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.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

ABSTRACT Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

PURPOSE: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. MATERIALS AND METHODS: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. RESULTS: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. CONCLUSION: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Retrospective Analysis.

PURPOSE: Extensive-stage small-cell lung cancer (esSCLC) is an incurable disease and represents a therapeutic challenge because of its poor prognosis. Studies in prophylactic cranial irradiation (PCI) in esSCLC have shown a decreased incidence of symptomatic brain metastases in patients who respond to systemic chemotherapy. However, its effect on overall survival is debatable. We evaluated the benefit of PCI in patients with esSCLC in terms of overall survival, progression-free survival, incidence of brain metastases, recurrence rate, and exposure to postrecurrence therapies. MATERIALS AND METHODS: We retrospectively reviewed electronic charts from patients diagnosed with esSCLC from 2008 to 2014 at our institution. All patients had negative baseline brain imaging before chemotherapy and PCI and received at least 4 cycles of platinum-based chemotherapy in the first-line setting without progressive disease on follow-up. PCI was performed at the discretion of the treating physician. Analyses were based on descriptive statistics. Survival curves were calculated by Kaplan-Meier method. RESULTS: Among 46 eligible patients, 16 (35%) received PCI and 30 (65%) did not. Compared with no PCI, PCI led to improved progression-free survival (median, 10.32 v 7.66 months; hazard ratio, 0.4521; 95% CI, 0.2481 to 0.8237; P < .001) and overall survival (median, 20.94 v 11.05 months; hazard ratio, 0.2655; 95% CI, 0.1420 to 0.4964; P < .001) as well as lower incidence of brain metastases (19% v 53%; P = .0273) and higher exposure to second-line chemotherapy (87% v 57%; P = .0479). CONCLUSION: Careful patient selection for PCI can improve not only brain metastases control and higher second-line chemotherapy exposure but also patient survival.

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. MATERIALS AND METHODS: An e-mail survey was sent to International Association for the Study of Lung Cancer members querying their personal perspectives and professional recommendations regarding PCI for limited-stage small-cell lung cancer. RESULTS: We received 295 responses. Most were from the United States (35%) and Europe (35%) and were radiation (45%) or medical (43%) oncologists. Of those responding, 88% and 50% reported they would recommend PCI to a 50- and 70-year-old patient, respectively. Also, 79% reported that they would wish to receive PCI if faced with this decision. The physicians who would have chosen PCI if faced with the decision were 27.6 and 12.9 times more likely to recommend PCI to a 50- and 70-year-old patient, respectively, than were physicians who would not undergo PCI themselves. Most of the respondents had positive responses to the proposed PDA. CONCLUSION: Physician bias appears to play a role in PCI counseling, and most physicians reported that the provided PDA was better than their present method for discussing PCI and would help patients make such value-laden choices.

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. PATIENTS AND METHODS: Metastatic SCLC patients without brain metastases were identified. To minimize treatment selection bias, patients with an overall survival (OS) < 6 months were excluded. Cox regression identified variables associated with OS. Patients were propensity score-matched on factors associated with receipt of PCI or OS. The effect of PCI on OS was examined using Kaplan-Meier estimates. RESULTS: In the overall cohort (n = 4257), treatment with PCI (n = 473) was associated with improved survival (hazard ratio, 0.66; 95% confidence interval, 0.60-0.74; P < .0001). Comparisons of propensity score-matched cohorts revealed a significant survival benefit for patients who received PCI in median OS (13.9 vs. 11.1 months; P < .0001), as well as 1- and 2-year OS (61.2% vs. 44.0% and 19.8% vs. 11.5%, respectively; P < .0001). This survival benefit persisted even after excluding patients who survived < 9 months (median: 15.3 vs. 12.9 months; P < .0001). In multivariable analysis, predictors of receipt of PCI were Caucasian race, younger age, and lower Charlson-Deyo score. CONCLUSION: Using a modern population-based data set, we showed that metastatic SCLC patients treated with PCI have significantly improved OS. This large retrospective study helps address the conflicting prospective data.

