Won Kyung Cho

Treatment outcome of hepatic re-irradiation in patients with hepatocellular carcinoma.

Purpose We evaluated the efficacy and toxicity of repeated high dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with unresectable hepatocellular carcinoma. Materials and Methods Between 1998 and 2011, 45 patients received hepatic re-irradiation with high dose 3D-CRT in Samsung Medical Center. After excluding two ineligible patients, 43 patients were retrospectively reviewed. RT was delivered with palliative or salvage intent, and equivalent dose of 2 Gy fractions for α/β = 10 Gy ranged from 31.25 Gy10 to 93.75 Gy10 (median, 44 Gy10). Tumor response and toxicity were evaluated based on the modified Response Evaluation Criteria in Solid Tumors criteria and the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. Results The median follow-up duration was 11.2 months (range, 4.1 to 58.3 months). An objective tumor response rate was 62.8%. The tumor response rates were 81.0% and 45.5% in patients receiving ≥45 Gy10 and <45 Gy10, respectively (p = 0.016). The median overall survival (OS) of all patients was 11.2 months. The OS was significantly affected by the Child-Pugh class as 14.2 months vs. 6.1 months (Child-Pugh A vs. B, p < 0.001), and modified Union for International Cancer Control (UICC) T stage as 15.6 months vs. 8.3 months (T1-3 vs. T4, p = 0.004), respectively. Grade III toxicities were developed in two patients, both of whom received ≥50 Gy10. Conclusion Hepatic re-irradiation may be an effective and tolerable treatment for patients who are not eligible for further local treatment modalities, especially in patients with Child-Pugh A and T1-3.

Supraclavicular and/or celiac lymph node metastases from thoracic esophageal squamous cell carcinoma did not compromise survival following neoadjuvant chemoradiotherapy and surgery

This study is to evaluate the prognostic significance of supraclavicular and/or celiac lymph node (LN) metastases in locally advanced thoracic esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiotherapy (NACRT) and surgery. Among the total 199 patients, 75 (37.7%) had supraclavicular and/or celiac LN metastasis. Surgery was performed following NACRT in 168 patients (84.4%). After the median 18.7 (1.0-147.2) months’ follow-up, 2-year rates of progression-free survival (PFS) and overall survival (OS) in all patients were 48.1% and 65.7%, respectively. In multivariate analyses, negative surgical margin (p < 0.001), ypT0 stage (p = 0.004), and ypN0 stage (p = 0.020) were significantly favorable factors for PFS, and negative surgical margin (p < 0.001) was the only significantly favorable factor for OS. Metastasis to the supraclavicular and/or celiac LNs was significant factor neither for PFS (p = 0.311) nor OS (p = 0.515). Supraclavicular and/or celiac LN metastasis did not compromise the clinical outcomes following NACRT and surgery.

Effect of Body Mass Index on Survival in Breast Cancer Patients According to Subtype, Metabolic Syndrome, and Treatment

Purpose To investigate the effect of body mass index (BMI) on survival in patients with breast cancer according to tumor subtype, metabolic syndrome, and systemic treatment. Patients and Methods We identified 5668 patients who underwent curative surgery for breast cancer between 1996 and 2013 from the clinical data of a single institution. Disease‐free survival (DFS) and overall survival (OS) were calculated and compared between the patients with BMI ≥ 25 kg/m2 and < 25 kg/m2 in all patients and in specific subgroups, including tumor subtype, metabolic syndrome, and systemic treatment. Results In all patients, BMI ≥ 25 kg/m2 was an unfavorable factor for OS (P = .030) but not for DFS. In the HR+/HER2− subgroup, DFS and OS were longer in patients with BMI < 25 kg/m2 than ≥ 25 kg/m2 (P = .012 and .005, respectively). In patients with more than one metabolic syndrome, BMI was an unfavorable factor for OS (hazard ratio, 2.669; P < .001) Conclusion BMI ≥ 25 kg/m2 was an unfavorable survival factor, particularly in patients with HR+/HER2− breast cancer. Micro‐Abstract Effect of body mass index (BMI) on survival in breast cancer patients has not yet been established. We analyzed disease‐free survival (DFS) and overall survival (OS) of 5668 patients who underwent curative surgery for breast cancer according to BMI in several subgroups. BMI ≥ 25 kg/m2 was an unfavorable factor for DFS and OS, particularly in patients with luminal subtype disease.

Elevated CEA is associated with worse survival in recurrent rectal cancer

This study investigated the prognostic impact of serum carcinoembryonic antigen (CEA) level in recurrent rectal cancer. We reviewed 745 patients who developed recurrence after curative treatment for rectal cancer between January 2000 and December 2012. Multivariate analyses for survival revealed that age > 60 years (p = 0.005), r-CEA ≥ 5 ng/ml (p < 0.001), disease free interval (DFI) < 12 months (p < 0.001), and palliative or conservative treatment (p < 0.001) were unfavorable factors.

Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells.

