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Neoadjuvant (Induction) Erlotinib Response in Stage IIIA Non–Small-Cell Lung Cancer

Department of Surgical Oncology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

Jacobus A. Burgers, Nico Van Zandwijk

Department of Thoracic Oncology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

Rick L.M. Haas

Department of Radiotherapy, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

Renée van Pel

Department of Pathology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

A 67-year-old never-smoking woman, who had been treated for four malignancies in the last 30 years (sarcoma of a lower extremity, bilateral breast cancer, and several basal cell carcinomas) presented with a suspect lesion on a chest x-ray. The computed tomography (CT) scan showed a density of 2 cm in the apex of the left lower lobe (Fig 1A) and enlargement of hilar nodes, the subcarinal lymph nodes (Naruke station 7; Fig 1B), and left lower para- and pretracheal lymph nodes (Naruke station 4). On [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET), all lesions showed increased [¹⁸F]FDG uptake (Figs 2A and 2B, arrows). The subcarinal lymph node was punctured using endo-esophageal ultrasound-guided fine-needle aspiration, revealing a Thyroid Transcription Factor-1–positive carcinoma, probably adenocarcinoma on pathological examination (Fig 3A, Giemsa stain, 200x). The fifth primary tumor revealed to be stage III non–small-cell lung cancer (NSCLC). Mediastinoscopy was performed to assess the feasibility of (chemo)radiation, and confirmed the presence of poorly differentiated NSCLC metastases in the pretracheal and left paratracheal lymph nodes. Although the right paratracheal nodes were tumor negative, radical radiotherapy covering all tumor sites in lung and mediastinum was considered impossible due to previous irradiation on the chest (mammary carcinoma). During our multidisciplinary consultation, two unconventional approaches were proposed. First, resection of the small peripherally located tumor by limited resection would leave a sufficiently small tumor area to allow radical radiotherapy. Second, neoadjuvant treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) was proposed, since an EGFR mutation analysis had revealed an exon 19 deletion, indicating that the chance for response to EGFR inhibitors was considerably higher than to standard platinum-based chemotherapy. Erlotinib was prescribed at a dose of 150 mg daily for a 3-week period and was monitored carefully by PET/CT. Adverse effects were confined to mild skin toxicity (grade 1). The PET/CT scan after 21 days of treatment showed a striking metabolic response (Figs 1C, 1D, 2C, and 2D). Seven days thereafter, an anatomic resection of the apex of the left lower lobe was performed via a muscle sparing lateral thoracotomy. Mediastinal lymph nodes were sampled, and all palpable lymph nodes in the subcarinal area were dissected. Postoperative recovery was uneventful. Pathological examination of the apex of the left lower lobe showed a 1.2-cm rest lesion with strong fibrotic degeneration. No vital tumor was initially detected, but additional staining did reveal a microscopic vital rest of 1.5 mm (maximal diameter) in the center of a widespread area of necrosis and inflammatory reaction (Fig 3B, hematoxylin-eosin stain, 100x, area in box is enlarged in Fig 3C, in which ovals indicate two regions where the vital tumor rests among lymphocytic infiltrate, proliferation of fibroblasts, collagen deposits, giant cells and numerous peripheral foamy macrophages; Fig 3C, high magnification of hematoxylin-eosin–stained resection specimen, 200x; and Fig 3D, complete view of all regions, pankeratin immunostain, 100x, brown color indicates vital tumor cells). All dissected lymph nodes (stations 7, 8, 9, 10, 11, 12) were free of tumor.

View larger version (46K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1.

View larger version (58K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2.

View larger version (134K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Employment or Leadership Position: None Consultant or Advisory Role: Nico Van Zandwijk, Roche (C), Merck (C), Eli Lilly & Co (U) Stock Ownership: None Honoraria: Nico Van Zandwijk, Roche, Merck Research Funding: Nico Van Zandwijk, Eli Lilly & Co; Houke M. Klomp, Roche Expert Testimony: None Other Remuneration: None

ACKNOWLEDGMENTS

We thank Renato Valdes Olmos, MD, PhD, nuclear medicine physician, and Jelle Teertstra, MD, radiologist, for their assistance in producing the [¹⁸F]FDG-PET/CT scan and CT scan images for this report. We thank our colleagues H. Rijna, MD, PhD, and C. Weenink, MD, from the Kennemer Gasthuis, Haarlem; H.E. Codrington, MD, from the HagaHospital, The Hague; and A. Dingemans, MD, PhD, from The Academic Hospital, Maastricht, the Netherlands, for their contribution to the M06-NEL study.

REFERENCE

1. van Zandwijk N, Mathy A, Boerrigter L, et al: EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: Retro- and prospective observations in non–small-cell lung cancer. Ann Oncol 18:99-103, 2007[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kappers, I. Articles by van Pel, R. Search for Related Content PubMed PubMed Citation Articles by Kappers, I. Articles by van Pel, R. Social Bookmarking                            What's this?