What is the optimal treatment volume in patients with limited stage SCLC receiving thoracic radiotherapy?

From Cancer Guidelines Wiki

Introduction

The addition of thoracic radiotherapy to chemotherapy improves survival for fit patients with LS SCLC.[1][2] The optimal radiotherapy treatment volume has however not yet been definitively elucidated. This is because no completed randomised trials have directly compared the inclusion versus omission of elective nodal volumes, and just a single trial has compared the inclusion of pre- vs. post-chemotherapy volumes in radiotherapy portals.

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Radiotherapy to pre- versus post-chemotherapy volume

In a randomised trial from 1987 Kies et al. reported no differences in relapse patterns or survival between patients receiving radiotherapy to pre-induction vs. post-induction chemotherapy tumour volumes.[3] In that trial, patients achieving a complete response to chemotherapy still received radiotherapy to mediastinal and ipsilateral hilar nodes. A recent trial examining the inclusion of pre- versus post-chemotherapy tumour extent reported an interim analysis also showing no significant difference in local control or survival between the two groups.[4] Since this was an interim report, the planned statistical power had not yet been achieved however. The North Central Cancer Treatment Group (NCCTG) performed a randomised trial of hyperfractionated versus split-course radiotherapy.[5] Radiotherapy in that trial encompassed only the post-chemotherapy disease extent. Never the less local failure outside the radiotherapy portals occurred in fewer than 7% of patients.

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Elective nodal irradiation

It should be noted that most randomised trials in LS SCLC incorporated elective nodal irradiation in their treatment protocols. No randomised trials have directly compared elective vs. involved nodal radiotherapy. However, several studies including phase II and phase III trials have reported outcomes for patients where radiotherapy was limited to involved nodal volumes only.[4][6][7][8][9][10][11][12][13] With the exception of one study[8] which reported an isolated nodal failure rate of 11%, all studies reported nodal failure rates well below 10%. Since toxicity, particularly oesophagitis is a significant problem with concurrent chemo-radiotherapy for SCLC, limiting radiotherapy portals to include only involved nodal regions is attractive.

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Evidence summary and recommendations

Evidence summary Level References
Delivery of thoracic radiotherapy to the post-chemotherapy extent of disease does not adversely affect local recurrence or overall survival.

Last reviewed December 2015

II [3], [4]
No mature high level evidence exists, however, available data suggests that the rates of isolated nodal failure are low using an involved field approach.

Last reviewed December 2015

II, III-2, IV [4], [7], [8], [9], [10], [11], [12], [13], [6]
Evidence-based recommendationQuestion mark transparent.png Grade
Where radiotherapy is delivered after chemotherapy has begun, radiotherapy target volumes should be based on the post-chemotherapy volume of disease. Radiotherapy should be delivered to all originally involved nodal regions irrespective of their response to chemotherapy.

Last reviewed December 2015

B
Evidence-based recommendationQuestion mark transparent.png Grade
Elective nodal irradiation may be omitted to reduce toxicity.

Last reviewed December 2015

C


Practice pointQuestion mark transparent.png

In the setting of SCLC, positron emission tomography (PET) appears useful both for staging as well as for the definition of radiotherapy volumes. Where available, information from PET scans should be incorporated into radiotherapy target definition.
Last reviewed December 2015

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References

  1. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992 Dec 3;327(23):1618-24 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1331787.
  2. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 1992 Jun;10(6):890-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1316951.
  3. 3.0 3.1 Kies MS, Mira JG, Crowley JJ, Chen TT, Pazdur R, Grozea PN, et al. Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study. J Clin Oncol 1987 Apr;5(4):592-600 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3031226.
  4. 4.0 4.1 4.2 4.3 Hu X, Bao Y, Zhang L, Guo Y, Chen YY, Li KX, et al. Omitting elective nodal irradiation and irradiating postinduction versus preinduction chemotherapy tumor extent for limited-stage small cell lung cancer: Interim analysis of a prospective randomized noninferiority trial. Cancer 2011 May 19 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21598237.
  5. Bonner JA, Sloan JA, Shanahan TG, Brooks BJ, Marks RS, Krook JE, et al. Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small-cell lung carcinoma. J Clin Oncol 1999 Sep;17(9):2681-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10561342.
  6. 6.0 6.1 Xia B, Chen GY, Cai XW, Zhao JD, Yang HJ, Fan M, et al. Is involved-field radiotherapy based on CT safe for patients with limited-stage small-cell lung cancer? Radiother Oncol 2011 Nov 4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22056536.
  7. 7.0 7.1 van Loon J, De Ruysscher D, Wanders R, Boersma L, Simons J, Oellers M, et al. Selective nodal irradiation on basis of (18)FDG-PET scans in limited-disease small-cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys 2010 Jun 1;77(2):329-36 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19782478.
  8. 8.0 8.1 8.2 De Ruysscher D, Bremer RH, Koppe F, Wanders S, van Haren E, Hochstenbag M, et al. Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial. Radiother Oncol 2006 Sep;80(3):307-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16949169.
  9. 9.0 9.1 Baas P, Belderbos JS, Senan S, Kwa HB, van Bochove A, van Tinteren H, et al. Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study. Br J Cancer 2006 Mar 13;94(5):625-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16465191.
  10. 10.0 10.1 Belderbos J, Baas P, Senan S. Reply: Patterns of nodal recurrence after omission of elective nodal irradiation for limited-stage small-cell lung cancer. BJC 2007;July 16; 97(2): 276. Abstract available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360309/.
  11. 11.0 11.1 Shirvani SM, Komaki R, Heymach JV, Fossella FV, Chang JY. Positron Emission Tomography/Computed Tomography-Guided Intensity-Modulated Radiotherapy for Limited-Stage Small-Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2011 Apr 12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21489716.
  12. 12.0 12.1 Colaco R, Sheikh H, Lorigan P, Blackhall F, Hulse P, Califano R, et al. Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer - Evidence from a phase II trial. Lung Cancer 2011 Oct 17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22014897.
  13. 13.0 13.1 Watkins JM, Wahlquist AE, Zauls AJ, Shirai K, Garrett-Mayer E, Aguero EG, et al. Involved-field radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer: disease control, patterns of failure and survival. J Med Imaging Radiat Oncol 2010 Oct;54(5):483-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20958948.

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Appendices

Further resources

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