Cancer Research and Treatment

Original Articles

Role and Effectiveness of Hypofractionated Proton Beam Therapy and Combinations with Systemic Chemotherapy in Inoperable Extrahepatic Cholangiocarcinoma: Sung Uk Lee, Tae Hyun Kim, Sang Myung Woo, Jung Won Chun, Hyunjae Shin, Yu Ri Cho, Bo Hyun Kim, Young-Hwan Koh, Sang Soo Kim, Yang-Gun Suh, Sung Ho Moon, Woo Jin Lee; Received August 19, 2024 Accepted December 16, 2024 Published online December 17, 2024; DOI: https://doi.org/10.4143/crt.2024.805 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aims to assess the clinical outcomes of hypofractionated proton beam therapy (PBT) for extrahepatic cholangiocarcinoma (EHCC) and to investigate the optimal sequencing for combining PBT with chemotherapy.
Materials and Methods
We retrospectively analyzed 59 consecutive patients with inoperable EHCC treated with PBT. The median prescribed dose of PBT was 50 GyE (range, 45 to 66 GyE) in 10 fractions. The combination sequences of PBT and chemotherapy were categorized as ‘Pre-PBT chemo’ (chemotherapy before PBT), ‘Post-PBT chemo’ (chemotherapy after PBT), and ‘No pre-/post-PBT chemo’ (no chemotherapy before or after PBT). Overall survival (OS), progression-free survival (PFS), and local PFS were estimated using the Kaplan-Meier method.
Results
All patients completed the planned treatments without any interruptions, and ≥ grade 3 acute adverse events were noted in 1.6% of the cases. The 1-year and 2-year freedom from local progression (FFLP) rates were 86.1% and 66.4%, respectively, with a median time of FFLP of 30.9 months. The 1- and 2-year OS rates were 74.5% and 25.3%, respectively, with a median survival time of 16.7 months. For prognostic factor analysis, pre- or post-PBT chemo was associated with a significantly reduced hazard ratio of 0.473 (95% confidence interval, 0.233 to 0.959; p=0.038) in the multivariate analysis. The median OS times for the groups receiving no pre-/post-PBT chemo, pre-PBT chemo, and post-PBT chemo were 14.6, 18.2, and 21.8 months, respectively (p < 0.05 for each).
Conclusion
Hypofractionated PBT for inoperable EHCC has demonstrated promising FFLP and OS rates with a safe toxicity profile. The combination of PBT with chemotherapy shows potential to improve clinical outcomes.

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General

Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea: Sung Uk Lee, Kyungmi Yang, Sung Ho Moon, Yang-Gun Suh, Gyu Sang Yoo; Cancer Res Treat. 2021;53(4):935-943. Published online May 17, 2021; DOI: https://doi.org/10.4143/crt.2021.409

Abstract PDF Supplementary Material PubReader ePub

Purpose
Proton beam therapy (PBT) is a state-of-the-art technology employed in radiotherapy (RT) for cancer patients. This study characterized how PBT has been used in clinical practice in Korea.
Materials and Methods
Patients who received any type of RT between 2007 and 2019 were identified from the radiation oncology registry of the two PBT facilities operating in Korea (National Cancer Center and Samsung Medical Center). The chi-square test was used to identify patient- and treatment-related characteristics associated with the receipt of PBT.
Results
A total of 54,035 patients had been treated with some form of RT in the two institutions, of whom 5,398 received PBT (10.0%). The number of patients who receive PBT has gradually increased since PBT first started, from 162 patients in 2007 to 1,304 patients in 2019. Among all types of cancer, PBT use in liver cancer has been steadily increasing from 20% in 2008-2009 to 32% in 2018-2019. In contrast, that in prostate cancer has been continuously decreasing from 20% in 2008-2009 to < 10% in 2018-2019. Male sex, very young or old age, stage I-II disease, residency in non-capital areas, a definitive setting, a curative treatment aim, enrollment in a clinical trial, re-irradiation and insurance coverage were significantly associated with the receipt of PBT (all p < 0.05).
Conclusion
Since PBT started in Korea, the number of patients receiving PBT has increased to more than 1,000 per year and treatment indications have expanded. Liver cancer is the most common primary tumor among all PBT cases in Korea.

