Prophylactic Cranial Irradiation Reduces Brain Metastases and Improves Overall Survival in High-Risk Metastatic Non-Small Cell Lung Cancer Patients: A Randomized phase 2 Study (PRoT-BM trial).

PURPOSE: To date, studies regarding the use of prophylactic cranial irradiation (PCI) versus standard of care (SoC) for patients with non-small cell lung cancer (NSCLC) have not shown a significant effect in terms of overall survival (OS). Additionally, the effect of PCI among high-risk patients has been scarcely studied. The objective of this randomized phase 2 study was to evaluate the role of PCI in a population of patients at high risk for development of brain metastases (BM). METHODS AND MATERIALS: Eligible patients had histologically confirmed NSCLC without baseline BM, harboring epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels at the time of diagnosis. Participants received systemic therapy according to molecular status, those without progressive disease were then assigned to receive SoC or SoC + PCI (25 Gy in 10 fractions). The primary outcome was cumulative incidence of brain metastases (CBM). The secondary endpoints included progression-free survival and OS. Quality of life and neurocognitive function are discussed in a separate article (Clinicaltrials.gov: NCT01603849). RESULTS: From May 2012 to December 2017, 84 patients were enrolled in the study, with 41 patients allocated to receive PCI and 43 received SoC. Patients allocated to receive PCI had a CBM at 24 months of 7% versus 38% in those allocated to the SoC arm. PCI was associated with a hazard ratio of 0.12 (95% confidence interval, 0.035-0.42) for developing BM. A benefit in OS was also observed (64.5 vs 19.8 months; hazard ratio: 0.41 (95% confidence interval, 0.22-0.78; P =∙007). CONCLUSIONS: Among a selected population at high risk for developing BM, PCI significantly decreased CBM in addition to increasing progression-free survival and OS. To our knowledge, this is the first study to evaluate PCI in epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels in patients with NSCLC, showing a significant improvement in CBM. This relevant information should be of particular importance in the context of patients without access to third-generation targeted agents. Further studies are warranted to ascertain this effect.

Consolidative stereotactic ablative radiotherapy (SABR) to intrapulmonary lesions is associated with prolonged progression-free survival and overall survival in oligometastatic NSCLC patients: A prospective phase 2 study.

OBJECTIVES: Stereotactic Ablative Radiotherapy (SABR) has shown high rates of local control and prolonged survival in early-stage non-small cell lung cancer (NSCLC), though its role in oligometastatic disease is undefined. This study aimed to evaluate SABR as a local consolidative therapy (LCT) in oligometastatic NSCLC patients. METHODS: In this prospective, single-arm phase 2 trial, we sought to evaluate SABR in patients with stage IV NSCLC, with ≤ five lesions, including the primary tumor. Patients received initial systemic therapy according to international guidelines. Patients without progression after front-line therapy (two months of targeted therapy and ≥ four cycles of chemotherapy) were evaluated by an 18F-FDG-PET/CT to receive consolidative SABR (45-60 Gy in 3-5 fractions) to the primary and all intrapulmonary metastatic sites. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. RESULTS: A total of 47 patients were included. Mean age was 58.9 years, 59.6 % were female, 87.2 % had adenocarcinoma histology, and the contralateral lung was the main site of metastases in 42.6 %. All patients received systemic front-line therapy, chemotherapy in 61.7 %, and a tyrosine kinase inhibitor (TKI) in 38.3 %. Disease control rate (DCR) and complete metabolic response (CMR) to SABR were 93.6 % and 70.2 %. Median PFS was 34.3 months (95 %CI; 31.1-38.8) for the total cohort; patients with a CMR had a median PFS of 53.9 monthsvs.31.9 months in those without CMR (p = 0.011). Median OS was not reached.Grade 1, 2, and 3 pneumonitis were observed in 79.5 % (31/39), 12.8 % (5/39) and 7.7 % (3/39), respectively. No grade ≥4 toxicities were observed. CONCLUSION: The use of SABR as LCT in oligometastatic NSCLC patients was well tolerated and showed favorable results regarding PFS and OS compared with historical data. The benefit was significantly higher in patients who reached a CMR as assessed by 18F-FDG-PET/CT.

