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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/β 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, Highlights • Multicenter retrospective study of salvage WBRT for recurrent brain metastasis. • Subsequent use of systemic treatment after salvage WBRT showing better OS. • Limitations of previous graded prognostic assessments for recurrent brain metastasis. • Novel RPA classification consisting of four simple clinical factors predicts OS.

Background It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy. Methods We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups. Results After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018). Conclusions IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low., Highlights • We evaluated the benefit of IMNI in modern era. • In taxane-based chemotherapy era, locoregional recurrence was very low (5.2%) in node-positive breast cancer. • IMNI was associated with improved survival.

Genetic testing for BRCA1 and BRCA2 is crucial in diagnosing hereditary breast and ovarian cancer syndromes and has increased with the development of multigene panel tests. However, results classified as variants of uncertain significance (VUS) present challenges to clinicians in attempting to choose an appropriate management plans. We reviewed a total of 676 breast cancer patients included in the Korean Hereditary Breast Cancer (KOHBRA) study with a VUS on BRCA mutation tests between November 2007 and April 2013. These results were compared to the ClinVar database. We calculated the incidence and odds ratios for these variants using the Korean Reference Genome Database. A total of 58 and 91 distinct VUS in BRCA1 and BRCA2 were identified in the KOHBRA study (comprising 278 and 453 patients, respectively). A total of 27 variants in the KOHBRA study were not registered in the Single Nucleotide Polymorphism database. Among BRCA1 VUSs, 20 were reclassified as benign or likely benign, four were reclassified as pathogenic or likely pathogenic, and eight remained as VUSs according to the ClinVar database. Of the BRCA2 VUSs, 25 were reclassified as benign or likely benign, two were reclassified as pathogenic or likely pathogenic, and 33 remained as VUS according to the ClinVar database. There were 12 variants with conflicting interpretations of pathogenicity for BRCA1 and 18 for BRCA2. Among them, p.Leu1780Pro showed a particularly high odds ratio. Six pathogenic variants and one conflicting variant identified using ClinVar could be reclassified as pathogenic variants in this study. Using updated ClinVar information and calculating odds ratios can be helpful when reclassifying VUSs in BRCA1/2.

To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). 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). 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 4) (p

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., Highlights • Internal mammary lymph node metastatic (IMN+) breast cancer is relatively uncommon. • Optimal treatment remains uncertain in IMN + breast cancer. • IMN-focusing radiotherapy resulted in favorable outcome even without IMN dissection.

This study aimed to identify the risk factors for locoregional recurrence (LR) and determine possible candidates for postoperative concurrent chemoradiotherapy (CCRT) in pathologic T3N0 (pT3N0) rectal cancer patients with a negative resection margin after total mesorectal excision (TME). Data from 365 patients who had pT3N0 rectal cancer between 2003 and 2012 in the Samsung Medical Center were reviewed. All patients underwent upfront surgery without preoperative treatment. Postoperative management involved either no adjuvant therapy (n = 122), chemotherapy alone (n = 100), or CCRT (n = 143). The median follow-up duration was 71 months. The 5-year overall survival, disease-free survival, and LR-free survival (LRFS) rates were 95.9%, 86.9%, and 96.3%, respectively. When comparing the three groups (surgery alone [n = 122], chemotherapy alone [n = 100], and CCRT [n = 143]), there was no significant difference in LRFS among them (94.0%, 93.4%, and 99.2%, respectively; p = 0.20). However, when patients were stratified by risk factors (distance from anal verge ≤ 5 cm and distal resection margin [DRM] ≤ 2 cm), the 5-year LRFS improved by more than 10% by adding CCRT (98.9% with CCRT vs. 87.4% without CCRT, p = 0.006) in those with more than one risk factor. Postoperative CCRT did not affect the 5-year LRFS (100% with CCRT vs. 99.0% without CCRT, p = 0.66) in patients with no risk factors. Postoperative CCRT significantly decreased LR in patients with pT3N0 rectal cancer with a negative resection margin but having a distance from the anal verge ≤ 5 cm or DRM ≤ 2 cm.

PurposeThe purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levels in improving the performance of magnetic resonance imaging (MRI) for the prediction of pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectalcancer.Materials and MethodsWe retrospectively reviewed the medical records of 524 rectal cancer patients who underwent NCRT and total mesorectal excision between January 2009 and December 2014. The performances of MRI with or without CEA parameters (initial CEA and CEA dynamics) for prediction of pathologic tumor response grade (pTRG) were compared by receiver-operating characteristic analysis with DeLong’s method. Cox regression was used to identify the independent factors associated to pTRG and disease-free survival (DFS) after NCRT.ResultsThe median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis, poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) and the mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed association with poor pTRG. The mrTRG plus CEA parameters showed significantly improved performances in the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEA were also identified as independent factors associated with DFS. The initial CEA further discriminated DFS in the subgroups with good mrTRG or that without mrMFI.ConclusionThe CEA parameters significantly improved the performance of MRI in the prediction of pTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initial CEA level in the groups with favorable MRI parameters.

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.

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.

