LSU HEALTH SCIENCES CENTER NSCLC Guidelines Feist-Weiller Cancer Center Molly Boyd, MD Glenn Mills, MD Syed Jafri, MD 1/1/2010
Initial Evaluation/Intervention: 1. Pathology Review 2. History and Physical (including performance status and weight loss evaluation) 3. CBC, platelets, chemistry profile 4. CT chest, upper abdomen including adrenals 5. PET scan when clinically indicated 6. Brain MRI for stage II and above 7. Bronchoscopy 8. EBUS when clinically indicated 9. Mediastinoscopy when clinically indicated 10. Smoking cessation counseling Pathologic Review: For classification of lung cancer type, extent of invasion, involvement status or surgical margins. Determination of abnormalities which predict for sensitivity vs. resistance to EGFR-TKI s (EGFR mutations exon 19 deletion, exon 21 mutation and exon 18, KRAS mutation) Tumor classification system used is defined by WHO Immunohistochemistry: TTF-1: distinguishes primary from metastatic adenocarcinoma; majority of primary lung cancer is positive for TTF-1; metastatic adenocarcinoma is almost always negative for TTF-1 Pulmonary adenocarcinoma usually is CK7+/CK20-; metastatic adenocarcinoma of colorectal origin usually is CK7-/CK20+. CDX-2 is sensitive and specific for primary GI malignancies. Chromogranin and Synaptophysin are usually positive in neuroendocrine tumors including all carcinoid, but are negative in 25% of small cell lung cancer cases
Staging: IASLC Lung Cancer Staging Project, J Thorac Oncol 2007;2:706-714. Tumor: TX T0 Tis T1 T1a T1b T2 T2a T2b T3 T4 Lymph Nodes: NX N0 N1 N2 N3 Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ Tumor 3 cm surrounded by lung or visceral pleura, w/o bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e. not main bronchus) Tumor 2 cm Tumor >2 cm but 3 cm Tumor >3 cm but 7 cm or with any of the following: -Involves the main bronchus, 2 cm distal to carina -Invades visceral pleura -Associated atelectasis or obstructive pneumonitis which extends to hilar region but does not involve the entire lung Tumor >3 cm but 5 cm Tumor >5 cm but 7 cm Tumor >7 cm or one that directly invades any of the following: -chest wall (including superior sulcus tumors), diaphragm, pherecnic nerve, mediastinal pleura, paretal pericardium -Tumor in the main bronchus <2 cm distal to carina, w/o involvement of carina -Associated atelectasis of obstructive pneumonitis of the entire lung -Separate tumor nodule in the same lobe Tumor of any size that invades any of the following: -mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina -Separate tumor nodule in a different ipsilateral lung Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension Metastasis in ipsilateral mediastinal and/or subcarinal lymph node Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node Distant Metastasis: MX Distant metastasis cannot be assessed M0 No distant metastasis M1a Separate tumor nodule in contralateral lung; malignant pleural nodules or effusion M1b Distant metastasis
Stage IA T1a,N0,M0 T1b,N0,M0 Stage IB Stage IIA Stage IIB Stage IIIA Stage IIIB Stage IV T2a,N0,M0 T1a,N1,M0 T1b,N1,M0 T2a,N1,M0 T2b,N0,M0 T2b,N1,M0 T3,N0,M0 T4(same lobe),n0,m0 T3,N1,M0 T3,N2,M0 T4(same lobe),n1,m0 T4(same lobe),n2,m0 T4(extension),N0,M0 T4(extension),N1,M0 T4(ipsilateral lung M1),N0,M0 T4(ipsilateral lung M1),N1,M0 T4(extension),N2,M0 T4(ipsilateral lung M1),N2,M0 Any T,N3,M0 Any T, Any N,M1a Any T, Any N,M1b
1. Resectable/Early Stage (TNM stage I, II, some IIIA) A. Surgical candidate: Surgery Lobectomy is preferred over segmentectomy or wedge resection. Lung sparing anatomic resection or sleeve lobectomy preferred over pneumonectomy B. Not a surgical candidate : SBRT for peripheral lesions C. Adjuvant Chemotherapy (T2,N0-high risk*; T3,N0; T1-T3,N1-N2) *High risk: poorly differentiated tumors, vascular invasion, wedge resection, minimal margins, tumors >4cm, visceral pleural involvement, unknown nodal status) D. Positive margins: Re-resection or chemo-radiotherapy
