ABSTRACT
Lung cancer is the leading cause of cancer death worldwide as well as in China. For many years, conventional oncologic treatments such as surgery, chemotherapy, and radiotherapy (RT) have dominated the field of non-small cell lung cancer (NSCLC). The recent introduction of immunotherapy in clinical practice, led to a paradigm shift in lung cancer as in many other solid tumors. Recent pre-clinical and clinical data have shown RT may also modify antitumor immune responses through induction of immunogenic cell death and reprogramming of the tumor microenvironment. This has led many to reexamine RT as a partner therapy to immuno-oncology treatments and investigate their potential synergy in an exponentially growing number of clinical trials. Clinical trials combining radiotherapy and immunotherapy are attracting major attention, experts were invited to discuss frontier and controversial academic topics: (1) Recent developments of clinical synergy between radiation and immune checkpoint inhibitors (ICIs) in the treatment of NSCLC; (2) Will immunotherapy and radiotherapy increase the toxicity risk for cancer patients; (3) How to cope the mixed responses/disassociated responses phenomenon in checkpoint inhibition therapy to NSCLC with local ablative therapy; (4) Combining radiotherapy and immunotherapy in the treatment of NSCLC brain metastases.
ABSTRACT
In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Diagnosis , Drug Therapy , Genetics , Pathology , Lung Neoplasms , Diagnosis , Drug Therapy , Genetics , Pathology , Mutation , PrognosisABSTRACT
Objective:This study was performed using preclinical transplanted animal experiments to analyce the effects and mechanisms of third-generation EGFR-TKIs combined with anti-angiogenic therapy, thereby providing theoretical basis for further clinical trials. Methods:Researchers constructed the transplant BALB/C nude mice models with H1975 lung adenocarcinoma cell line (EGFR T790M) and divided the mice into four groups and treated them with osimertinib (2.5 or 5 mg/kg/day, gavage) alone or plus bevacizumab (5 mg/kg/twice weekly, i.p.) when the tumors reached approximately 0.4-0.6 cm3 in volume. The tumor growth curve of tumor volume was drawn according to the time in every group. After 2 weeks of treatment, the mice were killed and the tumors were processed for immunohistochemical staining and Western blot analysis. Immunostaining was performed to detect:HIF-1α, VEGF, and microvessel density (MVD) by using SP method on paraffin sections. Western blot analysis was used to analyze the protein expression levels of EGFR, AKT, and ERK signal transduction pathways. Results:After 2 weeks of treatment in high-and low-dose osimertinib alone, tumor volume in the high-dose group was significantly less than in low-dose osimertinib-alone group (P0.05). In the high-dose osimertinib-plus-bevacizumab group, tumor growth was not significantly greater than that in the high-dose osimertinib-alone group (P=0.642). No significant difference was observed in the above factors.In the high-and low-dose osimertinib-plus-bevacizumab groups, tumor volume and the above factors did not exhibit significant differences (P>0.05). Conclusion:Osimertinib has obvious antitumor effects in EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab has a synergetic inhibitory effect with osimertinib against EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab enhanced the antitumor effects of osimertinib by reducing VEGF expression and the microvascular density of the tumor, thereby improving the tumor microenvironment. Bevacizumab can enhance the effect of osimertinib by suppressing EGFR, ERK, and AKT phosphorylation, thereby synergistically inhibiting EGFR activation and downstream signaling.
ABSTRACT
Objective The aim of this study was to retrospectively review the efficacy and safety of treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC).Methods A total of 98 patients treated in our hospital between January 2010 and December 2015 were enrolled in this study.Patients were divided into three groups:the thoracic radiotherapy (TRT) alone,concurrent chemoradiotherapy,and sequential chemoradiotherapy groups.The progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method,and compared with the log-rank/Breslow test.The prognostic factors were analyzed using the Kaplan-Meier and Cox multivariate proportional hazards models.Results The median PFS in the concurrent therapy group was longer than that in the TRT alone group (P ＜ 0.05).The median OS was improved in patients treated with concurrent or sequential therapy than in the TRT alone group (P ＜ 0.05).N stage,chemotherapy regimens,and radiotherapy modalities were independent prognostic factors of PFS in all patients (P ＜0.05).Similarly,N stage was an independent prognostic factor of OS in all patients (P ＜ 0.05).Overall,the treatment was deemed safe.The occurrence of hematotoxicity related to Karnofsky performance score (KPS) and chemotherapy regimens (P ＜ 0.05).Conclusion Patients with a lower N stage who received cisplatin-based double chemoradiotherapy demonstrated improved survival rates.Survival was significantly improved in LA-NSCLC patients treated with concurrent or sequential therapies compared with TRT alone.Overall,the treatment is safe.KPS and chemotherapy combination regimens may increase the occurrence of hematotoxicity.
