Stage I, II Non Small Cell Lung Cancer

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1 Stage I, II Non Small Cell Lung Cancer Best Results T1 (less 3 cm) N0 80% 5 year survival No Role Adjuvant Chemotherapy Radiation Therapy Reduces Local Recurrence No Improvement in Survival 1

2 Staging Mediastinal node on CT SCAN less 1 cm 8-15% risk cancer Greater 2 cm 60-80% risk cancer Sensitive = true positive/total positives Specific = true negative/total negative CT SCAN 75% sensitive; 66% specific for mediastinum PET SCAN 91% sensitive. 86% specific mediastinum Gold standard mediastinoscopy Consider CT Head/MRI Head in all Patients (occult 5-10% patients) 2

3 Stage III A Resectable Non Small Cell Lung Cancer Stage IIIA (N2 ipsilateral mediastinal nodes) Need mediastinoscopy Two small studies Closed early due to impressive interim survival advantage Chemotherapy prior to surgery Survival 5 years Surgery alone Survival 1 year 3

4 Adjuvant Chemotherapy Recent Controversial Data Suggests Improved Survival Chemotherapy with Cisplatinum after Resected Non Small Cell Lung Cancer 4

5 Unresectable Non Small Cell Lung Cancer Less than 2 cm from carina N3 nodes Contralateral mediastinal Supraclavicular Malignant Pleural Effusion Macroscopic Ipsilateral N2 Mediastinal Nodes Adequate Pulmonary Function Tests Predicted FEV-1> 800cc 5

6 Stage III not resectable Non Small Cell Lung Cancer no malignant pleural effusion Concurrent chemotherapy/radiation therapy More effective More side-effects than Sequential chemotherapy followed by radiation therapy Best Results: Cisplatinum, Etoposide (VP-16) with radiation therapy; followed by taxotere (Docetaxel) 3 year survival 40% percent 6

7 Pancoast Tumor Superior Sulcus Tumor Shoulder, Arm Pain (C8, T1, T2) Horner s Syndrome: ptosis, miosis, anhidrosis Treatment: Neoadjuvant chemotherapy/radiation followed surgery Prognosis better if no mediastinal lymph nodes 7

8 8

9 Advanced Metastatic Non Small Cell Lung Cancer Chemotherapy gives improved quality of life compared to supportive care Chemotherapy gives small improvement in survival Chemotherapy most effective in Patients with good performance status Measurable or evaluable disease 9

10 Definitions Partial Response Rate Percent patients whose disease shrinks Complete Response Rate Percent patients whose disease can not be detected Cure---disease is gone forever Median Survival Average Survival One year survival Percent patients alive at one year 10

11 Types of Chemotherapy Multiple relatively effective drugs Possibly doublets more effective single agent 1 year survival 35% Median Survival 8 months Response rate 20% 11

12 Types of Chemotherapy for Non Small Cell Lung Cancer Cisplatinum (Cisplatin)\ Carboplatinum (Carboplatin) Paclitaxel (Taxol) Docetaxel (Taxotere) Irinotecan (CPT-11) Gemcitabine (Gemzar) Vinorelbine (Navelbine) 12

13 Single Institution versus Cooperative Group Single Institution Selection Bias Measurement Bias More skilled team Cooperative Group Many institutions Generally, response rate is 10% higher with same chemotherapy for single institution 13

14 ECOG 1594: Kaplan-Meier Estimates Survival (%) of Overall Survival Cisplatin and paclitaxel Cisplatin and gemcitabine Cisplatin and docetaxel Carboplatin and paclitaxel Month Schiller et al. N Eng J Med; 2002; 346:

15 Second Line Therapy Non Small Cell Lung Cancer Docetaxel (Taxotere) 1 yr survival 30% Response rate 10% FDA approved 15

16 TAX 317B - Survival Taxotere 75 mg/m 2 vs BSC Cumulative Probability T75 BSC75 Median 7.5 vs 4.6 mos. Log-rank P = year 37% vs 12% Chi-square P = Shepherd et al JCO 2000;18: Survival Time (months) 16

17 TAX 317 Clinical benefit of Taxotere 75 mg/m 2 vs BSC Parameter Taxotere 75 BSC P-value Radiotherapy treatment 16% 41% <0.01 Mean decline in PS <0.05 >10% weight loss 2% 22% <0.01 Shepherd et al JCO 2000;18:

18 IRESSA ZD1839 Oral, selective, epidermal growth factor tyrosine kinase inhibitor EGFR overexpressed 32 to 81% lung cancer Patients failed two prior regimens 10% response rate Median survival 6 months Mild diarrhea, skin rash No improvement in survival when given with chemotherapy FDA Approved 18

19 SURVEILLANCE POST THERAPY No clear role for routine lab, CT SCAN, bone scans etc. Detection of asymptomatic recurrence 9 month lead-time bias (NO improvement survival) 19

20 Small Cell Lung Cancer Limited One Hemi-thorax No malignant pleural effusion No metastasis Extensive Liver, lung, brain, malignant pleural effusion 20

21 Treatment Limited Small Cell Lung Cancer Chemotherapy plus radiation Best Results Twice a day radiation therapy with concurrent Cisplatinum (Platinol); VP-16 (Etoposide) Radiation Therapy 6 weeks Response Rate 90% 47% two year; 26% 5 year survival Prophylactic cranial radiation If in complete remission 21

22 Extensive Small Cell Lung Cancer Chemotherapy or Palliative Radiation Rx: Best Results Japanese Study CPT-11 (Irinotecan)/Cisplatinum(Platinol) 20% two year survival Response Rate 90% 22

23 Superior Vena Cava Syndrome Symptoms Dyspnea Facial Swelling 80 % caused by malignancy Most common Small Cell 20% of Small Cell develop SVC syndrome Less common, Non small cell, lymphoma Thrombosis secondary in-dwelling catheters 23

24 Superior Vena Cava Syndrome Dx: CT SCAN; Venography Recent Review Usually Not Emergency Treat with standard chemotherapy and or radiation therapy Intraluminal metal stents 24

25 Hypercalcemia Lung Cancer Osteolytic Metastasis from Non-Small Cell Parathyroid Hormone Protein Squamous Treatment Bisphosphonates inhibit osteoclast bone resorption; also reduce pathological fractures Zometa (Zoledronic Acid) 4 mg Aredia (Pamidronate ) 90 mg IV fluids plus lasix 25

26 Spinal Cord Compression Vertebral Metastasis is more common that epidural cord compression 60% in thoraic spine Weakness, sensory deficits, urinary retention, constipation; spasticity; upgoing toes; hyperactive reflexes (upper motor neuron) 66% abnl plain radiographs spine MRI 26

27 Treatment Spinal Cord Compression Decadron Dexamethasone (10 mg stat) then high dose Radiation therapy Use neurosurgery no diagnosis; bony instability; radioresistant tumor Recent Data Neurosurgery more effective Radiation to improve neurological function 27

28 Brain Metastasis 5-10% at time of diagnosis (asymptomatic) 80% cerebral hemisphere Variety Neurological Symptoms MRI more sensitive than CT SCAN with contrast Resect Solitary Brain Metastasis Otherwise Radiation Therapy 28

29 Patient #1 Adenocarcinoma of the Lung RUL 2 cm Mass 2 cm Right Hilar lymph Node Malignant Right Pleural Effusion?? What Stage?? What Treatment?? 5 year Survival 29

30 Patient #2 Right Upper Lobe Mass Small Cell Right Mediastinal Node 2 cm??what Additional Tests?? What Treatment?? 5 year survival 30

31 Patient #3 75 year old man Adenocarcinoma of Right Upper Lobe Liver Metastasis Bed Ridden?? What Stage?? What Treatment?? 5 year survival 31

32 Patient #4 60 year white female Left Lower Lobe Squamous Cell Cancer Asymptomatic solitary brain metastasis?? Stage?? Treatment 32

33 Patient #5 Large Cell Carcinoma of Right Upper Lobe Mediastinoscopy microscopic potentially resectable right mediastinal node No other metastasis?? Stage?? Treatment?? Prognosis 33

34 Question Match Similar Type Therapies A: Extensive Small Cell Lung Cancer B: Stage III Unresectable Non Small Cell Lung Cancer (no pleural effusion) C: Stage IV non small cell lung cancer or malignant pleural effusion D: Limited Small Cell Lung Cancer 34

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