Cancer Research and Treatment

Original Articles

To Use or Not to Use: Temozolomide in Elderly Patients with IDH Wild-type MGMT Promoter Unmethylated Glioblastoma Treated with Radiotherapy: Chan Woo Wee, Joo Ho Lee, Hye In Lee, Jina Kim, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Ju Hyung Moon, Jaeho Cho, Chul-Kee Park, Chae-Yong Kim, Kihwan Hwang, Hong In Yoon, In Ah Kim; Received September 27, 2024 Accepted November 9, 2024 Published online November 11, 2024; DOI: https://doi.org/10.4143/crt.2024.945 [Accepted]

Abstract PDF: Purpose
To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).
Materials and Methods
Newly diagnosed patients with IDH wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.
Results
During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4–5 months in patients with residual disease (p<0.001), Karnofsky Performance Status ≥60 (p=0.033), and age ≤75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months, p=0.014).
Conclusion
The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

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Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients: Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon; Received July 22, 2024 Accepted September 10, 2024 Published online September 11, 2024; DOI: https://doi.org/10.4143/crt.2024.680 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods
This multi-institutional retrospective study included patients aged ≥ 65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results
A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3 to 149.9 months), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: hazard ratio [HR], 1.52; p < 0.001 and CFRT+TMZ vs. radiotherapy alone: HR, 2.52; p < 0.001). In a combined analysis with the NOA-08 and Nordic trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p < 0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion
CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

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Lung and Thoracic cancer

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy: Dowook Kim, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee, Suzy Kim, Tae Min Kim, Jin-Soo Kim, Byoung Hyuck Kim; Cancer Res Treat. 2024;56(2):430-441. Published online November 6, 2023; DOI: https://doi.org/10.4143/crt.2023.931

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment.
Materials and Methods
We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group.
Results
The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively).
Conclusion
In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

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Clinical outcomes and synergistic effect between radiotherapy and immunotherapy in patients with extensive-stage small cell lung cancer: a real-world study
Meiling Sun, Huaijun Ji, Fang Deng, Jingyi Li, Ning Xu, Yu Li
BMC Cancer.2024;[Epub] CrossRef

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Efficacy of Prophylactic Cranial Irradiation According to the Risk of Extracranial Recurrence in Limited-Stage Small Cell Lung Cancer: Tae Hoon Lee, Joo-Hyun Chung, Hong-Gyun Wu, Suzy Kim, Joo Ho Lee, Bhumsuk Keam, Jin-Soo Kim, Ki Hwan Kim, Byoung Hyuck Kim, Hak Jae Kim; Cancer Res Treat. 2023;55(3):875-884. Published online February 24, 2023; DOI: https://doi.org/10.4143/crt.2022.1583

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC).
Materials and Methods
We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors.
Results
The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026).
Conclusion
PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

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Efficacy evaluation of prophylactic cranial irradiation for limited stage small‑cell lung cancer in the magnetic resonance imaging era: A meta‑analysis
Lihua Shao, Yumei Dong, Meiqiao Jiang, Haixia Song, Yuexiao Qi, Liyun Guo, Jinhui Tian, Shihong Wei
Oncology Letters.2025;[Epub] CrossRef

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Predictors of Post-chemoradiotherapy Pulmonary Complication in Locally Advanced Non–Small Cell Lung Cancer: Tae Hoon Lee, Byung-Hee Kang, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee; Cancer Res Treat. 2023;55(3):865-874. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.1538

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Purpose
We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non–small cell lung cancer (LA-NSCLC).
Materials and Methods
Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS).
Results
PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001).
Conclusion
PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.

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Pneumonitis Risk After Chemoradiotherapy With and Without Immunotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Chong Han, Jingping Qiu, Lu Bai, Tingting Liu, Jun Chen, He Wang, Jun Dang
International Journal of Radiation Oncology*Biology*Physics.2024; 119(4): 1179. CrossRef
Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities
Mark Stares, Leo R. Brown, Dhruv Abhi, Iain Phillips
Cancers.2024; 16(8): 1508. CrossRef
Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis
Tingting Liu, Sihan Li, Silu Ding, Jingping Qiu, Chengbo Ren, Jun Chen, He Wang, Xiaoling Wang, Guang Li, Zheng He, Jun Dang
eClinicalMedicine.2023; 64: 102246. CrossRef

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General

Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers: Jae Sik Kim, Joo Ho Lee, Sang-Rok Jeon, Yongsub Kim, Seung Hyuck Jeon, Hong-Gyun Wu; Cancer Res Treat. 2023;55(3):737-745. Published online January 4, 2023; DOI: https://doi.org/10.4143/crt.2022.1414

Abstract PDF Supplementary Material PubReader ePub

Purpose
Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen.
Materials and Methods
Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction.
Results
We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1, and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.
Conclusion
The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Citations

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Uncovering the bookshelves of CRISPR-based libraries: Advances and applications in cancer studies
Nathalia Quintero-Ruiz, Wesley de Lima Oliveira, Marcos Vinicius Esteca, Daniela Campos Granato, Fernando Moreira Simabuco
Critical Reviews in Oncology/Hematology.2024; 196: 104287. CrossRef
CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy
Mingming Qin, Chunhao Deng, Liewei Wen, Guoqun Luo, Ya Meng
Journal of Translational Medicine.2024;[Epub] CrossRef

