Radiotherapy For Small Cell Lung Cancer Research Articles

Outcomes of Prophylactic Cranial Radiotherapy in Small-Cell Lung Cancer: A Retrospective Analysis

Outcomes of Prophylactic Cranial Radiotherapy in Small-Cell Lung Cancer: A Retrospective Analysis

Prospective Evaluation of Limited-Stage Small Cell Lung Cancer Radiotherapy Fractionation Regimen Usage and Acute Toxicity in a Large Statewide Quality Collaborative

National guidelines on limited stage small cell lung cancer (LS-SCLC) treatment give preference to a hyperfractionated regimen of 45 Gy/30 fractions delivered twice-daily, however use of this regimen is uncommon compared to once-daily regimens. The purpose of this study was to characterize the LS-SCLC fractionation regimens used throughout a statewide collaborative, analyze patient and treatment factors associated with these regimens, and describe real-world acute toxicity profiles of once- and twice-daily RT regimens. Demographic, clinical, and treatment data along with physician toxicity and patient-reported outcomes were prospectively collected by 29 institutions within the [quality consortium] between 2012 and 2021 for patients with LS-SCLC. We modeled the influence of RT fractionation and other patient-level variables clustered by treatment site on the odds of a treatment break specifically due to toxicity with multilevel logistic regression. Common Terminology Criteria for Adverse Events, version 4.0, incident Grade 2 or worse toxicity was longitudinally compared between regimens. There were 78 patients (15.6% overall) treated with twice-daily RT and 421 patients treated with once-daily RT. Patients receiving twice-daily RT were more likely to be married/living with someone (65% vs 51%, p=0.019) and to have no major comorbidities (24% vs 10%, p=0.017). Once-daily RT fractionation toxicity peaked during RT and twice-daily toxicity peaked within 1 month after RT. After stratifying by treatment site and adjusting for patient-level variables, once-daily treated patients had a 4.11 (95% confidence interval 1.31-12.87) higher odds of treatment break specifically due to toxicity than twice-daily treated patients. Hyperfractionation for LS-SCLC remains infrequently prescribed despite the lack of evidence demonstrating superior efficacy or lower toxicity of once-daily RT. With peak acute toxicity after RT and lower likelihood of a treatment break with twice-daily fractionation in real-word practice, providers may start utilizing hyperfractionated RT more frequently.

The Construction and Validation of Nomogram to Predict the Prognosis with Small-Cell Lung Cancer Followed Surgery.

Simple SummaryThe therapeutic effect of postoperative radiotherapy for small-cell lung cancer (SCLC) patients with limited stage remained unclear. The aim of this retrospective study was to construct and validate a nomogram to assess the prognosis of small-cell lung cancer patients followed surgery in a large cohort (882 patients) which involved patients from Shanghai Pulmonary Hospital and the Surveillance, Epidemiology and End Results database. The nomogram derived from the training cohort achieved good predictive ability and could discriminate low- and high-risk subgroups in four cohorts. Postoperative radiotherapy promoted survival for high-risk patients but had little effect on low-risk patients. Moreover, by subgroup analysis based on the N stage, we suggested that N2 patients in the high-risk subgroup could benefit more from postoperative radiotherapy. Therefore, our nomogram might help with clinical decisions on the strategy of postoperative radiotherapy for SCLC patients.This study constructed and validated a prognostic model to evaluate the survival of small-cell lung cancer (SCLC) patients following surgery, and shed light on the strategy of postoperative radiotherapy. A total of 882 patients from Shanghai Pulmonary Hospital and the Surveillance, Epidemiology and End Results database after lung resection were selected. Multivariable Cox analysis was used to identify the indicators affecting long-term survival in patients. A nomogram was constructed to predict the prognosis of eligible patients. Indices of concordance (C-index) was used to access the predictive ability of cancer-specific survival (CSS) for the prognostic model. CSS discrimination in the prognostic model was comparable in the training and validation cohorts (C-index = 0.637[NORAD-T], 0.660[NORAD-V], 0.656[RAD] and 0.627[our hospital], respectively. Stratification based on the cutoff value of the nomogram yielded low- and high-risk subgroups in four cohorts. For patients in the high-risk group, postoperative radiotherapy was considered a survival-promoting strategy (unadjusted HR 0.641, 95% CI 0.469–0.876, p = 0.0046). In the low-risk group, however, the implementation of radiotherapy barely had an influence on CSS. In conclusion, the nomogram we constructed and validated could predict the prognosis of SCLC patients followed surgery and identify high-risk patients who were likely to benefit from postoperative radiotherapy.

