What is the role of chemotherapy when added to radiotherapy in the treatment of inoperable stage II NSCLC?

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What is the role of chemotherapy when added to radiotherapy in the treatment of inoperable stage II NSCLC?

Introduction

Curative intent radiotherapy is a treatment option, however, there is scarce data available regarding the use of both chemotherapy and radiotherapy in the management of inoperable stage II NSCLC. Studies looking at concurrent and/or sequential chemotherapy and radiotherapy mainly include patients with stage III disease. Extrapolation of these data to stage II patients should be interpreted with caution.

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Radiation alone versus combination chemo-radiotherapy

In an individual patient meta-analysis of 1764 patients, comparing concomitant chemo-radiotherapy with radiation alone,[1] concomitant platin-based chemo-radiation was shown to improve survival for locally advanced NSCLC. Hazard ratio of death was 0.89(95%CI, 0.81-0.98; p=0.02). This corresponds to an absolute benefit of 4% at two years and 2.2% at five years. Toxicity data was not available in this analysis. However, the study mainly consisted of patients with stage III disease with stage II patients constituting only 2% of the total number of patients in each arm.

The Cochrane meta-analysis[2] showed that chemo-radiotherapy significantly reduced overall risk of death (HR 0.71, 95%CI 0.64 to 0.80; 1607 participants) and overall progression free survival at any site (HR 0.69, 95% CI 0.58 to 0.81; I2 45%; 1145 participants). Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemo-radiation. However the number of patients with stage II disease was small to make any definite conclusion for this group.

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Concurrent versus sequential therapy

In a meta-analysis of concomitant versus sequential radio-chemotherapy,[3] 1205 patients from six trials were included. With a median follow up of six years there was a significant benefit on overall survival for concomitant radio-chemotherapy (HR 0.84; 92%CI, 0.74-0.95; p=0.004). Concomitant therapy also improved loco-regional control (HR 0.77; 95% CI, 0.62-0.95; p=0.01).There was no effect on distant metastasis. Concomitant therapy was also associated with increased risk of acute Oesophagitis, however, there was no significant acute pulmonary toxicity. This analysis also mainly consisted of patients with stage III disease with very few patients (12) with stage II disease.

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Evidence summary and recommendations

Evidence summary Level References
There is insufficient evidence to support the use of chemotherapy along with radiation, given either concomitantly or sequentially, in the treatment of inoperable stage II disease.

Last reviewed August 2015

I [1], [3], [2]
Evidence-based recommendationQuestion mark transparent.png Grade
Insufficient evidence exists to recommend routine use of chemotherapy along with radiation for the treatment of patients with inoperable stage II NSCLC.

Last reviewed August 2015

C


Practice pointQuestion mark transparent.png

Patients with inoperable stage II disease could be offered radiotherapy with curative intent. Patients with good performance status and organ function may be considered for definitive concurrent chemo-radiation with a platin-based regime. This has to be balanced with an increased risk of toxicity. This is based on data extrapolated from studies mainly including inoperable stage III disease.
Last reviewed August 2015

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References

  1. 1.0 1.1 Aupérin A, Le Péchoux C, Pignon JP, Koning C, Jeremic B, Clamon G, et al. Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): a meta-analysis of individual data from 1764 patients. Ann Oncol 2006 Mar;17(3):473-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16500915.
  2. 2.0 2.1 O'Rourke N, Roqué I Figuls M, Farré Bernadó N, Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev 2010 Jun 16;(6):CD002140 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20556756.
  3. 3.0 3.1 Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010 May 1;28(13):2181-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20351327.

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Appendices

Further resources

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