Publications by authors named "Nalee Kim"

47 Publications

Correction to: Role of 23.4 Gy upfront whole-brain radiation therapy following high-dose methotrexate for primary central nervous system lymphoma: a comparative analysis of whole-brain radiation therapy versus no radiation therapy.

J Neurooncol 2021 Sep;154(2):219

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

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http://dx.doi.org/10.1007/s11060-021-03824-5DOI Listing
September 2021

Role of 23.4 Gy upfront whole-brain radiation therapy following high-dose methotrexate for primary central nervous system lymphoma: a comparative analysis of whole-brain radiation therapy versus no radiation therapy.

J Neurooncol 2021 Sep 31;154(2):207-217. Epub 2021 Jul 31.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Introduction: We aimed to investigate the role of upfront whole-brain radiation therapy (RT), with a reduced dose of 23.4 Gy, following high-dose methotrexate (HD-MTX) in patients with primary central nervous system lymphoma (PCNSL).

Methods: We retrospectively reviewed 185 patients with PCNSL treated with HD-MTX between January 2013 and January 2020; 145 patients underwent no RT and 40 patients underwent upfront RT. Using propensity score matching (PSM) to adjust for clinical factors, 40 patients were selected from each treatment group. Event-free survival (EFS) and overall survival (OS) were compared between treatment groups.

Results: At baseline, patients in the upfront RT group were younger, had higher LDH levels, received less frequent rituximab and stem cell transplantation than those in the no-RT group. Patients in the upfront RT group also showed a lower response rate after initial HD-MTX than those in the no-RT group (73% vs. 88%, p = 0.038). The median follow-up was 25.1 (interquartile range 13.7-43.0) months. Comparable 2-year EFS and OS rates were observed between the upfront RT and no-RT groups (56.6% vs. 53.8%, p = 0.170; and 81.7% vs. 75.3%, p = 0.097, respectively). Upfront RT was related to improved EFS and OS in patients with stable disease or progressive disease after HD-MTX, but not in patients with complete or partial response after HD-MTX. Upfront RT was also an independent predictor of EFS and OS in the PSM cohort. The cumulative incidences of treatment-related neurotoxicity at 3 years were 20.2% and 21.2% in the upfront RT and no-RT groups, respectively (p = 0.630).

Conclusions: Upfront RT with a reduced dose of 23.4 Gy, showed favorable outcomes in patients with stable disease or progressive disease after initial HD-MTX. In addition, upfront RT appears to be an effective treatment for PCNSL when rituximab or stem cell transplantation is not feasible.
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http://dx.doi.org/10.1007/s11060-021-03815-6DOI Listing
September 2021

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody.

Front Immunol 2021 8;12:701668. Epub 2021 Jul 8.

Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: We explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).

Methods: Among 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index <49 cm2/m2 for men and <31 cm2/m2 for women; 93 patients met criteria. We defined high neutrophil-to-lymphocyte ratio (hNLR) as NLR≥3. Palliative RT was performed in 37 patients (20%) before ICB.

Results: We frequently observed hNLR in patients with SAR (53% 35%, p = 0.02). The median overall survival (OS) for the entire cohort was 5 months. Stratification by risk factors of SAR or hNLR revealed a significant difference in median OS (0 [N = 60] 1 [N = 76] 2 [N = 49]: 7.6 6.4 2.2 months, p < 0.001). Patients with microsatellite instability-high (MSI-H, N = 19) or Epstein-Barr virus (EBV)-positive tumors (N = 13) showed favorable outcomes compared to those with microsatellite stable (MSS, N = 142) tumors (median OS, not reached 16.8 3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1 1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5 3.5 months, p = 0.03), but outcomes after RT in MSI-H tumor were not significantly different. In multivariable analysis, SAR/hNLR, molecular subtypes, and a history of RT were associated with OS (all p < 0.05).

Conclusions: We demonstrated the negative predictive value of SAR/hNLR on outcomes after ICB for AGC, and the history of RT could overcome the negative impact of SAR/hNLR and the MSS/EBV-negative subtype.
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http://dx.doi.org/10.3389/fimmu.2021.701668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298191PMC
July 2021

Clinical Outcomes of Pencil Beam Scanning Proton Therapy in Locally Advanced Non-Small Cell Lung Cancer: Propensity Score Analysis.

Cancers (Basel) 2021 Jul 13;13(14). Epub 2021 Jul 13.

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8-26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively ( = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT ( = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively ( = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.
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http://dx.doi.org/10.3390/cancers13143497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307066PMC
July 2021

Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study.

Breast Cancer Res Treat 2021 Aug 21;189(1):167-175. Epub 2021 Jun 21.

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: This study was performed to evaluate circulating tumor DNA (ctDNA) kinetics during postoperative radiotherapy (PORT) in patients with residual triple-negative breast cancer (TNBC) at surgery following neoadjuvant chemotherapy (NAC).

Methods: Stage II/III patients with post-NAC residual TNBC who required PORT were prospectively included in this study between March 2019 and July 2020. For 11 TNBC patients, next-generation sequencing targeting 38 genes was conducted in 55 samples, including tumor tissue, three plasma samples, and leukocytes from each patient. The plasma samples were collected at three-time points; pre-PORT (T0), after 3 weeks of PORT (T1), and 1 month after PORT (T2). Serial changes in ctDNA variant allele frequency (VAF) were analyzed.