This study aimed to identify high-risk factors for regional recurrence in patients with breast cancer with pathologically negative lymph nodes.We retrospectively analyzed 3800 patients with stage pT1-pT3 breast cancer and pathologically negative lymph nodes between 2004 and 2012. All patients underwent upfront surgery with curative intent. Adjuvant systemic treatments were administered to most patients (96.7%) based on contemporary guidelines.After a median follow-up of 83 months (range, 7-175 months), the estimated 10-year cumulative incidence rate of regional recurrence was 2.0%. Multivariate competing risk analysis revealed that high histologic grade, positive lymphovascular invasion, and stage pT2-3 were significant risk factors for any regional recurrence. Patients with ≥2 risk factors showed a significantly higher 10-year cumulative incidence rate of any regional recurrence than those with 1 or no risk factors (5.5% vs 1.2%; P.001). When the number of retrieved lymph nodes was less than 10, the difference in the incidence rate of regional recurrence between patients with ≥2 risk factors and those with 1 or no risk factors was greater (6.6% vs 1.3%, respectively; P.001). The 10-year disease-free survival was worse in patients with ≥2 risk factors than in those with 1 or no risk factors (84.7% vs 90.0%, respectively; P.001). Patients with ≥2 risk factors also showed worse 10-year overall survival than did those with 1 or no risk factors (91.3% vs 97.0%, respectively; P.001).Overall, the cumulative incidence rate of any regional recurrence was low at 10 years. However, patients with ≥2 risk factors showed an increased risk of any regional recurrence and worse disease-free survival, particularly when the number of retrieved lymph nodes was less than 10.

Purpose This first Korean prospective study is to evaluate the feasibility of prone breast radiotherapy after breast conserving surgery for left breast cancer patients who have relatively small breast size and we present dosimetric comparison between prone and supine positions. Materials and methods Fifty patients underwent two computed tomography (CT) simulations in supine and prone positions. Whole breast, ipsilateral lung, heart, and left-anterior-descending coronary artery were contoured on each simulation CT images. Tangential-fields treatment plan in each position was designed with total 50 Gy in 2-Gy fractions, and then one of the positions was designated for the treatment by comparing target coverage and dose to normal organs. Also, interfractional and intrafractional motion was evaluated using portal images. Results In total 50 patients, 32 cases were decided as prone-position-beneficial group and 18 cases as supine-position-beneficial group based on dosimetric advantage. Target dose homogeneity was comparable, but target conformity in prone position was closer to optimal than in supine position. For both group, prone position significantly increased lung volume. However, heart volumewas decreased by prone position for prone-position-beneficial group but was comparable between two positions for supine-position-beneficial group. Lung and heart doses were significantly decreased by prone position for prone-position-beneficial group. However, prone position for supine-position-beneficial group increased heart dose while decreasing lung dose. Prone position showed larger interfractional motion but smaller intra-fractional motion than supine position. Conclusion Prone breast radiotherapy could be beneficial to a subset of small breast patients since it substantially spared normal organs while achieving adequate target coverage.

Purpose In some patients who receive adjuvant radiotherapy (RT) for the left breast, the stomach is located inside the RT field. This study investigates the incidence of gastric complications following adjuvant RT for breast cancer using data of the Health Insurance Review and Assessment Service in South Korea. Methods We identified 37,966 women who underwent surgery and received adjuvant RT for breast cancer. The cumulative incidence rate of gastric hemorrhage and gastric cancer was calculated and compared for left and right breast cancers. Results Among 37,966 patients, 19,531 (51.4%) and 18,435 (48.6%) had right and left breast cancers, respectively. After a median follow-up duration of 6.3 years, the cumulative incidence of gastric cancer and gastric hemorrhage did not differ between right and left breast cancers (p = 0.414 and p = 0.166, respectively). The multivariable analysis revealed that old age was the only factor associated with the development of gastric cancer (p < 0.001) and gastric hemorrhage (p < 0.001). The incidence of gastric cancer and hemorrhage did not differ between patients who received adjuvant RT for right and left breast cancers. Conclusion Irradiation-related chronic complications of the stomach in patients with breast cancer are minimal. A study with a longer follow-up duration might be needed to assess the risk of gastric cancer.

Background Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status. Patients and Methods We analyzed 261 patients who received NAC followed by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation Oncology Group from 2005 to 2011. The tumors were classified into one of 3 subtypes: luminal (estrogen receptor positive or progesterone receptor positive and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor, progesterone receptor, and HER2 negative). We compared locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in different subgroups generated by the subtype and pCR statuses. Results In all patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%, respectively. In all patients, axillary lymph node dissection was found to be the only favorable factor for LRC (P = .023) and DFS (P = .001). Age ≥ 50 years (P = .027), negative resection margin (P = .002), and axillary lymph node dissection (P = .002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS. Subgroup analysis by tumor subtype and pCR showed that ENI was not associated with greater LRC or DFS in any subgroups. Conclusion In ypN0 patients after NAC and BCS, ENI did not improve LRC or survival, regardless of subtype or primary tumor response. This result should be verified through larger prospective trials.

Purpose The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). Methods A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). Results The median follow-up duration was 84 (range, 8-171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076-4.746; p = 0.031). Conclusion Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.

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.

