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The organocatalytic enantioselective conjugate reaction of 2-fluoro-1,3-diketones to nitroalkenes promoted by chiral binaphthyl-modified squaramide has been achieved. Treatment of 2-fluoro-1,3-diketones with nitroalkenes under mild reaction conditions afforded the corresponding Michael products containing fluorinated quaternary carbon stereocenter with excellent enantioselectivity (up to 98% ee).

Purpose In a recent meta-analysis, post-mastectomy radiotherapy (PMRT) reduced any first recurrence (AFR) and improved survival in N1 and N2 patients. We investigated risk factors for AFR in N1 after optimal systemic therapy without PMRT, to define a subgroup of patients who may benefit from PMRT. Materials and Methods One thousand three hundred eighty-two pT1-2N1M0 breast cancer patients treated with mastectomy without PMRT between 2005 and 2010 were retrospectively analyzed. Only 0.6% had no systemic therapy. Results After a median follow-up of 5.9 years, there were 173 AFR (53 loco-regional recurrence [LRR] without distant metastases [DM], 38 LRR with DM, and 82 DM without LRR). The 5-year LRR and AFR rates were 6.1% and 12.0%, respectively. Multivariate analysis revealed that close resection margin (p=0.001) was the only independent risk factor for LRR. Multivariate analysis for AFR revealed that age < 35 years (p=0.025), T2 stage (p=0.004), high tumor grade (p=0.032), close resection margin (p=0.035), and triple-negative biological subtype (p=0.031) were independent risk factors. Two or three positive lymph nodes (p=0.078) were considered a marginally significant factor. When stratified by these six factors, the 5-year LRR rates were 3.6% with 0-1 (n=606), 7.5% with 2-3 (n=655), and 12.7% with 4-6 (n=93) risk factors. The 5-year AFR rates were 7.1% with 0-1, 15.0% with 2-3, and 24.5% with 4-6 risk factors. Conclusion Patients with pT1-2N1M0 breast cancer who underwent mastectomy and optimal systemic therapy showed excellent loco-regional control and disease control. The patients with four or more risk factors may benefit from PMRT, and those with two or three risk factors merit consideration of PMRT.

Purpose In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. Materials and Methods Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. Results With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. Conclusion WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

Purpose The concentration of capecitabine peaks at 1-2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. Materials and methods We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals (1,650 mg/m2/day). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). Results The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Conclusions Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities.

Zinc oxide (ZnO), an inorganic compound that appears as a white powder, is used frequently as an ingredient in sunscreens. The aim of this review was to examine the toxicology and risk assessment of ZnO based upon available published data. Recent studies on acute, sub-acute, and chronic toxicities of ZnO indicated that this compound is virtually non-toxic in animal models. However, it was reported that ZnO nanoparticles (NP) (particle size, 40 nm) induced significant changes in anemia-related hematologic parameters and mild to moderate pancreatitis in male and female Sprague-Dawley rats at 536.8 mg/kg/day in a 13-week oral toxicity study. ZnO displayed no carcinogenic potential, and skin penetration is low. No-observed-adverse-effect level (NOAEL) ZnO was determined to be 268.4 mg/kg/day in a 13-week oral toxicity study, and a maximum systemic exposure dose (SED) of ZnO was estimated to be 0.6 mg/kg/day based on topical application of sunscreen containing ZnO. Subsequently, the lowest margin of safety (MOS) was estimated to be 448.2, which indicates that the use of ZnO in sunscreen is safe. A risk assessment was undertaken considering other routes of exposure (inhalation or oral) and major product types (cream, lotion, spray, and propellant). Human data revealed that MOS values (7.37 for skin exposure from cream and lotion type; 8.64 for skin exposure of spray type; 12.87 for inhalation exposure of propellant type; 3.32 for oral exposure of sunscreen) are all within the safe range (MOS1). Risk assessment of ZnO indicates that this compound may be used safely in cosmetic products within the current regulatory limits of 25% in Korea.

Purpose This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI). Materials and methods Twenty-four treatment-naive patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software. Results The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565±0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively. Conclusion The local controlrate and complication profile after PBT in patientswith choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI.