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CNS cancer

Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study: Hyun Ju Kim, Joo Ho Lee, Youngkyong Kim, Do Hoon Lim, Shin-Hyung Park, Seung Do Ahn, In Ah Kim, Jung Ho Im, Jae Wook Chung, Joo-Young Kim, Il Han Kim, Hong In Yoon, Chang-Ok Suh; Cancer Res Treat. 2023;55(1):41-49. Published online March 4, 2022; DOI: https://doi.org/10.4143/crt.2021.1514

Abstract PDF Supplementary Material PubReader ePub

Purpose
This multicenter retrospective study aimed to investigate clinical, radiologic, and treatment-related factors affecting survival in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) treated with radiotherapy.
Materials and Methods
Patients aged <30 years who underwent radiotherapy as an initial treatment for DIPG between 2000 and 2018 were included; patients who did not undergo magnetic resonance imaging at diagnosis and those with pathologically diagnosed grade I glioma were excluded. We examined medical records of 162 patients collected from 10 participating centers in Korea. The patients’ clinical, radiological, molecular, and histopathologic characteristics, and treatment responses were evaluated to identify the prognosticators for DIPG and estimate survival outcomes.
Results
The median follow-up period was 10.8 months (interquartile range, 7.5 to 18.1). The 1- and 2-year overall survival (OS) rates were 53.5% and 19.0%, respectively, with a median OS of 13.1 months. Long-term survival rate (≥ 2 years) was 16.7%, and median OS was 43.6 months. Age (< 10 years), poor performance status, treatment before 2010, and post-radiotherapy necrosis were independently associated with poor OS in multivariate analysis. In patients with increased post-radiotherapy necrosis, the median OS estimates were 13.3 months and 11.4 months with and without bevacizumab, respectively (p=0.138).
Conclusion
Therapeutic strategy for DIPG has remained unchanged over time, and the associated prognosis remains poor. Our findings suggest that appropriate efforts are needed to reduce the occurrence of post-radiotherapy necrosis. Further well-designed clinical trials are recommended to improve the poor prognosis observed in DIPG patients.

Citations

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Advancements in Image-Based Models for High-Grade Gliomas Might Be Accelerated
Guido Frosina
Cancers.2024; 16(8): 1566. CrossRef
The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma
Xiaojun Yu, Mingyao Lai, Juan Li, Lichao Wang, Kunlin Ye, Dong Zhang, Qingjun Hu, Shaoqun Li, Xinpeng Hu, Qiong Wang, Mengjie Ma, Zeyu Xiao, Jiangfen Zhou, Changzheng Shi, Liangping Luo, Linbo Cai
Neurosurgical Review.2024;[Epub] CrossRef
Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma
Lauren M. Arms, Ryan J. Duchatel, Evangeline R. Jackson, Pedro Garcia Sobrinho, Matthew D. Dun, Susan Hua
Journal of Controlled Release.2024; 370: 835. CrossRef
Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses
Xiaojun Yu, Shaoqun Li, Wenfeng Mai, Xiaoyu Hua, Mengnan Sun, Mingyao Lai, Dong Zhang, Zeyu Xiao, Lichao Wang, Changzheng Shi, Liangping Luo, Linbo Cai
European Radiology.2024; 34(12): 7962. CrossRef

5,391 View
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4 Crossref

Head and Neck cancer

Radiotherapy versus Surgery in Early-Stage HPV-Positive Oropharyngeal Cancer: Dong-Yun Kim, Hong-Gyun Wu, Jin Ho Kim, Joo Ho Lee, Soon-Hyun Ahn, Eun-Jae Chung, Keun-Yong Eom, Young Ho Jung, Woo-Jin Jeong, Tack-Kyun Kwon, Suzy Kim, Chan Woo Wee; Cancer Res Treat. 2022;54(2):406-416. Published online June 23, 2021; DOI: https://doi.org/10.4143/crt.2021.441

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus–positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment.
Materials and Methods
This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT.
Results
With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding.
Conclusion
We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

Citations

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Definitive radio(chemo)therapy versus upfront surgery in the treatment of HPV-related localized or locally advanced oropharyngeal squamous cell carcinoma
Jérémy Baude, Caroline Guigou, David Thibouw, Noémie Vulquin, Mireille Folia, Guillaume Constantin, Jihane Boustani, Christian Duvillard, Sylvain Ladoire, Gilles Truc, Aurélie Bertaut, Cédric Chevalier, Scott M. Langevin
PLOS ONE.2024; 19(7): e0307658. CrossRef
INFLUENCE OF CONFORMAL RADIOTHERAPY IN COMBINATION WITH RADIOMODIFIERS ON THE CONTENT OF VEGF, COX-2, AND PGE-2 IN BLOOD SERUM OF PATIENTS WITH HEAD AND NECK SQUAMOUS CELL CARCINOMA
N. MITRYAYEVA, L. GREBINYK, S. ARTIUKH, N. BILOZOR, V. STARENKIY
Experimental Oncology.2024; 46(3): 253. CrossRef
Assessment of Radiologic Extranodal Extension Using Combinatorial Analysis of Nodal Margin Breakdown and Metastatic Burden in Oropharyngeal Cancer
Sungryeal Kim, Hannah Park, Se Hyun Yeou, Jin Roh, Yoo Seob Shin, Chul-Ho Kim, Eun Ju Ha, Jeon Yeob Jang
Cancers.2023; 15(13): 3276. CrossRef
Expanding the role of combined immunochemotherapy and immunoradiotherapy in the management of head and neck cancer (Review)
Chun Wei, Xiaojun Lan, Maona Qiu, Ran Cui, Qiuxia Fu, Shafiu Umar Shinge, Tobias Muluh, Ou Jiang
Oncology Letters.2023;[Epub] CrossRef