Purpose This study was conducted to evaluate prognosis of patients with level I/II axillary lymph node metastases from occult breast cancer (OBC). Materials and methods Data of 53 patients with OBC who received axillary lymph node dissection (ALND) positive/negative (+/-) breast-conserving surgery between 2001 and 2013 were retrospectively collected at seven hospitals in Korea. The median number of positive lymph nodes (+LNs) was 2. Seventeen patients (32.1%) had >3 +LNs. A total of 48 patients (90.6%) received radiotherapy. Extents of radiotherapy were as follows: whole-breast (WB; n = 11), regional lymph node (RLN; n = 2), and WB plus RLN (n = 35). Results The median follow-up time was 85 months. Recurrence was found in four patients: two in the breast, one in RLN, and one in the breast and RLN. The 5-year and 7-year disease-free survival (DFS) rates were 96.1% and 93.5%, respectively. Molecular subtype and receipt of breast radiotherapy were significantly associated with DFS. Patients with estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) subtype had significantly lower 7-year DFS than those with non-ER-/PR-/HER2- tumor (76.9% vs. 100.0%; p = 0.03). Whole breast irradiation (WBI) was significantly associated with a higher 7-year DFS rate (94.7% for WBI group vs. 83.3% for non-WBI group; p = 0.01). Other factors including patient's age, number of +LNs, taxane chemotherapy, and RLN irradiation were not associated with DFS. Conclusion Patients with OBC achieved favorable outcome after ALND and breast-targeting treatment. Molecular subtype and receipt of WBI was significant factors for DFS.

Background: There has been few research on how to measure skin status quantitatively throughout the course of radiotherapy (RT). We evaluated the changes in the skin induced by 2 different RT techniques using objective measurements in breast cancer patients. Methods: In this prospective study, between August 2015 and March 2019, serial measurements of the dermatological factors during and after postmastectomy radiotherapy (PMRT) were made in 40 breast cancer patients. PMRT was performed using the conventional photon tangential technique (PTT) or patient-tailored bolus technique (PTB). We analyzed these measurements using a mixed effect model and compared the clinically evaluated radiation dermatitis and patient-reported outcomes (PROs). Results: The trend of changes in melanin and erythema was significantly different between the PTB and PTT groups (p = 0.045 and 0.016, respectively). At the 3-month follow-up erythema intensity and melanin were higher in the PTB group than in PTT group (both p < 0.001). Eight patients (40% in the PTB group) reported grade 2 radiation dermatitis and 1 patient (5% in the PTB group) reported grade 3 radiation dermatitis. No grade 2 or higher radiation dermatitis was found in the PTT group. Ten patients (50%) in the PTB group and 3 patients (15%) in the PTT group reported severe erythema likely due to questionable clinical evaluation, but hyperpigmentation was rarely reported at the follow-up visits. Conclusion: The PTB group showed higher intensity of erythema at the end of RT than the PTT group and the increase in melanin lasted until the 3-month follow-up visits in the PTB group. Moreover, patients subjectively appealed more severe symptoms following PTB in PROs.

Background In the current study, we sought to evaluate and compare the objective changes in biophysical parameters and patient-reported outcomes following radiation therapy (RT) in patients with breast cancer who underwent breast-conserving surgery (BCS) or modified radical mastectomy (MRM). Materials and methods Patients older than 18 years, with stage I to III breast cancer, who were expected to receive RT were recruited between August 2015 and March 2019. Skin hydration, sebum content, pigmentation, and elasticity of the irradiated and unirradiated breast or chest wall were assessed using a noninvasive bioengineering device. Assessments were performed before the initiation of RT (T0); after the 5th (T1), 15th (T2), and 25th (T3) fractions; and 1 (T4) and 3 months (T5) after the completion of RT. Patient-reported outcomes were also evaluated using Radiation Dermatitis Assessment for Breast Cancer 11. Results Hydration and sebum levels on the irradiated breast decreased during RT and had not returned to baseline at T5. Erythema on the irradiated breast increased two-fold between T0 and T3, and melanin levels were significantly higher than those at baseline and those of the contralateral unirradiated breast until T5 (106.0 vs. 115.8, P = .03). More than half of the patients continued to report skin color changes, dryness, and pain after RT. The erythema in the irradiated site at T1 was significantly higher in the MRM group than in the BCS group (P for interaction = .04), while there were no significant differences in the changes of the other parameters. Conclusion RT-induced changes in hydration, sebum, and melanin, and the majority of patient-reported pain, color changes, and dryness, even 3 months after the completion of treatment. There were no remarkable differences in the measurable skin parameters according to the surgery type, with the exception of erythema, which was higher in the MRM group 1 week after the start of RT.

Purpose In this study, we examined the impact of reconstruction using tissue expander insertion (TEI) on the risk of radiation dermatitis in patients undergoing postmastectomy radiotherapy (PMRT). Methods Between August 2015 and March 2019, patients with breast cancer who had received systemic chemotherapy and PMRT were prospectively included. Skin parameters, including melanin, erythema, hydration, sebum, and elasticity, were measured using a multi-probe instrument at 6 time points: before the initiation of radiotherapy (pre-RT), at weeks 1, 3, and 5 during radiotherapy (weeks 1-5), and 1 and 3-month after radiotherapy (post-RT-1m and post-RT-3m). Patient-reported outcomes (PROs) were assessed at each time point. Changes in biophysical parameters and PRO were compared between patients with and without TEI (TEI+ vs. TEI-). Results Thirty-eight patients, including 18 with TEI+ and 20 with TEI-, were analyzed. The pattern of time-course changes in biophysical parameters and PRO did not differ between TEI+ and TEI- patients. The melanin index was highest at post-RT-1m, while the erythema index was highest at week 5. At post-RT-3m, TEI+ patients presented higher melanin values than TEI- patients, with no statistical significance (coefficient, 47.9 vs. 14.2%; p = 0.07). In all patients, water content decreased throughout the measurement period. At post-RT-3m, TEI+ patients demonstrated a further decrease in water content, while the TEI- group nearly recovered the water content to pre-RT status (coefficient, -17.1, -2.5; p = 0.11). The sebum and elasticity levels were not altered by TEI. Conclusion In patients undergoing PMRT, TEI did not significantly affect the changing patterns of skin biophysical parameters and PRO during radiotherapy.

