Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.

Correlation Between Average Segment Width and Gamma Passing Rate as a Function of MLC Position Error in Volumetric Modulated Arc Therapy.

OBJECTIVE: This study analyzed the correlation between the average segment width (ASW) and gamma passing rate according to the multi-leaf collimator (MLC) position error. METHOD: To evaluate the changes in the gamma passing rate according to the MLC position error, 21 volumetric modulated arc therapy (VMAT) plans were generated using pelvic lymph node metastatic prostate cancer patient's data which is sensitive to MLC position errors as they involve several long, narrow, irregular fields. The ASW for each VMAT plan was calculated using our own code developed using Visual Basic for Applications (VBA). The gamma passing rate of the VMAT plan according to the MLC position error was evaluated using ArcCHECK (Sun Nuclear, Melbourne, FL, USA) while inducing symmetric MLC position errors in 0.25 mm intervals from -1 mm to +1 mm in the infinity medical linear accelerator (Elekta AB, Stockholm, Sweden). Finally, we examined the correlation between the change in the passing rate (γgradient) due to the MLC position error and the ASW in VMAT through linear regression analysis using the least squares method. RESULTS: The ASW and γgradient were found to have a linear correlation according to the MLC position error, and the coefficient of determination was 0.88. For a 1 mm position error of MLC in VMAT, the gamma passing rate improved by approximately 11.9% as the ASW increased by 10 mm. CONCLUSION: These results are expected to be employed as guidelines to minimize the dose uncertainty due to MLC position error in VMAT.

Which Is Better for Liver SBRT: Dosimetric Comparison Between DCAT and VMAT for Liver Tumors.

Stereotactic body radiotherapy (SBRT) is currently well-adopted as a curative treatment for primary and metastatic liver tumors. Among SBRT methods, dynamic conformal arc therapy (DCAT) and volumetric-modulated arc therapy (VMAT) are the most preferred methods. In this study, we report a comparison study measuring the dose distribution and delivery efficiency differences between DCAT and VMAT for liver SBRT. All patients who were treated with SBRT for primary or metastatic liver tumors with a curative aim between January 2016 and December 2017 at DIRAMS were enrolled in the study. For all patients, SBRT plans were designed using the Monte Carlo (MC) algorithm in Monaco treatment planning system (version 5.1). The planning goals were set according to the RTOG 0813, RTOG 0915, and RTOG 1112 protocols. A plan comparison was made on the metrics of dose volume histogram, planning and delivery efficiency, monitor unit (MU), and dosimetric indices. PTV coverage was evaluated using the following: Dmean, D95%, D98%, D2%, D50%, Dmax, V95%, heterogeneity index (HI), and conformality index (CI). For DCAT and VMAT, respectively, the Dmean was 5942.8 ± 409.3 cGy and 5890.6 ± 438.8 cGy, D50% was 5968.8 ± 413.1 cGy and 5954.3 ± 405.2 cGy, and CI was 1.05 ± 0.05 and 1.03 ± 0.04. The D98% and V95% were 5580.0 ± 465.3 cGy and 20.4 ± 12.0 mL for DCAT, and 5596.0 ± 478.7 cGy and 20.5 ± 12.0 mL for VMAT, respectively. For normal liver, V40, V30, V20, V17, V5, Dmean, Dmax were evaluated for comparison. The V30, V20, and V10 were significantly higher in DCAT; other parameters of normal livers showed no statistically significant differences. For evaluation of intermediate dose spillage, D2cm(%) and R50% of DCAT and VMAT were 45.8 ± 7.9 and 5.6 ± 0.9 and 45.1 ± 6.7 and 5.5 ± 1.2, respectively. Planning and delivery efficiency were evaluated using MU, Calculation time, and Delivery time. DCAT had shorter Calculation time and Delivery time with smaller MU. MU was smaller in DCAT and the average difference was 300.1 MU. For liver SBRT, DCAT is an effective alternative to VMAT plans that could meet the planning goals proposed by the RTOG SBRT protocol and increases plan and delivery effectiveness, while also ignoring the interplay effect.

Treatment outcomes of stereotactic ablative radiation therapy for non-spinal bone metastases: focus on response assessment and treatment indication.

