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Virchows Archiv

, Volume 462, Issue 5, pp 547–556 | Cite as

Complete pathological response is predictive for clinical outcome after tri-modality therapy for carcinomas of the superior pulmonary sulcus

  • Johannes L. BlaauwgeersEmail author
  • Ingrid Kappers
  • Houke M. Klomp
  • José S. Belderbos
  • Lea M. Dijksman
  • Egbert F. Smit
  • Pieter E. Postmus
  • Marinus A. Paul
  • Jan W. Oosterhuis
  • Koen J. Hartemink
  • Cornelis G. Vos
  • Jacobus A. Burgers
  • Max Dahele
  • Erik C. Phernambucq
  • Birgit I. Witte
  • Erik Thunnissen
Original Article

Abstract

The objective was to define the relationship between histopathological changes after pre-operative chemo-radiotherapy (CRT) and clinical outcome following tri-modality therapy in patients with superior sulcus tumours. A retrospective analysis of tumour material was performed in a series of 46 patients who received tri-modality therapy between 1997 and 2007. Median follow-up was 34 months (5–154). Pathological complete response (pCR) was present in 20/46 tumours (43 %). The most common RECIST score after CRT in patients with pCR was a partial response (PR; 10/17, three unknown), whereas in patients without a pCR, stable disease was the most common (22/26) (p = 0.002). In 26 specimens with residual tumour, this was mainly located in the periphery of the lesion rather than the centre (Spearman’s correlation = 0.67, p < 0.001). Prognosis was significantly better after a pCR compared to residual tumour (70 % 5-year overall survival vs. 20 %; p = 0.001) and in patients with fewer than 10 % vital tumour cells as compared to those with >10 % (65 % 5-year overall survival vs. 18 %; p < 0.001). A low mitotic count was associated with a longer disease-free survival (p = 0.02). Complete pathological response and the presence of fewer than 10 % vital tumour cells after pre-operative CRT are both associated with a more favourable prognosis. A modification of the pathological staging system after radiotherapy, incorporating the percentage of vital tumour cells, is proposed.

Keywords

Pancoast Lung cancer Chemoradiation Histopathology Prognosis 

Notes

Conflict of interest

None of the authors has any conflict of interest regarding the research discussed.

