Upfront Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients with Brain Metastases from Non-small cell lung cancer: A Retrospective Analysis of a 10-Year Bi-Institutional Experience.

Purpose: Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) are increasingly used as initial therapies for brain metastases (BM). We aimed to assess the outcomes of SRS/FSRT in patients aged ≥65 years who had 1-10 BM from non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively reviewed 91 elderly NSCLC patients with 222 BM who were treated with SRS/FSRT at two institutions between 2010 and 2020. The primary endpoint was overall survival (OS) after SRS/FSRT. In addition, in-field local control (IFLC) within the treated field was evaluated. Statistical analysis was performed to identify the prognostic factors affecting OS and IFLC. Results: During a median follow-up of 18 months, the median OS was 32 months. The 1- and 2-year survival rates were 69.8 and 56.1%, respectively. In multivariate analysis, the NSCLC-specific graded prognostic assessment (GPA) score (p=0.007) and administration of systemic therapy (p=0.039) were defined as prognosticators affecting OS. The median IFLC period was 31 months, and the 1- and 2-year IFLC rates were 75.9 and 57.6%, respectively. The total BM volume (p=0.042) significantly affected IFLC. No severe adverse events were reported after SRS/FSRT. Conclusion: SRS/FSRT is an effective upfront treatment option for BM arising from NSCLC in elderly patients, with a good OS without severe side effects. Higher GPA score and active systemic treatment were associated with improved OS, indicating that elderly patients are significant candidates for SRS/FSRT.

Optimizing contrast protocol for bone-subtraction CT angiography of intracranial arteries in normal dogs using 160-slice CT.

BACKGROUND: Bone-subtraction computed tomography angiography (CTA) (BSCTA) is a new technique designed to overcome the limitation of three-dimensional CTA, where the vessels surrounded by bone and calcification can be obscured. An optimal contrast CT protocol for intracranial artery visualization with BSCTA has yet to be established in dogs. OBJECTIVES: The purpose of this study was to determine the optimal contrast protocol of CTA for visualizing intracranial artery using an automatic bone-subtraction technique in dogs. METHODS: Brain CTA was performed four times for each of nine healthy beagle dogs to cover all the contrast protocols: two different contrast iodine concentrations (300 and 370 mgI/mL) and two different contrast media injection rates (2 and 4 mL/s). Bone removal post-processing was performed automatically by subtracting the non-enhanced CT data from the contrast CT data using a dedicated workstation. The bone-subtracted intracranial vessels were analysed for quantitative and qualitative evaluation. RESULTS: Quantitative evaluation showed significantly higher CT attenuation values for the group with a 370 mgI/mL iodine content at a rate of 4 mL/s than the two groups with a 300 mgI/mL iodine content at the rates of 2 and 4 mL/s (p < 0.001). Qualitative assessment revealed significantly higher mean scores for the 370 mgI/mL groups than the 300 mgI/mL groups and significantly higher mean scores for the 4 mL/s groups than the 2 mL/s groups (p < 0.05). CONCLUSIONS: The optimal contrast protocol for BSCTA suggests that high iodine material concentration and high injection rate should be used for strong arterial attenuation and great visualization of the intracranial arterial structure in dogs.

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.

Microplastics contamination and characteristics of agricultural groundwater in Haean Basin of Korea.

The quality of groundwater is critical to human health. MPs have access to groundwater from the soil, polluted by various agricultural activities. However, to date, there have been no studies on the occurrence of MP in groundwater from an agriculture field without any adjacent sources of contamination, such as nearby landfills. In this study, the occurrence and distribution of MPs in groundwater of an agricultural area in the Haean Basin, Korea, without any definite source of pollution, was examined. MP and groundwater samplings were conducted in the dry season in 2020, the wet and dry seasons in 2021, respectively. In this study, the reliability of MP analysis was improved through good practices from laboratory to field campaigns, collecting large groundwater samples (300-500 L) volumes. Any involvement of plastic materials was avoided during the full procedures as possible and. Detailed investigation was conducted for the distribution of potential plastics sources like mulching, plastic covers, dripping pipes and shading nets, and hydrogeological properties affecting MPs occurrence. Groundwater MP concentrations of 0.02-0.15 particles/L (median = 0.06 particles/L), 0.02-2.56 particles/L (median = 0.43 particles/L) and 0.20-3.48 particles/L (median = 0.83 particles/L) were found in three rounds of sampling that comprised of the exploratory investigation in 2020, the wet season, and the dry season in 2021, respectively. The identified polymer types were polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS) and polyamide (PA). The MPs concentrations showed no statistically significant seasonal variation but revealed an apparent strong positive correlation (r = 0.71) of MPs with the amount of groundwater use. Findings of this study need more clarification from repeated samplings for multiple years. This study reveals the occurrence of MPs in groundwater in Korea for the first time to the best of our knowledge.

