Southwest Oncology Group

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1 Suthwest Onclgy Grup Spring 2011 Meeting Thursday, April 14, 2011; San Francisc, Ca Kristine Dean Abueg, RN, MSN, OCN ; Kaiser Permanente Onclgy Clinical Trials LUNG CANCER OVERVIEW & EPIDEMIOLOGY Objective: Identify majr carcinmas f the lung. Objective: Discuss trends in lung cancer incidence and survival in lung cancer. SCLC, 15% Majr grups: Small Cell Lung Cancer (SCLC) and Nn -Small Lung Cancer (NSCLC). Significant differences in pathlgy, clinical curse, and treatment Epidemilgy: NSCLC 85% 2 nd mst cmmn cause f cancer Figure 1. Histlgical distributin f lung cancer 1 st mst cmmn cause f death due t cancer Significant decline in incidence/mrtality fr African American and White Males; Increase in incidence/mrtality fr females f bth races. Surce fr incidence and mrtality data: Surveillance, Epidemilgy, and End Results (SEER) Prgram and the Natinal Center fr Health Statistics. Additinal statistics and charts are available at cancer.gv/ Small 5 year survival Nn Small Cell Figure 2: Lung cancer survival trends: % f diagnsed patients alive after 5 years f diagnsis. Histrical trends in 5 year survival (%) have remained stagnant Inferences and Implicatins Decreasing incidence f lung cancer since Thught t be tied t smking cessatin effrts Minimal change in mrtality since 1975 have we made prgress in treatment? 1

2 LUNG CANCER SCREENING Cntrversial rle and future directins Objective: Discuss current recmmendatins and cntrversies surrunding lung cancer screening. Current Cntrversy Survival increases with early detectin (ie earlier stage) U.S. preventive services task Frce (USPSTF) recmmends against ppulatin based screening (full text available at Ratinale: insufficient evidence fr screening f asymptmatic persns with Rating: I Recmmendatin: lw dse cmputerized tmgraphy (LDCT) chest x-ray (CXR) sputum cytlgy -r a cmbinatin f these tests. Screening strategies decreased mrtality Risks: Invasive nature & false-psitive tests in certain ppulatins Therefre, the USPSTF culd nt determine the balance between the benefits and harms f screening fr lung cancer Research Directins is lung cancer screening in ur future? Natinal Lung Screening Trial (NLST, ACRIN A6554) N= 53,000 current r frmer smkers Objective: risk/benefit f lw-dse spiral CT vs. Chest X-ray Data: (Nvember 4, 2010) - final data is as yet unpublished, cmments belw based n NCI press release date 11/1/2010. Available at 20% reductin in mrtality due t lung cancer with lw-dse helical CT vs. CXR. 7% reductin in all-cause mrtality with lw-dse helical CT vs. CXR Internatinal Early Lung Cancer Actin Prgram (I-ELCAP) Objective: Benefit f annual screening with CT fr high risk patients Data: High rate f detectin f early stage lung cancer. 80% survival in treated ppulatin 100% mrtality in nn-treated ppulatin 2

3 LUNG CANCER CLINICAL COURSE Objective: Discuss main presenting symptm assciated with lung cancer Objective: Discuss the typical diagnstic events fr a patient with suspected lung cancer What are the cmmn presenting symptms f a lung cancer patient? Early stage lung cancer usually asymptmatic Symptms typically indicative f advancing disease. Lcal-Reginal effects Extrathracic Invlvement Systemic Symptms Often due t mechanical impact f tumr n Due t mechanical impact r neurendcrine impact f Can ccur thrughut treatment curse intrathracic structures distant metastases. Effect varies by site f metastases. Cugh Brain: Onclgic Emergencies Dsypnea Headache Superir vena cava Airway bstructin Change in LOC syndrme Brnchrrhea Seizures Cardiac effusin and Hemptysis Fcal weakness tampnade Wheezing Gastrintestinal Pleural effusin Harseness Bne: Pain Malignant spinal crd cmpressin Paraneplastic Syndrmes Hypercalcemia f malignancy Syndrme f inapprpriate Antidiuretic hrmne (SIADH) Ectpic andrecrticitrpic hrmne (Tysn, L.B. Patient Assessment in Lung Cancer, Site Specific Series, Hulihan, N.G., Ed. Onclgy Nursing Sciety, Diagnstic Testing fr lung cancer Presenting symptms Physical wrkup Physical Exam CBC Chemistry panel Chest X-ray Chest CT R/O Lung cancer: Diagnstic Testing Pathlgy: Needle Aspiratin (ften with CT) Brnchscpy Brnchealvelar lavage Staging PET/MRI/CT Brain scan if symptmatic Mediastinscpy 3

