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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.

Background The Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. Methods Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. Results We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. Conclusion We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

Objective To propose and evaluate an active method for sparing the small bowel in the treatment field of cervical cancer brachytherapy by prone position procedure. Methods The prone position procedure consists of five steps: making bladder empty, prone-positioning a patient on belly board, making the small bowel move to abdomen, filling the bladder with Foley catheter and finally turning the patient into the supine position. The proposed method was applied for the treatment of seven cervical cancer patients. Its effectiveness was evaluated and a correlation between the patient characteristics and the volumetric dose reduction of small bowel was also investigated. Brachytherapy treatment plans were built before and after the proposed method, and their dose-volume histograms were compared for targets and organs-at-risk. In this comparison, all plans were normalized to satisfy the same D90% for high-risk clinical target volume. Results For the enrolled patients, the average dose of small bowel was significantly reduced from 75.2 ± 4.9 Gy before to 60.2 ± 4.0 Gy after the prone position procedure, while minor dosimetric changes were observed in rectum, sigmoid and bladder. The linear correlation to body mass index, thickness and width of abdominopelvic cavity and bladder volume were 76.2, 69.7, 28.8 and −36.3%, respectively. Conclusions The application of prone position procedure could effectively lower the volumetric dose of the small bowel. The dose reduction in the small bowel had a strong correlation with the patient’s obesity and abdominal thickness. This means the patients for whom the proposed method would be beneficial can be judiciously selected for safe brachytherapy.

Aim This study was undertaken to investigate the role of postoperative radiotherapy (PORT) including post-breast conserving radiotherapy (PBCRT) and post-mastectomy radiotherapy (PMRT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR). Methods This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS). Results At a median follow-up of 48.9 months (range, 3.5-183.4 months), the median OS was 54.9 months (range, 5.3-185.9 months) with a 5 year OS rate of 59.6%. Lower clinical T stage, Luminal A or B type tumors and PBCRT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. In multivariate analysis for LRRFS, the PBCRT arm demonstrated significant superiority compared to the No PORT arm. A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. PBCRT arm demonstrated significantly superior LRRFS of 100% while PMRT and No PORT arm demonstrated 81.5% and 84.0%, respectively CONCLUSIONS: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT, especially PBCRT was predictive of LRRFS, suggesting that patients may benefit from this treatment.

Background To evaluate the clinical outcomes of combination of androgen deprivation therapy (ADT), whole pelvic radiotherapy (WPRT), and stereotactic body radiotherapy (SBRT) boost in high-risk prostate cancer patients. Methods This prospective phase I/IIa study was conducted between 2016 and 2017. Following WPRT of 44 Gy in 20 fractions, patients were randomized to two boost doses, 18 Gy and 21 Gy, in 3 fractions using the Cyberknife system. Primary endpoints were incidences of acute toxicities and short-term biochemical recurrence-free survival (BCRFS). Secondary endpoints included late toxicities and short-term clinical progression-free survival (CPFS). Results A total of 26 patients were enrolled. Twelve patients received a boost dose of 18 Gy, and the rest received 21 Gy. The Median follow-up duration was 35 months. There were no grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicities. Sixty-one and 4% of patients experienced grade 1–2 acute GU and GI toxicities, respectively. There were 12% late grade 1–2 GU toxicities and 8% late grade 1–2 GI toxicities. Patient-reported outcomes of urinary symptoms were aggravated after WPRT and SBRT boost. However, they resolved at 1 month and returned to the baseline level at 4 months. Three-year BCRFS was 88.1%, and CPFS was 92.3%. Conclusions The present study protocol demonstrated that the combination of ADT, WPRT, and SBRT boosts for high-risk prostate cancer is safe and feasible, and may reduce total treatment time to 5 weeks. Boost dose of 21 Gy in 3 fractions seems appropriate. Trial registration ClinicalTrials.gov, ID; NCT03322020 - Retrospectively registered on 26 October 2017.

