Cost Effectiveness of Modified Fractionation Radiotherapy versus Conventional Radiotherapy for Unresected Non–Small-Cell Lung Cancer Patients

IntroductionModified fractionation radiotherapy (RT), delivering multiple fractions per day or shortening the overall treatment time, improves overall survival for non -small-cell lung cancer (NSCLC) patients compared with conventional fractionation RT (CRT). However, its cost effectiveness is unknown. Therefore, we aimed to examine and compare the cost effectiveness of different modified RT schemes and CRT in the curative treatment of unresected NSCLC patients.MethodsA probabilistic Markov model was developed based on individual patient data from the meta-analysis of radiotherapy in lung cancer (N = 2000). Dutch health care costs, quality-adjusted life years (QALYs), and net monetary benefits (NMBs) were compared between two accelerated schemes (very accelerated RT [VART] and moderately accelerated RT [MART]), two hyperfractionated schemes (using an identical (HRTI) or higher (HRTH) total treatment dose than CRT) and CRT.ResultsAll modified fractionations were more effective and costlier than CRT (1.12 QALYs, €24,360). VART and MART were most effective (1.30 and 1.32 QALYs) and cost €25,746 and €26,208, respectively. HRTI and HRTH yielded less QALYs than the accelerated schemes (1.27 and 1.14 QALYs), and cost €26,199 and €29,683, respectively. MART had the highest NMB (€79,322; 95% confidence interval [CI], €35,478-€133,648) and was the most cost-effective treatment followed by VART (€78,347; 95% CI, €64,635-€92,526). CRT had an NMB of €65,125 (95% CI, €54,663-€75,537). MART had the highest probability of being cost effective (43%), followed by VART (31%), HRTI (24%), HRTH (2%), and CRT (0%).ConclusionImplementing accelerated RT is almost certainly more efficient than current practice CRT and should be recommended as standard RT for the curative treatment of unresected NSCLC patients not receiving concurrent chemo-radiotherapy

Migration von /sw vom AFS ins DCE/DFS

/sw ist eine verteilte Softwarebereitstellung mit dem Ziel, jedem Benutzer Software zentral zur Verfügung zu stellen, ohne daß er sich darum kümmern muß, woher er seine Software bekommt. Für eine Außenstehenden ergibt sich somit das Bild eines großen Softwarepools, aus dem er sich fertig installierte Software für seine Plattform herunterladen kann. Voraussetzung dafür ist, daß ein Benuzter an seiner Workstation über AFS (Andrew File System), DFS (Distributed File System) oder ftp verfügt. Zur Zeit werden vom /sw für 18 verschiedenen Unix-Plattformen 594 Programme in 1024 verschiedenen Installationen angeboten. Die meisten Architekturen vom /sw liegen im AFS, bis auf die Architekturen DEC ALPHA, IRIX 4.0 und Linux, die im NFS liegen. In Zukunft wird es für die gesamte /sw Software nur noch eine Quelle geben, das DFS. Mit der Migration von /sw aus dem AFS ins DFS entfällt dann die Trennung von /sw in einen AFS-Teil und einem NFS-Teil und damit auch der AFS/NFS-Translators, der recht unstabil läuft. Die gesamte Software von /sw wurde aus dem AFS bzw. NFS ins DFS migriert, so daß für alle vom /sw unterstützten Architekturen nur noch eine Quelle zur Verfügung steht, die Stuttgarter DCE-Zelle. Jeder AFS-Klient hat über den AFS/DFS-Translator Zugriff auf /sw und für die NFS-Klienten wird das /sw-Fi-lesystem exportiert, so daß jeder NFS-Klient die Möglichkeit hat das DFS-Filesystem /sw zu mounten. Eine Workstation kann sowohl AFS- als auch DCE/DFS-Klient sein

Self-Reported Cognitive Function and Quality of Life in Patients With SCLC in the Hippocampal Avoidance Prophylactic Cranial Irradiation Versus Prophylactic Cranial Irradiation Randomized Phase 3 Trial (NCT01780675)