4 Tp Five: SMALL CELL LUNG CANCERS SCLC Stage Distributin: Stage at Diagnsis 1) It s s distinct that everything else is nn small cell. 2) Represents 15% f all brnchgenic cancers 3) Nearly all cases f SCLC are attributable t smking 4) Very rapid spread: Majrity f SCLC diagnsed during extensive stage 5) Mre respnsive t chemtherapy and radiatin therapy but less curable 30% Lcalized Extensive Statistics 70% New Cases in 2010: 222,520 Death 157,300 Median survival 6-16 weeks withut tx. Represents decreasing trend with decreasing smking Staging Only tw stages: limited vs. extensive Traditinal TNM stage prgnstic value Limited (ipsilateral invlvement) Main tumr: ne hemithrax Ndal invlvement: mediastinal, cntralateral hilar, r ipsilateral supraclavicular r scalene must be captured in single radiatin prt. Extensive Hallmark structures: cannt be captured by definitin abve malignant pleural effusin Spread beynd supraclavicular areas Clinical Curse: Presenting symptms: Unusual t present asymptmatic Cnstitutinal: fatigue, anrexia, weight lss 10 Due t primary tumr: cugh, dyspnea, hemptysis 0 Indicatrs f intrathracic spread: superir vena cava syndrme, laryngeal palsy causing harseness, dysphagia, stridr Limited Stage Untreated LImited Stage Treated Extensive Stage Untreated Indicatrs f distant spread: Neur (brain), bne pain (bne), Abd pain (liver) Paraneplastic syndrmes (SCLC and neurendcrine): Syndrme f Inapprpriate Antidiuretic hrmne (SIADH) Weeks since dx 5 year survival by stage (%) and subtype Lcalized Reginal Distant Effect f Therapy n 2-yr Survival 48 Extensive Stage Treated SCLC 4

5 Superir Vena Cava Syndrme a. What is it? Cmpressin f the superir vena cava (great vessel) by a tumr. Usually assciated with brnchgenic carcinma (lung and lymphma) b. Presenting symptms/signs i. Dyspnea, cughing ii. Facial/upper trunk swelling, jugular vein distentin iii. Harseness, paralyzed vcal chrd iv. Diagnsis: radilgy c. Treatment i. Palliative radiatin therapy r chemtherapy (SCLC) ii. Surgical: thrmbectmy r stent placement Treatment ptins in SCLC: T Cut r Nt t Cut That is the questin 50% t 80% 5-year survival benefit f surgical resectin fr patients diagnsed with slitary pulmnary ndules in SCLC hwever data is questinable, because very, very few resectable limited stage patients culd be identified. (Szczesny et al 2003) Treatment Optins: Chemtherapy Stage Treatments Cmpiled frm data retrieved frm NCI (PDQ ) and Natinal Cmprehensive Cancer Netwrk TM Versin ) NCI Clinical Trials Limited Chemtherapy with cncurrent chest rads Limited Stage Trials Extensive Chem: preference fr platinum based dublet such as cisplatin/etpside Extensive Stage Trials Clinical trial SWOG studies: SWOG s0802 A Randmized Phase II Trial f Weekly Tptecan with and withut AVE0005 (Aflibercept; NSC ) in Patients with Platinum Treated Extensive Stage Small Cell Lung Cancer (E-SCLC) CTSU/CALGB Phase III Cmparisn f Thracic Raditherapy Regimens in Patients with Limited Small Cell Lung Cancer Als Receiving Cisplatin and Etpside - Phase III Intergrup 5

