Quantifying radiation-induced breast fibrosis by shear-wave elastography in patients with breast cancer: A 12-months-follow-up data of a prospective study.

Purpose: To assess radiation-induced fibrosis (RIF) using shear-wave elastography (SWE) in patients with breast cancer who received radiotherapy (RT) after breast conserving surgery. Methods: Forty-one patients were enrolled in a prospective study before RT. SWE and B-mode ultrasonography were performed to measure elasticity. For quantitative measurement, the maximum elasticity value was measured in the tumor bed and non-tumor bed of the treated breast, and contralateral breast before RT and at 3, and 12 months after RT. and RIF was recorded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The mean ± standard deviation elasticity values for the tumor bed, non-tumor bed, and contralateral breast were 71.2 ± 74.9 kPa, 19.4 ± 9.8 kPa and 20.3 ± 10.0 kPa before RT; 28.7 ± 26.3 kPa, 15.1 ± 7.0 kPa, and 14.7 ± 6.3 kPa at 12 months after RT, respectively. The elasticity values for all three measurement areas before and 12 months after RT were significantly different (p < 0.001 for tumor bed, p = 0.002 for non-tumor bed, p = 0.001 for contralateral breast). At 12 months follow-up, the distribution of grades of RIF evaluated by CTCAE grade was grade 0 in 43.9 %, grade 1 in 48.8 %, and grade 2 in 7.3 %. Conclusion: We demonstrated that SWE enables the evaluation of tissue stiffness to provide quantified information for the RIF of breast cancer. Further studies with long-term follow-up should provide more quantitative data.

Diagnostic assessments and treatment results of well-differentiated gastric-type adenocarcinoma of the uterine cervix (Adenoma malignum): A multicenter retrospective analysis of KROG 22-03 study.

OBJECTIVE: Among cervical adenocarcinomas, well-differentiated gastric adenocarcinoma of the uterine cervix (WD-GAS), previously termed adenoma malignum (minimal deviation adenocarcinoma) is not well understood. Because of its rarity and difficulty in diagnosis, there is no standard care for WD-GAS. Thus, we conducted the first multicenter retrospective study on WD-GAS to clarify prognostic factors for long-term survival and recurrence. METHODS: Patients diagnosed with WD-GAS at eight hospitals participated in this multi-center study. Overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Additionally, OS between the early and advanced FIGO stage groups were compared with the log-rank test. Cox regression analysis was conducted to identify significant factors associated with recurrence-free survival (RFS). RESULTS: A total of 73 patients from eight hospitals in South Korea were included in the analysis. The median follow-up period was 44.8 months, and all patients underwent curative surgical intervention as the primary treatment. Recurrence was observed in 17 patients (23.3%). Ten patients had locoregional recurrence, four patients had distant metastasis, and three patients presented with both locoregional recurrence and distant metastasis. The Cox regression analysis identified several statistically significant factors associated with RFS, including vaginal invasion (VI), parametrial invasion (PMI), resection margin (RM), and nodal and lymphovascular invasion (LVI). When considering these five factors together, patients without any of the factors exhibited recurrence-free survival (RFS) of 97.0% at three years and those with more than one of these factors had a 3-year RFS of 65.4% (P < 0.001). CONCLUSION: WD-GAS showed relatively high locoregional recurrence rate. Positive PMI, VI, RM, nodal involvement, and LVI were associated with a significant increase in recurrence or distant metastasis rates.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

Patterns of locoregional recurrences and suggestion of the clinical target volume in resected perihilar extrahepatic cholangiocarcinoma.

