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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.

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 Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. Methods Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. Results In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p, Highlights • Radiation dose is associated with the risk of breast reconstruction complications. • We conducted a retrospective multi-center observational study of 314 women in Korea. • Complication-related risk factors were identified using multivariate analysis. • Use of hypofractionated radiation therapy may improve breast reconstruction outcomes. • A prospective multi-center study is under way to further validate our findings.

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

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.

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.

PurposeTo evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomyMaterials and MethodsMedical 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

Patients with brain metastases (BM) can benefit from radiotherapy (RT), although the long-term benefits of RT remain unclear. We searched a Korean national health insurance claims database and identified 135,740 patients with newly diagnosed BM during 2002–2017. Propensity score matching (PSM) was used to evaluate survival according to RT modality, which included whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS). The 84,986 eligible patients were followed for a median interval of 6.6 months, and 37,046 patients underwent RT (43.6%). After the PSM, patients who underwent RT had significantly better overall survival after 1 year (42.4% vs. 35.3%, P

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

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 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.

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.

Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer.Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography.Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively.This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.

Purpose We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). Materials and methods A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. Results After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). Conclusion This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

Purpose: To evaluate the treatment outcomes of radiotherapy (RT) for breast cancer with ipsilateral supraclavicular (SCL) and/or internal mammary (IMN) lymph node involvement. Methods: A total of 353 patients from 11 institutions were included. One hundred and thirty-six patients had SCL involvement, 148 had IMN involvement, and 69 had both. All patients received neoadjvant systemic therapy followed by breast conserving surgery or mastectomy, and postoperative RT to whole breast/chest wall. As for regional lymph node irradiation, SCL RT was given to 344 patients, and IMN RT to 236 patients. The median RT dose was 50.4 Gy. Results: The median follow-up duration was 61 months (range, 7-173). In-field progression was present in SCL (n=20) and/or IMN (n=7). The 5-year disease-free survival (DFS) and overall survival rates were 57.8% and 75.1%, respectively. On multivariate analysis, both SCL/IMN involvement, number of axillary lymph node ≥4, triple negative subtype, and mastectomy were significant adverse prognosticators for DFS (p = 0.022, 0.001, 0.001, and 0.004, respectively). Regarding the impact of regional nodal irradiation, SCL RT dose ≥54 Gy was not associated with DFS (5-yr rate, 52.9% vs. 50.9%, p = 0.696) in SCL-involved patients, and the receipt of IMN RT was not associated with DFS (5-yr rate, 56.1% vs. 78.1%, p = 0.099) in IMN-involved patients. Conclusion: Neoadjuvant chemotherapy followed by surgery and postoperative RT achieved an acceptable in-field regional control rate in patients with SCL and/or IMN involvement. However, a higher RT dose to SCL or IMN RT was not associated with the improved DFS in these patients. Citation Format: Kim K, Jeong Y, Shin KH, Kim JH, Ahn SD, Kim SS, Suh C-O, Kim YB, Choi DH, Park W, Cha J, Chun M, Lee DS, Lee SY, Kim JH, Park HJ. Impact of regional nodal irradiation for breast cancer patients with supraclavicular and/or internal mammary lymph node involvement: A multicenter, retrospective study (KROG 16-14) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-12.

Modulated electro-hyperthermia (mEHT), also known as oncothermia, shows remarkable treatment efficacies for various types of tumours, including glioma. The aim of the present study was to investigate the molecular mechanism underlying phenotypic changes in oncothermic cancer cells.U87-MG and A172 human glioma cells were exposed to mEHT (42 °C/60 min) three times with a 2-day interval and subsequently tested for growth inhibition using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to mEHT, global changes in gene expression were examined using RNA sequencing. For in vivo evaluation of mEHT, we used U87-MG glioma xenografts grown in nude mice.mEHT inhibited glioma cell growth through the strong induction of apoptosis. The transcriptomic analysis of differential gene expression under mEHT showed that the anti-proliferative effects were induced through a subset of molecular alterations, including the up-regulation of E2F1 and CPSF2 and the down-regulation of ADAR and PSAT1. Subsequent Western blotting revealed that mEHT increased the levels of E2F1 and p53 and decreased the level of PARP-1, accelerating apoptotic signalling in glioma cells. mEHT significantly suppressed the growth of human glioma xenografts in nude mice. We also observed that mEHT dramatically reduced the portion of CD133(+) glioma stem cell population and suppressed cancer cell migration and sphere formation.These findings suggest that mEHT suppresses glioma cell proliferation and mobility through the induction of E2F1-mediated apoptosis and might be an effective treatment for eradicating brain tumours.