6 NON-SMALL CELL LUNG CANCER Key facts: 1) Represents 85% f all lung cancers 2) TNM staging prvides critical prgnstic infrmatin and guides treatment ptins 3) Sub-divided int 2 majr types a. Nn-squamus i. Adencarcinma (including brnchalvelar) ii. Large-Cell Carcinma iii. Others b. Squamus cell 4) Adencarcinma = mst frequently dx d lung cancer type. Majr Brnchgenic Tumrs Classificatins Histlgy and Subtypes: Based n the Wrld Health rganizatin/internatinal Assciatin fr the study f lung cancer histlgical classificatin f nn-small cell lung carcinma (NSCLC) Squamus cell carcinma Papillary. Clear cell. Small cell. Basalid. Adencarcinma Acinar Papillary. Brnchilalvelar carcinma. Nnmucinus. Mucinus. Mixed mucinus and nnmucinus r indeterminate cell type. Slid adencarcinma with mucin. Adencarcinma with mixed subtypes. Variants. Well-differentiated fetal adencarcinma. Mucinus (cllid) adencarcinma. Mucinus cystadencarcinma. Signet ring adencarcinma. Clear cell adencarcinma Squamus 30% Large Cell 15% Small Cell 15% Adencarcin ma 40% Large cell carcinma Variants. Large cell neurendcrine carcinma. Cmbined large cell neurendcrine carcinma. Basalid carcinma. Lymphepithelima-like carcinma. Clear cell carcinma. Large cell carcinma with rhabdid phentype. Other Majr Subtypes: Adensquamus carcinma, Carcinmas with plemrphic, sarcmatid, r sarcmatus elements; carcinid tumr; Carcinmas f salivary gland type, Unclassified carcinma. 6

7 Epidemilgy NSCLC Stage Distributin: Stage at Diagnsis Mst NSCLC is detected with distant mets (M1,M2) 54% 16% 22% Lcalized (I, II) Reginal (III) Distant Based n the prpsed AJCC 7 th ed, the Internatinal Assciatin fr the Study f Lung Cancer estimates that the verall 5-year survival rate f patients with pathlgic stage I disease t be 58% t 73%; stage II t be 36% t 46%; stage III t be 9% t 24%; and stage IV t be 13%. [Gldstraw 2007] 70% 60% 50% 40% 30% 20% 10% 0% 5 year survival (%) by stage at diagnsis AJCC Stage I AJCC Stage II AJCC Stage III AJCC Stage IV NSCLC Des histlgy (sub-type) play a rle in survival? General trends favrs nn-squamus histlgy Suggests interactin between histlgy and chemtherapy Suggests interactin between histlgy and tumr markers, with implicatins fr targeted therapy 7

