Cancer Research and Treatment

Original Article

Hematologic malignancy

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia: Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim; Cancer Res Treat. 2023;55(3):1011-1022. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1407

Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP^in-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIP^in-f CEBPA, and 28 had non-bZIP^in-f CEBPA. In the multivariate analysis, patients with NPM1^mut, those with bZIP^in-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITD^mut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP^in-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITD^pos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPA^dm), bZIP^in-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP^in-f CEBPA. Of 50 patients with bZIP^in-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIP^in-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIP^in-f CEBPA was associated with favorable outcomes in patients with CEBPA^dm. However, some mutations accompanying bZIP^in-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP^in-f CEBPA.

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CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
Blood Advances.2024; 8(6): 1487. CrossRef
CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
Blood Cancer Journal.2024;[Epub] CrossRef
Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
International Journal of Laboratory Hematology.2023; 45(6): 833. CrossRef

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Case Reports

Case Report of Erdheim-Chester Disease Successfully Treated with Pegylated Interferon: A Single-Center Experience: Yujin Lim, Sang Eun Yoon, Junhun Cho, Darae Kim, Chul Won Jung; Cancer Res Treat. 2023;55(3):1053-1057. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.1535

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Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.

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An Autopsied Case of Erdheim-Chester Disease with Severe Cardiovascular Involvement
Atsushi Matsunashi, Wang Zhipeng, Akihiko Sugimoto, Masakazu Fujimoto, Akihiko Yoshizawa, Ryo Sakamoto, Michihiro Uyama, Kohei Ikezoe, Kiminobu Tanizawa, Tomohiro Handa, Toyohiro Hirai
Internal Medicine.2025;[Epub] CrossRef
Advances in Understanding and Management of Erdheim-Chester Disease
Aniruddha Murahar Kulkarni, Prasanna Kumar Reddy Gayam, Jesil Mathew Aranjani
Life Sciences.2024; 348: 122692. CrossRef

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Orbital Infiltration as the First Site of Relapse of Primary Testicular T-cell Lymphoma: Hyun Jung Jun, Won Seog Kim, Ji Hyun Yang, Seong Yoon Yi, Young H. Ko, Jeeyun Lee, Chul Won Jung, Se Woong Kang, Keunchil Park; Cancer Res Treat. 2007;39(1):40-43. Published online March 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.1.40

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A 43-year-old male presented with a painless left testicular mass. The pathologic diagnosis of the radical orchiectomy specimen was peripheral T-cell lymphoma, unspecified (PTCL-u). According to the Ann Arbor staging system, his initial stage was III because of the right nasopharyngeal involvement. After first-line chemotherapy with four courses of the CHOP regimen and this was followed by involved-field radiotherapy, he achieved complete remission. Two months later, disease recurred to the left ciliary body of the left eye without evidence of involvement at other sites. Although the patient received intensive chemotherapy with autologous hematopoietic stem cell transplantation, he ultimately died of leptomeningeal seeding. Because both the central nervous system (CNS) and the orbit are sanctuary sites for chemotherapy, orbital infiltration of lymphoma should prompt physicians to evaluate involvement of the CNS and to consider performing prophylactic intrathecal chemotherapy as a treatment option.

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Relapse of Ocular Lymphoma following Primary Testicular Diffuse Large B-cell Lymphoma
Hye Ji Kwon, Joo Yong Lee
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Chronic lymphocytic leukemia and concurrent seminoma in the same testis
Kosuke Miyai, Fumihisa Kumazawa, Kimiya Sato, Hitoshi Tsuda
Journal of Pathology and Translational Medicine.2022; 56(1): 48. CrossRef
Diagnosis, prevention and treatment of central nervous system involvement in peripheral t-cell lymphomas
Natalia Zing, Thais Fischer, Massimo Federico, Carlos Chiattone, Andrés J.M. Ferreri
Critical Reviews in Oncology/Hematology.2021; 167: 103496. CrossRef
Primary testicular T-lymphoblastic lymphoma in a child
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Peripheral T-Cell Lymphoma, Not Otherwise Specified and Concurrent Seminoma in Testis
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Primary testicular lymphoma
Chan Y. Cheah, Andrew Wirth, John F. Seymour
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Testicular lymphoma, intraocular (Vitreoretinal) lymphoma, and brain lymphoma: Involvement of three immunoprivileged sites in one patient
Jacob Pe'er, Jacob M. Rowe, Shahar Frenkel, Eldad J. Dann
American Journal of Hematology.2010; 85(8): 631. CrossRef