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CNS cancer

The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-institutional Retrospective Study (KROG 18-11): Joo Ho Lee, Seung Hyuck Jeon, Chul-Kee Park, Sung-Hye Park, Hong In Yoon, Jong Hee Chang, Chang-Ok Suh, Su Jeong Kang, Do Hoon Lim, In Ah Kim, Jin Hee Kim, Jung Ho Im, Sung-Hwan Kim, Chan Woo Wee, Il Han Kim; Cancer Res Treat. 2022;54(1):65-74. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2021.142

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).
Materials and Methods
A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.
Results
The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).
Conclusion
This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

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Salah-Edine Safi, Julie Godfrain, Herbert Rooijakkers, Frederic Collignon, Mario Ganau
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Jingdian Liu, Sisi Wu, Kai Zhao, Junwen Wang, Kai Shu, Ting Lei
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Karineh Kazazian, Elizabeth G. Demicco, Marc de Perrot, Dirk Strauss, Carol J. Swallow
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Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae: Joo Ho Lee, Keun-Yong Eom, Ji Hoon Phi, Chul-Kee Park, Seung Ki Kim, Byung-Kyu Cho, Tae Min Kim, Dae Seog Heo, Kyung Taek Hong, Jung Yoon Choi, Hyoung Jin Kang, Hee Young Shin, Seung Hong Choi, Soon Tae Lee, Sung Hye Park, Kyu-Chang Wang, Il Han Kim; Cancer Res Treat. 2021;53(4):983-990. Published online January 13, 2021; DOI: https://doi.org/10.4143/crt.2020.1052

Abstract PDF PubReader ePub

Purpose
We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.
Materials and Methods
Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.
Results
The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.
Conclusion
De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Citations

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Optimal treatment approach for intracranial germinoma: a systematic review and meta-analysis
Zhirui Zhou, Jiabing Liu, Qi Yue, Lingxiao Chen, Xiwei Zhang, Xin Lin, Lin Zheng, Enmin Wang, Yang Wang, Ying Mao
BMC Cancer.2025;[Epub] CrossRef
NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors
Eric Eunshik Kim, Chul-Kee Park, Seung-Ki Kim, Ji Hoon Phi, Sun Ha Paek, Jung Yoon Choi, Hyoung Jin Kang, Joo Ho Lee, Jae Kyung Won, Hongseok Yun, Sung-Hye Park
Acta Neuropathologica Communications.2024;[Epub] CrossRef
Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up
Masayuki Kanamori, Shunji Mugikura, Osamu Iizuka, Naoko Mori, Yoshiteru Shimoda, Ichiyo Shibahara, Rei Umezawa, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Kyoko Suzuki, Hidenori Endo
Journal of Neuro-Oncology.2024; 170(1): 173. CrossRef
Excluding prepontine cistern from whole ventricle radiotherapy target volume in localized germinoma
Hyejo Ryu, Joo Ho Lee
Radiation Oncology Journal.2023; 41(1): 48. CrossRef
Intracranial Germinomas: Diagnosis, Pathogenesis, Clinical Presentation, and Management
Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore
Current Oncology Reports.2023; 25(7): 765. CrossRef
Proton therapy for pediatric diencephalic tumors
Adam J. Grippin, Susan L. McGovern
Frontiers in Oncology.2023;[Epub] CrossRef
Intracranial Germinoma—Association between Delayed Diagnosis, Altered Clinical Manifestations, and Prognosis
Iwona Jabłońska, Marcin Goławski, Elżbieta Nowicka, Katarzyna Drosik-Rutowicz, Anna Trybus, Rafał Tarnawski, Marcin Miszczyk
Cancers.2023; 15(10): 2789. CrossRef
Outcomes of intracranial germinoma—A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies
Kyung-Nam Koh, Ru Xin Wong, Dong-Eun Lee, Jung Woo Han, Hwa Kyung Byun, Hong In Yoon, Dong-Seok Kim, Chuhl Joo Lyu, Hyoung Jin Kang, Kyung Taek Hong, Joo Ho Lee, Il Han Kim, Ji Hoon Phi, Seung-Ki Kim, Tai-Tong Wong, Hsin-Lun Lee, I-Chun Lai, Yu-Mei Kang,
Neuro-Oncology.2022; 24(8): 1389. CrossRef
Photon versus proton whole ventricular radiotherapy for non‐germinomatous germ cell tumors: A report from the Children's Oncology Group
David Y. Mak, Zain Siddiqui, Zhihui Amy Liu, Hitesh Dama, Shannon M. MacDonald, Shengjie Wu, Erin S. Murphy, Matthew D. Hall, Victor Malkov, Arzu Onar‐Thomas, Sameera Ahmed, Girish Dhall, Derek S. Tsang
Pediatric Blood & Cancer.2022;[Epub] CrossRef
Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission
Takao Tsurubuchi, Kei Hara, Shingo Takano, Ai Muroi, Hiroko Fukushima, Masashi Mizumoto, Noriaki Sakamoto, Masahide Matsuda, Hiroyoshi Akutsu, Hideyuki Sakurai, Eiichi Ishikawa
World Neurosurgery.2022; 166: e325. CrossRef
Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma
Cristina Ilcus, Horatiu Silaghi, Carmen Emanuela Georgescu, Carmen Georgiu, Anca Ileana Ciurea, Simona Delia Nicoara, Cristina Alina Silaghi
Journal of Personalized Medicine.2021; 11(7): 661. CrossRef

