Advertisement

La radiologia medica

, Volume 121, Issue 9, pp 696–703 | Cite as

Resected pN1 non-small cell lung cancer: recurrence patterns and nodal risk factors may suggest selection criteria for post-operative radiotherapy

  • Paolo BorghettiEmail author
  • Fernando Barbera
  • Marco Lorenzo Bonù
  • Francesca Trevisan
  • Stefano Ciccarelli
  • Paola Vitali
  • Marta Maddalo
  • Luca Triggiani
  • Nadia Pasinetti
  • Sara Pedretti
  • Bartolomea Bonetti
  • Gianluca Pariscenti
  • Andrea Tironi
  • Alberto Caprioli
  • Michela Buglione
  • Stefano Maria Magrini
CHEST RADIOLOGY

Abstract

Purpose

To describe the pattern of recurrence in resected pN1 non-small cell lung cancer (NSCLC) and to identify factors predicting an increased risk of locoregional recurrence (LR) or distant metastasis (DM) to define a selected population who may benefit from postoperative radiotherapy (PORT).

Methods

285 patients with resected pN1 NSCLC were identified. Patients with positive surgical margins, undergoing neoadjuvant treatment or PORT, were excluded. LR was defined as first event of recurrence at the surgical bed, ipsilateral hilum or mediastinum, and other sites were considered as DM. Kaplan–Meier actuarial estimates of overall survival (OS), progression-free survival (PFS), freedom from LR (FFLR) and freedom from DM (FFDM) in different subgroups were compared with the log-rank test. Multivariate analysis was calculated.

Results

202 patients met the inclusion criteria, 24 % received adjuvant chemotherapy. The median follow-up was 39 months. The total number of recurrences was 118 (64.4 %): 44 (24 %) and 74 (40.4 %) for LR and DM, respectively. Five-year OS and PFS rates were 39.2 and 33.3 %, respectively. Extra capsular extension (ECE) (RR 2.10, p = 0.01) and lymph nodal ratio (LNR) >0:15 (RR 1.68, p = 0.015) were associated with a worse PFS. ECE and LNR >0.15 were significantly related to a worst FFLR (RR 3.04 and 4.42, respectively), and adenocarcinoma to an unfavorable FFDM (RR 1.97, p = 0.013).

Conclusions

Nodal factors as high LNR and ECE can predict an increased risk of worse FFLR and PFS. Prospective data on selected patients, treated with modern radiotherapy techniques, need to be collected to re-evaluate the role of radiotherapy.

Keywords

Locoregional recurrence Distant metastasis Pathologic N1 Non-small cell lung cancer Extra capsular extension Lymph node ratio 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study (retrospective study), formal consent is not required.