Purpose: To evaluate the patterns of locoregional recurrence (LRR) in patients with perihilar extrahepatic cholangiocarcinoma (PEHC) treated with radical resection and to suggest the optimal target volume for elective nodal irradiation. Methods: Medical records of PEHC patients who underwent radical resection between January 2000 and September 2021 at five institutions were reviewed. Patients who were confirmed with LRR in the follow-up imaging study were included. The LRR sites were mapped onto the corresponding sites in template computed tomography images. The margin around the vascular structure was investigated to generate the clinical target volume (CTV) covering the common sites of regional recurrences. Results: A total of 87 LRRs in 46 patients were identified, 29 (33.3%) of which were local recurrences and 58 (66.7%) were regional recurrences. The most common site of local recurrence was the liver resection margin (n = 16), followed by the anastomosis site (n = 8). Regional recurrences were observed most commonly in the para-aortic area (n = 13), followed by in the aortocaval space (n = 11), portal vein area (n = 11), and portocaval area (n = 9). Nodal CTV was generated by adding an individualized margin around the portal vein, aorta, common hepatic artery, celiac artery, and left gastric artery. Conclusions: The LRR patterns in the resected PEHC were evaluated and specific guidelines for nodal CTV delineation were provided, which may help physicians delineating the target volume in postoperative radiotherapy for PEHC. These findings need further validation in a lager cohort.

Incorporating axillary-lateral thoracic vessel juncture dosimetric variables improves model for predicting lymphedema in patients with breast cancer: A validation analysis.

Background: A relationship between the axillary-lateral thoracic vessel juncture (ALTJ) dose and lymphedema rate has been reported in patients with breast cancer. The purpose of this study was to validate this relationship and explore whether incorporation of the ALTJ dose-distribution parameters improves the prediction model's accuracy. Methods: A total of 1,449 women with breast cancer who were treated with multimodal therapies from two institutions were analyzed. We categorized regional nodal irradiation (RNI) as limited RNI, which excluded level I/II, vs extensive RNI, which included level I/II. The ALTJ was delineated retrospectively, and dosimetric and clinical parameters were analyzed to determine the accuracy of predicting the development of lymphedema. Decision tree and random forest algorithms were used to construct the prediction models of the obtained dataset. We used Harrell's C-index to assess discrimination. Results: The median follow-up time was 77.3 months, and the 5-year lymphedema rate was 6.8 %. According to the decision tree analysis, the lowest lymphedema rate (5-year, 1.2 %) was observed in patients with ≤ six removed lymph nodes and ≤ 66 % ALTJ V35Gy. The highest lymphedema rate was observed in patients with > 15 removed lymph nodes and an ALTJ maximum dose (Dmax) of > 53 Gy (5-year, 71.4 %). Patients with > 15 removed lymph nodes and an ALTJ Dmax ≤ 53 Gy had the second highest rate (5-year, 21.5 %). All other patients had relatively minor differences, with a rate of 9.5 % at 5 years. Random forest analysis revealed that the model's C-index increased from 0.84 to 0.90 if dosimetric parameters were included instead of RNI (P <.001). Conclusion: The prognostic value of ALTJ for lymphedema was externally validated. The estimation of lymphedema risk based on individual dose-distribution parameters of the ALTJ seemed more reliable than that based on the conventional RNI field design.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Development and Validation of a Normal Tissue Complication Probability Model for Lymphedema After Radiation Therapy in Breast Cancer.

PURPOSE: To develop and test a multivariable normal tissue complication probability (NTCP) model predicting lymphedema in patients with breast cancer receiving radiation therapy. METHODS AND MATERIALS: We retrospectively reviewed 1345 patients with breast cancer who received radiation therapy from 2 independent institutions. The patients were divided into a training cohort (institution A, n = 368, all treated with 3-dimensional conformal external beam radiation therapy [RT] with 2 Gy/fraction) and an external validation cohort (institution B, n = 977, treated either with 3-dimensional conformal external beam RT or with volumetric modulated RT and either with 1.8-2.0 Gy/fraction or with 2.67 Gy/fraction). Axillary-lateral thoracic vessel juncture (ALTJ) was delineated. The multivariable model was generated using dosimetric and clinical parameters. The performance of the model was comprehensively validated internally and externally. RESULTS: During a median follow-up of 78.7 months for the entire cohort, 97 patients (7.2%) developed lymphedema. The multivariable model that took into account the number of lymph nodes dissected, as well as the volume of the ALTJ receiving a dose ≥35 Gy equivalent doses in 2-Gy fractions (ALTJ V35), showed good agreement between predicted and observed results for both internal and external validation (Hosmer-Lemeshow P value > .05). The area under the receiver operating characteristic curve (AUC) and negative log-likelihood values for the multivariable NTCP model were 0.89 and 0.19 in internal validation and 0.83 and 0.19 in external validation. In addition, the multivariable model performance was acceptable for hypofractionated regimens (AUC 0.70) and volumetric modulated arc therapy (AUC 0.69). The number of lymph nodes dissected and ALTJ V35 were found to be the most important factors influencing lymphedema after radiation therapy. CONCLUSIONS: We first developed and validated the multivariable NTCP model for the lymphedema incidence in patients with breast cancer after radiation therapy. The multivariable NTCP model showed excellent performance and robustness in predicting lymphedema in both internal and completely independent external validations. The multivariable model for lymphedema prediction was robust and reliable for different treatment modalities and fractionation regimens.

