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Original Articles
Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial
Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim
Received December 11, 2024  Accepted January 27, 2025  Published online January 31, 2025  
DOI: https://doi.org/10.4143/crt.2024.1195    [Accepted]
AbstractAbstract PDF
Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAɑ inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).
Results
From Oct 2017 and Aug 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutations (H1047), patients with H1047 mutations exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutations showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of NGS testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.
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Phase II Trial of Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Combined with Pegteograstim for Unresectable, Locally Advanced Sinonasal Squamous Cell Carcinoma: KCSG HN18-07
Bhumsuk Keam, Ho Jung An, Seong Hoon Shin, Min Kyoung Kim, Jung Hae Cho, Seyoung Seo, Sung-Bae Kim
Received October 24, 2024  Accepted December 13, 2024  Published online December 16, 2024  
DOI: https://doi.org/10.4143/crt.2024.1025    [Accepted]
AbstractAbstract PDF
Purpose
The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population.
Materials and Methods
Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 stage or potential compromise of critical organ function on surgery. Three TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1, 5-fluorouracil 1,000 mg/m2 on days 1–4 every 3 weeks) cycles were administered with prophylactic pegteograstim. The primary outcome was the overall response rate (ORR); the secondary outcomes included 2-year progression-free survival (PFS), eyeball preservation rate, and safety.
Results
Among 28 patients screened, 25 were evaluable for efficacy (one screen-failure; two evaluable for safety only). The confirmed ORR was 72.0%. The definitive post-NAC treatment comprised chemoradiotherapy (n=15) and surgery (n=10). With a median follow-up of 25.5 months, median PFS was not reached and the 2-year PFS rate was 60.4%. Response to NAC was related to prolonged PFS (p=0.038). No patient underwent eyeball exenteration at the data cutoff point. Treatment-related adverse events of grade ≥3 were neutropenia (48.1%) including febrile neutropenia (14.8%), followed by acute kidney injury (22.2%), nausea/vomiting (11.1%), anemia (7.4%), thrombocytopenia (7.4%), and enterocolitis (3.7%).
Conclusion
TPF NAC showed a promising efficacy and might help preserve critical structures in this population, which needs to be validated in a large prospective trial (KCT0003377).
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Gastrointestinal cancer
Neoadjuvant Nivolumab Therapy for Esophageal Squamous Cell Carcinoma: A Single-Arm, Phase II Study
Sehhoon Park, Yurimi Lee, Jiyun Lee, Yang Won Min, Hong Kwan Kim, Joon Young Choi, Hyun Ae Jung, Yong Soo Choi, Yoon-La Choi, Young Mog Shim, Jong-Mu Sun
Cancer Res Treat. 2024;56(2):567-579.   Published online October 16, 2023
DOI: https://doi.org/10.4143/crt.2023.897
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC.
Materials and Methods
Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]).
Results
Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9).
Conclusion
Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.
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Head and Neck cancer
A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial
Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim
Cancer Res Treat. 2024;56(1):37-47.   Published online July 20, 2023
DOI: https://doi.org/10.4143/crt.2023.433
AbstractAbstract PDFPubReaderePub
Purpose
Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
Materials and Methods
The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Results
Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Conclusion
Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

Citations

Citations to this article as recorded by  
  • Targeting fibroblast growth factor receptor (FGFR) with inhibitors in head and neck cancers: Their roles, mechanisms and challenges
    Daowen Luo, Sirinart Kumfu, Nipon Chattipakorn, Siriporn C. Chattipakorn
    Biochemical Pharmacology.2025; 235: 116845.     CrossRef
  • One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents
    Michael Atef Fawzy, Karim Hagag Ibrahim, Ashraf A Aly, Asmaa H Mohamed, Sara Mohamed Naguib Abdel Hafez, Walaa Yehia Abdelzaher, Eslam B Elkaeed, Aisha A Alsfouk, El-Shimaa MN Abdelhafez
    Future Medicinal Chemistry.2024; 16(21): 2211.     CrossRef
  • Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck
    Prashant Puttagunta, Saagar V. Pamulapati, James E. Bates, Jennifer H. Gross, William A. Stokes, Nicole C. Schmitt, Conor Steuer, Yong Teng, Nabil F. Saba
    Frontiers in Oncology.2023;[Epub]     CrossRef
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Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Hana Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn, Dongryul Oh, Myung-Ju Ahn
Cancer Res Treat. 2023;55(4):1104-1112.   Published online May 17, 2023
DOI: https://doi.org/10.4143/crt.2023.502
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect.
Results
Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1).
Conclusion
The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