References

  1. 1.
    Edge SB, Byrd DR, Compton CC et al (2010) AJCC cancer staging manual, 7th edn. Springer, ChicagoGoogle Scholar
  2. 2.
    Higgins K, Chino J, Berry M, Ready N, Boyd J, Yoo D et al (2012) Local failure in resected N1 lung cancer: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 83(2):727–733. doi: 10.1016/j.ijrobp.2011.07.018 CrossRefPubMedGoogle Scholar
  3. 3.
    Fan C, Gao S, Hui Z, Liang J, Lv J, Wang X et al (2013) Risk factors for locoregional recurrence in patients with resected N1 non-small cell lung cancer: a retrospective study to identify patterns of failure and implications for adjuvant radiotherapy. Radiat Oncol 8:286. doi: 10.1186/1748-717X-8-286 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    NSCLC Meta-analyses Collaborative Group, Arriagada R, Auperin A, Burdett S, Higgins JP, Johnson DH, Le Chevalier T, Le Pechoux C, Parmar MK, Pignon JP et al (2010) Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet 375(9722):1267–1277. doi: 10.1016/S0140-6736(10)60059-1 CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Alam N, Shepherd F, Winton T, Graham B, Johnson D, Livingston R et al (2005) Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. an analysis of national cancer institute of canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer 47(3):385–394. doi: 10.1016/j.lungcan.2004.08.016 CrossRefPubMedGoogle Scholar
  6. 6.
    PORT meta-analysis trialists group (1998) Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet 352(9124):257–263. doi: 10.1016/S0140-6736(98)06341-7 CrossRefGoogle Scholar
  7. 7.
    Urban D, Bar J, Solomon B, Ball D (2013) Lymph node ratio may predict the benefit of postoperative radiotherapy in non-small-cell lung cancer. J Thorac Oncol 8(7):940–946. doi: 10.1097/JTO.0b013e318292c53e CrossRefPubMedGoogle Scholar
  8. 8.
    Varlotto J, Yao A, DeCamp M, Ramakrishna S, Recht A, Flickinger J et al (2015) Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival. Int J Radiat Oncol Biol Phys 91(4):765–773. doi: 10.1016/j.ijrobp.2014.12.028 CrossRefPubMedGoogle Scholar
  9. 9.
    Lardinois D, Suter H, Hakki H, Rousson V, Betticher D, Ris H (2005) Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer. Ann Thorac Surg 80(1):268–274. doi: 10.1016/j.athoracsur.2005.02.005 CrossRefPubMedGoogle Scholar
  10. 10.
    Pignon J, Tribodet H, Scagliotti GV et al (2008) Lung adjuvant cisplatin evaluation: a pooled analysis by the lace collaborative group. J Clin Oncol 26(21):3552–3559. doi: 10.1200/JCO.2007.13.9030 CrossRefPubMedGoogle Scholar
  11. 11.
    Douillard J, Rosell R, De Lena M, Riggi M, Hurteloup P, Mahe M (2008) Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant navelbine international trialist association (ANITA) randomized trial. Int J Radiat Oncol Biol Phys 72(3):695–701. doi: 10.1016/j.ijrobp.2008.01.044 CrossRefPubMedGoogle Scholar
  12. 12.
    PORT Meta-analysis Trialists Group (2000) Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2:CD002142. [(2003) Review. Update Cochrane Database Syst Rev 1:CD002142] Google Scholar
  13. 13.
    PORT Meta-Analysis Trialists Group (2003) Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev.1:CD002142. [(2005) Review. Update Cochrane Database Syst Rev 2:CD002142] Google Scholar
  14. 14.
    PORT Meta-analysis Trialists Group (2005) Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2:CD002142 Review Google Scholar
  15. 15.
    Billiet C, Decaluwé H, Peeters S, Vansteenkiste J, Dooms C, Haustermans K et al (2014) Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. Radiother Oncol 110(1):3–8. doi: 10.1016/j.radonc.2013.08.011 CrossRefPubMedGoogle Scholar
  16. 16.
    Kepka L, Bujko K, Orlowski T, Jagiello R, Salata A, Matecka Nowak M et al (2011) Cardiopulmonary morbidity and quality of life in non-small cell lung cancer patients treated with or without postoperative radiotherapy. Radiother Oncol 98(2):238–243. doi: 10.1016/j.radonc.2010.09.020 CrossRefPubMedGoogle Scholar
  17. 17.
    Vansteenkiste JF, De Leyn PR, Deneffe GJ, Stalpaert G, Nackaerts KL, Lerut TE et al (1997) Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases leuven lung cancer group. Ann Thorac Surg 63(5):1441–1450. doi: 10.1016/S0003-4975(97)00314-7 CrossRefPubMedGoogle Scholar
  18. 18.