To investigate whether combined chemoradiotherapy (CTRT) confers a benefit for survival outcome over radiotherapy (RT) alone after primary surgery in patients with FIGO stage IIIC endometrial adenocarcinoma.We conducted a multicenter retrospective study of patients with surgical stage IIIC endometrial cancer from 1990 to 2011. Adjuvant RT alone was performed in 85 patients (40.3%) and adjuvant CTRT in 126 patients (59.7%). Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model.Stage IIIC1 and stage IIIC2 accounted for 63% and 37%, respectively. FIGO IIIC2 had a higher recurrence rate than FIGO IIIC1 (38.5% vs. 29.3%, p=0.172). Five-year OS and DFS were lower in FIGO IIIC2 than FIGO IIIC1 (85.1% vs. 76.9%, p=0.417; 71.0% vs. 59.2%, p=0.108, respectively). Eighteen patients (13.5%) in stage IIIC1 developed PALN recurrence, whereas only one (3.3%) in stage IIIC2 had PALN recurrence (p=0.001). In multivariate analysis, predictors of DFS were parametrial invasion (HR, 3.49; 95% CI, 1.83-6.64; p0.001), higher grade (HR, 2.78; 95% CI, 1.31-5.89; p=0.008), and3 positive pelvic nodes (HR, 1.84; 95% CI, 1.11-3.05; p=0.019). Combined CTRT did not affect DFS or OS in IIIC1 and IIIC2 compared with RT alone.CTRT showed comparable survival outcome to RT alone. Half of relapses (46%) in stage IIIC1 occurred in PALN region, whereas relapse in stage IIIC2 primarily occurred in distant metastasis (90%). Future randomized studies are needed to determine which subgroup may be most likely to benefit from CCRT.

Purpose We aimed to assess prognostic value of metastatic pelvic lymph node (mPLN) in early-stage cervical cancer treated with radical surgery followed by postoperative chemoradiotherapy. Also, we sought to define a high-risk group using prognosticators for recurrence. Materials and methods A multicenter retrospective study was conducted using the data from 13 Korean institutions from 2000 to 2010. A total of 249 IB-IIA patients with high-risk factors were included. We evaluated distant metastasis-free survival (DMFS) and disease-free survival (DFS) in relation to clinicopathologic factors including pNstage, number of mPLN, lymph node (LN)ratio (number of positive LN/number of harvested LN), and log odds of mPLNs (log(number of positive LN+0.5/number of negative LN+0.5)). Results In univariate analysis, histology (squamous cell carcinoma [SqCC] vs. others), lymphovascular invasion (LVI), number of mPLNs (≤ 3 vs. g 3), LN ratio (≤ 17% vs. g 17%), and log odds of mPLNs (≤ ‒0.58 vs. g ‒0.58) were significant prognosticators for DMFS and DFS. Resection margin involvement only affected DFS. No significant survival difference was observed between pN0 patients and patients with 1-3 mPLNs. Multivariate analysis revealed that mPLN g 3, LVI, and non-SqCC were unfavorable index for both DMFS (p l 0.001, p=0.020, and p=0.031, respectively) and DFS (p l 0.001, p=0.017, and p=0.001, respectively). A scoring system using these three factors predicts risk of recurrence with relatively high concordance index (DMFS, 0.69; DFS, 0.71). Conclusion mPLN g 3 in early-stage cervical cancer affects DMFS and DFS. A scoring system using mPLNs g 3, LVI, and non-SqCC could stratify risk groups of recurrence in surgically resected early-stage cervix cancer with high-risk factors.