8 NON-SMALL CELL LUNG CANCER: Tumr Size (T) STAGING "Systems d nt exist in Nature but nly in men s minds." Claude Bernard ( ); as quted by Dr. A. De la Guerra, February 2010 Objective: Discuss T (primary tumr staging) Objective: Discuss changes in T (primary tumr staging) frm the 6th editin AJCC t 7th editin AJCC Summary f majr changes in T staging frm 6 th ed. AJCC t 7 th ed AJCC: Additin f new size landmarks: AJCC 6th: 3cm AJCC 7th: 2cm, 3cm, 5cm, and 7cm T1 subdivided int T1a and T1b; T2 subdivided int T2a and T2b Dwnstaging f separate ndules in the same lbe t T3 Subdivisin f pleural invasin (VPI) by tissue layer: PL1 (elastic layer); PL2 (cisceral pleural surface), and PL3 (parietal pleura) AJCC 6th Editin AJCC 7 th editin Tx Primary tumr cannt be assessed Tx Primary tumr cannt be assessed T0 N evidence f primary tumr T0 N evidence f primary tumr Tis Carcinma in Situ Tis Carcinma in Situ T1 T2 T3 T4 Any invasive tumr =<3cm in lngest dimensin Surrunded by lung r visceral pleura Nt in main brnchus: N brnchscpic invasin mre prximal that the lbar brnchus Tumr with any f the fllwing features f size r extent: >3cm r greater Invlves main brnchus, 2cm r mre distal t the carina Tumr f any size that invlves visceral pleura Atelectasis r bstructive pneumnitis that extends t the hilar regin but des nt invlve the entire lung Tumr f ANY size that directly invades any f the fllwing structures: chest wall, diaphragm, mediastinal pleura, parietal pericardium -r- Tumr in the main brnchus, <2cm distal t the carina but withut invlvement f the carina -r- Assciated with atelectasis r bstructive pneumnitis f the entire lung Tumr f any size that directly invades and f the fllwing: Mediastinum, heart, great vessels, trachea, esphagus, vertebral bdy, carina, Separate ndules f multicentric tumr f similar histlgy existing in the same lbe; r tumr with malignant pleural effusin. T1 T2 T3 T4 T1a T1b T2a T2b Any invasive tumr =<3cm in lngest dimensin Surrunded by lung r visceral pleura Nt in main brnchus: N brnchscpic invasin mre prximal that the lbar brnchus =<2cm >2cm t =<3cm >3cm t <=7cm with any f the fllwing Invlves main brnchus (peribrnchial) and/r 2cm r mre distal t the carina - and/r Invades visceral pleura (PL1 [beynd the elastic layer] r PL2[ t the pleural surface]) and/r Assciated with atelectasis r bstructive pneumnitis that extends t the hilar regin but des nt invlve the entire lung >3cm t =<5cm >5cm t =<7cm >7cm and/r invades any f the fllwing Parietal pleural (PL3) Chest wall (including superir sulcus tumrs) Diaphragm Phrenic nerve Mediastinal pleura Parietal pericardium Or tumr in the main brnchus <2cm distal t the carina but withut invlvement f the carina Assciated with atelectasis r bstructive pneumnitis f the entire lung Separate ndules f multicentric tumr f similar histlgy existing in the same lbe Tumr f any size that directly invades and f the fllwing: Mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esphagus, vertebral bdy, carina, separate tumr ndules in a different ipsilateral lbe 8

9 LUNG CANCER: NODAL (N) STAGING Objective: Discuss changes t AJCC nde classificatins Objective: Discuss changes t nde descriptrs and grupings prpsed in the AJCC 7 th editin. Where are the ndes: STATION Nde descriptrs by Statin Reprts are incnsistent regarding the relatinship t prgnsis f metastases t specific lymph nde statins (Muntain, 1997) Hwever: Andre, 2000: # statins and methd f detectin was clinically significant. Many variatins Naruke lymph nde map (Japan) Muntain and Dressler (Nrth America and Eurpe) Recent re-rganizatin: Internatinal Assciatin fr the Study f Lung Cancer (IASLC), 2009 (Memrial Slan Kettering Cancer Center, 2009) recmmended and used as the basis fr AJCC 7 th editin Rusch, et al (2009) Jurnal f Thracic Onclgy. Published by Lippinctt Williams & Wilkins. Used with permissin Familiarity useful fr radilgy interpretatin and CRF reprting N changes t N staging in AJCC 7th editin Prpsed changes t subdivide each N cmpnent t describe extent f invlvement (i.e. # f znes invlved), but data was nt validated and thus will nt be part f the new TNM changes clinical trial pprtunity? Reginal Lymph Ndes Simplified N0 N reginal lymph nde mets Negative Ndes N1 Mets t ipsilateral peribrnchial and/r ipsilateral hilar + ndes near primary tumr lymph ndes, and intrapulmnary ndes including invlvement by direct extensin f the primary tumr. N2 Metastases t ipsilateral mediastinal and/r subcarinal + ndes n ipsilateral mediastinum r subcarina ndes N3 Metastases t cntralateral mediastinal, cntralateral hilar, ipsilateral r cntralateral scalene, r supraclavicular lymph nde(s). + supraclavicular r scalene ndes (abve cllar bne) r + cntralateral ndes 9

