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Southwest Oncology Group Spring 2011 Meeting Thursday, April 14, 2011; San Francisco, Ca Kristine Deano Abueg, RN, MSN, OCN©; Kaiser Permanente Oncology Clinical Trials LUNG CANCER OVERVIEW & EPIDEMIOLOGY Objective: Identify major carcinomas of the lung. Objective: Discuss trends in lung cancer incidence and survival in lung cancer. SCLC, 15% Major groups: Small Cell Lung Cancer (SCLC) and Non-Small Lung Cancer (NSCLC). Significant differences in pathology, clinical course, and treatment NSCLC 85% Epidemiology: nd Figure 1. Histological distribution of lung cancer 2 most common cause of cancer st 1 most common cause of death due to cancer Significant decline in incidence/mortality for African American and White Males; Increase in incidence/mortality for females of both races. Source for incidence and mortality data: Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics. Additional statistics and charts are available at http://seer. cancer.gov/. 20 15 10 5 Small 5 year survival Non Small Cell 0 Figure 2: Lung cancer survival trends: % of diagnosed patients alive after 5 years of diagnosis. Historical trends in 5 year survival (%) have remained stagnant Inferences and Implications Decreasing incidence of lung cancer since 1975. Thought to be tied to smoking cessation efforts Minimal change in mortality since 1975 – have we made progress in treatment? 1 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER SCREENING Controversial role and future directions Objective: Discuss current recommendations and controversies surrounding lung cancer screening. Current Controversy o Survival increases with early detection (ie earlier stage) o U.S. preventive services task Force (USPSTF) – recommends against population based screening (full text available at http://www.preventiveservices.ahrq.gov) Rationale: insufficient evidence for screening of asymptomatic persons with Rating: I Recommendation: o low dose computerized tomography (LDCT) o chest x-ray (CXR) o sputum cytology o -or a combination of these tests. Screening strategies ≠ decreased mortality Risks: Invasive nature & ↑false-positive tests in certain populations o Therefore, the USPSTF could not determine the balance between the benefits and harms of screening for lung cancer Research Directions – is lung cancer screening in our future? National Lung Screening Trial (NLST, ACRIN A6554) www.cancer.gov/clinicaltrials. N= 53,000 current or former smokers Objective: risk/benefit of low-dose spiral CT vs. Chest X-ray Data: (November 4, 2010) - final data is as yet unpublished, comments below based on NCI press release date 11/1/2010. Available at http://www.cancer.gov/newscenter/qa/2002/nlstqaQA o 20% reduction in mortality due to lung cancer with low-dose helical CT vs. CXR. o 7% reduction in all-cause mortality with low-dose helical CT vs. CXR International Early Lung Cancer Action Program (I-ELCAP) http://www.ielcap.org/index.htm Objective: Benefit of annual screening with CT for high risk patients Data: o High rate of detection of early stage lung cancer. o 80% survival in treated population o 100% mortality in non-treated population 2 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER CLINICAL COURSE Objective: Discuss main presenting symptom associated with lung cancer Objective: Discuss the typical diagnostic events for a patient with suspected lung cancer What are the common presenting symptoms of a lung cancer patient? Early stage lung cancer usually asymptomatic Symptoms typically indicative of advancing disease. Local-Regional effects Extrathoracic Involvement Systemic Symptoms Often due to mechanical Due to mechanical impact or Can occur throughout treatment impact of tumor on neuroendocrine impact of course intrathoracic structures distant metastases. Effect varies by site of metastases. Oncologic Emergencies Cough Brain: o Headache Superior vena cava Dsypnea o Change in LOC syndrome Airway obstruction o Seizures Cardiac effusion and Bronchorrhea o Focal weakness tamponade Hemoptysis Gastrointestinal Pleural effusion Wheezing Bone: Pain Malignant spinal cord Hoarseness