Scalp dose analysis for transient and permanent alopecia following conventional cranial irradiation using Image Guided Radiotherapy (IGRT): A prospective study.

PURPOSE: The dosimetry of scalp dose was prospectively studied and correlated with alopecia following conventional cranial irradiation in primary brain tumors patients. MATERIALS AND METHODS: Patients with primary brain tumors who required conventional radiotherapy were enrolled. A hairline marker was applied to the patient's scalp to identify the entire scalp region. The maximal dose to 2% volume of interest (D2) for the entire scalp region were obtained. The radiation dosages at the localized hair-loss areas were evaluated during the final week of RT (transient alopecia) and six months after completing RT (permanent alopecia). Kruskal-Wallis tests were used to compare the dosimetric parameter values with statistical significance set as p < 0.05. RESULTS: Forty-eight patients were included in the analysis. The prescribed radiation doses ranged from 50.4 to 60.0 Gy. Thirty-two patients experienced alopecia (27 transient and 5 permanent). The median D2 values adjusted for the entire scalp were higher in the alopecia group (38.40 Gy for transient alopecia and 47.84 Gy for permanent alopecia vs 11.90 Gy for no alopecia, p < 0.001). The D2 value was determined as a predictive parameter for alopecia. The threshold values for transient and permanent alopecia over the entire scalp were 22.15 Gy and 36.81 Gy, respectively. At the localized hair-loss areas, the D2 values for transient and permanent alopecia were higher at 44.82 Gy and 50.00 Gy, respectively. The radiation intensity at the localized hair-loss areas was also related to the severity of alopecia, with D2 values of 35.14 Gy and 46.39 Gy for clinically assigned grade 1 and grade 2 transient alopecia, respectively, with the D2 value being even higher for permanent alopecia. CONCLUSIONS: The D2 parameter value could be used to predict the type and severity of alopecia.

Gynecological brachytherapy hybrid training: The Tata Memorial Centre and BrachyAcademy experience.

PURPOSE: The lack of training is a significant barrier to practicing brachytherapy (BT). Tata Memorial Centre, alongside international BT experts and BrachyAcademy, developed a hybrid gynecological BT training module. This study outlines the preparation, organization, and execution of the 2022-2023 Mumbai training, evaluates its effectiveness, and highlights areas for improvement. MATERIALS AND METHODS: Participants were radiation oncologists (RO) and medical physicists (MP) with experience in gynecological BT aiming to transition to image-guided brachytherapy (IGBT). The training covered cervical, endometrial, vaginal, vulvar, periurethral cancers, and pelvic reirradiation. The hybrid course included online pre and postcourse homework assignments, a live workshop with hands-on training, a 6-month online follow-up, and a 12-month opportunity to share the transition experience. RESULTS: The December 2022 Mumbai live workshop spanned 2.5 days, attracting 39 participants from 8 countries (Asia, Africa, Australia/Oceania). Feedback rated the course 9/10, with 78% fully meeting expectations. Forty-four percent suggested extending hands-on training. At the 6-month follow-up, response rates were low (33% RO, 11% MP). Among responding RO, 70% reported practice changes after attending the course, 40% implemented IGBT concepts in clinical practice, and 50% increased confidence in image-guided procedures. Overall, 45% of respondent sites could strengthen their intracavitary/interstitial program, while others faced limitations due to lack of access to advanced BT applicators. CONCLUSION: The hybrid gynecological BT training concept was successfully executed. Areas for improvement include extending hands-on training and enhancing participant engagement postcourse. Structured steps beyond training may be needed to improve the utilization of advanced brachytherapy for gynecological cancers.

The Dose Difference of Dominant Intraprostatic Lesions (DILs) Defined by Magnetic Resonance-Guided and arc-based Intensity Modulated Radiation Therapy (IMRT), and the Association between Dose Difference and Recurrent Prostate Cancer.