10 LUNG CANCER: METASTASES (M) STAGING Objective: Discuss changes t AJCC metastatic classificatins in the AJCC 7 th editin Objective: Identify cmmn sites f metastases Majr Changes: Upstaging f pericardial and pleural effusins as M1a (7 th ed) frm T4 (6 th ed) AJCC 6th Editin AJCC 7 th editin Mx Distant tumr cannt be assessed NA (MS designatin has been eliminated) M0 N evidence f distant metastases tumr M0 N evidence f distant metastases tumr M1 Distant metastasis Additinal ndules in the cntra lateral lung M1a Intrathracic metastases Pleural disseminatin (malignant pleural r pericardial effusins, pleural ndules). r Additinal ndules in the cntralateral lung (same histlgy). M1b Extrathracic metastases: Distant metastasis 10

11 LUNG CANCER: Changes t Grupings Bld: AJCC 7 th (AJCC 6 th ) T and M Descriptrs N0 N1 N2 N3 6th Editin TNM 7th Editin TNM Stage Stage Stage Stage T1 ( 3 cm) T2 (> 3 cm) T1a ( 2 cm) IA IIA IIIA T1b (> 2-3 cm) IA IIA IIIA T2a (> 3-5 cm) IB IIA (IIB) IIIA T2b (> 5-7 cm) IIA (IB) IIB IIIA T3 (> 7 cm) IIB (IB) IIIA (IIB) IIIA IIIB IIIB IIIB IIIB IIIB T3 invasin T3 IIB IIIA IIIA T4 (same lbe ndules) T3 IIB (IIIB) IIIA (IIIB) IIIA (IIIB) T4 (extensin) T4 IIIA (IIIB) IIIA (IIIB) IIIB M1 (ipsilateral lung) T4 IIIA (IV) IIIA (IV) IIIB (IV) T4 (pleural effusin) M1a IV (IIIB) IV (IIIB) IV (IIIB) M1 (cntralateral lung) M1a IV IV IV M1 (distant) M1b IV IV IV IIIB IIIB IIIB IIIB (IV) IV (IIIB) IV IV Key changes: 1) Wet IIIB [AJCC 6 th ] is nw IV [AJCC 7 th ] 2) Distributin f multicentric ndules: same ipsilateral lbe has been dwnstaged AS presented by Dr. Jan Schiller, MD in presentatin New Issues in Staging and Adjuvant Treatment f the Early-Stage NSCLC Patient available at 11

12 Staging Examples - All examples available frm the American Jint Cmmittee n Cancer at Case #1 Clinical Staging histry: Pathlgically cnfirmed (CT guided FNA) adencarcinma; Radilgical staging: 2cm primary lesin in right lwer lbe. N hilar r mediastinal adenpathy. PET/CT withut evidence f distant metastases. T N M Stage Grup Based n findings, surgical resectin with ndal sampling planned. What surgical resectin technique wuld be recmmended? Select ne a) Wedge Resectin b) Lbectmy c) Pneumnectmy Pathlgical staging: size f tumr 3.4 cm; mderately differentiated; visceral pleural invlved (PL2), margins negative. Margin sampling: 4 peribrnchial, 1 paraesphageal, 1 paratracheal, and 1 subcarinal nde. All ndes negative T N M Stage Grup Case #2 Clinical Staging histry: Pathlgically cnfirmed (CT guided FNA) adencarcinma in RUL; Radilgical staging: 5.3cm primary lesin in RUL. Mediastinscpy and CT + fr mediastinal ndes T N M Stage Grup 12