// Hae Jin Park 1 , Kyung Hwan Shin 2 , Jin Ho Kim 3 , Seung Do Ahn 4 , Su Ssan Kim 4 , Yong Bae Kim 5 , Won Park 6 , Yeon-Joo Kim 7 , Hyun Soo Shin 8 , Jin Hee Kim 9 , Sun Young Lee 10 , Kyubo Kim 11 , Kyung Ran Park 12 and Bae Kwon Jeong 13 1 Departments of Radiation Oncology, Hanyang University Hospital, Seoul, Korea 2 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea 3 Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea 4 Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul, Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea 6 Department of Radiation Oncology, Sungkyunkwan University School of Medicine, Seoul, Korea 7 Department of Radiation Oncology, Proton Therapy Center, National Cancer Center, Goyang, Korea 8 Department of Radiation Oncology, CHA University School of Medicine, Pocheon, Korea 9 Department of Radiation Oncology, Keimyung University School of Medicine, Daegu, Korea 10 Department of Radiation Oncology, Chonbuk National University Hospital, Jeonju, Korea 11 Department of Radiation Oncology, Ewha Womans University School of Medicine, Seoul, Korea 12 Department of Radiation Oncology, Ewha Womans University Mokdong Hospital, Seoul, Korea 13 Department of Radiation Oncology, Gyeongsang National University School of Medicine, Jinju, Korea Correspondence to: Kyung Hwan Shin, email: // Keywords : breast cancer, post-mastectomy radiotherapy, risk factors Received : January 02, 2017 Accepted : February 20, 2017 Published : March 15, 2017 Abstract Purpose: This study was performed to identify a subset of patients who may benefit from post-mastectomy radiotherapy (PMRT) among node-negative breast cancer patients. Materials and Methods: We retrospectively reviewed 1,828 patients with pT1-2N0 breast cancer, treated with mastectomy without PMRT from 2005 to 2010 at 10 institutions. Univariate and multivariate analyses for locoregional recurrence (LRR) and any first recurrence (AFR) were performed according to clinicopathologic factors and biologic subtypes. Results: During a median follow-up period of 5.9 years (range: 0.7-10.4 years), 98 patients developed AFR (39 isolated LRR, 13 LRR with synchronous distant metastasis, and 46 isolated distant metastasis), and 52 patients developed LRR. The 7-year LRR and AFR rates were 3.8% and 6.7%, respectively. Multivariate analysis revealed that age of ≤ 40 years ( p

OBJECTIVES There is no consensus on whether giving adjuvant concurrent chemoradiotherapy (CCRT) is more effective than adjuvant radiotherapy (RT) alone in patients with early stage cervical cancer and intermediate-risk factor(s). The purpose of this study was to evaluate survival difference according to adjuvant treatment in the intermediate-risk group. METHODS From 2000 to 2014, the medical records of patients with stage IB-IIA cervical cancer and a history of radical hysterectomy with pelvic lymph node dissection, followed by pelvic RT at a dose ≥40 Gy were retrospectively reviewed. Among these, 316 patients with one or more intermediate-risk factor(s) and no high-risk factors were included. The criteria defined the intermediate-risk group as those patients with any of the following intermediate-risk factors: lymphovascular space involvement, over one-half stromal invasion, or tumor size ≥4 cm. RESULTS The median follow-up duration was 70 months (range: 3-203 months). According to adjuvant treatment (adjuvant RT alone vs. adjuvant CCRT), the 5-year recurrence-free survival rates (90.8% vs. 88.9%, p=0.631) and 5-year overall survival rates (95.9% vs. 91.0%, p=0.287) did not show a significant difference in patients with any of the intermediate-risk factors. In multivariate analysis, a distinct survival difference according to adjuvant treatment was not found regardless of the number of risk factors. CONCLUSION The present study showed that giving RT together with chemotherapy is not more effective than RT alone for stage IB-IIA cervical cancer patients with intermediate-risk factor(s). TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01101451.

Ho Cheol Kim,1 Yeh Rim Kang,2 Wonjun Ji,1 Yeon Joo Kim,1 Shinkyo Yoon,3 Jae Cheol Lee,3 Chang-Min Choi1,31Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 2Medical Department, Oncology, Novartis Korea Pharmaceuticals, Seoul, South Korea; 3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaPurpose: BRAF mutations are found in 1–5% of non-small cell lung cancers, particularly adenocarcinomas. However, information regarding this mutation is limited in patients without EGFR/ALK aberrations, who have limited treatment options.Patients and methods: The medical records of 224 stage III/IV adenocarcinoma patients without EGFR/ALK aberrations and with available pathologic tissue, were retrospectively reviewed. BRAF mutations were evaluated using a PNAClampTM, BRAF mutation detection kit (Panagene, Daejeon, Korea). The outcomes in the study population were compared with stage III/IV adenocarcinoma patients harboring an EGFR mutation. A case report of targeted therapy against BRAF mutations was also presented.Results: A cohort of 222 adenocarcinoma patients with adequate pathologic tissue samples was analyzed. The median patient age was 63years, 68.8% of the patients were male and 68.7% were ever-smokers. The V600E BRAF mutation was detected in 4 patients (1.8%). The 222 study patients had a poorer survival outcome compared to stage III/IV adenocarcinoma patients with an EGFR mutation (median, 12 vs 67months, 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.

Phthalates are used for industrial plasticizers to impart flexibility and durability to polyvinyl chloride. Despite widespread use of phthalates, reported endocrine-disrupting properties raise safety concerns for consumers. Since phthalates are permitted as excipients in controlled-release capsules and enteric coatings, patients taking drugs containing these chemicals may potentially be at some health risk. In this study, 102 distinct pharmaceutical products were analyzed by gas chromatography/mass spectrometry to determine phthalate content and maximal phthalate exposure rate was calculated. In 102 drug samples, di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP) were detected in 9.8, 27.45, and 5.88% of cases, respectively. The highest level of DEP was found in extended-release (ER) capsules with concentrations ranging from 935.5 to 1535.37 ppb. The highest levels of DBP (1.32-7.07 ppb) were detected in tablets, whereas highest level (7.07 ppb) of DEHP was found in suspension preparations. The phthalate hazard index (HI) (human exposure tolerable daily intake) was calculated for each sample, but no sample exhibited an HI value exceeding 1; the minimum value taken to indicate a serious health risk. Thus, no apparent serious health risk from phthalate exposure arises from taking these medications. The low HI values suggest that phthalate contamination in pharmaceuticals may not pose an apparent significant risk to humans. However, the sources of phthalate present in pharmaceutical products still needs to be investigated and verified through on-site inspections in manufacturing processes in order to minimize human exposure. It is recommended that measures be taken to prevent phthalate contamination in pharmaceuticals.

