Choosing the right adjuvant therapy for stage III-IVA endometrial cancer: A comparative analysis of chemoradiotherapy and chemotherapy.

OBJECTIVE: The optimal adjuvant treatment for patients with locally advanced endometrial cancer (EC) remains debatable. We comparatively analyzed recurrence patterns and survival outcomes in patients with stage III-IVA EC treated with adjuvant chemotherapy (CT) exclusively or combined with radiotherapy (CRT). METHODS: We retrospectively analyzed 184 patients treated for stage III-IVA EC at 2 tertiary institutions between 2010 and 2021. All patients underwent standard primary surgery and received either CT alone (n = 89) or CRT (n = 95) as an adjuvant treatment. We compared the failure patterns, recurrence-free survival (RFS), and overall survival (OS) between the CT and CRT groups. RESULTS: The median follow-up period was 54.8 months. Most patients underwent pelvic (94.6%) or para-aortic (75.5%) lymphadenectomies. The 5-year RFS was 69.2% with CRT versus 56.3% with CT (P = 0.038), and 5-year OS was 86.1% versus 78.9% (P = 0.357). Pelvic and para-aortic recurrence rates were significantly higher in the CT group (pelvic: 29.2%; para-aortic: 20.2%) than in the CRT group (pelvic: 10.5%; para-aortic: 6.3%). The CRT group showed a higher rate of distant recurrence (CRT, 23.2% vs. CT, 14.6%) however, the 5-year cumulative incidence of distant recurrence was not significantly different between the two groups (CRT, 28% vs. CT, 35%). CONCLUSIONS: This study highlights the potential benefits of adjuvant CRT in patients with stage III-IVA EC. The incorporation of molecular classification is necessary to derive optimal personalized adjuvant treatment strategies for this patient population.

Tumor Heterogeneity of Breast Cancer Assessed with Computed Tomography Texture Analysis: Association with Disease-Free Survival and Clinicopathological Prognostic Factor.

Breast cancer is a heterogeneous disease, and computed tomography texture analysis (CTTA), which reflects the tumor heterogeneity, may predict the prognosis. We investigated the usefulness of CTTA for the prediction of disease-free survival (DFS) and prognostic factors in patients with invasive breast cancer. A total of 256 consecutive women who underwent preoperative chest CT and surgery in our institution were included. The Cox proportional hazards model was used to determine the relationship between textural features and DFS. Logistic regression analysis was used to reveal the relationship between textural features and prognostic factors. Of 256 patients, 21 (8.2%) had disease recurrence over a median follow-up of 60 months. For the prediction of shorter DFS, higher histological grade (hazard ratio [HR], 6.12; p < 0.001) and lymphovascular invasion (HR, 2.93; p = 0.029) showed significance, as well as textural features such as lower mean attenuation (HR, 4.71; p = 0.003) and higher entropy (HR, 2.77; p = 0.036). Lower mean attenuation showed a correlation with higher tumor size, and higher entropy showed correlations with higher tumor size and Ki-67. In conclusion, CTTA-derived textural features can be used as a noninvasive imaging biomarker to predict shorter DFS and prognostic factors in patients with invasive breast cancer.

The Effect of Respiratory Motion in Breast Intensity-modulated Radiation Therapy: 3D-Printed Dynamic Phantom Study.

BACKGROUND/AIM: This study evaluated the dosimetric effect of respiratory motion in intensity-modulated radiation therapy (IMRT) for breast cancer using a three-dimensional (3D)-printed dynamic phantom. MATERIALS AND METHODS: Computed tomography (CT) data from breast cancer patients were used to create a 3D-printed breast phantom. Various types of treatment plans were generated using CT images acquired at the exhalation phase. Different infill densities in the 3D-printed phantom were tested to validate their effect on simulating the average human breast tissue density. Plans were delivered to the 3D-printed dynamic phantom in the exhalation position and free-breathing motion. Dosimetric verification was performed using Gafchromic EBT3 films. RESULTS: After changing the infill density to obtain Hounsfield Unit values similar to those of human breast tissue, a realistic patient-specific breast phantom was fabricated using a 3D printer at 80% infill density. The gamma passing rates of the dose distribution delivered in the exhalation phase and free-breathing motion were 92% or more. In addition, the dynamic phantom doses with free-breathing motion were directly compared with the static phantom dose in terms of sagittal dose profiles. Gamma passing rates of >93% and 90% were achieved at 3%/3 mm and 3%/2 mm, respectively. CONCLUSION: Despite a blurred dose distribution, the dose map of the film measurement with respiratory motion could be delivered without significantly increasing the dose heterogeneity of the tumor bed or loss of target coverage. Our findings demonstrate that the impact of respiration on breast IMRT for whole-breast irradiation was not significant, even in the tumor bed.

StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the overall efficacy of StrataXRT, a topical gel dressing, in preventing acute radiation dermatitis (RD) in breast cancer patients undergoing radiotherapy (RT). METHODS: A systematic search was conducted on April 25, 2023 in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) assessing the effectiveness of StrataXRT in preventing acute RD in breast cancer patients undergoing adjuvant RT to the breast or chest wall with or without regional nodes were included. Pooled incidence odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model, with analysis and forest plots generated in RevMan v5.4. RESULTS: The analysis included three RCTs with a total of 189 patients assessed using per-protocol analysis. Two RCTs compared StrataXRT to standard of care, while the third compared it with Mepitel film and was reported separately. In the former RCTs, the odds ratio (OR) for developing acute grade 3 RD favored StrataXRT at 0.05 (95% CI, 0.01-0.22; P < 0.0001). The OR for developing acute grades 2-3 RD was 0.32 (95% CI, 0.03-3.18; P = 0.33). The RCT comparing StrataXRT with Mepitel film showed insignificant ORs for grade 3 and grades 2-3 RD. One RCT reported significantly lower erythema index (P = 0.008) and melanin index (P = 0.015) in StrataXRT patients. The use of StrataXRT did not raise additional safety concerns. CONCLUSION: StrataXRT may help prevent severe acute RD in breast cancer RT patients. Further high quality, large-scale studies are needed to confirm these findings.

Dosimetric Impact of Respiratory Motion During Breast Intensity-modulated Radiation Therapy Using Four-dimensional Dose Calculations.

BACKGROUND/AIM: The use of intensity-modulated radiation therapy (IMRT) in the treatment of breast cancer is increasing worldwide. Despite clear benefits concerning normal tissue sparing and dose homogeneity, the effects of breathing motion and setup error during breast IMRT should be considered. This study aimed to assess the dosimetric impact of respiratory motion on breast IMRT using four-dimensional (4D) dose calculations. PATIENTS AND METHODS: Multiple computed tomography datasets acquired in three representative respiratory amplitudes, were retrospectively re-planned. Based on the reference dose distribution (RDD), motion-adjusted dose distributions (MDD) were recalculated. All 4D dose distributions were calculated by the voxel-based accumulation of RDD and MDD using five temporal probabilities. The dosimetric parameters of the 4D plans were compared to those of RDD. RESULTS: The dosimetric parameters of the planning target volume (PTV) were not significantly different between the RDD and 4D plans. Of the parameters of tumor bed (TB) simultaneous-integrated boost (SIB), the mean dose and V95% for the 4D plans were significantly reduced compared to those of RDD, and the percentage difference in the TB V95% ranged from -1.1% to -5.7% (p<0.05). CONCLUSION: The breast IMRT plan was robust against respiratory motion during tidal breathing. However, special considerations should be made when designing the TB SIB.

Clinical Characteristics and Risk Factors for Fatality and Severity in Patients with Coronavirus Disease in Korea: A Nationwide Population-Based Retrospective Study Using the Korean Health Insurance Review and Assessment Service (HIRA) Database.

BACKGROUND: We aimed to investigate the clinical characteristics and risk factors for fatality and severity in these patients. METHODS: In this nationwide population-based retrospective study, we investigated the data of 7339 laboratory-confirmed COVID-19 patients, aged ≥ 18 years, using the Korean Health Insurance Review and Assessment Service (HIRA) database. Comorbidities and medications used were identified using HIRA codes, and severe COVID-19 was defined as that requiring oxygen therapy, mechanical ventilator, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation. The outcomes were death due to COVID-19 and COVID-19 severity. RESULTS: Mean patient age was 47.1 years; 2970 (40.1%) patients were male. Lopinavir/ritonavir, hydroxychloroquine, antibiotics, ribavirin, oseltamivir, and interferon were administered to 35.8%, 28.4%, 38.1%, 0.1%, 0.3%, and 0.9% of patients, respectively. After adjusting for confounding factors, diabetes mellitus, chronic kidney disease, previous history of pneumonia, aging, and male were significantly associated with increased risk of death and severe disease. No medication was associated with a reduced risk of fatality and disease severity. CONCLUSIONS: We found several risk factors for fatality and severity in COVID-19 patients. As the drugs currently used for COVID-19 treatment have not shown significant efficacy, all efforts should be made to develop effective therapeutic modalities for COVID-19.