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

BackgroundIn 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.MethodsData 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.ResultsOf 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.ConclusionsIn 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.

Correlation of the controlling nutritional status score and the prognostic nutritional index with the prognosis of patients treated with radiotherapy for small-cell lung cancer.

We aimed to explore the associations between the controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and prognostic outcomes in patients with small-cell lung cancer (SCLC) receiving radiotherapy. A total of 93 SCLC patients who received radiotherapy at the hematology department in the First Affiliated Hospital of Hainan Medical University were retrospectively included in this analysis. Patient CONUT and PNI values were calculated. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cut-off, the area under the curve (AUC), sensitivity, and specificity of CONUT and PNI in discriminating patient outcomes. Kaplan-Meier curve analysis was performed, and overall survival (OS) was compared for patients with CONUT >3 and ≤3, or those with PNI >47.7 and ≤47.7. Univariate and multivariate analysis using the Cox proportional hazard model was performed to identify the risk factors for patient death. The AUCs for CONUT and PNI were 0.95 and 0.82, respectively. The CONUT results indicated that patient OS decreased significantly from normal to mildly malnourished. Meanwhile, the OS for moderately malnourished patient decreased to severely malnourished (P for trend <0.001). Patients with CONUT >3 or PNI ≤47.7 had significantly shorter OS than those with CONUT ≤3 (median survival time 12 vs. 23 months; P<0.001) or with PNI >47.7 (median survival time 20 vs. 15 months; P=0.010). Multivariate analysis indicated that the TNM stage [hazard ratio (HR) =1.21; 95% confidence interval (CI): 1.03-1.66], CONUT score (HR =2.33; 95% CI: 1.76-3.91), and PNI ≤47.7 (HR =1.33; 95% CI: 1.09-1.99) were independent prognostic indicators for patient death. The CONUT and PNI were potential indicators for the outcome of patients with SCLC. CONUT >3 or PNI ≤47.7 indicated an unfavorable prognosis for SCLC patients.

Prophylactic cranial irradiation in SCLC.

Prophylactic cranial irradiation (PCI) has well established place in therapy for patients with limited-disease small cell lung cancer who responded to treatment. The data from randomized trials document that PCI reduces brain metastases rate from approximately 60% to 30%, and increases 3-year overall survival by approximately 5%. Currently, the dose of 25 Gy in 10 fractions is considered as standard. In attempt to reduce neuropsychological sequelae attributable to PCI hippocampal sparing techniques are employed. The existing studies suggest the benefit of hippocampal sparing in limiting memory and higher neurocognitive function losses, but with a risk of failures in the spared region. Ongoing studies will further validate the role of hippocampal sparing, both in terms of toxicity reduction and metastases prevention. PCI for patients who have undergone resection for stage I small cell lung cancer (SCLC) is not recommended, PCI may be, however, associated with a favourable outcome in SCLC patients who have undergone complete surgery in stages II−III. The role of PCI in extensive-disease (ED) SCLC has been evolving. Most recent evidence indicate that PCI is controversial in ED patients with response to initial chemotherapy and absence of brain metastases confirmed by contrast-enhanced MRI. The patients who do not receive PCI, must, however, receive periodic MRI examination during follow-up, i.e., remain under active surveillance with access to radiotherapy at brain relapse. The assessment of safety and effectiveness of hippocampal-sparing PCI, with or without drug neuroprotection in consideration of diverse combinations of radiotherapy, chemotherapy and immunotherapy create a background for future directions of research.

Evaluation of Hippo Pathway and CD133 in Radiation Resistance in Small-Cell Lung Cancer.

Although the Hippo pathway and CD133 have been reported to play pertinent roles in a variety of cancer, knowledge about their contribution to radiation resistance in small-cell lung cancer (SCLC) is limited. In this first-of-a-kind study, we have reported the expression of key Hippo pathway proteins in SCLC patients by immunohistochemical staining. We assessed the involvement of yes-associated protein 1 (YAP1) in radiation resistance by Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, we analysed the impact of CD133 on radiotherapy for SCLC. The mammalian Ste20-like serine/threonine kinase 2(MST2), pMST2, and pYAP1 in the Hippo pathway were not significantly associated with the disease stage and survival time in patients with SCLC. However, the pYAP1 expression showed some significance in the “YAP/TAZ subgroup” of SCLC patients. The proportion of CD133 in the SCLC cells was controlled by the YAP1 expression. The CD133 and YAP1 levels were significantly correlation with each other in tissues of SCLC patients. We sorted and isolated the CD133+ and CD133−cells in H69 and found that the cell surface glycoprotein may be associated with the radiation resistance of SCLC.In summary, we have firstly reported the expression of key Hippo pathway proteins in SCLC patients. Furthermore, we also identified that CD133 may be controlled by the expression of YAP1 in the Hippo pathway and that CD133 may be associated with the radiation resistance of SCLC.

