11/21/ M with LUL Mass Case Presentation / Round Table Discussion. Multiple-choice question What stage is this tumor?

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1 MS 62M with LUL Mass Case Presentation / Round Table Discussion Dr. Jasleen Kukreja and Johannes Kratz Department of Thoracic Surgery University of California, San Francisco 62M, presented to clinic 6/2009 PMH: R inguinal hernia, COPD, s/p cholecystectomy Meds: Nicoderm path All: Vicodin (nervousness) SHx: 90 pk-yr smoking history, quit 5 weeks PTA, then restarted with 5-10 cig/d. H/o EtOH addiction, quit 10 years ago, now in AA. FHx: prostate CA, bladder CA Functional status: 3 blocks / 2 flights of stairs before getting SOB Preparing to undergo R inguinal hernia repair 5/2009 Routine pre-op CXR revealed a LUL opacity Underwent a PET/CT PET/CT Multiple-choice question What stage is this tumor? cm LUL tumor with ipsilateral perihilar node T2a N1 M0 -> Stage IIA 29% 2. Dumbbell-shaped 7cm LUL tumor T3 N0 M0 -> Stage IIB 3. LUL tumor with satellite lesion T4 N0 M0 -> Stage IIIA 4. Other Stage 5. It s not a tumor 34% 29% 3% 5% 4.3 cm mass in LUL w/ small pleural attachment -> SUV cm mass inferior LUL near superior L hilum -> SUV cm LUL tum... Dumbbell-shape... LUL tumor with... Other Stage It s not a tum... 1

2 How to proceed in this 62M with h/o COPD, large LUL mass? 1. Proceed straight to surgery 58% 2. Needle biopsies of two separate tumor foci 3. Neoadjuvant chemotherapy 4. Neoadjuvant radiation therapy 5. Neoadjuvant chemoradiation therapy 6. 17% Forget the LUL mass, focus on the R inguinal hernia repair 8% Proceed straig... Needle biopsie... Neoadjuvant ch... 0% Neoadjuvant ra... 4% Neoadjuvant ch... 13% Forget the LUL... Evidence for neo-adjuvant therapy Classic RCT Studies Early Hope Rosell et al. NEJM pts, stage IIIA Induction cisplatin, mitomycin, and ifosfamide + surgery + XRT vs. surgery + XRT No difference in rate of resection 2 year median follow-up demonstrated threefold improvement in survival (26 vs 8 months) Roth et al. J Natl Cancer Inst pts, stage IIIA cisplatin, etoposide, and cyclophosphamide + surgery vs. surgery alone No difference in rate of resection 3 year media follow-up demonstrated sixfold improvement in survival (64 vs 11 months) Evidence for neo-adjuvant therapy Evidence for neo-adjuvant therapy Classic RCT Studies Long-term results unimpressive Rosell et al. Lung Cancer year median follow-up demonstrated demonstrated twofold improvement (22 vs 10 mo median survival) Not convincing because no survivors in surgery + XRT alone Repeat RCT with similar neoadjuvant arm did not demonstrate similar survival rates (11 mo survival) Roth et al. Lung Cancer year median follow-up demonstrated 21 vs 14 month improvement in medial survival No longer statistically significant Subsequent RCT Studies Depierre et al. J Clin Oncol 2002 Pisters et al. J Clin Oncol 2007 Gilligan et al. Lancet 2007 Scagliotti et al. J Clin Oncol 2008 Large (270 to 519 pts) IB-IIIA disease (Scagliotti also looked at IA disease) Overall, non-significant trends towards improved survival Exception: Depierre stage Ib, II pts showed statistically significant improvement in survival (RR 0.68) 1 meta-analysis (Berghmans et al. Lung Cancer 2005) and 1 systematic review (Burdett et al. J Thorac Oncol 2006) demonstrated small but statistically significant improvements in survival 2

3 MS: Outside Evaluation MS: UCSF Evaluation Saw local thoracic surgeon Recommendation -> proceed straight to surgery Saw local oncologist Fine needle CT-guided bx -> squamous cell CA Interestingly, bx complicated by PTX -> chest CT revealed tumor fell away from chest wall except for one apical lateral attachment Additional Testing PFTs FVC 4.38 (91% predicted) FEV (52% predicted) DLCO 32.3 (65% predicted) Negative brain MRI Came to UCSF for further evaluation UCSF Radiation Oncologist No precedence for gamma-knife radiation in T2N1 disease UCSF Thoracic Surgeon VATS may not be feasible due to size of lesion and possible chest wall involvement Recommended neoadjuvant therapy in light of possible N1 disease and to try to shrink mass Tumor Board consensus - agreed with neoadjvuant therapy Local Thoracic Oncologist Neoadjuvant therapy 7 cycles of weekly carboplatin and Taxol Well-tolerated Restaging PET/CT Restaging PET/CT Significant reduction in size of LUL mass, no evidence of pleural involvement SUV 12 -> 9 reduction in size of secondary focus SUV 9.5 -> 3.5 3

4 How to proceed now? MS 1. Proceed straight to surgery 2. Additional neoadjuvant chemotherapy 83% 3. Proceed with radiation therapy recommended by local oncologist 4. None of the above 5. I told you it wasn t a tumor UCSF Thoracic Surgery recommended proceeding straight to surgical resection Patient elected to undergo surgical resection without additional neoadjuvant therapy 7% 2% 5% 2% Proceed straig... Additional neo... Proceed with r... None of the ab... I told you it... Which surgical approach? 1. Minimally invasive lobectomy 2. Open lobectomy 3. Open pneumonectomy 4. I disagree with surgery and still 40% want more neoadjuvant therapy! Minimally inva... Open lobectomy 56% 0% Open pneumonec... 4% I disagree wit... Is minimally invasive approach safe after neoadjuvant therapy? Peterson et al. Ann Thorac Surg 2006 Retrospective 97 patients 2 arms 85 pts -> Thoracotomy 66/85 neoadjuvant chemorad 19/85 neoadjuvant chemo 12 pts -> Minimally invasive (VATS) 8/12 neoadjuvant chemorad 4/12 neoadjuvant chemo No significant difference in overall survival Pts undergoing VATS had expected benefits of a minimally invasive approach Decreased LOS (3.5 vs 5 d, p = ) Decreased CT duration (2 vs 4 d, p < 0.001) 4

5 MS: Surgical Resection Underwent a minimally invasive operation L VATS lobectomy and mediastinal LN dissection Findings LUL adhesions to parietal pleural in the region of the mass Multiple pleural biopsies negative on frozen No evidence of pleural effusion Pathology Poorly differentiated adenocarcinoma Only microscopic tumor foci identified in bed of necrotic tissue, mass did not reach visceral pleural surface T2 N0 (0/24) Mx -> Stage IIA Hospital Course Discharged home in good condition with a pneumostat How to proceed? 1. Send paraffin block off for molecular biomarker profiling 2. Adjuvant therapy 3. A & B 4. See you in post-op clinic! Send paraffin... 20% Adjuvant thera... 12% 37% 31% A & B See you in pos... MS: Follow-up Take-Aways Did not undergo molecular biomarker profiling or adjuvant therapy Seen in clinic, pneumostat removed one week postop Patient currently doing well Will receive follow-up CT in 4 months Neoadjuvant therapy may offer small improvement in overall survival, especially in early stage NSCLC Minimally invasive surgery after neoadjuvant therapy is safe and effective Neoadjuvant therapy can help downsize tumors allowing for less morbid operations 5

6 Thank you 6