    Bucci JA, Kennedy CW, Burn J, Gillett DJ, Carmalt HL, Donnellan MJ et al (2001) Implications of extranodal spread in node positive breast cancer: a review of survival and local recurrence. Breast 10(3):213–219. doi: 10.1054/brst.2000.0233 CrossRefPubMedGoogle Scholar
  19. 19.
    Carter RL, Bliss JM, Soo KC, O’Brien CJ (1987) Radical neck dissections for squamous carcinomas: pathological findings and their clinical implications with particular reference to transcapsular spread. Int J Radiat Oncol Biol Phys 13(6):825–832. doi: 10.1016/0360-3016(87)90094-0 CrossRefPubMedGoogle Scholar
  20. 20.
    Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB (1993) Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer 71(2):452–456. doi: 10.1002/1097-0142(19930115)71:2<452:AID-CNCR2820710228>3.0.CO;2-B CrossRefPubMedGoogle Scholar
  21. 21.
    Brasilino de Carvalho M (1998) Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx. Head Neck 20(1):16–21. doi: 10.1002/(SICI)1097-0347(199801)20:1<16:AID-HED3>3.0.CO;2-6 CrossRefPubMedGoogle Scholar
  22. 22.
    Ahn T, Kim H, Jeong C, Kwak C, Ku J (2015) Extracapsular extension of pelvic lymph node metastasis is an independent prognostic factor in bladder cancer: a systematic review and meta-analysis. Ann Surg Oncol 22(11):3745–3750. doi: 10.1245/s10434-014-4359-1 CrossRefPubMedGoogle Scholar
  23. 23.
    Heide J, Krüll A, Berger J (2004) Extracapsular spread of nodal metastasis as a prognostic factor in rectal cancer. Int J Radiat Oncol Biol Phys 58(3):773–778. doi: 10.1016/S0360-3016(03)01616-X CrossRefPubMedGoogle Scholar
  24. 24.
    Chang Y, Chung K, Chen L (2015) Recursive partitioning analysis of lymph node ratio in breast cancer patients. Medicine (Baltimore) 94(1):e208. doi: 10.1097/MD.0000000000000208 CrossRefGoogle Scholar
  25. 25.
    Li Z, Ding Z, Luo Q, Wu C, Liao M, Zhen Y et al (2013) Prognostic significance of the extent of lymph node involvement in stage II-N1 non-small cell lung cancer. Chest 144(4):1253–1260. doi: 10.1378/chest.13-0073 CrossRefPubMedGoogle Scholar
  26. 26.
    Wisnivesky J, Arciniega J, Mhango G, Mandeli J, Halm E (2011) Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer. Thorax 66(4):287–293. doi: 10.1136/thx.2010.148601 CrossRefPubMedGoogle Scholar
  27. 27.
    Jonnalagadda S, Arcinega J, Smith C, Wisnivesky JP (2011) Validation of the lymph node ratio as a prognostic factor in patients with N1 nonsmall cell lung cancer. Cancer 117(20):4724–4731. doi: 10.1002/cncr.26093 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Turker I, Arslan U, Yazici O, Uyeturk U, Oksuzoglu B, Budakoglu B et al (2014) Prognostic factors in operated stage IIIC, pathological N3a breast cancer patients. Breast Care (Basel) 9(6):421–427. doi: 10.1159/000366438 CrossRefGoogle Scholar
  29. 29.
    Wang N, Jia Y, Wang J, Wang X, Bao C, Song Q et al (2015) Prognostic significance of lymph node ratio in esophageal cancer. Tumour Biol 36(4):2335–2341. doi: 10.1007/s13277-014-2840-x CrossRefPubMedGoogle Scholar
  30. 30.
    Zhan H, Xu J, Wang L, Zhang G, Hu S (2015) Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer. World J Surg Oncol 13:105. doi: 10.1186/s12957-015-0510-0 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kiriyama M, Ebata T, Aoba T, Kaneoka Y, Arai T, Shimizu Y et al (2015) Prognostic impact of lymph node metastasis in distal cholangiocarcinoma. Br J Surg 102(4):399–406. doi: 10.1002/bjs.9752 CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Medical Radiology 2016

Authors and Affiliations

  • Paolo Borghetti
    • 1
    Email author
  • Fernando Barbera
    • 1
  • Marco Lorenzo Bonù
    • 2
  • Francesca Trevisan
    • 2
  • Stefano Ciccarelli
    • 2
  • Paola Vitali
    • 1
  • Marta Maddalo
    • 1
  • Luca Triggiani
    • 2
  • Nadia Pasinetti
    • 1
  • Sara Pedretti
    • 2
  • Bartolomea Bonetti
    • 1
  • Gianluca Pariscenti
    • 3
  • Andrea Tironi
    • 4
  • Alberto Caprioli
    • 5
  • Michela Buglione
    • 2
  • Stefano Maria Magrini
    • 2
  1. 1.Department of Radiation OncologySpedali Civili of BresciaBresciaItaly
  2. 2.Department of Radiation OncologyBrescia UniversityBresciaItaly
  3. 3.Department of Thoracic SurgerySpedali Civili of BresciaBresciaItaly
  4. 4.Department of PathologySpedali Civili of BresciaBresciaItaly
  5. 5.Department of PneumologySpedali Civili of BresciaBresciaItaly

Personalised recommendations