13 LUNG CANCER TREATMENT OPTIONS Optins by Stage Stage Grupings Treatments Cmpiled frm data retrieved frm NCI (PDQ ) and Natinal Cmprehensive Cancer Netwrk TM Versin ) NCI Clinical Trials In-Situ Tis, N0, M0 Surgery Stage 0 trials Stage i T1, N0, M0 Curative Surgical Resectin Stage I trials T2, N0, M0 Curative RT (if medically inperable) Clinical trial: recurrence preventin (adjuvant chem in highrisk patients) Stage II T1, N1, M0 T2, N1, M0 T3, N0, M0 Cmplete Resectin and LN dissectin Curative RT (if medically inperable) Mdest benefit t adjuvant chemtherapy (cisplatin based) (Pignn, 2008) Clinical trial: adjuvant radiatin Stage II trials Stage IIIA T1, N2, M0 T2, N2, M0 T3, N1, M0 T3, N2, M0 Resectable N2 (uncmmn): Cmplete resectin, CMLND & adjuvant chem (cisplatin based). Clinical trial: adjuvant radiatin; adjvuvant chem/rads; surgery and chem sequence UN-Resectable N2: Cncurrent chem/rads Radiatin therapy fr medically unfit patients Palliative radiatin fr symptmatic lcal invlvement Chest Wall tumr (T3, N1, M0) Resectin Resectin with adjuvant radiatin Radiatin alne Chem/rads/surgery Stage IIIA trials Stage IIIB Any T, N3, M0 T4, any N, M0 T4 (structure invasin) r N3 (abve cllar bne, r cntralateral) disease Cncurrent chem rads Rads alne in medically unfit Palliative radiatin fr symptmatic lcal invlvement N clinical trials as f 03/19/2011 Stage IV Any M Imprved survival with cisplatin-based chem Assess fr EGFR mutatin (+ erltinib; - cetuximab) Additin f bevacizumab in nn-squamus histlgy Secnd ling chem with dcetaxel, pemetrexed, r erltinib Stage IV trials Suggested Reference: NCCN Lung guidelines: 13

14 LUNG CANCER TREATMENT OPTIONS Surgical Resectin Objective: Identify apprpriate ppulatins by stage medical perability and stage (respectability) Objective: Define apprpriate surgical techniques Mainstay f early stage (Stage I and II) lung cancers Gal: Remve identified tumr and all affected lymphatic drainage Ppulatins: Stage I: curative Stage II: curative with adjuvant chemtherapy Stage III: reserved fr select patients; dependent n structure & lymphvascular invasin Resectability based n Medical perability Tumr accessibility Determinatin f medical perability: Pre-surgical wrkups (i.e. cmmn eligibility criteria?) Wrrisme pre-existing cnditins Pulmnary: Spirmetry minimum values Frced expiratry vlumes (FEV 1 ) in 1 secnd < 40% Diffusing capacity f carbn mnxide (DLCO) < 40% V0 2max < 15 ml/kg/min Cardiac: CHF as indicated n MUGA/ECHO and PE. LVEF <50% Ischemic heart disease as indicated n EKG Recent Mycardial infarctin Unstable angina Other significant systemic c mrbidities Diabetes Mellitus Renal insufficiency Hepatic insufficiency Immunsuppressin Thractmy Optins (illustratins Terese Winslw, available frm Wedge Resectin Lbectmy Pneumnectmy VATS: Vide assisted thractmy (limited resectin) VATS Open lbectmy Arrhythmia Reintubatin Bld tx Descriptin Indicatins Lcalized remval f tumr with sufficient margin. <1cm tumr (cntrversial) Pr lung functin * assciated with survival Parenchyma sparing Remval f entire lbe Generally preferred surgical apprach gld standard Remval f entire ipsilateral lung Centrally lcated tumr; r extensin int multiple lbes Significant reductin in cmplicatins(paul, et al 2010) 14