Purpose This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF-1α) of tumor was evaluated by immunohistochemical (IHC) staining. Results The mean tumor volumes (±standard error) at the 15th day after randomization were 1,382.0 (±201.2) mm3 (group 1), 559.9 (±67.8) mm3 (group 3), and 370.5 (± 48.1) mm3 (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and HIF-1α positivity in tumor cells were decreased when treated with captopril. Conclusion Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

Validation of a novel molecular RPA classification in glioblastoma (GBM-molRPA) treated with chemoradiation: A multi-institutional collaborative study

BACKGROUND AND PURPOSEnA novel molecular recursive partitioning analysis classification has recently been reported integrating the MGMT promoter methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM-molRPA) patients treated with temozolomide-based chemoradiation. The current study was initiated to validate the model in a multi-institutional study.nnnMATERIALS AND METHODSnFour-hundred seventy-one newly diagnosed GBM patients (validation cohort) were allocated to classes I-III of the previously reported GBM-molRPA model. Of the patients, 15.7%, 56.1%, and 28.2% patients were GBM-molRPA class I, II, and III, respectively. MGMTmeth and IDH1mut were observed in 32.3 and 8.8% of patients, respectively. In the training plus validation cohort of 692 patients, 16.2%, 60.8%, and 23.0% patients were class I, II, and III, respectively.nnnRESULTSnThe median follow-up for survivors and the median survival (MS) of patients was 23.3 and 18.4u202fmonths, respectively. The MS for GBM-molRPA class I, II, and III was 49.7 (95% CI, 22.8-76.6), 19.2 (95% CI, 16.2-22.1), and 13.8u202fmonths (95% CI, 11.8-15.4) (Pu202f<u202f.001 for all comparisons) in the validation cohort. In the training plus validation cohort, the MS was 58.5 (95% CI, 40.7-76.3), 21. (95% CI, 18.6-23.3), and 14.3u202fmonths (95% CI, 12.5-16.1) (Pu202f<u202f.001 for all comparisons) for class I, II, and III, respectively.nnnCONCLUSIONnThe GBM-molRPA is a valid model. This GBM-molRPA classification can be useful in clinics and guiding patient stratification in future clinical trials.

Which Patients with Left Breast Cancer Should be Candidates for Heart-Sparing Radiotherapy?

Purpose This study aimed to identify risk factors that have significant interaction with radiation exposure to the heart, and thus to determine candidates for heart-sparing radiotherapy (RT) among women with left breast cancer. Methods We identified 4,333 patients who received adjuvant RT following breast-conserving surgery for ductal carcinoma in situ or invasive breast cancer from 1996 to 2010. Incidence rates of cardiovascular disease were compared between left-sided and right-sided RT, and stratified by age and risk factors such as body mass index (BMI), smoking, hyperlipidemia, hypertension, diabetes, administration of anthracycline, and trastuzumab. Results In all patients, the cumulative incidence of cardiovascular disease was greater in patients treated with left-sided RT than in those treated with right-sided RT, but the difference was not significant (p=0.428). Smoking (hazard ratio [HR], 5.991; 95% confidence interval [CI], 2.109–17.022; p=0.002) and hyperlipidemia (HR, 5.567; 95% CI, 3.235–9.580; p<0.001) were the most powerful risk factors for cardiovascular disease. There was no significant factor that further increased the risk of cardiovascular disease after left breast RT compared to right breast RT. Conclusion Although hyperlipidemia and smoking are risk factors for cardiovascular disease, they have not been proven to increase the risk of RT-related cardiovascular disease in Korean women.

Role of Elective Nodal Irradiation in Patients With ypN0 After Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery (KROG 16-16)

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

Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients

Purpose This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients. Materials and Methods A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy. Results With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively. Conclusion The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

Stereotactic ablative body radiotherapy for spinal metastasis from hepatocellular carcinoma: its oncologic outcomes and risk of vertebral compression fracture

Spinal metastases from hepatocellular carcinoma (HCC) require high-dose irradiation for durable pain and tumor control. Stereotactic ablative body radiotherapy (SABR) enables the delivery of high-dose radiation. However, but vertebral compression fracture (VCF) can be problematic. The aim of his study is to evaluate the outcome and risk of VCF after SABR for spinal metastasis from HCC. We retrospectively reviewed 33 lesions in 42 spinal segments from 29 patients who received SABR with 1 fraction (16-20 Gy), or 3 fractions (18-45 Gy) from September 2009 to January 2015. The 1-year local control (LC) rate was 68.3%. Radiographic grade of cord compression (RGCC) was the only independent prognostic factor associated with LC (P = 0.007). The 1-year ultimate LC rate including the outcome of salvage re-irradiation was 87.2%. The pain response rate was 73.3% according to the categories of the International Bone Metastases Consensus Group. The 1-year VCF-free rate was 71.5%. Pre-existing VCF (P < 0.001) and only-lytic change (P = 0.017) were associated with a higher post-SABR VCF rate. One-third of post-SABR VCFs required interventions. SABR for spinal metastases from HCC provided efficacious LC, especially for lesions with RGCC ≤ II, and showed effective and durable pain relief. As VCF after SABR occurred frequently for vertebral segments with pre-existing VCF and only-lytic change, early preventive vertebroplasty is considerable for those high-risk vertebral segments.