BACKGROUND: With the aging of the population and the increased importance of lung cancer screening, the number of early-stage lung cancer patients has been on the rise in recent years, which can be classified into operable early-stage lung cancer and inoperable early-stage lung cancer. The most common pathological type is non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is the optimal treatment for inoperable early-stage NSCLC. The aim of this study was to investigate the prognosis of early-stage NSCLC patients treated with SBRT and its influencing factors in order to reduce the side effects of radiotherapy and improve the survival and quality of life. METHODS: Clinical data and follow-up outcomes of early-stage NSCLC patients treated with SBRT in our hospital from August 2010 to August 2020 were collected. Kaplan-Meier method was used to assess the prognosis, and the Cox proportional risk model was used for multivariate prognostic analysis. RESULTS: A total of 165 patients were included with a median follow-up time of 43.2 (range: 4.8-132.1) mon. The local control (LC) rates at 1-yr, 2-yr and 5-yr were 98.1%, 94.8% and 86.5% respectively. Karnofsky performance status (KPS) score greater than 80 was an independent prognostic factor for LC (P=0.02). The overall survival (OS) rates at 1-yr, 2-yr and 5-yr were 97.6%, 93.0% and 68.9% respectively. A biological equivalent dose when α/β=10 (BED10) greater than 132 Gy was an independent prognostic factor for OS (P=0.04). Progression-free survival (PFS) rates at 1-yr, 2-yr and 5-yr were 93.3%, 79.5% and 55.3% respectively. The distance metastasis free survival (DMFS) rates at 1-yr, 2-yr and 5-yr were 94.5%, 83.2% and 58.4% respectively. BED10 greater than 150 Gy was an independent prognostic factor for DMFS (P=0.02). The regional control (RC) rates at 1-yr, 2-yr and 5-yr were 98.8%, 95.4% and 87.9% respectively. CONCLUSIONS SBRT is effective in treating early-stage NSCLC. KPS greater than 80 is an independent prognostic factor for LC; BED10 greater than 132 Gy is an independent prognostic factor for OS; BED10 greater than 150 Gy is an independent prognostic factor for DMFS.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Radiosurgery/methods* ; Early Detection of Cancer ; Quality of Life ; Prognosis ; Small Cell Lung Carcinoma ; Retrospective Studies ; Treatment Outcome

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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Humans ; Lung Neoplasms/therapy* ; Early Detection of Cancer ; Lung/surgery* ; Treatment Outcome ; Radiosurgery/methods* ; Neoplasms, Multiple Primary/pathology*

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.
Colorectal Neoplasms ; Humans ; Liver/pathology* ; Lung/pathology* ; Prospective Studies ; Radiosurgery/methods*

OBJECTIVE: To evaluate the safety and efficacy of the coil-protected technique for liquid embolization in neurovascular malformations. MATERIALS AND METHODS: Twenty-two patients who underwent coil-protected liquid embolization for symptomatic cranial (n = 13) and spinal (n = 9) arteriovenous fistula (AVF) or arteriovenous malformations (AVMs) were identified. A total of 36 target feeder vessels were embolized with N-butyl cyanoacrylate and/or Onyx (Medtronic). This technique was used to promote delivery of a sufficient amount of liquid embolic agent into the target shunt or nidus in cases where tortuous feeding arteries preclude a microcatheter wedging techniqu and/or to prevent reflux of the liquid embolic agent in cases with a short safety margin. The procedure was considered technically successful if the target lesion was sufficiently filled with liquid embolic agent without unintentional reflux. Angiographic and clinical outcomes were retrospectively evaluated. RESULTS: Technical success was achieved for all 36 target feeders. Post-embolization angiographies revealed complete occlusion in 16 patients and near-complete and partial occlusion in three patients each. There were no treatment-related complications. Of the six patients who showed near-complete or partial occlusion, five received additional treatments: two received stereotactic radiosurgery for cerebral AVM, two underwent surgical removal of cerebral AVM, and one underwent additional embolization by direct puncture for a mandibular AVM. Finally, all patients showed complete (n = 19) or near-complete (n = 3) occlusion of the target AVF or AVM on follow-up angiographies. The presenting neurological symptoms improved completely in 15 patients (68.2%) and partially in seven patients (31.8%). CONCLUSION: The coil-protected technique is a safe and effective method for liquid embolization, especially in patients with various neurovascular shunts or malformations who could not be successfully treated with conventional techniques.
Angiography ; Arteries ; Arteriovenous Fistula ; Arteriovenous Malformations ; Cyanoacrylates ; Follow-Up Studies ; Humans ; Methods ; Punctures ; Radiosurgery ; Retrospective Studies

PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs). MATERIALS AND METHODS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system. RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group. CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.
Animals ; Annexin A5 ; Cell Line ; Colon ; Dendritic Cells ; Immune System ; Immunotherapy ; Injections, Intradermal ; Leg ; Methods ; Mice ; Phagocytosis ; Radiation Dosage ; Radiosurgery ; Survival Rate ; T-Lymphocytes ; Vaccination

