagina and dose at PIBS-2 cm were associated with grade 2 or higher vaginal stenosis.

Natural history and treatment outcome of radiotherapy for Kimura's disease.

BACKGROUND: Kimura's disease is a rare inflammatory disease that usually appears in head and neck region. We reported natural history of the disease and treatment outcome of radiotherapy (RT) in Chiang Mai University Hospital. METHODS: A retrospective review was performed for all Kimura's disease patients treated with radiotherapy at our center between 2002 and 2017. RESULTS: A total of 20 patients with Kimura's disease were reviewed. There were 14 men and 6 women. All patients presented with the mass in head and neck region. Eleven patients were treated with a definitive intent with RT, 9 patients were treated with RT after recurrence from other modalities. All patients were treated with local external beam RT with 2 Gy per fraction to a median total dose of 30 Gy (range 30-40). The median follow-up time was 4 years (range 1-16.5 years). One patient died from HIV opportunistic infection after 1.5 year of radiation with complete response of Kimura's disease. Most of the patients responded to radiotherapy and controlled the disease at the time of analysis. Two patients had multiple recurrences at new areas outside radiotherapy field. Skin toxicity grade 1 was the most common late side effect which was found in 8 (44%) patients. We did not find severe late toxicity or second malignancy in this patient cohort. CONCLUSION: : Good local control of Kimura's disease can be achieved, with a radiation dose of 30-40 Gy, with insignificant late toxicities. We suggest that radiotherapy should be one of the treatments of choice for Kimura's disease both in primary or recurrence setting.

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.

Dynamic changes in practical inflammation and immunity markers in cancer patients receiving immune-enhancing nutritional supplementation during concurrent chemoradiotherapy.

BACKGROUND: Immune-enhancing nutrition (IMN) strengthens the systematic inflammatory response and the immune system. Neutrophil to lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) are affected during cancer therapies. OBJECTIVE: We carried out an analysis of the dynamic changes in NLR and ALC over time in cancer patients with or without IMN supplementation. METHODS: 88 cancer patients receiving concurrent chemoradiotherapy (CCRT) were randomized into regular diet group, and regular diet and IMN group.Generalized estimation equation models were used to assess associations between patient's characteristics, IMN, and dynamic changes in NLR and ALC over time. RESULTS: NLR and ALC at pre-CCRT were significantly associated with dynamic changes in NLR (adjusted ß= 1.08, 95% confidence interval [CI]: 0.64-1.52) and ALC (adjusted ß= 0.41, 95% CI: 0.36-0.46). The magnitudes of the NLR and ALC changes through CCRT were lower in patients receiving IMN, although the differences were not statistically significant except ALC at the end of CCRT in head and neck cancer patients (P= 0.023). CONCLUSION: Dynamic negative changes in both markers were demonstrated throughout CCRT. There were non-significant trend in promising changes in both NLR and ALC values in the whole group in IMN supplementation.

Comparison of clinical outcomes achieved with image-guided adaptive brachytherapy for cervix cancer using CT or transabdominal ultrasound.

PURPOSE: This study aimed to evaluate retrospectively the treatment results when using various image-guided adaptive brachytherapy treatments for cervical cancer treated by radical radiotherapy. METHODS AND MATERIALS: From 2014 to 2017, 188 patients with cervical carcinoma were treated by whole pelvic radiotherapy plus four fractions of image-guided brachytherapy. Eight patients were excluded because of missing data. Consequently, 180 patients were analyzed. Of 180 patients, 92 were treated by CT-based brachytherapy (CT-BT), and transabdominal ultrasound-based brachytherapy (TAUS-BT) was used to treat another group. The treatment results and toxicity outcomes were evaluated by comparing the image-guidance techniques. RESULTS: The mean follow-up time was 32 months (interquartile range 29.5-42 months). The mean age was 57 years (interquartile range from 50 to 65 years). In the CT-BT group, the mean cumulative doses to high-risk clinical target volume, bladder, rectum, and sigmoid were 87.2 Gy, 84.0 Gy, 68.8 Gy, and 69.8 Gy, respectively. In the TAUS-BT group, the mean cumulative doses to the cervix reference, bladder, and rectum points were 84.0 Gy, 65.5 Gy, and 74.0 Gy, respectively. There were no differences in the 2-year local control rate (p = 0.88) and disease-free survival rate (p = 0.34) in both groups. No difference in gastrointestinal and genitourinary toxicity was observed in both groups, but there was higher vaginal toxicity in the TAUS-BT group compared with the CT-BT group (p = 0.03). CONCLUSIONS: No difference in treatment results was observed between CT-based and TAUS-based approaches. However, TAUS-BT had higher vaginal toxicity in our retrospective analysis.

Cost-utility analysis of 5-fluorouracil and capecitabine for adjuvant treatment in locally advanced rectal cancer.

BACKGROUND: Adjuvant chemotherapy at concurrent time with radiation therapy (RT) or at adjuvant time alone in locally advanced rectal cancer (LARC) is used with several regimens. The cost-utility analysis was conducted to compare administration of two 5-FU regimens and capecitabine in the aspect of provider and societal viewpoint. METHODS: Stage II or III rectal cancer patients who received pre-operative or post-operative concurrent chemoradiotherapy and adjuvant chemotherapy were compared by using decision tree model between (I) 5-FU plus leucovorin (LV) for 5 days per cycle (Mayo Clinic regimen); (II) 5-FU continuous infusion (CI) for 120-h per cycle (CAO/ARO/AIO-94 protocol); (III) standard regimen of capecitabine. All probability data were extracted from landmark study. Direct medical costs were the cost from database of Drug Medical Supply Information Center, while direct non-medical cost and utility were interviewed from stage II and III rectal cancer patients. The time horizon of this study was 5 years. Incremental cost-effectiveness ratio (ICER) was the final result in this study, which determined as the numerator of the difference of costs among three drug regimens, and the difference of quality-adjusted life years (QALYs) from each drug was the denominator. RESULTS: 5-FU plus LV was the cheapest and least efficacy for adjuvant treatment of LARC in both provider and societal viewpoint. In provider viewpoint, the ICERs of 5-FU CI and capecitabine were 334,550 THB/QALY (US $9,840/QALY) and 189,935 THB/QALY (US $5,586/QALY), respectively, with the corresponding societal viewpoint of 264,447 THB/QALY (US $7,778/QALY) and 119,120 THB/QALY (US $3,504/QALY) when 5-FU plus LV was used as comparator. The most influential parameter for value of treatment was acquisition cost of capecitabine. At the willingness to pay for one QALY gained in Thailand (160,000 THB or US $4,706), 5-FU plus LV, 5-FU CI and capecitabine had probabilities of cost-effectiveness of 63%, 2% and 35%, respectively. CONCLUSIONS: Capecitabine was the most expensive regimen but produced the higher effectiveness than 5-FU plus LV and 5-FU CI. The most influential parameter in the model was acquisition cost of capecitabine.