BACKGROUND: There is growing evidence that local recurrence after radiotherapy often occurs within the dominant intraprostatic lesions (DILs) in prostate cancer. This study aimed to evaluate the dose difference between DILs defined by Magnetic Resonance-guided and arc-based Intensity Modulated Radiation Therapy (IMRT) and to assess the association between the dose difference and biochemical recurrence-free survival. MATERIALS AND METHODS: Between 2015 and 2019, 48 prostate cancer patients with DILs visible from multiparametric Magnetic Resonance Imaging (mpMRI) underwent arc-based IMRT with 70 Gy (2.5 Gy each fraction) to the prostate gland. Pretreatment mpMRI DILs contoured the prostate gland retrospectively. RESULTS: Biochemical recurrence was 8.3%. There was a significant difference between the median dose of DILs from MRI-guided imaging, 69.22 Gy, and the median dose of the whole prostate from arc-based IMRT which was 67.09 Gy (p < 0.001*). The Kaplan-Meier survival curve compared by log-rank test showed an escalation dose of at least 2 Gy tends to improve biochemical recurrence-free survival. However, this tendency did not reach statistical significance (p = 0.2). CONCLUSIONS: The dose distribution within DILs defined by mpMRI is significantly higher than the whole prostate dose from arc-based IMRT. Escalation doses in DILs tend to improve biochemical recurrence-free survival, further validation in larger patient cohorts with extended follow-up is warranted.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. METHODS: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Improvement of treatment plan quality with modified fixed field volumetric modulated arc therapy in cervical cancer.

PURPOSE: This study aims to introduce modified fixed field volumetric modulated arc therapy (MF-VMAT) which manually opened the field size by fixing the jaws and comparing it to the typical planning technique, auto field volumetric modulated arc therapy (AF-VMAT) in cervical cancer treatment planning. METHODS AND MATERIALS: Previously treated twenty-eight cervical cancer plans were retrospectively randomly selected and replanned in this study using two different planning techniques: AF-VMAT and MF-VMAT, resulting in a total of fifty-six treatment plans. In this study, we compared both planning techniques in three parts: (1) Organ at Risk (OARs) and whole-body dose, (2) Treatment plan efficiency, and (3) Treatment plan accuracy. RESULTS: For OARs dose, bowel bag (p-value = 0.001), rectum (p-value = 0.002), and left femoral head (p-value = 0.001) and whole-body (p-value = 0.000) received a statistically significant dose reduction when using the MF-VMAT plan. Regarding plan efficiency, MF-VMAT exhibited a statistically significant increase in both number of monitor units (MUs) and control points (p-values = 0.000), while beam-on time, maximum leaf travel, average maximum leaf travel, and maximum leaf travel per gantry rotation were statistically significant decreased (p-values = 0.000). In terms of plan accuracy, the average gamma passing rate was higher in the MF-VMAT plan for both absolute dose (AD) (p-value = 0.001, 0.004) and relative dose (RD) (p-value = 0.000, 0.000) for 3%/3 and 3%/2 mm gamma criteria, respectively. CONCLUSION: The MF-VMAT planning technique significantly reduces OAR doses and decreases the spread of low doses to normal tissues in cervical cancer patients. Additionally, this planning approach demonstrates efficient plans with lower beam-on time and reduced maximum leaf travel. Furthermore, it indicates higher plan accuracy through an increase in the average gamma passing rate compared to the AF-VMAT plan. Consequently, MF-VMAT offers an effective treatment planning technique for cervical cancer patients.

Preliminary results of adjuvant image-guided vaginal brachytherapy alone for early stage endometrial carcinoma.

Objective: This retrospective study evaluated the preliminary outcomes of image-guided vaginal brachytherapy (IG-VBT) in the adjuvant treatment of high intermediate risk endometrial cancer. Materials and Methods: Data were collected from 48 patients who underwent adjuvant IG-VBT between 2019 and 2022 at the Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University. The vaginal cuff clinical target volume (CTV-VC) is composed of a 4-mm-thick band around vaginal cylinder at the upper 3 cm of the vaginal cuff. A total dose of 21 Gy in three fractions was delivered to the CTV-VC, and the dose to the bladder and rectum were evaluated. Treatment details, patient characteristics, and outcomes were analyzed. Descriptive statistics were used for analysis, and Kaplan-Meier method was employed for survival analysis. Results: The mean age was 62 years, with mainly endometrioid carcinoma pathology (96 %). All patients were at stage I, with 87.5 % receiving complete surgical staging. Mean total treatment time was 10 days with mean D90 of CTV-VC was 29.7 Gy, and D2cc of bladder, rectum, and sigmoid were 24.6 Gy, 21.0 Gy, and 7.7 Gy, respectively. At a median follow-up of 37 months, 3-year local control, disease-free survival, and overall survival rates were 100 %, 100 %, and 97.9 %. respectively. Two patients (4.2 %) experienced grade 1-2 gastrointestinal toxicity, while no genitourinary toxicity or serious adverse events were observed. Conclusions: The preliminary results of IG-VBT in endometrial cancer demonstrated favorable outcomes in terms of vaginal control and toxicity. Further studies with larger cohorts and longer follow-up durations are warranted.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Prediction of Cervical Cancer Patients' Survival Period with Machine Learning Techniques.

