Dual Oxidase 2 (DUOX2) as a Proteomic Biomarker for Predicting Treatment Response to Chemoradiation Therapy for Locally Advanced Rectal Cancer: Using High-Throughput Proteomic Analysis and Machine Learning Algorithm.

High-throughput mass-spectrometry-based quantitative proteomic analysis was performed using formalin-fixed, paraffin-embedded (FFPE) biopsy samples obtained before treatment from 13 patients with locally advanced rectal cancer (LARC), who were treated with concurrent chemoradiation therapy (CCRT) followed by surgery. Patients were divided into complete responder (CR) and non-complete responder (nCR) groups. Immunohistochemical (IHC) staining of 79 independent FFPE tissue samples was performed to validate the predictive ability of proteomic biomarker candidates. A total of 3637 proteins were identified, and the expression of 498 proteins was confirmed at significantly different levels (differentially expressed proteins-DEPs) between two groups. In Gene Ontology enrichment analyses, DEPs enriched in biological processes in the CR group included proteins linked to cytoskeletal organization, immune response processes, and vesicle-associated protein transport processes, whereas DEPs in the nCR group were associated with biosynthesis, transcription, and translation processes. Dual oxidase 2 (DUOX2) was selected as the most predictive biomarker in machine learning algorithm analysis. Further IHC validation ultimately confirmed DUOX2 as a potential biomarker for predicting the response of nCR to CCRT. In conclusion, this study suggests that the treatment response to RT may be affected by the pre-treatment tumor microenvironment. DUOX2 is a potential biomarker for the early prediction of nCR after CCRT.

Determining whether postoperative chemoradiotherapy is required in patients with pathologic T3N0 rectal cancer with negative resection margin.

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

Pretreatment clinical mediastinal nodal bulk and extent do not influence survival in N2-positive stage IIIA non-small cell lung cancer patients treated with trimodality therapy.

BACKGROUND: Treatment for patients with N2-positive stage IIIA non-small cell lung cancer has been a controversial issue. The current study evaluated the outcomes in patients treated with trimodality therapy, which consisted of neoadjuvant radiation therapy concurrent with chemotherapy followed by surgical resection, with emphasis on clinical and pathologic nodal status. METHODS: We reviewed the records of 355 patients who were treated with trimodality therapy between 1997 and 2011. RESULTS: After completion of neoadjuvant chemoradiation, overall down-staging and complete response rates were 50.4 % (179 patients), and 13.2 % (47 patients), respectively. With median follow-up of 35.3 months, median times of progression-free survival (PFS) and overall survival (OS) were 16.3 months and 45.5 months, respectively. Seventeen patients (4.8 %) died of postoperative complications, and the remaining 338 patients were analyzed on prognostic factors. Old age (p = 0.032), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were found to be the significant prognosticators for worse PFS, and old age (p = 0.013), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were related to worse OS. Clinical N2 status did not influence either OS or PFS: the number of involved stations (single station vs. multi-station; p = 0.187 for PFS; p = 0.492 for OS), and bulk (clinically evident vs. microscopic; p = 0.902 for PFS; p = 0.915 for OS). CONCLUSION: ypN stage was the most important prognosticator for both PFS and OS; however, neither initial bulk nor extent of cN2 disease influenced prognosis. Surgery following neoadjuvant chemoradiation should have contributed to improved clinical outcomes regardless of clinical nodal bulk and extent.

Evaluation of Pretreatment Albumin-Bilirubin Grade as a Better Prognostic Factor Compared to Child-Pugh Classification in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization Combined with Radiotherapy.