Results: Somatic variants were found in the tumor specimens in 9 out of 11 (81.8%) patients. Mutated genes included TP53 (n = 7); PIK3CA (n = 2); and AKT1, APC, CSMD3, MYC, PTEN, and RB1 (n = 1). These tumor mutations were not found in plasma samples. Plasma ctDNA variants were detected in three (27.3%) patients at T0. Mutations in EGFR (n = 1), CTNNB1 (n = 1), and MAP2K (n = 1) was identified with ctDNA analysis. In two (18.2%) patients, the ctDNA VAF decreased through T1 and T2 while increasing at T2 in one (9.1%) patient. After a median follow-up of 22 months, no patient showed cancer recurrence.

Conclusion: Among patients with post-NAC residual TNBC, more than a quarter exhibited a detectable amount of ctDNA after curative surgery. The ctDNA VAF changed variably during the course of PORT. Therefore, ctDNA kinetics can serve as a biomarker for optimizing adjuvant treatment.
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http://dx.doi.org/10.1007/s10549-021-06296-3DOI Listing
August 2021

Significance of serum CA125 level in surgically resected cervical adenocarcinoma with adverse features.

J Gynecol Oncol 2021 Sep 18;32(5):e72. Epub 2021 May 18.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: Unlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features.

Methods: A total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model.

Results: Using a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7-97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003).

Conclusion: In this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.
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http://dx.doi.org/10.3802/jgo.2021.32.e72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362813PMC
September 2021

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy.

Breast 2021 Oct 4;59:37-43. Epub 2021 Jun 4.

Department of Radiation Oncology, CHA Bundang Hospital, CHA University College of Medicine, Seongnam, South Korea. Electronic address:

Background: It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.

Methods: We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.

Results: After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045-0.966) and 0.460 (95% CI, 0.220-0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).

Conclusions: IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.
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http://dx.doi.org/10.1016/j.breast.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209280PMC
October 2021

Optimal Timing of Radiotherapy after Incomplete Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma.

Yonsei Med J 2021 May;62(5):409-416

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The optimal timing for radiotherapy (RT) after incomplete transarterial chemoembolization (TACE) remains unclear. This study investigated the optimal timing to initiate RT after incomplete TACE in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma.

Materials And Methods: This study included 116 lesions in 104 patients who were treated with RT after TACE between 2001 and 2016. The time interval between the last TACE session and RT initiation was retrospectively analyzed. The optimal cut-off time interval that maximized the difference in local failure-free rates (LFFRs) was determined using maximally selected rank statistics.

Results: The median time interval was 26 days (range: 2-165 days). At a median follow-up of 18 months (range: 3-160 months), the median overall survival was 18 months. The optimal cut-off time interval appeared to be 5 weeks; using this cut-off, 65 and 39 patients were classified into early and late RT groups, respectively. Early RT group had a significantly poorer Child-Pugh class and higher alpha-fetoprotein levels compared to late RT group. Other characteristics, including tumor size (7 cm vs. 6 cm; =0.144), were not significantly different between the groups. The 1-year LFFR was significantly higher in the early RT group than in the late RT group (94.6% vs. 70.8%; =0.005). On multivariate analysis, early RT was identified as an independent predictor of favorable local failure-free survival (hazard ratio: 3.30, 95% confidence interval: 1.50-7.29; =0.003).

Conclusion: The optimal timing for administering RT after incomplete TACE is within 5 weeks. Early administration of RT is associated with better local control.
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http://dx.doi.org/10.3349/ymj.2021.62.5.409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084693PMC
May 2021

Patterns of definitive radiotherapy practice for cervical cancer in South Korea: a survey endorsed by the Korean Radiation Oncology Group (KROG 20-06).

Authors:
Nalee Kim Won Park

J Gynecol Oncol 2021 05;32(3):e43

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: The Korean Radiation Oncology Group conducted a nationwide questionnaire survey to evaluate the patterns of clinical practice for patients with cervical cancer receiving definitive radiation therapy (RT) in South Korea.

Methods: Practicing radiation oncologists from 93 centers in South Korea were administered a questionnaire survey via e-mail. The survey focused on demographic characteristics, diagnostic evaluation, indications for definitive RT, RT techniques, RT field and dose prescription, lymph node (LN) boost RT, brachytherapy, and chemotherapy.

Results: The response rate was 62.4% (58/93 institutions). Of the 2,134 patients treated at the radiation oncology department in 2019, 48.8% underwent definitive RT. The selection of patients for definitive concurrent chemoradiation therapy and RT field, and RT dose prescription varied greatly. The upper border of the pelvis was commonly used as the bony landmark for external beam RT (81%-88% of respondents). Most (96.6%) centers performed LN boost RT with median total doses of 59 Gy and 59.2 Gy for pelvic and retroperitoneal LN, respectively. With 50% of the centers offering brachytherapy, image-guided brachytherapy and volume-based prescription were applied in 48.3% and 37.9%, respectively. Upfront concurrent chemoradiation therapy with varying prescription doses was considered by 60.4% respondents in cases of supraclavicular LN metastasis.

Conclusion: Most differences were noted in the indications for treatment, RT field, and prescription dose. This finding can serve as a reference for establishing practical RT guidelines for the management of locally advanced cervical cancer.
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http://dx.doi.org/10.3802/jgo.2021.32.e43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039174PMC
May 2021

Oncological and Functional Outcomes of Larynx-preserving Surgery for Hypopharyngeal Cancer: A Comparison with Definitive Radiation-based Treatment.