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.

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.

Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02).

PURPOSE: This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT. MATERIALS AND METHODS: This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively. RESULTS: The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3. CONCLUSION: PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

Radiotherapy for brain metastasis and long-term survival.

Patients with brain metastases (BM) can benefit from radiotherapy (RT), although the long-term benefits of RT remain unclear. We searched a Korean national health insurance claims database and identified 135,740 patients with newly diagnosed BM during 2002-2017. Propensity score matching (PSM) was used to evaluate survival according to RT modality, which included whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS). The 84,986 eligible patients were followed for a median interval of 6.6 months, and 37,046 patients underwent RT (43.6%). After the PSM, patients who underwent RT had significantly better overall survival after 1 year (42.4% vs. 35.3%, P < 0.001), although there was no significant difference at 2.6 years, and patients who did not undergo RT had better survival after 5 years. Among patients with BM from lung cancer, RT was also associated with a survival difference after 1 year (57.3% vs. 32.8%, P < 0.001) and a median survival increase of 3.7 months. The 1-year overall survival rate was significantly better for SRS than for WBRT (46.4% vs. 38.8%, P < 0.001). Among Korean patients with BM, especially patients with primary lung cancer, RT improved the short-term survival rate, and SRS appears to be more useful than WBRT in this setting.

Beneficial effects of modulated electro-hyperthermia during neoadjuvant treatment for locally advanced rectal cancer.

PURPOSE: Modulated electro-hyperthermia (mEHT) may enhance the tumor response, although the effectiveness of combined neoadjuvant therapy remains unclear. Therefore, we investigated the role of mEHT with neoadjuvant therapy for locally advanced rectal cancer. MATERIALS AND METHODS: Clinical data were analyzed for 120 patients who received neoadjuvant treatment for locally advanced rectal cancer (T3/4 or N+, M0) from May 2012 to December 2017. Capecitabine or 5-fluorouracil was administered along with radiotherapy. Patients were categorized into mEHT group (62 patients) and non-mEHT group (58 patients) depending on whether mEHT was added. Surgery was performed 6-8 weeks after the end of radiotherapy. RESULTS: The median age was 59 years (range, 33-83). The median radiation dose was significantly less for mEHT group (40 Gy) than for non-mEHT group (50.4 Gy). In mEHT group, 80.7% showed down-staging compared with 67.2% in non-mEHT group. For large tumors of more than 65 cm³ (mean), improved tumor regression was observed in 31.6% of mEHT group compared with 0% of non-mEHT group (p = .024). The gastrointestinal toxicity rate of mEHT group was 64.5%, which was found to be statistically significantly less than 87.9% of non-mEHT group (p = .010). The 2-year disease-free survival was 96% for mEHT group and 79% for non-mEHT group (p = .054). CONCLUSION: The overall mEHT group had a comparable response and survival using less radiation dosing compared with standard care; the subgroup with large tumors showed improved efficacy for tumor regression after mEHT.

Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study.

PURPOSE: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. METHODS: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. RESULTS: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/ß = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications. CONCLUSION: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.

Outcome of radiotherapy for clinically overt metastasis to the internal mammary lymph node in patients receiving neoadjuvant chemotherapy and breast cancer surgery.

PURPOSE: This study was aimed to assess the outcome of radiotherapy and determine prognostic factors for survival in breast cancer patients with clinically overt metastasis to the internal mammary lymph node (IMN+). METHODS: We retrospectively reviewed the medical records of 193 patients with IMN + breast cancer who received neoadjuvant chemotherapy (NAC), breast surgery without internal mammary lymph node (IMN) dissection, and postoperative radiotherapy at 9 hospitals between 2009 and 2013. Breast-conserving surgery or mastectomy was performed after taxane-based NAC. Radiotherapy was administered to the whole breast/chest wall and regional nodes. IMN-covering radiotherapy was performed in 92.2% of patients with median dose of 58.4 Gy (range, 44.9-69.1 Gy). The overall survival (OS), disease-free survival (DFS), and IMN failure-free survival (IMNFFS) were analyzed. RESULTS: After median follow-up of 71 months, 9 patients (4.7%) developed IMN failure and simultaneous distant metastasis. The 5-year DFS, OS, and IMNFFS was 68.6%, 81.8%, and 95.3%, respectively. Non-triple-negative breast cancer, Ki-67 ≤ 10%, pathological complete response (CR) in tumor and axillary node, and radiologic CR of IMN after NAC were significant factors for predicting higher DFS; however, IMN radiation dose was not significant determinants for DFS. The 5-year DFS of patients with IMN-dose ≤ 50.0 Gy and those with >50.0 Gy was 86.7% and 76.7%, respectively (p = 0.41). CONCLUSIONS: A multimodality strategy including NAC, breast surgery, and IMN-covering radiotherapy was effective for patients with overt IMN + breast cancer. Even without an IMN dissection, most patients were IMN failure-free with an IMN-focusing radiotherapy.