compression Paraneoplastic Syndromes Hypercalcemia of malignancy Syndrome of inappropriate Antidiuretic hormone (SIADH) Ectopic andreocorticitropic hormone (Tyson, L.B. “Patient Assessment” in Lung Cancer, Site Specific Series, Houlihan, N.G., Ed. Oncology Nursing Society, 2006. Diagnostic Testing for lung cancer Presenting symptoms Physical workup Physical Exam CBC Chemistry panel Chest X-ray →Chest CT R/O Lung cancer: Diagnostic Testing Pathology: • Needle Aspiration (often with CT) • Bronchoscopy • Broncheoalveolar lavage Staging • PET/MRI/CT • Brain scan if symptomatic • Mediastinoscopy 3 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg SMALL CELL LUNG CANCERS SCLC Stage Distribution: Stage at Diagnosis Top Five: 1) 2) 3) 4) 5) It’s so distinct that everything else is “non” small cell. Represents 15% of all bronchogenic cancers Nearly all cases of SCLC are attributable to smoking Very rapid spread: Majority of SCLC diagnosed during extensive stage More responsive to chemotherapy and radiation therapy – but less curable Statistics 30% Localized Extensive 70% New Cases in 2010: 222,520 Death 157,300 Median survival 6-16 weeks without tx. Represents decreasing trend with decreasing smoking 5 year survival by stage (%) and subtype 25 Staging 20 Only two stages: limited vs. extensive Traditional TNM stage ≠ prognostic value o Limited (ipsilateral involvement) Main tumor: one hemithorax Nodal involvement: mediastinal, contralateral hilar, or ipsilateral supraclavicular or scalene – must be captured in single radiation port. o Extensive Hallmark structures: cannot be captured by definition above malignant pleural effusion Spread beyond supraclavicular areas Clinical Course: 15 SCLC 10 5 0 Localized Regional Distant Effect of Therapy on 2-yr Survival Weeks since dx 90 80 70 60 50 40 30 20 10 0 80 48 Presenting symptoms: Unusual to present asymptomatic 12 6 o Constitutional: fatigue, anorexia, weight loss o Due to primary tumor: cough, dyspnea, hemoptysis o Indicators of intrathoracic spread: superior vena Limited LImited Extensive Extensive Stage Stage Stage Stage cava syndrome, laryngeal palsy causing Untreated Treated Untreated Treated hoarseness, dysphagia, stridor o Indicators of distant spread: Neuro (brain), bone pain (bone), Abd pain (liver) o Paraneoplastic syndromes (SCLC and neuroendocrine): Syndrome of Inappropriate Antidiuretic hormone (SIADH) 4 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg Superior Vena Cava Syndrome a. What is it? Compression of the superior vena cava (great vessel) by a tumor. Usually associated with bronchogenic carcinoma (lung and lymphoma) b. Presenting symptoms/signs i. Dyspnea, coughing ii. Facial/upper trunk swelling, jugular vein distention iii. Hoarseness, paralyzed vocal chord iv. Diagnosis: radiology c. Treatment i. Palliative radiation therapy or chemotherapy (SCLC) ii. Surgical: thrombectomy or stent placement Treatment options in SCLC: To Cut or Not to Cut…That is the question 50% to 80% 5-year survival benefit of surgical resection for patients diagnosed with solitary pulmonary nodules in SCLC…however data is questionable, because very, very few resectable limited stage patients could be identified. (Szczesny et al 2003) Treatment Options: Chemotherapy Stage Treatments NCI Clinical Trials Compiled from data retrieved from NCI (PDQ ®) and National Comprehensive Cancer Network TM Version 3.2011) Limited Chemotherapy with concurrent chest rads Extensive Chemo: preference for platinum based doublet such as cisplatin/etoposide Clinical trial Limited Stage Trials Extensive Stage Trials SWOG studies: SWOG s0802 A Randomized Phase II Trial of Weekly Topotecan with and without AVE0005 (Aflibercept; NSC-724770) in Patients with Platinum Treated Extensive Stage Small Cell Lung Cancer (E-SCLC) CTSU/CALGB 30610 Phase III Comparison of Thoracic Radiotherapy Regimens in Patients with Limited Small Cell Lung Cancer Also Receiving Cisplatin and Etoposide - Phase III Intergroup 5 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg NON-SMALL CELL LUNG CANCER Key facts: 1) Represents 85% of all lung cancers 2) TNM staging provides critical prognostic