Background and purpose Systemic therapy such as sorafenib is the standard for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC); however, the survival benefits are modest especially for HCC with macroscopic vascular invasion (MVI). Transarterial chemoembolization (TACE) plus external beam radiotherapy (RT) is an alternative treatment to sorafenib, with favorable clinical results. We evaluated the outcomes of respiratory-gated RT and TACE in treatment-naive BCLC stage C HCC patients with MVI and proposed a subclassification model. Methods In this study, 639 patients received TACE plus RT for HCC with MVI as a first-line treatment between January 2010 and December 2015. Results Main/bilateral portal vein and/or inferior vena cava tumor thrombus was observed in 353 (55.2%) patients. The median radiation dose was 39 Gy (range 24–50) with a 2.5-Gy (2–5) median fraction size. The median overall survival was 10.7 months, with 1- and 2-year survival rates of 46.5% and 23.9%, respectively. In the multivariate analysis, Child–Pugh classification B, tumor size >10 cm, infiltrative/diffuse type, presence of extrahepatic metastasis, alpha-fetoprotein >150,000 ng/mL, and radiation dose ≤40 Gy were significant predictors for poor overall survival. Subclassification of patients into very low, low, intermediate, and high-risk groups showed median survivals of 84.8, 14.7, 10.3, and 5.7 months, respectively (p Conclusion TACE plus RT is an effective and safe treatment for HCC with MVI and could be considered a first-line treatment option. The subclassification scheme accurately predicted the prognosis of these patients and may be useful for tailored treatment.

Objectives To perform a systematic review and meta-analysis of the prognostic value of post-treatment ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in uterine cervical cancer patients treated with radiotherapy (RT) with or without chemotherapy. Methods PubMed and Embase databases were searched up to July 22, 2018, for studies which evaluated the response outcomes of ¹⁸F-FDG PET following RT, and their prognostic significance in uterine cervical cancer was assessed with overall survival (OS) or progression-free survival (PFS) as endpoints. Hazard ratios (HRs) were meta-analytically pooled using the random-effects model. Results Eleven studies with 12 patient cohorts including 1,104 patients were included. For a quantitative synthesis of OS, 7 cohorts were included. Two cohorts which reported disease-specific survival instead of OS were also included with flexibility. Pooled HR of complete metabolic response (CMR) compared to partial metabolic response (PMR) was 0.19 (95% confidence interval [CI]=0.11-0.31). Pooled HR of CMR compared to progressive metabolic disease (PMD) was more evident at 0.07 (95% CI=0.04-0.12), and that of CMR compared to both PMR and PMD was 0.20 (95% CI=0.12-0.34). Quantitative synthesis for PFS was performed with a total of 8 cohorts. Pooled HR of CMR was 0.17 (95% CI=0.10-0.29) compared to PMR, 0.02 (95% CI=0.01-0.06) compared to PMD and 0.12 (95% CI=0.07-0.19) compared to both PMR and PMD. Conclusion Response results of post-RT ¹⁸F-FDG PET were significant prognostic factors in patients with uterine cervical cancer, and ¹⁸F-FDG PET could be a reasonable follow-up imaging modality.

SUMMARY: We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFNγ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFNγ in vitro exposure leads to a conserved transcriptome response unless cells have IFNγ receptor alterations. This conserved IFNγ transcriptome response in melanoma cells serves to amplify the antitumor immune response. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream IFNγ signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy. ETOC BLURB: Analyzing the transcriptome of biopsies of patients during immune checkpoint blockade therapy, Grasso et al. show that the increase of T cell infiltration and the downstream IFNγ signaling drive clinical responses.

SUMMARY The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YSHSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%–40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1−/− concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5–13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization., Graphical Abstract, In Brief Lee et al. identify LYVE1 as a marker that is highly enriched in yolk sac endothelium and definitive HSPCs during mid-gestation. Lyve1-Cre-labeled hematopoietic cells initiate fetal liver erythropoiesis and give rise to more than one-third of fetal and adult HSCs. The primitive erythroid lineage develops from LYVE1 negative precursors.

// 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.