S-1 chemotherapy is effective against advanced biliary tract cancer. The purpose was to evaluate the efficacy and safety of S-1-based concurrent chemoradiotherapy in patients with advanced biliary tract cancer. Patients with pathologically-proven advanced biliary tract cancer were eligible. S-1 was orally administered at a dose of 40 mg/m2, twice daily from day 1 to 14 and from day 22 to 35; concurrent radiotherapy of 180–200 cGy per fraction was delivered in 25–28 fractions. After treatment completion, tumor response was evaluated by computed tomography. In the first stage of the optimal two-stage phase II design, 18 patients were required. Twenty patients were enrolled between August 2006 and February 2009. The median age was 62.5 years (range 45–77 years). The median follow-up time was 11.6 months (range 1.9–49.1 months). Fifteen patients (75 %) had extrahepatic cholangiocarcinoma, two patients (10 %) had intrahepatic cholangiocarcinoma, and three patients (15 %) had gallbladder cancer. After treatment, a partial response was achieved in three patients (15 %), and stable disease was achieved in 14 patients (70 %). The overall response rate was 15 %, and the disease stabilization rate was 85 %. There was no grade 4 toxicity or treatment-related death. The common grade 3 toxicities were thrombocytopenia (15 %), neutropenia (10 %), and nausea (10 %). The median progression-free survival and median overall survival were 5.9 months (range 2.2–9.5 months) and 10.8 months (range 1.1–20.4 months), respectively. This study shows that S-1-based concurrent chemoradiotherapy is feasible and tolerable in patients with advanced biliary tract cancer. It will be further confirmed in a following large-scale phase II study.

PURPOSE The aim of this study was to assess the feasibility and efficacy of hypofractionated simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) using three-layered planning target volumes (PTV) for malignant gliomas. MATERIALS AND METHODS We conducted a retrospective analysis of 12 patients (WHO grade IV-10; III-2) postoperatively treated with SIB-IMRT with concurrent temozolomide. Three-layered PTVs were contoured based on gadolinium-enhanced magnetic resonance imaging as follows; high risk PTV (H-PTV) as the area of surgical bed including residual gross tumor with a 0.5 cm margin; low risk PTV (L-PTV) as the area surrounding the high risk PTV with 1.5 cm margin; moderate risk PTV (M-PTV) as a line at one-third the distance from high risk PTV to low risk PTV. Total dose to high risk PTV was 70 Gy in 8 and 62.5 Gy in 4 patients. RESULTS The median follow-up time was 52 months in surviving patients. The 2- and 5-year overall survival (OS) rates were 66.6% and 47.6%, respectively. The 2- and 5-year progression-free survival (PFS) rates were 57.1% and 45.7%, respectively. The median OS and PFS were 48 and 31 months, respectively. Six patients (50%) progressed: in-field only in one, out-field or disseminated in 4, and both in one patient. All patients completed planned treatments without a toxicity-related gap. Asymptomatic radiation necrosis was observed in 4 patients at post-radiotherapy 9-31 months. CONCLUSION An escalated dose of hypofractionated SIB-IMRT using three-layered PTVs can be safely performed in patients with malignant glioma, and might contribute to better tumor control and survival.

Purpose This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. Materials and methods We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. Results A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. Conclusion We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

Purpose To review the clinical outcomes of extended-field radiation therapy (EFRT) and to analyze prognostic factors significant for survival in patients receiving EFRT for uterine cervical carcinoma with para-aortic node (PAN) metastasis. Patients and methods We retrospectively reviewed 90 patients with stage IB-IVA cervical cancer and PAN metastasis between 1987 and 2012. Median age was 50 (range, 24–77). Patients received median 70.2 Gy (range, 56–93) to point A and median 50.4 Gy (range, 45–60.4) to PAN over median 69 elapsed days (range, 43–182). Forty-six patients (51.1%) received concurrent chemotherapy. Survival was calculated using the Kaplan–Meier method. We analyzed prognostic factors for overall actuarial survival (OS) and progression-free survival (PFS) using a Cox regression method. Results The median follow-up period for surviving patients was 55 months (range, 3–252). Seventy patients (77.8%) had complete remission. Forty-six patients experienced treatment failure as follows: 11 patients (12.2%) as local recurrence, 19 (21%) as regional recurrence and 33 (36.7%) as distant metastasis. The 5-yr OS and PFS were 62.6% and 43.9%, respectively. Treatment response was the only statistically independent prognostic factors for OS (p= 0.04) and PFS (p< 0.001) on multivariate analysis. Grade 3 or 4 hematologic gastrointestinal and urogenital toxicities were observed in about 10% of patients. Conclusions Our institutional experiences showed that EFRT was an effective treatment for cervical cancer patients with PAN metastasis. The addition of chemotherapy to EFRT seems to have uncertain survival benefit with higher hematologic toxicity. Electronic supplementary material The online version of this article (doi:10.1186/s13014-014-0320-5) contains supplementary material, which is available to authorized users.