information and guides treatment options 3) Sub-divided into 2 major types a. Non-squamous i. Adenocarcinoma (including bronchoalveolar) ii. Large-Cell Carcinoma iii. Others Major Bronchogenic Tumors b. Squamous cell Classifications 4) Adenocarcinoma = most frequently dx’d lung cancer type. Histology and Subtypes: Based on the World Health organization/International Association for the study of lung cancer histological classification of non-small cell lung carcinoma (NSCLC) Squamous 30% Small Cell 15% Squamous cell carcinoma Papillary. Clear cell. Small cell. Basaloid. Adenocarcinoma Acinar Papillary. Bronchioloalveolar carcinoma. o Nonmucinous. o Mucinous. o Mixed mucinous and nonmucinous or indeterminate cell type. Solid adenocarcinoma with mucin. Adenocarcinoma with mixed subtypes. Variants. o Well-differentiated fetal adenocarcinoma. o Mucinous (colloid) adenocarcinoma. o Mucinous cystadenocarcinoma. o Signet ring adenocarcinoma. o Clear cell adenocarcinoma Large Cell 15% Adenocarcin oma 40% Large cell carcinoma Variants. o Large cell neuroendocrine carcinoma. o Combined large cell neuroendocrine carcinoma. o Basaloid carcinoma. o Lymphoepithelioma-like carcinoma. o Clear cell carcinoma. o Large cell carcinoma with rhabdoid phenotype. Other Major Subtypes: Adenosquamous carcinoma, Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements; carcinoid tumor; Carcinomas of salivary gland type, Unclassified carcinoma. 6 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg Epidemiology 70% 60% 5 year survival (%) by stage at diagnosis 50% NSCLC Stage Distribution: Stage at Diagnosis Most NSCLC is detected with distant mets (M1,M2) 40% 30% 20% 10% 16% Localized (I, II) NSCLC 0% AJCC AJCC AJCC AJCC Stage I Stage II Stage III Stage IV Regional (III) Distant 54% 22% Based on the proposed AJCC 7th ed, the International Association for the Study of Lung Cancer estimates that the overall 5-year survival rate of patients with pathologic stage I disease to be 58% to 73%; stage II to be 36% to 46%; stage III to be 9% to 24%; and stage IV to be 13%.[Goldstraw 2007] Does histology (sub-type) play a role in survival? General trends favors non-squamous histology Suggests interaction between histology and chemotherapy Suggests interaction between histology and tumor markers, with implications for targeted therapy 7 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg NON-SMALL CELL LUNG CANCER: Tumor Size (T) STAGING www.cancerstaging.org "Systems do not exist in Nature but only in men’s minds." Claude Bernard (1813-1878); as quoted by Dr. A. De la Guerra, February 2010 Objective: Discuss T (primary tumor staging) Objective: Discuss changes in T (primary tumor staging) from the 6th edition AJCC to 7th edition AJCC th th Summary of major changes in T staging from 6 ed. AJCC to 7 ed AJCC: Addition of new size landmarks: o AJCC 6th: 3cm o AJCC 7th: 2cm, 3cm, 5cm, and 7cm T1 subdivided into T1a and T1b; T2 subdivided into T2a and T2b Downstaging of separate nodules in the same lobe to T3 Subdivision of pleural invasion (VPI) by tissue layer: PL1 (elastic layer); PL2 (cisceral pleural surface), and PL3 (parietal pleura) AJCC 6th Edition Tx T0 Tis T1 Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in Situ T2 Tumor with any of the following features of size or extent: >3cm or greater Involves main bronchus, 2cm or more distal to the carina Tumor of any size that involves visceral pleura Atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung Any invasive tumor =<3cm in longest dimension Surrounded by lung or visceral pleura Not in main bronchus: No bronchoscopic invasion more proximal that the lobar bronchus th AJCC 7 edition http://www.cancerstaging.org/staging/posters/lung24x30.pdf Tx Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in Situ T1 Any invasive tumor =<3cm in longest dimension Surrounded by lung or visceral pleura Not in main bronchus: No bronchoscopic invasion more proximal that the lobar bronchus T1a =<2cm T1b >2cm to =<3cm T2 T2a T2b T3 Tumor of ANY size that directly invades any of the following structures: chest wall, diaphragm, mediastinal pleura, parietal pericardium -or Tumor in