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.

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.

Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study.

PURPOSE: Numerous studies have suggested that metformin treatment can increase breast cancer survival; however, it is unclear whether its effects interact with intrinsic subtype or diabetic status. Therefore, we conducted a large nationwide study to assess this in women with surgically resected invasive breast cancer. METHODS: Patients with newly diagnosed breast cancer between 2007 and 2016 were identified using the national health insurance claims database of South Korea. Metformin or other drug exposures was defined as medication for ≥ 90 days. Breast cancer subtypes were classified into four groups based on hormonal therapy and anti-HER2 treatments. RESULTS: A total of 117,333 patients were included (median follow-up duration, 90 months). Type 2 diabetes mellitus (T2DM) affected significantly overall survival (OS, 7 years, 89.7% vs. 92.4%, p < 0.001). A significant interaction was found between the use of metformin and insulin in patients with T2DM (p = 0.018). Thus, the subsequent analysis was limited to these patients and propensity score matching was performed. We found significantly increased OS in patients treated with metformin (7-year OS, 88.3% vs. 85.6%, p < 0.001). Interestingly, a significant effect was observed in the hormonal therapy (HT)+/HER2-targeted therapy (Tx)- group (p < 0.001), whereas no specific association was observed in the HT-/HER2 Tx- group (p = 0.220). CONCLUSIONS: Metformin administration may be associated with reduced mortality in patients with surgically resected breast cancer, particularly in the HT+/HER2 Tx- group. Clinical trials investigating metformin as a combination agent in breast cancer should stratify patients by curative resection, intrinsic subtype, the presence of T2DM, and the use of insulin.

Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. METHODS: A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. RESULTS: All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44-0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38-0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). CONCLUSIONS: This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.

Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice.

PURPOSE: Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. METHODS: We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns. RESULTS: The 10-year overall survival rates of LA, LB-HER2(-), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P < 0.001). Distant metastatic events differed significantly according to molecular subtype (P < 0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(-), and LB-HER2(+) subtypes (P = 0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P = 0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5 years. CONCLUSION: From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.

Risk stratification and prognostic nomogram for post-recurrence overall survival in patients with recurrent extrahepatic cholangiocarcinoma.

BACKGROUND: This study aimed to investigate post-recurrence overall survival (PROS) in patients with recurrent extrahepatic cholangiocarcinoma (EHC) and to indicate which groups of patients need active salvage treatments. METHODS: We retrospectively reviewed the records of 251 consecutive patients who underwent curative surgery followed by adjuvant chemoradiotherapy for EHC. Among these, 144 patients experienced a recurrence and were included for further analysis. RESULTS: The median PROS was 7 months (range, 1-130). In multivariate analysis, poorly differentiated histology, short disease-free survival, poor performance status, and elevated CA 19-9 were identified as significant prognosticators for poor PROS. Based on this, we stratified study patients into three categories by the number of risk factors: group 1 (0 or 1 factors), group 2 (2 factors) and group 3 (3-4 factors). Median PROS for groups 1, 2, and 3 were 13, 7, and 5 months, respectively (p < 0.001). Group 1 patients showed a significant benefit from salvage treatment, but groups 2 and 3 did not demonstrate clear benefit. In addition, we developed a nomogram to specifically identify individual patient's prognosis. CONCLUSION: Our simple risk stratification as well as proposed nomogram can classify patients into subgroups with different prognosis and will help facilitate personalized strategies after recurrence.

Survival Benefit of Adjuvant Chemoradiotherapy in Patients With Ampulla of Vater Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis focusing on the impact of adjuvant radiotherapy (RT) on overall survival (OS) in ampulla of Vater (AoV) cancer. BACKGROUND: The adjuvant treatment for AoV cancer is a subject of controversy without convincing evidence from randomized study. METHODS: A comprehensive search was performed in the databases of EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to July 2014. We included studies, which compared survival between patients with or without adjuvant RT after curative surgery solely for AoV cancer. Hazard ratio (HR) for OS was extracted, and a random-effects model was used for pooled analysis. RESULTS: Ten retrospective studies including 3361 patients met all inclusion criteria and were included for the final meta-analysis. Adjuvant RT was delivered with concurrent chemotherapy, mostly 5-fluorouracil, in all institutional studies. Generally, adjuvant RT groups included more patients with locally advanced disease or lymph node metastasis than did the surgery alone groups. The pooled results demonstrated that adjuvant RT significantly reduced the risk of death (HR = 0.75; P = 0.01). Exploratory analyses showed that patients with lymph node metastasis (HR = 0.52; P = 0.001) and locally advanced disease (HR = 0.42; P = 0.001) may also have survival benefit from adjuvant RT. No clear evidence of publication bias was found. CONCLUSIONS: This is the first meta-analysis evaluating the role of adjuvant RT in AoV cancer. Our results suggest the potential for survival benefit of adjuvant chemoradiotherapy. Further studies, preferably randomized clinical trials, are needed to confirm our results.

Impact of multimodality approach for patients with leptomeningeal metastases from solid tumors.

