Abstract
Background
Most epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs) experience oligoprogressive disease. Local ablation for isolated resistant sites continued with the original EGFR-TKI showed good efficacy in these patients. We conducted this multicenter retrospective study to investigate the potential benefit of thermal ablation in NSCLC patients that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment.
Methods
A total of 71 EGFR-mutant patients treated with EGFR-TKIs were identified. Progression-free survival 1 (PFS1) was calculated from the initiation of TKI treatment to first progression. Patients with metastatic sites ≤ 3 in less than 3 extra-CNS organs suitable for local ablation therapy received either radiofrequency ablation or microwave ablation to these sites and continued on the original TKIs. PFS2 was defined from the first progression to second progression after ablation.
Results
The median PFS1 for all patients was 11.8 months. Eighty extra-CNS oligoprogressive lesions in 71 patients were ablated. Thirty-six of 71 patients progressed after thermal ablation and 31 of whom died during the study period. The median PFS2 after thermal ablation was 10.0 months, and the median overall survival was 26.4 months. PFS1 and PFS2 were highly correlated with OS, whereas PFS1 was not correlated with PFS2. The numbers of oligoprogressive lesions were significantly and independently associated with PFS2.
Conclusion
Local thermal ablation for the oligoprogressive lesions with continuous EGFR-TKI treatment is associated with additional 10 months of disease control and should be recommended in TKI acquired resistant-NSCLC patients.
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References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.
Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, Varella-Garcia M, Franklin WA, Aronson SL, Su PF, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998–2006.
Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327–34.
Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O’Byrne K, Feng J, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141–51.
Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label ENSURE study. Ann Oncol. 2015;26(9):1883–9.
Xu Y, Xie Z, Lu H. Detection of epidermal growth factor receptor mutation in the peripheral blood of patients with esophageal carcinoma to guide epidermal growth factor receptor-tyrosine kinase inhibitor treatment. J Cancer Res Ther. 2018;14(1):103–5.
Piotrowska Z, Sequist LV. Treatment of EGFR-mutant lung cancers after progression in patients receiving first-line EGFR tyrosine kinase inhibitors: a review. JAMA Oncol. 2016;2(7):948–54.
Zhang K, Yuan Q. Current mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and updated therapy strategies in human nonsmall cell lung cancer. J Cancer Res Ther. 2016;12(Supplement):C131–7.
Park K, Yu CJ, Kim SW, Lin MC, Sriuranpong V, Tsai CM, Lee JS, Kang JH, Chan KC, Perez-Moreno P, et al. First-line erlotinib therapy until and beyond response evaluation criteria in solid tumors progression in Asian patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer: the ASPIRATION study. JAMA Oncol. 2016;2(3):305–12.
Lo PC, Dahlberg SE, Nishino M, Johnson BE, Sequist LV, Jackman DM, Janne PA, Oxnard GR. Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer. Cancer. 2015;121(15):2570–7.
Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011;17(6):1616–22.
Weickhardt AJ, Scheier B, Burke JM, Gan G, Lu X, Bunn PA Jr, Aisner DL, Gaspar LE, Kavanagh BD, Doebele RC, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012;7(12):1807–14.
Yu HA, Sima CS, Huang J, Solomon SB, Rimner A, Paik P, Pietanza MC, Azzoli CG, Rizvi NA, Krug LM, et al. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8(3):346–51.
Solbiati L, Ierace T, Goldberg SN, Sironi S, Livraghi T, Fiocca R, Servadio G, Rizzatto G, Mueller PR, Del Maschio A, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. Radiology. 1997;202(1):195–203.
Dupuy DE, Zagoria RJ, Akerley W, Mayo-Smith WW, Kavanagh PV, Safran H. Percutaneous radiofrequency ablation of malignancies in the lung. AJR Am J Roentgenol. 2000;174(1):57–9.
Ambrogi MC, Lucchi M, Dini P, Melfi F, Fontanini G, Faviana P, Fanucchi O, Mussi A. Percutaneous radiofrequency ablation of lung tumours: results in the mid-term. Eur J Cardiothorac Surg. 2006;30(1):177–83.
Liu H, Steinke K. High-powered percutaneous microwave ablation of stage I medically inoperable non-small cell lung cancer: a preliminary study. J Med Imaging Radiat Oncol. 2013;57(4):466–74.
Ni Y, Bi J, Ye X, Fan W, Yu G, Yang X, Huang G, Li W, Wang J, Han X, et al. Local microwave ablation with continued EGFR tyrosine kinase inhibitor as a treatment strategy in advanced non-small cell lung cancers that developed extra-central nervous system oligoprogressive disease during EGFR tyrosine kinase inhibitor treatment: a pilot study. Medicine (Baltimore). 2016;95(25):e3998.
Liu B, Liu L, Hu M, Qian K, Li Y. Effect of percutaneous radiofrequency ablation after thoracoscopic pleurodesis for treating non-small cell lung cancer patients with malignant pleural effusion and/or pleural dissemination. Thorac Cancer. 2016;7(5):549–55.
Ye X, Fan W, Wang H, Wang J, Wang Z, Gu S, Feng W, Zhuang Y, Liu B, Li X, et al. Expert consensus workshop report: guidelines for thermal ablation of primary and metastatic lung tumors. J Cancer Res Ther. 2018;14(4):730–44.
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.
Shin DY, Lee DH, Kim CH, Koh JS, Lee JC, Baek HJ, Kim SW, Choi CM, Na II. Epidermal growth factor receptor mutations and brain metastasis in patients with nonadenocarcinoma of the lung. J Cancer Res Ther. 2016;12(1):318–22.
Qi C, Qi Q, Ding L, Hong X, Zhou N, Ying L, Wu H. Continuation of epidermal growth factor receptor tyrosine kinase inhibitor treatment prolongs disease control in non-small-cell lung cancers with acquired resistance to EGFR tyrosine kinase inhibitors. Oncotarget. 2015;6(28):24904–11.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D’Amico TA, Decamp MM, Dilling TJ, Dobelbower M. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15(4):504–35.
Shukuya T, Takahashi T, Naito T, Kaira R, Ono A, Nakamura Y, Tsuya A, Kenmotsu H, Murakami H, Harada H. Continuous EGFR-TKI administration following radiotherapy for non-small cell lung cancer patients with isolated CNS failure. Lung Cancer. 2011;74(3):457–61.
Wang Y, Li Y, Xia L, Niu K, Chen X, Lu D, Kong R, Chen Z, Sun J. Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment. Clin Transl Oncol. 2017;20:1–8.
Chmielecki J, Foo J, Oxnard GR, Hutchinson K, Ohashi K, Somwar R, Wang L, Amato KR, Arcila M, Sos ML. Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci Transl Med. 2011;3(90):90ra59.
Hakime A, Le Cesne A, Deschamps F, Farouil G, Boudabous S, Auperin A, Domont J, Debaere T. A role for adjuvant RFA in managing hepatic metastases from gastrointestinal stromal tumors (GIST) after treatment with targeted systemic therapy using kinase inhibitors. Cardiovasc Interv Radiol. 2014;37(1):132–9.
Minami T, Sato S, Watanabe Y, Matsuda R, Yotsuya S, Yamada A, Tanaka T, Kondo S, Ebihara T, Togo G, et al. Successful treatment of a gastrointestinal stromal tumor with liver metastases in a case that tolerated imatinib administration, by radiofrequency ablation using contrast-enhanced ultrasonography. Nihon Shokakibyo Gakkai Zasshi. 2010;107(3):442–8.
Carrafiello G, Mangini M, Fontana F, Di Massa A, Ierardi AM, Cotta E, Piacentino F, Nocchi Cardim L, Pellegrino C, Fugazzola C. Complications of microwave and radiofrequency lung ablation: personal experience and review of the literature. Radiol Med. 2012;117(2):201–13.
Kashima M, Yamakado K, Takaki H, Kodama H, Yamada T, Uraki J, Nakatsuka A. Complications after 1000 lung radiofrequency ablation sessions in 420 patients: a single center’s experiences. AJR Am J Roentgenol. 2011;197(4):W576–80.
Takeda A, Sanuki N, Eriguchi T, Kaneko T, Morita S, Handa H, Aoki Y, Oku Y, Kunieda E. Stereotactic ablative body radiation therapy for octogenarians with non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2013;86(2):257–63.
Yang X, Ye X, Huang G, Han X, Wang J, Li W, Wei Z, Meng M. Repeated percutaneous microwave ablation for local recurrence of inoperable Stage I nonsmall cell lung cancer. J Cancer Res Ther. 2017;13(4):683–8.
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The work was supported by National Natural Science Foundation of China (81502610).
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Ni, Y., Liu, B., Ye, X. et al. Local Thermal Ablation with Continuous EGFR Tyrosine Kinase Inhibitors for EGFR-Mutant Non-small Cell Lung Cancers that Developed Extra-Central Nervous System (CNS) Oligoprogressive Disease. Cardiovasc Intervent Radiol 42, 693–699 (2019). https://doi.org/10.1007/s00270-018-02153-x
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DOI: https://doi.org/10.1007/s00270-018-02153-x