Impact of Early Prophylactic Cranial Irradiation With Hippocampal Avoidance on Neurocognitive Function in Patients With Limited Disease Small Cell Lung Cancer. A Multicenter Phase 2 Trial (SAKK 15/12)

Vees, Hansjörg; Caparrotti, Francesca; Eboulet, Eric Innocents; Xyrafas, A.; Fuhrer, Andrea; Meier, Urs R.; Mark, Michael; Eliçin, Olgun; Aebersold, Daniel M.; Zwahlen, Daniel R.; Finazzi, Tobias; Allal, Abdelkarim Said; Putora, Paul Martin; Martucci, Francesco; Rudolf, Christine Biaggi; Ribi, Karin

doi:10.1016/j.ijrobp.2020.02.029

Cited by 30 publications

(25 citation statements)

References 38 publications

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“…PCI is identified as one of the major treatments for SCLC [ 6 ]; however, its preventive effect is not optimal due to high recurrence rate and neurotoxicity [ 5 , 23 – 25 ]. Several clinical studies have believed that hippocampus-sparing radiation avoids the neurotoxic side effects to some extent [ 8 , 26 – 28 ]. NRG CC001, a phase 3 trial based on the RTOG0933 study, showed that HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study

et al. 2021

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Objectives This study aimed to explore the spatial distribution of brain metastases (BMs) from small cell lung cancer (SCLC) a homogenous sample, and to identify the metastatic risk levels in brain regions. Methods T1-enhanced magnetic resonance imaging (MRI) from SCLC patients were retrospectively reviewed from three medical institutions in China. All images were registered to the standard brain template provided by the Montreal Neurological Institute (MNI) 152 database, followed by transformation of the location of all BMs to the space of standard brain. The MNI structural atlas and Anatomical Automatic Labeling (AAL) atlas were then used to identify the anatomical brain regions, and the observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. The locations and sizes of brain lesions were analyzed after image standardization. Results A total of 215 eligible patients with 1033 lesions were screened by MRI, including 157 (73%) males and 58 (27%) females. The incidence of crucial structures were as follows: hippocampus 0.68%, parahippocampal 0.97%, brainstem 2.05%, cauate 0.68%, putamen 0.68%, pallidum 0.2%, thalamus 1.36%. No BMs were found in the amygdala, pituitary gland, or pineal gland. The cumulative frequency of the important structures was 6.62%. Based on the results of MNI structural atlas, the cerebellum, deep white matter and brainstem was identified as a higher risk region than expected for BMs (P = 9.80 ×10−15, 9.04 ×10−6), whereas temporal lobe were low-risk regions (P = 1.65 ×10−4). More detailed AAL atlas revealed that the low-risk regions for BMs was inferior frontal gyrus (P = 6.971 ×10−4), while the high-risk regions for BMs was cerebellar hemispheres (P = 1.177 ×10−9). Conclusion Many crucial structures including the hippocampus, parahippocampus, pituitary gland and thalamus etc. have low frequency of brain metastases in a population of SCLC patients. This study provides the help to investigate the clinical feasibility of HA-WBRT and non-uniform dose of PCI in a population of SCLC patients.

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Section: Discussionmentioning

confidence: 99%

Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study

et al. 2021

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“…For SCLC patients, the incidence of BM in hippocampal is generally about 5% both at diagnosis and after PCI, 26,27 indicating that it may be feasible to decrease the BM rate and to reduce the neurocognitive toxicities by PCI with hippocampal avoidance. 28,29 A multicentre randomized phase 3 trial (NCT01780675) investigated memory functioning and safety after PCI with or without hippocampus sparing in SCLC using the Hopkins Verbal Learning Test-Revised (HVLT-R). The results showed that PCI with hippocampal sparing did not affect the decline of neurocognitive function and increased brain metastasis compared to standard PCI.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic cranial irradiation confers favourable prognosis for patients with limited‐stage small cell lung cancer in the era of MRI: A propensity score‐matched analysis

