Physician Bias in Prophylactic Cranial Irradiation Decision Making—An Opportunity for a Patient Decision Aid

Introduction

Guidelines have recommended prophylactic cranial irradiation (PCI) for patients with limited-stage small-cell lung cancer with at least a partial response after thoracic chemoradiation. However, the survival advantage has been small and was observed in an era before magnetic resonance imaging and surveillance. Neurotoxicity also remains a concern, especially in older adults. Thus, patients have a complex value-laden decision to make. We sought to better understand the role physicians play in patient decision making and introduce a patient decision aid (PDA) to potentially facilitate these discussions.

The Role of Advanced Imaging in Assessing Response to Definitive Chemoradiation Before Prophylactic Cranial Irradiation in Limited-Stage Small-Cell Lung Cancer

Introduction

Prophylactic cranial irradiation (PCI) improves survival for small-cell lung cancer (SCLC). Evidence for PCI in limited-stage SCLC largely derives from studies requiring only chest x-ray (CXR) to determine remission status. We analyzed thoracic chemoradiation therapy (TCRT) outcomes according to imaging modality to determine which patients benefitted most from PCI.

Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01)

BackgroundWe recently published the results of the PCI99 randomised trial comparing the effect of a prophylactic cranial irradiation (PCI) at 25 or 36 Gy on the incidence of brain metastases (BM) in 720 patients with limited small-cell lung cancer (SCLC). As concerns about neurotoxicity were a major issue surrounding PCI, we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life (QoL).Patients and methodsAt predetermined intervals, the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and brain module were used for self-reported patient data, whereas the EORTC–Radiation Therapy Oncology Group Late Effects Normal Tissue–Subjective, Objective, Management, Analytic scale was used for clinicians’ assessment. For each scale, the unfavourable status was analysed with a logistic model including age, grade at baseline, time and PCI dose.ResultsOver the 3 years studied, there was no significant difference between the two groups in any of the 17 selected items assessing QoL and neurological and cognitive functions. We observed in both groups a mild deterioration across time of communication deficit, weakness of legs, intellectual deficit and memory (all P < 0.005).ConclusionPatients should be informed of these potential adverse effects, as well as the benefit of PCI on survival and BM. PCI with a total dose of 25 Gy remains the standard of care in limited-stage SCLC.     

Prophylactic Cranial Irradiation for Patients With Limited-Stage Small-Cell Lung Cancer With Response to Chemoradiation

BackgroundPrevious clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI.Patients and MethodsThe Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks).ResultsThere were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively).ConclusionsPatients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation.     

Diagnostic Nodes of Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Among Colorectal Cancer Patients: A Swiss National Multicenter Survey

BackgroundThe management of patients with colorectal cancer (CRC) with peritoneal metastases is challenging, and the roles of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are unclear and debated among experts.Materials and MethodsThe experts of the Swiss Peritoneal Cancer Group were contacted and agreed to participate in this analysis. Experts from 9 centers in Switzerland provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Their responses were converted into decision trees on the basis of objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies.ResultsThe final treatment algorithms included a total of 5 decision criteria (age, Peritoneal Cancer Index [PCI], extraperitoneal metastases, Peritoneal Surface Disease Severity Score, and various risk factors [RF]) and 2 treatment options (HIPEC, yes or no). HIPEC was never recommended for patients without peritoneal metastases in the absence of RF for peritoneal metastases. For patients with a PCI ≤15 without organ metastases, all centers recommended CRS/HIPEC. There was also a consensus not to perform CRS/HIPEC in elderly patients (80 years and older), those with a PCI >20, and those with unresectable metastases. For patients with a PCI = 16 to 20, there was no consensus.ConclusionMultiple decision criteria relevant to all participating centers were identified. Because patient selection for CRS/HIPEC remains difficult, uniform criteria for the term “high risk” for peritoneal metastases and systemic metastases are helpful. Future trials and guidelines should take these criteria into account.     

Prophylactic cranial irradiation in small-cell lung cancer: Findings from a North Central Cancer Treatment Group Pooled Analysis

BackgroundThis pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials.Patients and methodsThree hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared.ResultsPCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52–0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018).ConclusionsPCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.     

Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary?

PurposeProphylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging.Methods and MaterialsWe identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology.ResultsNinety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01).ConclusionsOverall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging.     

Patient Selection for Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Cancer: Consensus on Decision Making Among International Experts

BackgroundColorectal cancer (CRC) treatment for patients with peritoneal metastases is complex. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has continued to be debated. The aim of the present study was to assess the consensus among international experts for decision-making regarding the use of CRS and HIPEC for patients with CRC.Materials and MethodsOf 15 experts invited, 12 had provided their decision algorithms for CRS and HIPEC for patients with, or at high risk of, peritoneal metastases from CRC. Using the objective consensus method, the results were transformed into decision trees to provide information on the consensus and discordance.ResultsOnly 1 scenario was found for which the consensus on performing HIPEC had reached 100%. The scenario was the treatment of young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of < 16 in the presence of certain risk factors. Five major decision criteria were identified: age, PCI, completeness of cytoreduction, extent of extraperitoneal metastases (EoMs), and, in the case of unverified EoMs, additional risk factors. Consensus was found regarding refraining from using HIPEC for older patients with a high PCI. The consensus further increased when addressing incomplete cytoreduction and an extensive extent of EoMs.ConclusionA definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance; however, owing to the heterogeneity of each individual situation, the impracticality of presenting the information through decision trees, and the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice could not be achieved.     

A Systematic Review of Risk Factors for Brain Metastases and Value of Prophylactic Cranial Irradiation in Non-Small Cell Lung Cancer

Background: The incidence of brain metastases (BM) varies in patients with non-small cell lung cancer(NSCLC), calls into question the value of prophylactic cranial irradiation (PCI). It is possible that clinicopathologiccharacteristics are associated with the development of BM, but these have yet to be identified in detail. Thus,we conducted the present meta-analysis on risk factors for BM and the value of PCI in patients with NSCLC.Methods: Eligible data were extracted and the risk factors for BM and the value of PCI in patients with NSCLCwere analyzed by calculating the pooled odds ratio (OR). Heterogeneity was detected using Q and I-squaredstatistics, and publication bias was tested by funnel plots and Egger’s test. Results: Six randomized controlledtrials with a focus on the value of PCI and 13 eligible studies with a focus on risk factors for BM were included.PCI significantly reduced the incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.34, 95% confidenceinterval = 0.37-0.59). Compared with non-squamous cell carcinoma, squamous cell carcinoma was associatedwith a low incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.47, 95% confidence interval =0.34-0.65). The funnel plot and Egger’s test suggested that there was no publication bias in the current meta-analysis.Conclusions: This meta-analysis provides statistical evidence that compared with non-squamous cell carcinoma,squamous cell carcinoma can be used as a predictor for BM in patients with NSCLC, and PCI might reduce theincidence of BM in patients with NSCLC, but does not provide a survival benefit.     

Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin

Background

Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact.

Aim

To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off.

Patients and methods

Patients (n = 139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations.

Results

All the patients with a PCI ≥15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was <15 vs 12% when it was ≥15 (p < 0.0001. The multivariate analysis retained two prognostic factors: PCI ≥15 (p = 0.02, HR = 1.8), and the involvement of area 12 (lower ileum) (p = 0.001, HR = 3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI <15 and area 12 involved was 15%, close to that of patients with a PCI ≥15 (12%) and far lower than that of patients with a PCI <15 and no area 12 involvement (70%).

Conclusion

A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS + HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.     

