Treatment for paraganglioma with stereotactic radiotherapy

BACKGROUND Paragangliomas(PG)are rare neoplasms of neuroendocrine origin that tend to be highly vascularized,slow-growing,and usually sporadic.To date,common treatment options are surgical resection(SR),with or without radiation therapy(RT),and a watch-and-wait approach.AIM To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT(FSRT)treatment in unresectable PG(uPG).METHODS We retrospectively evaluated patients with uPG(medically inoperable or refused SR)treated with FSRT with a Cyberknife System(Accuray Incorporated,Sunnyvale,California).Toxicity and initial efficacy were evaluated.RESULTS From May 2009 to January 2023,6 patients with a median age of 68(range 20-84)were treated with FSRT.The median delivered dose was 21 Gy(range 20-30 Gy)at a median isodose line of 75.5%(range 70%-76%)in 4 fractions(range 3-5 fractions).The median volume was 13.6 mL(range 12.4-65.24 mL).The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively.Site of origin involved were the timpa-nojugular glomus(4/6),temporal bone,and cervical spine.In 1 of the 6 patients,the follow-up was insufficient;5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%.We observed negligible toxicities during and after RT.The majority of patients showed stable symptoms during follow-up.Only 1 patient developed spine metastases.CONCLUSION Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy

Objective This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy(SBRT)cases,and evaluate the required planning target volume(PTV)margins.Methods A total of 11 liver tumor patients with a total of 57 fractions,who underwent SBRT with synchronous fiducial tracking,were enrolled for the present study.The correlation/prediction model error,geometric error,and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties.The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment.Results The correlation model error-related uncertainty was 4.3±1.8,1.4±0.5 and 1.8±0.7 mm in the superior-inferior(SI),left-right,and anterior-posterior directions,respectively.These were the primary contributors among all uncertainty sources.The geometric error significantly increased for treatments without rotation correction.The fraction-level composite uncertainties had a long tail distribution.Furthermore,the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions,and only 75%of uncertainties in the SI direction.In order to cover 90%of uncertainties in the SI direction,an 8-mm margin would be needed.For scenarios without rotation correction,additional safety margins should be added,especially in the superior-inferior and anterior-posterior directions.Conclusion The present study revealed that the correlation model error contributes to most of the uncertainties in the results.Most patients/fractions can be covered by a 5-mm margin.Patients with large treatment uncertainties might need a patient-specific margin.

Role of stereotactic body radiation therapy for hepatocellular carcinoma

The integration of new technologies has raised an interest in liver tumor radiotherapy,with literature evolving to support its efficacy.These advances,particularly stereotactic body radiation therapy(SBRT),have been critical in improving local control or potential cure in liver lesions not amenable to first-line surgical resection or radiofrequency ablation.Active investigation of SBRT,particularly for hepatocellular carcinoma(HCC),has recently started,yielding promising local control rates.In addition,data suggest a possibility that SBRT can be an alternative option for HCC unfit for other local therapies.However,information on optimal treatment indications,doses,and methods remains limited.In HCC,significant differences in patient characteristics and treatment availability exist by country.In addition,the prognosis of HCC is greatly influenced by underlying liver dysfunction and treatment itself in addition to tumor stage.Since they are closely linked to treatment approach,it is important to understand these differences in interpreting outcomes from various reports.Further studies are required to validate and maximize the efficacy of SBRT by a large,multi-institutional setting.

High rate of complete histopathological response in hepatocellular carcinoma patients after combined transarterial chemoembolization and stereotactic body radiation therapy

BACKGROUND Liver transplantation(LT)presents a curative treatment option in patients with early stage hepatocellular carcinoma(HCC)who are not eligible for resection or ablation therapy.Due to a risk of up 30%for waitlist drop-out upon tumor progression,bridging therapies are used to halt tumor growth.Transarterial chemoembolization(TACE)and less commonly stereotactic body radiation therapy(SBRT)or a combination of TACE and SBRT,are used as bridging therapies in LT.However,it remains unclear if one of those treatment options is superior.The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology.AIM To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone.METHODS In this multicenter retrospective study,27 patients who received liver transplantation for HCC were analyzed.Patients received either TACE or SBRT alone,or a combination of TACE and SBRT as bridging therapy to liver transplantation.Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies.Statistical analysis was performed using Fisher-Freeman-Halton exact test,Kruskal-Wallis and Mann-Whitney-U tests.RESULTS Fourteen patients received TACE only,four patients SBRT only,and nine patients a combination therapy of TACE and SBRT.There were no significant differences between groups regarding age,sex,etiology of underlying liver disease or number and size of tumor lesions.Strikingly,analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group(8/9,89%)showed no residual vital tumor tissue by histopathology,whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response(0/14,0%and 1/4,25%,respectively,P value<0.001).CONCLUSION Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.