This study assessed the use of pretreatment albumin--bilirubin (ALBI) grade as a prognostic factor in patients with hepatocellular carcinoma (HCC) receiving combined transarterial chemoembolization (TACE) and radiotherapy (RT). Patients who underwent RT following TACE between January 2011 and December 2020 were analyzed retrospectively. The survival outcomes of patients in regard to the ALBI grade and Child-Pugh (C-P) classification were evaluated. A total of 73 patients with a median follow-up of 16.3 months were included. Thirty-three (45.2%) and forty patients (54.8%) were categorized into ALBI grades 1 and 2-3, respectively, while sixty-four (87.7%) and nine (12.3%) were C-P classes A and B, respectively (p = 0.003). The median progression-free survival (PFS) and overall survival (OS) for ALBI grade 1 vs. 2-3 were 8.6 months vs. 5.0 months (p = 0.016) and 27.0 months vs. 15.9 months (p = 0.006), respectively. The median PFS and OS for C-P class A vs. B were 6.3 months vs. 6.1 months (p = 0.265) and 24.8 months vs. 19.0 months (p = 0.630), respectively. A multivariate analysis showed that ALBI grades 2-3 were significantly associated with worse PFS (p = 0.035) and OS (p = 0.021). In conclusion, the ALBI grade could be a good prognosticator in HCC patients who were treated with combined TACE-RT.

Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx.

PURPOSE: This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT). MATERIALS AND METHODS: Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients. RESULTS: With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS. CONCLUSION: Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.

Increased Risk of Diabetes after Definitive Radiotherapy in Patients with Indolent Gastroduodenal Lymphoma.

PURPOSE: This study aimed to evaluate the effect of radiotherapy (RT) on the risk of diabetes by assessing hemoglobin A1c (HbA1c) levels in patients with gastroduodenal indolent lymphoma. MATERIALS AND METHODS: This retrospective study included patients with stage I extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue or follicular lymphoma of the gastroduodenal region who were treated with Helicobacter pylori eradication and/or RT between 2000 and 2019 in our institution. Of total 79 patients with HbA1c test, 17 patients received RT (RT group), while 62 patients did not receive RT (control group). A diabetes-associated event (DAE) was defined as a ≥ 0.5% increase in HbA1c levels from baseline, and diabetes event (DE) were defined as HbA1c level of ≥ 6.5%. RESULTS: During the median follow-up of 49 months, no local failure occurred after RT and no patients died of lymphoma. The RT group had significantly higher risk for DAEs on univariable analysis (hazard ratio [HR], 4.18; 95% confidence interval [CI], 1.64 to 10.66; p < 0.01) and multivariable analysis (HR, 3.68; 95% CI, 1.42 to 9.56; p=0.01). Further, the DE risk was significantly higher in the RT group than in the control group (HR, 4.32; 95% CI, 1.08 to 17.30; p=0.04) and in patients with increased baseline HbA1c levels (HR, 35.83; 95% CI, 2.80 to 459.19; p=0.01). On multivariable analysis, RT significantly increased the risk of DEs (HR, 4.55; 95% CI, 1.08 to 19.19; p=0.04), even after adjusting baseline HbA1c level (HR, 40.97; 95% CI, 3.06 to 548.01; p=0.01). CONCLUSION: Patients who received RT for gastroduodenal indolent lymphoma had an increased risk of diabetes compared to those who did not.

Clinical Significance of Preoperative Hematological Parameters in Patients with D2-Resected, Node-Positive Stomach Cancer.

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180-2.376; HR 1.908, 95% CI 1.650-2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393-0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment.

Clinical features of post-radiation nasopharyngeal necrosis and their outcomes following surgical intervention in nasopharyngeal cancer patients.

PURPOSE: To investigate the incidence and clinical features of post-radiation nasopharyngeal necrosis (PRNN), and effectiveness of surgical intervention for its treatment. MATERIALS AND METHODS: Retrospectively, we reviewed 380 NPC patients who underwent high dose radiotherapy (RT) (single RT in 355 and re-RT in 25) from January 2008 till December 2017 at the authors' institute, among who 22 developed Grade ≥ 3 PRNN. The management of PRNN was discussed through weekly multidisciplinary head and neck oncology conference, and surgical debridement was performed when feasible. RESULTS: The incidence of PRNN was significantly higher following re-RT than in single RT (11/355, 3.1% vs. 11/25, 44.0%, p < 0.001). The PRNN patients in single RT group tended to be older and had more advanced initial tumor extents. The intervals from the latest RT start till PRNN assignment were similar between groups (7.3 vs. 6.6 months, p = 0.140). Nineteen patients underwent surgical debridement: two open; and 17 endoscopic approach, respectively. Endoscopic mucosal reconstruction was performed in eight patients. Resolution of PRNN was achieved in 11 patients (64.7%). The rates of 3-year overall survivals (OS) from the initial RT, latest RT (adjusting re-RT), and PRNN assignment were 84.4%, 70.9%, and 54.7%, respectively. Eight patients (36.4%) succumbed to death: NPC progression in three (13.6%); evidently PRNN-related events in two (9.1%), probably PRNN-related events in two (9.1%); and inter-current death in one (4.5%), respectively. CONCLUSION: PRNN needs close collaboration among head and neck oncologists and could be successfully recovered, without compromising survival, following timely surgical intervention.