Cancer Res Treat 2021 Mar 26. Epub 2021 Mar 26.

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Larynx-preserving surgery (LPS) have recently gained popularity and achieved comparable oncologic outcomes to conventional radical surgery for localized hypopharyngeal cancer (HPC). In the current study, the role of LPS has been assessed thoroughly in comparison with upfront radiation therapy (RT).

Materials And Methods: We retrospectively reviewed 185 candidates for LPS with cT1-2 disease; 59 patients underwent upfront LPS while 126 patients received upfront RT, respectively. Oncological and functional outcomes were investigated and compared.

Results: Following LPS, safe margin (≥ 5mm) was achieved in 37.3% of patients. Overall, better clinical outcomes at 5 years were achieved following upfront LPS than those following upfront RT: overall survival (OS) (72.7% vs. 59.0%, p=0.045), disease-free survival (DFS) (59.8% vs. 45.0%, p=0.039), and functional laryngeal preservation (100.0% vs. 89.7%, p=0.010). Although similar outcomes were observed in patients with cT1 disease, better 5-year DFS was achieved following upfront LPS in patients with cT2 disease (57.0% vs. 36.4%, p=0.023) by virtue of better local control. Despite frequent cN2-3 disease in upfront LPS group, comparable outcomes were observed between upfront RT and LPS group. However, multivariable analyses revealed that performance status and double primary cancer diagnosed within 6 months of HPC diagnosis affected OS significantly, while treatment modality per se did not.

Conclusion: Although upfront LPS could provide better local control than upfront RT in patients with cT2 disease, overall outcomes were comparable following either modality. Treatment selection of larynx-preserving approach for HPC should be individualized based on tumor and patient factors.
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http://dx.doi.org/10.4143/crt.2020.1197DOI Listing
March 2021

Adjuvant radiotherapy for cervical cancer in South Korea: a radiation oncology survey of the Korean Radiation Oncology Group (KROG 20-06).

Authors:
Nalee Kim Won Park

Jpn J Clin Oncol 2021 Jul;51(7):1107-1113

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Objective: Radiation therapy plays an important role in adjuvant treatment for surgically treated cervical cancer with adverse pathological findings. This was the first study to evaluate current practices of adjuvant radiation therapy among centres affiliated with the Korean Radiation Oncology Group.

Methods: A survey containing specific questions on the demographics in 2019, indications of adjuvant treatment, radiation therapy field, prescription radiation therapy dose, boost radiation therapy and chemotherapy was sent out by e-mail to 93 centres.

Results: The overall response rate was 62.4%. Regarding radiation therapy techniques, intensity-modulated radiation therapy was adopted in most institutions (41/58, 70.7%). Various risk group criteria were selected for adjuvant radiation therapy and concurrent chemoradiation therapy. One or two risk factors among tumour size, depth of invasion and lymphovascular invasion were considered for adjuvant radiation therapy by 20.7 and 60.3% of the respondents, respectively. The following criteria for concurrent chemoradiation therapy were considered by 60.3% of the respondents: parametrial extension, positive resection margin or lymph node metastasis. Various upper borders were preferred for pelvic radiation therapy by the institutions, and a total dose of 50.4 Gy in 28 fractions was the most prescribed dose scheme (37/58, 63.8%). Lymph node bed boost radiation therapy and vaginal cuff brachytherapy were considered for selected patients by 22.4% (13/58) and 60.3% (35/58) of the institutions.

Conclusion: This survey demonstrated the practice patterns of adjuvant treatment that are prevalent in the field of radiation oncology among members of the Korean Radiation Oncology Group. These findings warrant further consensus on radiation therapy guidelines in the context of adjuvant treatment for cervical cancer.
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http://dx.doi.org/10.1093/jjco/hyab035DOI Listing
July 2021

Practical aspects of the application of helical tomotherapy for craniospinal irradiation.

Sci Rep 2021 03 17;11(1):6120. Epub 2021 Mar 17.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

We investigated the practical aspects of the application of craniospinal irradiation using helical tomotherapy (HT-CSI) by evaluating interfractional setup errors and intrafractional movement during each treatment in 83 patients undergoing HT-CSI between January 2014 and December 2018. Interfractional setup errors in each axis (mediolateral; ML, craniocaudal; CC, and anteroposterior; AP) were assessed as differences between pre-treatment megavoltage computed tomography (MVCT) images scanned (zygomatic arch to the C4 spine) and planning CT images. Intrafractional movements were evaluated as the difference between pre-treatment and post-treatment MVCT (T12-L4 spine) images at each fraction. Median interfractional setup error was acceptable in every axis (ML: 1.6 mm, CC: 1.9 mm, AP: 3.1 mm). Seven patients (8.4%) experienced significant intrafractional displacement from 1 to 10 fractions (0.34% for ML, 0.74% for CC, 1.21% for AP). Weight loss grade 1+ during treatment (p = 0.016) was an independent risk factor for significant intrafractional displacement. The risk factor for significant intrafractional movement in pediatric patients was weight loss grade 1+ (p = 0.020), while there was no factor in adults. HT-CSI could be a feasible treatment modality with acceptable setup verification. Inter- and intrafractional errors were acceptable; paying attention to weight loss during treatment is necessary, especially in pediatric patients.
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http://dx.doi.org/10.1038/s41598-021-85574-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969733PMC
March 2021

Longitudinal impact of postmastectomy radiotherapy on arm lymphedema in patients with breast cancer: An analysis of serial changes in arm volume measured by infrared optoelectronic volumetry.