The purpose of this work was to identify prognostic factors for survival after magnetic resonance image (MRI)-guided brachytherapy combined with external beam radiotherapy for cervical cancer. External beam radiotherapy of 45–50.4 Gy was delivered by either three-dimensional conformal radiotherapy or helical tomotherapy. Patients also received high-dose-rate MRI-guided brachytherapy of 5 Gy in 6 fractions. We analyzed 128 patients with International Federation of Gynecology and Obstetrics stage IB–IVB cervical cancer who underwent MRI-guided brachytherapy. Most patients (96 %) received concurrent chemotherapy. Pelvic lymph node metastases and para-aortic lymphadenopathies were found in 62 % and 14 % of patients, respectively. The median follow-up time was 44 months. Complete remission was achieved in 119 of 128 patients (93 %). The 5‑year local recurrence-free, cancer-specific, and overall survival rates were 94, 89, and 85 %, respectively. Negative pelvic lymphadenopathy, gross tumor volume (GTV) dose covering 90 % of the target (GTV D90) of >110 Gy, and treatment duration ≤56 days were associated with better overall survival in univariate analyses. Multivariable analysis showed that GTV D90 of >110 Gy and treatment duration ≤56 days were possibly associated with overall survival with near-significant P-values of 0.062 and 0.073, respectively. The outcome of MRI-guided brachytherapy combined with external beam radiotherapy in patients with cervical cancer was excellent. GTV D90 of >110 Gy and treatment duration ≤56 days were potentially associated with overall survival.

Background Soft-tissue sarcomas (STS) of the distal extremities are a rare disease entity, hence proper treatment strategy is not well established. We evaluated the local control, survival and complications of treating sarcomas in the wrist, hand, ankle and foot with limb-sparing surgery (LSS) and postoperative radiotherapy (PORT). Patients and methods Seventeen patients with STS in wrist, hand, ankle and foot who received PORT after LSS from August 2008 to November 2015 were retrospectively reviewed. Primary outcome was 5-year local recurrence-free survival (LRFS). Secondary outcomes were 5-year distant metastasis-free survival (DMFS) and toxicities. Results The median age was 32 (range=12-78) years. The most frequent STS location was the foot in 11 patients (64%) followed by two patients each in the wrist, hand and ankle, respectively. Fourteen patients (82%) underwent wide resection with flap grafts and the same number of patients achieved clear resection margins. The median postoperative radiation dose was 54 (range=46-60) Gy. Five patients also received chemotherapy. At a median follow-up of 39 (range=6-87) months, 5-year LRFS and DMFS were both 100%. Only one patient experienced grade 3 radiation dermatitis and there was no major wound complication. Radiation-induced bone fracture occurred in two patients. Conclusion PORT after LSS showed excellent local control for STS in the wrist, hand, ankle and foot. Considering the good local control and saving of limb function without any significant toxicity, the combination of LSS followed by PORT could be an appropriate and safe modality for STS of the distal extremities.

A visible light-mediated photocatalytic bis(alkoxycarbonyl)methylation/ring expansion of alkenyl cyclobutanols is described. This approach provides a mild and operationally simple access to the synthesis of bis(alkoxycarbonyl)methyl-substituted cyclic ketones from the coupling reaction of 1-(1-arylvinyl)cyclobutanols with aryl bromomalonates.

Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and triggers the activation of myeloid differention factor 88 (MyD88) and the Toll/interleukin-1 receptor domain-containing adapter, inducing interferon-β (TRIF)-dependent major downstream signaling pathways. To evaluate the therapeutic potential of 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. Here, we investigated whether MNP modulates the TLR4 signaling pathways and which anti-inflammatory target in TLR4 signaling is regulated by MNP. MNP inhibited the activation of nuclear factor-κB (NF-κB) induced by LPS (TLR4 agonist), and it also inhibited the expression of cyclooxygenase-2 and inducible nitric oxide synthase. MNP inhibited LPS-induced NF-κB activation by targeting TLR4 dimerization in addition to IKKβ. These results suggest that MNP can modulate the TLR4 signaling pathway at the receptor level to decrease inflammatory gene expression.

Purpose This study was conducted to investigate the incidence and survival outcomes of second primary cancers after the diagnosis of cervical cancer. Materials and methods Data from the Korea Central Cancer Registry between 1993 and 2010 were reviewed and analyzed. Standardized incidence ratios (SIRs) of second primary cancers among women with cervical cancer were analyzed. Kaplan-Meier survival curves were constructed for cervical cancer patients with or without a second primary cancer. Results Among 72,805 women with cervical cancer, 2,678 (3.68%) developed a second primary cancer within a mean follow-up period of 7.34 years. The overall SIR for a second cancer was 1.08 (95% confidence interval, 1.04 to 1.12). The most frequent sites of second primary cancers were the vagina, bone and joints, vulva, anus, bladder, lung and bronchus, corpus uteri, and esophagus. However, the incidence rates of four second primary cancers (breast, rectum, liver, and brain) were decreased. The 5-year and 10-year overall survival rates were 78.3% and 72.7% in all women with cervical cancer, and for women with a second primary cancer, these rates were 83.2% and 65.5% from the onset of cervical cancer and 54.9% and 46.7% from the onset of the second primary cancer, respectively. Conclusion The incidence rates of second primary cancers were increased in women with cervical cancer compared to the general population, with the exception of four decreasing cancers. The 10-year overall survival rates were decreased in cervical cancer patients with a second primary cancer.

Yeon Joo Kim, Jin-hong Park, In-Ha Yun, Young Seok KimDepartment of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of KoreaPurpose: To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings.Methods: Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10–50Gy dose at 5-Gy intervals (V10–V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30Gy and 60Gy.Results: Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses.Conclusion: Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages.Keywords: prostate cancer, intensity-modulated radiotherapy, intestinal toxicity, citrulline

Purpose The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2–/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2–/Ki-67 ≥ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR–/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T–]) (HR–/HER2+, n=31), and triple negative (TN) (HR–/HER2–, n=61). Results After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T–), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T–), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T–) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion The TN and HER2(T–) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype.

