Watchful Observation of Patients With LD-SCLC Instead of the PCI
Watchful Observation of Patients With LD-SCLC Instead of the PCI
Prophylactic cranial irradiation (PCI) is a current standard of care after confirmed response
 to radical chemoradiotherapy for limited disease small cell lung cancer (LD-SCLC). This
 standard is mostly based on results of old randomized studies when brain imaging with
 magnetic resonance (MRI) was not available. Survival benefit of PCI in extended SCLC was
 recently challenged by results of randomized phase III study from Japan. We propose to
 carefully follow LD-SCLC patients with MRI instead of PCI in order to apply modern brain
 irradiation [stereotactic radiotherapy (SRT) in eligible patients or whole brain radiation
 therapy (WBRT)] to patients who develop metastases and to eliminate long terms neurocognitive
 deficits caused by PCI in patients who would never develop brain metastases.

 Methods and analysis This is a prospective multi-centre one-arm trial. A total of 80 patients
 diagnosed with LD-SCLC after confirmed response to standard of care radical chemoradiotherapy
 will be enrolled. Patients will be followed-up by brain MRI every 3 months up to 3 years.
 Neurocognitive function tests will be performed at baseline and after 12 and 24 months.
 Patients who develop brain metastases during observation will be irradiated. In case of
 limited number and volume of metastases SRT will be offered to patients; others will be
 treated with WBRT. The primary endpoint of the trial is overall survival. We have assumed
 that our approach will not compromise overall survival of treated patients. 2-year survival
 will be at least 50% in our trial compared to 36% for a group of 138 patients LD-SCLC from
 our institution treated in 2003-2006 with radical chemoradiotherapy and PCI. The secondary
 endpoints were designed to asses the risk of developing brain metastases without PCI; to
 assess the efficacy of radiotherapy of early detected brain metastases, including the
 feasibility and efficacy of SRT; to assess neurocognitive functions and QoL in the studied
 cohort. QLQ-C30 questionnaire and the California Verbal Learning Test (CVLT), Color
 connection test (CTT), Benton visual memory test (BNRT) and Verbal fluency test (VFT) will be
 carried out by the certified psychologist.

 Ethics and dissemination The trial received ethical approval from the local medical
 university Bioethical Review Board (Komisja Bioetyczna Collegium Medicum Uniwersytet
 Warmińsko-Mazurski w Olsztynie). The results of the trial will be disseminated through
 peer-reviewed publications and conference presentations.
Patients with diagnosed LD-SCLC, after radical treatment with remission or at least a good
 response after radical therapy, will be eligible for the study. Patients would have had
 radical radiotherapy to the chest with chemotherapy according to current international
 guidelines and institutional protocols. A detailed medical history will be collected
 regarding SCLC and comorbidities. During the qualification visit, the remission or good
 response should be confirmed based on chest/abdomen/pelvis CT examinations. After obtaining
 the patient's informed consent to participate in the clinical trial, a brain MRI (MRI-1) will
 be performed and a baseline assessment of cognitive functions will be carried out using the
 battery of test listed below.

 Patients who at MRI-1 will be diagnosed with cerebral metastasis, depending on the size and
 number of lesions will be eligible for WBRT (whole brain irradiation) or SRT (brain
 stereotactic radiotherapy). We propose SRT eligibility treatment criteria as in NSCLC
 according to the standards of the participating centers. All participating radiotherapy
 centers must have experience in SRT of brain metastases and up to date radiotherapy equipment
 suitable for SRT. Subjects who will not have cerebral metastases in the MRI-1 after
 chemo-radiotherapy will have their next follow-up every 3 months (+/- 2 weeks) up to 2 years,
 and then every 6 months (+/- 2 weeks) up to 3 years.

 At the qualifying visit before MRI-1, and then every 6 months +/- 2 weeks), the patients will
 have a cognitive examination performed using dedicated neuropsychological tests and QoL
 assessment using the QLQ-C30 questionnaire. The tests will be conducted in the following
 order: California verbal learning test (CVLT) with a delay of 15 min, Color connection test
 (CTT), CVLT (after delay), Benton visual memory test (BNRT), Verbal fluency test by the
 certified psychologist.
Inclusion Criteria:

 -  confirmed histologically small cell lung cancer, confirmed by staging limited disease
 SCLC, complete or good response to local chemoradiotherapy, good performance status
 (ECOG/WHO=0-2), signed informed consent

 Exclusion Criteria:

 -  disseminated disease (ED-SCLC), contraindication to MRI, not able to perform cognitive
 function tests, poor PS (ECOG/WHO >2)