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Kristaps Paļskis, Erika Korobeinikova, Dace Bogorada-Saukuma, Anna Maria Camarda, Rebecca Taylor, Elena Benedetto, Edgars Mamis, Maija Radziņa, Andrejs Ērglis, Diana Adliene, Manjit Dosanjh, Maurizio Vretenar, Toms Torims
Health and Technology.2024; 14(5): 965. CrossRef
Proton Therapy in The Treatment of Head And Neck Cancers- Review
Kamila Bała, Yana Samovich, Karolina Dorobisz
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PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer
J. Isabelle Choi, Camille Hardy-Abeloos, Alicia Lozano, Alexandra Hanlon, Carlos Vargas, John H. Maduro, Julie Bradley, Birgitte Offersen, Bruce Haffty, Mark Pankuch, Richard Amos, Nalee Kim, Shannon M. MacDonald, Youlia Kirova, Robert W. Mutter
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Special Article

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea: Jii Bum Lee, Minkyu Jung, June Hyuk Kim, Bo Hyun Kim, Yeol Kim, Young Seok Kim, Byung Chang Kim, Jin Kim, Sung Ho Moon, Keon-Uk Park, Meerim Park, Hyeon Jin Park, Sung Hoon Sim, Hong Man Yoon, Soo Jung Lee, Eunyoung Lee, June Young Chun, Youn Kyung Chung, So-Youn Jung, Jinsoo Chung, Eun Sook Lee, Hyun Cheol Chung, Tak Yun, Sun Young Rha; Cancer Res Treat. 2021;53(2):323-329. Published online March 15, 2021; DOI: https://doi.org/10.4143/crt.2020.1256

Abstract PDF PubReader ePub

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

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Original Articles

Head and Neck Cancer

Recent Treatment Patterns of Oropharyngeal Cancer in Korea Based on the Expert Questionnaire Survey of the Korean Society for Head and Neck Oncology (KSHNO): Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Ji-hoon Kim, Woo-Jin Jeong, Inn-Chul Nam, Jin Ho Kim, Hee Kyung Ahn, Sang Hoon Chun, Hyun Jun Hong, Young-Hoon Joo, Young-Gyu Eun, Sung Ho Moon, Jeongshim Lee; Cancer Res Treat. 2021;53(4):1004-1014. Published online January 29, 2021; DOI: https://doi.org/10.4143/crt.2020.973

Abstract PDF Supplementary Material PubReader ePub

Purpose
The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.
Materials and Methods
Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.
Results
Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).
Conclusion
In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

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Controversies in Lung Cancer: Heterogeneity in Treatment Recommendations for Stage III NSCLC According to Disease Burden and Oncogenic Driver Alterations
Jeremy P Harris, Dylann K Fujimoto, Misako Nagasaka, Eric Ku, Garrett Harada, Hari Keshava, Ali Mahtabifard, Javier Longoria, Niral Patel, Steven Seyedin, Aaron Simon, Allen Chen
Clinical Lung Cancer.2022; 23(4): 333. CrossRef
Survey of radiation field and dose in human papillomavirus-positive oropharyngeal cancer: is de-escalation actually applied in clinical practice?
Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Sung Ho Moon, Jeongshim Lee, Young-Taek Oh, Dongryul Oh, Jin Ho Kim, Jun Won Kim
Radiation Oncology Journal.2021; 39(3): 174. CrossRef

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Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer: Joohae Kim, Hyo Jae Kang, Sung Ho Moon, Jong Mog Lee, Hyae Young Kim, Geon-Kook Lee, Jin Soo Lee, Bin Hwangbo; Cancer Res Treat. 2019;51(4):1488-1499. Published online March 15, 2019; DOI: https://doi.org/10.4143/crt.2019.031