2. Superior sulcus tumor (T3-T4 N0 or N1): Neo-adjuvant chemo-radiotherapy followed by surgery preferred treatment or Definitive chemo-radiotherapy 3. Single N2 lymph node <3cm can be approached with Neo-adjuvant chemotherapy or chemo-radiotherapy followed by evaluation for surgery
2. Locally Advanced Disease (Unresectable IIIA, IIIB) A. Concurrent Chemo-radiotherapy : a) Clinical trial b) Concurrent chemo-radiotherapy c) Consolidation chemotherapy following concurrent chemo-radiotherapy
4. Advanced Disease (M1) a) Clinical trial b) Palliative chemotherapy c) Targeted therapy d) Maintenance therapy e) Second/Third line therapy
Chemotherapy regimens: A) Adjuvant chemotherapy Published regimens: a. Cisplatin 50mg/m2, days 1 and 8 Vinorelbine 25mg/m2, days 1,8,15,22 (Q28 days X 4 cycles) b. Cisplatin 100mg/m2, on day 1 Vinorelbine 30mg/m2, days 1,8,15,22 (Q28 days X 4 cycles) c. Cisplatin 75-80mg/m2, on day1 Vinorelbine 25-30mg/m2, days 1 and 8 (Q21 days X 4 cycles) d. Cisplatin 100mg/m2, on day 1 Etoposide 100mg/m2, days 1-3 (Q28 days X 4 cycles) e. Cisplatin 80mg/m2 on day 1,22,43,64 Vinblastine 4mg/m2, days 1,8,15,22 then Q2 wk after day 43 (Q21 days X 4 cycles) 2. Regimen for patients with comorbidities or not able to tolerate cisplatin: Carboplatin AUC 6, on day 1 Paclitaxel 200mg/m2, on day 1 (Q21 days)
B) Concurrent chemo-radiotherapy for locally advanced disease*: a) Clinical trial Cisplatin 50mg/m2, on day 1,8,29 and 36 Etoposide 50mg/m2 days 1-5, 29-33 Concurrent thoracic RT (total dose 61 Gy) Followed by histology based consolidation Non-squamous histology: Pemetrexed 500mg/m2 IV q 21 days for 4 cycles Squamous histology: Gemcitabine 1000mg/m2 days 1,8 q 21 days for 4 cycles b) Cisplatin 50mg/m2, on day 1,8,29 and 36 Etoposide 50mg/m2 days 1-5, 29-33 Concurrent thoracic RT (total dose 61 Gy) c) Cisplatin 100mg/m2, day 1 and 29 Vinblastine 5mg/m2, weekly X 5 Concurrent thoracic RT(total dose 60 Gy) d) Paclitaxel 45-50mg/m2 weekly over 1 hour Carboplatin AUC 2 over 30mg weekly Concurrent thoracic RT 63 Gy/7 weeks, 34 fractions e) Consolidation Chemotherapy for T4, N2-3 Following Cisplatin/Etoposide as above: a. Cisplatin 50mg/m2 and etoposide 50mg/m2 X 2 additional cycles(category 2B) Following Carboplatin/Paclitaxel as above: b. Paclitaxel 200mg/m2 and Carboplatin AUC 6 X 2 additional cycles(category 2B) *Randomised data supports use of cisplatin vs. carboplatin-based regimens
C) Advanced M1 disease a) S0819: A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizu-mab with or without Concurrent Cetuximab in Patients Advanced Non-Small Cell Lung Cancer (NSCLCClinical trial SWOG b) C30801 - A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung CancerCALGB c) Non-squamous histology: Do EGFR testing i) EGFR mutation positive Erlotinib first line preferred ii) EGFR mutation negative/unkown: Chemotherapy preferred d) Non-squamous histology chemotherapy regimens i) Chemotherapy alone ii) Chemotherapy +bevacizumab if criteria met e) Squamous histology i) Chemotherapy alone Pemetrexed and bevacizumab not indicated in squamous histology Cisplatin or carboplatin are each effective in combination with any of the following: paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, etoposide, vinblastine, pemetrexed (non-squamous) Preferred regimen: Carboplatin AUC 6 and Paclitaxel 175mg/m2 q 21 days +/- bevacizumab Carboplatin AUC 6 and Pemetrexed 500mg/m2 q 21 days +/- bevacizumab
f) Maintenance regimen: Non-squamous histology: i) Pemetrexed 500mg/m2 IV q 21 days ii) Erlotinib 150mg PO daily iii) Bevacizumab 15mg/kg IV q 21 days Squamous histology: i) Erlotinib 150 mg PO daily g) Second line chemotherapy: 1. Docetaxel single-agent is superior to best supportive care 2. Pemtrexed single-agent superior to docetaxel with less toxicity in patients with adenocarcinoma and large cell carcinoma 3. Erlotinib single-agent is superior to best supportive care with significantly improved survival and delayed time to symptom deterioration h) Third-Line: Erlotinib is superior to best supportive care with significantly improved survival