Background Genetic testing for BRCA1 and BRCA2 genes is crucial for diagnosing hereditary breast and ovarian cancer syndromes (HBOC). Testing for such genes has been on the rise due to the development of multigene panel tests. However, results classified as variants of uncertain significance (VUS) present challenges to clinicians trying to interpret their functions and choose appropriate management plans.Methods We reviewed a total of 676 breast cancer patients who had VUS on BRCA mutation tests between November 2007 and April 2013 in the KOHBRA study. These results were compared to the ClinVar database. We calculated the incidence and odds ratios for these variants using the Korean Reference Genome Database (KRGDB).Results A total of 58 and 91 distinct VUS in BRCA1 and 2 were identified in the KOHBRA study (comprising 258 and 453 patients, respectively). A total of 27 variants in the KOHBRA study were not registered in the SNP database. Of the BRCA1 VUS, 20 variants were reclassified as benign or likely benign, 4 variants were reclassified as pathogenic or likely pathogenic, and 8 variants remained as VUS according to the ClinVar database. Of the BRCA2 VUS variants, 25 variants were reclassified as benign or likely benign, two variants were reclassified as pathogenic or likely pathogenic, and 33 variants remained as VUS according to the Clinvar database. There were 12 variants with conflicting interpretations of pathogenicity for BRCA1 and 18 variants for BRCA2. Among them, p.Leu1780Pro showed a particularly high odds ratio.Conclusions Six pathogenic variants and one conflicting variant identified using ClinVar could be reclassified as pathogenic variants in this study. Using updated ClinVar and calculating odds ratios can be helpful when reclassifying VUS in BRCA1/2.

Purpose To investigate the effect of body mass index (BMI) on survival in patients with breast cancer according to tumor subtype, metabolic syndrome, and systemic treatment. Patients and Methods We identified 5668 patients who underwent curative surgery for breast cancer between 1996 and 2013 from the clinical data of a single institution. Disease-free survival (DFS) and overall survival (OS) were calculated and compared between the patients with BMI ≥ 25 kg/m2 and Results In all patients, BMI ≥ 25 kg/m2 was an unfavorable factor for OS (P = .030) but not for DFS. In the HR+/HER2− subgroup, DFS and OS were longer in patients with BMI Conclusion BMI ≥ 25 kg/m2 was an unfavorable survival factor, particularly in patients with HR+/HER2− breast cancer.

Purpose: There is uncertainty over the effect of systemic inflammatory response on oncologic outcomes in patients who underwent neoadjuvant chemoradiotherapy and surgery for rectal cancer. We investigated the association between neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as markers of systemic inflammation and tumor response and prognosis after treatment. Methods: A total of 176 patients who underwent neoadjuvant chemoradiotherapy and curative surgery for rectal cancer were analyzed retrospectively. Pretreatment hematologic parameters and the main clinical factors for patients and tumors were investigated with respect to their relationship with tumor regression and survival. Results: In the receiver operating characteristic analysis, NLR 2.0 and PLR 133.4 had the highest sensitivity and specificity in predicting tumor response. NLR Conclusions: Elevated NLR and PLR levels can be considered as predictors of poor pathologic response, and NLR can be considered a prognosticator in patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Purpose This study aimed to identify risk factors that have significant interaction with radiation exposure to the heart, and thus to determine candidates for heart-sparing radiotherapy (RT) among women with left breast cancer. Methods We identified 4,333 patients who received adjuvant RT following breast-conserving surgery for ductal carcinoma in situ or invasive breast cancer from 1996 to 2010. Incidence rates of cardiovascular disease were compared between left-sided and right-sided RT, and stratified by age and risk factors such as body mass index (BMI), smoking, hyperlipidemia, hypertension, diabetes, administration of anthracycline, and trastuzumab. Results In all patients, the cumulative incidence of cardiovascular disease was greater in patients treated with left-sided RT than in those treated with right-sided RT, but the difference was not significant (p=0.428). Smoking (hazard ratio [HR], 5.991; 95% confidence interval [CI], 2.109-17.022; p=0.002) and hyperlipidemia (HR, 5.567; 95% CI, 3.235-9.580; p

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (

To identify risk factors for local recurrence (LR) and investigate roles of adjuvant local therapy for malignant and borderline phyllodes tumors of the breast. From 1981 to 2014, 362 patients with malignant (n = 235) and borderline (n = 127) phyllodes tumors were treated by breast-conserving surgery (BCS) or total mastectomy (TM) at 10 centers. Thirty-one patients received adjuvant radiation therapy (RT), and those who received adjuvant chemotherapy were excluded from the study. Median follow-up was 5 years. LR developed in 60 (16.6%) patients. Regional recurrence occurred in 2 (0.6%) patients and distant metastasis (DM) developed in 19 (5.2%) patients. Patients receiving BCS (p = 0.025) and those not undergoing adjuvant RT (p = 0.041) showed higher LR rates. For malignant subtypes, local control (LC) rates at 5 years for BCS alone, BCS with adjuvant RT, TM alone, and TM with adjuvant RT were 80.7, 93.3, 92.4, and 100%, respectively (p = 0.033). Multivariate analyses revealed BCS alone, tumor size ≥ 5 cm, and positive margins as independent risk factors for LR. Margin-positive BCS alone showed poorest LC regardless of tumor size (62.5%, p = 0.007). For margin-negative BCS alone, 5-year LC rates for tumors ≥ 5 cm versus those

