PRophylactic Cerebral Irradiation or Active MAgnetic Resonance Imaging Surveillance in Small-cell Lung Cancer Patients (PRIMALung Study)

Inclusion Criteria:

• Age ≥ 18 years
• Histologically/cytologically proven diagnosis of SCLC
• Limited and extensive stage
• LS SCLC: Stage I-III (T any, N any, M0, according to UICC TNM staging v8.0) that canbe safely treated with definitive radiation doses. Excludes T3-4 due to multiple lungnodules that are too extensive or have tumour/nodal volume that is too large to beencompassed in a tolerable radiation plan.
• ES SCLC: Stage IV (T any, N any, M 1a/b), or T3-4 due to multiple lung nodules thatare too extensive or have tumour/nodal volume that is too large to be encompassed in atolerable radiation plan.
• Completed standard therapy prior to randomization:
• For patients with LS-SCLC, this includes a combination of 4-6 cycles of platinum-baseddoublet chemotherapy and either definitive thoracic radiotherapy (including SBRT forearly-stage T1-2 N0 M0 disease who do not undergo surgery) or definitive surgicalresection; thoracic radiation in addition to definitive surgical resection is allowedat the discretion of the treating physician, but is not mandated.
• For patients with ES-SCLC, this includes 4-6 cycles of platinum-based doubletchemotherapy either with or without thoracic radiotherapy o Immunotherapy concurrent with and/or adjuvant to standard therapy is allowed at thediscretion of the treating physician.
• Absence of progressive disease after completed standard therapy on systemic imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of Chest/Abdomen/Pelvisand brain MRI), 28 days before randomization.
• Absence of brain metastases or leptomeningeal disease after completed standard therapyon systemic imaging (computed tomography (CT) or magnetic resonance imaging (MRI) ofChest/Abdomen/Pelvis and brain MRI), within 28 days before randomization.
• Interval from day 1 of last cycle of chemotherapy to randomization of ≤8 weeks
• ECOG PS ≤ 2
• Estimated creatinine clearance ≥ 30 mL/min as calculated using the MDRD formula
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy testwithin 3 days prior to randomization. Note: women of childbearing potential are defined as premenopausal females capable ofbecoming pregnant (i.e. females who have had any evidence of menses in the past 12 months,with the exception of those who had prior hysterectomy). However, women who have beenamenorrheic for 12 or more months are still considered to be of childbearing potential ifthe amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight,ovarian suppression or other reasons.
• Patients Women of childbearing / reproductive potential should use adequate birthcontrol measures, as defined by the investigator, during the entire period of theradiotherapy treatment study participation and for at least 30 days after the lastdose of radiotherapy. A highly effective method of birth control is defined as amethod which results in a low failure rate (i.e. less than 1% per year) when usedconsistently and correctly. Such methods include:
• Combined (oestrogen and progestogen containing) hormonal contraception associated withinhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral,injectable, implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence (the reliability of sexual abstinence needs to be evaluated inrelation to the duration of the clinical trial and the preferred and usual lifestyleof the patient)
• Female subjects who are breast feeding should discontinue nursing prior to the firstdose of radiotherapy and during the entire period of the radiotherapy treatmentuntil 30 days after the administration of the last dose of radiotherapy.
• Patient is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations including followup
• Before patient registration/randomization, written informed consent must be givenaccording to ICH/GCP, and national/local regulations.

Exclusion Criteria:

• Prior radiotherapy to the brain or whole brain radiotherapy. Note: Patients who haveundergone prior stereotactic radiosurgery for benign tumours or conditions (e.g.,acoustic neuroma, grade I meningioma, trigeminal neuralgia) may be considered on acase-by-case basis. Discussion with EORTC Headquarters is mandatory, before therandomization.
• Known contraindication to imaging tracer or any product of contrast media, such asallergy or insufficient renal function. Known contraindication to MRI, such asimplanted metal devices or foreign bodies.
• Other active hematologic or solid tumour malignancy requiring current activetreatment.
• Any unresolved toxicities from prior therapy (e.g., chemotherapy, radiotherapy)greater than CTCAE grade 2 (according to CTCAE v5.0) at the time of randomization.
• Patient with severe active comorbidities, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within 6months prior to randomization
• Transmural myocardial infarction within 6 months prior to randomization
• Acute infection requiring treatment at the time of randomization
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory illnessprecluding study therapy at the time of randomization
• Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepaticdisease
• HIV positive with CD4 count < 200 cells/microliter. Note: patients who are HIVpositive are eligible, provided they are under treatment with highly activeantiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 16weeks prior to randomization.
• Any severe comorbidity that in the opinion of the Investigator might hamper theparticipation to the study and/or the treatment administration.
• Severe neurological (including dementia and epilepsy) or psychiatric disorderrequiring active treatment.
• Any psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule; those conditionsshould be discussed with the patient before randomization in the trial