Locally Advanced NSCLC: Case Presentation

Transcription

1 Locally Advanced NSCLC: Case Presentation Sun K. Yi, M.D. Allen M. Chen, M.D. Department of Radiation Oncology University of California, Davis Cancer Center Case history 51 yr-old female seeks medical attention for 2 month history of non-productive cough PMH: HTN, depression 70 pack-year tobacco history but recently quit Retired English teacher ROS/FH otherwise noncontributory No F/C/S/WL; KPS 90 PE unremarkable Radiographic Studies CXR (2 Views): R basilar density Radiographic Studies CT Chest: 3.3 cm RLL mass w/ R hilar and subcarinal LAN 1

2 Work-up CT guided biopsy: adenocarcinoma MRI brain: WNL Radiographic Studies PET/CT: Confirms hypermetabolism at primary and regional hilar and mediastinal lymph nodes Should mediastinoscopy be performed? Mediastinoscopy 1. Yes 2. No 76% Mediastinoscopy Level 7 Positive with ECE R2 Positive L4 Negative R4 Negative 24% Yes No 2

3 Pulmonary Function Tests FEV1 71% predicted DLCO 75% predicted DLCO/VA 60% predicted FVC 65% predicted Treatment Options 51 year-old with T2N2 NSCLC Locally advanced NSCLC 1. Surgery then adjuvant chemo +/- RT 2. Neoadjuvant chemo then surgery 3. Neoadjuvant chemoradiation then surgery 4. Chemoradiation alone 5. Chemoradiation then consolidation chemo 38% 15% 15% 15% 15% After lengthy discussion and informed consent, patient elects for preoperative chemoradiation followed by surgery Surgery then a... Neoadjuvant ch... Neoadjuvant ch... Chemoradiation... Chemoradiation... 3

4 Case history (cont d) 4500 cgy 4500 cgy in 180 cgy frx beginning day 1 of chemo Concurrent chemotherapy cisplatin (50 mg/m2) + etoposide (50 mg/m2) x 2 Tolerated chemoradiation uneventfully Radiographic Studies CT Chest (1 wk prior to completion of RT) stable disease Surgery (1 mo after chemort) R lower lobectomy with LN sampling 1.7 cm NSCLC with negative margins No LVSI 4/5 LN positive (R hilar and subcarinal) ECE present at subcarinal LN Postoperative course unremarkable 4

5 Further treatment? Postoperative options 1. Observation 2. More chemotherapy 3. Concurrent chemoradiation 54% 4. Chemotherapy then radiation 26% 5. Radiation then chemotherapy 6. Re-excision 15% 4% 2% 0% Observation More chemother... Concurrent che... Chemotherapy t... Radiation then... Re-excision 3 months post-treatment After lengthy discussion and informed consent, the patient elected for further chemotherapy (cisplatin/etopside x 2 cycles) 5

6 Is there a role for preoperative chemoradiation? (or does surgery really add anything after chemoradiation?) Discussion of INT 0139 What did we learn from SWOG 88-05? Preoperative CRT is feasible with pcr 21%. Pts who do best have mediastinal clearance. Approach is best suitable for stage IIIA Albain et al, JCO 1995 SWOG N2 status at surgery Patients: Intergroup pts with stage IIIA (pn2) NSCLC Randomization: Chemoradiation +/- Surgery Initial (induction) treatment: 4500 cgy with 2 cycles chemo (cisplatin 50 mg/m2 on days 1, 8, 29, 36 and etoposide 50 mg/m2 on days 1-5 and 29-33) Albain et al, JCO

7 INT 0139 Upfront Randomization Arm 1 1.Re-evaluate 2-4 wks after completion of induction regimen, if no progression -> 2.Surgery 3.Additional 2 cycles of chemotherapy starting 4-6 wks after surgery Arm 2 1.Re-evaluate 7 days before completion of induction regimen 2.Continue RT (no break); 16 Gy/ 2 frx with 2 additional cycles of chemotx. 3.Total dose 61 Gy INT 0139 These patients were all potentially resectable upfront before randomization INT 0139: Results INT 0139: Overall survival ChemoRT Surg ChemoRT N Median OS 24 mo 22 mo 5-year OS 27% 20% 5-year PFS 22% 11% Tx mortality 8% 2% P=0.10 for OS P=0.02 for PFS Source: Albain et al, Lancet 2009 Source: Albain et al, Lancet

8 INT 0139: Toxicity Most perioperative deaths due to ARDs, predominantly in the setting of pneumonectomy Therefore chemoradiation prior to pneumonectomy is generally not recommended Limitations of INT 0139 Relatively small study (N=396) No PET/CT Many patients in surgery arm did not receive cycles 3 and 4 of chemotherapy Variability of surgical technique Any OS benefit from surgery possibly diminished secondary to high mortality from pneumonectomy 45% pt0n0 underwent pneumonectomy (maybe unnecessarily) Source: Albain et al, Lancet 2009 Not all IIIAs are made equal Tumor bulk Location Number of lymph nodes Type of surgery (lobectomy vs. pneumo) Performance status Treatment of Stage III NSCLC needs to be individualized Multidisciplinary discussion is always preferred 8

9 Questions for discussion Thoracic Oncology at UCD How can we better improve patient selection for surgery after chemoradiation? What modalities are best for predicting pathological response? Is there any role for repeat mediastinoscopy after neoadjuvant chemoradiation? Is a potential role for more aggressive postsurgery treatment for those with residual pn2 disease? Medical Oncology D. Gandara, M.D. P. Lara, M.D. D. Lau, M.D., Ph.D. T. Li, M.D. Radiology D. Shelton, M.D. E. Moore, M.D. Thoracic Surgery R. Calhoun, M.D. D. Cooke, M.D. Pulmonology K. Yoneda M.D. Pathology C. Yu, M.D. R. Ramsamooj, M.D. 9