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.

Dosimetric definitions of total lung volumes in calculating parameters predictive for radiation-induced pneumonitis.

OBJECTIVES: The volume of normal lung receiving 20 Gy (V20) and the mean lung dose (MLD) represent dosimetric parameters used for identifying risk of radiation pneumonitis. However, the total lung volume for dosimetric analysis has been defined differently. Herein we investigate to quantify the dosimetric differences when analysis is based on either definition (ie, excluding planning target volume [PTV] vs. gross tumor volume [GTV] from the total bilateral lung volume). METHODS: Sixty-one patients with lung cancer who had undergone definitive radiation therapy were retrospectively reviewed. Dosimetric parameters were calculated when excluding GTV or PTV from the total bilateral lung volume. RESULTS: Median GTV to PTV margin was 1.3 cm (range, 0.4 to 3.8 cm). Median heterogeneity-corrected RT dose was 74 Gy with the median GTV of 110 mL (range, 13.79 to 665.8 mL) and the median PTV of 346 mL (range, 39.8 to 1258 mL).The MLD, V5, V10, V20, and V30 were all slightly higher and significant when excluding GTV from the total bilateral lung volume compared with similar dosimetric parameters when excluding PTV (P<0.001). Average MLD was 14.8 and 16.7 Gy when excluding PTV and GTV, respectively. Mean V5, V10, V20, and V30 were 49.8%, 38%, 25%, and 18.8% when excluding PTV versus 51.3%, 40%, 28%, and 21.5% when excluding GTV. There were 4 patients with clinical pneumonitis and all had the V20>23% when excluding the PTV versus the V20>27% when excluding the GTV from total bilateral lung volume. CONCLUSIONS: A small but significant difference exists between the 2 approaches used to calculate dosimetric variables for lung dose. This difference should be taken into account when comparing dosimetric information between different institutions and when optimizing treatment plans.

Effect of radiotherapy on the treatment of patients with extensive stage small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive disease, in which more than 80% of patients present distant metastases at the time of first diagnosis. Chemotherapy is considered as the main treatment of extensive disease of SCLC (ED-SCLC), while the role of radiotherapy in the treatment of ED-SCLC is controversial. A case-control study was undertaken of patients diagnosed as ED-SCLC between 2004 and 2010. Fifty-eight patients with overall survival (OS) over 1 year were chosen, and another 58 patients with OS less than 1 year were selected as the control group, with the age, gender, metastasis or no metastasis of the liver, and the response after the first line of chemotherapy matched. The 1-year, 2-year, 3-year, and median OS of the 75 ED-SCLC patients who received radiation were 81.47, 29.89, 22.77%, and 17 months, respectively, and were 61.18, 23.53, 0%, and 16 months, respectively, for patients who did not receive radiation. The χ(2) test and odds ratio (OR) estimate demonstrated that these differences were statistically significant (χ(2) = 6.38, P = 0.0116; OR = 2.74, 95% confidence interval = 1.24-6.05). These results show that radiotherapy also plays a role in responding patients with extensive stage of SCLC.

Thirty years of prophylactic cranial irradiation in patients with small cell lung cancer: a meta-analysis of randomized clinical trials.