ObjectiveThe aim of this study was to compare the clinical outcomes of chemoradiotherapy with or without bevacizumab in patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer.Methods41 patients with stage IVB cervical cancer who underwent chemoradiotherapy between August 2015 and December 2017 were retrospectively analyzed. This study included 11 patients who received bevacizumab before or after radiotherapy (group A) and 30 patients who received conventional chemoradiotherapy without bevacizumab (group B). We excluded the following patients: those with dual primary cancers; those whose pathologic diagnosis was neither squamous cell carcinoma nor adenocarcinoma; those who did not undergo radiotherapy; or those from whom follow-up data could not be collected. We analyzed the treatment responses, toxicities, progression-free survival, and overall survival rates.ResultsA total of 41 patients were included in the analysis. The median follow-up was 19 months (range 3–108). The response rates at 3 months after treatment were 90.9% in group A and 83.3% in group B (p=0.54). After completing all treatments, the complete response rates were 81.8% in group A and 47% in group B (p=0.04). Grade ≥3 gastrointestinal toxicities, including bleeding, fistula, perforation, and obstruction, were more frequent in group A (54.5%) than in group B (6.7%) (p=0.003). The 12 month progression-free survival and overall survival rates were similar in both arms (12 month progression-free survival: 45.5% vs 46.7%, respectively, p=0.22; 12 month overall survival: 81.8% vs 72.9%, respectively, p=0.57). Patients with node-only metastasis had better 12 month progression-free survival in group B than in group A (59.1% vs 42.9%, respectively, p=0.04). However, the responses to both treatments did not differ in patients with organ metastasis.ConclusionsBevacizumab for stage IVB cervical cancer is associated with higher complete response rates. However, patients treated with bevacizumab experienced more bowel toxicities. Bevacizumab did not improve progression-free survival among patients with node-only metastasis.

Background Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients. Methods We evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated. Results After CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0–28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed. Conclusions Patients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.

BackgroundFew studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC.Material and MethodsSeventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60–80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed.ResultsThe median follow-up time was 34.2 months (range, 11.5–56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9–105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3–10.5) and 39.3 months (95% CI, 33.2–51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8–41.0) and 71.7% (95% CI, 46.8–96.6), respectively. Grade 3 or higher adverse events were not observed.ConclusionPBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.

Background Radiation induced enteropathy is a common complication of radiotherapy for pelvic tumors and adversely affects patient quality of life. Probiotics are thought to restore bowel microflora to optimal levels and reinforce intestinal barrier capacity. Although probiotics are effective in the treatment of radiation induced enteropathy, less is known about their efficacy to prevent radiation induced enteropathy. Methods This double-blind randomized placebo-controlled study will investigate the efficacy of probiotics to prevent radiation-induced enteropathy in patients with gynecologic or urologic cancer who received pelvic radiotherapy. The study is designed to enroll 248 eligible patients, who will be randomized 1:1 to a probiotic or placebo group. Toxicities will be evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Discussion The primary aim of this study is to provide high level evidence for the ability of probiotics to prevent acute radiation induced enteropathy. The secondary aims are to determine the effects of probiotics on the incidence of chronic radiation induced enteropathy and the safety of probiotics in patients with gynecologic or urologic cancer. Trial registration ClinicalTrials.gov (NCT03978949, Registered on 7 June 2019).