Radiother Oncol 2021 05 3;158:167-174. Epub 2021 Mar 3.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background And Purpose: This study was conducted to evaluate the longitudinal impact of postmastectomy radiation therapy (PMRT) on persistent severe lymphedema (PSL) using arm volume measurements by an infrared optoelectronic volumetry.

Materials And Methods: Of the patients who underwent mastectomy between 2008 and 2016, we included 330 patients with secondary arm lymphedema. Percentage of excessive volume (PEV) of the arm were serially assessed using an optoelectronic volumetry 1, 3, 6, 12, 18, 24, 36, and 48 months after the lymphedema diagnosis (T). We defined PSL as 2 or more episodes of PEV ≥ 20%. Risk factors for PSL were evaluated using stepwise regression analyses.

Results: Patients who received PMRT (n = 202, 61.2%) were more likely to have larger extent of axillary node dissection (AND), and frequent stage II/III lymphedema at T than those who did not receive PMRT (p < 0.001). With a median follow-up of 72.5 months, PSL occurred in 71 (21.5%) patients. Patients with PSL were more frequently treated with AND of ≥ 20 nodes without reconstruction, had advanced lymphedema stage and higher PEV at T, and more frequent events of cellulitis compared to those without PSL. The risk of developing PSL was significantly associated with PMRT with regional node irradiation (RNI), AND of ≥20 nodes, lymphedema stage, and PEV at T, cellulitis, and compliance with physical therapy.

Conclusion: PMRT, especially RNI, was associated with a consistent increase in PEV in patients with arm lymphedema. Therefore, timely physical therapy is necessary for this patient population.
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http://dx.doi.org/10.1016/j.radonc.2021.02.033DOI Listing
May 2021

Hypofractionated volumetric-modulated arc therapy for breast cancer: A propensity-score-weighted comparison of radiation-related toxicity.

Int J Cancer 2021 07 8;149(1):149-157. Epub 2021 Mar 8.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

We assessed the clinical benefit of combining volumetric-modulated arc therapy (VMAT) and hypofractionated radiotherapy (HF-RT) considering the incidence of radiation-related toxicities. After a retrospective review for breast cancer patients treated with adjuvant RT between 2005 and 2017, a total of 4209 patients treated with three-dimensional conventional fractionation (CF-3D, 50.4 Gy/28 fractions) and 1540 patients treated with HF-RT (768 received HF-3D; 772, HF-VMAT; 40 Gy/15 fractions) were included. A total of 2229 patients (38.8%) received regional node irradiation (RNI): 1642 (39.0%), 167 (21.7%) and 420 (54.4%) received RNI via CF-3D, HF-3D and HF-VMAT, respectively. Acute/subacute and late toxicities were evaluated. Propensity scores were calculated via logistic regression. Grade 2+ acute/subacute toxicities was the highest in CF-3D group (15.0%, 2.6% and 1.6% in CF-3D, HF-3D and HF-VMAT, respectively; P < .001). HF-VMAT reduced Grade 2+ acute/subacute toxicities significantly compared to CF-3D (odds ratio [OR] 0.11, P < .001) and HF-3D (OR 0.45, P = .010). The 3-year cumulative rate of late toxicities was 18.0% (20.1%, 10.9% and 13.4% in CF-3D, HF-3D and HF-VMAT, respectively; P < .001). On sensitivity analysis, the benefit of HF-VMAT was high in the RNI group. Acute and late toxicities were fewer after HF-VMAT than after HF-3D or CF-3D, especially in women who underwent RNI.
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http://dx.doi.org/10.1002/ijc.33525DOI Listing
July 2021

Feasibility of Continual Deep Learning-Based Segmentation for Personalized Adaptive Radiation Therapy in Head and Neck Area.

Cancers (Basel) 2021 Feb 9;13(4). Epub 2021 Feb 9.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Korea.

This study investigated the feasibility of deep learning-based segmentation (DLS) and continual training for adaptive radiotherapy (RT) of head and neck (H&N) cancer. One-hundred patients treated with definitive RT were included. Based on 23 organs-at-risk (OARs) manually segmented in initial planning computed tomography (CT), modified FC-DenseNet was trained for DLS: (i) using data obtained from 60 patients, with 20 matched patients in the test set (DLSm); (ii) using data obtained from 60 identical patients with 20 unmatched patients in the test set (DLSu). Manually contoured OARs in adaptive planning CT for independent 20 patients were provided as test sets. Deformable image registration (DIR) was also performed. All 23 OARs were compared using quantitative measurements, and nine OARs were also evaluated via subjective assessment from 26 observers using the Turing test. DLSm achieved better performance than both DLSu and DIR (mean Dice similarity coefficient; 0.83 vs. 0.80 vs. 0.70), mainly for glandular structures, whose volume significantly reduced during RT. Based on subjective measurements, DLS is often perceived as a human (49.2%). Furthermore, DLSm is preferred over DLSu (67.2%) and DIR (96.7%), with a similar rate of required revision to that of manual segmentation (28.0% vs. 29.7%). In conclusion, DLS was effective and preferred over DIR. Additionally, continual DLS training is required for an effective optimization and robustness in personalized adaptive RT.
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http://dx.doi.org/10.3390/cancers13040702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915955PMC
February 2021

Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: A comparative analysis of proton versus photon therapy.