OBJECTIVES: The objective of this research is to apply machine learning (ML) algorithms to predict the survival of cervical cancer patients. The aim was to address the limitations of traditional statistical methods, which often fail to provide accurate answers due to the complexity of the problem. METHODS: This research employed visualization techniques for initial data understanding. Subsequently, ML algorithms were used to develop both classification and regression models for survival prediction. In the classification models, we trained the algorithms to predict the time interval between the initial diagnosis and the patient's death. The intervals were categorized as "<6 months," "6 months to 3 years," "3 years to 5 years," and ">5 years." The regression model aimed to predict survival time (in months). We used attribute weights to gain insights into the model, highlighting features with a significant impact on predictions and offering valuable insights into the model's behavior and decision-making process. RESULTS: The gradient boosting trees algorithm achieved an 81.55% accuracy in the classification model, while the random forest algorithm excelled in the regression model, with a root mean square error of 22.432. Notably, radiation doses around the affected areas significantly influenced survival duration. CONCLUSIONS: Machine learning demonstrated the ability to provide high-accuracy predictions of survival periods in both classification and regression problems. This suggests its potential use as a decision-support tool in the process of treatment planning and resource allocation for each patient.

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.

Radiation Oncology Research in Asia: Current Status and a Peep Into the Future From the Federation of Asian Organizations for Radiation Oncology.

PURPOSE: This survey was conducted to assess the current research practices among the 14 members of the Federation of Asian Organizations for Radiation Oncology (FARO) committee, to inform measures for research capacity building in these nations. MATERIALS AND METHODS: A 19-item electronic survey was sent to two research committee members from the 14 representative national radiation oncology organizations (N = 28) that are a part of FARO. RESULTS: Thirteen of the 14 member organizations (93%) and 20 of 28 members (71.5%) responded to the questionnaire. Only 50% of the members stated that an active research environment existed in their country. Retrospective audits (80%) and observational studies (75%) were the most common type of research conducted in these centers. Lack of time (80%), lack of funding (75%), and limited training in research methodology (40%) were cited as the most common hindrances in conducting research. To promote research initiatives in the collaborative setting, 95% of the members agreed to the creation of site-specific groups, with head and neck (45%) and gynecological cancers (25%) being the most preferred disease sites. Projects focused on advanced external beam radiotherapy implementation (40%), and cost-effectiveness studies (35%) were cited as some of the potential areas for future collaboration. On the basis of the survey results, after result discussion and the FARO officers meeting, an action plan for the research committee has been created. CONCLUSION: The results from the survey and the initial policy structure may allow facilitation of radiation oncology research in the collaborative setting. Centralization of research activities, funding support, and research-directed training are underway to help foster a successful research environment in the FARO region.

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.

Salvage Treatment and Outcomes of Locally Advanced Cervical Cancer after Failed Concurrent Chemoradiation with or without Adjuvant Chemotherapy: Post Hoc Data Analysis from the ACTLACC Trial.

OBJECTIVES: To evaluate the type of salvage treatment and outcomes of patients with locally advanced cervical cancer who failed treatment with concurrent chemoradiation with or without adjuvant chemotherapy. METHODS: This was post hoc analyses of data from the randomized trial which included 259 patients who had FIGO stage IIB-IVA and had either pelvic radiation therapy concurrent with cisplatin followed by observation or paclitaxel plus carboplatin. Data of the patients who failed primary treatment were collected: type of salvage treatments, time to progress after salvage therapy, progression-free (PFS) and overall survivals (OS). RESULTS: After primary treatment, 85 patients had either persistence (36.5%), progression (18.8%), or recurrences (44.7%). The sites of failure were loco/regional in 52.9%, systemic failure in 30.6%, and loco-regional and systemic in 16.5%. Chemotherapy was given in 51.8%, being the sole therapy in 34.1%. Majority were combination agents (31.8%), with paclitaxel/carboplatin as the most common regimen. Radiation to the metastatic sites along with chemotherapy was used in 14.1% whereas palliative radiation therapy or supportive care was used in approximately 10% of each. The median time from the start of salvage treatment to progression was 9.2 months (range 0.2-64.0 months) with median PFS of 11.2 months (95% CI, 7.2-15.3 months). Median overall survival 27.3 months (95% CI, 4.4-69.6 months). CONCLUSIONS: Chemotherapy, either alone or with radiation therapy, was the most common salvage treatment in LACC after failure from primary treatment. The time to progress and PFS were less than 1 year with OS of approximately 2 years.