Prophylactic Cranial Irradiation for Small-Cell Lung Cancer: Time for a Reassessment.

Prophylactic cranial irradiation (PCI) has been an accepted part of the management of both limited and small-cell lung cancer; however, the data that support its use in limited-stage disease is based on an analysis of trials done before currently accepted approaches to staging (i.e., brain MRI and/or PET scanning) were available. For extensive disease, data are available from two randomized studies that are in direct conflict. This article explores the basic rationale for PCI and the evidence indicating that it is time to readdress the question of its routine use.

Current and future strategies in radiotherapy for small-cell lung cancer

Radiotherapy is a critical component of multimodality treatment of SCLC. This article can help physicians to improve medical knowledge and find better ways to treat their SCLC patients.

Abstract 3925: A screen for epigenetic radiosensitizers in small cell lung cancer

Abstract Objective: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy. Post-platinum-based chemotherapy, rapid relapse of chemoresistant tumor is commonly seen. Unidentifiable causative mutations and from reversible nature of acquired chemoresistance, involvement of epigenetic switch regulating SCLC progression is evident. Aim of this screen is to identify epigenetic modifiers that could sensitize SCLC cells to ionizing radiation (IR). Methods: To recapitulate molecular diversity of patients, a range of SCLC cell lines (n=10) from classic or variant and ASCL1 or NeuroD1 sub-groups, driven by varying MYC family amplifications were picked. Short term viability experiment was setup in 3 groups: (a) Epigenetic monotherapy: cells were screened with 10 epigenetic modifiers (0 to 10 µM). (b) IR monotherapy: cells were irradiated from 0 to 8 gy. (c) Combination therapy: cells were treated with different doses of epigenetic probes and IR. Radiosensitization was measured as dose modifying factor at SF63 for each epigenetic modulator. Results: (a) Epigenetic monotherapy: All 10 cell lines were responsive to GSK-J4 (KDMi, IC50 3.1-0.9 µM), SAHA (HDACi, IC50 2.9-0.79 µM) and JIB04 (Jumonji KDMi, IC50 74-2.4 nM). Other interesting epi-probe to which 9/10 cell lines responded was JQ1 (BET-BRDi, IC50 5.7 to 0.15 µM, except SBC-5). Compounds with lesser universal potency were MS023 (PRMTi), UNC0642 (G9a/GLPi) and UNC1999 (EZH2i). All cell lines were irresponsive to PFI3 (SMARCA2/4 BRDi), BAY598 (SMYD2 MTi) and OICR-9429 (WDR5i). (b) IR monotherapy: All 10 cell lines demonstrated different sensitivities to 4 days of IR. They’re ranked in descending order of radiosensitivity as H446, H82, SHP77, LX22, H889, H1092, H196, H69, SBC5, H526. (c) Epi-probes + IR combination therapy: Epi-probes ranked in descending order of number of cell lines they radiosensitized are JQ1, JIB-04, GSK-J4, SAHA, UNC0642, BAY598, MS023, UNC1999, OICR9429 and PFI3. Interestingly, drugs that demonstrated potency as a single agent did not necessarily radiosensitize the cell lines. On the contrary, certain epi-probes that were ineffective as monotherapy radiosensitized a few of the cell lines. H82 is a sensitive cell line which was radiosensitized by all epi-probes used. Conclusions: This screen shows that treating cells with IR in conjunction with epigenetic modifiers may potentially improve therapeutic efficacy of radiotherapy in SCLC. Further validation is being done with long term colonogenic assays followed by in vivo studies for the potent radiosensitizing candidate drugs. It would be therapeutically relevant to correlate the probability of radiosensitization by an epi-probe with the molecular profile of the patients for more predictive targeted therapeutics. Citation Format: Mansi K. Aparnathi, Lifang Song, Ratheesh Subramaniam, Richard Marcellus, Rima Al-awar, Benjamin H. Lok. A screen for epigenetic radiosensitizers in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3925.

