Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

Inclusion Criteria:

• Lung cancer or 1-2 oligometastatic pulmonary lesions planned for radical intentradiotherapy [minimal Biologically Effective Does (BED) of 48 Gy10 (Gray) orbiological equivalent].

• Pathologically (histologically or cytologically) proven diagnosis of cancer is notrequired, but strongly recommended.

• If the risk of biopsy is unacceptable, pathologic confirmation is not requiredproviding there is growth over time on Computed Tomography (CT) imaging and/orFluorodeoxyglucose (FDG) avidity that is strongly suggestive of malignancy.

• Fibrotic Interstitial Lung Disease (ILD) of any subtype, as diagnosed by arespirologist 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 ofIdiopathic Pulmonary Fibrosis (IPF) or non-IPF fibrotic ILD (e.g. nintedanib,pirfenidone) and/or corticosteroids, if those are part of their current ILDtreatment 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 systemictherapies, including biologic targeted agents or immunotherapy, or any drugs withknown radiosensitive effects, must be stopped for 2 weeks prior and 2 weeks aftertreatment.

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) whileon this study, except at disease progression

• Any medical condition that could, in the opinion of the investigator, precluderadiotherapy or prevent follow-up after radiotherapy

• Pregnancy

• If not pregnant, use of effective contraception methods for women ofchildbearing 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 andinform their study doctor.

• Male participants should use adequate forms of birth control with theirpartners.

• 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 acontraindication to dexamethasone or NAC