Background: For huge hepatocellular carcinoma (HCC), therapeutic decisions have varied from local therapy to systemic therapy, with radiotherapy (RT) playing only a palliative role. In this study, we investigated whether multimodality treatment involving RT could be effective in huge HCC. Results: This study was performed in 116 patients with HCC >10 cm. The number of patients in stage II, III and IV was 12, 54 and 50, respectively. RT was given as a combined modality in most patients. The median dose was 45 Gy, with 1.8 Gy per fraction. The median overall survival (OS) and progression-free survival (PFS) were 14.8 and 6.5 months, respectively. The median infield PFS was not reached. Infield failure, outfield intrahepatic and extrahepatic failure were observed in 8.6, 18.1, and 12.1% of patients, respectively. For OS and PFS, number of tumors, initial alpha-fetoprotein (AFP) level, treatment response, percent AFP decrement, and hepatic resection were significant prognostic factors. Tumor characteristics and treatment response were significantly different between long-term survivors and the other patients. Conclusion: Although huge HCC presents an aggressive clinical course, multimodality approaches involving RT can offer an opportunity for prolonged survival.

Objective: In this study, we investigated the effects of radiotherapy � 60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II–III esophageal cancer. Methods: A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of ,60 Gy (standard-dose group), while 77 received a total radiation dose of � 60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45–59.4 Gy) and 63 Gy (range, 60–81 Gy), respectively. Results: The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P , 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P ¼ 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P ¼ 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. Conclusions: High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II –I II esophageal cancer. Our study could provide the basis for future randomized clinical trials.

S-1 is a novel oral fluoropyrimidine anticancer agent designed to enhance clinical efficacy, reduce gastrointestinal toxicity, and enhance radiotherapy effectiveness. A phase II trial was conducted to evaluate the efficacy and safety of preoperative chemoradiation with S-1 and cisplatin in locoregionally advanced esophageal cancer.Eligible patients had stage IIA-IVA esophageal cancer. Patients received two cycles of S-1 (days 1-14 and days 22-35) and cisplatin (days 1 and 22) with concurrent radiotherapy (50.4 Gy total; 1.8 Gy/fraction). Esophagectomy was performed between weeks 12 and 18 as determined by the specialist multidisciplinary team.Sixty patients were enrolled in this study between March 2008 and August 2011, and 59 were eligible. The clinical stage was ≥T3 in 28 patients (47 %) and N1 in 43 patients (72 %), with squamous cell carcinoma histology in 58 patients (97 %). Fifty-four patients (90 %) completed the planned chemoradiation. After chemoradiation, the clinical tumor response rate was 64.4 %. The primary toxicities included neutropenia (24 %) and esophagitis (8.5 %). Three treatment-related deaths were noted. Twenty-five patients (42 %) underwent esophagectomy following chemoradiation, and 15 achieved complete pathologic regression. The estimated overall survival and progression-free survival rates after 2 years were 65 and 48 %, respectively.Concurrent chemoradiation with S-1 and cisplatin exhibited encouraging results with complete pathologic regression. The survival data were promising compared with the historical data of 5FU/cisplatin and should be confirmed in a randomized phase III trial. Toxicities were significant but clinically manageable.

Purpose To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. Materials and methods From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy). Results Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last follow-up, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. Conclusion Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

Background The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T1-2N0-1 oral tongue squamous cell carcinoma (OSCC) and to evaluate survival and prognostic factors. Methods Retrospective analysis of 86 patients with T1-2N0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3%) received postoperative radiotherapy (PORT). Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed. Results The median follow-up was 45 months. The five-year overall survival (OS) and disease-free survival (DFS) rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth). In the risk group, there was no local failure in patients with postoperative radiotherapy. Conclusions In T1-2N0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features.

