Profile and outcome of treatment in non-small cell lung cancer with brain metastasis

Background: Brain metastasis is a common problem in patients with NSCLC. This study was done to study the risk factors associated with the development of brain metastasis and assess treatment response in NSCLC to improve patient survival. Methods: This was a retro-prospective study in which 126 patients with non-small cell lung carcinoma with brain metastasis were taken for the study. Results: The mean age in study group was 56.1±12.72 years. Adenocarcinoma was found in 57.1% and squamous cell carcinoma in 41.3% patients. 65.9% patients received chemotherapy for primary disease followed by targeted therapy in 34 (27.0%) patients. 53.9% patients received WBRT after diagnosis of brain metastasis and 23% WBRT and systemic chemotherapy while as14.3% received WBRT and targeted therapy and 2.4% received WBRT, systemic chemotherapy and targeted therapy, 1.6% patients received systemic chemotherapy, WBRT and local RT to the primary site and 0.8% each was treated with gamma knife therapy; surgery, WBRT and targeted therapy; SRS and WBRT. Median overall survival of patients with brain metastasis who received WBRT was 2.5 months and patients who received WBRT and systemic chemotherapy was 9.0 months while patients with brain metastasis who received WBRT and targeted therapy was 14.3 months. Conclusions: The median overall survival as per treatment received after diagnosis of brain metastasis was higher in patients who received WBRT and targeted therapy as compared to patients who received WBRT and systemic chemotherapy and patients who received WBRT only.

Addition of temozolamide as radiosensitizer in brain metastasis: experience from a resource limited centre in sub-Himalayan region

Background: Brain metastasis is a common, debilitating and undesirable neurological complication of systemic cancer and a significant cause of morbidity and mortality. Methods: 39 patients of brain metastasis with Ca breast/Ca lung as primaries were randomized into a study arm and control arm in between 1st August 2018 to 31st July 2019 at IGMC Shimla. Control arm consisted of WBRT (30 GY/10 fractions/5 days a week). Study arm consisted of WBRT with same dose and temozolamide administered 75mg /m2/day during RT days. Results: Out of 39 patients 34 patients completed treatment out of which 17 in study and 17 in control arm. Response to brain lesions could not be assessed in 20 out of 39 patients. In remaining 19 patients 36.8% patients in study arm and 20% patients in control arm had partial response (PR). 5.3% patient in study arm and none in control arm has complete response (CR). 25% patients in control arm and 15.8% patients in study arm had stable disease. Improvement in QOL (FACT- G) seen in both study and control arm post Rx, however improvement sustained in study arm at 1st F/u. Conclusions: Leveraging the additional radio-sensitizing effect of TMZ may hold promise as an attractive strategy to enhance the quality of life in patients with a favourable performance status. Moreover, RPA could serve as a decisive factor in tailoring the treatment approach, guiding the choice between palliative radiotherapy and best supportive care for these individuals.

Dosimetric study on middle ear with three whole-brain radiotherapy techniques / 中国辐射卫生

Objective This study aims to compare the advantages and disadvantages of the three techniques in improving the target volume dose and protecting the auris media cavity and eustachian tube isthmus region by investigating the dosimetric differences of three whole-brain radiotherapy techniques. Methods Thirty patients with whole brain metastases were randomly selected to design fixed field intensity modulated radiotherapy (ff-IMRT) plan, volumetric arc modulated therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) plan, and to meet a 95% PTV prescription dose (40 Gy). The dosimetric parameters and monitor units of the target volume and organ at risk (OAR) in the three groups of treatment plans were compared and analyzed. Results The Conformity Index (CI) of the ff-IMRT plan (0.93 ± 0.02) was better than the VMAT plan (0.89 ± 0.01) and the 3DCRT plan (0.73 ± 0.03), respectively, and the difference was statistically significant (P < 0.05). The Homogeneity Index (HI) of the three plans were ff-IMRT (0.05 ± 0.01)、VMAT(0.08 ± 0.1) and 3DCRT (0.08 ± 0.01), respectively, and the difference was not statistically significant (P > 0.05). The Gradient Index (GI) were ff-IMRT (1.77 ± 0.1), VMAT (1.61 ± 0.07), 3DCRT (1.39 ± 0.08), respectively. The difference was statistically significant (P < 0.05). The monitor units (MU) were ff-IMRT (1551.97 ± 85.02), VMAT (303.7 ± 24.28) and 3DCRT (226.2 ± 2.5), respectively, the difference was statistically significant (P < 0.05). The Dmax of the middle ear of the three plans were ff-IMRT (2557.54 ± 477.39) cGy, VMAT (3107.9 ± 362.28) cGy, 3DCRT (4055.37 ± 71.45) cGy, respectively. The Dmax of the eustachian tube isthmus were ff-IMRT (2425 ± 380.4) cGy, VMAT (2902.4 ± 526.3) cGy and 3DCRT (3862.7 ± 135.9) cGy, the difference were statistically significant (P < 0.05). Conclusion In whole-brain radiotherapy, ff-IMRT and VMAT significantly reduced the dose of the bilateral middle ear cavities and eustachian tube isthmus compared with 3DCRT. VMAT is recommended for WBRT for reducing the number of monitor units significantly.