Locoregional control and toxicity after pleurectomy/decortication and intensity-modulated pleural radiation therapy in patients with malignant pleural mesothelioma.

BACKGROUND: Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM. METHODS: We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields. RESULTS: A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months. CONCLUSIONS: Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.

A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma.

PURPOSE: Low-dose, prolonged infusion of gemcitabine has effects similar to standard doses in several cancers. We evaluated the toxicity and efficacy of low-dose gemcitabine in prolonged infusion plus cisplatin in patients with advanced pleural mesothelioma. METHODS: Patients with mesothelioma received gemcitabine (250 mg/m(2)) in a 6-h infusion plus cisplatin (35 mg/m(2)) on days 1 and 8 every three weeks. We used the modified response evaluation criteria in solid tumours. This study is registered in clinical trials (NCT01869023). RESULTS: We included 39 patients; 82.1 % were low risk according to the European Organisation for Research and Treatment of Cancer prognostic group. Partial response was observed in 53.8 % (21/39), stable disease in 33.3 % (13/39) and progression in 12.8 % (5/39). The median progression-free survival was 6.9 months (95 % CI 3.2-10.6 months), and the associated factors were the EORTC risk and histology. The median overall survival was 20.7 months (95 % CI 10.7-30.8 months). The functional, physical and emotional roles and dyspnoea, insomnia and pain symptom scales improved. The most commonly graded 3/4 side effects were neutropenia (24.4 %), lymphopenia (14.6 %), thrombocytopenia (14.7 %) and anaemia (12.2 %). CONCLUSIONS: Low-dose, prolonged gemcitabine infusion plus cisplatin has acceptable toxicity and high efficacy with improved quality of life, representing an affordable regimen for the low-income population.

Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation.

BACKGROUND: Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. METHODS: We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. RESULTS: Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038). CONCLUSIONS: Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment.

Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC represents 15% of all invasive breast cancers, but some studies have suggested that its prevalence differs between races. To the authors' knowledge, no previous studies have determined the prevalence of TNBC and its risk factors among Hispanic women. METHODS: The authors identified 2074 Hispanic women with breast cancer who attended the National Cancer Institute in Mexico City from 1998 to 2008. All histopathologic and immunohistochemical diagnoses were rereviewed by a breast cancer pathologist. The prevalence of TNBC, its association with clinicopathologic characteristics, and its prognostic impact were determined. RESULTS: The median patient age at diagnosis (±standard deviation) was 50 ± 12 years. The overall prevalence of TNBC was 23.1%. Younger age (P < .001), premenopausal status (P = .002), increased parity (P = .029), hormonal contraceptive use (P = .04) high histologic grade (P < .001), and advanced disease (P < .001) were associated independently with TNBC. Postmenopausal patients who had a body mass index (BMI) <25 kg/m(2) (P = .027) or <30 kg/m(2) (P < .001) were more likely to have TNBC. In multivariate analysis, patients with TNBC had a higher risk of locoregional recurrence (LRR), lower disease-free survival (DFS) (hazard ratio, 1.62; 95% confidence interval, 1.13-2.32; P = .009), and a lower cancer-specific survival (CSS) rate (hazard ratio, 1.66; 95% confidence interval, 1.20-2.30; P = .002) than patients with non-TNBC. CONCLUSIONS: The median age at diagnosis of Hispanic women with breast cancer was 11 years younger than the average age reported in the United States. The prevalence of TNBC in this study population was higher than that reported in white women with breast cancer. TNBC was associated with a higher risk of LRR and with lower DFS and CSS than those in patients with non-TNBC.