Patient Case Discussion Advanced NSCLC Robert Pirker Medical University of Vienna

1. Patient Case Discussion Advanced NSCLC  Robert Pirker Medical University of Vienna

2. Case Discussion Advanced NSCLC A 62-year old man with symptoms of brain metastasis and a lung tumor

3. Case Discussion Advanced NSCLC 62-year old male Smoker (~40 pack years) No history of serious illnesses, no weight loss Developed severe nausea plus headache in Feb 2001; collapsed on Feb 27, 2001 Admission to hospital

4. Case Discussion Advanced NSCLC 178 cm, 82 kg, ECOG-1 Heart & lung normal, RR 140/80, 80/min Liver & spleen normal No enlarged lymph nodes No edema No signs of neurological deficits

5. Case Discussion Advanced NSCLC MRI of the brain: Lesion (~ 2 cm) fronto-basal on the right site plus edema

6. Case Discussion Advanced NSCLC MRI of the brain: Lesion (~ 2 cm) fronto-basal on the right site plus edema Chest X-ray: Suspicion of tumor in left lung CT Scan of thorax & upper abdomen: Tumor left upper lobe (~ 3.5 cm) No enlarged mediastinal lymph nodes Normal liver and adrenal glands Bronchoscopy: Not done

9. Case Discussion Advanced NSCLC 62-y old male smoker ECOG 1 Lung cancer suspected Single brain lesion single lung lesion cT2N0M1 clinical stage IV

10. Question Which additional staging procedure(s) surgery would you perform? PET Scan 2) Bone scan Both PET & bone scan Other(s) None

11. Question Which of the following therapies would you recommend as initial therapy for this patient with NSCLC stage IV ? 1) Surgical resection of cerebral metastasis 2) Stereotactic radiosurgery of brain metastasis +/- whole-brain radiotherapy 3) Palliative chemotherapy

12. Case Discussion Advanced NSCLC Dexamethasone Resection of cerebral metastasis as initial therapy March 20, 2001 Severe symptoms required rapid relief Squamous cell carcinoma plus large cell carcinoma with neuroendocrine features, compatible with NSCLC Rapid postoperative recovery Nausea & headache disappeared Postoperative whole-brain radiotherapy 30 Gy (May � June 2001)

13. Brain metastasis Frequent in lung cancer Synchronous Metachronous Therapy Surgery Stereotactic radiosurgery Whole-brain radiotherapy Disease status outside of the brain must be considered

14. Therapy of brain metastasisPeacock KH & Lesser GJ. Curr Treat Options Oncol 2006, 7, 479 Surgery Single metastasis >3.5 cm Immediate tumor relief necessary Pathological diagnosis required Small tumors with minimal edema & surgically accessible Stereotactic radiosurgery Metastasis <3.5 cm in surgically inaccessible areas Patients not suited fur surgery Small tumors with minimal edema (even when surgically accessible)

15. Stereotactic radiosurgery plus/minus whole-brain radiotherapyAoyama H et al. JAMA 2006, 295, 2483 142 patients, 1 - 4 metastases (< 3 cm) SRS SRS+WBRT p value Os median 8 mo 7.5 0.4 1-year 28% 38% Brain relapse 76% 47% <0.001 Salvage therapy brain ? WBRT decreases brain relapse rate but does not improve survival

16. Brain metastasis Metachronous Better prognosis than synchronous lesions (33 vs. 9 months from time of diagnosis of NSCLC, p=0.001) but no difference from time of metastasis (12 vs. 8 months, p=0.5) Flannery TW et al. Lung Cancer 2003, 42, 327 Surgical resection + whole brain radiotherapy Patchell RA et al. NEJM 1990, 322, 494 Synchronous Resection of brain metastasis + whole-brain radiotherapy Billing PS et al. J Thor Cardiovasc Surg 2001, 122, 548 Surgical resection of primary tumor ?

17. Question Which of the following therapies would you recommend for this patient after resection of brain metastasis Resection of the primary tumor Resection of the primary tumor followed by systemic chemotherapy Systemic chemotherapy None

18. Case Discussion Advanced NSCLC 62-y old male smoker Surgery of primary tumor: Lobectomy left upper lobe + mediastinal lymphadenectomy (20.4.2001) complete tumor resection Final diagnosis: NSCLC (squamous cell + large cell carcinoma) pT2pN0M1 pathological stage IV complete tumor resection

19. Question Which treatment would you recommend for this patient after resection of the brain metastasis (plus whole-brain radiotherapy) and after resection of the primary tumor No further treatment Systemic chemotherapy

20. Question Which of the following protocols would you use for systemic chemotherapy in this patient with good performance status and normal organ functions? 1) Cisplatin-based doublet 2) Carboplatin-based doublet 3) Non-platinum-based doublet 4) Other

21. Case Discussion Advanced NSCLC Cisplatin/vinorelbine, 4 cycles July - October 2001 Regular follow-up No further smoking CT scans thorax plus upper abdomen & MRI of the brain Patient alive 6 years after initial diagnosis Last follow-up on Jan 24, 2007

22. Unresectable NSCLC: Follow-upASCO guidelinesPfister DG et al. JCO 2004, 22, 3330 History & physical examination every 3 months during first 2 years every 6 months thereafter through year 5 yearly thereafter Chest radiographs Only in symptomatic patients MRI brain Only in symptomatic patients Smoking cessation

23. Case Discussion Advanced NSCLC Case 2: 43-year old female smoker NSCLC IB (1999): lobectomy right upper lobe adjuvant chemotherapy (IALT) 2 metachronous brain lesions (June 2000): stereotactic radiosurgery of both lesions plus whole-brain radiotherapy Continuous clinical remission in 2007

24. Case Discussion Advanced NSCLC Case 3: 53-year old male smoker NSCLC IV (2005) with single brain metastasis: surgical resection + whole-brain radiotherapy lobectomy systemic chemotherapy Brain relapse (June 2006): stereotactic radiosurgery Currently stable disease

25. Patient Case Discussion Advanced NSCLC Summary Brain metastases are frequent in lung cancer (synchronous, metachronous) Surgery, stereotactic radiosurgery, whole-brain radiotherapy Resection of single brain metastasis and primary tumor can result in long-term survival in patients with good performance status and absence of mediastinal lymph node involvement Resection or radiosurgery (+/- whole-brain radiotherapy) of metachronous single metastasis can also result in long-term survival Not all of the treatment decisions were based on randomized trials

28. Question Which therapy would you recommend for this patient with completely resected NSCLC stage IV ? 1) No further therapy 2) Adjuvant cranial irradiation 3) Chemotherapy 4) Chemotherapy and radiotherapy 

29. Case studyNSCLC Brain metastasis frequent in patients with NSCLC Patients with single brain metastasis lesion and single lung lesion benefit from surgical resection of both lesions Postoperative cranial irradiation & systemic chemotherapy

30. Surgery in NSCLC IV Resection of single cerebral metastasis Resection of lung metastasis Single lung metastasis rare at initial diagnosis Staging Secondary primary Resection of single bone lesion Palliative Resection of adrenal gland metastasis ?? Resection of liver metastasis Single lesion is rare Far advanced disease