Radiother Oncol 2021 03 24;156:166-173. Epub 2020 Dec 24.

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Hypothesis: We investigated differences in severe radiation-induced lymphopenia (SRL) after pencil beam scanning proton therapy (PBSPT) or intensity-modulated (photon) radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer.

Methods: We retrospectively reviewed 223 patients who received definitive concurrent chemoradiotherapy with PBSPT (n = 29) or IMRT (n = 194). SRL was defined when ≥2 events of absolute lymphocyte counts (ALCs) of <200 cells/μL were observed in weekly laboratory tests conducted during treatment. Stepwise multivariate logistic regression with 10-fold cross-validation was performed to identify predictive values of SRL. Furthermore, 1:2 propensity score matching (PSM) analysis was performed between the PBSPT and IMRT groups.

Results: Baseline ALC was comparable between the PBSPT and IMRT groups (median, 2130 vs. 2040 cells/μL; p = 0.983). Lung volumes receiving ≥ 5-20 GyE and the mean dose were significantly lower in patients receiving PBSPT than those receiving IMRT (p < 0.001). Among 72 (32.3%) patients with SRL; 69 (95.8%) and 3 (4.2%) patients were treated with IMRT and PBSPT, respectively. After multivariable analysis, PBSPT reduced SRL compared to IMRT (odds ratio [OR] 0.13, p = 0.003). Specifically, lung V5Gy were identified as the strongest predictor of SRL before (OR 1.11) and after PSM (OR, 1.07) (p < 0.05). With a median follow-up of 23.0 months, the 2-year overall survival in patients with SRL was worse than that those without SRL (63.4% vs. 79.9%; p = 0.003).

Conclusions: Reduced irradiated lung volumes of PBSPT consequently reduced SRL. In addition, lung V5Gy contributed to the SRL. Reduction of SRL through the optimized RT might be essential to improve the outcomes.
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http://dx.doi.org/10.1016/j.radonc.2020.12.019DOI Listing
March 2021

Magnetic resonance imaging-based validation of the 2018 FIGO staging system in patients treated with definitive radiotherapy for locally advanced cervix cancer.

Gynecol Oncol 2021 03 22;160(3):735-741. Epub 2020 Dec 22.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objective: To validate the revised 2018 International Federation of Gynecologic and Obstetrics (FIGO) staging system in patients who underwent diagnostic magnetic resonance imaging (MRI) and radiotherapy (RT) for locally advanced cervix cancer.

Methods: We analyzed 677 patients who were diagnosed with pelvic MRI and treated with definitive (chemo-)RT for locally advanced cervix cancer (stage IB2/IIA2-IVA or N+) between 1992 and 2018. Patients were classified according to 2009 and 2018 FIGO staging, and survival outcomes were compared. We developed a nomogram to improve prediction of progression-free survival (PFS).

Results: Pelvic and paraaortic lymph nodes were positive in 331 (48.9%) and 78 (11.5%) patients, respectively. At a median follow-up of 77.9 months, the 5-year PFS was 83.5%, 65.2%, 71.0%, 60.6%, 37.6% and 38.9% for IB, IIA, IIB, IIIA, IIIB and IVA according to FIGO 2009 and 88.9%, 60.0%, 73.8%, 66.7%, 36.3%, 68.9%, 43.6%, and 38.9% for IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA according to FIGO 2018, respectively. Survival of stage IIIC cervix cancer depended on the local extent of the tumor: the 5-year PFS of T1, T2, and T3 stages were 80.3%, 73.9%, and 45.5% for IIIC1 and 100%, 44.9%, and 23.4% for IIIC2. Histology, tumor size, node metastasis, FIGO 2009, and treatment modality were independent prognostic factors in the Cox regression analysis, and the nomogram incorporating these factors outperformed FIGO 2009 and FIGO 2018 (AUC 0.718 vs. 0.616 vs. 0.594).

Conclusions: FIGO 2018 revision was associated with heterogenous outcomes among stage III cervix cancer patients. Our nomogram can assist the FIGO system in predicting PFS after definitive RT.
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http://dx.doi.org/10.1016/j.ygyno.2020.12.012DOI Listing
March 2021

Early Metabolic Response Assessed Using 18F-FDG-PET/CT for Image-Guided Intracavitary Brachytherapy Can Better Predict Treatment Outcomes in Patients with Cervical Cancer.

Cancer Res Treat 2021 Jul 9;53(3):803-812. Epub 2020 Dec 9.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer.

Materials And Methods: We identified 116 patients treated with definitive RT, including FDG-PET/CT-guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed.

Results: We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors.

Conclusion: Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.
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http://dx.doi.org/10.4143/crt.2020.1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291185PMC
July 2021

Use of bevacizumab before or after radiotherapy increases the risk of fistula formation in patients with cervical cancer.

Int J Gynecol Cancer 2021 01 3;31(1):59-65. Epub 2020 Dec 3.

Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Objective: Several reports have documented the risk of fistula formation after bevacizumab in patients previously treated with radiation therapy. The aim of this study was to investigate the risk of fistula formation with bevacizumab and radiotherapy compared with radiotherapy alone.

Methods: We retrospectively analyzed patients with stage I-IV cervical cancer between January 2013 and December 2018. Patients who had a history of pelvic radiotherapy, who were treated with intracavitary brachytherapy alone, received radiotherapy at another hospital, received concurrent bevacizumab and radiotherapy, or had missing follow-up data or a short follow-up period (<6 months) were excluded. The fistula rates were compared between the groups using the Cox proportional hazards model and propensity score analyses.