A robotic couch capable of six degrees of freedom (6-DoF) of motion was introduced for state-of-the-art radiation therapy. Patient treatment requires precise quality assurance (QA) of 6-DoF. Unfortunately, conventional methods do not provide the requisite accuracy and precision. Therefore, we developed a high-precision automated QA system using a visual tracking system (VTS). The VTS comprises four motion-sensing cameras, a cube with infrared reflective markers. To acquire data in treatment room coordinates, a transformation matrix from VTS coordinates to treatment room coordinates was determined. The mean error and standard deviation of linear and rotational motions, as well as couch sagging were analyzed from continuously acquired images in the moving couch. The accuracy of VTS was 0.024 mm deviation for the sinusoidal motion, and the accuracy of the transformation matrix was 0.02 mm. In a cross-comparison, the difference between Laser Tracker (FARO) measurements was 0.14 ± 0.12 mm for translation and 0.032 ± 0.026° on average for yaw rotation. The new system provides QA of yaw, pitch and roll motion as well as sagging of the couch and sub-millimeter/degree accuracy together with precision.

Purpose Information on tubular carcinoma (TC) of breast is limited due to its rarity. A multi-institutional study was performed to investigate the prognosis and failure patterns of TC compared to invasive ductal carcinoma (IDC). Materials and methods We collected retrospective data on 205 patients with TC from eleven institutions. For each TC case, 3 cases with IDC were matched according to similar size, t-stage, and n-stage from the same institution. Patterns of failure, disease free survival (DFS) and overall survival (OS) were assessed and compared between the groups. Results DFS at 5 years was 98.8% and 97.3% and OS at 5 years was 99.5% and 99.6% in TC and IDC, respectively. Among the patients with TC, 5 patients (2.4%) developed contralateral breast cancer, while 3 patients (0.5%) presented with contralateral breast cancer in patients with IDC. Conclusions The TC of breast presents an excellent prognosis, but the contralateral breast cancer tends to be more frequently observed compared to IDC in Korean women.

PURPOSE The aim of this study is to compare the treatment outcomes of breast conserving surgery (BCS) plus radiotherapy (RT) versus mastectomy for patients with pT1-2N1 triple-negative breast cancer (TNBC). Materials and Methods Using two multicenter retrospective studies on breast cancer, a pooled analysis was performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS (n=212) receivedwhole breast RTwith orwithoutregional nodal RT,while nonewho underwent mastectomy (n=108)received it. All patients received taxane-based adjuvant chemotherapy. The median follow-up periods were 65 months in the BCS+RT group, and 74 months in the mastectomy group. RESULTS The median age of all patients was 48 years (range, 24 to 70 years). Mastectomy group had more patients with multiple tumors (p < 0.001), no lymphovascular invasion (p=0.001), higher number of involved lymph node (p=0.028), and higher nodal ratio ≥ 0.2 (p=0.037). Other characteristics were not significantly different between the two groups. The 5-year locoregionalrecurrence-free, disease-free, and overall survivalrates of BCS+RT group versus mastectomy group were 94.6% versus 87.7%, 89.5% versus 80.4%, and 95.0% versus 87.8%, respectively, and the differences were statistically significant after adjusting for covariates (p=0.010, p=0.006, and p=0.005, respectively). CONCLUSION In pT1-2N1 TNBC, breast conservation therapy achieved better locoregional recurrencefree, disease-free, and overall survival rates compared with mastectomy.

Highlights • Vertebral compression fracture (VCF) may occur after ablative radiotherapy. • Rates and risk factors of VCF were analyzed in patients with spine metastasis. • Twenty-one (12.8%) patients experienced VCF and the 1-year VCF rate was 12.1%. • VCF rates were significantly different by PTV receiving ≥15 Gy (PTV_V15Gy). • The 1-year rates were 3.8% and 22.1% in PTV_V15Gy ≤42 and >42 cm3, respectively., Objectives This analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). Methods A retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10–90% volume, and irradiated volume receiving more than 10–25 Gy (PTV_V10 – 25 Gy). Results Among 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V15 Gy > 42 cm3 (p