Liver magnetic resonance imaging for evaluation of response to treatment after stereotactic body radiation therapy of hepatocellular carcinoma

BACKGROUND Although stereotactic body radiation therapy(SBRT)is increasingly used,its application has not yet been regulated by the main international guidelines,leaving the decision to multidisciplinary teams.AIM To assess magnetic resonance imaging(MRI)features of hepatocellular carcinoma(HCC)treated with SBRT,highlighting the efficacy of the treatment and the main aspects of the lesion before and after the procedure.METHODS As part of a retrospective study,49 patients who underwent SBRT for HCC between January 2013 and November 2019 were recruited.Each patient under went a pre-treatment MRI examination with a hepatospecific contrast agent and a similar followup examination within 6 mo of therapy.In addition,22 patients underwent a second follow-up examination after the first 6 mo.The following characteristics were analysed:Features analysed compared to pre-treatment MRI examination,presence or absence of infield and outfield progression,ring-like enhancement,signal hyperintensity in T2-weighted sequences in the perilesional parenchyma,capsular retraction,and"band"signal hypointensity in T1-weighted gradient echo fat saturated sequences obtained during hepatobiliary excretion.RESULTS Signal hyperintensity in the T2-weighted sequences showed a statistically significant reduction in the number of lesions at the post-SBRT first control(P=0.0006).Signal hyperintensity in diffusionweighted imaging-weighted sequences was decreased at MRI first control(P<0.0001).A statistically significant increase of apparent diffusion coefficient values from a median of 1.01 to 1.38 at the first post-control was found(P<0.0001).Capsular retraction was increased at the late evaluation(P=0.006).Band-like signal hypointensity in the hepatobiliary phase was present in 94%at the late control(P=0.006).The study of the risk of outfield progression vs infield progression revealed a hazard ratio of 9.CONCLUSION The efficacy of SBRT should be evaluated not in the first 6 mo,but at least 9 mo post-SBRT,when infield progression persists at very low rates while the risk of outfield progression increases significantly.

Stereotactic body radiation therapy:A good dance partner of oligometastatic non-small cell lung cancer to the sound of SINDAS study

The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both primary and metastatic)should be amenable to radical intent treatment with acceptable toxicity.Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes;however,due to the diverse selection criteria and treatment strategies used in those studies,it is difficult to compare directly results to draw definitive conclusions.In recent years,prospective phase II trials,such as the SABR-COMET and"Oligomez"trials,have shown that stereotactic body radiation therapy(SBRT)improves outcomes in patients with OMD.More recently,interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer.In the present editorial,we review the definition and historical context of advanced non-small cell lung cancer with OMD.In addition,we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies.We also discuss in depth the results of the SINDAS study,including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.

Gefitinib combined with γ-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen

Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is still under investigation. Methods： The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefitinib combined with y-ray stereotactic body radiation therapy （SBRT）. Group B was the 20 patients treated with gefitinib alone. All of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with y-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week. Results： All the patients were examined by enhanced double helix CT at the second month. The tumor response rate （RR） of group A was 81.8% （18/22）. Disease control rate （DCR） was 90.9% （20/22）. The median overall survival （OS） was 24.2 months （range 8-58 months ） and the progression-free survival （PFS） was 18.6 months. The overall 1-year survival rate was 72.3% （16/22） and 2-year survival rate was 54.5% （12/22）. The main side effects included skin rash and diarrhea. The RR of group B was 50.0 % （10/20）. DCR was 75.0% （15/20）. OS was 17.4 months （range 6-32 months ） and PFS was 12.1 months. The overall 1-year survival rate was 60.0% （12/20） and 2-year survival rate was 40.0% （8/20）. The main side effects included skin rash and diarrhea. The group A who were treated with gefitinib combined with y-ray stereotactic body radiation therapy had a higher short term therapeutic effects （RR） and long term therapeutic effects （OS） than group B who were treated with gefitinib alone respectively （81.8% vs 50.0%, P = 0.029 〈 0.05, x2 = 4.773 and 24.2 vs 17.4, P = 0.024 〈 0.05, X2 = 5.098）. Conclu. sion： Gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen. The side affects are acceptable.

Research Progress in Brain Metastasis of Breast Cancer

The incidence rate of breast cancer is very high.Some patients were diagnosed as stage IV patients at the first diagnosis and had distant metastasis.Bone,lung and liver are the common metastatic sites of breast cancer.Although brain is the least common metastatic site of breast cancer,the incidence of brain metastasis in newly diagnosed breast cancer patients is increasing year by year.After brain metastasis,the disease develops rapidly,and because of the existence of blood cerebrospinal fluid barrier,it is difficult for drugs to reach the focus,and the curative effect is poor,leading to poor prognosis of patients with brain metastasis of breast cancer.Previous studies have also explored the clinical characteristics of brain metastases from breast cancer and the factors affecting prognosis.Different ages,races,histological grades,T stages,N stages,molecular subtypes,and pathological types are the main factors affecting the occurrence and prognosis of brain metastases from breast cancer.Studies on the characteristics,mechanisms,and treatment plans of brain metastases from breast cancer have also been reported at home and abroad.This article reviews the clinical characteristics,pathogenesis and treatment progress of brain metastases from breast cancer,aiming to provide some ideas and basis for clinical diagnosis and treatment and drug research of brain metastases from breast cancer.

Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy

Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells（ECs） initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment.Radiotherapy（RT） is a vital tumor treatment modality. Currently, more than 60% of patients with malignant tumors receive RT at certain points during their treatment. Hypoxia induced by abnormal microvessels can hamper the cytotoxic effect of ionizing radiation, particularly, stereotactic body radiotherapy（SBRT）. Anti-angiogenesis（AA） agents are known to reduce and renormalize microvessels in tumors, and hence alleviate hypoxia. The combination of AA agents with SBRT may have a synergistic role in inhibiting the growth of tumors. On the contrary, large doses of irradiation may affect tumor microvessels itself. In this review, we aim to clarify the relationship between SBRT and microvessel formation in tumors. In addition, we provide a retrospective analysis of the combination therapy involving SBRT and AA agents in preclinical and clinical practice to define its role in antitumor treatment.

Role of stereotactic body radiotherapy for oligometastasis from colorectal cancer

Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases because they can be cured by removal of oligometastatic lesions. One of the most frequently reported tumor histologies for oligometastases is colorectal cancer. Resection is the standard therapy in most settings of oligometastases. Recently, studies have shown that stereotactic body radiotherapy (SBRT) may become a treatment option that provides high local control with minimal morbidity. Two-year local control rates following SBRT for hepatic and pulmonary oligometastases are almost over 80% and are even higher for patients treated with high-dose regimens. The indications of SBRT for other metastatic sites or conditions include isolated lymph nodes, spinal and adrenal metastasis, and post-surgical pelvic recurrence. Many retrospective studies have indicated that SBRT for various lesions results in good outcomes with low morbidity, both in the curative and palliative setting. However, few reports with a high level of evidence have indicated the efficacy of SBRT compared to standard therapy. Hereafter, the optimal indication of SBRT needs to be prospectively investigated to obtain convincing evidence.

Advances of stereotactic body radiotherapy in pancreatic cancer

Pancreatic cancer（PCA） is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy（SBRT） era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma.

Clinical evaluation of 4D dynamic dose for thoracic tumor stereotactic body radiation therapy with variable parameters

Objective:To evaluate the dose uncertainty in stereotactic body radiation therapy induced by respiratory motion using a 4D dynamic dose(4DDD)reconstruction method.Methods:A retrospective analysis was conducted on five lung cancer patients who received static intensitymodulated radiation therapy.The 4DDD was constructed using beam delivery log files,four-dimensional computed tomography(4DCT)scans,and treatment plans.To evaluate the impact of respiratory motion,4DDD calculations were performed with 10 starting phases for each field.A total of 270 field doses were simulated and calculated.The differences between the cumulative volume histogram in whole-course treatment and the field doses'gamma passing rate(GPR)were compared.The correlations between plan complexity metrics and the dose deviation caused by respiratory motion were evaluated independently.The phase distributions of 398 subfields were calculated and evaluated for the influence of dose rate and breathing frequency.Results:The GPRs of all fields were different among various starting phases,with the highest range from 62.20% to 76.87% for 2 mm/3%GPR.The deviation of mean point dose was(5.42±5.21)%,and the deviation in the mean dose and D98% within the internal gross tumor volume were(0.97±0.71)% and(0.77±0.53)%,respectively.There was a significant correlation between the beam aperture-to-volume(BA2V)ratio and the average 2 mm/2%GPR(R?0.601,P<0.01).Lower dose rates led to a more homogeneous distribution of phases among subfields(t?44.100,P<0.001).Conclusions:Different beam starting phases had a limited impact on the overall treatment evaluation.However,the respiratory motion could be observed to induce dose deviations using the 4DDD reconstruction model,particularly for fields with small BA2V.

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer

Non-small cell lung cancer(NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy(curative-intent or palliative). Technological advancesincluding highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy(SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.