Abstract PDF Supplementary Material PubReader ePub

Purpose
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used for the diagnosis and staging of lung cancer. However, evidence of its usefulness for re-biopsy in treated lung cancer, especially according to the previous treatment, is limited. We evaluated the role of EBUS-TBNA for re-biopsy and its diagnostic values in patients with different treatment histories.
Materials and Methods
We reviewed the medical records of patients who underwent EBUS-TBNA for re-biopsy of suspicious recurrent or progressive lesions between January 2006 and December 2016 at the National Cancer Center in South Korea. Patients were categorized into three groups based on the previous treatment modalities: surgery, radiation, and palliation.
Results
Among the 367 patients (surgery, n=192; radiation, n=40; palliation, n=135) who underwent EBUS-TBNA for re-biopsy, the overall sensitivity, negative predictive value (NPV), and diagnostic accuracy of EBUS-TBNA in detecting malignancy were 95.6%, 82.7%, and 96.3%, respectively. The sensitivity was lower in the radiation group (83.3%) when compared with the surgery (95.7%, p=0.042) and palliation (97.7%, p=0.012) groups. The NPV was lower in the palliation group (50.0%) than in the surgery group (88.5%, p=0.042). The sample adequacy of EBUS-TBNA specimens was lower in the radiation group (80.3%) than in the surgery (95.4%, p < 0.001) or palliation (97.8%, p < 0.001) groups. EGFR mutation analysis was feasible in 94.6% of the 92 cases, in which mutation analysis was requested. There were no major complications. Minor complications were reported in 12 patients (3.3%).
Conclusion
EBUS-TBNA showed high diagnostic values and high suitability for EGFR mutation analysis with regard to re-biopsy in patients with previously treated lung cancer. The sensitivity was lower in the radiation group and NPV was lower in the palliation group. The complication rate was low.

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Repeat biopsy versus initial biopsy in terms of complication risk factors and clinical outcomes for patients with non-small cell lung cancer: a comparative study of 113 CT-guided needle biopsy of lung lesions
Yangyang Wang, Yongyuan Zhang, Nana Ren, Fangting Li, Lin Lu, Xin Zhao, Zhigang Zhou, Mengyu Gao, Meng Wang
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Artificial Intelligence Algorithm Can Predict Lymph Node Malignancy from Endobronchial Ultrasound Transbronchial Needle Aspiration Images for Non-Small Cell Lung Cancer
Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
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F. Wallyn, C. Fournier, V. Jounieaux, D. Basille
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Ying-Yi Chen, Ying-Shian Chen, Tsai-Wang Huang
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Wen-Chien Cheng, Yi-Cheng Shen, Chieh-Lung Chen, Wei-Chih Liao, Hung-Jen Chen, Te-Chun Hsia, Chia-Hung Chen, Chih-Yen Tu
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Maja Guberina, Kaid Darwiche, Hubertus Hautzel, Till Ploenes, Christoph Pöttgen, Nika Guberina, Ken Herrmann, Lale Umutlu, Axel Wetter, Dirk Theegarten, Clemens Aigner, Wilfried Ernst Erich Eberhardt, Martin Schuler, Rüdiger Karpf-Wissel, Martin Stuschke
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WITHDRAWN:The Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer: Joohae Kim, Hyo Jae Kang, Sung Ho Moon, Jong Mog Lee, Hyae Young Kim, Geon-Kook Lee, Jin Soo Lee, Bin Hwangbo; Received April 16, 2018 Accepted August 21, 2018 Published online September 3, 2018; DOI: https://doi.org/10.4143/crt.2018.222 [Accepted]