OBJECTIVE: To report treatment outcomes of stereotactic ablative radiation therapy (SABR) for non-spinal bone metastases in a single institution, and to compare assessments of Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 and the University of Texas MD Anderson Cancer Center (MDA) criteria. METHODS: From July 2011 to January 2017, 33 patients with 38 non-spinal bone metastatic lesions were treated using SABR. Treatment intent was categorized as follows: single metastasis or oligo-metastases; oligo-progression; and dominant areas of progression. Tumor responses were evaluated according to the RECIST and MDA criteria. Local control (LC) was defined as lesions that were not classified as progressive disease on both criteria. RESULTS: The median follow-up period was 10.4 months (range, 2.5-47.4). Both 1- and 2 year LC rates were 94.2 %. The median overall survival (OS) was 20.2 months, and the median progression-free survival (PFS) was 6.9 months. Treatment intent was a significant factor for OS in multivariate analysis. The 1 year OS rates for single metastasis or oligo-metastasis, for oligo-progression, and for dominant areas of progression were 84.2%, 66.7%, and 0.0%, respectively ( p < 0.001). Overall response rate was 86.8 % according to MDA criteria, and 75.7 % according to RECIST criteria. When using MDA criteria, there appeared to be significant associations both between response and PFS (median 7.6 months for responders vs 2.5 months for non-responders; p = 0.036) and between response and OS. In contrast, when using RECIST criteria, the associations were significant neither between response and PFS (median 5.8 months for responders vs 9.3 months for non-responders; p = 0.522) nor between response and OS (25.7 months for responders vs 18.5 months for non-responders; p = 0.811). CONCLUSION: SABR for non-spinal bone metastases demonstrated high LC rates with acceptable toxicity. The MDA criteria demonstrated advantages in predicting survival outcomes. ADVANCES IN KNOWLEDGE: SABR for non-spinal bone metastases is a promising treatment option to achieve good local control. The MDA criteria, which is a newly proposed response evaluation criteria for bone metastases, has advantages in predicting survival outcomes compared to other established criteria.

Stereotactic Body Radiotherapy for Centrally Located Primary Non-Small-Cell Lung Cancer: A Meta-Analysis.

BACKGROUND: The purpose of the study was to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for centrally located, primary non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Systematic search of 4 databases (PubMed, MEDLINE, EMBASE, and Cochrane Library) was performed for literature published until May 9, 2018. Primary (overall survival [OS] and local control [LC] rates) and secondary (Grade ≥3 toxicity) endpoints were reported. RESULTS: Thirteen studies encompassing 599 patients with central NSCLCs were included. Median values of T1 tumor proportion, tumor size, and median survival were 55.3% (range, 0%-75%), 3.3 (range, 2.1-4.1) cm, and 26 (range, 14-68.9) months, respectively. Pooled rates of 1-, 2-, and 3-year OS rates were 84.3% (95% confidence interval [CI], 75.7-90.3), 64.0% (95% CI, 52.9-72.2), and 50.5% (95% CI, 39.4-61.5), respectively. Pooled rates of 1-, 2-, and 3-year LC rates were 89.4% (95% CI, 80.8-94.4), 82.2% (95% CI, 71.7-89.4), and 72.2% (95% CI, 55.0-84.7), respectively. Pooled rate of Grade ≥3 complication was 12.0% (95% CI, 7.3-19.0). Meta-regression analyses showed significant positive relationships between biologically equivalent dose using an α/ß of 10 Gy in the linear quadratic model (BED10Gy) and 1- and 2-year LC rates (P < .001 and P < .001), and 1- and 2-year OS rates (P = .0178 and P = .032), and Grade ≥3 complication rate (P = .0029). In subgroup comparisons between BED10Gy <100 Gy versus ≥100 Gy, 1- and 2-year LC rates were significantly different but not for OS and Grade ≥3 complication rates. CONCLUSION: Our results suggests that SBRT is potent for tumor control in central NSCLC, although complications should be further minimized through optimization of dose-fractionation scheme and accurate planning. Using BED10Gy ≥100 Gy yielded higher LC rates, and dose escalation was related to OS, LC, and complications.

