scholarly journals Analysis of the efficacy and prognostic factors of linear accelerator-based hypofractionated stereotactic radiotherapy for brain metastasis of non-small-cell lung cancer

2020 ◽  
Author(s):  
Xi Wu ◽  
Yaoxiong Xia ◽  
Yu Hou ◽  
Lan Li ◽  
Li Wang ◽  
...  

Abstract Objective To investigate the efficacy and prognostic factors of treatment of brain metastases (BMs) of non-small-cell lung cancer (NSCLC) patients with hypofractionated stereotactic radiotherapy (HSRT) based on linear accelerators. Methods A total of 80 NSCLC patients with BMs were treated with HSRT under the image guidance of tomotherapy (TOMO) or volumetric modulated arc therapy (VMAT) in Yunnan Cancer Hospital from Jan 1 st , 2017 to Aug 7 th , 2019. The outcome measures included overall survival (OS), intracranial local progression-free survival (iLPFS) and intracranial regional progression-free survival (iRPFS). The related prognostic factors were analyzed. Results The median OS, iLPFS and iRPFS in 80 patients were 29.2 months, 19.3 months and 20.5 months, respectively. Using HSRT to treat BMs, whether combined with platinum-containing chemotherapy, targeted therapy, or both chemotherapy and targeted therapy, could improve OS ( P =0.027), iLPFS ( P =0.050) and iRPFS ( P =0.124). Among these patients, there were no significant differences in median OS (28.5 months vs 28.3 months, P =0.785), 6-month iLPFS rates (81.3% vs 72.9%, P =0.998) and 6-month iRPFS rates (92.9% vs 74.8%, P =0.974) between patients with 4-10 BMs and those with 1-3 BMs. Conclusion The use of HSRT to treat BMs of NSCLC based on linear accelerators is safe and effective. Use of HSRT in combination with other antitumor therapies to treat BMs is a favorable prognostic factor that can affect OS and iLPFS. HSRT treatment of 4-10 BMs or 1-3 BMs resulted in similar OS, and there were no significant differences in 6-month iLPFS rates and 6-month iRPFS rates.

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1257
Author(s):  
Foteinos-Ioannis Dimitrakopoulos ◽  
Achilleas Nikolakopoulos ◽  
Anastasia Kottorou ◽  
Fotini Kalofonou ◽  
Elias Liolis ◽  
...  

Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic management of advanced non-small cell lung cancer (aNSCLC) over the last decade. However, there is an unmet need for clinically useful biomarkers in this patient subgroup. The aim of this study was to combine baseline clinical characteristics of aNSCLC patients, in the form of a scoring system, and to investigate its predictive and prognostic value in NSCLC patients treated with ICIs. A total of 112 patients with advanced (stages IIIA to IV) NSCLC, treated with nivolumab or pembrolizumab, were enrolled in this study. Patras Immunotherapy Score (PIOS) was developed based on four of the studied parameters (performance status (PS), body mass index (BMI), age, and lines of treatment (LOT), which were incorporated into our formula (PS × BMI/ LOT × age). PIOS score was strongly associated with best overall responses (BOR), with those patients having benefit/good response (stable disease (SD) or partial (PR) or complete response (CR), achieving a higher score compared to patients who developed progressive disease (PD) (p < 0.001). Furthermore, PIOS score was associated with progression-free survival (PFS), since high-score patients had longer PFS (p < 0.001, hazard ratio (HR) = 0.469). Moreover, PIOS was associated with post-immunotherapy overall survival (OS), with high-score patients having improved OS (log-rank p = 0.019). This study suggests that a combination of baseline parameters, which give rise to PIOS score, may predict the best response of NSCLC patients treated with anti-program cell death -1 (PD-1) monotherapy as well as it may have a potent prognostic value for PFS and post immunotherapy OS.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21636-e21636
Author(s):  
Wolfgang M. Brueckl ◽  
Martin Reck ◽  
Harald Schäfer ◽  
Cornelius Kortsik ◽  
Tobias Gaska ◽  
...  

e21636 Background: Afatinib is an irreversible ErbB family blocker, which is approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Here we report the final results of the prospective non-interventional study (NIS) GIDEON, which was initiated to investigate the efficacy and tolerability of afatinib in the daily clinical routine in Germany. Methods: EGFR-mutated NSCLC patients were treated with afatinib according to label until progression, death or discontinuation. Efficacy (progression-free survival (PFS) rate at 12 months, objective response rate, ORR; disease control rate, DCR; progression-free survival, PFS and overall survival, OS) was prospectively assessed by investigators. Data about tolerability were collected during routine treatment. Results: In total, 161 patients were enrolled at 41 sites in Germany, 152 patients received at least one dose of afatinib (treated set; TS) and 146 patients were treated according to the protocol (PPS). The majority of patients for the entire TS had exon 19 deletions (64.5%), followed by L858R point mut. (22.4%) and uncommon mut. (exon 18-21 point mut.; 13.1%). The primary objective was PFS-rate at 12 months, which was 50.2% in the PPS. Median PFS amounted to 12.2 months. ORR and DCR were 74.6% and 91.5% in the PPS, respectively. Median OS was 30.4 months with 1- and 2-year survival rates of 79.1% and 57.7%, respectively. Among pat. with uncommon EGFR-mut., the 12-months PFS rate was 40.2% with a mPFS of 10.7 months. ORR and DCR were 83.3% and 91.7%, respectively. The most frequent documented adverse drug reactions (ADRs) were diarrhea and rash/acne with 13.8% and 7.2% of grade 3 but no grade 4 or higher. Conclusions: Afatinib is a standard therapy for patients with activating EGFR mut. in Germany. The final results of this prospective NIS confirm the robust clinical data for afatinib in the clinical routine setting, including patients with uncommon exon 18-21 point mutations. Clinical trial information: NCT02047903.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21202-e21202
Author(s):  
John P. Palmer ◽  
Yenong Cao ◽  
Samer Ibrahim ◽  
Natasha Dhawan ◽  
Muhammad Zubair Afzal ◽  
...  