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The Effect of Hospital Case Volume on Clinical Outcomes in Patients with Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Analysis (KROG-1106): Boram Ha, Kwan Ho Cho, Sung Ho Moon, Chang-Geol Lee, Ki Chang Keum, Yeon-Sil Kim, Hong-Gyun Wu, Jin Ho Kim, Yong Chan Ahn, Dongryul Oh, Jae Myoung Noh, Jong Hoon Lee, Sung Hwan Kim, Won Taek Kim, Young-Taek Oh, Min Kyu Kang, Jin Hee Kim, Ji-Yoon Kim, Moon-June Cho, Chul Seoung Kay, Jin Hwa Choi; Cancer Res Treat. 2019;51(1):12-23. Published online February 5, 2018; DOI: https://doi.org/10.4143/crt.2017.273

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC).
Materials and Methods
Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS).
Results
At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170).
Conclusion
A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.

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Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single Institute in Korea: Tae Wan Kim, Euncheol Choi, Jeonghoon Park, Dong-ho Shin, Su Kyung Jung, Susie Seok, Kwan Ho Cho, Joo-Young Kim, Dae Yong Kim, Tae Hyun Kim, Yang Kwon Suh, Yeon Joo Kim, Sung Ho Moon; Cancer Res Treat. 2018;50(2):335-344. Published online April 19, 2017; DOI: https://doi.org/10.4143/crt.2017.070

Abstract PDF PubReader ePub

Purpose
This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI).
Materials and Methods
Twenty-four treatment-naïve patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software.
Results
The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565±0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively.
Conclusion
The local controlrate and complication profile after PBT in patientswith choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI.

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Preliminary Dosimetric Study of Proton Minibeam Radiation Therapy for the Treatment of Choroidal Melanoma
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Comparison of the Clinical Outcomes of Patients with Squamous Cell Carcinoma of the Tonsil Receiving Postoperative Ipsilateral Versus Bilateral Neck Radiotherapy: A Propensity Score Matching Analysis (KROG 11-07): Youngkyong Kim, Kwan Ho Cho, Sung Ho Moon, Chang Geol Lee, Ki Chang Keum, Sang-wook Lee, Yong Chan Ahn, Dongryul Oh, Yeon-Sil Kim, Yong Kyun Won, Hong-Gyun Wu, J. Hun Hah, Young-Taek Oh; Cancer Res Treat. 2017;49(4):1097-1105. Published online February 9, 2017; DOI: https://doi.org/10.4143/crt.2016.425

Abstract PDF PubReader ePub

Purpose
The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively.
Materials and Methods
Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patientswere identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test.
Results
The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groupswere similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively.
Conclusion
INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.

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Proton pencil beam scanning radiotherapy in the postoperative treatment of p16 positive squamous cell tonsillar cancer – evaluation of toxicity and effectivity
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Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil
Niema B. Razavian, Ralph B. D’Agostino, Cole R. Steber, Corbin A. Helis, Ryan T. Hughes
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Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status: Youngjoo Lee, Ji-Youn Han, Sung Ho Moon, Byung-Ho Nam, Kun Young Lim, Geon Kook Lee, Heung Tae Kim, Tak Yun, Hye Jin An, Jin Soo Lee; Cancer Res Treat. 2017;49(4):981-989. Published online January 6, 2017; DOI: https://doi.org/10.4143/crt.2016.522

Abstract PDF Supplementary Material PubReader ePub

Purpose
Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status.
Materials and Methods
Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D).
Results
Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities.
Conclusion
Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.