Melanoma is a cancer of melanocytes, which develop from neural crest cells during embryogenesis. One of the ways melanoma can resist targeted therapy or adoptive T cell transfer therapy (ACT) is by dedifferentiation, whereby the tumor becomes less melanocytic and more neural crest-like. ACT-induced dedifferentiation and therapy resistance was a result of tumor necrosis factor (TNF) from antitumor T cells (Landsberg, Nature 2012), which can serve as a positive control for inflammatory cytokine-induced melanoma plasticity. To study whether immune checkpoint blockade induces melanoma dedifferentiation, we analyzed RNA-seq data from paired biopsies of 68 patients before and during anti-PD-1 therapy. Surprisingly, the tumors of patients with complete or partial response dedifferentiate following therapy (paired p= 0.00015), but those of stable or progressive disease do not (paired p= 0.31 and 0.32, respectively). As the presence of interferon-gamma signatures in biopsies is best correlated with response to anti-PD-1 therapy, we hypothesized that interferon-gamma mediates dedifferentiation. We dedifferentiated four human melanoma cell lines by in vitro exposure to long-term (three to five weeks) interferon-gamma and compared it to three days of TNF as positive control. Although TNF and long-term interferon-gamma induced similar phenotypic changes based on flow cytometry, ATAC-seq showed that they each drive different global chromatin remodeling. Motif enrichment analyses revealed STAT6, TFAP2C, and SOX proteins are key transcription factors involved in interferon-gamma-induced dedifferentiation. Inferred protein activity analysis of the matching RNA-seq data showed that these regulators, as well as IRF3 and HMGA1, alter in activity selectively with dedifferentiation. In conclusion, dedifferentiation may be a marker of positive response to anti-PD-1 therapy, mediated by chronic exposure to T cells producing interferon-gamma. Citation Format: Yeon Joo Kim, Katherine M. Sheu, Jennifer Tsoi, Gabriel Abril-Rodriguez, Catherine Grasso, Alexander Hoffmann, Stephen T. Smale, Thomas G. Graeber, Cristina Puig-Saus, Antoni Ribas. Interferon-gamma-induced melanoma plasticity and response to PD-1 blockade therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3155.

Objectives To perform a systematic review and meta-analysis of the prognostic value of post-treatment 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in uterine cervical cancer patients treated with radiotherapy (RT) with or without chemotherapy. Methods PubMed and Embase databases were searched up to July 22, 2018, for studies which evaluated the response outcomes of 18F-FDG PET following RT, and their prognostic significance in uterine cervical cancer was assessed with overall survival (OS) or progression-free survival (PFS) as endpoints. Hazard ratios (HRs) were meta-analytically pooled using the random-effects model. Results Eleven studies with 12 patient cohorts including 1,104 patients were included. For a quantitative synthesis of OS, 7 cohorts were included. Two cohorts which reported disease-specific survival instead of OS were also included with flexibility. Pooled HR of complete metabolic response (CMR) compared to partial metabolic response (PMR) was 0.19 (95% confidence interval [CI]=0.11–0.31). Pooled HR of CMR compared to progressive metabolic disease (PMD) was more evident at 0.07 (95% CI=0.04–0.12), and that of CMR compared to both PMR and PMD was 0.20 (95% CI=0.12–0.34). Quantitative synthesis for PFS was performed with a total of 8 cohorts. Pooled HR of CMR was 0.17 (95% CI=0.10–0.29) compared to PMR, 0.02 (95% CI=0.01–0.06) compared to PMD and 0.12 (95% CI=0.07–0.19) compared to both PMR and PMD. Conclusion Response results of post-RT 18F-FDG PET were significant prognostic factors in patients with uterine cervical cancer, and 18F-FDG PET could be a reasonable follow-up imaging modality.

Purpose We performed a systematic review and meta-analysis on the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from pretreatment F-FDG PET/CT in patients with esophageal cancer. Methods PubMed and EMBASE databases were searched until April 12, 2018, for studies that evaluated MTV or TLG as prognostic factors in esophageal cancer, with overall survival (OS) and event-free survival serving as the end points. Hazard ratios (HRs) were meta-analytically pooled using a random-effects model. Subgroup analyses based on the clinicopathological and PET variables were performed. Results In total, 16 studies with 1294 patients were included. The pooled HRs of MTV and TLG for OS were 2.26 (95% confidence interval [CI], 1.73-2.96) and 2.23 (95% CI, 1.73-2.87), respectively. Regarding event-free survival, the pooled HRs of MTV and TLG were 2.03 (95% CI, 1.66-2.49) and 2.57 (95% CI, 1.82-3.62), respectively. Metabolic tumor volume was found to be a significant prognostic factor for OS consistently across multiple subgroups classified based on stage, histological subtype, treatment, delineation of volume of interest, and the determination method of cutoff value, with pooled HRs ranging from 1.96 to 2.54. Conclusions In patients with esophageal cancer, MTV and TLG derived from pretreatment F-FDG PET are significant prognostic factors. As prognostic biomarkers, volumetric metabolic parameters may bolster the role of F-FDG PET in the management of esophageal cancer.