Long-Term Clinical Outcome and Predictive Factors for Relapse after Radiation Therapy in 145 Patients with Stage I Gastric B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type.

This study aimed to evaluate the clinical outcomes of radiation therapy (RT) for stage I gastric mucosa-associated lymphoid tissue (MALT) lymphoma and find predictive factors for relapse after RT. This retrospective study included 145 patients without a prior history of treatment, except Helicobacter pylori eradication therapy, who were irradiated for stage I gastric MALT lymphoma. The gastric body was the most commonly involved location of the dominant lesion (66.9%), and H. pylori infection at first diagnosis was detected in 61 (42.1%) patients. The median RT dose was 30 Gy (range, 24-40). Seven patients had an autoimmune disease. All patients except one achieved a complete remission at post-treatment endoscopic biopsy after a median of 2 months (range, 1-36). During the median follow-up at 51 months (range, 2-146), 11 patients experienced relapses: in the stomach (n = 5), in a distant site (n = 4), and in both (n = 2). The five-year overall, local relapse-free, distant relapse-free, and relapse-free survival (RFS) rates were 98.6%, 94.0%, 97.1%, and 92.3%, respectively. In multivariate analysis for RFS, the location of MALT lymphoma other than in the gastric body was significantly associated with an increased risk of relapse (hazard ratio 5.85 (95% CI 1.49-22.9), p = 0.011). RT results in favorable clinical outcomes in patients with stage I gastric MALT lymphoma. Tumor location could be a predictive factor for relapse after RT.

Clinical importance of the absolute count of neutrophils, lymphocytes, monocytes, and platelets in newly diagnosed hepatocellular carcinoma.

Although several studies have confirmed the clinical significance of the systemic inflammation markers in hepatocellular carcinoma (HCC), evaluating the clinical significance of each blood cell remains to be conducted. We aimed to evaluate the clinical importance of absolute counts of blood cells in the overall survival (OS) of patients with newly diagnosed HCC. We recruited patient cohorts from the prospective registry of newly diagnosed and previously untreated HCC at Samsung Medical Center, which included a training set of 6619 patients (2005-2013) and a validation set of 2084 patients (2014-2016). More than three-quarters of all patients had hepatitis B virus (HBV)-related HCC in both training and validation sets. The optimal cutoff values of the absolute counts of neutrophils, lymphocytes, monocytes, and platelets were 3917, 488, 1379, and 22,100, respectively, which correlated significantly with OS. The absolute blood cell counts categorized by each optimal cutoff value significantly correlated with liver function status determined by Child-Pugh class/albumin-bilirubin (ALBI) grade and the HCC burden determined by several staging systems/portal vein tumor thrombosis. Although the prognostic model based on these blood cells (ABC model) showed a lower prognostic ability than the Japan Integrated Staging or ALBI-T staging systems, it provided significant discrimination of survival in the subgroups of ALBI-T and showed the highest prognostic ability in the present study in the training and validation sets. Absolute counts of blood cells are independently associated with OS, though it is also significantly associated with liver function and tumor burden in newly diagnosed HCC.

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients.

PURPOSE: To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. MATERIALS AND METHODS: The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks' RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. RESULTS: With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). CONCLUSIONS: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01).