the main bronchus, <2cm distal to the carina but without involvement of the carina -or Associated with atelectasis or obstructive pneumonitis of the entire lung T3 T4 Tumor of any size that directly invades and of the following: Mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina, Separate nodules of multicentric tumor of similar histology existing in the same lobe; or tumor with malignant pleural effusion. T4 >3cm to <=7cm with any of the following o Involves main bronchus (peribronchial)– and/or o 2cm or more distal to the carina - and/or o Invades visceral pleura (PL1 [beyond the elastic layer] or PL2[ to the pleural surface]) – and/or o Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung >3cm to =<5cm >5cm to =<7cm >7cm and/or invades any of the following o Parietal pleural (PL3) o Chest wall (including superior sulcus tumors) o Diaphragm o Phrenic nerve o Mediastinal pleura o Parietal pericardium Or tumor in the main bronchus <2cm distal to the carina but without involvement of the carina Associated with atelectasis or obstructive pneumonitis of the entire lung Separate nodules of multicentric tumor of similar histology existing in the same lobe Tumor of any size that directly invades and of the following: Mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, separate tumor nodules in a different ipsilateral lobe 8 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER: NODAL (N) STAGING o Objective: Discuss changes to AJCC node classifications Objective: Discuss changes to node descriptors and th groupings proposed in the AJCC 7 edition. Where are the nodes: STATION Node descriptors by Station “Reports are inconsistent regarding the relationship to prognosis of metastases to specific lymph node stations” (Mountain, 1997) However: “Andre, 2000: # stations and method of detection was clinically significant. Many variations o Naruke lymph node map (Japan) o Mountain and Dressler (North America and Europe) Recent re-organization: o International Association for the Study of Lung Cancer (IASLC), 2009 (Memorial Sloan Kettering Cancer Center, 2009) – recommended and used as the basis for th AJCC 7 edition Rusch, et al (2009) © Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. Used with permission o Familiarity useful for radiology interpretation and CRF reporting No changes to N staging in AJCC 7th edition o N0 N1 N2 N3 Proposed changes to subdivide each N component to describe extent of involvement (i.e. # of zones involved), but data was not validated and thus will not be part of the new TNM changes…clinical trial opportunity? Regional Lymph Nodes No regional lymph node mets Mets to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes including involvement by direct extension of the primary tumor. Metastases to ipsilateral mediastinal and/or subcarinal nodes Metastases to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s). “Simplified” Negative Nodes + nodes near primary tumor + nodes on ipsilateral mediastinum or subcarina + supraclavicular or scalene nodes (above collar bone) or + contralateral nodes 9 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER: METASTASES (M) STAGING th Objective: Discuss changes to AJCC metastatic classifications in the AJCC 7 edition Objective: Identify common sites of metastases th th Major Changes: Upstaging of pericardial and pleural effusions as M1a (7 ed) from T4 (6 ed) AJCC 6th Edition Mx M0 M1 Distant tumor cannot be assessed No evidence of distant metastases tumor Distant metastasis Additional nodules in the contra lateral lung th AJCC 7 edition http://www.cancerstaging.org/staging/posters/lung24x30.pdf NA (MS designation has been eliminated) M0 No evidence of distant metastases tumor M1a Intrathoracic metastases Pleural dissemination (malignant pleural or pericardial effusions, pleural nodules). – or Additional nodules in the contralateral lung (same histology). M1b Extrathoracic metastases: Distant metastasis 10 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER: Changes to Groupings th th Bold: AJCC 7 (AJCC 6 ) T and M Descriptors 6th Edition TNM N0 N1 N3 N2 Stage 7th Edition TNM Stage Stage Stage T1a (≤ 2 cm) IA IIA