The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12).

PURPOSE: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. MATERIALS AND METHODS: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). RESULTS: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. CONCLUSION: The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Treatment Outcomes according to the EndoPredict Score in ER-Positive, HER2-Negative Early Breast Cancer.

Purpose: The purpose of this study was to evaluate the treatment outcomes of estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer according to the risk group using EndoPredict (EP) score. Patients and Methods: Between 2015 and 2019, 207 patients with ER+/HER2- pN0-N1 early breast cancer who underwent surgery, EP test, and adjuvant radiotherapy were accrued. The EPclin score, which combines the molecular EP score with nodal status and tumor size, was calculated, and patients were divided into EPclin low- or high-risk groups by the cutoff value of 3.3. Results: There were 154 and 53 patients in the EPclin low- and high-risk groups, respectively. Forty-one patients (81.1%) of the high-risk group received adjuvant chemotherapy, while only 1 (0.6%) of the low-risk group did. With a median follow-up of 54.1 months (range 8.2-76.6), the 5-year disease-free survival rates of low- and high-risk groups were 100% and 88.9%, respectively (p < 0.001). Conclusions: The EPclin score was associated with recurrences in ER+/HER2- early breast cancer.

Postmastectomy Radiation Therapy for Node-Negative Breast Cancer of 5 cm or Larger Tumors: A Multicenter Retrospective Analysis (KROG 20-03).

PURPOSE: To evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomy. MATERIALS AND METHODS: Medical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p <0.001, 0.018, and <0.001, respectively). Other characteristics were not significantly different between the two groups. RESULTS: With a median follow-up of 95 months (range, 1-249), there were 9 locoregional recurrences, and 20 distant metastases. The 8-year locoregional recurrence-free survival rates were 98.0% with PMRT and 91.3% without PMRT (p=0.133), and the 8-year disease-free survival (DFS) rates were 91.8% with PMRT and 73.9% without PMRT (p=0.008). On multivariate analysis incorporating age, histologic grade, lymphovascular invasion, hormonal therapy, chemotherapy, and PMRT, the absence of lymphovascular invasion and the receipt of PMRT were associated with improved DFS (p=0.025 and 0.009, respectively). CONCLUSION: Locoregional recurrence rate was very low in node-negative breast cancer of 5cm or larger tumors treated with mastectomy regardless of the receipt of PMRT. However, PMRT was significantly associated with improved DFS. Further investigation is needed to confirm these findings.

Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Novel prognostic classification predicts overall survival of patients receiving salvage whole-brain radiotherapy for recurrent brain metastasis from breast cancer: A recursive partitioning analysis (KROG 16-12).

BACKGROUND: To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. MATERIALS AND METHODS: We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000-2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT. RESULTS: The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/ß of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P < 0.001). CONCLUSIONS: In our RPA classification according to the control of both primary BC and extracranial metastasis and the dose of salvage WBRT, significant differences in OS were observed. The subsequent use of a systemic treatment showed better OS.

Ovarian Function Preservation in Patients With Cervical Cancer Undergoing Hysterectomy and Ovarian Transposition Before Pelvic Radiotherapy.