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

PurposeThis study was to evaluate anti-tumor efficacy of osimertinib in patients positive for acquired epidermal growth factor receptor (EGFR) T790M mutation in liquid biopsy using plasma, bronchoalveolar lavage fluid (BALF) or bronchial washing fluid (BWF), and pleural effusion.Materials and MethodsAmong patients benefited from previous EGFR‒tyrosine kinase inhibitor treatment followed by treatment failure, patients in whom T790M mutations are detected in at least one of the samples including tumor tissues, BALF/BWF, plasma, and pleural effusion were enrolled. T790M mutation was detected by extracting cell free DNA from liquid biopsy samples, using PANA Mutyper. Objective response rate (ORR) and progression-free survival (PFS) with osimertinib treatment were evaluated.ResultsBetween January 2018 and December 2019, 63 patients were enrolled and received osimertinib. Mean age was 63 years, and 38 (60.3%) were female. Twenty-six patients had T790M mutation in both liquid and tissue samples (group A), 19 patients had only in tissue biopsy samples (group B), and 18 patients had T790M mutation only in liquid biopsy samples (group C). ORR in overall population was 63.5%, and was 61.5% in group A, 68.4% in group B, and 61.1% in group C, respectively. Median PFS in overall patients was 15.6 months (95% confidence interval, 10.7 to 24.2). There was no significant difference in ORR or PFS between groups. ConclusionOsimertinib showed favorable efficacy in lung cancer patients with acquired resistance to prior EGFR-TKI therapies, who screened positive for harboring T790M mutation detected from cell free DNA extracted from plasma, BALF/BWF, and pleural effusion.

Purpose 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 63 years, 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 67 months, P

We evaluated the clinical outcome of patients with stage III to IV thymomas (Ts) or stage II to IV thymic carcinomas (TCs) treated with complete thymectomy and local radiation therapy (LRT, targeting the tumor bed and anterior mediastinal areas only) or elective nodal irradiation (ENI, targeting the entire mediastinal and supraclavicular regions).Data from 47 patients diagnosed with Ts or TCs and treated with surgery and adjuvant RT from May 2002 to May 2015 were analyzed. The standard RT dose was 50.4 Gy in 28 fractions; patients with a positive resection margin received a further 4 to 10 Gy. Survival outcomes determined at 5 years included local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival.Five-year local recurrence-free survival was similar in both groups (LRT, 94.7% vs. ENI, 96.2%; P = .849). Significant differences were seen in 5-year regional recurrence-free survival (LRT, 55.1% vs. ENI, 83.7%; P = .006); however, tumor size was seen to be a significant factor (7 cm, 95.2% vs. ≥ 7 cm, 48.9%; P .001), and the LRT group contained a greater proportion of patients with ≥ 7-cm tumors (70% vs. 33%). Multivariate analysis demonstrated that tumor size was the only significant prognostic factor (P .001). No differences in 5-year overall survival were seen (LRT, 91.7% vs. ENI, 100%; P = .106).ENI may not be indicated in all cases, as additional benefit in reducing recurrence or improving survival was not predominant. LRT seems to be a feasible option with favorable patient outcomes.

Background We performed a prospective phase II study to compare acute toxicity among five different hypofractionated schedules using proton therapy. This study was an exploratory analysis to investigate the secondary end-point of biochemical failure-free survival (BCFFS) of patients with long-term follow-up. Methods Eighty-two patients with T1-3bN0M0 prostate cancer who had not received androgen-deprivation therapy were randomized to one of five arms: Arm 1, 60 cobalt gray equivalent (CGE)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; and Arm 5, 35 CGE/5 fractions/4 weeks. In the current exploratory analysis, these ardms were categorized into the moderate hypofractionated (MHF) group (52 patients in Arms 1–3) and the extreme hypofractionated (EHF) group (30 patients in Arms 4–5). Results At a median follow-up of 7.5 years (range, 1.3–9.6 years), 7-year BCFFS was 76.2% for the MHF group and 46.2% for the EHF group (p = 0.005). The 7-year BCFFS of the MHF and EHF groups were 90.5 and 57.1% in the low-risk group (p = 0.154); 83.5 and 42.9% in the intermediate risk group (p = 0.018); and 41.7 and 40.0% in the high risk group (p = 0.786), respectively. Biochemical failure tended to be a late event with a median time to occurrence of 5 years. Acute GU toxicities were more common in the MHF than the EHF group (85 vs. 57%, p = 0.009), but late GI and GU toxicities did not differ between groups. Conclusions Our results suggest that the efficacy of EHF is potentially inferior to that of MHF and that further studies are warranted, therefore, to confirm these findings. Trial registration This study is registered at ClinicalTrials.gov, no. NCT01709253; registered October 18, 2012; retrospectively registered).

Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. Methods and Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524–0.588, p &lt, 0.001). Gleason score, iPSA &lt, 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p &lt, 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.

Background/aim To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. Patients and methods We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. Results Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. Conclusion There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

Objective External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. Methods In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. Results The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p, Synopsis This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. We used data from the Korea Central Cancer Registry and Korean National Health Insurance Service. Brachytherapy use is independently associated with significantly higher survival.

Background The establishment of biomarkers that can be used to predict the response to immunotherapy for malignancy is extremely important. In particular, noninvasive analysis of immune cells from peripheral blood before treatment has gained increased attention, and natural killer (NK) cell activity has been shown to be related to treatment response. Here, we aimed to confirm the relationship between the response to immunotherapy and NK cell activity. Methods In this prospective observational study, patients with advanced NSCLC who were scheduled for immunotherapy from October 2018 to December 2019 were enrolled. Baseline NK cell activity was compared according to the best clinical response to immunotherapy. Results A total of 54 patients with advanced NSCLC were enrolled, and 34 patients were analyzed. The baseline NK cell activity was significantly higher in the non‐PD group than in the PD group (P = 0.002). At the cutoff level of ≥1200 pg/mL, baseline NK cell activity yielded a sensitivity of 80% and a specificity of 68.4% in predicting the response to immunotherapy (AUC = 0.8, P, In this prospective observational study, patients with advanced NSCLC who were scheduled for immunotherapy from October 2018 to December 2019 were enrolled. The baseline NK cell activity was significantly higher in the non‐PD group than in the PD group. NK cell activity from peripheral blood before immunotherapy is a non‐invasive, simple, and novel way to predicting the treatment response in patients with NSCLC.

To perform a systematic review and meta-analysis of the impact of brachytherapy (BT) technique (two-dimensional [2D] or three-dimensional image-guided [3D]) on outcomes of cervical cancer patients. PubMed and EMBASE databases were searched up to April 16, 2019, for studies which evaluated the effect of 3D-BT compared to 2D-BT in cervical cancer. Endpoints included cumulative incidence of severe toxicity, locoregional recurrence-free survival (LRRFS), progression-free survival (PFS), and overall survival (OS). Hazard ratios (HRs) were pooled in the meta-analysis using the random-effects model. Six studies of eight cohorts were included in the quantitative synthesis. The pooled HR regarding toxicity was evaluated in five cohorts in three studies, and the HR of 3D-BT compared to 2D-BT was 0.54 (95% confidence interval [CI] 0.37–0.77). All six studies were included for the synthesis for LRRFS, and the pooled HR favors 3D-BT (0.61 [95% CI 0.40–0.93]). For PFS, three studies were included for analysis and 3D-BT was superior to 2D-BT (HR = 0.75 [95% CI 0.59–0.96]). Five studies were included for the pooled HR regarding OS, and pooled HR of 3D-BT compared to 2D-BT was 0.65 (95% CI 0.40–1.06). 3D-BT might reduce severe toxicity and improve LRRFS and PFS in patients with cervical cancer. 3D-BT should be considered for standard management of cervical cancer, and efforts for adopting this procedure in Korea should be pursued.

To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A total of 262 patients were identified, among them, 67 received definitive CRT (group A), and 195 received hysterectomy (group B). Adjuvant therapy was administered to 88.7% of group B. There were no significant differences between group A and group B regarding the 5-year overall survival rates (89.2% vs. 89.0%) as well as disease-free survival rates (80.6% vs. 82.7%), and patterns of failure. Distant metastasis was the major failure pattern identified in both groups. In multivariate analysis, non-squamous histology was significantly associated with poorer overall survival. As there are no significant differences in 5-year OS, DFS, and patterns of failure, definitive CRT could avoid the combined modality therapy without compromising oncologic outcomes.