OBJECTIVE: To determine the role of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). METHODS: We searched various databases, selecting randomized clinical trials published in journals or conference proceedings within the last 30 years and investigating the role of PCI in the mortality of patients with SCLC, submitted to PCI or not. RESULTS: Sixteen randomized clinical trials, collectively involving 1,983 patients, were considered eligible for inclusion. Of those 1,983 patients, 1,021 were submitted to PCI and 962 were not. Overall mortality was 4.4% lower in the patients submitted to PCI than in those who were not (OR = 0.73; 95% CI: 0.57-0.97; p = 0.01), especially among the patients showing a complete response after induction chemotherapy (OR = 0.68; 95% CI: 0.50-0.93; p = 0.02) and in those submitted to PCI after that treatment (OR = 0.68; 95% CI: 0.49-0.94; p = 0.03). That decrease did not correlate with the stage of the disease: limited disease (OR = 0.73; 95% CI: 0.55-0.97; p = 0.03); and extensive disease (OR = 0.48; 95% CI: 0.26-0.87; p = 0.02). CONCLUSIONS: Our findings suggest that PCI decreases mortality in patients with SCLC, especially in those showing a complete response after induction chemotherapy and in those submitted to PCI after that treatment, regardless of the stage of the disease.

Trinta anos de irradiação craniana profilática em pacientes com câncer de pulmão de pequenas células: uma meta-análise de ensaios clínicos randomizados / Thirty years of prophylactic cranial irradiation in patients with small cell lung cancer: a meta-analysis of randomized clinical trials

OBJETIVO: Determinar o papel da irradiação craniana profilática (ICP) em pacientes com câncer de pulmão de pequenas células (CPPC). MÉTODOS: Foi realizada uma pesquisa para selecionar estudos em várias bases de dados, com os seguintes critérios de inclusão: ensaios clínicos randomizados, publicados em periódicos ou em anais de congressos nos últimos 30 anos, avaliando o papel da ICP sobre a mortalidade em pacientes com CPPC que receberam ICP ou não. RESULTADOS: Foram considerados elegíveis 16 estudos clínicos randomizados, os quais envolveram 1.983 pacientes. Entre esses, 1.021 foram submetidos a ICP e 962 não foram submetidos a ICP. Houve uma redução absoluta na mortalidade de 4,4% nos pacientes submetidos a ICP quando comparados com o grupo controle (OR = 0,73; IC95%: 0,57-0,97; p = 0,01), principalmente naqueles com resposta completa à quimioterapia de indução (OR = 0,68; IC95%: 0,50-0,93; p = 0.02) e que foram submetidos a ICP ao término desse tratamento (OR = 0,68; IC95%: 0,49-0,94; p = 0.03). A diminuição da mortalidade não se correlacionou com o estádio da doença: doença limitada (OR = 0,73; IC95%: 0,55-0,97; p = 0,03) e doença extensa (OR = 0,48; IC95%: 0,26-0,87; p = 0,02). CONCLUSÕES: Nossos achados sugerem que a ICP reduz a mortalidade em pacientes com CPPC, principalmente naqueles com resposta a quimioterapia de indução e que sejam submetidos a ICP ao término desse tratamento, independentemente do estadiamento da doença.

OBJECTIVE: To determine the role of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). METHODS: We searched various databases, selecting randomized clinical trials published in journals or conference proceedings within the last 30 years and investigating the role of PCI in the mortality of patients with SCLC, submitted to PCI or not. RESULTS: Sixteen randomized clinical trials, collectively involving 1,983 patients, were considered eligible for inclusion. Of those 1,983 patients, 1,021 were submitted to PCI and 962 were not. Overall mortality was 4.4% lower in the patients submitted to PCI than in those who were not (OR = 0.73; 95% CI: 0.57-0.97; p = 0.01), especially among the patients showing a complete response after induction chemotherapy (OR = 0.68; 95% CI: 0.50-0.93; p = 0.02) and in those submitted to PCI after that treatment (OR = 0.68; 95% CI: 0.49-0.94; p = 0.03). That decrease did not correlate with the stage of the disease: limited disease (OR = 0.73; 95% CI: 0.55-0.97; p = 0.03); and extensive disease (OR = 0.48; 95% CI: 0.26-0.87; p = 0.02). CONCLUSIONS: Our findings suggest that PCI decreases mortality in patients with SCLC, especially in those showing a complete response after induction chemotherapy and in those submitted to PCI after that treatment, regardless of the stage of the disease.