OBJECTIVE: To investigate long-term outcomes of locally advanced rectal cancer (LARC) patients with postchemoradiotherapy (post-CRT) pathologic complete response of primary tumor (ypT0) and determine prognostic significance of post-CRT pathologic nodal (ypN) status. BACKGROUND: LARC patients with post-CRT pathologic complete response were suggested to have favorable long-term outcomes, but prognostic significance of ypN status has never been specifically defined in ypT0 patients. METHODS: The Korean Radiation Oncology Group collected clinical data for 333 LARC patients with ypT0 following preoperative CRT and curative radical resections between 1993 and 2007. Sphincter preservation surgery and abdominoperineal resection were performed in 283 (85.0%) and 50 (15.0%) patients, respectively. Postoperative chemotherapy was given to 285 (85.6%) patients. Survival was estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used in multivariate analyses. RESULTS: After median follow-up of 43 (range = 14-172) months, 5-year disease-free survival (DFS) was 84.6% and overall survival (OS) was 92.8%. The ypN status was ypT0N0 in 304 (91.3%), ypT0N1 in 22 (6.6%), and ypT0N2 in 7 (2.1%) patients. The ypN status was the most relevant independent prognostic factor for both DFS and OS in ypT0 patients. The 5-year DFS and OS was 88.5% and 94.8% in ypT0N0 patients, and 45.2% and 72.8% in ypT0N+ patients (both, P < 0.001). CONCLUSIONS: LARC patients achieving ypT0N0 after preoperative CRT had favorable long-term outcomes, whereas positive ypN status had a poor prognosis even after total regression of primary tumor.

Multi-Parametric Deep Learning Model for Prediction of Overall Survival after Postoperative Concurrent Chemoradiotherapy in Glioblastoma Patients.

This study aimed to investigate the performance of a deep learning-based survival-prediction model, which predicts the overall survival (OS) time of glioblastoma patients who have received surgery followed by concurrent chemoradiotherapy (CCRT). The medical records of glioblastoma patients who had received surgery and CCRT between January 2011 and December 2017 were retrospectively reviewed. Based on our inclusion criteria, 118 patients were selected and semi-randomly allocated to training and test datasets (3:1 ratio, respectively). A convolutional neural network-based deep learning model was trained with magnetic resonance imaging (MRI) data and clinical profiles to predict OS. The MRI was reconstructed by using four pulse sequences (22 slices) and nine images were selected based on the longest slice of glioblastoma by a physician for each pulse sequence. The clinical profiles consist of personal, genetic, and treatment factors. The concordance index (C-index) and integrated area under the curve (iAUC) of the time-dependent area-under-the-curve curves of each model were calculated to evaluate the performance of the survival-prediction models. The model that incorporated clinical and radiomic features showed a higher C-index (0.768 (95% confidence interval (CI): 0.759, 0.776)) and iAUC (0.790 (95% CI: 0.783, 0.797)) than the model using clinical features alone (C-index = 0.693 (95% CI: 0.685, 0.701); iAUC = 0.723 (95% CI: 0.716, 0.731)) and the model using radiomic features alone (C-index = 0.590 (95% CI: 0.579, 0.600); iAUC = 0.614 (95% CI: 0.607, 0.621)). These improvements to the C-indexes and iAUCs were validated using the 1000-times bootstrapping method; all were statistically significant (p < 0.001). This study suggests the synergistic benefits of using both clinical and radiomic parameters. Furthermore, it indicates the potential of multi-parametric deep learning models for the survival prediction of glioblastoma patients.

Clinical Significance of Systemic Inflammation Markers in Newly Diagnosed, Previously Untreated Hepatocellular Carcinoma.

This study aimed to investigate the clinical significance of systemic inflammation markers (SIMs)-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-in patients with newly diagnosed, previously untreated hepatocellular carcinoma (HCC). The present study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC from a single institution. The training set included 6619 patients from 2005 to 2013 and the validation set included 2084 patients from 2014 to 2016. The SIMs as continuous variables significantly affected the overall survival (OS), and the optimal cut-off value of NLR, PLR, and LMR was 3.0, 100.0, and 3.0, respectively. There were significant correlations between SIMs and the albumin-bilirubin grade/Child-Turcotte-Pugh class (indicative of liver function status) and the staging system/portal vein invasion (indicative of the tumor burden). The OS curves were well stratified according to the prognostic model of SIMs and validated using the bootstrap method (1000 times, C-index 0.6367, 95% confidence interval (CI) 0.6274-0.6459) and validation cohort (C-index 0.6810, 95% CI 0.6570-0.7049). SIMs showed significant prognostic ability for OS, independent of liver function and tumor extent, although these factors were significantly correlated with SIMs in patients with newly diagnosed, previously untreated HCC.