e21202 Background: Increased systemic inflammatory state and increased inflammation within tumor micro-environment (TME) have been associated with a worse prognosis and lower responsiveness to immune checkpoint inhibitors (ICI). Systemic inflammatory immune index (SII) reflects the changes in the systemic inflammatory matrix. Studies have shown the association of SII with cancer survival and treatment outcomes. We aim to study the effect of SII on treatment outcomes in non-small cell lung cancer (NSCLC) patients being treated with ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs (pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab) alone or in combination with chemotherapy. SII is the product of platelets multiplied by neutrophils divided by lymphocytes. Baseline and 8-week SIIs were obtained. Radiographic response, duration of radiographic response (date of best response to radiographic progression), overall survival (OS), and progression-free survival (PFS) were evaluated. A high SII was defined as a value greater than the median SII. Cox regression univariate and multivariate analyses were performed. Logistic regression, t-test, and Chi-square tests were applied. Results: Overall, 81% patients had adenocarcinoma and 19% patients had squamous, adenosquamous or large cell carcinoma. The majority of the patients were female (56.2% vs. 43.8%). Median SII at baseline was 1335. The objective response rate (ORR) was 45.1%. The disease control rate was 75.8%. The ORR was 51% in patients receiving ICI first-line compared to 35% in those who received ICI as a second-line therapy. At baseline, there was no difference in the mean SII between responders and non-responders (2146.2 vs. 1917.5, P = 0.5); however at 8 weeks, the mean SII was significantly lower in responders compared to non-responders (1198.8 vs. 2880.2, P = 0.02). A total of 15 (10.9%) patients were found to have pseudoprogression or mixed response on follow-up imaging. Among these, 11(73.3%) patients had low SII at 8 weeks (P = 0.04). The median OS was significantly higher in patients with low SII at baseline (29.6 months vs. 10.1 months, P = 0.001 95% CI 10.6 – 22.1). Similarly, there was a significant difference in median PFS in patients with low SII (14.6 months vs. 6.7 months, P = 0.002, 95% CI 5.6 – 11.6). There was no correlation between high or low SII on the incidence of immune-related adverse events. Conclusions: SII may have significant impact on OS and PFS and could be serially monitored to assess the response to ICI. A low SII may help to differentiate pseudoprogression vs. true progression. Prospective studies are needed to validate these findings. Further, it will be interesting to see if SII could be incorporated into predictive models to determine the duration of cytotoxic therapy in selected patients.


2020 ◽  
Author(s):  
Nozomu Motono ◽  
Shun Iwai ◽  
Yoshihito Iijima ◽  
katsuo Usuda ◽  
Hidetaka Uramoto

Abstract Background: The relationship between operative invasiveness and the prognosis in non-small cell lung cancer (NSCLC) patients who have undergone surgery has been controversial.Methods: Clinical data were analyzed for 463 NSCLC patients. Operative invasiveness was defined by wound length, operation time, and the postoperative C-reactive protein (postCRP) level. The operative approach was divided into video-assisted thoracic surgery (VATS) and thoracotomy.Results: The wound length and operation time were significantly correlated with the postCRP level (correlation coefficient (CC) = 0.39, p<0.01; CC = 0.54, p<0.01, respectively). The postCRP level in the VATS group was significantly lower than that in the thoracotomy group (12.2 mg/dl vs 20.58 mg/dl, p<0.01). The relapse-free survival differed significantly based on wound length (p<0.01), operation time (p=0.01), CRP level (p<0.01), and operative approach (p<0.01). The carcinoembryonic antigen level (hazard ratio [HR], 1.58; p = 0.02), pathological stage (pStage) (HR, 2.57; p < 0.01), vascular invasion (HR, 1.95; p = 0.01), and preoperative CRP level (preCRP) (HR, 1.91; p < 0.01) were identified as significant prognostic factors for relapse-free survival in a multivariate analysis. Furthermore, the multivariate analysis showed that smoking history (HR, 2.36; p = 0.03), pStage (HR, 3.26; p < 0.01), and preCRP level were significant prognostic factors for overall survival.Conclusion: Preoperative CRP level was associated with poor prognosis. Although the VATS approach might be less invasive procedure for NSCLC patients, operative invasiveness does not affect the prognosis. Trial registrationThe Institutional Review Boards of Kanazawa Medical University approved the protocol (approval number: I392), and written informed consent was obtained from all of the patients.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20679-e20679 ◽  
Author(s):  
Motohiro Tamiya ◽  
Akihiro Tamiya ◽  
Hidekazu Suzuki ◽  
Takako Inoue ◽  
Yoshihiko Taniguchi ◽  
...  

