Lung Cancer Update. HARMESH R NAIK, MD. February 28, 2001

Transcription

1 Lung Cancer Update HARMESH R NAIK, MD. February 28, 2001

2 Progress update Prevention Screening Staging Treatment

3 Epidemiology Estimated 169,500 new cases Estimated 157,400 deaths Second commonest cancer diagnosis in men and women Leading cause of cancer death in men and women A significant disease burden

4 Pathology Lung cancer (100%) non small cell-80% small cell-20% adenoca-40% squamous-30% large cell-10%

5 Etiologic factors Tobacco exposure: related in 87% of cases Second hand smoke: 3000 annual cases Asbestos exposure Occupational hazard Uranium miners exposed to radioactive dust Industrial radon exposure?? Residential radon exposure?? Dietary factors

6 Smoking and lung cancer Exposure to tobacco smoke is underlying factor in 87% of the cases Avoidable casual factor Half of US adults are current or former smokers 25% of the adults still smoke Significant number of youth smokes

7 Smoking history and lung cancer Harvard MDAnd 10 0 no smoking curr smoking past smoking

8 Smoking exposure, airflow obstruction and lung cancer PPD 41-60PPD 61+PPD reduced airflow normal airflow

9 Smoking and risk of lung Cancer Increases the risk of Lung cancer by 20 fold Dose response effect frequency: number of cigarettes per day duration: number of smoking years Risk declines after smoking cessation over time beginning at 5 years Risk still persists for 25 years Cessation at younger age has greater benefit

10 Prevention STOP SMOKING NEVER START

11 Current prevention strategy EDUCATION

12 Chemoprevention Beta carotene Low betacarotene intake increased risk Two randomized trials Risk of death actually increased in treated Possibly dietary interaction with other nutrient Secondary prevention On going trials with Isotretinoin

13 Overall 5 year survival All White Black

14 Improvements in 5-year lung cancer survival decade

15 Five year survival by stage- NSCLC IA IB II IIIA IIIB-IV 10 0

16 NSCLC-Survival data Stage 5 year survival I 55-75% II 25-50% IIIA 20-40% IIIB <5% IV <5%

17 SCLC: Median Survival with therapy limited extensive 5 0 months

18 Small cell lung cancer survival SCLC Stage Limited SCLC Median survival (with treatment) months Extensive SCLC months

19 Key to a better prognosis Early diagnosis

20 Stage at diagnosis-nsclc Most cases diagnosed at late stage Only 16% cases are localized

21 Stage at diagnosis SCLC % limited extensive

22 Key to early diagnosis Good screening methods

23 Screening: Unanswered questions Is screening effective? Is screening indicated for all? Who is the target population? What is optimal screening method? How frequent testing is necessary?

24 Target high risk population Current smoking history Prior smoking history Exposure to significant second hand smoke Occupational history Beware of the risk of lung cancer Should be informed about what is known

25 Screening methods Chest x-ray Spiral or helical Computed tomography Sputum cytology Future methods Molecular screening Genetic damage assessment by PCR PET scan

26 Sputum cytology Little advantage over chest x-ray No reduction in lung ca deaths in trials only one in four cancers were found Majority were squamous cell Does not define the location of cancer Refinements in methods are ongoing

27 Low dose radiation CT methods More sensitive than chest x-ray Promising data from ELCAP trial 1000 volunteers with 10 pack yr. smoking Ongoing recruitment A prospective trial is planned to verify the results

28 ELCAP trial-non randomized Spiral CT Chest x-ray Non calc. nodules Cancers 27 7 Stage Resectable 26 --

29 Screening data No prospective data showing survival benefit of screening Chest x-ray alone is not effective Sputum cytology is not effective Spiral CT is promising Molecular methods are in the infancy PLCO trial underway

30 Lung cancer screening in US Routine population based screening is not recommended by any organization

31 ACS recommendation for individuals Individual physician and patients may decide that the evidence is sufficient to warrant the use of these screening tests on an individual basis

32 Staging procedures Old methods CT chest Mediastinoscopy Mediastinotomy Thoracotomy Newer methods PET scan Mediastinal FNA Bronchoscopic ultrasound FNA Esophageal ultrasound FNA

33 Image guided FNA for staging Anterior mediastinal nodes CT guided transthoracic FNA (CT FNA) Middle mediastinum Endoscopic ultrasound FNA (EU FNA) subcarinal noses and post. Mediastinum CT FNA or EU FNA AP window CT FNA or thoracoscopy or thoracotomy Univ. Texas, Savage et al

34 IHC and PCR in lymph node micrometastases IHC finds nodal micromets. When Hand E staining is negative Direct correlation between negative nodes and Disease free survival RT-PCR assays based on MUC1 and Surfactant protein A-D may be even more accurate and sensitive Needs to await more data and technical improvements

35 Uses of PET scan in lung cancer Evaluation of focal pulmonary abnormalities Staging of lung cancer Determining tumor recurrences Assessing the prognosis Assessing the response Further role is being defined

36 FDG-PET scan limitations False negatives Small < 10 mm cancers Carcinoids and Bronchoalveloar histology False positives Infections: TB, hstoplasmosis Inflammatory disorders: RA, sarcoidosis Post radiation for 4-5 months