Simple Summary Many interventions have been introduced to promote PA among patients with breast cancer. While patients have become active and their PA levels have improved during interventions, they discontinued their PA and became inactive once the study ended. Recently, interventions that use new technologies, such as wearable activity trackers (WATs) or smartphones, have become popular and replaced traditional face-to-face interventions emphasizing its efficiency. However, the use of wearable devices would not be sufficient for intervening in PA among patients with breast cancer, as each patient has different physical conditions, baseline PA levels, and clinical characteristics requiring individual counseling. Therefore, we conducted a randomized controlled trial to evaluate whether WAT in addition to counseling would reinforce leisure-time PA (LTPA) among patients with breast cancer under radiation therapy (RT) in comparison with counseling only. We found that the counseling with WAT application group had increased LTPAs immediately after the intervention and they were more likely to maintain long-term LTPAs (6 months after the intervention). We also found that patients who did not perform regular PAs before cancer diagnosis had significantly increased step counts (steps/day) compared with those who did perform regular PAs before cancer diagnosis. Abstract This randomized controlled trial aimed to compare the effectiveness of a wearable activity tracker (WAT) in addition to counseling (WAT+counseling) and counseling only for reinforcing leisure-time physical activity (LTPA) among breast cancer patients during radiotherapy (RT). A total of 152 breast cancer patients who were planning to undergo radiation therapy (RT) after surgery participated in the study. The WAT+counseling group (n = 76) underwent physical activity (PA) self-monitoring using a WAT and participated in counseling. The counseling-only group (n = 76) received telephone counseling once a week during RT and did not receive WAT. The WAT+counseling group had increased relative change in self-reported LTPA (102.8) compared with the counseling-only group (57.8) immediately after RT compared to baseline. Although the relative changes of self-reported LTPA of the WAT+counseling group were higher at three and six months after the end of RT compared to in the counseling-only group, the results were not significant. The mean average daily step count of the WAT+counseling group was 9351.7, which increased to 11,592.2 during RT and 12,240.1 after RT. In the subgroup analysis, patients who did not perform regular PA before cancer diagnosis had significantly increased step counts. This study shows the feasibility of WAT with counseling to reinforce PA among breast cancer patients.

e14008 Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM > 4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p = 0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis showed that shorter time interval to BM, TNBC subtype, extracranial systemic disease, number of BM > 4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p = 0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 > 37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS.

Purpose The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. Materials and methods We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. Results We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [-]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). Conclusion PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.

Purpose Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. Materials and Methods Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. Results The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). Conclusion Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.

To find out which symptoms most frequently and severely affect breast cancer patients during radiotherapy and how patients manage the symptoms and unmet needs.A cross-sectional survey was conducted with 111 patients who receive radiotherapy for breast cancer from January to April 2015 at Samsung Medical Center in Seoul, South Korea. Participants were asked about symptoms and discomfort due to radiotherapy, management methods for radiation dermatitis, unmet needs for radiation dermatitis care, and clinical and socio-demographic information.Of total, 108 out of 111 patients (97.3%) reported symptoms related to radiation dermatitis. Hyperpigmentation was the most commonly reported uncomfortable symptom followed by erythema. On average, patients reported 8.6 radiotherapy-induced skin problems (range, 0-11). Of total, 59 (53.2%) patients stated that they wanted care for radiation dermatitis, and 80.0, 59.4, and 51% of patients searched for information, used products, and visited the hospital to manage radiotherapy-related skin problems. Patients who experienced dryness, burning feelings, irritation, roughness, and hyperpigmentation were 11.73, 7.02, 5.10, 4.27, and 2.80 times more likely to have management needs than patients without those symptoms, respectively, adjusting age, current cycle of radiation therapy, chemotherapy, and type of surgery.Most of the breast cancer patients experience multiple symptoms associated with radiation dermatitis. Hyperpigmentation was the most common and uncomfortable symptom followed by erythema. Majority of patients wanted management for radiation dermatitis and patients who experienced dryness, burning feelings, irritation, roughness, and hyperpigmentation had higher needs for radiation dermatitis management.

To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast.Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82). The median tumor size was 7 mm (range, 0.01-76). Margin width was1 cm in 85 patients (27.3%), and nuclear grade was high in 37 patients (11.9%). Two hundred and three patients (65.3%) received tamoxifen.With a median follow-up of 74 months (range, 5-189), there were 11 local recurrences (invasive carcinoma in 6 and DCIS in 5) and 1 regional recurrence. The 7-year LRR rate was 3.8%. On univariate analysis, age and margin width were significant risk factors influencing LRR (p = 0.017 and 0.014, respectively). When age and margin width were combined among 211 patients whose margin width were available, the 7-year LRR rates were as follows (p 0.001): (1) 0% in patients with age50 years and any margin width status (n = 64), (2) 1.2% in age ≤50 years and margin width ≥1 cm (n = 93), (3) 13.1% in age ≤50 years and margin width1 cm (n = 54).The LRR rate was very low in selected DCIS patients treated with breast-conserving surgery without postoperative RT. However, adjuvant RT should be considered for those with age ≤50 years and margin width1 cm.

Aim We evaluated the tumor response and clinical outcomes according to molecular subtypes in stage II–III breast cancer patients who received neo-adjuvant chemotherapy (NAC) followed by surgery and radiotherapy. Methods We retrospectively analyzed 329 patients with clinical stage II–III breast cancer who received NAC followed by surgery and radiotherapy. Luminal A and B, HER2-enriched and triple-negative subgroups were identified. Results The overall pathologic complete response (pCR) rate after NAC was 20.1% and the HER2-enriched subgroup had the highest pCR rate (43.6%), whereas luminal A showed the lowest rate of pCR (4.6%). The median follow-up duration was 55 months (range, 5–98 months). The 5-year overall survival (OS) and disease-free survival (DFS) rates were 88.9% and 72.9%, respectively. In subgroup analysis, according to the pathologic response (pCR vs non-pCR), the triple-negative subtype exhibited a significant difference in 5-year OS rate (100.0% vs 71.6%, P = 0.005) and 5-year DFS rate (93.1% vs 55.1%, P < 0.001). A distinct survival difference according to molecular subtype was found, particularly in the non-pCR group (5-year OS and DFS, P < 0.001, respectively). Conclusions The non-pCR group showed significantly decreased 5-year OS and DFS rates compared to the pCR group, especially in triple negative and HER2-enriched breast cancer patients. A significant difference in survival rates and molecular subtypes was found in patients who failed to attain pCR.

