Rationale for a phase III study of erythropoietin as a neurocognitive protectant in patients with lung cancer receiving prophylactic cranial irradiation

2002 ◽  
Vol 29 (6 Suppl 19) ◽  
pp. 47-52 ◽  
Author(s):  
Neil Senzer
Keyword(s):  
Lung Cancer ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Phase Iii ◽  
Phase Iii Study

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study

2021 ◽  
pp. JCO.21.00639
Author(s):  
Núria Rodríguez de Dios ◽  
Felipe Couñago ◽  
Mauricio Murcia-Mejía ◽  
Mikel Rico-Oses ◽  
Patricia Calvo-Crespo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Free Recall ◽  
Brain Metastases ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Hippocampal Avoidance

PURPOSE Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

Nationwide shift in patterns of prophylactic cranial irradiation utilization for extensive-stage small cell lung cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20099-e20099
Author(s):  
Olsi Gjyshi ◽  
Ethan B. Ludmir ◽  
Todd A. Pezzi ◽  
David Boyce-Fappiano ◽  
Timur Mitin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Practice Patterns ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Radiation Oncologists ◽  
Extensive Stage ◽  
Mri Surveillance ◽  
The Impact

e20099 Background: A recent phase III trial (Takahashi et al., 2017) showed no overall survival (OS) benefit in patients with extensive-stage small cell lung cancer (ES-SCLC) treated with prophylactic cranial irradiation (PCI), casting doubt on the practice of PCI as established in a prior phase III trial (Slotman et al., 2007). We undertook a nationwide survey of radiation oncologists to ascertain the impact of the Takahashi trial on the utilization of PCI for ES-SCLC patients. Methods: A total of 3,646 ASTRO-registered radiation oncologists in the United States were invited to answer an anonymous survey on their use of PCI in ES-SCLC, and the impact of the recent Takahashi et al. trial on their practice. The survey consisted of 35 questions created using a branching logic system via RedCAP. Results: A total of 438 (12%) radiation oncologists completed the survey. Responders were well-distributed across geographic regions, practice environment, age, gender, practice size and lung cancer volume. Most respondents (92%) were aware of the Takahashi trial. While 71% routinely offered PCI to ES-SCLC patients prior to the publication of this trial, only 43% continue to do so after its publication (p < 0.001). Most respondents (66%) had altered their practice in response to the study. There was no difference in post-publication practice patterns between academic and private practice radiation oncologists (43% vs. 44%, p = 0.81). While 43% of participants who were aware of the Takahashi trial still offered PCI after its publication, 82% of those unaware of the trial still continued to offer PCI (p < 0.001). Additionally, 25% of participants noted that they have experienced a decrease in medical oncology referrals for PCI for ES-SCLC patients. Twenty-two percent of participants stated that the Takahashi trial impacted their practice with regards to limited-stage SCLC patients as well. Looking toward the future, 47% of respondents reported that they would be willing to enroll both LS- and ES-SCLC patients on a randomized trial comparing active MRI-surveillance to PCI; 15% stated that they would enroll only LS-SCLC patients on such a trial, and 20% would enroll only ES-SCLC patients. Conclusions: The phase III data from Takahashi et al. (2017) has markedly impacted the current practice patterns in the US by reducing PCI utilization for ES-SCLC patients across all practice settings and measured demographic variables. Most respondents expressed openness to a randomized trial comparing active MRI surveillance to PCI for SCLC patients.

NRG Oncology CC003: A randomized phase II/III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8578-TPS8578
Author(s):  
Vinai Gondi ◽  
Stephanie L Pugh ◽  
Minesh P. Mehta ◽  
Wolfgang Tome ◽  
Tammie Benzinger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Randomized Phase Ii ◽  
Hippocampal Avoidance

TPS8578 Background: Multiple clinical trials have shown that prophylactic cranial irradiation (PCI) prevents brain metastases and may prolong survival in small cell lung cancer (SCLC). However,prophylactic cranial irradiation can lead to decline in cognitive function. Preclinical evidence suggests that the pathogenesis of this toxicity includes inflammatory injury to proliferating neuronal progenitor cells in the peri-hippocampal stem cell niches. We hypothesized that conformal avoidance of the hippocampal neural stem cell compartment during brain irradiation using intensity-modulated radiotherapy (IMRT) would decrease the likelihood and/or severity of this toxicity. This hypothesis was recently validated by positive results from NRG Oncology CC001, a phase III trial of hippocampal avoidance during whole-brain radiotherapy for patients with brain metastases. NRG Oncology CC003 is an ongoing randomized phase II/III trial of hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) for small cell lung cancer, conducted in parallel with NRG Oncology CC001. Methods: The primary endpoints of the phase IIR and III components are 12-month intracranial relapse rate and 6-month deterioration in Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall, respectively. This is a seamless phase IIR/III trial, with the phase IIR designed to demonstrate non-inferiority. If the non-inferiority margin of the phase IIR component is not exceeded, then the trial would transition to the phase III component. Following accrual of 182 of planned 172 patients on the phase IIR component, the trial closed to accrual on 10/13/17 to assess the phase IIR primary endpoint. The DSMB evaluated the IIR outcomes, and on 1/9/19, the trial was reactivated to accrue an additional 122 patients to the phase III component. Eligibility criteria include: 1) small cell lung cancer with at least partial response to chemotherapy; 2) contrast-enhanced thin-slice volumetric MRI scan; and, 3) Zubrod performance status 0-2. Supported by grant UG1CA189867 (NCORP) from the National Cancer Institute. Clinical trial information: NCT02635009.

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