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Central nervous system

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma: Changhee Park, Tae Min Kim, Jeong Mo Bae, Hongseok Yun, Jin Wook Kim, Seung Hong Choi, Soon-Tae Lee, Joo Ho Lee, Sung-Hye Park, Chul-Kee Park; Cancer Res Treat. 2021;53(2):389-398. Published online November 9, 2020; DOI: https://doi.org/10.4143/crt.2020.694

Abstract PDF Supplementary Material PubReader ePub

Purpose
The treatment outcomes and genomic profiles of diffuse midline glioma (DMG) in adult patients are rarely characterized. We performed a retrospective study to evaluate the clinicogenomic profiles of adult patients with brain DMG.
Materials and Methods
Patients aged ≥ 18 years diagnosed with brain DMG at Seoul National University Hospital were included. The clinicopathological parameters, treatment outcomes, survival, and genomic profiles using 82-gene targeted next-generation sequencing (NGS) were analyzed. The 6-month progression-free survival (PFS6) after radiotherapy and overall survival (OS) were evaluated.
Results
Thirty-three patients with H3-mutant brain DMG were identified. The median OS from diagnosis was 21.8 months (95% confidence interval [CI], 13.2 to not available [NA]) and involvement of the ponto-medullary area tended to have poor OS (median OS, 20.4 months [95% CI, 9.3 to NA] vs. 43.6 months [95% CI, 18.2 to NA]; p=0.07). Twenty-four patients (72.7%) received radiotherapy with or without temozolomide. The PFS6 rate was 83.3% (n=20). Patients without progression at 6 months showed significantly prolonged OS compared with those with progression at 6 months (median OS, 24.9 months [95% CI, 20.4 to NA] vs. 10.8 months [95% CI, 4.0 to NA]; p=0.02, respectively). Targeted NGS was performed in 13 patients with DMG, among whom nine (69.2%) harbored concurrent TP53 mutation. Two patients (DMG14 and DMG23) with PIK3CA^R38S+E545K and KRAS^G12A mutations received matched therapies. Patient DMG14 received sirolimus with a PFS of 8.4 months.
Conclusion
PFS6 after radiotherapy was associated with prolonged survival in adult patients with DMG. Genome-based matched therapy may be an encouraging approach for progressive adult patients with DMG.

Citations

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The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study
Vincenzo Di Nunno, Giuseppe Lombardi, Matteo Simonelli, Giuseppe Minniti, Angela Mastronuzzi, Valentina Di Ruscio, Martina Corrà, Marta Padovan, Marta Maccari, Mario Caccese, Giorgia Simonetti, Arianna Berlendis, Mariangela Farinotti, Bianca Pollo, Manila
Journal of Neuro-Oncology.2024; 167(1): 145. CrossRef
Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort
Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano
Acta Neuropathologica Communications.2024;[Epub] CrossRef
Genetic alteration analysis of non-pediatric diffuse midline glioma, H3 K27-altered
Hanbin Jang, Seyoung Moon, Hyun Jung Kwon, Sejoon Lee, Gheeyoung Choe, Kyu Sang Lee
Human Pathology.2024; 154: 105709. CrossRef
How to treat histone 3 altered gliomas: molecular landscape and therapeutic developments
Vincenzo Di Nunno, Enrico Franceschi, Lidia Gatto, Alicia Tosoni, Stefania Bartolini, Alba Ariela Brandes
Expert Review of Clinical Pharmacology.2023; 16(1): 17. CrossRef
Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis
Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, Sung-Hye Park
Scientific Reports.2023;[Epub] CrossRef
Radiotherapy and radio‐sensitization in H3K27M‐mutated diffuse midline gliomas
Chao Liu, Shuwen Kuang, Lei Wu, Quan Cheng, Xuan Gong, Jun Wu, Longbo Zhang
CNS Neuroscience & Therapeutics.2023; 29(7): 1721. CrossRef
Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy
A. Knight, P. Horsley, A. Yuile, J. Yim, M. Suh, V. Venketesha, M. Kastelan, H. Wheeler, M. Back
Journal of Neuro-Oncology.2023; 163(1): 281. CrossRef
Differences in survival prognosticators between children and adults with H3K27M‐mutant diffuse midline glioma
Xuan Gong, Shuwen Kuang, Dongfeng Deng, Jun Wu, Longbo Zhang, Chao Liu
CNS Neuroscience & Therapeutics.2023; 29(12): 3863. CrossRef
Adult spinal cord diffuse midline glioma, H3 K27-altered mimics symptoms of central nervous system infection: a case report
Xue Chen, Yi Li, Hui Bu, YueLi Zou, JunYing He, Hu Liu
Frontiers in Neurology.2023;[Epub] CrossRef
Clinicogenetic characteristics and the effect of radiation on the neural stem cell niche in subventricular zone-contacting glioblastoma
Jee Ye Kahng, Byung-Hee Kang, Soon-Tae Lee, Seung Hong Choi, Tae Min Kim, Chul-Kee Park, Jae-Kyung Won, Sung-Hye Park, Jaeman Son, Joo Ho Lee
Radiotherapy and Oncology.2023; 186: 109800. CrossRef
H3 K27M-Altered Diffuse Midline Gliomas: A Review
Karol Wiśniewski, Andrew Ghaly, Kate Drummond, Andreas Fahlstrӧm
Indian Journal of Neurosurgery.2023; 12(02): 104. CrossRef
Adult diffuse midline gliomas H3 K27-altered: review of a redefined entity
Carlos Axel López-Pérez, Xochitl Franco-Mojica, Ricardo Villanueva-Gaona, Alexandra Díaz-Alba, Marco Antonio Rodríguez-Florido, Victor Garcia Navarro
Journal of Neuro-Oncology.2022; 158(3): 369. CrossRef
H3K27M-Altered Diffuse Midline Gliomas Among Adult Patients: A Systematic Review of Clinical Features and Survival Analysis
Othman Bin-Alamer, Adrian E. Jimenez, Tej D. Azad, Chetan Bettegowda, Debraj Mukherjee
World Neurosurgery.2022; 165: e251. CrossRef
Molecular profile and clinical features of patients with gliomas using a broad targeted next generation‑sequencing panel
Ourania Romanidou, Paraskevi Apostolou, Kyriakos Kouvelakis, Kyriakos Tsangaras, Alexia Eliades, Achilleas Achilleos, Charalambos Loizides, Christos Lemesios, Marios Ioannides, Elena Kypri, George Koumbaris, Kyriaki Papadopoulou, Athanasios Papathanasiou,
Oncology Letters.2022;[Epub] CrossRef