IIIA IIIB T1b (> 2-3 cm) IA IIA IIIA IIIB T2a (> 3-5 cm) IB IIA (IIB) IIIA IIIB T2b (> 5-7 cm) IIA (IB) IIB IIIA IIIB T3 (> 7 cm) IIB (IB) IIIA (IIB) IIIA IIIB T3 invasion T3 IIB IIIA IIIA IIIB T4 (same lobe nodules) T3 IIB (IIIB) IIIA (IIIB) IIIA (IIIB) IIIB T4 (extension) T4 IIIA (IIIB) IIIA (IIIB) IIIB IIIB M1 (ipsilateral lung) T4 IIIA (IV) IIIA (IV) IIIB (IV) IIIB (IV) T4 (pleural effusion) M1a IV (IIIB) IV (IIIB) IV (IIIB) IV (IIIB) M1 (contralateral lung) M1a IV IV IV IV M1 (distant) M1b IV IV IV IV T1 (≤ 3 cm) T2 (> 3 cm) Key changes: th th 1) “Wet IIIB” [AJCC 6 ] is now IV [AJCC 7 ] 2) Distribution of multicentric nodules: same ipsilateral lobe has been downstaged AS presented by Dr. Joan Schiller, MD in presentation “New Issues in Staging and Adjuvant Treatment of the Early-Stage NSCLC Patient” available at http://www.clinicaloptions.com 11 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg Staging Examples - All examples available from the American Joint Committee on Cancer at http://www.cancerstaging.org/staging/index.html Case #1 Clinical Staging history: Pathologically confirmed (CT guided FNA) adenocarcinoma; Radiological staging: 2cm primary lesion in right lower lobe. No hilar or mediastinal adenopathy. PET/CT without evidence of distant metastases. o T____ o N_____ o M____ o Stage Group______ Based on findings, surgical resection with nodal sampling planned. What surgical resection technique would be recommended? Select one a) Wedge Resection b) Lobectomy c) Pneumonectomy Pathological staging: size of tumor 3.4 cm; moderately differentiated; visceral pleural involved (PL2), margins negative. Margin sampling: 4 peribronchial, 1 paraesophageal, 1 paratracheal, and 1 subcarinal node. All nodes negative o T____ o N_____ o M____ o Stage Group______ Case #2 Clinical Staging history: Pathologically confirmed (CT guided FNA) adenocarcinoma in RUL; Radiological staging: 5.3cm primary lesion in RUL. Mediastinoscopy and CT + for mediastinal nodes o T____ o N_____ o M____ o Stage Group______ 12 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER TREATMENT OPTIONS Options by Stage Stage Groupings Treatments NCI Clinical Trials Compiled from data retrieved from NCI (PDQ ®) and National Comprehensive Cancer TM Network Version 3.2011) In-Situ Stage i Tis, N0, M0 T1, N0, M0 T2, N0, M0 Surgery Curative Surgical Resection Curative RT (if medically inoperable) Clinical trial: recurrence prevention (adjuvant chemo in highrisk patients) Stage 0 trials Stage I trials Stage II T1, N1, M0 T2, N1, M0 T3, N0, M0 Complete Resection and LN dissection Curative RT (if medically inoperable) Modest benefit to adjuvant chemotherapy (cisplatin based) (Pignon, 2008) Clinical trial: adjuvant radiation Stage II trials Stage IIIA T1, N2, M0 T2, N2, M0 T3, N1, M0 T3, N2, M0 Resectable N2 (uncommon): Complete resection, CMLND & adjuvant chemo (cisplatin based). Clinical trial: adjuvant radiation; adjvuvant chemo/rads; surgery and chemo sequence UN-Resectable N2: Concurrent chemo/rads Radiation therapy for medically unfit patients Palliative radiation for symptomatic local involvement Chest Wall tumor (T3, N1, M0) Resection Resection with adjuvant radiation Radiation alone Chemo/rads/surgery Stage IIIB Any T, N3, M0 T4, any N, M0 T4 (structure invasion) or N3 (above collar bone, or contralateral) disease Concurrent chemo rads Rads alone in medically unfit Palliative radiation for symptomatic local involvement No clinical trials as of 03/19/2011 Improved survival with cisplatin-based chemo Assess for EGFR mutation (+ → erlotinib; - cetuximab) Addition of bevacizumab in non-squamous histology Second ling chemo with docetaxel, pemetrexed, or erlotinib Stage IV trials Stage IV Any M Stage IIIA trials Suggested Reference: NCCN Lung guidelines: Http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf 13 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER TREATMENT OPTIONS Surgical Resection Objective: Identify appropriate populations by stage medical operability and stage (respectability) Objective: Define appropriate surgical techniques Mainstay of early stage (Stage I and II) lung cancers Goal: Remove