Introduction: In the randomized controlled trial in patients with SCLC comparing standard prophylactic cranial irradiation (PCI) with hippocampal avoidance PCI (HA-PCI), we did not observe beneficial effects of HA-PCI on tested cognition. Here, we report findings on self-reported cognitive functioning (SRCF) and quality of life (QoL). Methods: Patients with SCLC were randomized to receive PCI with or without HA (NCT01780675) and assessed at baseline (82 HA-PCI and 79 PCI patients) and at 4, 8, 12, 18, and 24 months of follow-up, using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ—brain cancer module (BN20). SRCF was assessed with the cognitive functioning scale of the EORTC QLQ-C30 and the Medical Outcomes Study questionnaire. A change of 10 points was used for minimal clinically important differences. Percentages of patients classified with having improved, stable, or deteriorated SRCF were compared between groups using chi-square tests. Changes in mean scores were analyzed using linear mixed models. Results: There was no significant difference in the percentage of patients with deteriorated, stable, or improved SRCF between the treatment arms. Depending on the evaluated time point, 31% to 46% and 29% to 43% of patients in the HA-PCI and PCI arm, respectively, reported a deteriorated SRCF on the basis of the EORTC QLQ-C30 and Medical Outcomes Study. QoL outcomes were not significantly different between the study arms, except for physical functioning at 12 months (p = 0.019) and motor dysfunction at 24 months (p = 0.020). Conclusions: Our trial did not find beneficial effects of HA-PCI over PCI on SRCF and QoL. The cognitive benefit of sparing the hippocampus in the context of PCI is still a subject of debate

Survival of patients with <i>KRAS </i>G12C mutated stage IV non-small cell lung cancer with and without brain metastases treated with immune checkpoint inhibitors

Introduction: Few data is available on whether brain metastases (BM) influence survival in patients with stage IV KRAS G12C mutated (KRAS G12C+ ) non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI) +/- chemotherapy ([chemo]-ICI). Methods: Data was retrospectively collected from the population-based Netherlands Cancer Registry. The cumulative incidence of intracranial progression, overall survival (OS) and progression free survival (PFS) was determined for patients with KRAS G12C+ stage IV NSCLC diagnosed January 1 – June 30, 2019, treated with first-line (chemo)-ICI. OS and PFS were estimated using Kaplan-Meier methods and BM+ and BM− groups were compared using log-rank tests. Results: Of 2489 patients with stage IV NSCLC, 153 patients had KRAS G12C+ and received first-line (chemo)-ICI. Of those patients, 35% (54/153) underwent brain imaging (CT and/or MRI), of which 85% (46/54) MRI. Half of the patients with brain imaging (56%; 30/54) had BM, concerning one-fifth (20%; 30/153) of all patients, of which 67% was symptomatic. Compared to BM−, patients with BM+ were younger and had more organs affected with metastasis. Around one-third (30%) of patients with BM+ had ≥5 BM at diagnosis. Three quarters of patients with BM+ received cranial radiotherapy prior to start of (chemo)-ICI. The 1-year cumulative incidence of intracranial progression was 33% for patients with known baseline BM and 7% for those without (p = 0.0001). Median PFS was 6.6 (95% CI 3.0–15.9) and 6.7 (95% CI 5.1–8.5) months for BM+ and BM− (p = 0.80), respectively. Median OS was 15.7 (95% CI 6.2–27.3) and 17.8 (95% CI 13.4–22.0) months for BM+ and BM− (p = 0.77), respectively. Conclusion: Baseline BM are common in patients with metastatic KRAS G12C+ NSCLC. During (chemo)-ICI treatment, intracranial progression was more frequent in patients with known baseline BM, justifying regular imaging during treatment. In our study, presence of known baseline BM did not influence OS or PFS.</p

Risk factors for cognitive impairment in radically treated stage III NSCLC: Secondary findings of the NVALT-11 study

Aim: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC). Methods: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy ± surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score -10, p < 0.05). Cognitive functioning declined over time (β = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (β = 0.141, p = 0.33). Conclusion: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176)

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

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). Methods: In 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. Results: From 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. Conclusions: This 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