References

  1. 1.
    Chansky K, Sculier J-P, Crowley JJ, Giroux D, van Meerbeeck J, Goldstraw P (2009) The International Association for the Study of Lung Cancer staging project. Prognostic factors and pathologic TNM stage in surgically managed non small cell lung cancer. J Thor Oncol 4:729–801CrossRefGoogle Scholar
  2. 2.
    Takeda S, Maeda H, Okada T, Yamaguchi T, Nakagawa M, Yokota S, Sawabata N, Ohta M (2006) Results of pulmonary resection following neoadjuvant therapy for locally advanced (IIIA–IIIB) lung cancer. Eur J Cardiothorac Surg 30:184–189PubMedCrossRefGoogle Scholar
  3. 3.
    Caglar HB, Baldini EH, Othus M, Rabin MS, Bueno R, Sugarbaker DJ, Mentzer SJ, Jänne PA, Johnson BE, Allen AM (2009) Outcomes of patients with stage III non small cell lung cancer treated with chemotherapy and radiation with and without surgery. Cancer 115:4156–4166PubMedCrossRefGoogle Scholar
  4. 4.
    Kappers I, van Sandick JW, Burgers JA, Belderbos JS, Wouters MW, van Zandwijk N, Klomp HM (2009) Results of combined modality treatment in patients with non-small-cell lung cancer of the superior sulcus and the rationale for surgical resection. Eur J Cardiothorac Surg 36:741–746PubMedCrossRefGoogle Scholar
  5. 5.
    Peedell C, Dunning J, Bapusamy A (2010) Is there a standard of care for the radical management of non-small cell lung cancer involving the apical chest wall (Pancoast tumours)? Clin Oncol 22:334–346CrossRefGoogle Scholar
  6. 6.
    Pourel N, Santelmo N, Naafa N, Serre A, Hilgers W, Mineur L, Molinari N, Reboul F (2008) Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response. Eur J Cardiothorac Surg 33:829–836PubMedCrossRefGoogle Scholar
  7. 7.
    Rusch VW, Giroux DJ, Kraut MJ, Crowley J, Hazuka M, Winton T, Johnson DH, Shulman L, Shepherd F, Deschamps C, Livingston RB, Gandara D (2007) Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol 25:313–318PubMedCrossRefGoogle Scholar
  8. 8.
    Junker K, Thomas M, Schulmann K, Klinke F, Bosse U, Müller KM (1997) Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment. J Cancer Res Clin Oncol 123:469–477PubMedCrossRefGoogle Scholar
  9. 9.
    Liu-Jarin X, Stoopler MB, Raftopoulos H, Ginsburg M, Gorenstein L, Borczuk AC (2003) Histologic assessment of non-small cell lung carcinoma after neoadjuvant therapy. Mod Pathol 16:1102–1108PubMedCrossRefGoogle Scholar
  10. 10.
    Yamane Y, Ishii G, Goto K, Kojima M, Nakao M, Shimada Y, Nishiwaki Y, Nagai K, Kohrogi H, Ochiai A (2010) A novel histopathological evaluation method predicting the outcome of non-small cell lung cancer treated by neoadjuvant therapy. The prognostic importance of the area of residual tumor. J Thor Oncol 5:49–55CrossRefGoogle Scholar
  11. 11.
    Detterbeck FC (2003) Changes in the treatment of Pancoast tumors. Ann Thorac Surg 75:1990–1997PubMedCrossRefGoogle Scholar
  12. 12.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRefGoogle Scholar
  13. 13.
    Curtin F, Schulz P (1998) Multiple correlations and Bonferroni’s correction. Biol Psychiatry 44:775–777PubMedCrossRefGoogle Scholar
  14. 14.
    Thunnissen FB, Schuurbiers OC, den Bakker MA (2006) A critical appraisal of prognostic and predictive factors for common lung cancers. Histopathology 48(7):779–786PubMedCrossRefGoogle Scholar
  15. 15.
    Fischer S, Darling G, Pierre AF, Sun A, Leighl N, Waddell TK, Keshavjee S, de Perrot M (2008) Induction chemoradiation therapy followed by surgical resection for non-small cell lung cancer (NSCLC) invading the thoracic inlet. Eur J Cardiothorac Surg 33:1129–1134PubMedCrossRefGoogle Scholar
  16. 16.
    Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23PubMedCrossRefGoogle Scholar
  17. 17.
    Bollschweiler E, Metzger R, Drebber U, Baldus S, Vallböhmer D, Kocher M, Hölscher AH (2009) Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis. Ann Oncol 20:231–238PubMedCrossRefGoogle Scholar
  18. 18.
    Harrison L, Blackwell K (2004) Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy? Oncologist 9(Suppl 5):31–40PubMedCrossRefGoogle Scholar
  19. 19.
    Brown JM (2002) Tumor microenvironment and the response to anticancer therapy. Cancer Biol Ther 1:453–458PubMedGoogle Scholar
  20. 20.
    Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y (2001) The new World Health Organization classification of lung tumours. Eur Respir J 18:1059–1068PubMedCrossRefGoogle Scholar
  21. 21.
    Rami-Porta R, Crowley JJ, Goldstraw P (2009) The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 15:4–9PubMedGoogle Scholar
  22. 22.
    Goldstraw P (2009) The IASLC staging manual in thoracic oncology. Editorial Rx, Orange Park, pp 37–38Google Scholar
  23. 23.
    Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, Böttcher K, Siewert JR, Höfler H (2003) Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 98(7):1521–1530PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Johannes L. Blaauwgeers
    • 1
    Email author
  • Ingrid Kappers
    • 2
  • Houke M. Klomp
    • 2
  • José S. Belderbos
    • 3
  • Lea M. Dijksman
    • 4
  • Egbert F. Smit
    • 5
  • Pieter E. Postmus
    • 5
  • Marinus A. Paul
    • 6
  • Jan W. Oosterhuis
    • 6
  • Koen J. Hartemink
    • 6
  • Cornelis G. Vos
    • 6
  • Jacobus A. Burgers
    • 7
  • Max Dahele
    • 8
  • Erik C. Phernambucq
    • 8
  • Birgit I. Witte
    • 9
  • Erik Thunnissen
    • 10
  1. 1.Department of PathologyOnze Lieve Vrouwe GasthuisAmsterdamThe Netherlands
  2. 2.Department of SurgeryNetherlands Cancer Institute (NKI-AVL)AmsterdamThe Netherlands
  3. 3.Department of RadiotherapyNetherlands Cancer Institute (NKI-AVL)AmsterdamThe Netherlands
  4. 4.Department of Teaching HospitalOnze Lieve Vrouwe GasthuisAmsterdamThe Netherlands
  5. 5.Department of PulmonologyVU University Medical Center (VUmc)AmsterdamThe Netherlands
  6. 6.Department of SurgeryVU University Medical Center (VUmc)AmsterdamThe Netherlands
  7. 7.Department of PulmonologyNetherlands Cancer Institute (NKI-AVL)AmsterdamThe Netherlands
  8. 8.Department of Radiation OncologyVU University Medical Center (VUmc)AmsterdamThe Netherlands
  9. 9.Department of Epidemiology and BiostatisticsVU University Medical Center (VUmc)AmsterdamThe Netherlands
  10. 10.Department of PathologyVU University Medical Center (VUmc)AmsterdamThe Netherlands

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