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Terufumi Kato, Ignacio Casarini, Manuel Cobo, Corinne Faivre-Finn, Fiona Hegi-Johnson, Shun Lu, Mustafa Özgüroğlu, Suresh S. Ramalingam
Lung Cancer.2024; 187: 107414. CrossRef
The ASCENT Trial: a phase 2 study of induction and consolidation afatinib and chemoradiation with or without surgery in stage III EGFR-mutant NSCLC
Allison E B Chang, Andrew J Piper-Vallillo, Raymond H Mak, Michael Lanuti, Alona Muzikansky, Julia Rotow, Pasi A Jänne, Mari Mino-Kenudson, Scott Swanson, Cameron D Wright, David Kozono, Paul Marcoux, Zofia Piotrowska, Lecia V Sequist, Henning Willers
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Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario
Valeria Fuorivia, Ilaria Attili, Carla Corvaja, Riccardo Asnaghi, Ambra Carnevale Schianca, Pamela Trillo Aliaga, Ester Del Signore, Gianluca Spitaleri, Antonio Passaro, Filippo de Marinis
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Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer
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Jerold Loh, Jia Li Low, Manavi Sachdeva, Peter QJ Low, Rachel Su Jen Wong, Yiqing Huang, Puey Ling Chia, Ross A Soo
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Aruz Mesci, Theodoros Tsakiridis, Anand Swaminath
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Choi Eunsook, Park Sunhee
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Miguel J Sotelo, José Luis García, Cesar Torres-Mattos, Héctor Milián, Carlos Carracedo, María Ángeles González-Ruiz, Xabier Mielgo-Rubio, Juan Carlos Trujillo-Reyes, Felipe Couñago
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Can Wu, Chunlu Wang, Lu Sun, Keming Xu, Wenying Zhong
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Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea: Sanghyuk Song, Ji Hyun Chang, Hak Jae Kim, Yeon Sil Kim, Jin Hee Kim, Yong Chan Ahn, Jae-Sung Kim, Si Yeol Song, Sung Ho Moon, Moon June Cho, Seon Min Youn; Cancer Res Treat. 2017;49(3):688-694. Published online October 31, 2016; DOI: https://doi.org/10.4143/crt.2016.219

Abstract PDF Supplementary Material PubReader ePub

Purpose
Stereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea.
Materials and Methods
We conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants’ opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey.
Results
SABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule.
Conclusion
The results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

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Erratum

ERRATUM: Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy: Min Kyu Kang, Dongryul Oh, Kwan Ho Cho, Sung Ho Moon, Hong-Gyun Wu, Dae-Seog Heo, Yong Chan Ahn, Keunchil Park, Hyo Jung Park, Jun Su Park, Ki Chang Keum, Jihye Cha, Jun Won Kim, Yeon-Sil Kim, Jin Hyoung Kang, Young-Taek Oh, Ji-Yoon Kim, Sung Hwan Kim, Jin-Hee Kim, Chang Geol Lee; Cancer Res Treat. 2016;48(1):425-425. Published online January 10, 2016; DOI: https://doi.org/10.4143/crt.2014.141.2; Corrects: Cancer Res Treat 2015;47(4):871

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Original Articles

The Role of Neoadjuvant Chemotherapy in the Treatment of Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Study (KROG 11-06) Using Propensity Score Matching Analysis: Jin Ho Song, Hong-Gyun Wu, Bhum Suk Keam, Jeong Hun Hah, Yong Chan Ahn, Dongryul Oh, Jae Myoung Noh, Hyo Jung Park, Chang Geol Lee, Ki Chang Keum, Jihye Cha, Kwan Ho Cho, Sung Ho Moon, Ji-Yoon Kim, Woong-Ki Chung, Young Taek Oh, Won Taek Kim, Moon-June Cho, Chul Seung Kay, Yeon-Sil Kim; Cancer Res Treat. 2016;48(3):917-927. Published online December 28, 2015; DOI: https://doi.org/10.4143/crt.2015.265

Abstract PDF PubReader ePub

Purpose
We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). Materials and Methods A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed.
Results
After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). Conclusion This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

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H. M. Li, P. Li, Y. J. Qian, X. Wu, L. Xie, F. Wang, H. Zhang, L. Liu
BMC Cancer.2016;[Epub] CrossRef

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Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization: Jin Ho Kim, Sung Ho Moon, Mina No, Jae Jin Kim, Eun Jung Choi, Bong Jun Cho, Jae Sung Kim, Il Han Kim, In Ah Kim; Cancer Res Treat. 2016;48(3):1130-1140. Published online November 17, 2015; DOI: https://doi.org/10.4143/crt.2015.206

Abstract PDF Supplementary Material PubReader ePub

Purpose
Histone deacetylase (HDAC) inhibitors radiosensitize tumor cells. To elucidate mechanisms underlying radiosensitization by HDAC inhibition, understanding of differential contributions of HDAC isotypes is needed. The aim of this study was to investigate involvement of known HDAC isotypes in modulation of cellular radiosensitivity. Materials and Methods Because pharmacologic HDAC inhibitors lack isotype-specificity, RNA interference against 11 HDAC isotypes was used to inhibit HDAC in an isotype-specific manner. Radiation cell survival was evaluated using a clonogenic assay in SQ20B cells transfected with small interfering RNA specifically targeting HDAC isotypes. Immunocytochemistry was performed for detection of γH2AX foci. Protein expression was measured using Western blotting.
Results
Among 11 HDAC isotypes tested, specific inhibition of 7 isotypes (HDAC1, HDAC3, HDAC4, HDAC6, HDAC7, HDAC10, and HDAC11) enhanced radiation lethality in SQ20B cells. Radiosensitization by inhibition of these HDAC isotypes was accompanied by delay of DNA double strand break repair. Radiosensitivity of SQ20B cells was not altered by selective inhibition of the remaining four isotypes (HDAC2, HDAC5, HDAC8, and HDAC9). Inhibition of HDAC isotypes resulted in downregulation of various proteins involved in pro-survival and DNA damage repair pathways. Conclusion Isotype-specificity exists in HDAC inhibition-induced radiosensitization. Different HDAC isotypes are differentially involved in modulation of cellular radiosensitivity.

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Histone Deacetylase 6 (HDAC6) in Ciliopathies: Emerging Insights and Therapeutic Implications
Zhiyi Wang, Xiaofan Zhu, Zhenzhou Huang, Kaidi Ren, Jie Ran, Yang Yang
Advanced Science.2025;[Epub] CrossRef
Effects of a novel HDAC6-selective inhibitor’s radiosensitization on cancer cells
Huixiao Hu, Qi Wang, Yuni Zhang, Shuhua Yang, Aihua Shen, Junfang Yan, Denggao Zhao, Burong Hu
Molecular Biology Reports.2024;[Epub] CrossRef
HDAC11: A novel target for improved cancer therapy
Yan Liu, Xuechao Tong, Weina Hu, Da Chen
Biomedicine & Pharmacotherapy.2023; 166: 115418. CrossRef
Histone deacetylase 10, a potential epigenetic target for therapy
Fajuan Cheng, Bin Zheng, Jianwei Wang, Guiting Zhao, Zhongshun Yao, Zhihong Niu, Wei He
Bioscience Reports.2021;[Epub] CrossRef
Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
Hoon Sik Choi, Jin Hyun Kim, Si Jung Jang, Jeong Won Yun, Ki Mun Kang, Hojin Jeong, In Bong Ha, Bae Kwon Jeong
Cancer Research and Treatment.2021; 53(3): 685. CrossRef
HDAC11: a rising star in epigenetics
Shan-Shan Liu, Fei Wu, Yue-Mei Jin, Wei- Qin Chang, Tian-Min Xu
Biomedicine & Pharmacotherapy.2020; 131: 110607. CrossRef
Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro
Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Cancer Research and Treatment.2019; 51(2): 696. CrossRef
Molecular imaging HDACs class IIa expression-activity and pharmacologic inhibition in intracerebral glioma models in rats using PET/CT/(MRI) with [18F]TFAHA
Maxwell T. Laws, Robin E. Bonomi, Swatabdi Kamal, David J. Gelovani, Jeremy Llaniguez, Shreya Potukutchi, Xin Lu, Thomas Mangner, Juri G. Gelovani
Scientific Reports.2019;[Epub] CrossRef
Mechanism of the Antitumor and Radiosensitizing Effects of a Manganese Porphyrin, MnHex-2-PyP
Sung-Won Shin, Changhoon Choi, Ga-Haeng Lee, Arang Son, Su-Hyeon Kim, Hee Chul Park, Ines Batinic-Haberle, Won Park
Antioxidants & Redox Signaling.2017; 27(14): 1067. CrossRef
MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated signaling
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H. Kim, David J Lee, In Ah Kim
Oncotarget.2017; 8(39): 65457. CrossRef
Targeting Histone Deacetylase 8 as a Therapeutic Approach to Cancer and Neurodegenerative Diseases
Alokta Chakrabarti, Jelena Melesina, Fiona R Kolbinger, Ina Oehme, Johanna Senger, Olaf Witt, Wolfgang Sippl, Manfred Jung
Future Medicinal Chemistry.2016; 8(13): 1609. CrossRef