Ding

Yang

et al. 2021

J Med Imag Rad Onc

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Introduction: Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small cell lung cancer (LS-SCLC) who achieve good response after chemoradiotherapy. But PCI is neurotoxic. Magnetic resonance imaging (MRI) is the standard tool for evaluating brain metastasis (BM). This study was to retrospectively analyse the necessity of PCI in the era of MRI in LS-SCLC. Methods: From July 2013 to June 2017, 190 patients with LS-SCLC who were treated with definitive chemoradiotherapy were included and analysed in this study. They were divided into the PCI group and non-PCI group. Propensity score matching (PSM) analysis was used to balance the variable differences. The Kaplan-Meier method was applied to estimate survival with log-rank test to ascertain significance between different groups. Results: Seventy-seven patients (40.5%) received PCI after chemoradiotherapy. After adjustment for propensity scores, 69 pairs of patients were matched between two groups. After PSM, the 1-year and 3-year OS rates were 96.9% and 48.5% in PCI group versus 89.9% and 25.0% in non-PCI group (HR: 0.419, 95% CI: 0.251-0.701, P = 0.001). The 1-year and 3-year BMFS in PCI group were 96.8% and 67.5% versus 62.3% and 37.9% in non-PCI group (HR: 0.247, 95% CI: 0.132-0.460, P < 0.001). Conclusion:For patients showing no BM on MRI after definitive CRT, PCI confers less BM and better OS in LS-SCLC.

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“…Our current study adds to the emerging body of evidence on HA-PCI from RT0G 0933 [5] and, more recently, from Redmond et al [13], OC-0503 [14], and SAKK 15/12 (15). RTOG 0933 [5] randomised 110 patients who already had brain metastases at least 5mm beyond the hippocampi to whole brain radiotherapy or hippocampal-avoidance whole brain radiotherapy.…”

Section: Discussionmentioning

confidence: 88%

“… In the SAKK 15/12 trial the expansion from the hippocampi to the hippocampal avoidance zones was 2 mm, where specified all other trials used a 5mm expansion [ 15 ]. CTC — clinical target volume; HAZ — hippocampal avoidance zone; PTV — planning target volume …”

Section: Figurementioning

confidence: 99%

Patterns of relapse following hippocampal avoidance prophylactic cranial irradiation for small cell lung carcinoma

Cook

Hoffmann²,

Ross

et al. 2021

Rep Pract Oncol Radiother.

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Introduction: Hippocampal avoidance techniques are an evolving standard of care for patients undergoing cranial irradiation. Our aim was to assess the oncological outcomes and patterns of failure following hippocampal avoidance prophylactic cranial irradiation (HA-PCI) as a standard of care in unselected patients with both limited and extensive stage small cell lung carcinoma. Materials and methods:Consecutive patients with small cell lung carcinoma with a complete (limited stage) or good partial (extensive stage) response following chemotherapy were eligible to receive HA-PCI, with a total dose of 25 Gray in 10 fractions. All patients had a negative baseline MRI brain scan with gadolinium prior to HA-PCI. Patients had baseline and follow up Common Toxicity Criteria Adverse Event assessments. Following completion of HA-PCI, all patients had three-monthly MRI brain scans with gadolinium until confirmation of intracranial relapse, as well as three-monthly CT of the chest, abdomen and pelvis. Overall and progressionfree survival were calculated using the Kaplan-Meier method.Results: A total of 17 consecutive patients, 9 men and 8 women, with a mean age of 70 years received HA-PCI between May 2016 and June 2020 after completion of their initial chemotherapy. There were no Grade 4 or greater adverse events. No patient had an isolated hippocampal avoidance zone relapse alone; three of 17 patients had multifocal relapses that included the hippocampal avoidance zone. Conclusion:In our series, there were no hippocampal only relapses and we conclude that HA-PCI is a safe alternative to standard PCI in the setting of small cell lung cancer.

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Impact of Early Prophylactic Cranial Irradiation With Hippocampal Avoidance on Neurocognitive Function in Patients With Limited Disease Small Cell Lung Cancer. A Multicenter Phase 2 Trial (SAKK 15/12)

Cited by 30 publications

References 38 publications

Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study

Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study

Prophylactic cranial irradiation confers favourable prognosis for patients with limited‐stage small cell lung cancer in the era of MRI: A propensity score‐matched analysis

Patterns of relapse following hippocampal avoidance prophylactic cranial irradiation for small cell lung carcinoma

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