Citations

Citations to this article as recorded by  
  • Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review
    Akihiro Sakai, Koji Ebisumoto, Hiroaki Iijima, Mayu Yamauchi, Daisuke Maki, Tsuyoshi Fukuzawa, Kenji Okami
    Cancer Reports.2024;[Epub]     CrossRef
  • Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects
    Makoto Ito, Souichiro Abe, Sou Adachi, Yukihiko Oshima, Arisa Takeuchi, Wataru Ohashi, Takashi Iwata, Tetsuya Ogawa, Akiko Ota, Yasuaki Kubota, Takahito Okuda, Kojiro Suzuki
    Japanese Journal of Radiology.2024; 42(4): 424.     CrossRef
  • Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis
    Xiao Han, Haidong Zhang, Kai Sun, Jing Li, Wanjuan Wu, Kai Liu, Zhenkun Yu
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Kaplan lecture 2023: lymphopenia in particle therapy
    Marco Durante
    International Journal of Radiation Biology.2024; 100(5): 669.     CrossRef
  • Clinical application of high‐LET radiotherapy combined with immunotherapy in malignant tumors
    Kexin Meng, Haijun Lu
    Precision Radiation Oncology.2024; 8(1): 42.     CrossRef
  • Research progress of immunotherapy for advanced head and neck cancer
    Anchi Sun, Zhiwei Xing, Rongrong Lv, Pengyuan Niu, Bao Zhao, Shiyin Ma, Hui Li
    Medical Oncology.2024;[Epub]     CrossRef
  • A review and bibliometric analysis of global research on proton radiotherapy
    Ge Song, Zhi Zheng, Yingming Zhu, Yaoting Wang, Song Xue
    Medicine.2024; 103(19): e38089.     CrossRef
  • Cutaneous Squamous Cell Carcinoma: An Updated Review
    Rina Jiang, Mike Fritz, Syril Keena T. Que
    Cancers.2024; 16(10): 1800.     CrossRef
  • Radiotherapy and immunology
    Liangliang Wang, Connor Lynch, Sean P. Pitroda, András Piffkó, Kaiting Yang, Amy K. Huser, Hua Laura Liang, Ralph R. Weichselbaum
    Journal of Experimental Medicine.2024;[Epub]     CrossRef
  • The Evolving Paradigm of Immunotherapy in Head-and-neck Squamous Cell Cancers
    Riccardo Gili, Paolo Bossi
    Journal of Head & Neck Physicians and Surgeons.2024; 12(1): 13.     CrossRef
  • Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach
    Alessia Zotta, Maria Luisa Marciano, Francesco Sabbatino, Alessandro Ottaiano, Marco Cascella, Monica Pontone, Massimo Montano, Ester Calogero, Francesco Longo, Morena Fasano, Teresa Troiani, Fortunato Ciardiello, Fabiana Raffaella Rampetta, Giovanni Salz
    Biomedicines.2024; 12(10): 2337.     CrossRef
  • Emerging Radiotherapy Technologies for Head and Neck Squamous Cell Carcinoma: Challenges and Opportunities in the Era of Immunotherapy
    Carmen Kut, Harry Quon, Xuguang Scott Chen
    Cancers.2024; 16(24): 4150.     CrossRef
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Outcomes of Salvage Therapy for Oropharyngeal Cancer Recurrence Following Upfront Radiation Therapy and Prognostic Factors
Nayeon Choi, Hack Jung Kim, Heejun Yi, Heejung Kim, Tae Hwan Kim, Han-Sin Jeong, Young-Ik Son, Chung-Hwan Baek, Dongryul Oh, Yong Chan Ahn, Man Ki Chung
Cancer Res Treat. 2023;55(4):1123-1133.   Published online May 8, 2023
DOI: https://doi.org/10.4143/crt.2022.1046
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment.
Materials and Methods
A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment.
Results
After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting.
Conclusion
In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

Citations

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  • Toxicities and prognostic factors in elderly HPV‐associated oropharyngeal cancer patients treated with radiotherapy or chemoradiotherapy
    Erkan Topkan, Efsun Somay, Ugur Selek
    Journal of Medical Virology.2024;[Epub]     CrossRef
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  • 213 Download
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  • 1 Crossref
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Gastrointestinal cancer
Role of Esophagectomy after Chemoradiation Therapy in Patients with Locally Advanced Squamous Cell Carcinoma: A Comparative Analysis Stratified by Clinical Response to Chemoradiation Therapy
Jesang Yu, Jong Hoon Kim, Sung-Bae Kim, Sook Ryun Park, Young-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Ho June Song, Kye Jin Song, Jeong Yun Jang, Yoon Young Jo, Ye Jin Yoo
Cancer Res Treat. 2022;54(4):1148-1156.   Published online December 20, 2021
DOI: https://doi.org/10.4143/crt.2021.885
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery.
Materials and Methods
We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW).
Results
The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001).
Conclusion
In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

Citations

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  • Diagnosing Complete Response to Preoperative Chemoradiation in Esophageal Cancer Using Dynamic Contrast-Enhanced MRI Response Criteria
    Yura Ahn, Jooae Choe, Hyun Joo Lee, Sook Ryun Park, Jong-Hoon Kim, Ho June Song, Min-Ju Kim, Yong-Hee Kim
    Korean Journal of Radiology.2025; 26(3): 269.     CrossRef
  • Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis
    Junli Ke, Yujie Xie, Shenyang Huang, Wei Wang, Zhengang Zhao, Wanli Lin
    Asian Journal of Surgery.2024; 47(9): 3827.     CrossRef
  • Multi-disciplinary management of esophageal carcinoma: Current practices and future directions
    Chanyoot Bandidwattanawong
    Critical Reviews in Oncology/Hematology.2024; 197: 104315.     CrossRef
  • Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma
    Tae Hee Hong, Tae Ho Kim, Genehee Lee, Jeonghee Yun, Yeong Jeong Jeon, Junghee Lee, Sumin Shin, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jong-Mu Sun, Dongryul Oh, Hong Kwan Kim
    European Journal of Cardio-Thoracic Surgery.2024;[Epub]     CrossRef
  • Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study
    Tongpeng Xu, Jianan Bai, Kun Zhao, Xiaofeng Chen, Shuhui Wang, Shusheng Zhu, Chongqi Sun, Chenhui Zhao, Ting Wang, Ling Zhu, Meizhen Hu, Fei Pang, Junling Zhang, Wei Wang, Yongqian Shu, Fang Li, Yue Zhou
    Annals of Surgical Oncology.2024; 31(13): 9321.     CrossRef
  • Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review
    Rakesh Acharya, Ananya Mahapatra, Henu Kumar Verma, L. V. K. S. Bhaskar
    Current Oncology.2023; 30(11): 9542.     CrossRef
  • Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma
    Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
    Gastroenterology Report.2023;[Epub]     CrossRef
  • 6,024 View
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  • 9 Web of Science
  • 7 Crossref
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Lung and Thoracic cancer
Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples
Chang Gok Woo, Seung-Myoung Son, Ho-Chang Lee, Hye Sook Han, Ki Hyeong Lee, Dohun Kim, Eung-Gook Kim, Ok-Jun Lee
Cancer Res Treat. 2022;54(3):737-743.   Published online September 24, 2021
DOI: https://doi.org/10.4143/crt.2021.773
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.
Materials and Methods
We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.
Results
Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.
Conclusion
The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Citations

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  • Patients outcomes in lung adenocarcinoma transforming to small-cell lung cancer after tyrosine kinase inhibitor therapy
    Shuai Wang, Yongsen Wang, Xuan Wu, Li Yang, Xiaoju Zhang
    World Journal of Surgical Oncology.2025;[Epub]     CrossRef
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    Mohammadali Ahmadipour, Jorge Castilo Prado, Benyamin Hakak‐Zargar, Malik Quasir Mahmood, Ian M. Rogers
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    Shuo Li, Wenyuan Li, Bin Liu, Kostyantyn Krysan, Steven M. Dubinett
    Cancer Research Communications.2024; 4(7): 1738.     CrossRef
  • Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases
    Alessandro Bonis, Andrea Dell’Amore, Vincenzo Verzeletti, Luca Melan, Giovanni Zambello, Chiara Nardocci, Giovanni Maria Comacchio, Federica Pezzuto, Fiorella Calabrese, Federico Rea
    Journal of Clinical Medicine.2023; 12(4): 1411.     CrossRef
  • Gene‐level dissection of chromosome 3q locus amplification in squamous cell carcinoma of the lung using the nCounter assay
    Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
    Thoracic Cancer.2023; 14(26): 2635.     CrossRef
  • Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience
    Jeong Yun Jang, Su Ssan Kim, Si Yeol Song, Young Seob Shin, Sei Won Lee, Wonjun Ji, Chang-Min Choi, Eun Kyung Choi
    Cancer Research and Treatment.2023; 55(4): 1181.     CrossRef
  • Challenges and Opportunities for Immunoprofiling Using a Spatial High-Plex Technology: The NanoString GeoMx® Digital Spatial Profiler
    Sharia Hernandez, Rossana Lazcano, Alejandra Serrano, Steven Powell, Larissa Kostousov, Jay Mehta, Khaja Khan, Wei Lu, Luisa M. Solis
    Frontiers in Oncology.2022;[Epub]     CrossRef
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  • 8 Web of Science
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Gastrointestinal cancer
Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors
Jwa Hoon Kim, Bokyung Ahn, Seung-Mo Hong, Hwoon-Yong Jung, Do Hoon Kim, Kee Don Choi, Ji Yong Ahn, Jeong Hoon Lee, Hee Kyoung Na, Jong Hoon Kim, Yong-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Sung-Bae Kim, Sook Ryun Park
Cancer Res Treat. 2022;54(2):505-516.   Published online June 23, 2021
DOI: https://doi.org/10.4143/crt.2020.1198
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.
Materials and Methods
Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.
Results
The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.
Conclusion
The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

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Head and Neck cancer
Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01)
Yun-Gyoo Lee, Eun Joo Kang, Bhumsuk Keam, Jin-Hyuk Choi, Jin-Soo Kim, Keon Uk Park, Kyoung Eun Lee, Hyo Jung Kim, Keun-Wook Lee, Min Kyoung Kim, Hee Kyung Ahn, Seong Hoon Shin, Hye Ryun Kim, Sung-Bae Kim, Hwan Jung Yun
Cancer Res Treat. 2022;54(1):109-117.   Published online April 27, 2021
DOI: https://doi.org/10.4143/crt.2020.1329
AbstractAbstract PDFPubReaderePub
Purpose
Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods
Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results
Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion
Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.

Citations

Citations to this article as recorded by  
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Gastrointestinal cancer
Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma Incorporating Hematological Biomarkers
Yingjia Wu, Jinbin Chen, Lei Zhao, Qiaoqiao Li, Jinhan Zhu, Hong Yang, Suping Guo, Mian Xi
Cancer Res Treat. 2021;53(1):172-183.   Published online September 4, 2020
DOI: https://doi.org/10.4143/crt.2020.594
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics.
Materials and Methods
Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated.
Results
Absolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78).
Conclusion
Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×109/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

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Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma
Liyuan Dai, Qigen Fang, Peng Li, Junfu Wu, Xu Zhang
Cancer Res Treat. 2020;52(1):109-116.   Published online May 30, 2019
DOI: https://doi.org/10.4143/crt.2019.202
AbstractAbstract PDFPubReaderePub
Purpose
The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design.
Materials and Methods
Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method.
Results
Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS.
Conclusion
NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

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    Wei Du, Qigen Fang, Shanting Liu, Defeng Chen, Ruihua Luo, Xu Zhang
    Frontiers in Oncology.2020;[Epub]     CrossRef
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    Bo Gu, Qigen Fang, Yao Wu, Wei Du, Xu Zhang, Defeng Chen
    BMC Cancer.2020;[Epub]     CrossRef
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Intensity-Modulated Radiotherapy versus Three-Dimensional Conformal Radiotherapy in Definitive Chemoradiotherapy for Cervical Esophageal Squamous Cell Carcinoma: Comparison of Survival Outcomes and Toxicities
Nai-Bin Chen, Bo Qiu, Jun Zhang, Meng-Yun Qiang, Yu-Jia Zhu, Bin Wang, Jin-Yu Guo, Ling-Zhi Cai, Shao-Min Huang, Meng-Zhong Liu, Qun Li, Yong-Hong Hu, Qi-Wen Li, Hui Liu
Cancer Res Treat. 2020;52(1):31-40.   Published online April 30, 2019
DOI: https://doi.org/10.4143/crt.2018.624
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques.
Materials and Methods
A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test.
Results
With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence.
Conclusion
No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

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    Renxian Xie, Qingxin Cai, Tong Chen, Hongxin Huang, Chuangzhen Chen
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    Lin-Rui Gao, Jiajun Zhang, Ning Huang, Wei Deng, Wenjie Ni, Zefen Xiao, Mei Liu
    International Journal of Molecular Sciences.2024; 25(11): 6082.     CrossRef
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    Xiao-Han Zhao, Wen-Cheng Zhang, Xin Wang, Jun-Qiang Chen, Yuan-Ji Xu, Kuai-Le Zhao, Wei Huang, Pu-Dong Qian, Ya-Tian Liu, Xiao-Lin Ge, Xiao-Jie Xia, Chen-Gang Weng, Chun-Yue Gai, He-Song Wang, Hong-Mei Gao, Wen-Bin Shen, Shu-Chai Zhu
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    Journal of Cancer Research and Clinical Oncology.2023; 149(3): 1029.     CrossRef
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    Journal of Oncology.2022; 2022: 1.     CrossRef
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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Res Treat. 2019;51(3):1052-1063.   Published online October 24, 2018
DOI: https://doi.org/10.4143/crt.2018.411
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

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    Lilibeth Stephania Escoto-Vasquez, Javier Portilla-Robertson, Josué Orlando Ramírez-Jarquín, Luis Fernando Jacinto-Alemán, Alejandro Alonso-Moctezuma, Carla Monserrat Ramírez-Martínez, Osmar Alejandro Chanes-Cuevas, Fabiola Salgado-Chavarria
    Dentistry Journal.2024; 12(10): 327.     CrossRef
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    Kondajji Ramachandra Vijayalakshmi, Vanshika Jain
    National Journal of Maxillofacial Surgery.2023; 14(3): 341.     CrossRef
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    Zhibin Cui, Hyunseok Kang, Jennifer R. Grandis, Daniel E. Johnson
    Molecular Cancer Research.2021; 19(1): 14.     CrossRef
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    Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
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    Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park, Sang Yun Ha
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    Daniel E. Gracilla, Praveen Kumar Korla, Ming‐Tsung Lai, An‐Jen Chiang, Wen‐Shiung Liou, Jim Jinn‐Chyuan Sheu
    Molecular Oncology.2020; 14(12): 3065.     CrossRef
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    Eun Kyung Kim, Yoon Ah Cho, Mi-kyoung Seo, Hyunmi Ryu, Byoung Chul Cho, Yoon Woo Koh, Sun Och Yoon
    Scientific Reports.2019;[Epub]     CrossRef
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    Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
    Head & Neck.2019; 41(1): 198.     CrossRef
  • 8,094 View
  • 254 Download
  • 10 Web of Science
  • 9 Crossref
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Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same
Vishal Sahu, Lokesh Nigam, Vertica Agnihotri, Abhishek Gupta, Shashank Shekhar, Naidu Subbarao, Suman Bhaskar, Sharmistha Dey
Cancer Res Treat. 2019;51(1):313-325.   Published online May 9, 2018
DOI: https://doi.org/10.4143/crt.2018.105
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same.
Materials and Methods
Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors.
Results
We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket.
Conclusion
In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