AIM This study was performed to evaluate patterns of breast cancer subtypes in Korean patients with synchronous (SBC) or metachronous bilateral breast cancer (MBC). METHODS We retrospectively reviewed records of 302 patients with SBC (n = 161) or MBC (n = 141) who received curative surgery at our hospital between 1995 and 2013. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry (IHC) staining. We categorized breast cancers into the following subtypes: ER+ or PR+, HER2- (i.e., luminalA); ER+ or PR+, HER2+ (i.e., luminalB HER2+); ER-, PR- and HER2+ (i.e., HER2-enriched); ER-, PR- and HER2- (i.e., triple negative, TN). RESULTS More patients with MBC were ≤40 years at the time of breast cancer diagnosis than patients with SBC (34.6% vs. 19.3%, P

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&ndash, 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 (&gt, 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 &gt, 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.

PURPOSE This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. MATERIALS AND METHODS We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. RESULTS The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor ≤5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06-47.30). Patients with level of tumor ≤5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. CONCLUSION In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor ≤5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested.

Background A positive resection margin after breast-conserving surgery (BCS) usually requires re-excision, which impairs cosmetic outcomes and causes considerable distress. This study aimed to evaluate the prognosis of patients with positive resection margin after BCS and the role of radiation therapy (RT) in these patients. Materials and methods We analyzed 297 patients who underwent BCS for breast cancer and had invasive carcinoma or ductal carcinoma in situ (DCIS) within less than 1 mm from the resection margin in Samsung Medical Center from January 2000 to June 2012. The association between RT dose and the incidence rate of ipsilateral breast tumor recurrence (IBTR) was examined. Results After a median follow-up of 78 months, the incidence rate of IBTR in all patients was 4.6% after 5 years. In the multivariate analysis, the unfavorable factors associated with IBTR were age 66 Gy, p = 0.012; 60–66 Gy vs. > 66 Gy, p = 0.017), and discontinuation of hormone therapy (p = 0.001). Conclusions Among the patients with invasive carcinoma or DCIS within less than 1 mm from the resection margin, adjuvant RT with higher dose > 66Gy EQD2 might improve local control. Further prospective studies are warranted to validate the benefit and risk of a high dose boost after BCS in patients with a positive resection margin.

Background As a large-scale study of Koreans, we evaluated the association between BRCA mutation and the prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. Methods We organized familial pedigrees of 2555 patients with breast cancer who underwent genetic screening for BRCA1/2 in Samsung Medical Center between January 2002 and May 2018. Families with a member that had a history of cancer other than of the breast or ovary were regarded positive for other primary cancer. Results The median age of the population was 40 years (range, 19 to 82 years). BRCA mutation was detected in 377 (14.8%) of the patients. The BRCA-positive group had a higher frequency of family history of breast or ovarian cancer (p

The purpose of this study was to analyze the effectiveness of electron beam therapy (EBT) with patient-tailored bolus (PTB) using three-dimensional printing technology to reduce heart and lung doses during post-mastectomy radiotherapy (PMRT). For 28 patients with left breast cancer, we designed customized virtual bolus for PMRT to compensate for surface irregularities on computed tomography images and developed optimized plans for EBT. As comparison between the PTB and tangential plans, the PTB plan reduced unnecessary exposure to heart and ipsilateral lung with better target coverage compared with the tangential technique.

Trastuzumab/pertuzumab improved outcomes for patients (pts) with HER2+ breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of these agents apparently contributes to increased incidence of brain metastases (BM). Lapatinib (L) crosses the BBB and demonstrates activity against BM. Based upon pre/early clinical data, it’s hypothesized that L + whole brain radiotherapy (WBRT) or Stereotactic Radiosurgery (SRS) would improve intracranial control compared to WBRT/SRS (RT) alone. This randomized phase II trial included HER2+ breast cancer pts with ≥ 1 measurable, unirradiated parenchymal BM. Pts were randomized 1:1 to WBRT (37.5 Gy/3 weeks) or SRS +/- concurrent L (1000 mg dailyx6 weeks), andwere stratified by graded prognostic assessment (GPA), use of non-CNS penetrating anti-HER2 therapies, and previous SRS/resection. The primary endpoint was intracranial complete response (CR) rate 12weeks (wk) after RT. Secondary endpoints included objective response rate (ORR), lesion-specific response rate, CNS progression-free survival, and overall survival. 114 of 143 pts were evaluable for 12-wk CR (52 RT, 62 RT+L). Rate of grade 3 and 4 adverse events were 8% and 0% for RT and 29% and 6% for RT+L. 92% and 90% pts received concurrent and adjuvant L per protocol/acceptable variation. There were no significant differences in 12 or 4wk CR rates (p=0.97 and p=0.77); 5.8% and 0% at 12wk and 3.6% and 1.5% at 4wk for RT and RT+L, respectively. The ORR at 4 wk was 42% and 56% (p=0.059, RECIST), 40% and 58% (p=0.027, WHO) in the RT and RT+L, respectively. Although the addition of lapatinib to WBRT/SRS did not improve the 12wk CR rate, it showed meaningful clinical benefit by demonstrating a trend toward improvement of 4 wk ORR. Results of ongoing central review of MRIs using RECIST1.1, WHO and RANO-BM criteria including secondary endpointswill be reported. Support: NCI grants U10CA180868, U10CA180822, UG1CA189867, and Novartis