Whole brain radiotherapy for patients with brain metastasis from lung cancer – Prognostic significance of RTOG-RPA score

Background: Whole brain radiotherapy for patients with brain metastasis from lung cancer – prognostic significance of RTOG-RPA score. Aim: To evaluate the prognostic significance of Recursive partition Analysis (RPA) score in predicting the survival in patients with brain metastasis from Non-Small Cell Lung Cancer (NSCLC). Materials and methods: 35 patients diagnosed to have brain metastasis (BM) from primary NSCLC who had received palliative whole brain radiotherapy (WBRT) with or without chemotherapy from March 2014 to Mar 2017 were analyzed in this study. Data regarding the patient age, gender, performance status, histology, number of BM, time of metastasis, neurosurgical resection, radiotherapy details were collected and analyzed. Patients were divided into 3 groups according to RPA classification. The differences in clinical characteristics and treatment variables were analyzed by chi square test and overall survival analysis using Kaplan Mayer. The Cox proportional hazards regression model was used to determine statistically significant variables related to survival. Results: In univariate analysis histology, number of BM, extra cranial metastases, KPS and RPA score were identified to have prognostic significance. The result of multivariate analysis by the Cox proportional hazard model showed that RPA, no of mets and Extra cranial mets were significant. S. Jeeva, K. Chandralekha, V. Vanitha, M. Sornam, Balasubramanium, P. Vidya. Whole brain radiotherapy for patients with brain metastasis from lung cancer – Prognostic significance of RTOG-RPA score. IAIM, 2019; 6(5): 32-39. Page 33 Conclusions: Our study showed that RPA is good prognostic indicator in assessing the prognosis of patients with brain metastasis in NSCLC.

Effect of whole-brain radiotherapy and TKIs on suvival of patients with brain metastases from non-small cell lung cancer stratified by EGFR mutation status / 中国肿瘤临床

Objective: To compare overall survival (OS) and intracranial progression-free survival (iPFS) effects of whole-brain radiotherapy (WBRT) and tyrosine kinase inhibitors (TKIs) in NSCLC patients with brain metastases (BM) stratified by EGFR mutation status (mutant, wild-type). Methods: We performed a retrospective analysis of 215 NSCLC BM patients diagnosed in January 2013 to January 2015 with known EGFR status and followed up to December 1, 2016. Stratified Kaplan-Meier curves and multivariate Cox models were used to evaluate the effects of WBRT (defined as≥30 Gy, "W") and TKIs (after BM, "T") on OS and iPFS independently and jointly. Two-sided P>0.20 was considered non-significant (ns). Results: In patients with BM, the mean age was 58 years, 52% were female, and 93% had adenocarcinoma. Those with EGFR mutations (114 patients) had "W" (35 patients) and "T" (87 patients) with adjusted hazard ratios (HRs) (P) of 1.135 (ns) and 0.202 (P<0.001) for OS, respectively, and 1.122 (ns) and 0.275 (P<0.001) for iPFS, respectively. "W+T" (22 patients), "T only" (65 patients), "W only"(13 patients), and "neither" (14 patients) had OS-median survival time (MST) of 14.1, 15.3, 7.1, and 4.3 months, respectively; their iPFS-MST were 14.1, 13.4, 6.8, and 4.5 months, respectively. Their adjusted HRs (P) were 0.196 (P=0.003), 0.114 (P<0.001), 0.434 (ns), 1.000 (ref) for OS, respectively, and 0.272 (P=0.012), 0.200 (P<0.001), 0.622 (ns), 1.000 (ref) for iPFS, respectively. Compared with "T only," "W+T" was not associated with better survival and "W only" had adjusted HRs (P) of 3.804 (P=0.025) for OS and 3.114 (P=0.032) for iPFS. The EGFR wild-type (101 patients) used "W" in 43 patients with OS-MST of 11.3 (7.1) and iPFS of 11.2 (4.8) months; the adjusted HRs (P) of "W"were 0.539 (P=0.105) for OS and 0.485 (P=0.048) for iPFS. Conclusions: In EGFR-mutant NSCLC BM patients, TKIs are associated with improved survival, whether, WBRT alone or combined are not. In cases of EGFR wild-type, WBRT confers the improved the iPFS.

Progress in the treatment of non-small cell lung cancer with brain metastases / 中国肿瘤临床

Lung cancer is a malignant tumor,leading to the highest morbidity and mortality worldwide.Non-small cell lung cancer (NSCLC)accounts for approximately 80% of all lung cancer types.Out of all the patients with advanced NSCLC,more than 40% develop brain metastasis,and lung cancer associated with brain metastasis indicates poor prognosis.Traditional treatment options,such as ra-diotherapy,chemotherapy and surgery,have an extremely limited role in improvement of prognosis of such patients.In recent years, with the development of stereotactic radiotherapy and targeted therapy,particularly chemotherapy combined with targeted therapy, radiotherapy combined with targeted therapy and other types of therapies,NSCLC patients with brain metastases could benefit from these therapies with an improved quality of life and prolonged median overall survival. However, the ideal treatment regimen for NSCLC patients with brain metastases remains controversial.Recent advances in NSCLC with brain metastases will be described elabo-rately in this paper,to provide a theoretical basis for selecting a reasonable treatment plan for non-small lung cancer patients with brain metastasis.