Early Closure of a Phase 1 Clinical Trial for SABR in Early-Stage Glottic Cancer.

PURPOSE: The early results of a phase 1 study of stereotactic ablative radiation therapy for early-stage glottis cancer were previously reported. However, additional late adverse events occurred in the second arm during the follow-up period. In this study, the dose-limiting toxicities and premature closure of the clinical trial are reported. METHODS AND MATERIALS: Thirteen patients with cT1-2N0M0 squamous cell carcinoma of the glottis were enrolled between May 2015 and July 2018. Seven patients in the first arm received 59.5 Gy to the gross tumor volume and 47.6 Gy to the remaining larynx, delivered in 17 fractions. The second arm dose was 55 Gy and 40.7 Gy in 11 fractions to the gross tumor volume and the remaining larynx, respectively. Patients were treated according to the simultaneous integrated boost approach with volumetric modulated arc therapy. RESULTS: The median follow-up was 37 months (range, 6-41.4) for the first arm and 14.5 months (range, 4.8-21.5) for the second arm. Maximum acute toxicity was grade 2 laryngeal mucositis for each arm. Maximum chronic toxicity was grade 3 laryngeal inflammation, occurring in 2 patients (33.3%) in the second arm. One patient underwent a laryngomicrosurgical biopsy for a vocal cord ulcer, and another patient underwent supraglottic laryngectomy because of arytenoid cartilage necrosis. In the first arm, chronic toxicity was not observed, except for grade 1 laryngeal edema in 1 patient. CONCLUSIONS: The phase 1 dose escalation study was terminated early because of the unexpected dose-limiting toxicities occurring in patients in the second arm. It was concluded that stereotactic ablative radiation therapy is not feasible for early-stage glottic cancer owing to treatment-related toxicity.

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

OBJECTIVE: Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. METHODS: Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). RESULTS: Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). CONCLUSION: This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2560-2565, 2018.

Does fluid collection impact radiotherapy outcomes after wide excision of lower extremity soft tissue sarcoma?

BACKGROUND: Fluid collection (FC) of lymph or blood may accumulate at the site of excision after surgery for soft tissue sarcoma, with reported incidence rates from 10% to 36%. The purpose of this study is to analyze the impact of FC on local recurrence (LR) and wound complication rates after adjuvant postoperative radiotherapy (PORT) in lower extremity soft tissue sarcoma (LE-STS). METHODS: Eighty-eight patients diagnosed with LE-STS were curatively treated with wide excision and PORT. FC developed in 51.1% of patients. Full FC volumes were included in the irradiation field throughout the full course of PORT for 36 patients (80.0%). A median of 61.2 and 63 Gy was prescribed for patients with and without FC, respectively. RESULTS: After a median follow-up of 4.3 years, patients with and without FC had 5-year local control rates of 77.7% and 90.8% (P = 0.105). Eight patients with FC had LR, of which six patients had recurrent tumors at or within 4 cm of the FC wall and three of these patients had out-of-field LR. Wound complication occurred after RT in 3 (6.7%) of 45 patients with FC and 1 (2.3%) of 43 patients without FC. CONCLUSIONS: FC presents a potential risk for increased LR, particularly near the FC wall. Based on reasonable wound complication rates, we suggest the need and feasibility of fully including FC volumes in the irradiation field.

Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells.

Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification. Lapatinib down-regulated phosphorylated (p)-HER2, p-epidermal growth factor receptor, p-AKT, and p-extracellular signal-regulated kinase. Pretreatment of lapatinib increased the radiosensitivity of SKBR3 (sensitizer enhancement ratio [SER]: 1.21 at a surviving fraction of 0.5) and BT474 (SER: 1.26 at a surviving fraction of 0.5) cells and hindered the repair of DNA damage, as suggested by the prolongation of radiation-induced γH2AX foci and the down-regulation of phosphorylated DNA-dependent protein kinase, catalytic subunit (p-DNAPKcs). Increases in radiation-induced apoptosis and senescence were suggested to be the major modes of cell death induced by the combination of lapatinib and radiation. Furthermore, lapatinib did not radiosensitize a HER2- negative breast cancer cell line or normal human astrocytes.These findings suggest that lapatinib can potentiate radiation-induced cell death in HER2-overexpressing breast cancer cells and may increase the efficacy of radiotherapy. A phase II clinical trial using lapatinib concurrently with whole-brain radiation therapy (WBRT) is currently being conducted.