Utility of Molecular Imaging with 2-Deoxy-2-[Fluorine-18] Fluoro-DGlucose Positron Emission Tomography (18F-FDG PET) for Small Cell Lung Cancer (SCLC): A Radiation Oncology Perspective.

Although accounting for a relatively small proportion of all lung cancers, small cell lung cancer (SCLC) remains to be a global health concern with grim prognosis. Radiotherapy (RT) plays a central role in SCLC management either as a curative or palliative therapeutic strategy. There has been considerable progress in RT of SCLC, thanks to improved imaging techniques leading to accurate target localization for precise delivery of RT. Positron emission tomography (PET) is increasingly used in oncology practice as a non-invasive molecular imaging modality. Herein, we review the utility of molecular imaging with 2-deoxy-2-[fluorine-18] fluoro-Dglucose PET (18F-FDG PET) for SCLC from a radiation oncology perspective. There has been extensive research on the utility of PET for SCLC in terms of improved staging, restaging, treatment designation, patient selection for curative/palliative intent, target localization, response assessment, detection of residual/recurrent disease, and prediction of treatment outcomes. PET provides useful functional information as a non-invasive molecular imaging modality and may be exploited to improve the management of patients with SCLC. Incorporation of PET/CT in staging of patients with SCLC may aid in optimal treatment allocation for an improved therapeutic ratio. From a radiation oncology perspective, combination of functional and anatomical data provided by integrated PET/CT improves discrimination between atelectasis and tumor, and assists in the designation of RT portals with its high accuracy to detect intrathoracic tumor and nodal disease. Utility of molecular imaging for SCLC should be further investigated in prospective randomized trials to acquire a higher level of evidence for future potential applications of PET.

Talazoparib Is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and Xenografts.

Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a critical need for novel therapies. Our goal was to determine whether PARP inhibition could sensitize SCLC cells to ionizing radiation (IR) and if so, to determine the contribution of PARP trapping to radiosensitization.Experimental Design: Short-term viability assays and clonogenic survival assays (CSA) were used to assess radiosensitization in 6 SCLC cell lines. Doses of veliparib and talazoparib with equivalent enzymatic inhibitory activity but differing PARP trapping activity were identified and compared in CSAs. Talazoparib, IR, and their combination were tested in three patient-derived xenograft (PDX) models.Results: Talazoparib radiosensitized 5 of 6 SCLC cell lines in short-term viability assays and confirmed in 3 of 3 cell lines by CSAs. Concentrations of 200 nmol/L talazoparib and 1,600 nmol/L veliparib similarly inhibited PAR polymerization; however, talazoparib exhibited greater PARP trapping activity that was associated with superior radiosensitization. This observation further correlated with an increased number of double-stranded DNA breaks induced by talazoparib as compared with veliparib. Finally, a dose of 0.2 mg/kg talazoparib in vivo caused tumor growth inhibition in combination with IR but not as a single agent in 3 SCLC PDX models.Conclusions: PARP inhibition effectively sensitizes SCLC cell lines and PDXs to IR, and PARP trapping activity enhances this effect. PARP inhibitors, especially those with high PARP trapping activity, may provide a powerful tool to improve the efficacy of radiotherapy in SCLC. Clin Cancer Res; 24(20); 5143-52. ©2018 AACR.

Prophylactic cranial irradiation in small-cell lung cancer: update on patient selection, efficacy and outcomes.

Over 10% of small-cell lung cancer (SCLC) patients have brain metastases (BM) at initial diagnosis; more than 50% will develop BM within 2 years. BM are detected in up to 80% of all patients at autopsy. After primary treatment, prophylactic cranial irradiation (PCI) has been established as standard of care in SCLC patients responding to initial therapy. Based on level I evidence, PCI significantly decreases the risk of intracranial relapse and shows a modest survival benefit after 3 years. However, the role of PCI in defined patient subgroups such as resected SCLC, elderly and extensive stage patients with access to magnetic resonance imaging surveillance and stereotactic radiotherapy is yet to be fully clarified. Furthermore, strategies to effective prevention of neurocognitive decline after PCI remain unclear. All these factors significantly impact treatment decision making and should be evaluated in prospective settings. New concepts such as hippocampal avoidance and drug neuroprotection prevent chronic neurocognitive effects reducing treatment-related side effects of PCI. The aim of this review is to present a summary and update of the latest evidence for patient selection, efficacy and outcome of PCI.

