Palliative Thoracic Radiation Therapy for Non-Small Cell Lung Cancer: An Update of an ASTRO Evidence-Based Guideline Endorsed by the European Society for Radiotherapy & Oncology and the Royal Australian and New Zealand College of Radiologists

Citation This slide set is adapted from the Palliative Thoracic Radiation Therapy for Non-Small Cell Lung Cancer Guideline Update. Published in the July-August 2018 issue of Practical Radiation Oncology (PRO): https://www.practicalradonc.org/article/S1879- 8500(18)30069-9/pdf The full-text guideline is also available on the ASTRO website: www.astro.org

Guideline Task Force Chair Members Benjamin Moeller, MD, PhD Ehsan Balagamwala, MD Aileen Chen, MD Giuseppe Giaccone, MD, PhD Matthew Koshy, MD Kimberly Creach, MD Sandra Zaky, MD, MS George Rodrigues, MD, PhD

Introduction to Guideline Original palliative thoracic guideline was published in 2011. In February 2016, the Guidelines Subcommittee formed a work group to evaluate the guideline for updating. Based on new evidence published since the original guideline, the work group recommended 1 key question be updated: Key Question: What is the role of chemotherapy administered concurrently with radiation for the palliation of lung cancer? The proposed update was approved by the ASTRO Board of Directors in July 2016. The final draft was approved by the Board and published July/August 2018.

Systematic Review MEDLINE® PubMed - 03/01/2010 (last date in original guideline) – 07/27/2016 Both MeSH terms and text words used Outcomes: OS, local and regional control, distant failure, acute and late toxicity, quality of life Inclusion: age ≥18 years locally-advanced or metastatic lung cancer treatment with RT with palliative intent Exclusion: curative intent, pediatric, non-English, non-human, case report, abstract only, no clinical outcomes reported, not relevant to KQs 113 abstracts retrieved  31 articles included and abstracted into evidence tables

Grading Evidence + Recommendations Strength of Recommendation Definition* Quality of Evidence Recommendation Wording Strong Benefits clearly outweigh risks and burden, or risks and burden clearly outweigh benefits. All or almost all informed people would make the recommended choice for or against an intervention. Any (usually high or moderate) “Recommend” “Should” Etc. Conditional Benefits are finely balanced with risks and burden or appreciable uncertainty exists about the magnitude of benefits and risks. Most informed people would choose the recommended course of action, but a substantial number would not. There is a strong role for patient preferences & shared-decision making. Any (usually moderate to low) “Suggest” “Might” “May” Quality of evidence: High: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.^ * Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol. 2013;66(7):719-725. ^ Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-406.

Consensus Methodology Modified Delphi approach Task force members rated their agreement with each recommendation using an online consensus survey Five-point Likert scale from “strongly disagree” to “strongly agree” Consensus defined using pre-specified threshold of ≥75% agreement Recommendations for which consensus was not achieved were removed or were revised and re-surveyed. Recommendations that achieved consensus but were edited for other reasons were also re-surveyed.

Recommendation strength KQ: What is the role of chemotherapy administered concurrently with radiation for the palliation of lung cancer? Incurable stage III NSCLC Statement A: In the management of patients with stage III NSCLC deemed unsuitable for curative therapy but who are (1) candidates for chemotherapy, (2) have an ECOG PS of 0-2, and (3) have a life expectancy of at least 3 months, administration of a platinum-containing chemotherapy doublet concurrently with moderately hypofractionated palliative thoracic radiation therapy is recommended over treatment with either modality alone. Recommendation strength Strong Moderate Quality of evidence 100% Consensus

Recommendation strength KQ: What is the role of chemotherapy administered concurrently with radiation for the palliation of lung cancer? Stage IV NSCLC Statement B: In the palliative management of patients with stage IV NSCLC, routine use of concurrent thoracic chemoradiation is not recommended. This practice should remain primarily reserved for clinical trials or multi-institutional registries. Recommendation strength Strong Low Quality of evidence 100% Consensus