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Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy: Min Kyu Kang, Dongryul Oh, Kwan Ho Cho, Sung Ho Moon, Hong-Gyun Wu, Dae-Seog Heo, Yong Chan Ahn, Keunchil Park, Hyo Jung Park, Jun Su Park, Ki Chang Keum, Jihye Cha, Jun Won Kim, Yeon-Sil Kim, Jin Hyoung Kang, Young-Taek Oh, Ji-Yoon Kim, Sung Hwan Kim, Jin-Hee Kim, Chang Geol Lee; Cancer Res Treat. 2015;47(4):871-878. Published online February 13, 2015; DOI: https://doi.org/10.4143/crt.2014.141; Correction in: Cancer Res Treat 2016;48(1):425

Abstract PDF PubReader ePub

Purpose
To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. Materials and Methods From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy).
Results
Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last followup, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. Conclusion Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

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Concurrent chemoradiotherapy versus radiotherapy alone in older patients with stage II nasopharyngeal carcinoma after intensity-modulated radiotherapy: A propensity score-matched cohort study
Fang Wang, Lu Zhou, Li-Jun Zhang, Chang-Bin Xie, Zhi-Wei Liao, Xiao-Dan Lin, Yue-Feng Wen
Radiotherapy and Oncology.2024; 191: 110081. CrossRef
A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma
Yao-Can Xu, Kai-Hua Chen, Zhong-Guo Liang, Xiao-Dong Zhu
Frontiers in Oncology.2022;[Epub] CrossRef
MRI-identified multidimensional nodal features predict survival and concurrent chemotherapy benefit for stage II nasopharyngeal carcinoma
Yang Liu, Jianghu Zhang, Jingbo Wang, Runye Wu, Xiaodong Huang, Kai Wang, Yuan Qu, Xuesong Chen, Yexiong Li, Ye Zhang, Junlin Yi
Radiology and Oncology.2022; 56(4): 479. CrossRef
The efficacy of chemotherapy in survival of stage II nasopharyngeal carcinoma
Xin-Bin Pan, Ling Li, Song Qu, Long Chen, Shi-Xiong Liang, Xiao-Dong Zhu
Oral Oncology.2020; 101: 104520. CrossRef
Survival of stage II nasopharyngeal carcinoma patients with or without concurrent chemotherapy: A propensity score matching study
Di‐Han Liu, Xiao‐Yu Zhou, You‐Guang Pan, Si Chen, Zheng‐Hao Ye, Gang‐Dong Chen
Cancer Medicine.2020; 9(4): 1287. CrossRef
Concurrent Chemoradiotherapy With or Without Induction Chemotherapy for Patients with Stage II Nasopharyngeal Carcinoma: An Update
Ting Jin, Qun Zhang, Dong-Hua Luo, Feng Jiang, Qi-Feng Jin, Yuan-Yuan Chen, Xiao-Zhong Chen, Wei-Min Mao
Translational Oncology.2020; 13(1): 25. CrossRef
Predictive factors of chemotherapy use in stage II nasopharyngeal carcinoma
Xin-Bin Pan, Shi-Ting Huang, Kai-Hua Chen, Yan-Ming Jiang, Xiao-Dong Zhu
Medicine.2019; 98(7): e14512. CrossRef
The role of chemotherapy in the treatment of stage II nasopharyngeal carcinoma: Retrospective analysis of the national cancer database
Zaheer Ahmed, Lara Kujtan, Kevin Kennedy, Valerie Wood, David Schomas, Janakiraman Subramanian
Cancer Medicine.2019; 8(4): 1500. CrossRef