8,564 View
229 Download
14 Web of Science
14 Crossref

Sarcopenia Predicts Prognosis in Patients with Newly Diagnosed Hepatocellular Carcinoma, Independent of Tumor Stage and Liver Function: Yeonjung Ha, Daejung Kim, Seungbong Han, Young Eun Chon, Yun Bin Lee, Mi Na Kim, Joo Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang; Cancer Res Treat. 2018;50(3):843-851. Published online September 4, 2017; DOI: https://doi.org/10.4143/crt.2017.232

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC).
Materials and Methods
Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias.
Results
Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m² for males and ≤ 43.0 cm/m² for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival.
Conclusion
The presence of sarcopenia at HCC diagnosis is independently associated with survival.

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Redefining the Positive Circumferential Resection Margin by Incorporating Preoperative Chemoradiotherapy Treatment Response in Locally Advanced Rectal Cancer: A Multicenter Validation Study: Joo Ho Lee, Eui Kyu Chie, Seung-Yong Jeong, Tae-You Kim, Dae Yong Kim, Tae Hyun Kim, Sun Young Kim, Ji Yeon Baek, Hee Jin Chang, Min Ju Kim, Sung Chan Park, Jae Hwan Oh, Sung Hwan Kim, Jong Hoon Lee, Doo Ho Choi, Hee Chul Park, Sung-Bum Kang, Jae-Sung Kim; Cancer Res Treat. 2018;50(2):506-517. Published online May 24, 2017; DOI: https://doi.org/10.4143/crt.2016.607

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Purpose
This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer.
Materials and Methods
Clinical data of 197 patientswith positive circumferentialresection margin defined as ≤ 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009were collected forthis multicenter validation study. All patients underwent median 50.4Gy radiationwith concurrentfluoropyrimidine based chemotherapy. Treatmentresponse was dichotomized to good response, including treatmentresponse of grade 2 or 3, and poor response, including grade 0 or 1.
Results
After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poorresponderswith involved margin hadworst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001).
Conclusion
Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤ 2 mm for poor responders.

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Tailored Strategy for Locally Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results From a Multicenter, Randomized, Open-Label, Phase II Trial
Philippe Rouanet, Eric Rullier, Bernard Lelong, Philippe Maingon, Jean-Jacques Tuech, Denis Pezet, Florence Castan, Stephanie Nougaret
Diseases of the Colon & Rectum.2022; 65(8): 986. CrossRef
Colorectal Cancer Surgery Quality in Manitoba: A Population-Based Descriptive Analysis
Iresha Ratnayake, Jason Park, Natalie Biswanger, Allison Feely, Grace Musto, Kathleen Decker
Current Oncology.2021; 28(3): 2239. CrossRef

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Influence of Comorbidities on the Efficacy of Radiotherapy with or without Chemotherapy in Elderly Stage III Non-small Cell Lung Cancer Patients: Joo Ho Lee, Hong-Gyun Wu, Hak Jae Kim, Dong-Wan Kim, Se-Hoon Lee, Tae Min Kim, Young Whan Kim, Dae Seog Heo; Cancer Res Treat. 2012;44(4):242-250. Published online December 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.4.242

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PURPOSE
The current study was conducted in order to evaluate the clinical outcome of radical radiotherapy (RT) with or without chemotherapy for elderly patients with stage III non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Between 1990 and 2010, 125 patients, aged 70 years or more, received radical RT with or without chemotherapy for treatment of stage III NSCLC. We reviewed the patients' prognostic factors, including comorbidities. Comorbidity status was evaluated using a simplified comorbidity score (SCS). Of the patients reviewed, 82 received radical RT alone, whereas the other 43 patients underwent chemoradiotherapy (CRT). A platinum-based chemotherapy regimen was most commonly used (42/43).
RESULTS
The two-year overall-survival (OS) and progression-free survival (PFS) rates were 32.2% and 21.8%, respectively. SCS was the independent prognostic factor for OS. In the frail elderly subgroup with a SCS of > or =10, CRT demonstrated a significant difference in PFS, but not in OS. In contrast, OS and PFS following CRT were significantly superior to RT in the fit elderly subgroup with a SCS of <10. The incidence of severe pulmonary toxicities in the frail elderly subgroup was significantly higher than that in the fit elderly subgroup.
CONCLUSION
Multiple comorbidities evaluated according to the SCS are related to poor OS in elderly patients with stage III NSCLC. CRT improved clinical outcome when compared to RT in the fit elderly subgroup, however, the gain from this treatment was negated in the frail elderly subgroup with multiple comorbidities. Therefore, evaluation of comorbidity is necessary in order to determine whether chemotherapy should be combined with RT in elderly patients with stage III NSCLC.