Purpose Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis ( p = 0.043). There were no radiation-related deaths. Conclusions Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

Purpose: The purpose of this study is to compare the dosimetry of electron beam (EB) plans and three-dimensional helical tomotherapy (3DHT) plans for the patients with left-sided breast cancer, who underwent breast conserving surgery. Materials and Methods: We selected total of 15 patients based on the location of tumor, as following subsite: subareolar, upper outer, upper inner, lower lateral, and lower medial quadrants. The clinical target volume (CTV) was defined as the area of architectural distortion surrounded by surgical clip plus 1 cm margin. The conformity index (CI), homogeneity index (HI), quality of coverage (QC) and dose-volume parameters for the CTV, and organ at risk (OAR) were calculated. The following treatment techniques were assessed: single conformal EB plans; 3DHT plans with directional block of left anterior descending artery (LAD); and 3DHT plans with complete block of LAD. Results: 3DHT plans, regardless of type of LAD block, showed significantly better CI, HI, and QC for the CTVs, compared with the EB plans. However, 3DHT plans showed increase in the V1Gy at skin, left lung, and left breast. In terms of LAD, 3DHT plans with complete block of LAD showed extremely low dose, while dose increase in other OARs were observed, when compared with other plans. EB plans showed the worst conformity at upper outer quadrants of tumor bed site. Conclusion: 3DHT plans offer more favorable dose distributions to LAD, as well as improved target coverage in comparison with EB plans.

Purpose Sorafenib is an effective systemic agent for advanced hepatocellular carcinoma. To increase its efficacy, we evaluated the feasibility and benefit of sorafenib combined with radiotherapy. Materials and Methods From July 2007 to July 2011, 31 patients were treated with a daily dose of 800 mg of sorafenib and radiotherapy. Among them, 13 patients who received radiotherapy on the bone metastasis were excluded. Thirteen patients received 30-54 Gy of radiotherapy on the primary tumor (primary group) and 5 patients received 30-58.4 Gy on the measurable metastatic lesions (measurable metastasis group). Tumor responses at 1 month after the completion of radiotherapy and overall survival were evaluated. Results The in-field response rate was 100% in the primary group and 60% in the measurable metastasis group. A decrease of more than 80% in the tumor marker α-fetoprotein was observed in 7 patients in the primary group (54%). Toxicities of grades 3-4 were hand-foot syndrome in 3 (17%) patients, duodenal bleeding in 1 (6%) patient, thrombocytopenia in 3 (17%) patients and elevation of aspartate transaminase in 1 (6%) patient. The median overall survival was 7.8 months (95% confidence interval, 3.0-12.6). Conclusion The combined treatment of sorafenib and radiotherapy was feasible and induced substantial tumor responses in the target lesions. The results of this study emphasize the importance of individualized approach in the management of advanced hepatocellular carcinoma and encourage the initiation of a controlled clinical trial.

Background: POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. Methods: In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman’s disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). Results: The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). Conclusions: Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field.

Purpose To compare photon thunderbird with deep match (technique 1) with 3-field technique with electron inguinal boost (technique 2) in acute skin toxicity, toxicity-related treatment breaks and patterns of failure in elective inguinal radiation therapy (RT) for curative chemoradiation in anal cancer. Materials and Methods Seventeen patients treated between January 2008 and September 2010 without evidence of inguinal and distant metastasis were retrospectively reviewed. In 9 patients with technique 1, dose to inguinal and whole pelvis area was 41.4 to 45 Gy and total dose was 59.4 Gy. In 8 patients with technique 2, doses to inguinal, whole pelvis, gross tumor were 36 to 41.4 Gy, 36 to 41.4 Gy, and 45 to 54 Gy, respectively. The median follow-up period was 27.6 and 14.8 months in group technique 1 and 2, respectively. Results The incidences of grade 3 radiation dermatitis were 56% (5 patients) and 50% (4 patients), dose ranges grade 3 dermatitis appeared were 41.4 to 50.4 Gy and 45 to 54 Gy in group technique 1 and 2, respectively (p = 0.819). The areas affected by grade 3 dermatitis in 2 groups were as follow: perianal and perineal areas in 40% and 25%, perianal and inguinal areas in 0% and 50%, and perianal area only in 60% and 25%, respectively (p = 0.196). No inguinal failure has been observed. Conclusion Photon thunderbird with deep match technique and 3-field technique with electron inguinal boost showed similar incidence of radiation dermatitis. However, photon thunderbird with deep match seems to increase the possibility of severe perineal dermatitis.