identified tumor and all affected lymphatic drainage Populations: o Stage I: curative o Stage II: curative with adjuvant chemotherapy o Stage III: reserved for select patients; dependent on structure & lymphovascular invasion Resectability based on o Medical operability o Tumor accessibility Determination of medical operability: Pre-surgical workups (i.e. common eligibility criteria?) Worrisome pre-existing conditions Pulmonary: Spirometry minimum values o Forced expiratory volumes (FEV1 ) in 1 second < 40% o Diffusing capacity of carbon monoxide (DLCO) < 40% o V02max < 15 ml/kg/min Cardiac: o CHF as indicated on MUGA/ECHO and PE. LVEF <50% o Ischemic heart disease as indicated on EKG o Recent Myocardial infarction o Unstable angina Other significant systemic co morbidities o Diabetes Mellitus o Renal insufficiency o o Hepatic insufficiency Immunosuppression Thoracotomy Options (illustrations © Terese Winslow, available from www.cancer.gov) Description Indications Localized removal of tumor with sufficient margin. <1cm tumor (controversial) Poor lung function * associated with ↓survival Parenchyma sparing Removal of entire lobe Removal of entire ipsilateral lung Generally preferred surgical approach “gold standard” Centrally located tumor; or extension into multiple lobes VATS: Video assisted thoractomy VATS Open lobectomy Blood tx Pneumonectomy Reintubation Lobectomy Arrhythmia Wedge Resection (limited resection) Significant reduction in complications(Paul, et al 2010) 14 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg Primary tumor resection: Less is more? Or is More...More? – Lobectomy vs. Limited Resection NCCN recommends lobectomy Lobectomy or pneumonectomy requirement for most trials Ginsberg & Rubinstein, 1995: No significant perioperative benefit in morbidity, mortality, or late post-op pulmonary function with limited resection Increased mortality and locoregional recurrence with limited resection o Active trials: CALGB/ECOG 140503 Compare the disease-free survival of patients with small (≤ 2 cm) peripheral stage IA non-small cell lung cancer undergoing lobectomy vs. sublobar resection (wedge resection or segmentectomy). Treatment Arms: Arm I: Patients undergo lobectomy by open thoracotomy or video-assisted thorascopic surgery (VATS). Arm II: Patients undergo a wedge resection or anatomical segmentectomy by open thoracotomy or VATS. Trial identifier: NCT00499330 Nodes Resection: Less is more?: Complete Ipsilateral Mediastinal Lymph Node Dissection (CMLND) vs. Lymph Node Sampling o Modest benefit to CMLND o Decision based on pre-operative radiology staging o Darling, et al 2011 NO significant benefit for CMLND if sampling was negative for EARLY stage NSCLC o o o 15 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER TREATMENT OPTIONS Chemotherapy Objective: Discuss appropriate populations for chemotherapy by stage Objective: Discuss general chemotherapy classes used in adjuvant and metastatic NSCLC Appropriate, but controversial, in many settings o Stage I: controversial benefit o Stage II: adjuvant post-resection, but benefits are very modest and with significant toxicity o Stage III: combined modality therapy: rad onc and chemo. Sequential chemotherapy/radiation more beneficial than radiation therapy alone (Sause, 2000) Concomitant radiochemotherapy more beneficial than sequential radiochemotherapy, but with increased AE’s (especially esophageal toxicity) Auperin (2010 o Stage IV: palliation What to use? o Preference for 4-6 cycles of platinum (Cisplatin or Carboplatin) doublets Paclitaxel Gemcitabine Etoposide Docetaxel Vinorelbine Pemetrexed o Cisplatin vs. Carboplatin controversial Conflicting results Cisplatin contraindicated in patients with multiple co-morbidities and poor PS o Elderly population: individualized treatment o Significant research (serum samples and tissue blocs !!) on identifying early predictors of adjuvant chemo benefit o At best we can only offer 5-10% survival benefit with adjuvant chemotherapy Targeted Therapies? (Stage III & IV) - suspicion that any benefit is reserved for specific molecular subgroups o KRAS mutation not predictive nor prognostic