Is there a role for thoracic radiotherapy in patients with extensive stage SCLC?

From Cancer Guidelines Wiki

Three trials employing modern radiotherapy techniques and platinum containing chemotherapy have investigated thoracic radiotherapy as part of the initial management of extensive stage small cell lung cancer patients.[1][2][3]

An international collaborative randomized control trial of 498 patients confirmed a survival benefit at 2 years from the addition of consolidative thoracic radiotherapy in patients attaining response to initial chemotherapy.[3] Patients were randomised to 30Gy in 10 fractions preferably commencing within 6 weeks of chemotherapy cessation and usually about 1 week after PCI, or to no further treatment. As might be expected, given that many patients had metastatic ED SCLC, the primary endpoint of overall survival at 1 year was not met; but planned secondary analyses of overall survival at 2 years (13% vs 3%), intra-thoracic control and progression free survival were all significantly improved with radiotherapy. This was achieved without any significant increase in toxicity. Patients in whom chemotherapy had induced a complete response in the chest appeared not to benefit from thoracic radiotherapy.[4]

Jeremic et al. performed a single institution randomised trial of concurrent chemo-radiotherapy versus chemotherapy alone in 206 patients who had achieved a CR in their extra-thoracic disease after three chemotherapy cycles and at least a PR in their chest.[1] The addition of thoracic radiotherapy (54Gy in 36 BD fractions) resulted in a statistically significant survival advantage. Apart from radiotherapy-related oesophagitis in 27% of patients, no further significant radiotherapy toxicities were observed.

A metanalysis of the two randomised trials above confirmed a statistically significant survival advantage to thoracic RT in ED SCLC (random-effects model HR, 0.81; 95% CI, 0.69-0.95; P = .01).[5] While there were no differences in bronchopulmonary toxicity between irradiated and non-irradiated groups, grade 3 oesophageal toxicity was significantly higher in the irradiated group (6.6% vs 0%). However, this was almost exclusively found in patients receiving 54Gy in the Jeremic et al trial[1] as opposed to those who received 30Gy in the trial by Slotman et al[3] (27% vs 2%).

Yee at al.[2] performed a prospective single arm trial of consolidative thoracic radiotherapy in patients achieving an objective response to chemotherapy. In this small trial, maximal toxicity was grade 2 oesophagitis in 56% of patients. Similar to the trial of Jeremic et al. no further radiotherapy related toxicities were observed.

The role of thoracic radiotherapy in extensive stage small cell lung cancer is currently also being addressed through the RTOG 0937 trial.

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Evidence summary and recommendations

Evidence summary Level References
In ED SCLC patients responding to initial chemotherapy, moderate dose thoracic radiotherapy to 30Gy in 10 fractions improves overall survival at time points greater than 18 months with no severe acute or late toxic effects.

Last reviewed December 2015

II [3], [1]
Evidence-based recommendationQuestion mark transparent.png Grade
Strongly consider administering moderate dose consolidative chest radiotherapy (30 Gy in 10 fractions) to chemotherapy responders, especially those with residual disease in the thorax.

Last reviewed December 2015

B


Practice pointQuestion mark transparent.png

Chest radiotherapy was administered 6-7 weeks after chemotherapy and usually 1 week after completion of prophylactic cranial irradiation.

Those patients with the heaviest extrathoracic metastatic burden and poor response to chemotherapy may be expected to benefit the least from thoracic radiotherapy. In addition, patients with no residual disease in the thorax after chemotherapy derived no benefit from consolidative thoracic radiotherapy in a post hoc analysis by Slotman et al.
Last reviewed December 2015

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References

  1. 1.0 1.1 1.2 1.3 Jeremic B, Shibamoto Y, Nikolic N, Milicic B, Milisavljevic S, Dagovic A, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: A randomized study. J Clin Oncol 1999 Jul;17(7):2092-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10561263.
  2. 2.0 2.1 Yee D, Butts C, Reiman A, Joy A, Smylie M, Fenton D, et al. Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer. Radiother Oncol 2011 Sep 17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21930323.
  3. 3.0 3.1 3.2 3.3 Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet 2014 Sep Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25230595.
  4. Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, et al. Radiotherapy for extensive stage small-cell lung cancer - Authors' reply. Lancet 2015 Apr 4;385(9975):1292-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25890910.
  5. Palma DA, Warner A, Louie AV, Senan S, Slotman B, Rodrigues GB. Thoracic Radiotherapy for Extensive Stage Small-Cell Lung Cancer: A Meta-Analysis. Clin Lung Cancer 2015 Oct 1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26498503.

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Appendices

Further resources

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