Results: A total of 302 patients were included in the study: 249 patients were treated with definitive or adjuvant radiotherapy, and 53 patients were treated with radiotherapy before or after bevacizumab. With a median follow-up of 35.9 (IQR 22.8-53.5) months, the 3 year cumulative fistula incidence rate was significantly higher in the radiotherapy + bevacizumab group than in the radiotherapy group (27.0% vs 3.0%, p<0.001). Bevacizumab administration was significantly associated with fistula formation in the multivariable adjusted model (HR 4.76, 95% CI 1.71 to 13.23) and three propensity score adjusted model (all p<0.05). Biologically equivalent dose in 2 Gy fractions for 2 cc of the rectum more than 76 Gy was also associated with fistula formation (HR 4.30, 95% CI 1.52 to 12.18). Additionally, a 10 month interval between radiotherapy and bevacizumab reduced the incidence of fistula formation in the radiotherapy + bevacizumab group (p=0.032).

Conclusions: In patients with cervical cancer treated with pelvic radiotherapy, the addition of bevacizumab substantially increased the risk of fistula formation. Physicians should perform pelvic radiotherapy in combination with bevacizumab with caution; moreover, close monitoring for fistula formation is warranted in these patients.
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http://dx.doi.org/10.1136/ijgc-2020-002031DOI Listing
January 2021

Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab.

Cancer Immunol Immunother 2021 Jun 24;70(6):1593-1603. Epub 2020 Nov 24.

Statistics and Data Center, Samsung Medical Center, Research Institute for Future Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: We investigated the combined effects of sarcopenia and inflammation on outcomes in patients with HCC treated with nivolumab.

Materials And Methods: We reviewed 102 patients treated with nivolumab between 2017 and 2018. Sarcopenia was diagnosed when the L3 skeletal muscle indices were < 42 cm/m and < 38 cm/m in men and women, respectively. Baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count were used as surrogate markers of inflammation and immune cell reservoir. High NLR (hNLR) was defined as NLR ≥ 3, and severe lymphopenia (sLP) was defined as lymphocyte < 800/μL. The overall survival (OS) and progression-free survival (PFS) were analyzed.

Results: With a median follow-up of 21.9 (interquartile range, 8.3-58.3) months, patients with sarcopenia showed shorter OS than those without sarcopenia (median, 2.9 vs. 7.5 months, respectively). Patients with either hNLR or sLP exhibited inferior survival than those without risk factor (median OS, 2.8 vs. 14.5 months; median PFS, 1.3 vs. 3.7 months, respectively). Among 70 patients treated with RT, benefit of RT was observed in patients with sarcopenia or those without hNLR/sLP (all p < 0.05). After multivariable analysis, RT, hNLR/sLP, albumin-bilirubin (ALBI) grade, and alpha-fetoprotein were significantly associated with OS (all p < 0.05), and hNLR/sLP was also associated with decreased PFS together with ALBI grade, alpha-fetoprotein, and RT (all p < 0.05).

Conclusion: The current study hypothetically demonstrated that the risk group stratified by hNLR/sLP outweighs the significance of sarcopenia in predicting outcomes after nivolumab. Furthermore, patients with sarcopenia might benefit from RT, especially those without risk factors of hNLR/sLP.
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http://dx.doi.org/10.1007/s00262-020-02794-3DOI Listing
June 2021

Dose-Response Relationship in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: A Pooled Analysis of an Asian Liver Radiation Therapy Group Study.

Int J Radiat Oncol Biol Phys 2021 02 20;109(2):464-473. Epub 2020 Nov 20.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Purpose: Despite the worldwide implementation of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC), there is a lack of consensus guideline on prescription dose. Herein, this multinational study aimed to investigate the effects of the prescribed radiation dose on oncologic outcomes of SBRT for HCC.

Methods And Materials: The multi-institutional retrospective cohort included 510 patients treated with SBRT between 2010 and 2016. All relevant clinical factors and factors related to SBRT were analyzed to evaluate freedom from local progression (FFLP) and overall survival (OS). Based on a biologically effective dose (BED) cutoff value of 100 Gy, 198 tumors were selected from each group in propensity score matching (PSM).

Results: Baseline characteristics in the BED <100 Gy group were unfavorable (Child-Pugh class B, 19%; advanced stage, 72%; median tumor size was 4 cm) compared with the BED ≥100 Gy group. With a median follow-up of 22 (interquartile range, 9.8-37.6) months, the 2-year FFLP and OS rates were 77% and 73%, respectively. Patients treated with a BED ≥100 Gy showed better rates of 2-year FFLP and OS than patients treated with a BED <100 Gy (FFLP, 89% vs 69%; OS, 80% vs 67%; P < .001). In the multivariable analysis before and after PSM, BED ≥100 Gy was identified as the main prognostic factor for both FFLP and OS (P < .01). Additionally, a dose-response relationship was observed between FFLP and BED (odds ratio, 0.92 per 5 Gy, P = .048).

Conclusions: A BED ≥100 Gy was significantly associated with outcomes, and a dose-response relationship was observed between local tumor progression and BED. Given that SBRT is being increasingly used in HCC, detailed consensus guidelines regarding SBRT dose prescription should be established.
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http://dx.doi.org/10.1016/j.ijrobp.2020.09.038DOI Listing
February 2021

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer.

J Gynecol Oncol 2020 Nov;31(6):e78

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.