e20679 Background: Nivolumab (Nivo) is applicable for all metastatic or unresectable non-small cell lung cancer (NSCLC), however only some patients benefit from it. Therefore, identifying biomarkers predicting efficacy is a crucial topic in the “real world’’ setting. We conducted a retrospective study to analyze the impact of metastatic status on the effect of Nivo in NSCLC patients. Methods: This is a retrospective multicenter study conducted by the three medical centers in Japan. All patients treated with Nivo from January 2016 to July 2016 in these centers were retrospectively reviewed. We collected clinical data including age, sex, smoking history, performance status (PS), and metastatic cites (lymph nodes: lym, liver, brain, bone, pleural effusion, and intrapulmonary metastasis: lung) at the time of starting Nivo treatment. We investigated relationship between metastatic sites and progression free survival (PFS) of Nivo. Patients were followed-up until 30th September 2016. Results: Two hundred and one patients treated with Nivo were enrolled. At the time of administration of Nivo, median age was 68 years old, 137 patients were male, 155 patients had history of smoking status, 152 patients were PS 0 or 1, and 46 patients had squamous cell carcinoma (SQ). For all participants, median PFS was 2.5 months. In univariate analysis, female (hazard ratio (HR): 1.43, 95% confidence interval (CI): 1.02-2.00; p = 0.036), never-smoker (HR: 1.51 , 95% CI: 1.05 – 2.17; p = 0. 0262), PS 2 or more (HR: 1.68, 95% CI: 1.17-2.41; p = 0.0045), metastasis to liver (HR: 2.02, 95% CI: 1.30-3.15; p = 0.0015), brain (HR: 1.42, 95% CI: 0.99-2.03; p = 0.0574), bone (HR: 1.42, 95% CI: 1.01-1.98; p = 0.0642), lung (HR: 1.57, 95% CI: 1.13-2.20; p = 0.0076), and malignant pleural effusion (HR: 1.47, 95% CI: 1.06-2.04; p = 0.0195) had significantly correlated with poor PFS. In multivariate analysis, liver metastasis (HR: 1.59, 95% CI: 0.97-2.61; p = 0.0642) and malignant pleural effusion (HR: 1.47, 95%CI: 1.04–2.07; p = 0.0294) had significantly correlated with poor PFS. Conclusions: Liver metastasis and malignant pleural effusion were independent poor prognostic factors of Nivo treatment in NSCLC patients. (UMIN-ID: UMIN000025908)


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nozomu Motono ◽  
Shun Iwai ◽  
Yoshihito Iijima ◽  
Katsuo Usuda ◽  
Hidetaka Uramoto

Abstract Background The relationship between operative invasiveness and the prognosis in non-small cell lung cancer (NSCLC) patients who have undergone surgery has been controversial. Methods Clinical data were analyzed for 463 NSCLC patients. Operative invasiveness was defined by wound length, operation time, and the postoperative C-reactive protein (postCRP) level. The operative approach was divided into video-assisted thoracic surgery (VATS) and thoracotomy. Results The wound length and operation time were significantly correlated with the postCRP level (correlation coefficient (CC) = 0.39, p <  0.01; CC = 0.54, p <  0.01, respectively). The postCRP level in the VATS group was significantly lower than that in the thoracotomy group (12.2 mg/dl vs 20.58 mg/dl, p <  0.01). The relapse-free survival differed significantly based on wound length (p <  0.01), operation time (p = 0.01), CRP level (p <  0.01), and operative approach (p <  0.01). The carcinoembryonic antigen level (hazard ratio [HR], 1.58; p = 0.02), pathological stage (pStage) (HR, 2.57; p <  0.01), vascular invasion (HR, 1.95; p = 0.01), and preoperative CRP level (preCRP) (HR, 1.91; p <  0.01) were identified as significant prognostic factors for relapse-free survival in a multivariate analysis. Furthermore, the multivariate analysis showed that smoking history (HR, 2.36; p = 0.03), pStage (HR, 3.26; p <  0.01), and preCRP level were significant prognostic factors for overall survival. Conclusion Preoperative CRP level was associated with poor prognosis. Although the VATS approach might be less invasive procedure for NSCLC patients, operative invasiveness does not affect the prognosis.


2016 ◽  
Vol 34 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Kimberly L. Johung ◽  
Norman Yeh ◽  
Neil B. Desai ◽  
Terence M. Williams ◽  
Tim Lautenschlaeger ◽  
...  

Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Min Hu ◽  
Xiaojiang Sun ◽  
Yuanjun Liu ◽  
Yaoyao Zhu ◽  
Qinghua Xu ◽  
...  

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.


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