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Three Cases of Synchronous Solid Tumor and Multiple Myeloma: Sang Hoon Ji, Joon Oh Park, Jeeyun Lee, Mi Jung Oh, Do Hyoung Lim, Byeong-Bae Park, Keun Woo Park, Se-Hoon Lee, Kihyun Kim, Won Seog Kim, Chul Won Jung, Young Suk Park, Young-Hyuck Im, Won Ki Kang, Mark H Lee, Keunchil Park; Cancer Res Treat. 2004;36(5):338-340. Published online October 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.5.338

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The association between a multiple myeloma and a secondary solid tumor is not well established. Some reports showed an increased risk of secondary solid neoplasms in multiple myeloma patients, but others have not. Three cases of the synchronous occurrence of multiple myelomas and solid tumors, namely, a small cell carcinoma of the lung, an adenocarcinoma of the colon and a squamous carcinoma of the pyriform sinus were experienced at our hospital. Therefore, herein is reported the clinical courses and treatment results. The stage of multiple myeloma was Durie-Salmon stage I in all of three cases; therefore, the solid tumors were treated as a primary target because the prognosis of early stage multiple myeloma is generally better than that of advanced solid tumor, while a smoldering or stage I myeloma do not need primary therapy until progression of the multiple myeloma. Two patients died of their solid tumors, but one patient is alive.

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Three-year progression-free survival of a patient with concomitant mucinous adenocarcinoma of the colon with peritoneal dissemination and multiple myeloma who received lenalidomide: a case report
Koki Tamai, Hajime Hirose, Yo Akazawa, Yukihiro Yoshikawa, Masatoshi Nomura, Hiroshi Takeyama, Masahiro Tokunaga, Mitsuyoshi Tei, Shu Okamura, Yusuke Akamaru
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The importance of oncological alertness in the differential diagnosis of inflammatory changes in the lungsdetected as a result of differential diagnosis of pneumonia
M. F. Petrukhnova, O. O. Voronkova, O. E. Buyanova, O. N. Antyufeeva, A. E. Kamalova, M. V. Kozhevnikova, I. S. Ilgisonis, Yu. N. Belenkov
Meditsinskiy sovet = Medical Council.2024; (9): 100. CrossRef
Synchronous multiple myeloma and lung adenocarcinoma: A clinical series
Fang Ye, Huan Wang, Ningning Li, Aijun Liu, Wenming Chen
Indian Journal of Pathology and Microbiology.2024; 67(2): 390. CrossRef
Simultaneous multiple myeloma and non‑small cell lung carcinoma: A case report and review of the literature
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Rapid progression of gastric cancer with liver metastasis after discontinuation of lenalidomide in a patient with concurrent multiple myeloma: A case report
Naoto Ujiie, Yoshitaka Enomoto, Naruhito Takido, Yasushi Kawaharada, Masashi Zuguchi, Yosuke Kubota
International Journal of Surgery Case Reports.2021; 81: 105834. CrossRef
Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma
Wenli Zuo, Xinghu Zhu, Jingke Yang, Zhenyang Mei, Mei Deng, Quande Lin, Yongping Song, Qingsong Yin
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Rishu Agarwal, Ritu Gupta, Archana Bhaskar, Atul Sharma, Sanjay Thulkar, Lalit Kumar
Journal of Clinical Oncology.2008; 26(35): 5814. CrossRef

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Esophageal Squamous Cell Carcinoma Recurring as a Solitary Renal Mass: Do Hyoung Lim, Young-Hyuck Im, Sang Hoon Ji, Byeong-Bae Park, Mi Jung Oh, Jeeyun Lee, Keun Woo Park, Se-Hoon Lee, Joon-Oh Park, Kihyun Kim, Won Seog Kim, Chul Won Jung, Young Suk Park, Won Ki Kang, Mark H Lee, Kwanmien Kim, Young Mog Shim, Keunchil Park; Cancer Res Treat. 2004;36(4):271-274. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.271

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Herein, a case of solitary, unilateral renal metastasis in a patient with curatively resected thoracic esophageal carcinoma, who achieved a pathological complete remission after neoadjuvant concurrent chemoradiotherapy, is reported. The kidney is the 4^th or 5^th most common visceral metastasis site of a primary esophageal carcinoma. More than 50% of renal metastases typically show bilateral involvement. Solitary, unilateral renal metastasis is extremely rare. Renal metastases from a primary esophageal carcinoma are usually latent and its diagnosis is very unusual in a live patient. The solitary renal metastasis in this case was not accompanied by metastases to other sites. The value of a nephrectomy in solitary renal metastasis of esophageal cancer is not known due to the rarity of such cases. A nephrectomy could be justified in limited situations, such as with uncertainty of histological diagnosis, severe life-threatening hematuria, which cannot be controlled by embolization, or solitary renal metastasis with a long disease-free interval.