Reducing Radiation Dermatitis Using a Film-forming Silicone Gel During Breast Radiotherapy: A Pilot Randomized-controlled Trial.

BACKGROUND/AIM: To evaluate whether topical use of a film-forming silicone gel (StrataXRT®) could reduce radiation dermatitis compared to a moisturizing cream (X-derm®) in patients receiving whole breast radiotherapy. PATIENTS AND METHODS: A total of 56 patients with breast cancer were randomized to use StrataXRT or X-derm. The severity of radiation dermatitis was graded using physiological skin parameters, clinician-assessed visual rating scales and patient-reported symptoms. Changes in these parameters from baseline to 4 weeks post-radiotherapy were evaluated every two weeks. RESULTS: Two-way repeated-measures ANOVA revealed different patterns of changes in the erythema index (F=3.609, p=0.008) and melanin index (F=3.475, p=0.015). The post hoc analysis demonstrated a significantly lower erythema index and melanin index in the patients allocated to the StrataXRT group. CONCLUSION: The use of StrataXRT can reduce radiation dermatitis with respect to objectively measured physiological skin parameters. The results of the present study will support the feasibility of conducting a larger randomized controlled trial.

Dose gradient curve: A new tool for evaluating dose gradient.

PURPOSE: Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. METHODS: The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. RESULTS: Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. CONCLUSIONS: The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Cardiac risk index as a simple geometric indicator to select patients for the heart-sparing radiotherapy of left-sided breast cancer.

INTRODUCTION: This is a dosimetric study to identify a simple geometric indicator to discriminate patients who meet the selection criterion for heart-sparing radiotherapy (RT). The authors proposed a cardiac risk index (CRI), directly measurable from the CT images at the time of scanning. METHODS: Treatment plans were regenerated using the CT data of 312 consecutive patients with left-sided breast cancer. Dosimetric analysis was performed to estimate the risk of cardiac mortality using cardiac dosimetric parameters, such as the relative heart volumes receiving ≥25 Gy (heart V25 ). For each CT data set, in-field heart depth (HD) and in-field heart width (HW) were measured to generate the geometric parameters, including maximum HW (HWmax ) and maximum HD (HDmax ). Seven geometric parameters were evaluated as candidates for CRI. Receiver operating characteristic (ROC) curve analyses were used to examine the overall discriminatory power of the geometric parameters to select high-risk patients (heart V25  ≥ 10%). RESULTS: Seventy-one high-risk (22.8%) and 241 low-risk patients (77.2%) were identified by dosimetric analysis. The geometric and dosimetric parameters were significantly higher in the high-risk group. Heart V25 showed the strong positive correlations with all geometric parameters examined (r > 0.8, p < 0.001). The product of HDmax and HWmax (CRI) revealed the largest area under the curve (AUC) value (0.969) and maintained 100% sensitivity and 88% specificity at the optimal cut-off value of 14.58 cm2 . CONCLUSIONS: Cardiac risk index proposed as a simple geometric indicator to select high-risk patients provides useful guidance for clinicians considering optimal implementation of heart-sparing RT.

The Predictive Value of Tumor Size, Volume, and Markers During Radiation Therapy in Patients With Cervical Cancer.

OBJECTIVES: We investigated the prognostic significance of changes in primary tumor volume and serum squamous cell carcinoma antigen (SCC-ag) levels during radiation therapy (RT) in patients with cervical cancer. METHODS: We conducted a review of 40 patients treated with RT. All patients received external beam RT and intracavitary brachytherapy. The primary tumor volume and squamous cell carcinoma antigen levels were measured pre-RT and mid-RT. Overall survival (OS) and progression free survival (PFS) were estimated, and possible prognostic factors for survival were analyzed. RESULTS: The correlation coefficient between primary tumor volume reduction rate (pTVRR) and serum squamous cell carcinoma antigen reduction rate in all patients was 0.550 (P < 0.001). In univariate analysis, stage more than II (P <0.001), pre-RT pTV of 55 cm or more (P = 0.05), mid-RT tumor size of 4 cm or more (P = 0.004), and pTVRR of 90% or less (P = 0.031) were significant unfavorable prognostic factors for PFS, whereas stage (P = 0.009) was the only significant prognostic factor for OS. Multivariable analysis revealed that none of these factors were independently associated with PFS or OS. CONCLUSIONS: There was a significant correlation between pTVRR and squamous cell carcinoma antigen reduction rate. Our findings indicate that the tumor parameters such as pre-RT pTV, mid-RT tumor size, and pTVRR are associated with PFS in women with cervical cancer.