ObjectivesThe most appropriate treatments for brain metastases from ovarian cancer have not been established mainly because of its rarity. The objective of this study was to describe clinical results of treatment and prognostic factors of patients with brain metastases from ovarian cancer treated at a single institution.Materials and MethodsWe retrieved information from the electronic medical records of 56 consecutive patients (2.8%) with brain metastases, from a total of 2008 patients with ovarian cancer. Endpoints were the pattern of treatment failure, progression-free survival, and overall survival (OS).ResultsRadiation was the most common initial treatment for brain metastases (59%), followed by surgery (23%). The median progression-free survival was 9.8 months. Radiological progression was confirmed in 20 patients: 7 had leptomeningeal carcinomatosis (37%), 8 had local recurrence, and 5 had distant recurrence. Median OS was 11.25 months, and the 1-year OS rate was 48.2%. Patients received surgery for single metastasis as initial treatment showed median OS of 24.1 months, which was significantly prolonged compared with the other patients (P = 0.0002). Of the 48 patients who died, 29 (60%) died of systemic disease and 7 (15%) died of central nervous system progression. Karnofsky Performance Status greater than or equal to 70, control of systemic cancer, serous histology, and surgery for brain metastases were associated with improved OS in multivariable analysis (P < 0.05).ConclusionsSurgical resection for single or symptomatic brain metastases from ovarian cancer prolonged OS significantly. Multimodality treatment, including control of systemic cancer, appeared to be an important factor in prolonging OS.

The purpose of this study is to perform a systematic review and meta-analysis of volume-basedThe PubMed and EMBASE databases were systematically searched until January 19, 2018. We included studies that evaluated pretreatment MTV or TLG as a prognostic factor in uterine cervical cancer with event-free (EFS) and overall survival (OS) as the endpoints. Effect sizes of the prognostic value of MTV and TLG were measured in terms of hazard ratio (HR) and were meta-analytically pooled. Multiple subgroup analyses stratified to clinicopathologic and PET/CT variables were performed to explore heterogeneity.Twelve studies including 660 patients were included. Prognoses were worse in patients with high MTV and TLG, with pooled HRs of 5.89 (95% CI, 3.85-9.01; p0.00001) and 5.82 (95% CI, 3.62-9.35; p0.00001), respectively, for EFS and 6.62 (95% CI, 3.44-12.73; p0.00001) and 7.75 (95% CI, 3.48-17.27; p0.00001), respectively, for OS. At multiple subgroups analyses, the prognostic values of MTV and TLG for EFS were consistently significant, with pooled HRs of 5.08-7.30 and 4.80-15.83, respectively.Volume-based FDG PET/CT parameters were significant prognostic factors in patients with uterine cervical cancer. In spite of clinical and methodologic differences across the studies, patients with high MTV or TLG had a higher risk of adverse events or death.

A promising arsenal of targeted and immunotherapy treatments for metastatic melanoma has emerged over the last decade. With these therapies, we now face new mechanisms of tumor-acquired resistance. We report here a patient whose metastatic melanoma underwent dedifferentiation as a resistance mechanism to adoptive T-cell transfer therapy (ACT) to the MART1 antigen, a phenomenon that had been observed only in mouse studies to date. After an initial period of tumor regression, the patient presented in relapse with tumors lacking melanocytic antigens (MART1, gp100) and expressing an inflammation-induced neural crest marker (NGFR). We demonstrate using human melanoma cell lines that this resistance phenotype can be induced in vitro by treatment with MART1 T cell receptor–expressing T cells or with TNFα, and that the phenotype is reversible with withdrawal of inflammatory stimuli. This supports the hypothesis that acquired resistance to cancer immunotherapy can be mediated by inflammation-induced cancer dedifferentiation. Significance: We report a patient whose metastatic melanoma underwent inflammation-induced dedifferentiation as a resistance mechanism to ACT to the MART1 antigen. Our results suggest that future melanoma ACT protocols may benefit from the simultaneous targeting of multiple tumor antigens, modulating the inflammatory response, and inhibition of inflammatory dedifferentiation-inducing signals. Cancer Discov; 8(8); 935–43. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 899

Background Combined stereotactic body radiotherapy (SBRT) for lung lesions and conventional radiotherapy (CRT) for nodal areas may be more effective than CRT alone in patients with locally advanced lung cancer. Methods This study included 21 patients with small primary lung tumors distant from the regional nodal areas. The SBRT dose was 40–60 Gy in 4 fractions. CRT doses were 66 Gy in 30 fractions for non-small cell lung cancer and 52.5 Gy in 25 fractions for small cell lung cancer. Results The median follow-up duration was 12 months, and the median survival was 13 months. The 1 year overall survival, local recurrence-free survival, and distant metastasis-free survival rates were 60.5, 84.8, and 62.1%, respectively. Two patients experienced in-field local recurrence combined with out-field regional recurrence and/or distant failure. The major recurrence pattern was distant failure (crude incidence, 43%). Three patients aged ≥79 years experienced grade ≥ 3 acute radiation pneumonitis, and one also had idiopathic interstitial pneumonia. Conclusion The combination of SBRT for the lung lesion and CRT for the nodal region seems to be effective and safe for lung malignancies. However, patients older in age and/or with underlying pulmonary disease require stricter lung dose constraints.