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.

Identification of Candidate Genes and Pathways Associated with Obesity-Related Traits in Canines via Gene-Set Enrichment and Pathway-Based GWAS Analysis.

The present study aimed to identify causative loci and genes enriched in pathways associated with canine obesity using a genome-wide association study (GWAS). The GWAS was first performed to identify candidate single-nucleotide polymorphisms (SNPs) associated with obesity and obesity-related traits including body weight and blood sugar in 18 different breeds of 153 dogs. A total of 10 and 2 SNPs were found to be significantly (p < 3.74 × 10-7) associated with body weight and blood sugar, respectively. None of the SNPs were identified to be significantly associated with obesity trait. We subsequently followed up the GWAS analysis with gene-set enrichment and pathway analyses. A gene-set with 1057, 1409, and 1243 SNPs annotated to 449, 933 and 820 genes for obesity, body weight, and blood sugar, respectively was created by sub-setting the GWAS result at a threshold of p < 0.01 for the gene-set enrichment analysis. In total, 84 GO and 21 KEGG pathways for obesity, 114 GO and 44 KEGG pathways for blood sugar, 120 GO and 24 KEGG pathways for body weight were found to be enriched. Among the pathways and GO terms, we highlighted five enriched pathways (Wnt signaling pathway, adherens junction, pathways in cancer, axon guidance, and insulin secretion) and seven GO terms (fat cell differentiation, calcium ion binding, cytoplasm, nucleus, phospholipid transport, central nervous system development, and cell surface) that were found to be shared among all the traits. Our data provide insights into the genes and pathways associated with obesity and obesity-related traits.

Cervical Lymph Node Involvement above the Supraclavicular Fossa in Breast Cancer: Comparison with Stage IIIC (KROG 18-02).

PURPOSE: We aimed to analyze the treatment outcomes of ipsilateral cervical lymph node (CLN)-positive breast cancer without other distant metastasis and compare the outcomes with those of supraclavicular lymph node (SCL)-positive breast cancer. METHODS: Seventy-eight patients with breast cancer and ipsilateral CLN metastasis above the supraclavicular fossa (CLN[+] group) were treated at 7 institutions (2000-2014). Seventy-four patients received systemic chemotherapy and breast surgery followed by locoregional radiotherapy. Outcomes of the CLN(+) group were compared with those of the SCL(+) group, which included 183 patients with SCL involvement. RESULTS: The median follow-up duration was 55.9 months. Twenty-two regional failures were found in 15 patients-axillary lymph node (LN) in 8, SCL in 6, internal mammary LN in 3, previously involved CLN in 4, and previously uninvolved ipsilateral CLN in one patient. The 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates were 68.6%, 46.7%, 68.4%, and 57.0%, respectively. Neck dissection did not improve LRRFS and DFS (p = 0.86 and p = 0.26, respectively). Multivariate analysis showed that hormone receptor negativity and the presence of extracapsular extension were prognostic factors for poor DFS. On comparison with stage IIIC using propensity score matching, survival outcomes of the CLN(+) and SCL(+) groups were not different (5-year OS, p = 0.75; DFS, p = 0.88; LRRFS, p = 0.86; and DMFS, p = 0.45). CONCLUSION: The comparable clinical outcomes indicate that patients with breast cancer who have ipsilateral CLN metastasis without other distant metastasis may benefit from locoregional treatment of the ipsilateral breast and systemic therapies, as do those with N3c disease.

Post-mastectomy radiation therapy in breast reconstruction: a patterns of care study of the Korean Radiation Oncology Group.