MTE 04.01 Role of Radiotherapy in Multimodality Treatment for SCLC

Major advances in SCLC include improvements in RT techniques, the use of prophylactic cranial irradiation (PCI) for all stages of SCLC and the improved combination of chemotherapy and RT (Califano). The role of thoracic radiotherapy is well established in the management of stage I-III SCLC (Pignon). There is increasing evidence in the literature in favor of early concurrent chemo-radiotherapy, and a standard of care for patients with a good performance status is twice-daily thoracic radiotherapy (45 Gy in 3 weeks) with concurrent cisplatin and etoposide (Turrisi). Although current clinical trials are exploring the efficacy of new chemotherapeutic strategies, essential questions related to the optimization of thoracic radiotherapy and the benefit of chemo-radiotherapy in sub-groups of patients remain unanswered, e.g. the elderly (Blackhall). The CONVERT trial (twice-daily (BD) versus once daily (OD) radiotherapy given concurrently with chemotherapy in stage I-III SCLC) was reported at ASCO 2016 (Faivre-Finn). OD RT did not result in a superior survival or worse toxicity than BD RT (two-year survival was 56% (95% CI 50-61) vs 51% (95% CI 45-57), p= 0.14). The survival for both regimens was higher than previously reported and using modern RT techniques radiation toxicities were lower than expected. In the stage IV setting the CREST trial as shown that the addition on thoracic RT to chemotherapy and PCI leads to a significant reduction in intrathoracic recurrence and, despite the lack of a significant benefit in overall survival at 1 year, there were significant improvements in overall survival at 2 years (Slotman). It is crucial that patients with SCLC are given the opportunity to participate in clinical research in order to continue to improve the survival of this disease. Molecular studies are ongoing aiming to gain improved insight into the molecular biology of SCLC, discover and/or validate candidate biomarkers for response, resistance to or toxicity of systemic treatment and radiation. It is expected that this understanding will lead to the development of targeted therapies that will not only prove efficacious but also less toxic than more conventional chemotherapy treatments. In combination with advanced RT techniques and better imaging, it is hoped that the rates of long term survivors will increase significantly in the future. We will address the following controversial questions: 1) Should BDRT be considered standard of care in stage I-III SCLC? 2) Role of CTRT in stage I-II SCLC 3) Role of CTRT in elderly patients with LS-SCLC 4) Should thoracic RT be given to all patients with stage IV SCLC? 1. Califano R, et al. Management of small cell lung cancer: recent developments for optimal care. Drugs. 2012 5;72(4):471-90. 2. Pignon JP, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992; 327:1618-1622. 3. Turrisi AT, et al. Twice daily compared to once-daily thoracic radiotherapy in limited-stage small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999; 340: 265-271. 4. Auperin A, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341(7):476-84. 5. Blanchard P, et al. Prophylactic cranial irradiation in lung cancer. Curr Opin Oncol. 2010; 22(2):94-101. 6. Blackhall F et al. Treatment of limited small cell lung cancer: an old or new challenge? Curr Opin Oncol. 2011; 23(2):158-62. 7. Faivre-Finn C, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18(8):1116-1125. 8. Slotman BJ, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 3;385(9962):36-42. 9. Slotman BJ, et al. Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial. Lung Cancer. 2017; 108:150-153. small-cell, radiotherapy, thoracic

Recent developments in radiotherapy for small-cell lung cancer: a review by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard treatment in patients with limited-stage disease is radiotherapy combined with chemotherapy. In extensive SCLC, the importance of consolidation thoracic radiotherapy in patients with a good treatment response has become increasingly recognized. In both limited and extensive disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer (NSCLC). Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present study we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway in order to identify future trends.

ED14.02 Thoracic Radiotherapy of SCLC

ED14.02 Thoracic Radiotherapy of SCLC

Advances in radiotherapy for small cell lung cancer in the East and West

Small cell lung cancer (SCLC) is one common type of lung cancer in China. No remarkable progress has been made in systemic therapy for SCLC since the 90’s. However, there are some advances in radiotherapy (RT) for SCLC, which make it possible to improve treatment outcomes of SCLC. Those advances are mainly made in thoracic RT and prophylactic cranial irradiation for extensive-stage SCLC, radiation dose and technology of thoracic RT for limited-stage SCLC, and significance of prophylactic cranial irradiation for early-stage SCLC. The paper reviews the research advances in the East and West to provide some help and references for readers. Key words: Carcinoma, small cell lung/radiotherapy; Prophylactic cranial irradiation

Neurotoxicity due to prophylactic cranial irradiation for small-cell lung cancer: A retrospective analysis.