Objective: Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining.

Methods: We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0-1+) (n=120 patients) and moderate/strong (2-3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors.

Results: Patients with KLK5 2-3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0-1+. With a median follow-up of 60.8 (interquartile range, 47.5-77.9) months, patients with KLK5 2-3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0-1+ group) and 59.4% (vs. 72.8% in the KLK5 0-1+ group), respectively (all p<0.05). KLK5 2-3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis.

Conclusions: KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.
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http://dx.doi.org/10.3802/jgo.2020.31.e78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593226PMC
November 2020

Simple calculation using anatomical features on pre-treatment verification CT for bladder volume estimation during radiation therapy for rectal cancer.

BMC Cancer 2020 Oct 1;20(1):942. Epub 2020 Oct 1.

Department of Nuclear Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Background: Despite detailed instruction for full bladder, patients are unable to maintain consistent bladder filling during a 5-week pelvic radiation therapy (RT) course. We investigated the best bladder volume estimation procedure for verifying consistent bladder volume.

Methods: We reviewed 462 patients who underwent pelvic RT. Biofeedback using a bladder scanner was conducted before simulation and during treatment. Exact bladder volume was calculated by bladder inner wall contour based on CT images (V). Bladder volume was estimated either by bladder scanner (V) or anatomical features from the presacral promontory to the bladder base and dome in the sagittal plane of CT (V). The feasibility of V was validated using daily megavoltage or kV cone-beam CT before treatment.

Results: Mean V was 335.6 ± 147.5 cc. Despite a positive correlation between V and V (R = 0.278) and between V and V (R = 0.424), V yielded more consistent results than V, with a mean percentage error of 26.3 (SD 19.6, p < 0.001). The correlation between V and V was stronger than that between V and V (Z-score: - 7.782, p < 0.001). An accuracy of V was consistent in megavoltage or kV cone-beam CT during treatment. In a representative case, we can dichotomize for clinical scenarios with or without bowel displacement, using a ratio of 0.8 resulting in significant changes in bowel volume exposed to low radiation doses.

Conclusions: Bladder volume estimation using personalized anatomical features based on pre-treatment verification CT images was useful and more accurate than physician-dependent bladder scanners.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-020-07405-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528380PMC
October 2020

Clinical evaluation of atlas- and deep learning-based automatic segmentation of multiple organs and clinical target volumes for breast cancer.

Radiother Oncol 2020 12 28;153:139-145. Epub 2020 Sep 28.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Manual segmentation is the gold standard method for radiation therapy planning; however, it is time-consuming and prone to inter- and intra-observer variation, giving rise to interests in auto-segmentation methods. We evaluated the feasibility of deep learning-based auto-segmentation (DLBAS) in comparison to commercially available atlas-based segmentation solutions (ABAS) for breast cancer radiation therapy. This study used contrast-enhanced planning computed tomography scans from 62 patients with breast cancer who underwent breast-conservation surgery. Contours of target volumes (CTVs), organs, and heart substructures were generated using two commercial ABAS solutions and DLBAS using fully convolutional DenseNet. The accuracy of the segmentation was assessed using 14 test patients using the Dice Similarity Coefficient and Hausdorff Distance referencing the expert contours. A sensitivity analysis was performed using non-contrast planning CT from 14 additional patients. Compared to ABAS, the proposed DLBAS model yielded more consistent results and the highest average Dice Similarity Coefficient values and lowest Hausdorff Distances, especially for CTVs and the substructures of the heart. ABAS showed limited performance in soft-tissue-based regions, such as the esophagus, cardiac arteries, and smaller CTVs. The results of sensitivity analysis between contrast and non-contrast CT test sets showed little difference in the performance of DLBAS and conversely, a large discrepancy for ABAS. The proposed DLBAS algorithm was more consistent and robust in its performance than ABAS across the majority of structures when examining both CTVs and normal organs. DLBAS has great potential to aid a key process in the radiation therapy workflow, helping optimise and reduce the clinical workload.
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http://dx.doi.org/10.1016/j.radonc.2020.09.045DOI Listing
December 2020

ATM mutations improve radio-sensitivity in wild-type isocitrate dehydrogenase-associated high-grade glioma: retrospective analysis using next-generation sequencing data.

Radiat Oncol 2020 Jul 31;15(1):184. Epub 2020 Jul 31.

Brain Tumor Center, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background: To identify the association between somatic ataxia-telangiectasia mutated (ATM) mutations and improved radio-sensitivity, we retrospectively reviewed next-generation sequencing data from patients diagnosed with isocitrate dehydrogenase (IDH)-wildtype high-grade glioma.

Methods: We included 39 individuals with (IDH)-wildtype high-grade glioma (diffuse astrocytoma n = 2, anaplastic astrocytoma n = 10, and glioblastoma n = 27) not subjected to gross tumor resection and undergoing radiation therapy with a median total dose of 60 Gy in 30 fractions. The mutational status of the ATM gene was obtained through next-generation sequencing using a TruSight Tumor 170 cancer panel. Disease progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria as well as neurologic and clinical findings.

Results: Among the 39 samples, ATM mutations (ATM mut(+)) were detected in 26% of cases (n = 10). No significant differences were observed in the characteristics of the patients or tumors. Among the 10 patients in the ATM mut(+) group, there were 6 patients with glioblastoma and 4 patients with anaplastic astrocytoma. Most mutations were missense mutations (n = 8, 80%). With a median follow-up of 16.5 mo (interquartile range, 11.4-19.8), ATM mut(+) exhibited 1-year in-field control of 100% compared with 44.1% in the ATM mut(-) group (p = 0.002). There was no difference in the out-field control rate or overall survival between the two groups (p = 0.861 and p = 0.247, respectively).