The aim of this study was to perform a systematic review of the prognostic value of texture parameters derived byPubMed and EMBASE databases were searched up to March 12, 2018, for original articles involving texture analysis for the prediction of prognosis in patients with lung cancer. Risk of bias in the studies was critically assessed using the QUIPS tool. The results of survival analysis in the included studies were compared.Of the 446 articles retrieved, 17 studies were eligible for inclusion. Our review suggests that the prognostic value of texture parameters in lung cancer remains unproven. Most studies had a moderate to high risk of bias. Texture parameters that described prognosis were not replicated across studies. Conflicting results on hazard ratios were found among the studies. This discrepancy is partly explained by false-positive findings originating from statistical error and variability caused by different methodologies used for image acquisition and processing in the included studies.Based on currently available evidence, there is insufficient evidence to support the prognostic value of texture analysis in

Background Combination therapy using external-beam radiotherapy (EBRT) with a brachytherapy boost has demonstrated superior biochemical control than dose-escalated EBRT alone. Whereas brachytherapy is disadvantageous because it is an invasive procedure, stereotactic body-radiotherapy (SBRT) using CyberKnife could emulate the dose distribution of brachytherapy and is a non-invasive and safe modality to control intra-fractional movement. We therefore adopted SBRT using CyberKnife as a boost therapy after whole-pelvic radiotherapy (WPRT). Methods/design In this prospective, randomized, single-center, pilot study for intermediate- and high-risk prostate cancer without nodal or distant metastasis, after androgen-deprivation therapy and WPRT, patients will be randomized to one of two SBRT boost regimens, i.e., 18 or 21 Gy administered in three fractions every other day. Discussion The aim of this trial is to evaluate acute toxicities using both physician- and patient-reported outcomes and short-term biochemical control with SBRT boost following WPRT. Additionally, chronic toxicities and long-term biochemical control will be evaluated as secondary endpoints in this trial. Based on the generated results, we will plan the full-scale phase II study for selecting the SBRT boost dose. Trial registration ClinicalTrials.gov, ID; NCT03322020. Retrospectively registered on 26 October 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2574-y) contains supplementary material, which is available to authorized users.

We performed a systematic review and metaanalysis of the performance of

To perform a systematic review and meta-analysis to evaluate the impact ofPubmed and EMBASE databases were searched up to January 20, 2018. We included studies that reported proportion of management change afterFifteen studies (1163 patients) were included. The pooled proportion of management changes was 54% (95% confidence interval 47-60%). At meta-regression analyses, PET positivity (%) was a significant factor of heterogeneity (p=0.0486). For patients with biochemical failure, the proportion of radiotherapy (from 56% to 61%), surgery (from 1% to 7%), focal therapy (from 1% to 2%), and multimodal treatment (from 2% to 6%) increased, whereas that of systemic treatment (from 26% to 12%) and no treatment (from 14% to 11%) decreased withWe reviewed all previous studies assessing the impact of

Prostate cancer is generally considered to have a low α/β ratio. With this biological rationale and the development of radiation techniques, hypofractionation is now rapidly performed in radiation oncology field. Several prospective trials have been conducted to evaluate the moderate hypofractionation and demonstrated that moderate hypofractionation is not superior but equivalent to conventional fractionation regimen in terms of biochemical control. The data on extreme hypofractionation is still immature, but promising. Also, combined treatment with external beam radiotherapy and brachytherapy has demonstrated better biochemical control than that of external beam radiotherapy alone. In this chapter, we review the dose, technique, and fractionation scheme for the prostate cancer.

Purpose To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.

This study investigated the clinical manifestations of lower extremity edema (LEE) in locally advanced cervical cancer patients treated with two different strategies. In total, 79 cervical cancer survivors with International Federation of Gynecology and Obstetrics stage IB2-IIB were included. Six survivors with stage IB1 and who had been suspicious for lymph node metastasis on pretreatment image also were included. Forty-two patients received radiotherapy after pretreatment laparoscopic surgical staging (Group 1), and 43 patients received primary radiotherapy (Group 2). The patients’ medical records and survey results of the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) were analyzed. The incidence of LEE was higher in Group 1 than in Group 2 (69.0 vs. 11.6 %; P

Purpose. The purpose of this study was to investigate level of knowledge and attitude about organ donation in university and provide basic information on correct education and promotion. Method. The sample is consisted of 90 the students related to health and 90 general college students ; total 180 students in J city. The questionnaires were used to obtain the results. Data was collected from November 6th to 8th, 2013. For data analysis, the SPSS for window 12.0 K program was utilized to get descriptive statistics including the percentage, average, standard deviation and t-test. Results. Comparing the results between a series of health students and general college students, a series of health students showed high level of more knowledge and more positive attitude about organ donation than general college students. A series of health showed significant correlation but general college didn't show significant correlation. Conclusion. To educate correct knowledge draw positive attitude about organ donation is needed to improve the level of Knowledge and Attitude about organ donation.