To examine the factors associated with ovarian failure (OF) and assess the effectiveness of ovarian transposition (OT) before pelvic irradiation for preserving ovarian function in patients with cervical cancer (CC) undergoing hysterectomy. During 2003 to 2017, patients who underwent hysterectomy with preservation of one or both ovaries were retrospectively enrolled. Patients were divided into 4 groups, depending on whether radiotherapy (RT) and OT were performed: group 1, RT(+) and OT(+); group 2, RT(+) and OT(-); group 3, RT(-) and OT(+); group 4, RT(-) and OT(-). OF was defined as serum follicle-stimulating hormone levels of ≥30 mIU/mL. Sixty-six patients (59 [89.4%] invasive CC and 7 [10.6%] cervical intraepithelial neoplasia) were included. The 2-year OF-free survival rate was 61.4% (95% confidence interval [CI] 37.8-86.0), 0%, 91.7% (95% CI 76.0-100), and 75.8% (95% CI 58.2-93.4) for groups 1, 2, 3, and 4, respectively. In groups 1 and 2 receiving RT, OT, and combination of external beam radiotherapy and vaginal brachytherapy were associated with OF on multivariate analysis (MVA) (P-value = .002 and .046, respectively). In groups 3 and 4 without RT, older age (40 years old) and OT did not affect OF; however, the number of remaining ovaries was independently associated with OF in MVA (P = .035). OT could effectively preserve ovarian function in patients treated with adjuvant RT, while OT procedure itself did not affect ovarian failure. OT should be considered in the management of premenopausal cervical cancer patients.

Role of adjuvant radiotherapy in extrahepatic bile duct cancer: A multicenter retrospective study (Korean Radiation Oncology Group 18-14).

PURPOSE: To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer. METHODS: Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group). RESULTS: The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p < 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68). CONCLUSIONS: Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.

Inter-institutional Variation in Intensity-modulated Radiotherapy for Breast Cancer in Korea (KROG 19-01).

BACKGROUND/AIM: To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. PATIENTS AND METHODS: We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. RESULTS: Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. CONCLUSION: There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

CT findings of acute radiation-induced pneumonitis in breast cancer.

OBJECTIVES: To evaluate the CT findings of acute radiation pneumonitis (RP) in breast cancer patients undergoing post-operative radiotherapy, and to analyze clinicodosimetric factors associated with acute RP. METHODS: Between 2015 and 2017, 61 patients with breast cancer who underwent follow-up chest CT at 3 months after radiotherapy were analyzed. The degree of acute RP on CT was evaluated by the change of extent and scoring system (grade 0, no RP; Grade 1, ground-glass opacities (GGOs); Grade 2, GGOs and/or consolidations; Grade 3, clear focal consolidation; Grade 4, dense consolidation). The dosimetric parameters were calculated from the dose-volume histogram of RT. RESULTS: The acute RP on CT was scored as follows: Grade 0, in 37.7%, Grade 1 in 13.1%, Grade 2 in 44.3%, and Grade 3 in 4.9%. The median extent of RP in patients with Grades 1 to 3 was 6.2 ml (range, 0.2-95.9). There were no clinicodosimetric factors significantly associated with the presence of RP or its severity. One patient developed symptomatic RP. CONCLUSION: This study showed no correlation between acute RP and clinicodosimetric factors, and acute RP based on CT findings were much more common than symptomatic RP. ADVANCES IN KNOWLEDGE: CT findings of acute RP or extent of RP were not significantly related to clinicodosimetric factors in breast cancer patients.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Immune expression signatures as candidate prognostic biomarkers of age and gender survival differences in cutaneous melanoma.

This study aims to investigate the difference of gene expression and its prognostic significance in younger women with melanoma. Significantly upregulated genes in tumors compared to normal skin tissues were extracted. Among these genes, genes that significantly affected survival according to expression level were selected, and pathway annotation was performed. The patient proportion with high/low expression of the most significant pathways was analyzed in each age (< 50, 50-59, ≥ 60) and gender group. Survival was analyzed according to age, gender, and pathways. The most significant pathways that were upregulated in tumor tissues and also had impacts on survival were programmed cell death protein [PD]-1, interferon-γ, and interferon-α/ß pathways. In women, the immune signaling rate in patients was higher than men and decreased with age (63.5%, 53.8%, and 47.6%). In men, the decreasing tendency was minimal (47.6%, 50.0%, and 41.6%). In patients aged < 60 years, women had a favorable survival rate than men (p = 0.055). Except for patients with high immune signaling, no survival difference was observed between genders (p = 0.6). In conclusion, younger female melanoma patients had high immune signaling than older women and men. This immune signaling improved survival of the younger female patients.