PURPOSE: The details of breast reconstruction and radiation therapy (RT) vary between institutions; therefore, we sought to investigate the practice patterns of radiation oncologists who specialize in breast cancer. MATERIALS AND METHODS: We identified the practice patterns and inter-hospital variations from a multi-center cohort of women with breast cancer who underwent post-mastectomy RT (PMRT) to the reconstructed breast at 16 institutions between 2015 and 2016. The institutions were requested to contour the target volume and produce RT plans for one representative case with five different clinical scenarios and answer questionnaires which elicited infrastructural information. We assessed the inter-institutional variations in RT in terms of the target, normal organ delineation, and dose-volume histograms. RESULTS: Three hundred fourteen patients were included; 99% of them underwent immediate reconstruction. The most irradiated material was tissue expander (36.9%) followed by transverse rectus abdominis musculocutaneous flap (23.9%) and silicone implant (12.1%). In prosthetic-based reconstruction with tissue expander, most patients received PMRT following partial deflation. Conventional fractionation and hypofractionation RT were used in 66.6% and 33.4% patients, respectively (commonest: 40.05 Gy in 15 fractions [17.5%]). Furthermore, 15.6% of the patients received boost RT and 53.5% were treated with bolus. Overall, 15 physicians responded to the questionnaires and six submitted their contours and RT plans. There was a significant variability in target delineations and RT plans between physicians, and between clinical scenarios. CONCLUSION: Adjuvant RT following post-mastectomy reconstruction has become a common practice in Korea. The details vary significantly between institutions, which highlights an urgent need for standard protocol in this clinical setting.

Survival outcomes of breast cancer patients with brain metastases: A multicenter retrospective study in Korea (KROG 16-12).

PURPOSE: This study evaluated the influence of prognostic factors and whole brain radiotherapy (WBRT) on overall survival (OS) of breast cancer (BC) patients with brain metastases (BM). METHODS AND MATERIALS: Medical records of 730 BC patients diagnosed with BM from 2000 to 2014 at 17 institutions were retrospectively reviewed. OS was calculated from BM diagnosis. Median follow-up duration was 11.9 months (range, 0.1-126.2). RESULTS: Median OS was 15.0 months (95% CI: 14.0-16.9). Patients with different BC-specific graded prognostic assessment (GPA) scores showed significant differences (p < 0.001) in OS. In multivariate analysis, histologic grade 3 (p = 0.014), presence of extracranial metastasis (p < 0.001), the number of BM (>4; p = 0.002), hormone receptor negativity (p = 0.005), HER2-negativity (p = 0.003), and shorter time interval (<30 months) between BC and BM diagnosis (p = 0.007) were associated with inferior OS. By summing the ß-coefficients of variables that were prognostic in multivariate analyses, we developed a prognostic model that stratified patients into low-risk (≤0.673) and high-risk (>0.673) subgroups; the high-risk subgroup had poorer median OS (10.1 months, 95% CI: 7.9-11.9 vs. 21.9 months, 95% CI: 19.5-27.1, p < 0.001). Univariate and multivariate analyses of propensity score-matched patients diagnosed with BM ≥ 30 months after BC diagnosis (n = 389, "late BM") revealed that WBRT-treated patients showed superior OS compared to non-WBRT-treated patients (p = 0.070 and 0.030, respectively). CONCLUSION: Our prognostic model identified high-risk BC patients with BM who might benefit from increased surveillance; if validated, our model could guide treatment selection for such patients. Patients with late BM might benefit from WBRT as initial local treatment.

Aggressive Surgical Excision of Supraclavicular Lymph Node Did Not Improve the Outcomes of Breast Cancer With Supraclavicular Lymph Node Involvement (KROG 16-14).

INTRODUCTION: The purpose of this study was to evaluate the outcomes of upfront surgery followed by radiation therapy (RT) for ipsilateral supraclavicular (SCN) and/or internal mammary (IMN) node-positive breast cancer. MATERIALS AND METHODS: One hundred fifty-eight patients were included; among these, 91 patients were SCN-positive, 54 were IMN-positive, and 13 were SCN- and IMN-positive. Patients underwent breast conserving surgery (n = 74) or mastectomy (n = 84) followed by systemic therapy, and adjuvant RT to whole breast/chest wall with or without regional nodal RT. Regarding regional treatments for SCN and IMN, SCN excision was performed in 59 (37.3%) patients, IMN excision in 10 (6.3%) patients, SCN RT in 143 (90.5%) patients, and IMN RT in 68 (43.0%) patients. RESULTS: The median duration of follow-up was 72 months (range, 7-182 months). There were 20 locoregional recurrences and 45 distant metastases. In-field failure was observed only in SCN (n = 8), and 6 of these patients initially underwent SCN excision. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 87.3%, 71.6%, and 89.7%, respectively. Neither SCN excision nor SCN RT dose ≥ 54 Gy improved locoregional control (P = .927 and P = .693, respectively) or DFS (P = .394 and P = .686, respectively). Having ≥ 10 involved axillary lymph nodes was the only independent prognosticator for DFS after adjusting for covariates (P = .003). CONCLUSION: Regional control rate in initially involved SCN and/or IMN was acceptable in patients treated with upfront surgery followed by systemic therapy plus adjuvant RT. More aggressive regional therapy such as SCN excision did not improve locoregional control or survival.