A Case of Primary Breast Diffuse Large B-Cell Lymphoma Treated with Chemotherapy Followed by Elective Field Radiation Therapy: A Brief Treatment Pattern Review from a Radiation Oncologist's Point of View.

We here report a case of primary breast lymphoma (PBL). A 44-year-old woman presented with a painless mass in the right breast. Fine needle aspiration cytology and excisional biopsy were performed. Excisional biopsy revealed low grade lymphoma, which was subsequently confirmed with histopathology and diagnosed as diffuse large B-cell lymphoma (DLBCL). A chest computed tomography scan revealed a 3.5 cm sized breast mass with skin thickening and a small sized lymphadenopathy in the ipsilateral axilla. Radiation therapy including the right whole breast and ipsilateral axilla and supraclavicular lymph node was performed after the patient received four courses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab) chemotherapy. At the follow-up period of 42 months, the patient is surviving with no evidence of disease. No morbidities occurred in this patient during the follow-up period. We also briefly review the current practice pattern in PBL patients with DLBCL.

Cardiac dose reduction with breathing adapted radiotherapy using self respiration monitoring system for left-sided breast cancer.

PURPOSE: To quantify the cardiac dose reduction during breathing adapted radiotherapy using Real-time Position Management (RPM) system in the treatment of left-sided breast cancer. MATERIALS AND METHODS: Twenty-two patients with left-sided breast cancer underwent CT scans during breathing maneuvers including free breathing (FB), deep inspiration breath-hold (DIBH), and end inspiration breath-hold (EIBH). The RPM system was used to monitor respiratory motion, and the in-house self respiration monitoring (SRM) system was used for visual feedback. For each scan, treatment plans were generated and dosimetric parameters from DIBH and EIBH plans were compared to those of FB plans. RESULTS: All patients completed CT scans with different breathing maneuvers. When compared with FB plans, DIBH plans demonstrated significant reductions in irradiated heart volume and the heart V25, with the relative reduction of 71% and 70%, respectively (p < 0.001). EIBH plans also resulted in significantly smaller irradiated heart volume and lower heart V25 than FB plans, with the relative reduction of 39% and 37%, respectively (p = 0.002). Despite of significant expansion of lung volume using inspiration breath-hold, there were no significant differences in left lung V25 among the three plans. CONCLUSION: In comparison with FB, both DIBH and EIBH plans demonstrated a significant reduction of radiation dose to the heart. In the training course, SRM system was useful and effective in terms of positional reproducibility and patient compliance.

Establishment of linear accelerator-based image guided radiotherapy for orthotopic 4T1 mouse mammary tumor model.

This study was conducted to assess the feasibility of image guided radiotherapy (IGRT) for orthotopic 4T1 mouse mammary tumor using linear accelerator (LINAC). Eighteen Balb/C mice were inoculated with 4T1 cells on left mammary fat pad and nine of them were irradiated using LINAC. Tumors, planning target volumes (PTV), bowels adjacent to tumors, bones and lungs were delineated on planning CT images. IGRT plans were generated to irradiate prescription dose to at least 90% of the PTV and then compared with conventional 2-dimensional plans with anterior-posterior and posterior-anterior beams with 5 mm margins (2D AP/PA plan). Homemade dose-build-up-cradle was designed to encompass mouse bed for homogeneous dose build up. To confirm the irradiated dose, tumor doses were measured using diode detector placed on the surface of tumors. Plan comparison demonstrated equivalent doses to PTV while sparing more doses to normal tissues including bowel (from 90.9% to 40.5%, median value of mean doses) and bone marrow (from 12.9% to 4.7%, median value of mean doses) than 2D AP/PA plan. Quality assurance using diode detector confirmed that IGRT could deliver 95.3-105.3% of the planned doses to PTV. Tumors grew 505.2-1185.8% (mean 873.3%) in the control group and 436.1-771.8% (mean 615.5%) in the irradiated group. These results demonstrate that LINAC-based IGRT provides a reliable approach with accurate dose delivery in the radiobiological study for orthotropic tumor model maintaining tumor microenvironment.