Objective This study investigated the effect of para-aortic lymph node sampling or dissection in recently revised International Federation of Gynecology and Obstetrics IIIC1p cervical cancer treated with primary surgery and adjuvant radiation therapy with concurrent chemotherapy. Methods We retrospectively reviewed the records of 343 patients with early-stage cervical cancer and pathologically proven pelvic lymph node metastasis following curative surgery from 2001 to 2014. No patient had imaging evidence of para-aortic lymph node involvement, and all patients received adjuvant concurrent chemotherapy with or without concurrent chemotherapy. We investigated the significance of para-aortic lymph node sampling or dissection on disease-free survival and overall survival. Results After median follow-up of 58.3 months, 5-year disease-free survival and overall survival in all patients were 69.9 and 80.2%, respectively. Disease-free survival and overall survival did not differ between the para-aortic lymph node dissection group and the No para-aortic lymph node dissection group (P = 0.700 and P = 0.605). However, patients with para-aortic lymph node-positive disease had poorer disease-free survival and overall survival compared with those with para-aortic lymph node-negative disease (P Conclusions This study found no survival benefit of para-aortic lymph node evaluation among patients with International Federation of Gynecology and Obstetrics IIIC1p cervical cancer who were clinically para-aortic lymph node-negative. Although para-aortic lymph node metastasis is a poor prognosticator, the benefit of para-aortic lymph node dissection in terms of survival needs further investigation.

The purpose of this study was to evaluate the impact of high-risk factors on the survival of patients with cervical cancer treated with surgery followed by adjuvant chemoradiotherapy.From 2000 to 2014, medical records of 897 patients with International Federation of Gynecology and Obstetrics stage IB-IIA disease treated with surgery were retrospectively reviewed. Among them, 483 patients with high-risk factors, including pelvic lymph node metastasis, parametrial invasion, or resection margin involvement, were analyzed.The median follow-up time was 57 months (range, 6-205 months). For patients with single and multiple high-risk factors, the 5-year DFS rates were 80.4% and 65.7%, respectively (p 0.001), and 5-year OS rates were 87.3% and 75.1%, respectively (p = 0.001). Distant metastasis was the most common pattern of recurrence (86.1%). Furthermore, distant metastasis-free survival significantly differed with the number of high-risk factors present (single 82.7% vs. multiple 68.8%, p 0.001). In the multivariate analysis, while parametrial invasion and resection margin involvement showed no association, the adenocarcinoma histology, pelvic lymph node metastasis, higher metastatic lymph node ratio, and multiple high-risk factors were independent prognosticators associated with poor DFS and OS.Patients with early-stage cervical cancer having multiple high-risk factors, adenocarcinoma histologic type, and pelvic lymph node metastasis accompanied by a higher lymph node ratio after surgery are more likely to have occult distant metastasis. Further, consolidation with systemic chemotherapy after adjuvant therapy might be considered to improve the survival outcome in this patient population.

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.

Objective To evaluate the efficacy and safety of involved-field radiation therapy (IFRT) in patients with locoregionally confined recurrent or persistent epithelial ovarian cancer. Methods This study included patients with recurrent epithelial ovarian cancer eligible for IFRT either during diagnosis of the recurrence or after salvage therapies. IFRT was performed at a dose of ≥45 Gy for all tumors with 10–15-mm margins as seen on standard imaging. The primary endpoint was progression-free survival (PFS); the secondary endpoints were safety, response rate, local control, and overall survival (OS). Results Thirty patients with a mean number of 5.7 metastatic lesions each were enrolled between 2014 and 2016. Seventeen were treated with 3-D conformal radiation therapy (RT) and 13 with intensity-modulated RT. IFRT was well tolerated in all patients, and acute toxicity ≥ grade 2 was not observed. One case of grade 3 abdominal pain was reported 10 months post-RT. The overall and complete response rates were 85.7% and 50%, respectively. After a median follow-up of 28 (range, 17–42) months, the median PFS was 7 months. The 2-year PFS rate was 39.3%. Six of the 16 patients who developed outfield disease progression after IFRT were successfully treated with repeat IFRT as salvage treatment. The 3-year local control and OS rates were 84.4% and 55.8%, respectively. Conclusions Although the primary endpoint was not met, IFRT might be safe and effective for in-field tumor control in patients with persistent epithelial ovarian cancer with a limited number of metastatic foci. We plan to conduct a larger scale multi-center phase II prospective study.