Impact of Radiotherapy on Kidney Function among Patients Who Received Adjuvant Treatment for Gastric Cancer: Logistic and Linear Regression Analyses.

We investigated the incidence of renal function impairment after adjuvant treatment for gastric cancer and analyzed the impact of radiotherapy on estimated glomerular filtration rate (eGFR) five years after gastric surgery. We reviewed the medical records of 1490 patients with stomach cancer who underwent curative surgery and adjuvant treatment for gastric cancer. Finally, we included 663 patients who were followed up for ≥5 years without disease recurrence and whose baseline eGFR was ≥60 mL/min/1.73 m2. Logistic and linear regression analyses were performed to determine independent factors associated with the five-year eGFR. A total of 13 (2.0%) patients developed renal function impairment (five-year eGFR <60 mL/min/1.73 m2). In logistic regression analysis, the baseline eGFR was identified as a prognostic factor for renal function impairment (odds ratio (OR), 0.878; 95% confidence interval (CI), 0.831-0.927; p < 0.001), but radiotherapy was not (OR, 1.130; 95% CI, 0.366-3.491; p = 0.832). In linear regression analysis, age (B = -0.350, p < 0.001), baseline eGFR (B = 0.576, p < 0.001), cisplatin (B = -2.056, p = 0.010), and radiotherapy (B = -2.628, p < 0.001) were predictive variables for the five-year eGFR. Among patients who received adjuvant radiotherapy, age (B = -0.277, p < 0.001), hypertension (B = -4.986, p = 0.004), baseline eGFR (B = 0.665, p < 0.001), and volume of the kidneys receiving ≥20 Gy (B = -0.209, p = 0.012) were predictive variables for the five-year eGFR. Development of renal function impairment after adjuvant treatment for gastric cancer was rare among patients with normal baseline kidney function. While radiotherapy was negatively associated with the five-year eGFR, its impact would have been minimal if the kidneys were properly shielded. Further studies are needed to confirm the impact of radiotherapy in patients with poor kidney function.

Effect of baseline sarcopenia on adjuvant treatment for D2 dissected gastric cancer: Analysis of the ARTIST phase III trial.

BACKGROUND AND PURPOSE: This study evaluated the clinical significance of preoperative sarcopenia according to adjuvant concurrent chemo-radiotherapy (XP-RT) or chemotherapy alone (XP) in the D2 dissected gastric cancer patient cohort of the ARTIST trial. MATERIALS AND METHODS: Skeletal muscles at the L3 vertebra level from preoperative computed tomography images among the ARTIST trial participants were measured using validated in-house software. Skeletal muscle index (SMI) was defined as the measured skeletal muscle area divided by the square of the height, and sarcopenia was defined according to the Korean-specific cutoff, i.e. L3 SMI ≤ 49 cm2/m2 for men and ≤31 cm2/m2 for women. RESULTS: Among the 440 patients in whom we were able to evaluate L3 SMI, 75 (17.0%) met the definition for preoperative sarcopenia. No differences in treatment-related toxicities or treatment compliance were observed according to the presence of preoperative sarcopenia in either treatment arm. In the subgroup of patients without preoperative sarcopenia, recurrence was significantly lower in the XP-RT arm than that in the XP arm (p = 0.02). Recurrence-free survival (RFS) was also significantly higher in the XP-RT arm (p = 0.02, hazard ratio 0.633, 95% confidence interval 0.433-0.926) in this subgroup. In the multivariate analysis, and after adjusting for significant prognostic factors, the superior outcome of XP-RT arm regarding RFS was maintained in the subgroup of the patients without preoperative sarcopenia. CONCLUSIONS: Superior clinical outcomes of adjuvant XP-RT over XP were only observed in patients without preoperative sarcopenia.

Prognostic significance of anatomic subsites: results of radiation therapy for 66 patients with localized orbital marginal zone B cell lymphoma.