The purpose of this study was to evaluate treatment patterns, outcome and prognosticators for patients with leptomeningeal metastases from solid tumor. Medical records of 80 patients from January 1, 2004 to May 31, 2011 were retrospectively reviewed. Most frequent site of origin was the lung (59%) followed by the breast (25%). Most patients were treated with intrathecal chemotherapy (90%) and/or whole brain radiotherapy (67.5%). Systemic therapy was offered to 27 patients (33.8%). Percentage of patients treated with single, dual, and triple modality were 32.5%, 43.8%, and 23.8%, respectively. Median survival was 2.7 months and 1 yr survival rate was 11.3%. Multivariate analysis showed that negative cerebrospinal fluid cytology, fewer chemotherapy regimen prior to leptomeningeal metastases, whole brain radiotherapy, systemic therapy, and combined modality treatment (median survival; single 1.4 vs. dual 2.8 vs. triple 8.3 months, P<0.001) had statistical significance on survival. Subgroup analysis of non-small cell lung cancer (NSCLC) patients showed that targeted therapy had significant independent impact on survival (median survival; 10.5 vs. 3.0 months, P=0.008). Unlike previous reports, survival of patients with NSCLC primary was comparable to breast primary. Furthermore, combined modality treatment for all patients and additionally targeted therapy for NSCLC patients should be considered in the treatment of leptomeningeal metastases from solid tumor.

Long-term toxicities after allogeneic hematopoietic stem cell transplantation with or without total body irradiation: a population-based study in Korea.

PURPOSE: To compare long-term toxicity incidences, including secondary cancer (SC) with or without total body irradiation (TBI), in Asian patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using a nationwide database. MATERIALS AND METHODS: We identified 4,554 patients receiving HSCT for leukemic disease from 2009 to 2016 using the healthcare bigdata system of Korea. Incidence rate ratios (IRRs) for SC, cataracts, hypothyroidism, chronic kidney disease (CKD), myocardial infarction, or strokes were compared, and standardized incidence ratios (SIR) of SC was also estimated. RESULTS: TBI was conducted on 1,409 patients (30.9%). No overall survival differences based on TBI were observed. With a median follow-up duration of 58.2 months, 143 patients were diagnosed with subsequent SC (3.4%). Incidence rates per 1,000 person-year were 6.56 (95% confidence interval [CI], 4.8-8.8) and 7.23 (95% CI, 5.9-8.8) in the TBI and no-TBI groups, respectively (p = 0.594). Also, the SIR (95% CI) was not significantly increased by TBI (1.32 [0.86-1.94] vs. 1.39 [1.08-1.77] in the no-TBI group). In the young age group (0-19 years), SIRs were increased in both groups regardless of TBI (8.60 vs. 11.96). The IRRs of cataracts (1.60; 95% CI, 1.3-2.0), CKD (1.85; 95% CI, 1.3-2.6), and hypothyroidism (1.50; 95% CI, 1.1-2.1) were significantly increased after TBI. However, there were no significant differences in the occurrence of myocardial infarction and stroke according to TBI. CONCLUSION: Our results suggest that modern TBI may not additionally increase the risk of SC after allogeneic HSCT, although increased risks of other diseases were noted. Physicians should carefully consider individualized risks and benefits of TBI, with a particular focus by age group.

Risk of clinically significant cardiovascular disease associated with postoperative radiotherapy in non-small cell lung cancer patients receiving surgical resection followed by adjuvant chemotherapy: A Korean nationwide cohort study.

BACKGROUND: There are no large-scale datasets that analyze the relationship between postoperative radiotherapy (PORT) and various cardiovascular diseases (CVDs) in patients with locally advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to investigate the incidences of CVDs with PORT using a national population-based database. METHODS: Patients diagnosed with NSCLC who underwent curative surgery followed by adjuvant chemotherapy were included from 2007 to 2017. Patients with a prior diagnosis of heart failure (HF), atrial fibrillation (AFib), or heart surgery were excluded. A total of 11,141 patients were included in the final analysis. PORT was used in 1334 patients. Most patients received lobectomy with mediastinal lymph node dissection. RESULTS: Major adverse cardiac events mostly occurred within 3-4 years from the diagnosis. After the median follow-up duration of 70.6 months, HF was the most diagnosed disease (5.3 %), followed by AFib (4.5 %), stroke (4.1 %), and pulmonary embolism (3.5 %). All the incidences of clinically significant CVDs did not differ by PORT. This result remained unchanged after the propensity score matching comparison. Age ≥ 65, underlying hypertension, and history of ischemic heart disease were the most related factors to the occurrence of HF and AFib. No significant difference in CVD-free survivals according to PORT status was observed. When stratified by proposed scoring, there were no subgroups showed increased incidence by PORT. CONCLUSIONS: These results suggest that PORT had no significant impact on various CVD occurrences in NSCLC patients without underlying heart disease.

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14).

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for Adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). The recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with 5 of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in 5 patients (5.4%) and 4 cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in 2 patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and local recurrence mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Novel scoring system guiding the incorporation of adjuvant RT for neuroendocrine neoplasms treated with surgical resection followed by chemotherapy.