o epidermal growth factor receptor (EGFR) inhibitors : monoclonal antibody cetuximab. (Juneko, 2010) anti-EGFR Tyrosine Kinase Inhibitors: Erlotinib and Gefitinib (disappointing, inconsistent study results) o vascular endothelial growth factors: monoclonal antibody bevacizumab Anti-VEGFR tyrosine kinase inhibitors: sunitinib only in clinical trial o Anaplastic lymphoma kinase (ALK) inhibitors: Crizotinib in the ALK mutant population – in clinical trial 16 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg LUNG CANCER TREATMENT OPTIONS Radiation Therapy Objective: Discuss appropriate populations for radiation therapy by stage Objective: Discuss key toxicities Appropriate for o Stage I – resected with positive margins o Stage II – chemo/rads o Stage III - chemo/rads o Stage IV – palliation and local control Toxicities: o Radiation pneumonitis Incidence > fist 1-6 months s/S: Nonproductive cough, shortness of breath, weakness, fever with CT changes in radiation portal o Pulmonary fibrosis Incidence – occurs gradually months to years post tx S/S: shortness of breath, decreased lung elasticity, poor PFT’s 17 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg REFERENCES Recommended References used throughout this presentation: th Greene, F. (2002) American Joint Committee on Cancer, 6 edition, Cancer Staging Handbook. Chicago: Springer th Edge, S (2010) American Joint Committee on Cancer, 7 edition, Cancer Staging Handbook. Chicago: Springer Clinical Care Options Oncology inPractice point of care textbook: http://www.clinicaloptions.com/inPractice/Index/Oncology.aspx Govidan, R (ed) Lung Cancer, Site Specific Series; Houlihan, N.G., Ed. Oncology Nursing Society, 2006. National Cancer Institute: PDQ® Non-Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified 03/01/2011 Available at: http://www.cancer.gov/cancertopics/pdq/treatment/non-small-celllung/healthprofessional. Accessed 03/19/2011 National Comprehensive Cancer Network Clinical practice Guidelines in Oncology (NCCN Guidelines TM), Version 3.2011. Available at http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics. Statistics and charts are available at http://seer. cancer.gov BIBLIOGRAPHY Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, Brouchet L, Quoix E, Westeel V, Le Chevalier T. (2000) Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol. 2000 Aug;18(16):2981-9. Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. (2010) Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):218190. Epub 2010 Mar 29. Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, Jones DR, McKenna RJ, Landreneau RJ, Rusch VW, Putnam JB Jr. (2011) Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011 Mar;141(3):662-70. Flieder, et al (2005) Tumor size is a determinant of stage distribution in T1 non-small cell lung cancer, Chest, 128;2304-2308 DOI 10.1378/chest 128.4.2304. Goldstraw P, et al (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumors. J Thorac Oncol. Aug;2(8):706-14. Juneko, E, et al (2010). Optimal management of stage III non-small cell lung cancer, Clinical care options in oncology. http://www.clinicaloptions.com/inPractice/Oncology/Lung_Cancer/ch22_Lung-NSCLC_Stage_III.aspx. Date last modififed 11/17/2010. Accessed. 03/19/2011. Mountain & Dressler (1997) Regional Lymph Node Classification for Lung Cancer Staging, Chest, 111;1718-1723. DOI 10.1378/chest.111.6.1718 Pignon JP, Tribodet H, Scagliotti GV, et al.: Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 26 (21): 3552-9, 2008. Rusch, Valerie W.; Asamura, Hisao; Watanabe, Hirokazu; Giroux, Dorothy J.; Rami-Porta, Ramon; Goldstraw, Peter; The IASLC Lung Cancer Staging Project on Behalf of the Members of the IASLC Staging Committee Journal of Thoracic Oncology. 4(5):568-577, May 2009.doi: 10.1097/JTO.0b013e3181a0d82e Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, Emami B, Curran W Jr, Byhardt R, Dar AR, Turrisi A 3rd. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 2000 Feb;117(2):358-64 Szczesny, T.J., et al (2003) Surgical treatment of small cell lung cancer. Seminars in Oncology, 30 (1), 47-56. 18 SWOG 2011 Spring Meeting: Lung Cancer; K Abueg