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Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review
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Secondary Tumors of the Kidney: A Comprehensive Clinicopathologic Analysis
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Surgery for metachronous oligometastatic esophageal cancer: Is there enough evidence?
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Cirugía Española.2021; 99(7): 490. CrossRef
Surgery for metachronous oligometastatic esophageal cancer: Is there enough evidence?
Dimitrios Schizas, Michail Vailas, Maria Sotiropoulou, Ioannis A. Ziogas, Konstantinos S. Mylonas, Ioannis Katsaros, Alkistis Kapelouzou, Theodore Liakakos
Cirugía Española (English Edition).2021; 99(7): 490. CrossRef
The role of surgical treatment in isolated organ recurrence of esophageal cancer—a systematic review of the literature
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World Journal of Surgical Oncology.2018;[Epub] CrossRef
Esophageal Cancer with Solitary Renal Metastasis Treated with Multidisciplinary Therapy: A Case Report and Mini Review of the Literature
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The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2017; 17(1): 39. CrossRef
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BioMedicine.2016;[Epub] CrossRef
Unilateral renal metastases after definitive chemoradiation in squamous cell carcinoma of esophagus: A case report and review literature
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Asian Journal of Oncology.2016; 02: 046. CrossRef
Renal metastasis after esophagectomy of esophageal squamous cell carcinoma: a case report and literature review
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Thomas D. Willson, Matthew J. Blecha, Mark M. Connolly, Francis J. Podbielski
Journal of Gastrointestinal Cancer.2013; 44(3): 351. CrossRef
Synchronous Squamous Cell Carcinomas of the Esophagus and Renal Pelvis
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Use of GCDFP-15 (BRST-2) as a Specific Immunocytochemical Marker for Diagnosis of Gastric Metastasis of Breast Carcinoma: Keon Woo Park, Young Hyuck Im, Jeeyun Lee, Eungho Kim, Hyuk Lee, Bong Geun Song, Joon Oh Park, Kihyun Kim, Chul Won Jung, Young Suk Park, Won Ki Kang, Mark H Lee, Keunchil Park; Cancer Res Treat. 2003;35(5):460-464. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.460

Abstract PDF

Metastasis of breast cancer to the stomach is relatively uncommon and typically occurs in patients with disseminated diseases. This may cause difficulty in differentiating it from primary gastric carcinoma. The correct diagnosis of the primary source is important, since the treatment and prognosis of metastatic breast cancer is quite different from those of metastatic gastric cancer. Immunohistochemical staining with GCDFP-15 (gross cystic disease fluid protein-15) can be used to differentiate primary gastric carcinoma and gastric metastasis from breast cancer. We report two cases of gastric metastasis of breast cancer by describing their clinical course, illustrating the histologic findings, and showing the results of immunohistochemical staining with GCDFP-15.

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Journal of the Korean Society of Coloproctology.2008; 24(2): 144. CrossRef

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Original Articles

Role of PET Scan in Staging Work - up and Reevaluation after Therapy in Lymphoma: Young Jin Yuh, Chul Won Jung, Seock Ah Im, Dae Seog Heo, Yung Jue Bang, Seonyang Park, June Key Chung, Myung Chul Lee, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(5):1011-1017.

Abstract PDF: PURPOSE
The authors evaluated the usefulness of the positron emission tomography (PET) with fluorine-18-tluorodeoxyglucose (8F-FDG) in initial staging, reevaluation after radical therapy and diagnosis of recurrence for non-Hodgkin's lymphoma, compaired to conventional imaging studies.
MATERIALS AND METHODS
FDG-PET (ECAT Exact 47, Siemens) and conventional chest X-ray and computerized tomography (CT) were studied in patients with non-Hodgkins lymphoma.
RESULTS
There were 17 patients (13 male, 4 female). Age was ranged from 18 to 62 years (median 49). By histological subgroup, diffuse large cell were 8 cases, peripheral T cell were 2 cases, diffuse mixed was 1 case, follicular mixed was 1 case, Burkitt's lymphoma was 1 case, Hodgkin's disease were 3 cases. The aims for PET were the initial staging work-up in 7 cases, the reevaluation of residual disease after radical therapy in 7 cases, the diagnosis of recurrence after complete remission in 3 cases. Between PET image and the conventional image, there were 3 cases with discrepancy, 1 case for initial staging work-up and 2 cases for the reevaluation of residual disease after radical therapy. Among the 3 cases with discrepancy, the 2 cases for the reevaluation of residual disease after radical therapy revealed that PET image reflects the involvement of lymphoma more accurately than the conventional image.
CONCLUSION
The visual analysis of FDG-PET would be helpful in determining the residual disease of lymphoma after radical therapy.