Prophylactic cranial irradiation improved the overall survival of patients with surgically resected small cell lung cancer,but not for stage I disease

ObjectivesWe conducted a retrospective study to evaluate the role of prophylactic cranial irradiation (PCI) on patients with surgically resected small cell lung cancer (SCLC).Patients and methodsBetween January 2003 and December 2009, the records of completely resected patients who were diagnosed with SCLC and definitive pTNM stage on the basis of histological proof were reviewed. According to the therapy modality, patients were allocated to PCI group and non-PCI group.ResultsA total of 193 patients were finally included, 67 patients in PCI group and 126 in non-PCI group. The OS rates at 2-year and 5-year in PCI group were 92.5%, and 54.9%, respectively, and those of non-PCI were 63.2% and 47.8%, respectively (p = 0.005). The BMFS rate at 2-year and 5-year in PCI group was significantly better than those of non-PCI group (96.8%, 76.6% and 79.4%, 75.5%, respectively, p = 0.014). But PCI could not confer survival benefit in the patients with p-stage I. Multivariate analysis revealed that PCI (HR = 2.339; p = 0.001) was an independent prognostic factor of the overall survival.ConclusionsPCI could improve the OS of patients with surgically resected SCLC, but not for p-stage I patients.     

Treatment Response and Prophylactic Cranial Irradiation Are Prognostic Factors in a Real-life Limited-disease Small-cell Lung Cancer Patient Cohort Comprehensively Staged With Cranial Magnetic Resonance Imaging

Introduction

Prophylactic cranial irradiation (PCI) has proven to decrease the incidence of brain metastases (BMs), with a modest improvement in survival.

Utility of Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer in the Modern Era with Magnetic Resonance Imaging Surveillance

AimsTo retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening.Materials and methodsPatients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II–III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan–Meier and Cox proportional hazards models.ResultsIn total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II–III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08–0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12–0.51; P < 0.01) and symptomatic brain metastasis-free survival (hazard ratio 0.21, 95% confidence interval 0.08–0.55; P < 0.01), but not improved overall survival. Two-year neurological survival estimates within the propensity matched cohort were 96.8% (95% confidence interval 87.6–99.2%) with PCI and 77.2% (95% confidence interval 63.0–86.4%) without PCI and 1- and 2-year estimates of incidence of brain metastases were 3.9% (95% confidence interval 1.3–11.7%) and 11.7% (95% confidence interval 5.6–23.5%) in the PCI group and 31.6% (95% confidence interval 22.1–43.9%) and 40.4% (95% confidence interval 29.2–54.0%) in the no PCI group, respectively.ConclusionsIn the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II–III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.     

The Role of Prophylactic Cranial Irradiation in Patients With Extensive Stage Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Introduction

The role of prophylactic cranial irradiation (PCI) is controversial in patients with extensive stage small cell lung cancer. The aim of this study was to determine the impact of PCI in these patients.

Effect of Accurate Staging Using Positron Emission Tomography on the Outcomes of Prophylactic Cranial Irradiation in Patients With Limited Stage Small-Cell Lung Cancer

Background

Prophylactic cranial irradiation (PCI) was reported to offer survival benefits in patients with limited stage small-cell lung cancer (LS-SCLC). However, earlier studies did not routinely use positron emission tomography (PET) as part of the initial evaluation, thereby reducing the accuracy of tumor staging. We examined the effect of more accurate staging with PET on the role of PCI in patients with LS-SCLC.

Effect of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

Introduction

Patients with small-cell lung cancer (SCLC) have a high incidence of occult brain metastases and are often treated with prophylactic cranial irradiation (PCI). Despite a small survival advantage in some studies, the role of PCI in extensive stage SCLC remains controversial. We used the National Cancer Database to assess survival of patients with metastatic SCLC treated with PCI.

Predictive value of peritoneal cancer index for survival in patients with mucinous peritoneal malignancies treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a single centre experience

Objectives: This study investigated the correlation between the peritoneal carcinomatosis index (PCI) and patient outcome depending on the tumour type.

Background: Peritoneal surface malignancy (PSM) treatment depends on tumour type. Mucinous PSM (m-PSM) is associated with a better prognosis than non-mucinous PSM (nm-PSM). The PCI’s predictive ability has not yet been evaluated.

Methods: We analysed 123 patients with PSM treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) between 2008 and 2015. The m-PSM group (n?=?75) included patients with appendiceal cancer (n?=?15), colorectal cancer (n?=?21), or low-grade appendiceal mucinous neoplasm (n?=?39); the nm-PSM group (n?=?48) included patients with gastric (n?=?18) or colorectal (n?=?30) cancer. The PCI’s predictive ability was evaluated by multiple Cox-proportional hazard regression analysis and Kaplan–Meier curves.