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    Chemistry & Biodiversity.2024;[Epub]     CrossRef
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    Qinwen Zheng, Shutong Li, Aoxue Wang, Man Zhe, Panpan Yang, Yongya Wu, Min Zhao, Yumeng Zhu, Yi Luo, Guan Wang, Liang Ouyang
    MedComm – Oncology.2023;[Epub]     CrossRef
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    Sharmistha Dey, Abhay Kumar Singh, Abhinay Kumar Singh, Kartik Rawat, Joyita Banerjee, Vertica Agnihotri, Deepak Upadhaya
    Medical Oncology.2022;[Epub]     CrossRef
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    Hyungyeong Choi, Jeong-Hyun Yoon, Kumju Youn, Mira Jun
    Biomedicine & Pharmacotherapy.2022; 147: 112651.     CrossRef
  • Role of p38 MAP kinase in cancer stem cells and metastasis
    Sriya Kudaravalli, Petra den Hollander, Sendurai A. Mani
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  • Tim‐3 suppresses autoimmune hepatitis via the p38/MKP‐1 pathway in Th17 cells
    Hongwei Wu, Shiyue Tang, Mengya Zhou, Jiji Xue, Zhenjun Yu, Jiansheng Zhu
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    Débora Bublitz Anton, Rodrigo Gay Ducati, Luís Fernando Saraiva Macedo Timmers, Stefan Laufer, Márcia Inês Goettert
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  • Atypical p38 Signaling, Activation, and Implications for Disease
    Jeremy C. Burton, William Antoniades, Jennifer Okalova, Morgan M. Roos, Neil J. Grimsey
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    Zhenning Li, Fa-yu Liu, Keith L. Kirkwood
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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma
Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim
Cancer Res Treat. 2019;51(1):300-312.   Published online May 9, 2018
DOI: https://doi.org/10.4143/crt.2018.012
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

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Preclinical Study of Novel Curcumin Analogue SSC-5 Using Orthotopic Tumor Xenograft Model for Esophageal Squamous Cell Carcinoma
Lai Nar Tung, Senchuan Song, Kin Tak Chan, Mei Yuk Choi, Ho Yu Lam, Chung Man Chan, Zhiyong Chen, Hector K. Wang, Hoi Ting Leung, Simon Law, Yanmin Huang, Huacan Song, Nikki P. Lee
Cancer Res Treat. 2018;50(4):1362-1377.   Published online January 24, 2018
DOI: https://doi.org/10.4143/crt.2017.353
AbstractAbstract PDFPubReaderePub
Purpose
Tumor xenograft model is an indispensable animal cancer model. In esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft model establishes tumor xenograft in the animal esophagus, which allows the study of tumorigenesis in its native microenvironment.
Materials and Methods
In this study,we described two simple and reproducible methods to develop tumor xenograft at the cervical or the abdominal esophagus in nude mice by direct injection of ESCC cells in the esophageal wall.
Results
In comparing these two methods, the cervical one presented with more clinically relevant features, i.e., esophageal stricture, body weight loss and poor survival. In addition, the derived tumor xenografts accompanied a rapid growth rate and a high tendency to invade into the surrounding structures. This model was subsequently used to study the anti-tumor effect of curcumin, which is known for its potential therapeutic effects in various diseases including cancers, and its analogue SSC-5. SSC-5 was selected among the eight newly synthesized curcumin analogues based on its superior anti-tumor effect demonstrated in an MTT cell proliferation assay and its effects on apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor growth and invasion.
Conclusion
Taken together, we have established a clinically relevant orthotopic tumor xenograft model that can serve as a preclinical tool for screening new anti-tumor compounds, e.g., SSC-5, in ESCC.

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Nationwide Trends in the Incidence of Melanoma and Non-melanoma Skin Cancers from 1999 to 2014 in South Korea
Chang-Mo Oh, Hyunsoon Cho, Young-Joo Won, Hyun-Joo Kong, Yun Ho Roh, Ki-Heon Jeong, Kyu-Won Jung
Cancer Res Treat. 2018;50(3):729-737.   Published online July 14, 2017
DOI: https://doi.org/10.4143/crt.2017.166
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This descriptive study was aimed to examine trends in the incidence of melanoma and nonmelanoma in South Korea.
Materials and Methods
The nationwide incidence data for melanoma and non-melanoma skin cancer was obtained from the Korea Central Cancer Registry. Age-standardized rates were calculated and analyzed, using a Joinpoint regression model.
Results
The incidence of basal cell carcinoma has increased dramatically both in men (average annual percentage change [AAPC], 8.0 [95% confidence interval (CI), 6.0 to 10.1]) and women (AAPC, 9.0 [95% CI, 7.5 to 10.4]). Squamous cell carcinoma has also steadily increased both in men (AAPC, 3.3 [95% CI, 2.6 to 4.0]) and women (AAPC, 6.8 [95% CI, 5.3 to 8.4]). Cutaneous melanoma increased continuously from 1999 to 2014 inwomen (AAPC, 3.5 [95% CI, 2.4 to 4.6]), whilst rapidly increasing in men until 2005 (APC, 7.9 [95% CI, 2.4 to 13.7]) after which no increase has been observed (APC, ‒0.2 [95% CI, ‒2.3 to 2.0]).
Conclusion
The incidence rates of melanoma and non-melanoma skin cancer have increased over the past years, with the exception of melanoma in men. Further studies are required to investigate the reasons for the increased incidence of these skin cancers in South Korea.