Prophylactic cranial irradiation (PCI) is an established part of standard therapy for small-cell lung cancer (SCLC). However, the concerns regarding severe late neurotoxicity following PCI have not yet been systematically investigated. Therefore, the aim of this study was to investigate the neurocognitive functioning of SCLC patients treated with PCI. Limited-disease SCLC (LD-SCLC) patients (n=40) treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital (Tokyo, Japan) between January, 2004 and December, 2011 were retrospectively reviewed. A total of 18 LD-SCLC patients were treated with PCI (median age, 65.5 years; range, 52-75 years), whereas 22 LD-SCLC patients did not receive PCI (median age, 65.5 years; range, 57-84 years). The median follow-up for PCI and non-PCI patients was 22 months (range, 4-85 months) and 14.5 months (range, 2-49 months), respectively. Brain metastases occurred in 6 (33%) PCI patients and 11 (50%) non-PCI patients. In the PCI group, dementia occurred in 5 of the 12 PCI patients without brain metastases (42%, 3-40 months after PCI) and in 1 of the 11 non-PCI patients without brain metastases (9%, 4 months after initial treatment). The frequency of dementia in the PCI group was significantly higher compared with that in the non-PCI group (P=0.0357). In the PCI group, all the patients who developed dementia were aged >65 years (range, 66-75 years). Gait disturbance appeared in 25% of the PCI patients without brain metastases (9-27 months after PCI); these patients were also aged >65 years. Patients aged >65 years were significantly more likely to develop dementia (P=0.0028) and gait disturbance (P=0.0291). Therefore, neurotoxicity due to PCI tends to appear more frequently in older patients.

Small-cell lung cancer: local therapy for a systemic disease?

In The Lancet, Ben Slotman and colleagues report the results of a phase 3 trial of thoracic radiotherapy for small-cell lung cancer. 1 Slotman BJ van Tinteren H Praag JO et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2014; (published online Sept 14.)http://dx.doi.org/10.1016/S0140-6736(14)61085-0 PubMed Google Scholar The trial is the most recent in a long line of studies showing that local radiotherapy benefits patients with small-cell lung cancer, a disease characterised by a bulky intrathoracic mass at presentation, a high propensity for metastasis, and high chemosensitivity, but with a poor prognosis. 2 van Meerbeeck JP Fennell DA De Ruysscher DK Small-cell lung cancer. Lancet. 2011; 378: 1741-1755 Summary Full Text Full Text PDF PubMed Scopus (690) Google Scholar Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trialThoracic radiotherapy in addition to prophylactic cranial irradiation should be considered for all patients with ES-SCLC who respond to chemotherapy. Full-Text PDF Open Access

Circulating tumor cells correlate with recurrence in stage III small-cell lung cancer after systemic chemoradiotherapy and prophylactic cranial irradiation.

We investigated the correlation between circulating tumor cells and the incidence of brain metastases as a first site of recurrence among patients with small-cell lung cancer after systemic chemoradiotherapy and prophylactic cranial irradiation. In addition, we assessed the contribution of circulating tumor cells for planning the appropriate total dose of prophylactic cranial irradiation for small-cell lung cancer. Patients (n = 112) with diagnosed Stage III small-cell lung cancer were treated with four cycles of platinum-based regimen and concurrent chest irradiation, and then prophylactic cranial irradiation. Blood samples for circulating tumor cell analysis were obtained before the initiation of chemotherapy and after the first and fourth cycle of chemotherapy. Circulating tumor cells after the first cycle of chemotherapy correlated with tumor response after completion of chemotherapy (P = 0.012). Patients with brain as the first site suffered a higher rate of further metastases to other organs, and local recurrence, compared with those whose first site was the other organs (P < 0.001), and their survival rates were worse. Circulating tumor cells at baseline were the sole independent prognostic factor for specific progression-free survival. Receiver operating characteristic curves based on median specific progression-free survival revealed a circulating tumor cell cutoff at baseline of 218, and circulating tumor cells ≤218 at baseline correlated with significantly higher progression-free survival (P = 0.007), specific progression-free survival (P = 0.001) and overall survival (P = 0.001). Circulating tumor cells prior to the initiation of chemotherapy are a valuable predictor of specific progression-free survival in Stage III small-cell lung cancer. For patients with circulating tumor cells >218, prophylactic cranial irradiation at a total dose of 30 Gy in 15 fractions is insufficient.