Prognostic Impact of Lymph Node Ratio in Patients Undergoing Preoperative Chemoradiotherapy Followed by Curative Resection for Locally Advanced Rectal Cancer.

BACKGROUND/AIM: To analyze the prognostic significance of nodal status in patients undergoing preoperative chemoradiotherapy (CRT) followed by curative resection for locally advanced rectal cancer. PATIENTS AND METHODS: Between 2000 and 2015, 80 consecutive patients with rectal cancer underwent preoperative CRT followed by curative resection. The lymph node ratio (LNR) was defined as the number of positive lymph nodes (LNs) divided by the examined LNs, and log odds of positive lymph nodes (LODDS) was the log of the ratio between positive and negative LNs. The prognostic value of these indicators was evaluated in terms of overall (OS) and disease-free (DFS) survival. RESULTS: The median follow-up period for patients overall was 59 months (range=11-190 months). The median number of examined LNs and number of positive LNs were 10 (range=1-29) and 2 (range=1-27), respectively, and the median LNR and LODDS values were 0.0 (range=0.0-0.96) and -1.0 (range=-1.7-1.3), respectively. The 5-year OS and DFS were 83% and 64%, respectively. In multivariate analysis, LNR was an independent prognostic factor in terms OS (p=0.041) but not for DFS (p=0.075). LODDS was not significantly associated with OS or DFS. In patients with clinical stage III rectal cancer, LNR was significantly associated with OS and DFS when the number of evaluated LNs was greater than 12 (p=0.038 for OS, p=0.006 for DFS). CONCLUSION: Our study suggests that LNR is a more effective prognostic factor than LODDS in terms of predicting survival. LNR was a significant predictor for survival for patients with clinical stage III rectal cancer with >12 harvested LNs.

Displacement of Surgical Clips in Patients with Human Acellular Dermal Matrix in the Excision Cavity during Whole Breast Irradiation Following Breast-Conserving Surgery.

PURPOSE: The purpose of this study was to investigate the displacement of surgical clips in the excision cavity during whole breast irradiation following breast-conserving surgery (BCS) with or without acellular dermal matrix (ADM) insertion, and to analyze clinicopathologic factors associated with the displacement of surgical clips. MATERIALS AND METHODS: From 2016 to 2017, 100 consecutive breast cancer patients who underwent BCS with the placement of surgical clips (superior, inferior, medial, lateral, and deep sides) in the tumor bed were included in this study. All patients took first planning computed tomography (CT) scan (CT 1) before whole breast irradiation and second CT scan (CT 2) before boost irradiation. Between two sets of planning CT, the displacement of surgical clips was calculated from the ΔX (lateral-medial), ΔY (anterior-posterior), ΔZ (superior-inferior), and three-dimensional (3D) directions. Patients were divided into two groups according to the breast volume replacement with ADM: group A with ADM and group B without ADM. RESULTS: The means and 1 standard deviations of 3D displacement for superior, inferior, medial, lateral and deep clips were 5.2±2.9, 5.2±3.2, 5.6±4.5, 5.6±4.3, and 4.9±4.9 mm in entire cohort (n=100); 5.6±2.6, 6.0±3.5, 6.7±5.8, 6.7±5.7, and 6.1±7.4 mm in group A (n=38); 4.9±3.1, 4.8±3.0, 5.0±3.5, 5.0±2.9, and 4.3±2.8 mm in group B (n=62), respectively. The 3D displacements of group A were longer than those of group B, but only significant difference was observed in lateral clip (p=0.047). CONCLUSION: This study demonstrated displacement of surgical clips during whole breast irradiation in patients with ADM insertion. For patients who had breast volume replacement using ADM, adaptive boost planning should be considered.