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Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Cancer Res Treat. 2018;50(2):356-365.   Published online May 26, 2017
DOI: https://doi.org/10.4143/crt.2017.125
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease.
Materials and Methods
A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients’ peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants.
Results
Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR.
Conclusion
In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.

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Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18
Xiaohui Xu, Cheng Song, Zhihua Chen, Chenxiao Yu, Yi Wang, Yiting Tang, Judong Luo
Cancer Res Treat. 2018;50(1):71-87.   Published online February 24, 2017
DOI: https://doi.org/10.4143/crt.2017.013
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC).
Materials and Methods
In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3’-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used.
Results
In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay.
Conclusion
HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.

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Prevalence of Mutations in Discoidin Domain-Containing Receptor Tyrosine Kinase 2 (DDR2) in Squamous Cell Lung Cancers in Korean Patients
Mi-Sook Lee, Eun Ah Jung, Sung Bin An, Yu Jin Kim, Doo-Yi Oh, Ji-Young Song, Sang-Won Um, Joungho Han, Yoon-La Choi
Cancer Res Treat. 2017;49(4):1065-1076.   Published online January 25, 2017
DOI: https://doi.org/10.4143/crt.2016.347
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer.
Materials and Methods
We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2 mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2 mutants were confirmed by in vitro assays.
Results
We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied. One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant–bearing cells.
Conclusion
Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2 mutations were located in a kinase domain and induced an increase in cell proliferation rate.

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Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer
Youngjoo Lee, Ki Hyeong Lee, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Yun Jung Go, Jin Soo Lee, Ji-Youn Han
Cancer Res Treat. 2017;49(4):1001-1011.   Published online January 13, 2017
DOI: https://doi.org/10.4143/crt.2016.546
AbstractAbstract PDFPubReaderePub
Purpose
This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).
Materials and Methods
Patientswith advancedNA-NSCLCwho progressed after one ortwo chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).
Results
Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).
Conclusion
There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.

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Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE2
Ivan Ho Yuen Pun, Dessy Chan, Sau Hing Chan, Po Yee Chung, Yuan Yuan Zhou, Simon Law, Alfred King Yin Lam, Chung Hin Chui, Albert Sun Chi Chan, Kim Hung Lam, Johnny Cheuk On Tang
Cancer Res Treat. 2017;49(1):219-229.   Published online July 18, 2016
DOI: https://doi.org/10.4143/crt.2016.190
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis.
Materials and Methods
A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E2 (PGE2) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450.
Results
83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft.
Conclusion
The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.

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Optimal Adjuvant Treatment for Curatively Resected Thoracic Esophageal Squamous Cell Carcinoma: A Radiotherapy Perspective
Kyung Hwan Kim, Jee Suk Chang, Ji Hye Cha, Ik Jae Lee, Dae Joon Kim, Byoung Chul Cho, Kyung Ran Park, Chang Geol Lee
Cancer Res Treat. 2017;49(1):168-177.   Published online June 23, 2016
DOI: https://doi.org/10.4143/crt.2016.142
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate the benefits of adjuvant treatment for curatively resected thoracic esophageal squamous cell carcinoma (ESCC) and determine the optimal adjuvant treatments.
Materials and Methods
One hundred ninety-five patients who underwent a curative resection for thoracic ESCC between 1994 and 2014 were reviewed retrospectively. Postoperatively, the patients received no adjuvant treatment (no-adjuvant group, n=68), adjuvant chemotherapy (AC group, n=62), radiotherapy (RT group, n=41), or chemoradiotherapy (CRT group, n=24). Chemotherapy comprised cisplatin and 5-fluorouracil administration every 3 weeks. The median RT dose was 45.0 Gy (range, 34.8 to 59.4 Gy). The overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and distant metastasis (DM) rates were estimated.
Results
At a median follow-up duration of 42.2 months (range, 6.3 to 215.2 months), the 5-year OS and DFS were 37.6% and 31.4%, respectively. After adjusting for other clinicopathologic variables, the AC and CRT groups had a significantly better OS and DFS compared to the no-adjuvant group (p < 0.05). The LRR rate was significantly lower in the RT and CRT groups than in the no-adjuvant group (p < 0.05), whereas no significant difference was observed in the AC group. In the no-adjuvant and AC groups, 25% of patients received high-dose salvage RT due to LRR. The DM rates were similar. The anastomotic stenosis and leakage were similar in the treatment groups.
Conclusion
Adjuvant treatment might prolong survival after an ESCC resection, and RT contributes to a reduction of the LRR. Overall, the risks and benefits should be weighed properly when selecting the optimal adjuvant treatment.