OBJECTIVE: We investigated the effect of optimization in dose-limiting shell method on the dosimetric quality of CyberKnife (CK) plans in treating brain metastases (BMs).METHODS: We selected 19 BMs previously treated using CK between 2014 and 2015. The original CK plans (CKoriginal) had been produced using 1 to 3 dose-limiting shells : one at the prescription isodose level (PIDL) for dose conformity and the others at lowisodose levels (10–30% of prescription dose) for dose spillage. In each case, a modified CK plan (CKmodified) was generated using 5 dose-limiting shells : one at the PIDL, another at intermediate isodose level (50% of prescription dose) for steeper dose fall-off, and the others at low-isodose levels, with an optimized shell-dilation size based on our experience. A Gamma Knife (GK) plan was also produced using the original contour set. Thus, three data sets of dosimetric parameters were generated and compared.RESULTS: There were no differences in the conformity indices among the CKoriginal, CKmodified, and GK plans (mean 1.22, 1.18, and 1.24, respectively; p=0.079) and tumor coverage (mean 99.5%, 99.5%, and 99.4%, respectively; p=0.177), whereas the CKmodified plans produced significantly smaller normal tissue volumes receiving 50% of prescription dose than those produced by the CKoriginal plans (p < 0.001), with no statistical differences in those volumes compared with GK plans (p=0.345).CONCLUSION: These results indicate that significantly steeper dose fall-off is able to be achieved in the CK system by optimizing the shell function while maintaining high conformity of dose to tumor.
Brain ; Dataset ; Methods ; Neoplasm Metastasis ; Prescriptions ; Radiosurgery

PURPOSE: To evaluate the adequacy of retreatment, including hypofractionated re-irradiation (HFReRT), after surgery for recurrent glioblastoma (GBM) and related prognosticators of outcomes. MATERIALS AND METHODS: From 2011 to 2014, 25 consecutive patients with recurrent (n=17) or secondary (n=7) disease underwent maximal surgery and subsequent HFReRT after meeting the following conditions: 1) confirmation of recurrent or secondary GBM after salvage surgery; 2) Karnofsky performance score (KPS) ≥60; and 3) interval of ≥12 months between initial radiotherapy and HFReRT. HFReRT was delivered using a simultaneous integrated boost technique, with total dose of 45 Gy in 15 fractions to the gross tumor volume (GTV) and 37.5 Gy in 15 fractions to the clinical target volume. RESULTS: During a median follow-up of 13 months, the median progression-free and overall survival (OS) were 13 and 16 months, respectively. A better KPS (p=0.026), no involvement of the eloquent area at recurrence (p=0.030), and a smaller GTV (p=0.005) were associated with better OS. Additionally, OS differed significantly between risk groups stratified by the National Institutes of Health Recurrent GBM Scale (low-risk vs. high-risk, p=0.025). Radiologically suspected radiation necrosis (RN) was observed in 16 patients (64%) at a median of 9 months after HFReRT, and 8 patients developed grade 3 RN requiring hospitalization. CONCLUSION: HFReRT after maximal surgery prolonged survival in selected patients with recurrent GBM, especially those with small-sized recurrences in non-eloquent areas and good performance.
Adult ; Brain Neoplasms/mortality/pathology/*therapy ; Dose Hypofractionation ; Female ; Glioblastoma/mortality/pathology/*therapy ; Humans ; Karnofsky Performance Status ; Male ; Middle Aged ; Neoplasm Recurrence, Local/mortality/pathology/*therapy ; Prognosis ; *Radiosurgery ; Re-Irradiation/*methods ; Salvage Therapy/methods ; Survival Rate ; Treatment Outcome

With increasing clinical use, radiotherapy (RT) has been considered reliable and effective method for hepatocellular carcinoma (HCC) treatment, depending on extent of disease and patient characteristics. RT for HCC can improve therapeutic outcomes through excellent local control, downstaging, conversion from unresectable to resectable status, and treatments of unresectable HCCs with vessel invasion or multiple intrahepatic metastases. In addition, further development of modern RT technologies, including image-guided radiotherapy (IGRT), intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy, has expanded the indication of RT. An essential feature of IGRT is that it allows image guidance therapy through in-room images obtained during radiation delivery. Compared with 3D-conformal RT, distinctions of IMRT are inverse treatment planning process and use of a large number of treatment fields or subfields, which provide high precision and exquisitely conformal dose distribution. These modern RT techniques allow more precise treatment by reducing inter- and intra-fractional errors resulting from daily changes and irradiated dose at surrounding normal tissues. More recently, particle therapy has been actively investigated to improve effectiveness of RT. This review discusses modern RT strategies for HCC, as well as optimal selection of RT in multimodal approach for HCC.
Carcinoma, Hepatocellular* ; Humans ; Methods ; Neoplasm Metastasis ; Radiosurgery ; Radiotherapy* ; Radiotherapy, Image-Guided ; Radiotherapy, Intensity-Modulated

BackgroundThe role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy.

MethodsThe clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively. Cox regression was used for multivariate analysis. Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.

ResultsOf 216 included patients, 67.1% received stereotactic radiosurgery (SRS), 24.1% received whole-brain radiation therapy (WBRT), and 8.8% received both. After radiotherapy, systemic therapy was administered in 58.3% of patients. Multivariate analysis found that postradiation systemic therapy (yes vs. no) (hazard ratio [HR] = 0.361, 95% confidence interval [CI] = 0.202-0.648, P = 0.001), radiation technique (SRS vs. WBRT) (HR = 0.462, 95% CI = 0.238-0.849, P = 0.022), extracranial metastasis (yes vs. no) (HR = 3.970, 95% CI = 1.757-8.970, P = 0.001), and Karnofsky performance status (<70 vs. ≥70) (HR = 5.338, 95% CI = 2.829-10.072, P < 0.001) were independent factors for survival. Further analysis found that subsequent tyrosine kinase inhibitor (TKI) therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class II (HR = 0.411, 95% CI = 0.183-0.923, P = 0.031) or with a GPA score of 1.5-2.5 (HR = 0.420, 95% CI = 0.182-0.968, P = 0.042). However, none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.

ConclusionRTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM if TKIs were chosen as postradiation systemic therapy.

Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms ; pathology ; surgery ; Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Radiosurgery ; methods ; Treatment Outcome