Reirradiation Dose Escalation in Thoracic Cancers

Prior treatment

• Persistent toxicity from previously delivered radiation therapy
• Prior development of symptomatic radiation pneumonitis or immunotherapy-related pneumonitis from previous treatment, even if resolved
• Cumulative radiation dose for all organs-at-risk is already below dose constraints without a recovery factor applied, or with a recovery factor less than the current dose level of the trial. This will be confirmed by the enrolling team after the planning is completed.
• Any prior thoracic radiotherapy \< 6 months ago; OR prior thoracic radiotherapy delivered twice daily (compensation for holiday breaks are OK), thoracic radiotherapy delivered by brachytherapy, radionuclides, proton beams, or electron beams.
• Plans for patient to receive daily adaptive radiotherapy in current plan (computed tomography or magnetic resonance based).
• Concurrent systemic therapy (i.e. on the same days as radiation) is not allowed, EXCEPT for patients being treated for intrathoracic lung cancer (NSCLC or SCLC) with curative intent.
• For other patients receiving systemic therapy, they are still eligible for enrollment as long as there is a break in systemic therapy during the course of radiation. For example, if a patient has been on palliative pemetrexed and is planning to continue, they can still be enrolled and would continue to receive pemetrexed; reirradiation would be delivered between cycles, possibly requiring a break in systemic therapy. See Section 6.9 for further details.
• Prior surgical intervention that has significantly changed the position of an organ-at-risk that is expected to be a dose-limiting structure.

Other illness

• Plans for the patient to receive other local therapy (including standard fractionated radiotherapy and/or surgery) while on this study, except at disease progression.
• The following autoimmune and connective tissue diseases will be excluded: Scleroderma and Systemic lupus erythematosus.
• Patients with interstitial lung disease (ILD).

Other

• The reirradiation dose-limiting structure is expected to be spinal cord, chest wall, and/or stomach.
• Pregnancy

• Pathologically (histologically or cytologically) proven diagnosis of malignancy, with disease in the thorax requiring re-irradiation for any treatment intent. This may include primary lung cancer of any type, esophageal cancer, recurrences, and/or metastasis from any primary. The intrathoracic disease at the time of enrollment does not itself require a biopsy if a prior biopsy has been obtained at that location or another body site. If the risk of biopsy is unacceptable and there is no prior confirmation of malignancy even at the time of the initial course of radiation, enrollment is permitted provided that the case is discussed at a multidisciplinary tumor board or peer-review rounds.
• Must have received prior photon thoracic radiotherapy ≥ 6 months ago
• Life expectancy \> 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age ≥ 18 years
• The current radiation course, when added to the previous radiation doses, exceeds the normal tissue constraints used for de novo treatments for esophagus, heart, lungs, trachea, bronchus, great vessels, or brachial plexus. Forgiveness of the previous dose (i.e. reduction of the previous dose in the cumulative dose calculation) is required to meet constraints. Submission of a pre-plan summary showing the estimated accumulation of current and previously delivered doses is required for registration.