ABSTRACT
Objective To investigate the intensity modulated radiation therapy (IMRT) planning optimization method to reduce the additional dose resulting from megavoltage cone-beam CT (MVCBCT) imaging for nasopharyngeal carcinoma IMRT treatment. Methods MVCBCT images collection process was simulated using XiO treatment planning system. The mean doses of MVCBCT ( DMVCBCT ) were calculated in gross tumor volume ( GTV), clinical target volume ( CTV ) and risk at organ or tissue using 27. 4 cm× 27.4 cm portal radiation 8 MU,5 MU (A,C) and 27.4 cm× 15.0 cm portal radiation 8 MU,5 MU (B,D). The dose correct factor of MVCBCT (CFMVCBCT) according to IMRT TPS and DMVCBCT ,but CFMVCBCT plus MVCBCT imaging process for radiotherapy planning optimization. The paired t-test was play for A∶ B,C∶ D,A∶ C,B∶ D of DMVCBCT. Results The DMVCBCT and CFMVCBCT of A, B, C, D were 7. 78,5. 78,4. 88,3.55 cGy ( A∶ C, t =24.41,P＜0.01) and 0.993 -0.997 in GTV,with 7.88,6.95,4.88,4.38 cGy (A∶ B,A∶ C,B∶ C,t=3. 85, -31.82, -8.52, all P＜0. 01) and 0.992 -0.996 in CTV1 ,with 8.28,6.67,5. 17,4. 17 cGy (A ∶B,A∶C,B∶C,B∶D,t=6.41 -18.24,all P＜0. 01) and 0.991 -0.996 in CTV2;with 6.88,5.00,4.28,3. 50 cGy ( A∶ B, A∶ C,t = 2. 83,11.03, all P ＜ 0. 05 ) and 0. 989 - 0. 995 in spinal cord, with 7.88,7. 38,4. 95,4. 62 cGy and 0. 984 -0. 990 in left parotid, with 8. 67,0. 28,5. 33,0. 28 cGy and 0. 963 -0. 999 in left optic nerve,with 9. 17,0.22,5.72,0. 17 cGy and 0.821 -0.997 in left eye lens,with 6.95,2. 17,4. 38,1.38 cGy and 0. 987 -0. 997 in brain stem, with 7.78,0.45,4. 95,0. 28 cGy and 0. 978 -0. 999 ( A ∶ B,A∶ C,B∶ C,B∶ D for five organ or tissue,t =5. 06 -335. 16 ,all P ＜0. 01 ) in optic chiasm. Conclusions The MVCBCT imaging process resulted in radiation doses to patient. The impact of MVCBCT image acquired dose on IMRT treatment plan for NPC was eliminated by a compensation method.
ABSTRACT
Objective To compare radiation-induced lung injury (RILI) between concurrent and sequential combination of postoperative radiotherapy and endocrine therapy. Methods A total of 118 patients subjected by radical or modified radical operation of breast cancer were enrolled in this study and received radiotherapy and endocrine therapy between Jan 2003 and December 2007. All the patients were categorized into four groups: radiotherapy (RT) plus concurrent aromatase inhibitor(AI): RT+AI; RT plus sequential AI:RT-AI; RT plus tamoxifen (TAM): RT+TAM; RT plus sequential TAM: RT-TAM. Radiotherapy was delivered by using various energy of electron (6, 9, 12 Mev β-ray) or 6 M.V X-ray for different target with a dose of 50 Gy (2 Gy/Fx, 5 fractions per week). RILI grades were classified according to RTOG/EORTC and Aoki evaluation criteria from one month to at least one year after radiotherapy. Results 30/118(25.4 %) patients was observed with RILI, RT+AI 22.7 % vs. RT-AI 20.0 %(P =0.806), RT+TAM 35.7 % vs. RT-TAM 24.2 %(P =0.328). The incident rate of RILI was higher in elder patients(>60 yr) than in other patients (33.9 % vs.16.9 %, P =0.05). Patients with positive chemotherapy history had a higher risk of RILI than those with chemotherapy-negtive history (P =0.039). Conclusion These findings suggest that RILI are associated with age and chemotherapy history, but not correlated with the sequence of radiotherapy and endocrine therapy.