// Haeyoung Kim 1 , Won Park 2 , Jeong Il Yu 2 , Doo Ho Choi 2 , Seung Jae Huh 2 , Yeon-Joo Kim 3 , Eun Sook Lee 3 , Keun Seok Lee 3 , Han-Sung Kang 3 , In Hae Park 3 , Kyung Hwan Shin 4 , Kyubo Kim 5 , Kyung Ran Park 5 , Yong Bae Kim 6 , Sung Ja Ahn 7 , Jong Hoon Lee 8 , Jin Hee Kim 9 , Mison Chun 10 , Hyung-Sik Lee 11 , Jung Soo Kim 12 and Jong-Young Lee 13 1 Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi, South Korea 2 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea 3 Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea 4 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea 5 Department of Radiation Oncology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, South Korea 6 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea 7 Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, South Korea 8 Department of Radiation Oncology, St. Vincent’s Hospital, The Catholic University of Korea College of Medicine, Suwon, South Korea 9 Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea 10 Department of Radiation Oncology, Ajou University School of Medicine, Suwon, Gyeonggi, South Korea 11 Department of Radiation Oncology, Dong-A University Hospital, Dong-A University School of Medicine, Busan, South Korea 12 Department of Radiation Oncology, Chonbuk National University Medical School, Jeonju, Jeollabuk, South Korea 13 Department of Radiation Oncology, Wonju Severance Christian Hospital, Wonju, Kangwon, South Korea Correspondence to: Won Park, email: // Keywords : breast neoplasms, radiotherapy, dose-response relationship, prognosis Received : May 17, 2016 Accepted : August 25, 2016 Published : October 25, 2016 Abstract Background and Purpose: This study was performed to determine optimal radiation dose in pN1 breast cancer patients who received breast conserving surgery (BCS) and anthracycline plus taxane (AT)-based chemotherapy. Materials and Methods: Retrospective chart reviews were performed in 1,147 patients who were treated between January 2006 and December 2010. The impact of radiation dose on treatment outcomes was evaluated. Results: Median follow-up time was 66 months. The 5-year rate of disease-free survival (DFS) was 93.2%. Larger tumor size (> 20 mm), positive lymphovascular invasion, high histologic grade, and high ratio of positive nodes (> 0.1) were significantly associated with inferior DFS. By using the 4 factors related to DFS, patients were categorized into high-risk (with ≥ 3 factors) and low-risk (with 60.3 Gy EQD2 ) was significantly associated with better DFS than the lower dose (≤ 60.3 Gy EQD2 ). However, the radiation dose did not impact DFS in the low-risk group. Conclusions: Dosing of radiation affects the outcome of post-BCS radiotherapy in pN1 breast cancer. Doses of over 60.3 Gy EQD2 were associated with better outcome in the high-risk patients.

PURPOSE To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. MATERIALS AND METHODS We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. RESULTS Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). CONCLUSION Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary.

Purpose The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. Materials and methods Overall, 235 Korean patientswith BRCA1/2 mutation-negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. Results A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. Conclusion No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.

// Jeong Il Yu 1,* , Hyebin Lee 5,* , Hee Chul Park 1 , Doo Ho Choi 1 , Yoon-La Choi 2 , In-Gu Do 6 , Hee Cheol Kim 3 , Woo Yong Lee 3 , Seong Hyeon Yun 3 , Yong Beom Cho 3 , Jung Wook Huh 3 , Yoon Ah Park 4 , Young Suk Park 4 , Joon Oh Park 4 , Seung Tae Kim 4 and Won Park 1 1 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea * These authors have contributed equally to this work as first authors Correspondence to: Won Park, email: // Keywords : rectal neoplasm, total mesorectal excision, radiotherapy, survivin, prognosis Received : May 05, 2016 Accepted : June 18, 2016 Published : July 06, 2016 Abstract Background & Aims: This study is designed to investigate the expression of survivin and p53 in human rectal cancer tissues and analyze associations between expression and clinical outcomes in terms of disease recurrence and survival duration. Results: During follow-up (median 119.0, range 6.6 to 161.3 months), tumor recurrence was detected in 50 patients (43.1%), and local recurrence developed as a first failure site in 13 patients (11.2%). Positive immunostaining of nuclear and cytoplasmic survivin was observed in about one quarter of patients, and about half of all patients had positive staining for p53. Both survivin and p53 were significant prognostic factors of disease-free survival in the univariate analyses, but only survivin remained a significant prognostic factor in the multivariate analysis. Methods: We performed a retrospective study with 116 locally advanced rectal cancer patients who underwent total mesorectal excision (TME) followed by postoperative concurrent chemo-radiation therapy (CCRT). Immunohistochemical staining was conducted using antibodies for survivin or p53, and their expression was analyzed using an individual score that combined the percentage of positive cells and staining intensity. Conclusions: Overexpression of nuclear and cytoplasmic survivin in locally advanced rectal cancer patients was associated with a higher recurrence rate in rectal cancer patients treated with TME followed by postoperative CCRT.