Clinical Significance of Lymph-Node Ratio in Determining Supraclavicular Lymph-Node Radiation Therapy in pN1 Breast Cancer Patients Who Received Breast-Conserving Treatment (KROG 14-18): A Multicenter Study.

This study evaluated the clinical significance of the lymph-node ratio (LNR) and its usefulness as an indicator of supraclavicular lymph-node radiation therapy (SCNRT) in pN1 breast cancer patients with disease-free survival (DFS) outcomes. We retrospectively analyzed the clinical data of patients with pN1 breast cancer who underwent partial mastectomy and taxane-based sequential adjuvant chemotherapy with postoperative radiation therapy in 12 hospitals (n = 1121). We compared their DFS according to LNR, with a cut-off value of 0.10. The median follow-up period was 66 months (range, 3-112). Treatment failed in 73 patients (6.5%) and there was no significant difference in DFS between the SCNRT group and non-SCNRT group. High LNR (>0.10) showed significantly worse DFS in both univariate and multivariate analyses (0.010 and 0.033, respectively). In a subgroup analysis, the effect of SCNRT on DFS differed significantly among patients with LNR > 0.10 (p = 0.013). High LNR can be used as an independent prognostic factor for pN1 breast cancer patients treated with partial mastectomy and postoperative radiotherapy. It may also be useful in deciding whether to perform SCNRT to improve DFS.

Impact of Regional Nodal Irradiation for Breast Cancer Patients with Supraclavicular and/or Internal Mammary Lymph Node Involvement: A Multicenter, Retrospective Study (KROG 16-14).

PURPOSE: The purpose of this study was to evaluate the treatment outcomes of radiotherapy (RT) for breast cancer with ipsilateral supraclavicular (SCL) and/or internal mammary (IMN) lymph node involvement. MATERIALS AND METHODS: A total of 353 patients from 11 institutions were included. One hundred and thirty-six patients had SCL involvement, 148 had IMN involvement, and 69 had both. All patients received neoadjuvant systemic therapy followed by breast-conserving surgery or mastectomy, and postoperative RT to whole breast/chest wall. As for regional lymph node irradiation, SCL RT was given to 344 patients, and IMN RT to 236 patients. The median RT dose was 50.4 Gy. RESULTS: The median follow-up duration was 61 months (range, 7 to 173 months). In-field progression was present in SCL (n=20) and/or IMN (n=7). The 5-year disease-free survival (DFS) and overall survival rates were 57.8% and 75.1%, respectively. On multivariate analysis, both SCL/IMN involvement, number of axillary lymph node ≥ 4, triple-negative subtype, and mastectomy were significant adverse prognosticators for DFS (p=0.022, p=0.001, p=0.001, and p=0.004, respectively). Regarding the impact of regional nodal irradiation, SCL RT dose ≥ 54 Gy was not associated with DFS (5-year rate, 52.9% vs. 50.9%; p=0.696) in SCL-involved patients, and the receipt of IMN RT was not associated with DFS (5-year rate, 56.1% vs. 78.1%; p=0.099) in IMN-involved patients. CONCLUSION: Neoadjuvant chemotherapy followed by surgery and postoperative RT achieved an acceptable in-field regional control rate in patients with SCL and/or IMN involvement. However, a higher RT dose to SCL or IMN RT was not associated with the improved DFS in these patients.

Comparison of Breast Conserving Surgery Followed by Radiation Therapy with Mastectomy Alone for Pathologic N1 Breast Cancer Patients in the Era of Anthracycline Plus Taxane-Based Chemotherapy: A Multicenter Retrospective Study (KROG 1418).

PURPOSE: We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups. RESULTS: The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly. CONCLUSION: There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III.