15 Primary tumr resectin: Less is mre? Or is Mre...Mre? Lbectmy vs. Limited Resectin NCCN recmmends lbectmy Lbectmy r pneumnectmy requirement fr mst trials Ginsberg & Rubinstein, 1995: N significant periperative benefit in mrbidity, mrtality, r late pst-p pulmnary functin with limited resectin Increased mrtality and lcreginal recurrence with limited resectin Active trials: CALGB/ECOG Cmpare the disease-free survival f patients with small ( 2 cm) peripheral stage IA nn-small cell lung cancer underging lbectmy vs. sublbar resectin (wedge resectin r segmentectmy). Treatment Arms: Arm I: Patients underg lbectmy by pen thractmy r vide-assisted thrascpic surgery (VATS). Arm II: Patients underg a wedge resectin r anatmical segmentectmy by pen thractmy r VATS. Trial identifier: NCT Ndes Resectin: Less is mre?: Cmplete Ipsilateral Mediastinal Lymph Nde Dissectin (CMLND) vs. Lymph Nde Sampling Mdest benefit t CMLND Decisin based n pre-perative radilgy staging Darling, et al 2011 NO significant benefit fr CMLND if sampling was negative fr EARLY stage NSCLC 15

16 LUNG CANCER TREATMENT OPTIONS Chemtherapy Objective: Discuss apprpriate ppulatins fr chemtherapy by stage Objective: Discuss general chemtherapy classes used in adjuvant and metastatic NSCLC Apprpriate, but cntrversial, in many settings Stage I: cntrversial benefit Stage II: adjuvant pst-resectin, but benefits are very mdest and with significant txicity Stage III: cmbined mdality therapy: rad nc and chem. Sequential chemtherapy/radiatin mre beneficial than radiatin therapy alne (Sause, 2000) Cncmitant radichemtherapy mre beneficial than sequential radichemtherapy, but with increased AE s (especially esphageal txicity) Auperin (2010 Stage IV: palliatin What t use? Preference fr 4-6 cycles f platinum (Cisplatin r Carbplatin) dublets Paclitaxel Gemcitabine Etpside Dcetaxel Vinrelbine Pemetrexed Cisplatin vs. Carbplatin cntrversial Cnflicting results Cisplatin cntraindicated in patients with multiple c-mrbidities and pr PS Elderly ppulatin: individualized treatment Significant research (serum samples and tissue blcs!!) n identifying early predictrs f adjuvant chem benefit At best we can nly ffer 5-10% survival benefit with adjuvant chemtherapy Targeted Therapies? (Stage III & IV) - suspicin that any benefit is reserved fr specific mlecular subgrups KRAS mutatin nt predictive nr prgnstic epidermal grwth factr receptr (EGFR) inhibitrs : mnclnal antibdy cetuximab. (Junek, 2010) anti-egfr Tyrsine Kinase Inhibitrs: Erltinib and Gefitinib (disappinting, incnsistent study results) vascular endthelial grwth factrs: mnclnal antibdy bevacizumab Anti-VEGFR tyrsine kinase inhibitrs: sunitinib nly in clinical trial Anaplastic lymphma kinase (ALK) inhibitrs: Criztinib in the ALK mutant ppulatin in clinical trial 16

17 LUNG CANCER TREATMENT OPTIONS Radiatin Therapy Objective: Discuss apprpriate ppulatins fr radiatin therapy by stage Objective: Discuss key txicities Apprpriate fr Stage I resected with psitive margins Stage II chem/rads Stage III - chem/rads Stage IV palliatin and lcal cntrl Txicities: Radiatin pneumnitis Incidence > fist 1-6 mnths s/s: Nnprductive cugh, shrtness f breath, weakness, fever with CT changes in radiatin prtal Pulmnary fibrsis Incidence ccurs gradually mnths t years pst tx S/S: shrtness f breath, decreased lung elasticity, pr PFT s 17

