IntroductionDefinitive radiation therapy is considered standard therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). However, for patients with tumors located near to structures like the proximal tracheobronchial tree, esophagus, heart, spinal cord, and brachial plexus, the optimal management regimen is controversial. The objective was to develop expert multidisciplinary consensus guidelines on the management of medically inoperable NSCLC located in a central or ultra-central location relative to critical organs-at-risk. Materials and MethodsCase variants regarding centrally and ultra-centrally located lung tumors were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel. A comprehensive review of the English medical literature was performed from 1/1/46 to 12/31/23 to inform consensus guidelines. Modified Delphi methodology was used by the panel to evaluate the variants and procedures, with ≤3 rating points from median defining agreement/consensus. The guideline was then approved by the ARS Executive Committee and released for public comment per established ARS procedures. ResultsThe Thoracic ARS AUC Panel identified 90 relevant references and obtained consensus in all variants. Radiotherapy alone was considered appropriate, with additional immunotherapy to be considered primarily in the clinical trial setting. Hypofractionated radiotherapy in 8-18 fractions was considered appropriate for ultra-central lesions near proximal tracheobronchial tree, upper trachea, and esophagus. For other ultra-central lesions near heart, great vessels, brachial plexus, and spine, or for non-ultra-central but still central lesions, 5-fraction SBRT was also considered an appropriate option. Intensity-modulated radiotherapy was considered appropriate and 3D-conformal radiotherapy inappropriate for all variants. Other treatment planning techniques to decrease the risk of overdosing critical organs-at-risk were also considered. DiscussionThe ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of stage I NSCLC in a central or ultra-central location.