Citations

Citations to this article as recorded by

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Considerations of Medical Preparedness to Assess and Treat Various Populations During a Radiation Public Health Emergency
Thomas A. Winters, David R. Cassatt, Jenna R. Harrison-Peters, Brynn A. Hollingsworth, Carmen I. Rios, Merriline M. Satyamitra, Lanyn P. Taliaferro, Andrea L. DiCarlo
Radiation Research.2023;[Epub] CrossRef
Independent Predictors for Hospitalization-Associated Radiation therapy Interruptions
Adam Hubler, Daniel V. Wakefield, Lydia Makepeace, Matt Carnell, Ankur M. Sharma, Bo Jiang, Austin P. Dove, Wesley B. Garner, Drucilla Edmonston, John G. Little, Esra Ozdenerol, Ryan B. Hanson, Michelle Y. Martin, Arash Shaban-Nejad, Maria Pisu, David L.
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Cancer incidence and survival analysis among elderly people in Bingol province
Burak METE, Vedat SÖYİLER, Bilal BUZGAN
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Comorbidity Assessment Using Charlson Comorbidity Index and Simplified Comorbidity Score and Its Association With Clinical Outcomes During First-Line Chemotherapy for Lung Cancer
Navneet Singh, Potsangbam Sarat Singh, Ashutosh N. Aggarwal, Digambar Behera
Clinical Lung Cancer.2016; 17(3): 205. CrossRef
A review of the management of elderly patients with non-small-cell lung cancer
R. Blanco, I. Maestu, M.G. de la Torre, A. Cassinello, I. Nuñez
Annals of Oncology.2015; 26(3): 451. CrossRef
Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC
Olfred Hansen, Tine Schytte, Morten Nielsen, Carsten Brink
Acta Oncologica.2015; 54(3): 333. CrossRef
How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non–Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial
Hans H. Strøm, Roy M. Bremnes, Stein H. Sundstrøm, Nina Helbekkmo, Ulf Aasebø
Clinical Lung Cancer.2015; 16(3): 183. CrossRef
Therapie des Analkarzinoms
I. Fraunholz, G. Woeste, R.-D. Hofheinz
Der Onkologe.2014; 20(2): 173. CrossRef
Changes in non-surgical management of stage III non-small cell lung cancer at a single institution between 2003 and 2010
Ellen J. F. van Reij, Max Dahele, Peter M. van de Ven, Patricia F. de Haan, Wilko F. A. R. Verbakel, Egbert F. Smit, Ben J. Slotman, Suresh Senan
Acta Oncologica.2014; 53(3): 316. CrossRef
The Efficacy of External Beam Radiotherapy for Airway Obstruction in Lung Cancer Patients
Jeong Won Lee, Jong Hoon Lee, Hoon-Kyo Kim, Byoung Yong Shim, Ho Jung An, Sung Hwan Kim
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Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel or cisplatin/etoposide in stage III non–small cell lung cancer
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Expression of CD44 Standard, Variant 6 and Relationship to the Lymph Node Metastasis in Gastric Adenocarcinoma: Joo Ho Lee, Hang Jong Yu, Byung Jo Suh, Mee Ju, Hae Kyung Lee, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(4):665-673.

Abstract PDF: PURPOSE
The transmembrane glycoprotein CD44 exists in a variety of isoforms generated by alternative splicing of the pre-mRNA. We studied the role of CD44-standard (CD44s) and CD44-variant6 (CD44v6) in gastric adenocarcinoma.
MATERIALS AND METHODS
Immunohistochemical staining was performed in 101 patients with gastric adenocarcinoma who underwent radical gastrectomy at KGCC, Seoul Paik Hospital. The relationship of CD44s, CD44v6 expressions to the clinicopathologic parameters, p53 and Ki-67 were evaluated.
RESULTS
CD44s and CD44-v6 expressions were found in 56.4% and 48.5%, respectively. CD44s expression was significantly correlated with lymph node metastasis, lymphatic invasion, and Borr mann type. CD44v6 expression was significantly correlated with sex, lymph node metastasis, lymphatic invasion, and perineural invasion and had a tendency toward p53 expression. In inte stinal type adenocarcinoma, CD44s expression had correlations with lymph node metastasis and CD44v6 had correlations with lymph node metastasis, lymphatic invasion. However, in diffuse type adenocarcinoma, CD44s and CD44v6 expressions had correlations with only Borrmann type. In multivariate analysis, lymph node metastasis was the most significant risk factor for CD44s and CD44v6 expressions in total cases and intestinal type adenocarcinoma.
CONCLUSION
These data suggest that expression of CD44 v6 may play an important role in the regulation of lymph node metastasis in intestinal type adenocarcinoma of stomach.

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Expression of p53, p21/WAF1, bcl-2 and Loss of Heterozygosity for the Study of Apoptosis in Gastric Carcinoma: Hang Jong Yu, Joo Ho Lee, Woo Ho Kim, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(3):447-457.