Results: The 5-year survival and PCI were higher in m-PSM patients (67.0%; 20.5?±?12.1) than in nm-PSM patients (32.6%; p?=?0.013; 8.9?±?6.0; p?vs. 68.1%; p?=?0.935). Underlying disease (HR 5.666–16.240), BMI (HR 1.109), and PCI (HR 1.068) significantly influenced overall survival in all patients.

Conclusions: PCI is prognostic in nm-PSM, but not in m-PSM. CRS and HIPEC may benefit not only patients with low PCI, but also those with high PCI and m-PSM.     

The pattern of peritoneal colorectal metastasis predicts survival after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy

BackgroundPeritoneal cancer index (PCI) has been used reliably to prognosticate patients with peritoneal metastasis, however, it fails to describe the patterns of peritoneal spread and to correlate these patterns to survival outcomes. We aim to define the scattered peritoneal spread (SPS) as a pattern associated with worse survival in colorectal peritoneal metastasis.MethodsA retrospective analysis of metastatic colorectal cancer patients from a prospectively maintained database of peritoneal surface malignances (n = 280) between 2015 and 2020. SPS was defined by the presence of at least two distant and non-contiguous PCI regions. We compared patients with SPS (n = 73) and clustered peritoneal spread (CPS) (n = 88) for demographics, perioperative and survival outcomes.ResultsNo difference in demographics or post-operative course was noted between the groups. The median follow-up was 15.4 months (0.4–70.8 months). Worse disease-free survival (DFS) in the SPS group with an estimated median of 8.2 months compared to 22.5 months in the CPS spread group, (p = 0.001). The estimated median overall survival (OS) for SPS group was 35.7 months whereas in the CPS group the median was not reached (p = 0.025). The same effect of SPS was preserved even after stratification of PCI.ConclusionsWe defined and described the association of the peritoneal spread pattern to survival outcomes. SPS patients exhibit worse DFS and OS independent of the PCI level. Integration of malignant spread pattern into prognostication models along with PCI may aid in predicting oncological outcomes.     

Understanding the Major Factors Affecting Response Shift Effects on Health-Related Quality of Life: What the Then-Test Measures in a Longitudinal Prostate Cancer Registry

BackgroundLocalized prostate cancer (PCa) treatments provide high survival rates, with patients often surviving a decade or longer after treatment. Therefore, treatment options are progressively based on quality of life. The objective of this research was to investigate magnitude of response shift (RS) in health-related quality of life (HRQOL) responses in men with clinically localized PCa using a generic questionnaire and a disease-specific questionnaire in an observational longitudinal patient registry study.Patients and MethodsA cohort study was conducted using the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database. Patients were annually surveyed using the Medical Outcomes Study Questionnaire Short Form 36 (SF-36) and the UCLA Prostate Cancer Index (PCI) HRQOL measures. A total of 3161 active patients were eligible for a one-off supplemental study asking retrospective HRQOL scores (then-test). We calculated RS, observed change, and RS adjusted change. Statistical difference was determined by t test.ResultsPatients consistently reported higher recalled pretreatment HRQOL compared to baseline scores for SF-36 and PCI, confirming the existence of a RS (P < .05). On average, PCI demonstrated larger RS by a factor of 2 than SF-36. More specific, RS was greater especially in SF-36 physical domains compared to mental health items. PCI measured PCa-specific physical adverse effects only. Patients whose cancer had recurred reported slightly lower SF-36 RS than those whose cancer had not recurred.ConclusionRS occurrence was measured in both the disease-specific questionnaire and the generic HRQOL questionnaire, demonstrating continued low health and symptom scores after RS adjustment. Therefore, health professionals should adjust for this phenomenon when assessing patient’s HRQOL treatment responses, and clinicians should address their continued sexual and urinary functional loss.     

Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)

IntroductionTo compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA).MethodsIn a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test—Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival.ResultsFrom April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%–29%) for the PCI arm and 16% (95% confidence interval: 7%–24%) for the HA-PCI arm.ConclusionsThis randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm.