Chemosensitivity of lung cancer: Differences between the primary lesion and lymph node metastasis

Maniwa,Yoshimasa; Yoshimura,Masahiro; Hashimoto,Shotaro; Takata,Masahiko; Nishio,Wataru

doi:10.3892/ol_00000061

Chemosensitivity of lung cancer: Differences between the primary lesion and lymph node metastasis

Authors:
- Yoshimasa Maniwa
- Masahiro Yoshimura
- Shotaro Hashimoto
- Masahiko Takata
- Wataru Nishio
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Affiliations: Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Published online on: March 1, 2010 https://doi.org/10.3892/ol_00000061
Pages: 345-349

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Abstract

In this study, chemosensitivity tests were performed on both primary lesions (PLs) and lymph node metastases (LMs) from surgically resected non-small cell lung cancer (NSCLC). Differences between the results obtained were evaluated. Operative specimens were obtained from 13 patients with NSCLC [6 with squamous cell carcinoma (SQ) and 7 with adenocarcinoma (AD)] whose lymph nodes were confirmed to be positive for metastasis. Both the PL and LM from the same patient were examined immediately after resection. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was used as the chemosensitivity test against six anticancer drugs [5-fluorouracil (5-FU), cisplatin, gemcitabine, docetaxel, vinorelbine and SN-38 (an active metabolite of irinotecan)]. When the growth rate, determined by the T/C ratio (T, signal for viable cells in the treated group and C, signal in the control) was less than 50%, the tumor cells were considered to be sensitive to the drug. Only in 4 cases (2 SQ and 2 AD) was the chemosensitivity of the primary lesion identical to that of LM. In the SQ cases, chemosensitivity of the primary lesions to 5-FU tended to be consistent with that of LMs. In contrast, the primary lesions in 4 of the 7 AD cases were negative for chemosensitivity to 5-FU; however, LMs were sensitive. In many cases, the chemosensitivity of the PLs to each anticancer drug differed from that of the LMs. In conclusion, both primary and metastatic tumors should be examined to ensure maximum clinical efficacy of in vitro drug-sensitivity testing for adjuvant chemotherapy after complete resection of n1 and n2 NSCLC.

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1	Freeman AE and Hoffman RM: In vivo-like growth of human tumors in vitro. Proc Natl Acad Sci USA. 83:2694–2698. 1986. View Article : Google Scholar : PubMed/NCBI
2	Cole SP: Rapid chemosensitivity testing of human lung tumor cells using the MTT assay. Cancer Chemother Pharmacol. 17:259–263. 1986.PubMed/NCBI
3	Kobayashi H, Tanisaka K, Doi O, et al: An in vitro chemosensitivity test for solid human tumors using collagen gel droplet embedded cultures. Int J Oncol. 11:449–455. 1997.
4	Shaw GL, Gazdar AF, Phelps R, et al: Individualized chemotherapy for patients with non-small cell lung cancer determined by prospective identification of neuroendocrine markers and in vitro drug sensitivity testing. Cancer Res. 53:5181–5187. 1993.PubMed/NCBI
5	Gazdar AF, Steinberg SM, Russell EK, et al: Correlation of in vitro drug-sensitivity testing with response to chemotherapy and survival in extensive-stage small cell lung cancer: a prospective clinical trial. J Natl Cancer Inst. 82:117–124. 1990. View Article : Google Scholar : PubMed/NCBI
6	Cortazar P, Gazdar AF, Woods E, et al: Survival of patients with limited-stage small cell lung cancer treated with individualized chemotherapy selected by in vitro drug sensitivity testing. Clin Cancer Res. 3:741–747. 1997.PubMed/NCBI
7	Higashiyama M, Kodama K, Yokouchi H, et al: Cisplatin-based chemotherapy for postoperative recurrence in non-small cell lung cancer patients: Relation of the in vitro chemosensitive test to clinical response. Oncol Rep. 8:279–283. 2001.PubMed/NCBI
8	Takamura Y, Kobayashi H, Taguchi T, et al: Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers. Int J Cancer. 98:450–455. 2002. View Article : Google Scholar : PubMed/NCBI
9	Kikuchi T, Daigo Y, Katagiri T, et al: Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene. 22:2192–2205. 2003. View Article : Google Scholar : PubMed/NCBI
10	Yamaue H, Tanimura H, Noguchi K, et al: Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay. Br J Cancer. 66:794–799. 1992. View Article : Google Scholar : PubMed/NCBI
11	Takamura Y, Kobayashi H, Taguchi T, Motomura K, Inaji H and Noguchi S: Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers. Int J Cancer. 98:450–455. 2002. View Article : Google Scholar : PubMed/NCBI
12	Nakahara T, Sakaeda T, Nakamura T, et al: Chemosensitivity assessed by collagen gel droplet embedded culture drug sensitivity test, and MDR1, MRP1 and MRP2 mRNA expression in human colorectal adenocarcinomas. Pharm Res. 21:406–412. 2004. View Article : Google Scholar : PubMed/NCBI
13	Nagai N, Minamikawa K, Mukai K, Hirata E, Komatsu M and Kobayashi H: Predicting the chemosensitivity of ovarian and uterine cancers with the collagen gel droplet culture drug-sensitivity test. Anticancer Drugs. 16:525–531. 2005. View Article : Google Scholar : PubMed/NCBI
14	Shimizu T, Murata S, Mekata E, et al: Clinical potential of an antitumor drug sensitivity test and diffusion-weighted MRI in a patient with a recurrent solid pseudopapillary tumor of the pancreas. J Gastroenterol. 42:918–922. 2007. View Article : Google Scholar : PubMed/NCBI
15	Cartazar P and Johnson BE: Review of the efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing for patients with cancer. J Clin Oncol. 17:1625–1631. 1999.PubMed/NCBI
16	Bunn PA and Kelly K: New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: a review of the literature and future directions. Clin Cancer Res. 5:1087–1100. 1998.PubMed/NCBI
17	Schiller JH, Harrington D, Belani CP, et al; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med. 346:92–98. 2002. View Article : Google Scholar
18	Goya T, Asamura H, Yoshimura H, et al: The Japanese Joint Committee of Lung Cancer Registry. Prognosis of 6644 resected non-small cell lung cancers in Japan: a Japanese Lung Cancer Registry Study. Lung Cancer. 50:227–234. 2005. View Article : Google Scholar : PubMed/NCBI
19	The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 350:350–360. 2004.PubMed/NCBI
20	Kato H, Ichinose Y, Ohta M, et al: A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 350:1713–1721. 2004. View Article : Google Scholar : PubMed/NCBI
21	Tada H, Tsuchiya R, Ichinose Y, et al: A randomized trial comparing adjuvant chemotherapy versus surgery alone for completely resected pN2 non-small cell lung cancer. Lung Cancer. 43:167–173. 2004. View Article : Google Scholar : PubMed/NCBI
22	Keller SM, Adak S, Wagner H, et al: A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small cell lung cancer. N Eng J Med. 343:1217–1222. 2000. View Article : Google Scholar : PubMed/NCBI