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Clinical Characteristics and Prognostic Factors of Metastatic Tumor of Unknown Primary: Eun Kyung Cho, Keun Seok Lee, Chul Won Jung, Won Seog Kim, Ki Hyeong Lee, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(3):607-616.

Abstract PDF: PURPOSE
For malignant diseases, predictions about tumor behavior and determination of appropriate therapy are based on the primary tumor sites, but 2-9% of cancer patients are diagnosed without identifiable primary tumor sites. Metastatic tumors of unknown primary origin (MUO) are a heterogeneous group of tumors with variable natural histories. The majority of these patients fall outside of treatable subjects and seldom respond to therapy. To define further the natural history of MUO and identify prognostic factors, we undertook a clinical analysis of 141 consecutive patients with a presumed diagnosis of MUO.
MATERIALS AND METHODS
One hundred forty-one patients were diagnosed with unknown primary tumor from Jan. 1, 1992 through Aug. 31, 1995. The primary end point for the study was survival, which was calculated from the first day of patient registration diagnosed histologically. The survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. To identify important prognostic factors, univariate and multivariate analyses were conducted.
RESULTS
Most of the 141 patients had histologic or cytologic evidence of adenocarcinoma and had more than one site metastatically involved. The predominant sites of tumor involvement were lymph node, peritoneum, bone, liver, lung, and pleura. Univariate and multivariate analyses identified numerous important prognostic factors with a significant influence on survival, including performance status (P 0.0001), specific organ sites involved (lung P 0.0076 or liver P 0.0310), and chemotherapy group (P- 0.0480).
CONCLUSION
This study validated clinical courses and important prognostic factors that had an impact on survival in MUO.

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A Phase 2 Study of VP-16 , Ifosfamide , and Cisplatin ( VIP ) Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Limited Small Cell Lung Cancer: Seok Ah Im, Moon Hee Lee, Chul Won Jung, Dae Seog Heo, Yung Jue Bang, Young Soo Shim, Chan Il Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(2):306-312.

Abstract PDF: PURPOSE
A phase II study of etoposide, ifosfamide, cisplatin combination chemotherapy and concurrent thoracic irradiation in patients with untreated limited small cell lung cancer (SCLC) was conducted to assess toxicities, response rate, response duration, and median survival.
MATERIALS AND METHODS
Patients with histologically confirmed SCLC with a ECOG criteria 2 and adequate renal function and bone marrow reserve were eligible. Each cycle consisted of VP-16 100 mg/m i.v, days 1-3, ifosfamide 1,200 mg/m i.v. days 1-3 with Mesna, and cisplatin 30 mg/m i.v. days 1-3. Cycles were repeated every 21 days. Concutrent thoracic itradiation was given as total 40-45 Gy for 4-5 weeks beginning within 24 hours of the third cycle. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle.
RESULT
Forty two patients with limited SCLC were treated at Seoul National University Hospital between December 1993 and August 1996. Three patients were not evaluable because of lost to follow up (2 patients) and one treatment-related early death. Of 39 evaluable patients, responses were seen in 38 (97%) patients including 22 (56%) complete responses and 16 (41%) partial responses. The median remission duration was 65 wks. The median disease free survival was 60 wks. The median overall survival was not reached and 2-year survival was 69% with median duration of follow up of 63.5 wks. Hematologic side effects (WHO Gr>III/IV) of evaluable 228 cycles of chemotherapy were leukopenia in 34%, thrombocytopenia in 16%. One patient expired after prolonged leukopenia and sepsis. Nonhematologic side effects (WHO Gr>II) included nausea and vomiting (17%) and peripheral neuropathy (2%).
CONCLUSION
VIP combination chemotherapy with concurrent thoracic irradiation is effective and tolerable in limited SCLC.