Patterns of Failure and Survival Trends in 3,808 Patients with Stage II Nasopharyngeal Carcinoma Diagnosed from 1990 to 2012: A Large-Scale Retrospective Cohort Study
Xue-Song Sun, Di-Han Liu, Sai-Lan Liu, Qiu-Yan Chen, Shan-Shan Guo, Yue-Feng Wen, Li-Ting Liu, Hao-Jun Xie, Qing-Nan Tang, Yu-Jing Liang, Xiao-Yun Li, Jin-Jie Yan, Ming-Huang Hong, Jun Ma, Lin-Quan Tang, Hai-Qiang Mai
Cancer Research and Treatment.2019; 51(4): 1449. CrossRef
Combined chemoradiation vs radiation therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis of the published literature
Sufang Wang, Shan Li, Liangfang Shen
Current Problems in Cancer.2018; 42(3): 302. CrossRef
The efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma in intensity modulated radiotherapy era
Pei-Jing Li, Hao-Yuan Mo, Dong-Hua Luo, Wei-Han Hu, Ting Jin
Oral Oncology.2018; 85: 95. CrossRef
Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy
Xin-Bin Pan, Shi-Ting Huang, Kai-Hua Chen, Yan-Ming Jiang, Jia-Lin Ma, Song Qu, Ling Li, Long Chen, Xiao-Dong Zhu
Oncotarget.2017; 8(8): 14029. CrossRef
Chemotherapy use and survival in stage II nasopharyngeal carcinoma
Xin-Bin Pan, Shi-Ting Huang, Kai-Hua Chen, Xiao-Dong Zhu
Oncotarget.2017; 8(60): 102573. CrossRef
Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era
Qiaojuan Guo, Tianzhu Lu, Shaojun Lin, Jingfeng Zong, Zhuhong Chen, Xiaofei Cui, Yu Zhang, Jianji Pan
Japanese Journal of Clinical Oncology.2016; 46(3): 241. CrossRef
Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy and intensity-modulated radiotherapy alone for stage II nasopharyngeal carcinoma
Kai-Hua Chen, Xiao-Dong Zhu, Ling Li, Song Qu, Zhen-Qiang Liang, Xia Liang, Xin-Bin Pan, Zhong-Guo Liang, Yan-Ming Jiang
Oncotarget.2016; 7(42): 69041. CrossRef
Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era
Lu-Ning Zhang, Yuan-Hong Gao, Xiao-Wen Lan, Jie Tang, Zhen Su, Jun Ma, Wuguo Deng, Pu-Yun OuYang, Fang-Yun Xie
Oncotarget.2015; 6(41): 44019. CrossRef

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Phase I Dose-Escalation Study of Proton Beam Therapy for Inoperable Hepatocellular Carcinoma: Tae Hyun Kim, Joong-Won Park, Yeon-Joo Kim, Bo Hyun Kim, Sang Myung Woo, Sung Ho Moon, Sang Soo Kim, Young-Hwan Koh, Woo Jin Lee, Sang Jae Park, Joo-Young Kim, Dae Yong Kim, Chang-Min Kim; Cancer Res Treat. 2015;47(1):34-45. Published online September 11, 2014; DOI: https://doi.org/10.4143/crt.2013.218

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients.
Materials and Methods
Inoperable HCC patients who had naïve, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade ≥ 3 acute toxicity.
Results
Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3- and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3- and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003).
Conclusion
PBT is safe and effective and an EQD2 ≥ 78 GyE10 should be delivered for achievement of local tumor control.

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