To perform a systematic review and meta-analysis on the prognostic value of 18F-FDG PET-derived volume-based parameters regarding metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with ovarian cancer. Pubmed and EMBASE databases were searched up to February 12, 2018 for studies which evaluated MTV or TLG as a prognostic factor in ovarian cancer with progression-free (PFS) and overall survival (OS) as the endpoints. Hazard ratios (HRs) were meta-analytically pooled using the random-effects model. Multiple subgroup analyses based on clinicopathological and PET variables were performed. Eight studies with 473 patients were included. The pooled HRs of MTV and TLG for PFS were 2.50 (95% CI 1.79–3.48; p

Context 68Gallium prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) is an emerging imaging modality for assessment of prostate cancer. Recent studies show promising results regarding its ability to detect recurrent or metastatic prostate cancer superior to that of conventional imaging modalities. However, the impact of 68Ga-PSMA PET on management of patients with prostate cancer has not been well established. Objective To perform a systematic review and meta-analysis to evaluate the impact of 68Ga-PSMA PET on management of patients with prostate cancer. Evidence acquisition Pubmed and EMBASE databases were searched up to January 20, 2018. We included studies that reported proportion of management change after 68Ga-PSMA PET in patients with prostate cancer. The quality of the studies was evaluated using the GRADE system. The proportion of management changes were pooled using random-effects model. Subgroup analyses and meta-regression analyses were performed to explore heterogeneity. Evidence synthesis Fifteen 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 with 68Ga-PSMA PET. Conclusions 68Ga-PSMA PET had a large impact on the management of patients with prostate cancer. Greater PET positivity was associated with higher proportion of management changes. Patient summary We reviewed all previous studies assessing the impact of 68Gallium prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) in patients with prostate cancer. We found that 68Ga-PSMA PET altered the management in approximately half of the patients.

The aim of this study was to perform a systematic review of the prognostic value of texture parameters derived by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with lung cancer. PubMed 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 18F-FDG PET in lung cancer. Further studies implementing well-established methodologies and statistical evidence are warranted for proper validation of these promising imaging biomarkers.

The aim of the present study was to verify the dosimetric accuracy of two-dimensional (2D) in vivo rectal dosimetry using an endorectal balloon (ERB) with unfoldable EBT3 films for high-dose-rate (HDR) brachytherapy for cervical cancer. The clinical applicability of the technique was discussed.ERB inflation makes the EBT3 films unrolled, whereas its deflation makes them rolled. Patient-specific quality assurance (pQA) tests were performed in 20 patient plans using an Ir-192 remote afterloading system and a water-filled cervical phantom with the ERB. The dose distributions measured in ERBs were compared with those of the treatment plans.The absolute dose profiles measured by the ERBs were in good agreement with those of treatment plans. The global gamma passing rates were 96-100% and 91-100% over 20 pQAs under the criteria of 3%/3 mm and 3%/2 mm, respectively, with a 30% low-dose threshold. Dose-volume histograms of the rectal wall were obtained from the measured dose distributions and showed small volume differences less than 2% on average from the patients' plans over the entire dose interval. The positioning error of the applicator set was detectable with high sensitivity of 12% dose area variation per mm. Additionally, the clinical applicability of the ERB was evaluated in volunteers, and none of them felt any pain when the ERB was inserted or removed.The 2D in vivo rectal dosimetry using the ERB with EBT3 films was effective and might be clinically applicable for HDR brachytherapy for cervical and prostate cancers to monitor treatment accuracy and consistency as well as to predict rectal toxicity.

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

Purpose 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.

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.

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.

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.

// 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.

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.

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.