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Study on Growth Suppression Effect of Vetamin D3 Mediated by Transfrorming Growth Factor-B1(TGF-B1) in Acute Myelogenous Leukemic Cell: Chul Won Jung, Sang Jae Lee, Myung Joo Ahn, Tae Joon Jung, In Soon Kim, Il Young Choi, Jae Koo Seol, Eun Sil Kim, Byung Kook Kim, Young Yeol Lee; J Korean Cancer Assoc. 1998;30(4):827-841.

Abstract PDF: PURPOSE
Vitamin D3 was shown to arrest the growth of acute myelogenous leukemic cells and transforming growth factor- B1 (TGF- B1) was reported to be involved in the mechanism of vitamin D3. We studied the growth inhibitory effect of 1,25(OH)2-vitamin D3(C) and its analogue (EB1089) in leukemic cell lines and the changes in the secretion or the activation of TGF-B1 in the supernatant and the status of TGF-B1 type II receptor.
MATERIALS AND METHODS
Growth inhibition by vitamin D3 and TGF-B1 in 5 leukemic cell lines (HEL, HL-60, U937, KG-1, K562) were assessed with clonogenic and [3H]thymidine assay respectively. TGF-B type II receptor status was examined by Southern and Northern blotting. The concentrations of TGF- B1 in the supernatant were quantitated by enzyme immunoassay.
RESULTS
The growth of HEL, HL-60, U937 were inhibited in a dose-dependent fashion by both C and EB1089, more markedly by the latter. Anti-TGF-B neutralizing antibody partially reversed the growth inhibition. TGF-B1 markedly inhibited the growth of HEL, U937, KG-1, SNU-16 dose dependently while HL-60 and K562 showed no growth inhibition. HEL secreted latent TGF- 1 and HL-60 activated latent TGF- B1 or secreted active TGF-B1 irrespective of the treatment with vitamin D3. In U937, vitamin D3 increased the concentration of both active and latent TGF-B1. Deletion or abnormal expression of TGF- B type II receptor gene was not found in the 5 cell lines examined.
CONCLUSION
Vitamin D3 has various pattern of growth inhibition in acute myelogenous leukemia and inhibits the growth of some cell lines by secretion or activation of TGF-B1. Abnormality of TGF-B type II receptor DNA or mRNA seems to be rare.

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Effects of Combination Chemotherapy Depending on The Expression of Neuron Specific Enolase (NSE), P-Glycoprotein (PgP) and Glutathione S-Transferase (GST)-pai in Advanced Non-Small Cell Lung Cancer: Chul Won Jung, Jong Wook Shin, Sang Jae Lee, Eon Sub Park; J Korean Cancer Assoc. 1997;29(2):189-197.

Abstract PDF: PURPOSE
Neuroendocrine differentiation and expression of drug resistance may affect the response to chemotherapy and the prognosis of advanced non-small cell lung cancer. We conducted retrospective study to evaluate the possibilities of neuroendocrine differentiation and drug resistance markers being used as prognostic factors in patients with non-small cell lung cancer. MATERIAL AND METHOD: Immunohistochemical staining of NSE, PgP and GST-pai with polyclonal antibodies in pathologic specimens of 47 patients with non-small cell lung cancer were done. The relationship between the expression of the markers and the response to cisplatin-based chemotherapy and the overall survival were assessed.
RESULTS
NSE staining was positive in 17% and there was no difference between adenocarcinoma and squamous cell carcinoma. NSE positive patients showed increased response rate (63% vs 26%, p=0.049) and prolonged response duration (15.8mo vs 4.5mo, p=0.0007). But there was no difference in overall survival between NSE positive and negative groups. The PgP positive rate was 17% and GST-pai positive rate was 47%. No correlations were found among the expression of drug resistance, the sensitivity to chemotherapy and overall survival.
CONCLUSION
Patients with non-small cell lung cancer with positive NSE showed increased response rate to chemotherapy and prolonged response duration but overall survival was not related to NSE expression. Expression of PgP and GST- were not important in predicting the prognosis in non-small cell lung cancer.

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Combination Chemotherapy with 5-Fluorouracil and Carboplatin for Advanced Head and Neck Cancer: Eun Kyung Cho, Won Sup Lee, Chul Won Jung, Keun Seok Lee, Won Seog Kim, Ki Hyeong Lee, Dae Seog Heo, Yung Jue Bang, Kwang Hyun Kim, Charn II Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1996;28(1):94-104.