PURPOSE: This study aimed to investigate the role of adjuvant radiotherapy (RT) in neuroendocrine tumors (NET) treated with primary resection and systemic chemotherapy and guide to incorporate adjuvant RT based on individualized prediction. METHODS: We identified 4324 eligible patients using the SEER database. The most common histology was small cell carcinoma (SCC), followed by neuroendocrine carcinoma and carcinoid tumor. As the patients treated with RT were not randomly assigned, we performed propensity score matching (PSM). RESULTS: RT was administered to 1693 (39.2%) patients who had more unfavorable features [higher proportion of SCC, N2/3 stage, and poorly/undifferentiated (PD) tumors]. After PSM, old age, male sex, SCC, advanced T or N stage, PD tumors, large tumor size, and no use of RT were all significantly associated with a poor prognosis. After multivariate analysis, the survival benefit of RT was preserved (HR 0.82, 95% CI 0.73‒0.91, p < 0.001). Exploratory analysis suggested that primary site, PD tumors, SCC, tumor size < 2 cm, or LN negativity were the factors for which adjuvant RT appeared desirable. Further, we proposed a novel scoring system using aforementioned factors; site-thorax/genitourinary, PD tumor, tumor size < 2 cm, LN negativity. Based on individually calculated scores, we found that RT significantly increased survival in patients with scores of 2-4 but not in those with scores of 0-1. CONCLUSIONS: Our study highlights the necessity of guiding adjuvant RT for these rare types of cancer. We proposed a novel scoring system to carefully recommend RT in selected patients.

Low-dose irradiation could mitigate osteoarthritis progression via anti-inflammatory action that modulates mitochondrial function.

PURPOSE: The use of low-dose radiation therapy (LDRT) for osteoarthritis (OA) are rarely implemented, except in some European regions. Its clinical effects are controversial but little is known about how LDRT affects actual disease progression. We conducted a preclinical study to reveal the potential underlying mechanisms related to its disease modifying abilities. METHODS AND MATERIALS: Using primary cultured human chondrocytes and synovium-derived cells obtained from OA patients, the effects of LDRT were measured by quantitative real-time PCR, western blotting, and mRNA sequencing. For in vivo validation, a surgically-induced isolated OA model was used after anterior cruciate ligament transection or surgical destabilization of the medial meniscus. RESULTS: LDRT decreased the expression of pro-inflammatory factor matrix metalloproteinase 13 (MMP13) in chondrocytes. By contrast, collagen type 2 (COL2) protein expression was increased. LDRT induced large transcriptomic changes in both chondrocytes/synoviocytes, especially in mitochondrial activities. Gene set variation analysis demonstrated inverted U-shaped response in several categories, such as mitochondrial unfolded protein responses and extracellular matrix interactions. Growth differentiation factor 15 (GDF15), which is a mitohormetic signaling factor, was increased after LDRT and mediated the anti-inflammatory effects. Aggrecan was increased in synoviocyte's medium and TNF-α was decreased in chondrocyte's medium after LDRT. Conversely, knockdown of GDF15 did not result in decreased MMP13 expression by LDRT. Next, OA rats treated with LDRT exhibited a decreased OA severity when compared with the no-irradiation group at 10 weeks post-surgery (mean OARSI score 3.7 in 0 Gy, 2.8 in 0.5 Gy, and 1.8 in 1 Gy; p = 0.003). Osteoclast activity was significantly reduced in the LDRT group. CONCLUSIONS: Taken together, these data show that LDRT could mitigate osteoarthritis progression by exerting its anti-inflammatory effects via mitochondrial function modulation.

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.

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.

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.

Is There a Role for Perioperative Pelvic Radiotherapy in Surgically Resected Stage IV Rectal Cancer?: A Propensity Score-matched Analysis.

OBJECTIVES: This study aimed to determine whether perioperative pelvic radiotherapy (RT) improves outcomes in stage IV rectal cancer patients treated with primary surgical resection and systemic chemotherapy and to identify predictive factors for selection of patients for these approaches. MATERIALS AND METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed between 2010 and 2015 with stage IV rectal cancer, but without brain or bone metastases. After applying the exclusion criteria, a total of 26,132 patients were included in the analysis; propensity score matching was used to balance their individual characteristics. RESULTS: Overall, 3283 (12.6%) patients received perioperative RT; the 3-year overall survival (OS) rates were 43.6% in the surgery group and 50.5% in the surgery with RT group (P<0.001). The survival benefit of RT was maintained after propensity score matching and multivariate adjustment (hazard ratio: 0.70; 95% confidence interval: 0.66-0.81; P<0.001). Interaction testing of the prognostic variables showed a significant interaction between RT and the presence of lung metastasis (P<0.001): the benefit of RT was observed only in patients without lung metastases (3 y OS 52.1% vs. 44.1%, P<0.001), but it was observed regardless of liver metastases. In addition, we developed a web-based calculator (http://bit.do/mRC_surv) to provide individualized estimates of OS benefit based on the receipt of perioperative pelvic RT. CONCLUSIONS: Perioperative pelvic RT significantly improved OS rates, especially in patients without lung metastases. We successfully developed a nomogram and web-based calculator that could predict survival benefit with the addition of RT for these patients.

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.

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.