Abstract PDF: PURPOSE
The purpose of this study was to correlate the immunohistdegrees Chemical expressions of p53, p21 and bcl-2, with their loss of heterozygosity (LOH) and clinical significance.
MATERIALS AND METHODS
Paraffin-embedded tissue sections from 30 patients with gastric car cinomas were examined for immunohistdegrees Chemical staining and LOH study. Primary antibodies used in immunohistdegrees Chemical staining were mouse mondegrees Clonal antibody to human p53, p21/ WAF1 and bcl-2. For PCR-LOH assays, D6S271, D6S105, D18S386, TP53, D17S796, and D17S786 microsatellite markers were used.
RESULTS
The expression rates of p53, p21 and bcl-2 were 76.7%, 80% and 3.3%, respectively. The expression of p21 was correlated with lymph node metastasis. LOH were found in 20.8% at D6S271, 42.3% at D6S105, 31.6% at D18S386, 39.1% at TP53, 40.9% at D17S796, and 50.0% at D17S786. No correlation was found between the immunohistdegrees Chemical expression and the LOH in these gene sites.
CONCLUSION
p53 and p21 were detected in high rate, whereas bcl-2 expression rate was very low in gastric adendegrees Carcinoma. Of them, overexpression of p21 was correlated with the tumor progression. High incidence rate of LOH may play an important role in gastric carcinogenesis. These findings suggest that the effects on apoptosis and cell cycle by p53 and p21 were important in development and progression of gastric cancer.

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Clinicopathologic Characteristics and p53, c-erbB2, nm23 Protein Expression in Gastric Remnant Cancer: Joo Ho Lee, Yoe Kyu Youn, Woo Ho Kim, Hang Jong Yu, Byoung Jo Suh, Han Kwang Yang, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(1):26-37.

Abstract PDF: PURPOSE
The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer.
MATERIALS AND METHODS
We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23.
RESULTS
The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC.
CONCLUSION
Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.

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Clinicopathological Analysis of Female Gastric Cancer - Comparative study according to the sex fo the patients: Jin Pok Kim, Hang Jong Yu, Young Chul Kim, Soo Jin Kim, Joo Ho Lee, Han Kwang Yang; J Korean Cancer Assoc. 1998;30(5):879-885.

Abstract PDF: PURPOSE
The purpose of this study is to evaluate the differences of the clinicopathological features and survival rates in gastric cancer according to the sex of the patients.
MATERIALS AND METHODS
We reviewed 5,784 cases of gastric cancer patients who underwent laparotomy at the Department of Surgery, Seoul National University Hospital fmm Jan. 1986 to Dec. 1995. We have analyzed clinicopathologic features including tumor location, Bonmann type, depth of invasicm, lymph node metastasis, distant metastasis, TNM stage, histologic differentiation and survival rates according to the sex of the patients.
RESULTS
The mean age of female patients was 52.4 years, which is lower than that of male, 54.8 years. There were no differences in tumor location, Borrmann type, depth of invasion, lymph node metastasis, distant metastasis, TNM stage of tumor between male and female. But there were some differences in histologic differentiation; well- and moderately differentiated cancers were more common in male and signet-ring cell cancers were more common in female. Female shows slightly better prognosis than male. But the prognosis of young female was poorer than that of young male.
CONCLUSION
In gastric cancer patients, differences in histologic differentiation and more aggressive nature of the signet-ring cell cancer in female may affect the survival differences according to the sex.

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Clinicopathologic Features of Multiple Synchronous Gastric Cancer: Jin Bok Kim, Min Kyu Choi, Joo Ho Lee, Seung Ik Ahn, Soo Jin Kim, Hang Jong Yu, Han Kwang Yang; J Korean Cancer Assoc. 1998;30(4):652-659.

Abstract PDF: PURPOSE
With recent advances of diagnostic methods and precise histopathologic examination, the incidence of synchronous multiple gastric cancer has increased. The purpose of this study was to evaluate the clinicopathologic features of patients with synchronous multiple gastric cancer.
MATERIALS AND METHODS
We reviewed the clinicopathologic features of 189 patients with synchronous multiple gastric cancer out of 8,101 patients who underwent gastric resections for gastric cancers during 20 years from January 1977 to December 1996 at the Department of Surgery, Seoul National University Hospital, and compared them with single gastric cancer patients. The clinicopathologic features evaluated were age, sex, diagnostic method and accuracy, location of lesions, tumor size, histologic differentiation, Lauren classification, macroscopic classification, depth of invasion, lymph node metastasis, TNM stage, and type of operation and prognosis.
RESULTS
The overall incidence of multiple synchronous gastric cancer was 2.33%. The mean age was 57.2 years old (27~84) and peak incidence was sixth decade. Male was predominant, that the sex ratio was 3.9: 1. Multiple gastric cancer was more frequent in old age, male and early gastric cancer patients. The number of lesions ranged from 2 to 5. In most cases, the lesions were located in lower two-thirds of the stomach. However, in 13 cases, lesions were located in both upper one-third and lower one-third. Only 33.3% of multiple cancer was diagnosed preoperatively, with the diagnostic accuracy of GFS was 30.0% and that of UGIS 26.1%. The most frequently missed lesions at preoperative examination were located in upper third of stomach, posterior wall of middle third and anterior wall of lower third of stomach. The most common macroscopic type was Borrmann type III (54.5%) in advanced lesions and type IIc (47.0%) in early lesions. Regarding the histologic differentiation, 58.7% of the cases were of the same differentiation and the cases composed of well differentiated adenocarcinomas were most common. According to the Laurens classification, 66.7% of lesions were intestinal type. As to the progression of the lesions, all lesions were early cancers in 75 cases, advanced cancers in 39 cases and advanced cancers were coexist with early cancers in 75 cases. Lymph node metastasis was less frequent than in single gastric cancer. Total gastrectomy was performed more frequently in multiple cancer patients than in single gastric cancer patients. The 5-year survival rate of patients with multiple gastric cancer was 70.2%, which was not significantly different from that of patients with single gastric cancer.
CONCLUSIONS
Surgeons must keep in mind the possibility of multiple gastric lesions. More careful preoperative and intraoperative examination is mandatory to detect the possible accessory lesions, and postoperative periodic follow-up is necessary to detect any missed lesions, especially in the old age, male and early gastric cancer patients.