37 FDG-PET scan for focal pulmonary abnormalities High probability of cancer if PET is positive ( >90% in age over 60) Low probability of cancer if PET is negative (<5% probability) Lesions with low FDG uptake can be followed radiologically recognizing the limitations of the study

38 Positron Emission Tomography (PET) scan in lung cancer 18F-2-deoxy-D-glucose (FDG), a d-glucose analogue increased glucose metabolism by malignant cells results in increase uptake and accumulation of FDG helping tumor detection Payable by Medicare for lung cancer

39 FDG-PET in staging of lung cancer High negative predictive value (>90%) for mediastinal nodes May avoid mediastinoscopy if PET is neg. Whole body PET scan can detect 11-14% more mets and alters management in up to 40% of the patients Very sensitive for adrenal metastases

40 FDG-PET scan in detection of lung cancer recurrence Distinguish between persistent or recurrent tumor from scarring or fibrosis More accurate than CT or MR scans Not to be done until 4-5 months post-rt False positive from radation induced inflammation

41 FDG-PET scan as a prognostic tool Possible role as a prognostic marker Significantly increased uptake in primary, predicted worse survival relative to modest uptake Normal FDG scan after treatment predicted longer disease free interval Improved survival directly correlated to magnitude of decrease in uptake after chemotherapy

42 Goals of lung cancer treatment Provide palliation Improve quality of life Prolong survival Cure the disease Minimize the side effects of treatment

43 Prognostic factors Stage-most important factor Performance status Weight loss Molecular factors C-erb-2 Epidermal growth factor (EGF) Ras mutations

44 ECOG performance status scale 0: no symptoms 1: symptomatic but no extra time in bed 2: in bed <50% of the day, can care for self 3: in bed >50% of the day, minimal self care 4: completely bed ridden Good predictor of treatment tolerance

45 Videothoracoscopic lobectomy Minimally invasive surgery concept Technically feasible Concerns Adequate tumor control inadequate lymph-node dissection local recurrence at toracoport site safety of hilar dissection

46 University of Pittsburgh data Measure Open surgery Videothorac. # of nodes Op. time mins mins Hospital stay days 7.07 days Chest tube 8.16 days 4.77 days ICU days

47 Adjuvant therapy for completely resected lung cancer Overall results of randomized trials remains discouraging so far. New generation of trials with newer combinations are in progress

48 Combined chemo-radiation in stage III NSCLC Cisplatinum based chemotherapy with RT is associated with reduction in mortality at 1 and 2 years

49 Summary Stage III NSCLC results RT alone 5-10% 5 yr... survival Surgery alone Mediastinoscopy +N2: 9% Incidental N2: 24% Induction therapy: 17-37% pre-op chemo: 17-19% pre-op chemo-rt: 22-37%

50 First line chemotherapy in stage IV NSCLC Cisplatin based regimens provide survival benefit compared to supportive care alone at 1 year A small improvement in quality of life has been determined in randomized controlled trials in favor of chemotherapy Toxicity may be greater in patients with ECOG PS 3 or 4

51 Chemotherapy vs supportive care in stage IV NSCLC agent Hazard ratio P value Median survival 1 yearr survival Alkylating Agents Vinca or Etoposide Cisplatin based mo -6% mo 4% mo 10* BMJ 1995; 311:

52 Second line chemotherapy in NSCLC Secondline Docetaxel improved survival in patients who previously received cisplatin based chemotherapy Median survival 7 months Vs 4.6 months

53 Treatment paradigm shift stage IV NSCLC First line chemo Palliative care Hospice care First line chemo Second line chemo palliative care Hospice care

54 Targeted therapies

55 Epidermal growth factor pathway in lung cancer EGFR pathway contributes to the aggressiveness of the tumor EGFR tyrosine-kinase inhibitor, ZD 1839 (Iressa) is in clinical trials

56 HER-2 in lung cancer as a potential therapeutic target HER-2 overexpression in NSCLC is associated with poor outcome HER-2 overexpression contributes to tumor progression Monoclonal antibodies can target HER-2 Chemotherapy + Herceptin trials are ongoing in NSCLC

57 Future therapies Antiangiogenesis agents Tumor vaccines Gene replacement therapy Antisense oligonucleotides?? 50% 5 year survival

58 Thalidomide Angiogenesis Inhibitor Angiogensis suppression result in balancing of tumor cell proliferation and cell death resulting in dormancy of metastases in mice Hypothesis: Any strategy promoting dormancy of micromets may add to the results of standard chemo-rt in locally advanced lung cancer

59 Pilot trial of Chemotherapy + Thalidomide University of Wisconsin trial Nine patients Taxol+Carboplatin+Thalidomide Feasible ECOG 3598 is a randomized comparison of chemo-rt with or without Thalidomide

60 Small cell lung cancer Combination chemoradiotherapy for limited stage Finding new chemotherapy combinations for extensive stage Irinotecan+Cisplatin-new standard in Japan??Triple combinations containing a Taxane, etoposide and platinum

61 JCOG 9511 in SCLC EP CP Med survival 41 wks 55.7 wks 1 year 37.3% 58.4% 2-year 6.5% 18.9%