Objective Measurement of Cosmetic Outcomes of Breast Conserving Therapy Using BCCT.core.

PURPOSE: The purpose of this study is to evaluate objective cosmetic outcomes and factors related to breast-conserving therapy (BCT) using the BCCT.core software. MATERIALS AND METHODS: Fifty-one patients who received BCT with informed consent were evaluated using the BCCT.core software. Patients were divided into two groups based on the BCCT score: excellent or good (n=42) vs. fair or poor (n=9). Analysis of clinical factors was performed to determine factors affecting cosmetic outcomes. RESULTS: The objective cosmetic outcome of BCT measured using the BCCT.core software was excellent in 10% of patients, good in 72%, and fair in 18%. None of the patients were classified as poor outcome. Tumor characteristics, systemic adjuvant therapy (chemotherapy and hormonal therapy), and radiation dose or energy of electron boost did not show correlation with the score measured by the BCCT.core program (p > 0.05). In univariate analysis, maximum dose within the breast (Dmax), width of tangential field, and excised tumor volume were smaller in patients with excellent or good by the BCCT.core compared to those with fair or poor (Dmax, 110.2 ± 1.5% vs. 111.6 ± 1.7%, p=0.019; width of tangential field, 8.0 ± 1.1 cm vs. 8.6 ± 0.7 cm, p=0.034; excised tumor volume, 64.0 ± 35.8 cm(3) vs. 95.3 ± 54.4 cm(3), p=0.067). In multivariate analysis, only Dmax was a significant factor for breast cosmetic outcome with a risk ratio of 1.697 (95% confidence interval, 1.006 to 2.863; p=0.047). CONCLUSION: Objective measurement of cosmetic outcome of BCT using the BCCT.core software was feasible. The cosmetic outcome of BCT may be affected by the maximum dose within the breast.

A multicenter study of anaplastic oligodendroglioma: the Korean Radiation Oncology Group Study 13-12.

Although some existing evidence supports the addition of chemotherapy (CT) to radiation therapy (RT) for anaplastic oligodendroglioma treatment, controversy about both the criteria for suitable candidates and the optimal treatment schedule remains. We reviewed data from 376 newly diagnosed anaplastic oliogodendroglial tumor patients from nine Korean institutes were reviewed from 2000 to 2010. Total tumor removal was performed in 146 patients. More than 85% of the entire patients received postoperative RT, and 59% received CT. Approximately 50% (n = 189) received CT in addition to RT and 9% (n = 32) received CT only. A multivariate analysis revealed that younger age, frontal lobe location of the tumor, gross total removal, 1p/19q codeletion, and initial RT were associated with longer progression-free and overall survival rates. No difference was observed in outcomes from the treatment that included either temozolomide or PCV (procarbazine, lomustine, and vincristine) in addition to RT regardless of the 1p/19q deletion status. A clear improvement in progression-free and overall survival was observed for RT and combined CT/RT in compared with CT only. Postoperative RT appears to improve survival for entire group thus total removal and 1p/19q codeletion may not be sufficient criteria to omit RT as a treatment option. These results suggest that RT should continue to be offered as the standard treatment option for patients with anaplastic oligodendroglial tumors.

Outcome analysis in patients with uterine sarcoma.

PURPOSE: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. MATERIALS AND METHODS: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). RESULTS: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. CONCLUSION: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

Pattern of care of anaplastic oligodendroglioma and oligoastrocytoma in a Korean population: the Korean Radiation Oncology Group study 13-12.