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.

Stereotactic radiosurgery for limited brain metastasis using three different techniques: helical tomotherapy, volumetric modulated arc therapy, and cone-based LINAC radiosurgery.

PURPOSE: Specific radiation delivered to tumors by stereotactic radiosurgery (SRS) has become widely used in the treatment of brain metastasis. This study aimed to compare radiation therapy planning and its parameters from SRS using three different modalities: helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and cone-based linac radiosurgery (Cone-based). MATERIALS AND METHODS: Each contouring dataset of patents who experienced one to four brain metastasis received SRS in our center was re-planned to create radiation therapy planning in all three treatment systems (HT, VMAT, and Cone-based). The parameters of conformity index (CI), homogeneity index (HI), CI50, and gradient index (CGI) were analyzed to compare the effects of the three techniques. Decision score analysis was used to evaluate the performance on dosimetric and organs-at-risk parameters among the different techniques by applying the Cone-based technique as a benchmark. RESULTS: A total of 21 patients with 39 lesions were included in this study. The results from the decision score analysis demonstrated statistically identical CI, CI50, and CGI values between Cone-based and VMAT for single lesions. For multiple lesions, VMAT also provided better CI when compared to Cone-based technique while HT exhibited the poorest dosimetric parameters. Moreover, VMAT exhibited the lowest BrainV5Gy value and displayed the shortest beam-on time calculation. CONCLUSION: We have conducted a comprehensive comparison of SRS planning approaches. The Cone-based technique revealed the highest HI value, while VMAT provided the best estimated beam-on time value. HT displayed a feasible SRS modality for single lesions, but not for multiple lesions.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

OBJECTIVES: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

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.

Nomogram Predicting Overall Survival in Patients With Locally Advanced Cervical Cancer Treated With Radiochemotherapy Including Image-Guided Brachytherapy: A Retro-EMBRACE Study.

PURPOSE: To present a nomogram for prediction of overall survival (OS) in patients with locally advanced cervical cancer (LACC) undergoing definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). METHODS AND MATERIALS: Seven hundred twenty patients with LACC treated with radiochemotherapy including IGABT in 12 institutions (median follow-up 56 months) were analyzed; 248 deaths occurred. Thirteen candidate predictors for OS were a priori chosen on the basis of the literature and expert knowledge. Missing data (7.2%) were imputed using multiple imputation and predictive mean matching. Univariate analysis with a multivariable Cox regression model for OS stratified by center was performed. Stepwise selection of predictive factors with the Akaike Information Criterion was used to obtain a predictive model and construct a nomogram for OS predictions 60 months from diagnosis; this was internally validated by concordance probability as a measure of discrimination and a calibration plot. RESULTS: Thirteen potential predictive factors were evaluated; 10 factors reached statistical significance in univariate analysis (age, Hemoglobin, FIGO Stage2009, tumor width, corpus involvement, lymph node involvement, concurrent chemotherapy, dose to 90% of the high-risk clinical target volume, volume of CTV at the first brachytherapy [CTVHRVolumeBT], overall treatment time [OTT]). Four factors were confirmed significant within the multivariable Cox regression model (FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT). The predictive model and corresponding nomogram were based on 7 Akaike Information Criterion-selected factors (age, corpus involvement, FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT, OTT) and showed promising calibration and discrimination (cross-validated concordance probability c = 0.73). CONCLUSIONS: This is the first nomogram to predict OS in patients with LACC treated with IGABT. In addition to previously reported factors (age, FIGO2009 stage, corpus involvement, chemotherapy delivery, OTT, lymph node involvement), status of primary tumor at the time of brachytherapy seems to be an essential outcome predictor. These results can facilitate individualized tailoring of treatment and patient counseling during the treatment.