Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

In this double-blind phase II randomized controlled trial, patients with lung cancer or ≤2 oligometastatic pulmonary lesions and a concomitant diagnosis of ILD who are planned for radical Radiation Therapy (RT) will be randomized using a 2 x 2 factorial design to oral N-acetylcysteine (NAC) versus placebo, and also to short course corticosteroids versus placebo.

Inclusion Criteria: * Lung cancer or 1-2 oligometastatic pulmonary lesions planned for radical intent radiotherapy \[minimal Biologically Effective Does (BED) of 48 Gy10 (Gray) or biological equivalent\]. * Pathologically (histologically or cytologically) proven diagnosis of cancer is not required, but strongly recommended. * If the risk of biopsy is unacceptable, pathologic confirmation is not required providing there is growth over time on Computed Tomography (CT) imaging and/or Fluorodeoxyglucose (FDG) avidity that is strongly suggestive of malignancy. * Fibrotic Interstitial Lung Disease (ILD) of any subtype, as diagnosed by a respirologist and confirmed by central review * Eastern Cooperative Oncology Group (ECOG) performance status 0-3 * Age ≥ 18 * Life expectancy \> 6 months * Patients are allowed to receive anti-fibrotic agents used in the treatment of Idiopathic Pulmonary Fibrosis (IPF) or non-IPF fibrotic ILD (e.g. nintedanib, pirfenidone) and/or corticosteroids, if those are part of their current ILD treatment regimen. Other immunosuppressive drugs such as mycophenolate, azathioprine, cyclophosphamide, and rituximab must be stopped for 2 weeks prior and 2 weeks after Radiation Therapy (RT). * Concurrent standard chemotherapy is allowed where indicated. All other systemic therapies, including biologic targeted agents or immunotherapy, or any drugs with known radiosensitive effects, must be stopped for 2 weeks prior and 2 weeks after treatment. Exclusion Criteria: * Prior lung radiotherapy * Current use of oral or intravenous corticosteroids * Plans for the patient to receive other local therapy to the target lesion(s) while on this study, except at disease progression * Any medical condition that could, in the opinion of the investigator, preclude radiotherapy or prevent follow-up after radiotherapy * Pregnancy * If not pregnant, use of effective contraception methods for women of childbearing age is required which can include: * hormonal methods (e.g. oral, injected, implanted), * placement of an intrauterine device, * barrier methods (i.e. condoms), * sterilization of the partner (e.g. previous vasectomy) * abstinence * Women who become pregnant should stop taking NAC and/or dexamethasone and inform their study doctor. * Male participants should use adequate forms of birth control with their partners. * Currently breastfeeding * Current or recent use of NAC * Contraindications to dexamethasone or N-Acetyl Cysteine (NAC). These include: * Previous intolerance or allergy to dexamethasone or NAC * Scleroderma * Active infection * Glaucoma * Psychiatric disorder that could be exacerbated by dexamethasone * Cystinuria * Any other condition that the treating physician believes to be a contraindication to dexamethasone or NAC