Hansjörg Vees1, Francesca Caparrotti2, Eric Innocents Eboulet3, Alexandros Xyrafas3, Andrea Fuhrer3, Urs Meier4, Michael Mark5, Olgun Elicin6, Daniel M Aebersold6, Daniel R Zwahlen5, Tobias Finazzi7, Abdelkarim Said Allal8, Paul Martin Putora9, Francesco Martucci10, Christine Biaggi Rudolf3, Karin Ribi11. 1. Radiotherapy Institute, Hirslanden Klinik, Zurich, Switzerland. Electronic address: hansjoerg.vees@hirslanden.ch. 2. Radiation Oncology, University Hospital of Geneva - HUG, Geneva, Switzerland. 3. SAKK Coordinating Center, Bern, Switzerland. 4. Radiation Oncology, Cantonal Hospital of Winterthur, Winterthur, Switzerland. 5. Medical Oncology, Cantonal Hospital of Graubünden, Chur, Switzerland. 6. Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland. 7. Clinic of Radiotherapy and Radiation Oncology, University Hospital of Basel, Basel, Switzerland. 8. Radiation Oncology, Cantonal Hospital of Fribourg - HFR, Fribourg, Switzerland. 9. Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland; Radiation Oncology, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland. 10. Radiation Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. 11. Quality of Life Office SAKK Coordinating Center and International Breast Cancer Study Group (IBCSG) Coordinating Center, Bern, Switzerland.
Abstract
PURPOSE: Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC). METHODS AND MATERIALS: In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment. RESULTS: Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%). CONCLUSIONS: The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population.
PURPOSE: Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC). METHODS AND MATERIALS: In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment. RESULTS: Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%). CONCLUSIONS: The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population.