ESTRO 2023

Session Item

Sunday

May 14

16:45 - 17:45

Plenary Hall

Lung

Co-Chair: Caroline Maguire, United Kingdom;

Chair: , Italy

Session Code: 2520

Session Type: Proffered Papers

Track: Clinical

16:45 - 16:55

Pattern of brain metastases after HA-PCI and SRCF in SCLC: pooled findings of NCT01780675 and PREMER

Haiyan Zeng, The Netherlands

Presentation Number: OC-0607

Abstract

Abstract Title:

Pattern of brain metastases after HA-PCI and SRCF in SCLC: pooled findings of NCT01780675 and PREMER

Authors:

Haiyan Zeng¹, Sanne Schagen², Lizza Hendriks³, Gonzalo Sánchez-Benavides⁴, Jaap Jaspers⁵, Rosa Manero⁶, Yolande Lievens⁷, Maurico Murcia-Mejía⁸, Marianne Kuenen², Mikel Rico-Oses⁹, Michiel de Ruiter², Felipe Couñago¹⁰, Edith Dieleman¹¹, Katrien de Jaeger¹², Patricia Calvo-Crespo¹³, Maarten Lambrecht¹⁴, Pilar Samper¹⁵, José Belderbos¹⁶, Dirk De Ruysscher¹⁷, Núria Rodríguez de Dios¹⁸

¹GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Department of Radiation Oncology (Maastro), Maastricht, The Netherlands; ²The Netherlands Cancer Institute, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands; ³GROW - School for Oncology and Re production, Maastricht University Medical Center+, Department of Pulmonary Diseases, Maastricht, The Netherlands; ⁴Hospital del Mar Medical Research Institute (IMIM), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; ⁵Erasmus MC Cancer Institute, Department of Radiotherapy, Rotterdam, The Netherlands; ⁶Hospital del Mar, Department of Neurology, Barcelona, Spain; ⁷Ghent University Hospital and Ghent University, Radiation Oncology, Gent, Belgium; ⁸Hospital Universitario Sant Joan de Reus, Department of Radiation Oncology. , Reus, Spain; ⁹Complejo Hospitalario Navarra, Department of Radiation Oncology, Pamplona, Spain; ¹⁰San Francisco de Asís and La Milagrosa Hospitals, Genesis Care Madrid Clinical Director, Madrid, Spain; ¹¹Amsterdam UMC- Location AMC, Radiation Oncology, Amsterdam, The Netherlands; ¹²Catharina Hospital, Radiation Oncology, Eindhoven, The Netherlands; ¹³Hospital Universitario de Santiago de Compostela, Department of Radiation Oncology, Santiago de Compostela, Spain; ¹⁴ Leuven Cancer Institute, , Department of Radiation Oncology, Leuven, Belgium; ¹⁵Hospital Universitario Rey Juan Carlos. Móstoles. Spain., Department of Radiation Oncology. , Madrid, Spain; ¹⁶The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Department of Radiation Oncology, Amsterdam, The Netherlands; ¹⁷GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands., Department of Radiation Oncology (Maastro), Maastricht, The Netherlands; ¹⁸Hospital del Mar, Radiation Oncology, Barcelona, The Netherlands

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Purpose or Objective

To investigate whether hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) increases the risk of brain metastases (BM) development within the HA area and preserves self-reported cognitive functioning (SRCF) in small cell lung cancer (SCLC) using the pooled data of two phase III randomized clinical trials: NCT01780675 (Dutch-Flemish) and PREMER/NCT02397733 (Spanish).

Material and Methods

Patients with stage I-IV SCLC were randomized to PCI or HA-PCI. Brain MRI with contrast enhancement was performed at baseline, 4, and 12 months in the Dutch trial and at baseline, 3, 12, and 24 months in the PREMER trial. In patients who developed new neurological symptoms, brain MRI /CT was preformed ad interim. In case of BM in the proximity of the lower dose regions, the MRI/ CT-scan were matched to the planning CT-scan and visually inspected to see if the BM were located in the HA zone (hippocampus with 5mm volumetric expansion). χ2-test/Fisher’s exact test was performed to compare the BM location between arms.
SRCF was assessed using the cognitive functioning scale of the EORTC-QLQ-C30 at pre-specified time points (both: baseline, 12, and 24 months after completion of PCI; Dutch: 4, 8, and 18 months; Spanish: 3 and 6 months). Measurements within the time window (until the start of PCI for baseline, within 2 weeks for 3~8 months, within 1 month for 12~24 months) were analyzed, others were scored as missing. We used the threshold of SCRF<75 to examine clinically relevant cognitive impairment. Generalized estimating equation (GEE) was performed to identify the impact of HA on SRCF.

Results

In total, 168 (84 in each arm) patients were randomized in the Dutch trial and 150 (75 in each arm) were randomized in the Spanish trial (Table 1). Median follow up was 41.7 (95%CI 35.7-47.6) months. In total, 202 of 318 patients died (104 in PCI, 98 in HA-PCI), 61 (19.2%) developed BM (30 in PCI, 31 in HA-PCI). The BM was single in 15 patients (7 in PCI, 8 in HA-PCI, p=0.8). Nine of the 61 patients had BM within HA area (4 in PCI, 5 in HA-PCI, p=1.0). One had single BM within HA area (HA arm, p=1.0)
Overall, 47 out of 953 (4.9%) SRCF assessments were out of the time window. The compliance rate within the time window dropped from 97.5% at baseline to 64.7% at 24-months, the cognitive impairment incidence ranged from 25.6% to 53.8% (Figure 1), which were not statistically significant between arms. Six patients did not assessed SRCF and 147 of 312 (47.1%) patients experienced cognitive impairment at least once (78 in PCI, 69 in HA-PCI, p=0.3). GEE analysis showed that HA-PCI did not have a significant impact on SCRF (β = 1.7, p=0.4) nor cognitive impairment (SRCF<75) (OR 0.8, 95%CI 0.6 – 1.2, p = 0.3).

Conclusion

The occurrence and location of BM were similar between HA-PCI and standard PCI. In a longitudinal assessment, the percentage of patients with clinically relevant self-reported cognitive impairment was high and did not differ between HA-PCI and PCI.