Abstract PDF: Twenty-nine patients with previously untreated, locally advanced head and neck cancer were treated with two or three cycles of combination chemotherapy consisting of 5- fluorouracil infusion and carboplatin, followed by surgery and/or curative radiotherapy. Nine patients with recurrent head and neck cancer were treated with the same combination chemotherapy. The results were as follows; 1) Among 28 evaluable patients, response rate was 71.4%(partial response) after neoadjuvant chemotherapy. Following local modality(surgery and/or radiotherapy), response rate was 79%(complete response 51.4%, and partial response 25%). 2) One year survival rate in neoadjuvant group was 83% and one year progression-free survival rate, 68.8%. The progression-free survival of responders was significantly prolonged in comparison with that of non-responders(p<0.05). 3) In palliative treatment group, one partial response(11%) was observed among nine patients. Median time to progression was 6.8 weeks and median survival was 17.7 weeks; there was no significant difference between responders and non-responders. 4) Nausea and vomiting were frequently observed but easily controlled. Hematologic toxicities-leukopenia and thrombocytopenia were observed but were reversible. In conclusion, combination chemotherapy with carboplatin and 5-FU was effective for locally advanced head and neck cancer in neoadjuvant setting, but it had limited benefits for recurrent diseases. Toxicities were tolerable and neurotoxicity, ototoxicity, and nephrotoxicity were not observed.

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Phase 2 study of Ifosfamide Single and Ifosfamide and Doxorubicin Combination Chemotherapy for Hepatocellular Carcinoma: Soo Jeong Park, Hyeoung Joon Kim, Chul Won Jung, Sang Jae Lee; J Korean Cancer Assoc. 1996;28(4):718-726.

Abstract PDF: Though hepatocellular carcinoma(HCC) is one of the ten most common cancers in the world, the prognosis is dismal because most tumors are not suitable for surgical resection at the time of diagnosis. Doxorubicin is the only chemotherapeutic agent generally accepted to be of some use in its treatment. Doxorubicin is first described by Olweny et al in 1975 to cause regression in all ll HCC subjects evaluated, later trials showed response rate varying from 0% to 44%. However, the median survival was not increased. In 1988, intravenous ifosfamide has also been reported in unresectable HCC to induce partial remission and more longer survival duration than previous study. Therefore, we conducted a phase II trial ifosfamide, and combining ifosfamide and doxorubicin in previously untreated patients with histologically confirmed HCC and evaluate the efficacy and combining effect of ifosfamide. Each cycle consisted of ifosfamide 1.5gm/§³ i.v. days 1~5 with mesna in single therapy and ifosfamide 1.3gm/§³ i.v. days 1~5 with mesna and doxorubicin 40mg/§³ i.v. day 1 in combination chemotherapy, repeated every 4 weeks. Thirty-three patients were enrolled (ifosfamide: 16, ifosfamide and doxorubicin: 17). Five patients were not evaluated beacause of lost to follow-up and refusal to further therapy. Of twenty-eight evaluable patients, four patients achieved partial remissions, one in ifosfamide and three in combination chemotherapy and overall remission rate was 14%(8% in ifosfamide and 19% in combination chemotherapy). The median remission duration of ifosfamide and combining ifosfamide and doxorubicin were 5 and 4.5 months, respectively. The median follow-up duration were 2.5 months(0.5~8.5 months) in ifosfamide and 4 months(0.5~10 months) in combination chemotherapy. The median survivals in ifosfamide and combination chemotherapy were 2.5 months and 4.5 months, respectively(p=0.16 for survival curves by log rank test). Hematologic side effects(WHO Gr¡A2) of evaluable 92 cycles of chemotherapy (ifoefamide: 33, ifosfamide and doxorubicin: 59) were anemia in 5 occassions (ifosfamide: 1, ifosfamide and doxorubicin: 4), leukopenia in 10 occasions(ifosfamide: 2, ifosfamide and doxorubicin: 8), and 1 occassion thrombocytopenia in combination chemotherapy. Non-hematologic side effects(WHO Gr¡A2) included alopecia(7%), nausea and vomiting(21%), without hemorrhagic cystitis and other toxicities. In conclusion, ifosfamide, and ifosfamide and doxorubicin combination chemotherepy seems to be similar effect for far advanced hepatocellular carcinoma and can not be prolongation of patients survival. Since those responses seen were generally incomplete and transient, further clinical trials of this agent used in combination or sequentially with other agents are indicated.

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