Conclusions: Our results demonstrated that ATM mutations might be involved in the increased radio-sensitivity with excellent in-field control despite the aggressive nature of IDH-wildtype high-grade glioma. Further studies are necessary to uncover the potential role of ATM as a biomarker and candidate therapeutic target in high-grade gliomas.
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http://dx.doi.org/10.1186/s13014-020-01619-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393839PMC
July 2020

Predictive value of interim 18F-FDG-PET in patients with non-small cell lung cancer treated with definitive radiation therapy.

PLoS One 2020 20;15(7):e0236350. Epub 2020 Jul 20.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: We evaluated that early metabolic response determined by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiotherapy (RT), predicts outcomes in non-small cell lung cancer.

Material And Methods: Twenty-eight patients evaluated using pretreatment 18F-FDG-PET/CT (PETpre) and interim 18F-FDG-PET/CT (PETinterim) after 11 fractions of RT were retrospectively reviewed. Maximum standardized uptake value (SUVmax) was calculated for primary lesion. Predictive value of gross tumor volume (ΔGTV) and SUVmax (ΔSUVmax) changes was evaluated for locoregional control (LRC), distant failure (DF), and overall survival (OS). Metabolic responders were patients with ΔSUVmax >40%.

Results: Metabolic responders showed better trends in 1-year LRC (90.9%) than non-responders (47.1%) (p = 0.086). Patients with large GTVpre (≥120 cc) demonstrated poor LRC (hazard ratio 4.14, p = 0.022), while metabolic non-responders with small GTVpre (<120 cc) and metabolic responders with large GTVpre both had 1-year LRC rates of 75.0%. Reduction of 25% in GTV was not associated with LRC; however, metabolic responders without a GTV response showed better 1-year LRC (83.3%) than metabolic non-responders with a reduction in GTV (42.9%). Metabolic responders showed lower 1-year DF (16.7%) than non-responders (50.0%) (p = 0.025). An ΔSUVmax threshold of 40% yielded accuracy of 64% for predicting LRC, 75% for DF, and 54% for OS. However, ΔGTV > 25% demonstrated inferior diagnostic values than metabolic response.

Conclusions: Changes in tumor metabolism diagnosed using PETinterim during RT better predicted treatment responses, recurrences, and prognosis than other factors historically used.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236350PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371172PMC
September 2020

Reply to: "Stereotactic body radiation therapy vs. radiofrequency ablation for HCC: More questions than answers".

J Hepatol 2020 10 6;73(4):973-974. Epub 2020 Jul 6.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2020.05.031DOI Listing
October 2020

Reply to: "Can sorafenib use influence outcome when comparing stereotactic body radiation therapy with radiofrequency ablation in patients with hepatocellular carcinoma?"

J Hepatol 2020 08 25;73(2):468-469. Epub 2020 May 25.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2020.04.016DOI Listing
August 2020

Atlas-based auto-segmentation for postoperative radiotherapy planning in endometrial and cervical cancers.

Radiat Oncol 2020 May 13;15(1):106. Epub 2020 May 13.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Background: Since intensity-modulated radiation therapy (IMRT) has become popular for the treatment of gynecologic cancers, the contouring process has become more critical. This study evaluated the feasibility of atlas-based auto-segmentation (ABAS) for contouring in patients with endometrial and cervical cancers.

Methods: A total of 75 sets of planning CT images from 75 patients were collected. Contours for the pelvic nodal clinical target volume (CTV), femur, and bladder were carefully generated by two skilled radiation oncologists. Of 75 patients, 60 were randomly registered in three different atlas libraries for ABAS in groups of 20, 40, or 60. ABAS was conducted in 15 patients, followed by manual correction (ABAS). The time required to generate all contours was recorded, and the accuracy of segmentation was assessed using Dice's coefficient (DC) and the Hausdorff distance (HD) and compared to those of manually delineated contours.

Results: For ABAS-CTV, the best results were achieved with groups of 60 patients (DC, 0.79; HD, 19.7 mm) and the worst results with groups of 20 patients (DC, 0.75; p = 0.012; HD, 21.3 mm; p = 0.002). ABAS-CTV performed better than ABAS-CTV in terms of both HD and DC (ABAS [n = 60]; DC, 0.84; HD, 15.6 mm; all p < 0.017). ABAS required an average of 45.1 s, whereas ABAS required 191.1 s; both methods required less time than the manual methods (p < 0.001). Both ABAS-Femur and simultaneous ABAS-Bilateral-femurs showed satisfactory performance, regardless of the atlas library used (DC > 0.9 and HD ≤10.0 mm), with significant time reduction compared to that needed for manual delineation (p < 0.001). However, ABAS-Bladder did not prove to be feasible, with inferior results regardless of library size (DC < 0.6 and HD > 40 mm). Furthermore, ABAS-Bladder required a longer processing time than manual contouring to achieve the same accuracy.

Conclusions: ABAS could help physicians to delineate the CTV and organs-at-risk (e.g., femurs) in IMRT planning considering its consistency, efficacy, and accuracy.
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http://dx.doi.org/10.1186/s13014-020-01562-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218589PMC
May 2020
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