Multi-station N2 Ca Lung Dr. Adrian Chan Resident, Department of Clinical Oncology Tuen Mun Hospital, Hong Kong Asian NSCLC Preceptorship 16/6/16 (

Case history M/67 Spinal stenosis, otherwise good past health Noted incidental finding of abnormal CXR during pre-operative workup for spinal stenosis

CXR

CT thorax (2/2015) CT thorax  (27/2/2015) -4.1cm mass in apicoposterior segment of left upper lobe. -2.1cm enlarged left hilar lymph node. -Prominent subcarinal lymph node measured 0.7cm x 2.3cm is seen. A few lymph nodes are noted in aortopulmonary window, up to 1.3cm x 0.5cm in size.

Case history Bronchoscopy (26/2/2015) no endobronchial lesion EBUS (4/3/2015) Subcarinal and 11L FNAC Non-small cell carcinoma favour adenocarcinoma

PET-CT (lung tumour) PET-CT (18/3/2015): -Hypermetabolic mass 3x3.9x4.8cm in left upper lobe. - Left hilar (1.9 x 2.2 x 2.3cm SUV max 6.9), AP window (0.9 x 1.3cm, SUV max 2.6), subcarinal LN (1 x 3 x 1.9cm, SUV max 5.9) and superior mediastinal LN (0.6cm, SUV max 1.9) - No distant metastasis

PET-CT (Hilar LN)

PET-CT (Subcarinal LN)

PET-CT (AP window LN)

Neoadjuvant chemoirradiation MDT decision Neoadjuvant chemoirradiation Surgery

Treatment Paclitaxel (175 mg / m2) & Carboplatin (AUC 5) Followed by RT 60Gy / 30fr / 6weeks concurrent with 2 cycles of Etoposide-Carboplatin given on D1 – D3 of every 21-day cycles Followed one more cycle of Paclitaxel-Carboplatin after chemoirradiation

RT contouring Co-registered with PET-CT Primary lung tumour as GTV_T Lt hilar LN, subcarinal LN & AP window LN as GTV_N

RT contouring CTV_T = GTV_T + 8mm CTV_N = GTV_N + 5mm and peri-tracheal region PTV = CTV_T + 15mm and CTV_T + 5mm AP window LN included for benefit of doubt. Involved node irradiation is used in our centre

Radiotherapy plan

Radiotherapy plan

Radiotherapy plan

Dose volume histogram Dose contraints Mean lung dose (Whole lung – GTV): 19.5 Gy V20: 28.1%

Re-staging PET-CT Re-staging PET-CT was done 2 weeks after RT There was improvement in both the size & metabolic activity of the primary tumour & the mediastinal lymph node.

Re-staging PET-CT Re-staging PET-CT was done 2 weeks after RT There was improvement in both the size & metabolic activity of the primary tumour & the mediastinal lymph node.

Re-staging PET-CT Re-staging PET-CT was done 2 weeks after RT There was improvement in both the size & metabolic activity of the primary tumour & the mediastinal lymph node.

Re-staging PET-CT Re-staging PET-CT was done 2 weeks after RT There was improvement in both the size & metabolic activity of the primary tumour & the mediastinal lymph node.

Re-staging EBUS (7/2015): Subcarinal LN, 10.9 x 12.2 mm, FNA taken 11L LN, 8.3 mm, FNA taken 4L LN, 3.1mm, no FNA taken Subcarinal & 11L FNA: scanty atypical cells seen

Further workup MRI brain (7/2015) No brain metastasis Lung function test (7/2015) PFT FEV1 1.98 FVC 2.38 DLCO 95%

Surgery Left VATS LUL lobectomy & mediastinal LN dissection done on 25/8/15 Intra-op finding Tumour at lateral aspect of LUL Multiple enlarged mediastinal LNs around the interlobar PA and LUL bronchus Multiple pleural plaque seen

Pathology Pathology: non-small cell carcinoma, ypT1N0 Tumour size: 25 x 20 x 28mm Lymph node dissection Inter-lobar: 0/1 Lobar: 0/8 Subcarinal: 0/1 AP window: 0/2 Pulmonary ligament: 0/2 Pleural plaque: no malignancy

Latest follow up Clinically in remission PET-CT (3/2016), 7 months after surgery Post-operative changes No evidence of recurrence

Controversy Role of surgery after concurrent chemoirradiation Role of neoadjuvant chemotherapy Re-staging procedure after chemoirradiation & before surgery

Role of surgery Lancet 2009; 374: 379 - 86

Role of surgery Study population: 396 stage IIIA non-small cell lung cancer patients Control arm: Concurrent chemoirradiation alone Experimental arm: Concurrent chemoirradiation followed by surgery

Role of surgery Induction chemotherapy concurrent with 45Gy, 1.8Gy daily fraction Reassessment CT & pulmonary function test (2 – 4 weeks post treatment) Complete surgical resection Reassessment CT & pulmonary function test (1 week before completion of chemoRT) Radiation continued to 61Gy without interruption Chemo TJ / EC

Role of surgery PFS benefit favouring surgical group, but no OS benefit

Role of surgery Possible explanation: 16 (8%) patients in surgical arm die from non-cancer causes, including 10 within 30 day post-op Among the 16 patients who died, 14 had pneumonectomy and 1 had lobectomy High mortality after surgery might have obscured the survival benefit from increase in PFS

Role of surgery This prompted to an exploratory subgroup analysis, stratified by the type of operation: Survival benefit favouring the lobectomy group Median survival 33.6 months vs 21.7 months in (p = 0.002) In our centre, most patients who have surgery after chemoRT have lobectomy done.

Role of chemotherapy CALGB-39801: No benefit from induction chemotherapy before concurrent chemoirradiation KCSG-LU05-04: No benefit from consolidation chemotherapy after concurrent chemoirradiation May be omitted in poor tolerance

Role of chemotherapy Can start treatment early For chemotherapy Can start treatment early May eliminate micrometastasis Against chemotherapy More treatment toxicity May stimulate tumour repopulation No benefit in phase 3 RCTs

Re-staging procedure Mediastinoscopy is not done after neoadjuvant chemoRT in our centre, in view of the high procedure risk after RT. A Systematic Review of Restaging After Induction Therapy for Stage IIIa Lung Cancer: Prediction of Pathologic Stage Journal of Thoracic Oncology. 5(3):389-398, March 2010.

Acknowledgement Dr. Winnie Tin, Tuen Mun Hospital Dr. SH Lo, Dr Y Tung & Radiotherapists of Tuen Mun Hospital