Purpose Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has emerged as an alternative treatment option when curative treatment modalities cannot be applied. Although excellent local tumor control has been achieved with SBRT, the targeting accuracy in real-life practice remains poorly understood. We proposed an in vivo assessment of targeting accuracy using hepatic parenchymal changes observed on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)–enhanced magnetic resonance (MR) images and applied this method to investigate the “real-life” targeting accuracy of image-guided SBRT. Methods and Materials We selected 29 patients with available follow-up MR images acquired 2 to 4 months after completion of SBRT. All patients were administered 45 Gy in 3 fractions. The treated HCC and the region of hepatic parenchymal changes in the hepatobiliary phase of MR images were delineated. We evaluated the discrepancies between the center of the HCC and that of the parenchymal change area (intercenter discrepancy [ICD]). We also analyzed the difference in ICDs between those who underwent SBRT with intrahepatic marker guidance and those with diaphragm guidance. Results The median ICD in the 3-dimensional direction was 6.81 mm (interquartile range [IQR], 4.27-9.61 mm). Those for the craniocaudal, left–right, and anteroposterior components were 2.70 mm (IQR, 1.83-4.06 mm), 1.63 mm (IQR, 0.76-3.49), and 4.12 mm (IQR, 1.20-6.96 mm), respectively. The median ICD for patients who underwent treatment with intrahepatic marker guidance and those with diaphragm guidance was 7.53 mm (IQR, 6.63-10.86 mm) and 5.60 mm (IQR, 4.28-8.18 mm), respectively. There was no significant difference in ICD between those who underwent treatment with intrahepatic marker guidance and those with diaphragm guidance (P = .296). Conclusions The hepatic parenchymal changes observed on Gd-EOB-DTPA–enhanced MR images can be used to assess the targeting accuracy after SBRT for HCC.

To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability–high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730–49. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663

In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). The data from the patients participating in two South Korean multi-institutional studies (KROG 14–22; N = 1842 and KROG 14–23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. The median follow-up time was 72.2 months (range 0.8–125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

Aim In the present study we assessed if postoperative radiotherapy (PORT) using conventional fractionation confers a benefit in cutaneous melanoma patients with lymph node (LN) metastasis. Patients and methods Sixty-two patients with axillary or inguinal LN metastasis were retrospectively reviewed. Twenty-eight patients received PORT. The median RT dose was 50 Gy in 25 fractions. The high-risk group was defined by the presence of any of the following: ≥3 LNs, size ≥3 cm, extranodal extension. Results The median follow-up time was 34 months. PORT showed a significant benefit on 5-year axilla-inguinal recurrence-free survival (RFS) in high-risk patients (RT 100% vs. No-RT 37%, p=0.001). There was also a benefit of RT on 5-year out-field RFS in the high-risk population (RT 93% vs. No-RT 29%, p=0.002). There were no ≥grade 2 lymphedemas after RT. Conclusion PORT using conventional fractionation for high-risk LN metastasis from cutaneous melanoma is feasible with comparable regional control and minimal toxicity.

International audience; For the independent validation of treatment plans, we developed a fully automated Monte Carlo (MC)-based patient dose calculation system with the tool for particle simulation (TOPAS) and proton therapy machine installed at the National Cancer Center in Korea to enable routine and automatic dose recalculation for each patient. The proton beam nozzle was modeled with TOPAS to simulate the therapeutic beam, and MC commissioning was performed by comparing percent depth dose with the measurement. The beam set-up based on the prescribed beam range and modulation width was automated by modifying the vendor-specific method. The CT phantom was modeled based on the DICOM CT files with TOPAS-built-in function, and an in-house-developed C++ code directly imports the CT files for positioning the CT phantom, RT-plan file for simulating the treatment plan, and RT-structure file for applying the Hounsfield unit (HU) assignment, respectively. The developed system was validated by comparing the dose distributions with those calculated by the treatment planning system (TPS) for a lung phantom and two patient cases of abdomen and internal mammary node. The results of the beam commissioning were in good agreement of up to 0.8 mm2 ${\rm g}^{-1}$ for B8 option in both of the beam range and the modulation width of the spread-out Bragg peaks. The beam set-up technique can predict the range and modulation width with an accuracy of 0.06% and 0.51%, respectively, with respect to the prescribed range and modulation in arbitrary points of B5 option (128.3, 132.0, and 141.2 mm2 ${\rm g}^{-1}$ of range). The dose distributions showed higher than 99% passing rate for the 3D gamma index (3 mm distance to agreement and 3% dose difference) between the MC simulations and the clinical TPS in the target volume. However, in the normal tissues, less favorable agreements were obtained for the radiation treatment planning with the lung phantom and internal mammary node cases. The discrepancies might come from the limitations of the clinical TPS, which is the inaccurate dose calculation algorithm for the scattering effect, in the range compensator and inhomogeneous material. Moreover, the steep slope of the compensator, conversion of the HU values to the human phantom, and the dose calculation algorithm for the HU assignment also could be reasons of the discrepancies. The current study could be used for the independent dose validation of treatment plans including high inhomogeneities, the steep compensator, and riskiness such as lung, head & neck cases. According to the treatment policy, the dose discrepancies predicted with MC could be used for the acceptance decision of the original treatment plan.