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Case Report
HPV-Related Retroperitoneal Squamous Cell Carcinoma of Unknown Primary: A Case Report
Hyun Jin Oh, Eun Hye Park, Yeong Bok Lee, Jooyeun Hu, Guk Jin Lee, Sang Hoon Chun, Mi Yeong Lee, Dae Woo Lee, Jeana Kim, Jong-Youl Jin
Cancer Res Treat. 2015;47(4):954-957.   Published online February 17, 2015
DOI: https://doi.org/10.4143/crt.2014.111
AbstractAbstract PDFPubReaderePub
A 56-year-old female was referred to our hospital due to a mass measuring 5 cm in size in the left pelvic cavity, which was found incidentally during a health examination by ultrasonography. Exploratory laparotomy was performed and the mass was located at the left retroperitoneal parametrium without invasion of the uterus and ovary. The pathology report confirmed squamous cell carcinoma. Even after further studies, we did not find any other primary lesion. Human papillomavirus (HPV) DNA chip test (HPV 9G DNA Membrane Kit, Biometrixtechnology Inc.) showed that the surgical specimen was positive for HPV 18. She received adjuvant chemotherapy and would receive radiation therapy for the possibility of occult gynecologic cancer. Retroperitoneal squamous cell carcinoma of unknown primary is extremely rare and little is known about it. It is reported that HPV may be associated with the disease. Hence, the result of HPV test could have an impact on finding a suspicious primary lesion and treatment modality in this case.

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Original Articles
Long-Term Outcome of Definitive Radiotherapy for Early Glottic Cancer: Prognostic Factors and Patterns of Local Failure
Yu Jin Lim, Hong-Gyun Wu, Tack-Kyun Kwon, J. Hun Hah, Myung-Whun Sung, Kwang Hyun Kim, Charn Il Park
Cancer Res Treat. 2015;47(4):862-870.   Published online February 13, 2015
DOI: https://doi.org/10.4143/crt.2014.203
AbstractAbstract PDFPubReaderePub
Purpose
This study evaluates the long-term results of definitive radiotherapy (RT) for early glottic cancer. Clinical and treatment factors related to local control and patterns of failure are analyzed. Materials and Methods We retrospectively reviewed 222 patients with T1-2N0 squamous cell carcinoma of the glottic larynx treated with definitive RT from 1981 to 2010. None of the patients received elective nodal RT or combined chemotherapy. The median total RT dose was 66 Gy. The daily fraction size was < 2.5 Gy in 69% and 2.5 Gy in 31% of patients. The RT field extended from the hyoid bone to the cricoid cartilage.
Results
The median age was 60 years, and 155 patients (70%) had T1 disease. The 5-year rates of local recurrence-free survival (LRFS) and ultimate LRFS with voice preservation were 87.8% and 90.3%, respectively. T2 (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.08 to 4.94) and anterior commissural involvement (HR, 3.37; 95% CI, 1.62 to 7.02) were significant prognostic factors for LRFS. In 34 patients with local recurrence, tumors recurred in the ipsilateral vocal cord in 28 patients. There were no contralateral vocal cord recurrences. Most acute complications included grade 1-2 dysphagia and/or hoarseness. There was no grade 3 or greater chronic toxicity.
Conclusion
Definitive RT achieved a high cure rate, voice preservation, and tolerable toxicity in early glottic cancer. T2 stage and anterior commissural involvement were prognostic factors for local control. Further optimization of the RT method is needed to reduce the risk of ipsilateral tumor recurrence.

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Nomogram to Predict Treatment Outcome of Fluoropyrimidine/Platinum-Based Chemotherapy in Metastatic Esophageal Squamous Cell Carcinoma
Hyun Ae Jung, Antoine Adenis, Jeeyun Lee, Se Hoon Park, Chi Hoon Maeng, Silvia Park, Hee Kyung Ahn, Young Mog Shim, Nicolas Penel, Young-Hyuck Im
Cancer Res Treat. 2013;45(4):285-294.   Published online December 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.4.285
AbstractAbstract PDFPubReaderePub
PURPOSE
The degree of benefit from palliative chemotherapy differs widely among patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose of this study was to develop and validate a prognostic nomogram to predict survival and aid physicians and patients in the decision-making process regarding treatment options.
MATERIALS AND METHODS
Clinicopathologic variables and treatment outcomes of 239 patients who were diagnosed with MESCC and received either fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) as first-line chemotherapy were reviewed. A nomogram was developed as a prognostic scoring system incorporating significant clinical and laboratory variables based on a multivariate Cox proportional hazards regression model. An independent series of 61 MESCC patients treated with FP served as an independent data set for nomogram validation.
RESULTS
No difference in response rate was observed between the FP group (44.8%) and the XP group (54.2%). Similarly, no significant differences in median progression-free survival and median overall survival were observed between regimen groups. Multivariate analysis showed that poor performance status (Eastern Cooperative Oncology Group [ECOG] status> or =2), weight loss (10% of the weight loss for 3 months), low albumin level (< or =3.5 g/dL), and absence of previous esophagectomy at the time of chemotherapy were significantly associated with low OS in both groups (p<0.05). Based on these findings, patients were classified into favorable (score, 0 to 90), intermediate (91-134), and poor (>135) prognostic groups. The median survival for those with a favorable ECOG was 13.8 months (95% confidence interval [CI], 10.8 to 18.6 months), for intermediate 11.2 months (95% CI, 8.7 to 11.9 months), and for poor, 7.0 months (95% CI, 3.6 to 10.0 months). External validation of the nomogram in a different patient cohort yielded significantly similar findings.
CONCLUSION
The nomogram described here predicts survival in MESCC patients and could serve as a guide for the use of FP/XP chemotherapy in MESCC patients.