18 REFERENCES Recmmended References used thrughut this presentatin: Greene, F. (2002) American Jint Cmmittee n Cancer, 6 th editin, Cancer Staging Handbk. Chicag: Springer Edge, S (2010) American Jint Cmmittee n Cancer, 7 th editin, Cancer Staging Handbk. Chicag: Springer Clinical Care Optins Onclgy inpractice pint f care textbk: Gvidan, R (ed) Lung Cancer, Site Specific Series; Hulihan, N.G., Ed. Onclgy Nursing Sciety, Natinal Cancer Institute: PDQ Nn-Small Cell Lung Cancer Treatment. Bethesda, MD: Natinal Cancer Institute. Date last mdified 03/01/2011 Available at: Accessed 03/19/2011 Natinal Cmprehensive Cancer Netwrk Clinical practice Guidelines in Onclgy (NCCN Guidelines TM), Versin Available at Surveillance, Epidemilgy, and End Results (SEER) Prgram and the Natinal Center fr Health Statistics. Statistics and charts are available at cancer.gv BIBLIOGRAPHY Andre F, Grunenwald D, Pignn JP, Dujn A, Pujl JL, Brichn PY, Bruchet L, Quix E, Westeel V, Le Chevalier T. (2000) Survival f patients with resected N2 nn-small-cell lung cancer: evidence fr a subclassificatin and implicatins. J Clin Oncl Aug;18(16): Auperin A, Le Pechux C, Rlland E, Curran WJ, Furuse K, Furnel P, Belderbs J, Clamn G, Ulutin HC, Paulus R, Yamanaka T, Bznnat MC, Uitterheve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignn JP. (2010) Meta-analysis f cncmitant versus sequential radichemtherapy in lcally advanced nn-small-cell lung cancer. J Clin Oncl May 1;28(13): Epub 2010 Mar 29. Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, Jnes DR, McKenna RJ, Landreneau RJ, Rusch VW, Putnam JB Jr. (2011) Randmized trial f mediastinal lymph nde sampling versus cmplete lymphadenectmy during pulmnary resectin in the patient with N0 r N1 (less than hilar) nn-small cell carcinma: Results f the American Cllege f Surgery Onclgy Grup Z0030 Trial. J Thrac Cardivasc Surg Mar;141(3): Flieder, et al (2005) Tumr size is a determinant f stage distributin in T1 nn-small cell lung cancer, Chest, 128; DOI /chest Gldstraw P, et al (2007) The IASLC Lung Cancer Staging Prject: prpsals fr the revisin f the TNM stage grupings in the frthcming (seventh) editin f the TNM Classificatin f malignant tumrs. J Thrac Oncl. Aug;2(8): Junek, E, et al (2010). Optimal management f stage III nn-small cell lung cancer, Clinical care ptins in nclgy. Date last mdififed 11/17/2010. Accessed. 03/19/2011. Muntain & Dressler (1997) Reginal Lymph Nde Classificatin fr Lung Cancer Staging, Chest, 111; DOI /chest Pignn JP, Tribdet H, Scaglitti GV, et al.: Lung adjuvant cisplatin evaluatin: a pled analysis by the LACE Cllabrative Grup. J Clin Oncl 26 (21): , Rusch, Valerie W.; Asamura, Hisa; Watanabe, Hirkazu; Girux, Drthy J.; Rami-Prta, Ramn; Gldstraw, Peter; The IASLC Lung Cancer Staging Prject n Behalf f the Members f the IASLC Staging Cmmittee Jurnal f Thracic Onclgy. 4(5): , May 2009.di: /JTO.0b013e3181a0d82e Sause W, Klesar P, Taylr S IV, Jhnsn D, Livingstn R, Kmaki R, Emami B, Curran W Jr, Byhardt R, Dar AR, Turrisi A 3rd. Final results f phase III trial in reginally advanced unresectable nn-small cell lung cancer: Radiatin Therapy Onclgy Grup, Eastern Cperative Onclgy Grup, and Suthwest Onclgy Grup. Chest Feb;117(2): Szczesny, T.J., et al (2003) Surgical treatment f small cell lung cancer. Seminars in Onclgy, 30 (1),