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

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

3. CXR

4. CT thorax (2/2015)
CT thorax  (27/2/2015) -4.1cm mass in apicoposterior segment of left upper lobe cm 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.

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

6. 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

7. PET-CT (Hilar LN)

8. PET-CT (Subcarinal LN)

9. PET-CT (AP window LN)

10. Neoadjuvant chemoirradiation
MDT decision
Neoadjuvant chemoirradiation
Surgery

11. 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

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

13. 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

14. Radiotherapy plan

15. Radiotherapy plan

16. Radiotherapy plan

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

18. 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.

19. 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.

20. 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.

21. 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.

22. 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

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

24. 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

25. 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

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

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

28. Role of surgery
Lancet 2009; 374:

29. 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

30. 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

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

32. 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

33. 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.

34. 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

35. 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

36. 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): , March 2010.

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