BACKGROUND AND PURPOSE: To evaluate the prognostic significance of anatomic subsites for marginal zone B cell lymphoma confined to the orbit. MATERIALS AND METHODS: From 1995 to 2005, 66 patients (80 lesions) with marginal zone B cell lymphoma, confined to the orbit, received radiation therapy at Samsung Medical Center. The most frequent site of involvement was conjunctiva (29 patients) followed by retrobulbar (20 patients), eyelid (10 patients) and lacrimal gland (7 patients). The median follow-up duration was 50 (13-114) months. RESULTS: Local relapse developed in two patients, systemic relapse in three, and metachronous relapse in two. The 5-year relapse-free survival rate was 92.0%. A primary tumor located at lacrimal gland was the only poor prognostic factor for relapse (p=0.023, HR=12.263, 95% CI=1.360-110.602). The 5-year actuarial relapse-free survival rate was 57.1% for lacrimal tumor versus 95.8% for non-lacrimal tumors (p=0.002). CONCLUSIONS: Localized primary orbital MALT lymphomas respond extremely well to moderate-dose RT, with a high local control rate and durable disease free status. However, primary lacrimal involvement maybe related to future relapse more frequently than other orbital subsites.

The effect of cyclooxygenase-2 expression on tumor volume response in patients treated with radiotherapy for uterine cervical cancer.

We investigated the correlation between Cyclooxygenase-2 (COX-2) expression and the tumor response in patients with cervical cancer that were treated with curative radiotherapy (RT). Fifty-seven patients with squamous cell carcinoma were treated with concurrent radiochemotherapy (CRCT, n=29) or RT alone (n=28). The response of each patient was evaluated by three serial Magnetic Resonance Imaging examinations: before the start of RT, at four weeks after the start of RT (mid-RT) and at four weeks after the completion of RT (post-RT). Forty-three patients had positive COX-2 expression. The COX-2 negative patients achieved a higher rate of complete response (CR) at mid-RT than did the COX-2 positive patients (28.6% vs. 7.0%, P=0.054), but not at post-RT (64.3% vs. 69.8%). The initial tumor volume was a significant predictor of CR at mid-RT (P=0.003) and post-RT (P=0.004). The multivariate analysis showed that the initial tumor volume (at mid-RT and post-RT) and CRCT (at post-RT) were significant predictors of CR; however, the COX-2 expression was not. In conclusion, the COX-2 expression status has no significant correlation with the tumor response. Further studies on the changes in COX-2 expression levels during RT may be helpful for determination of its role in the tumor response to treatment and patient prognosis.

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.

Dosimetric predictors for postoperative pulmonary complications in esophageal cancer following neoadjuvant chemoradiotherapy and surgery.

BACKGROUND AND PURPOSE: In locally advanced esophageal cancer, the optimal dose constraints for neoadjuvant chemoradiotherapy (NACRT) have yet to be established. This study is carried out to identify the most reliable dosimetric predictors for pulmonary complications following NACRT and surgery for esophageal cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 308 patients with esophageal cancer who received surgery following NACRT for locally advanced esophageal cancer from January 2005 to June 2017. Dose-volume histograms (DVH) of both lungs were computed for each patient along with total lung volume, mean lung dose (MLD), V5, V10, V20, and V30. The effect of each parameter on postoperative pulmonary complications was estimated in univariate and multivariate logistic regression analysis. RESULTS: Postoperative pulmonary complications occurred in 22.1% of all patients. Univariate analysis for pulmonary complications showed that location of tumor (P = 0.017), pre-RT FEV1 (P = 0.003), MLD (P = 0.002), V5 (P < 0.001), V10 (P < 0.001), and V20 (P = 0.007) were all significant risk factors. Significant factors for postoperative pulmonary complications in multivariate analysis were MLD (odds ratio (OR) 1.118, 95% confidence interval (CI) 1.025-1.219, P = 0.012) and pre-RT FEV1 (OR 0.483, 95% CI 0.294-0.795, P = 0.004). CONCLUSIONS: In patients who received NACRT and surgery for esophageal cancer, MLD was the parameter most related to postoperative pulmonary complications. Further studies are needed to establish the optimal DVH constraints for NACRT in order to minimize the risk of postoperative pulmonary complications in esophageal cancer patients.