This study investigated the treatment of anaplastic oligodendroglial tumors across nine Korean institutions. We reviewed the medical records from 381 patients with histologically confirmed anaplastic oligodendroglioma or anaplastic oligoastrocytoma (AOA) from 2000 to 2010. Clinical factors and treatment patterns were analyzed for each year. Post-operative therapy was performed in 354 patients (94.1 %), of which 133 received radiotherapy (RT) alone and 189 received both RT and chemotherapy. RT alone was the preferred treatment toward the end of the study period (29.4 % in 2000-2001 vs. 56.3 % in 2010, P = 0.005). The use of procarbazine, lomustine, and vincristine (PCV) decreased (57.6 % in 2000-2001 vs. 28.6 % in 2010, P = 0.001) and the use of temozolomide (TMZ) increased (0 % in 2000-2001 vs. 61.9 % in 2010, P < 0.001) over the study period. A combination of chemotherapy and RT was used more often than RT alone in young patients (P = 0.036) and patients with a good performance status (P = 0.023). The 1p/19q co-deletion status and O-6-methyguanine-DNA methyltransferase methylation were analyzed since 2004 but were not significant factors for determining whether to administer chemotherapy. Among the patients who received chemotherapy, TMZ was used more often in patients with AOA (P = 0.007) and PCV was used more often in patients with either multiple lesions (P = 0.027) or the 1p/19q co-deletion (P = 0.026). Our results demonstrate that the treatment pattern for oligodendroglial tumors changed significantly across the study period. In particular, TMZ has replaced PCV, and the use of molecular markers as well as RT alone has increased, but a unified protocol remains to be established.

Dose-volumetric parameters for predicting hypothyroidism after radiotherapy for head and neck cancer.

OBJECTIVE: To investigate predictors affecting the development of hypothyroidism after radiotherapy for head and neck cancer, focusing on radiation dose-volumetric parameters, and to determine the appropriate radiation dose-volumetric threshold of radiation-induced hypothyroidism. METHODS: A total of 114 patients with head and neck cancer whose radiotherapy fields included the thyroid gland were analysed. The purpose of the radiotherapy was either definitive (n = 81) or post-operative (n = 33). Thyroid function was monitored before starting radiotherapy and after completion of radiotherapy at 1 month, 6 months, 1 year and 2 years. A diagnosis of hypothyroidism was based on a thyroid stimulating hormone value greater than the maximum value of laboratory range, regardless of symptoms. In all patients, dose volumetric parameters were analysed. RESULTS: Median follow-up duration was 25 months (range; 6-38). Forty-six percent of the patients were diagnosed as hypothyroidism after a median time of 8 months (range; 1-24). There were no significant differences in the distribution of age, gender, surgery, radiotherapy technique and chemotherapy between the euthyroid group and the hypothyroid group. In univariate analysis, the mean dose and V35-V50 results were significantly associated with hypothyroidism. The V45 is the only variable that independently contributes to the prediction of hypothyroidism in multivariate analysis and V45 of 50% was a threshold value. If V45 was <50%, the cumulative incidence of hypothyroidism at 1 year was 22.8%, whereas the incidence was 56.1% if V45 was ≥50% (P = 0.034). CONCLUSIONS: The V45 may predict risk of developing hypothyroidism after radiotherapy for head and neck cancer, and a V45 of 50% can be a useful dose-volumetric threshold of radiation-induced hypothyroidism.

Fluorodeoxyglucose positron-emission tomography ratio in non-small cell lung cancer patients treated with definitive radiotherapy.

PURPOSE: To determine whether the maximum standardized uptake value (SUV) of [(18)F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio of lymph node to primary tumor (mSUVR) could be a prognostic factor for node positive non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy (RT). MATERIALS AND METHODS: A total of 68 NSCLC T1-4, N1-3, M0 patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen based on overall survival (OS). Independent prognosticators were identified by Cox regression analysis. RESULTS: The most significant cutoff value for mSUVR was 0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49% for those with mSUVR ≤ 0.9 (p = 0.01). In a multivariate analysis, including age, performance status, stage, use of chemotherapy, and mSUVR, only performance status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS. Two-year OS for patients with both good performance (Eastern Cooperative Oncology Group [ECOG] ≤ 1) and mSUVR ≤ 0.9 was significantly better than that for patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs. 23%, p = 0.04). CONCLUSION: Our results suggested that the mSUVR was a strong prognostic factor among patients with lymph node positive NSCLC following RT. Addition of mSUVR to performance status identifies a subgroup at highest risk for death after RT.