Radiotherapy Timing in the Treatment of Limited-stage Small Cell Lung Cancer: The Impact of Thoracic and Brain Irradiation on Survival

Scotti, Vieri; Meattini, Icro; Franzese, Ciro; Saieva, Calogero; Bertocci, Silvia; Meacci, F.; Furfaro, Ilaria; Scartoni, D.; Cecchini, Silvia; Desideri, Isacco; Ferrari, Katia; Bruni, Alessio; Cardillo, Carla De Luca; Bastiani, P.; Agresti, Benedetta; Mangoni, Monica; Livi, Lorenzo; Biti, Giampaolo

doi:10.1177/1578.17206

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…Dedicated research on novel medical therapy is being fostered in an attempt to provide systemic treatment of SCLC. 27 Recently, the comprehensive genomic profile of 110 patients with SCLC was investigated; the investigation found evidence of biallelic inactivation of the tumor protein p53 gene (TP53) and the retinoblastoma 1 gene (RB1) in more than 90% of the cases and inactivating mutations in NOTCH family genes in 25% of them. 28 Overall, the study identified several novel candidate genes, some of which appear to be possible targets for more efficacious therapy for SCLC.…”

Section: Discussionmentioning

confidence: 99%

Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer

Silva

Galeone

Sverzellati

et al. 2016

Journal of Thoracic Oncology

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Section: Discussionmentioning

confidence: 99%

Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer

Silva

Galeone

Sverzellati

et al. 2016

Journal of Thoracic Oncology

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“…In addition to symptomatic BM, we found that the pre-PCI BM (BM immediately before PCI) was investigated in one study (36) and the first isolated BM event, rather than overall BM during the whole disease course, was analyzed in five studies (37)(38)(39)(40)(41). Both the first isolated BM and overall BM were reported in eight papers (28)(29)(30)(42)(43)(44)(45)(46) and showed that the first isolated BM incidence was lower than the overall BM incidence (Table 1). We only performed meta-analysis for overall BM because this is more relevant than a first isolated BM event.…”

Section: Study Selection and Quality Assessmentmentioning

confidence: 99%

“…We also found that the definition of time to BM events varied among studies, which indicates that heterogeneity also exists between RCTs: from the date of initial diagnosis (n = 19) (45, 49, 51, 53, 55, 58-62, 64, 66, 71, 72, 74-76, 78, 81); from the date of randomization (n = 16) (5, 9, 25, 26, 28-32, 34, 35, 41, 46, 68, 79, 80); from the date of treatment initiation (n = 6) (37,42,47,57,69,77); from the end of chemoradiotherapy (CRT) (n = 5) (44,47,67,70,78); from the date of PCI (n = 4) (27,48,54,65); from the date of chemotherapy initiation (n = 3) (33,38,39); from the date of TRT initiation (n = 2) (43,56); from the date of surgery (n = 1) (50); five studies had no information (36,40,52,63,73), two studies applied two definitions (47,78).…”

Section: Study Selection and Quality Assessmentmentioning

confidence: 99%

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

et al. 2022

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The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17–0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54–0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16–2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99–1.54; P = 0.06) tended to be a risk factor, and better PS (0–1) (HR = 0.66, 95% CI: 0.42–1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26–1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55–0.99; P = 0.04). Compared to M0–M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.

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“…One Japanese study did not show significant differences between the PCI and non-PCI groups in terms of OS ( P = 0.54) or PFS ( P = 0.72) [ 21 ]. An Italian retrospective study also reported that PCI did not seem to influence OS ( P = 0.21) or PFS ( P = 0.34) [ 22 ]. However, the current study used nationwide multicenter cohort data from the central lung cancer registry.…”

Section: Discussionmentioning

confidence: 99%

Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging

2022

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Background In the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI. Methods Data from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI. Results Of 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up. Conclusions In the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI.

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Radiotherapy Timing in the Treatment of Limited-stage Small Cell Lung Cancer: The Impact of Thoracic and Brain Irradiation on Survival

Abstract: Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

Cited by 7 publications

References 28 publications

Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer

Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer

Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging

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