Early-stage locally advanced non-small cell lung cancer (NSCLC) Clinical Case Discussion

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Early-stage locally advanced non-small cell lung cancer (NSCLC) Clinical Case Discussion Pieter Postmus The Clatterbridge Cancer Centre Liverpool Heart and Chest Hospital Liverpool, United Kingdom 1

2

Symptoms Patient DLG 1937 Pain left shoulder Question: Is there relation between pain left shoulder and tumour LLL? LLL, left lower lobe

Diagnosis Patient DLG 1937 Transthoracic CT guided biopsy Squamous cell carcinoma p63 positive MRI brain without metastases ct2acn0cm0, Stage IB T3 (invading parietal pleura) or T4 (invading diaphragm)???? CT, computed tomography; MRI, magnetic resonance imaging

Algorithm lymph node staging

Tumour board Patient DLG 1937 Comorbidities: - Coronary heart disease - COPD Stage 2, with severe diffusion impairment COPD, chronic obstructive pulmonary disease

Preoperative cardiac evaluation. AHA/ACC, American Heart Association/American College of Cardiology; CABG, coronary artery bypass grafting; ECG, electrocardiogram; PCI, percutaneous coronary intervention; RCRI, revised cardiac risk index; TIA, transient ischaemic attack.

Preoperative respiratory evaluation DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume in 1 second; ppo, predicted postoperative; VO2, oxygen consumption.

Algorithm for patients with stage I lung cancer and emphysema CT, computed tomography; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume 1; FVC, forced vital capacity; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; LVRS, lung volume reduction surgery; RFA, radiofrequency ablation; RV, reserve volume; SBRT, stereotactic body radiotherapy; TLC, total lung capacity

Treatment Patient DLG 1937 ct2acn0cm0, Stage IB Radiotherapy: 10x 6 Gy TNM, tumour, node, metastasis

Follow-up (3 years) Patient DLG 1937

No symptoms X-ray thorax as part of check-up Patient BU 1956

Diagnostic Patient BU 1956 rebus (radial endobronchial ultrasound) Biopsy lung: adenocarcinoma cells EBUS done through 21G or 22G needle usually gives only aspirate, difficult for pathologist to classify adenocarcinoma further; 19G gives tissue core

2015 WHO terminology for small biopsies and cytology 2015 WHO Classification 2015 WHO Resections Small Biopsy/Cytology ADENOCARCINOMA Lepidic Acinar Papillary Micropapillary Solid No 2004 WHO counterpart most will be solid adenocarcinomas SQUAMOUS CELL CARCINOMA Keratinizing Nonkeratinizing Basaloid No 2004 WHO counterpart LARGE CELL CARCINOMA Morphologic adenocarcinoma patterns clearly present: Adenocarcinoma, describe identifiable patterns present Morphologic adenocarcinoma patterns not present (supported by special stains; i.e TTF-1 +; p40 -): Non-small cell carcinoma, favor adenocarcinoma Morphologic squamous cell patterns clearly present: Squamous cell carcinoma Morphologic squamous cell patterns not present (supported by stains; i.e. p40+, TTF-1 -): Non-small cell carcinoma, favor squamous cell carcinoma Non-small cell carcinoma, not otherwise specified (NOS)

Papillary Micropapillary Adenocarcinoma Lepidic Acinar Solid

Pathology and N involvement Type (predominant) % with nodes % N2 solid (SOL) 47.5 23.1 micropapillary (MIP) 47.2 23.6 variants of invasive AC (VIA) 24.0 11.3 papillary (PAP) 18.9 8.7 acinar (ACI) 18.2 8.8 lepidic (LEP) 0 0 minimally invasive AC (MIA) 0 0 AC in situ (AIS) 0 0 Yu Y et al. Eur J Surg Oncol 2016

Lymphnodes Primary tumour Staging Patient BU 1956 SUVmax 16.3 MRI brain, no metastases SUVmax hilum: 3.0 MRI, magnetic resonance imaging; SUVmax, maximum standardised uptake value

SUV, survival and lymph node involvement SUV max pn0 pn1-3 < 3.0 83 (91.2%) 8 (8.8%) > 3.0 81 (68.6%) 37 (31.4%) p < 0.001 Nakamura H et al. Ann Surg Oncol 2015

Lymphnodes Primary tumour Staging Patient BU 1956 ct2acn1cm0, stage IIB TNM, tumour, node, metastasis

Treatment Patient BU 1956 Resection: Left lower lobe resection with Lymphadenectomy (position: left 9, 11, 8, 12 & 7, 5) Pathology report (AJCC, 7th edition): Acinar Adenocarcinoma pt2a, pn2* (6/10), G3, R0; KRASmut, Stage IIIA *N2: positive at level 11L & 7 AJCC, American Joint Committee on Cancer; TNM, tumour, node, metastasis Rush, JTO 2009

Treatment algorithm stage IIIA ACCP, American College of Chest Physicians; CT, computed tomography; LN, lymph node; NSCLC, non-small-cell lung cancer; PET, positron-emission tomography

- 575 Resected Adenocarcinoma from LACE-Bio study Benefit of adjuvant chemotherapy after resection Disease-free survival: Acinar/papillary subgroups Chemotherapy versus observation Disease-free survival: Micropapillary/solid subgroups Chemotherapy versus observation Tsao MS et al. J Clin Oncol 2015