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Pancreaticoduodenectomy for gastric Cancer: Jae Cheol Byun, Joo Ho Lee, Hang Jong Yu, Soo Jin Kim, Kuhn Uk Lee, Jin Pok Kim; J Korean Cancer Assoc. 1998;30(1):72-79.

Abstract PDF: PURPOSE
We purpose of this retrospective study is to evaluate the role of pancreaticoduadenectomy (PD) in gastric cancer which invades neighboring organs.
MATERIALS AND METHODS
We analysed 28 patients with locally advanced gastric cancer which invaded to pancreas and/or duodenum who received surgical resection from Jan. 1989 to Dec. 1996. Patients were divided into two groups: Group A (n=12) who received PD and Group B (n=16) who received gastrectomy only. Indication of PD in group A is locally advanced gastric cancer which invaded to pancreas and/or duodenum but had no evidence of widespread nodal involvement, extended hepatic metastasis, or peritoneal dissemination.
RESULTS
The operation time, amount of blood loss during operation, and postoperative hospital stay were greater in group A than in group B. Operative mortality was found in 1 case in group B but none in group A. Postoperative complications were similar in both groups. Four patients had liver metastases in both group during follow up period, whereas 2 and 4 patients had disseminated peritoneal seeding in group A and B, respectively. When survival rates were compared, Group A shows better survival than Group B (p= 0.043).
CONCLUSION
These results suggest that PD is a rational and safe method for treatment of gastric cancer infiltrating into pancreatic head and/or duodenum.

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Clinicopathologic Features and Prognosis of Gastric Remnant Cancer after Partial Gastrectomy for Benign and Malignant Gastric Lesions: Joo Ho Lee, Soo Jin Kim, Hang Jong Yu, Han Kwang Yang, Jin Pok Kim; J Korean Cancer Assoc. 1997;29(6):1076-1084.

Abstract PDF: PURPOSE
Despite the decreasing incidence of primary gastric cancer, the incidence of gastric cancer in the remnant stomach has been increasing. This study evaluated the clinicopathologic features and prognosis of gastric cancer in the remnant stomach.
METHODS
AND MATERIALS: The clinicopathologic features and prognosis of 31 cases of gastric cancers in the remnant stomach were evaluated retrospectively. 19 patients among them underwent partial gastrectomy for benign gastroduodenal disease (Group I), while 12 patients for malignant disease (Group II) which were detected at least 5 years after initial surgery and the clinicopathologic features and survival curves of two groups were compared. The clinicopathologic features evaluated included age, sex, interval between operations, type of operation, location of tumor, tumor size, Borrmann type, depth of invasion, lymph node metastasis, distant metastasis, TNM stage, histologic differentiation and Lauren classification.
RESULTS
The median age was 59 years, 28 patients (90.3%) were male and median time interval between operations was 15 years. Group I gastric remnant cancers were detected late after initial gastrectomy and have a significant tendency toward lymph node metastasis. Resection was carried out in 25 patients (81.0%) in which 22 patient (71.0%) underwent resections with curative intent. The overall 5 year survival rate was 45.5% and no significant difference was observed between the survival curves for patients with group I and group II. Depth of invasion, lymph node metastasis, distant metastasis, tumor size and curability of operation have prognostic significance in univariate analysis and multivariate analysis performed with above 5 factors has revealed that depth of invasion is the only independent prognostic factor.
CONCLUSIONS
Both groups are similar in survival rate and clinicopathologic characteristics except time interval between operations and lymph node metastasis. Early detection by periodic endoscopic follow-up and radical resection is a reasonable policy as a treatment of gastric remnant cancer.

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Clinicopathologic Features, Survival Rates and Prognostic Factors of Gastric Cancer in Young Age Group under 30 Years of Age: Dong Hyeon Jo, Soo Jin Kim, Joo Ho Lee, Hang Jong Yu, Han Kwang Yang, Jin Pok Kim; J Korean Cancer Assoc. 1997;29(6):1069-1075.

Abstract PDF: PURPOSE
The purpose of this report is to clarify the clinicopathologic features, survival rates and prognostic factors of gastric cancers in young age group.
MATERIALS AND METHODS
We reviewed 133 patients with gastric cancer under 30 years of age who underwent surgery from January 1986 to December 1995 at the Department of Surgery, Seoul National University Hospital. We have analyzed the sex, age, Borrmann type, histologic differentiation, Lauren classification, depth of invasion, lymph node metastasis, distant metastasis, location of tumor, size of tumor, curability and extent of operation. The 5 year survival rates and prognostic factors were also evaluated. The Kaplan-Meier method, Log-Rank test and Cox hazards proportional mode were used for the statistical analyses.
RESULTS
The overall 5 year survival rate was 55.3% in all 133 patients in contrast to 67.4% in 108 patients who underwent gastric resections. Significant prognostic factors were Borrmann type, histologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, location of tumor, size of tumor, curability and extent of operation in univariate analysis. Lymph node metastasis was the only significant independent prognostic factor in multivariate analysis.
CONCLUSION
In our study, the 5 year survival rate in young age group was comparable to that of prevalent age group. This is attributed to the relatively higher incidence of early gastric cancer and more frequent curative resections in this young age group.

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