Citations

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Clinical Prognostic Factors for Locally Advanced Esophageal Squamous Carcinoma Treated after Definitive Chemoradiotherapy
Dae-Eun Kim, Uh-Jin Kim, Won-Young Choi, Mi-Young Kim, Seung-Hun Kim, Min-Jee Kim, Hyun-Jeong Shim, Jun-Eul Hwang, Woo-Kyun Bae, Ik-Joo Chung, Taek-Keun Nam, Kook-Joo Na, Sang-Hee Cho
Cancer Res Treat. 2013;45(4):276-284.   Published online December 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.4.276
AbstractAbstract PDFPubReaderePub
PURPOSE
Locally advanced esophageal cancers are generally treated with neoadjuvant chemoradiotherapy, followed by surgery in operable candidates. However, even if the patients were diagnosed as operable disease, surgery could not be performed on patients with poor condition or other comorbidity. In this case, definitive chemoradiotherapy (dCRT) is the other option for localized esophageal cancer. Therefore, the purpose of this study was to evaluate the efficacy and clinical prognostic factors for dCRT in locally advanced esophageal cancer.
MATERIALS AND METHODS
We conducted a review of patients who received dCRT for locally advanced squamous esophageal cancer from 2004 to 2010, focusing on stages III and IVa. All patients received at least two cycles of platinum-based chemotherapy during radiation, and all tumor burdens were included in the radiation field. The treatment results were analyzed for patterns of failure and prognostic factors associated with survival.
RESULTS
In total, 63 patients were enrolled in this study. The overall response rate was 84.1%. Relief from dysphagia after dCRT was achieved in 48 patients. The most frequent failure was local recurrence. The median overall survival (OS) was 23.0 months, and the 2-year survival rate was 45.4%. Similar results were observed for elderly study patients. Significant prognostic factors for OS were duration of smoking, high grade of dysphagia (score of 3 or 4), and shorter duration of progression-free and dysphagia-free survival. Maintenance chemotherapy after dCRT did not influence OS. However, "good risk" patients receiving maintenance chemotherapy showed better OS than those who did not receive maintenance chemotherapy (30.4 months vs. 12.0 months, p=0.002).
CONCLUSION
dCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer, even in elderly patients. Maintenance chemotherapy after dCRT may be effective in prolonging survival in "good risk" patients.

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Case Report
A Case Report of Paraneoplastic Pemphigus Associated with Esophageal Squamous Cell Carcinoma
Jin Hyun Cho, Nam Jun Kim, Sung Min Ko, Chunghun Kim, Hee Kyung Ahn, Jina Yun, Yeon Hee Park
Cancer Res Treat. 2013;45(1):70-73.   Published online March 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.1.70
AbstractAbstract PDFPubReaderePub
Paraneoplastic pemphigus is an autoimmune blistering and erosive mucocutaneous syndrome associated with underlying neoplasm. It is primarily associated with lymphoproliferative disorders, and uncommonly with malignancies of epithelial origin. We report on a case of a 68-year-old male who presented with whole body bullous and erosive skin lesions. Findings on upper gastrointestinal endoscopy and skin biopsy revealed esophageal squamous cell carcinoma and paraneoplastic pemphigus. Palliative chemotherapy and systemic glucocorticoid were started, however, the patient died of overwhelming sepsis on the ninth day of chemotherapy. This case demonstrates that paraneoplastic pemphigus can occur in esophageal squamous cell carcinoma and could be a cause of morbidity.

Citations

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  • Pemphigus
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Original Article
Prognostic Value of Different Patterns of Squamous Cell Carcinoma Antigen Level for the Recurrent Cervical Cancer
Bae Kwon Jeong, Seung Jae Huh, Doo Ho Choi, Won Park, Duk Soo Bae, Byoung-Gie Kim
Cancer Res Treat. 2013;45(1):48-54.   Published online March 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.1.48
AbstractAbstract PDFPubReaderePub
PURPOSE
In some unusual cases, in patients with cervical cancer, an elevation of squamous cell carcinoma antigen (SCC-Ag) was not observed at diagnosis but was observed on recurrence, or vice versa. The objective of this study was to identify patient-, disease-, and treatment-related factors associated with this unusual level of SCC-Ag, and to determine whether SCC-Ag is a useful tumor marker in such patients.
MATERIALS AND METHODS
Among 129 patients with recurrence, 14 who showed a normal SCC-Ag level at diagnosis but an elevated level at recurrence were classified as group I; 22 patients with an elevated SCC-Ag level at diagnosis but not at recurrence were classified as group II; and 76 patients with an elevated SCC-Ag level at both diagnosis and recurrence were classified as group III.
RESULTS
In univariate analysis, unusual SCC-Ag showed statistically significant relationships with pathology and biochemical response to treatment. However, in the multivariate analysis, none of the clinicopathologic factors showed a statistical relationship with unusual levels of SCC-Ag. The 5-year disease-free survival rates for groups I, II, and III were 7.1%, 9.1%, and 0% (p=0.418), and the 5-year overall survival rates were 34.3%, 58.4%, and 33.3% (p=0.142), respectively.
CONCLUSION
The value of SCC-Ag has been confirmed in all patients; thus, check of SCC-Ag level at follow-up should be considered. Although no statistically significant differences were observed among the groups, we conclude that patients with a high initial SCC-Ag and elevated SCC-Ag at relapse have poor prognosis due to high SCC-Ag level.

Citations

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