Stereotactic body radiation therapy favors long-term overall survival in patients with lung metastases： five-year experience of a single-institution

Background Metastatic lung cancer is one of the most common oncologic problems. This study aimed to evaluate the long-term clinical outcome of stereotactic body radiation therapy （SBRT） for metastatic lung tumors. Methods We retrospectively reviewed the 71 patients with lung metastases, who had 172 lesions treated with SBRT from January 2000 to December 2006. All patients were unfit or failed after surgery and/or chemotherapy. The median total dose was 48 Gy （range, 30-60） in 4 （range, 2-12） fractions. The median size of the irradiated lesions was 2.1 cm （range, 0.9-7.9 cm）. Results All but two patients received follow up. The median follow-up time was 24.7 months （range, 2.9-114.4 months）. The median follow-up time for living patients was 86.8 months （range, 58.1-114.4 months）. The 1-, 3-, 5-year local control and overall survival rates were 88.8%, 75.4%, 75.4% and 78.9%, 40.8%, 25.2%. Multivariate analysis showed that the absence of extrapulmonary metastases （P=-0.024; hazard ratio （HR）, 1.894; 95% confidence interval （C/）, 1.086-3.303） and disease-free interval 〈12 months （P=0.014; HR, 0.511; 95% Cl, 0.299-0.873） were independent prognostic factors. No grade 3 or more acute and late toxicities occurred. Only one patient developed a non-symptomatic rib fracture. Conclusion SBRT could be an alternative treatment to surgery for subsets of patients with lung metastases with favorable long-term survival and tolerable complications.

Stereotactic body radiation therapy versus radiofrequency ablation in patients with small hepatocellular carcinoma:a systematic review and meta-analysis

Background:This study aimed to compare the clinical outcomes and toxicity between small hepatocellular carcinoma(HCC)patients treated with stereotactic body radiation therapy(SBRT)and those treated with radiofrequency ablation(RFA).Methods:We searched databases for relevant clinical studies.The primary outcomes of interest were overall survival(OS)at 1 and 2 years,freedom from local progression(FFLP)rate at 2 years,and complications.Results:Five cohorts from 5 retrospective studies and 4,814 patients with HCC were included.Pooled OS at 2 years was significantly lower for SBRT than for RFA[odds ratio(OR):0.63;95%confidence interval(CI):0.51-0.79;P<0.0001],but the pooled FFLP rate at 2 years was higher for SBRT than for RFA(OR:1.66;95%CI:1.05-2.61;P=0.03).In addition,there was no significant difference in the local and liver toxicities of the two treatments.The contradictory conclusion between the OS and FFLP outcome may be attributed to the difference in radiological dose and location,but there were no uniform criteria to illustrate the radiological dose and location in the included studies.Conclusions:SBRT had a higher local control ratio but poorer prognosis than RFA in patients with small HCC.The local toxicity was comparable in both treatments.Further trials should be designed with uniform standards for SBRT and RFA treatments.

Precision radiotherapy for brain tumors A 10-year bibliometric analysis

OBJECTIVE： Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; （b） type of articles： original research articles and reviews; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） Corrected papers or book chapters. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） top cited publications; （5） distribution according to journals; and （6） comparison of study results on precision radiotherapy for brain tumors. RESULTS： The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies. CONCLUSION： Precision radiotherapy for brain tumors remains a highly active area of research and development.

Strategies to tackle the challenges of external beam radiotherapy for liver tumors

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.

Extrahepatic metastasis of hepatocellular carcinoma to the paravertebral muscle:A case report

Identification of extrahepatic metastases(EHM) of hepatocellular carcinoma(HCC) has been paradoxically increasing due to an increase in the survival of HCC patients. However, metastasis of HCC to the skeletal muscle tissue is extremely rare. We describe a unique case of HCC metastasizing to the paravertebral muscle. A 55-year-old man with a history of hepatitis B cirrhosis underwent partial liver resection with complete removal of HCC. Three months later, a computed tomography(CT) scan showed intrahepatic recurrence. The tumors were treated with yttrium-90 microspheres, transcatheter arterial chemoembolization, and sorafenib. Six months later, a CT scan showed an enhancing lesion of the left paravertebral muscle that on biopsy were consistent with metastatic HCC. The tumor was treated with stereotactic hypo-fractionated imageguided radiation therapy(SHFRT). A follow-up scan 3 mo post-radiotherapy revealed a stable appearance of the paravertebral muscle metastasis. Because of the progression in the intrahepatic tumors, the patient was treated with capecitabine, which was changed to dasatinib 6 mo later. The patient passed away three years after the primary surgical resection. Management of EHM poses an extreme challenge. This is the first case of HCC with EHM to the paravertebral muscle in which stability of disease was achieved using SHFRT. This case highlights the importance of early detection of hepatitis B viral infection and initiation of anti-viral therapy to decrease recurrence of HCC and prevent EHM.

Validation of the eighth edition of the AJCC staging system for patients with pancreatic adenocarcinoma initially receiving chemoradiotherapy and proposal of modifications

Objective:To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy,and to propose modifications to improve prognostic accuracy.Methods:Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system.Meanwhile,another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi(PV±PVTT)were retrieved for survival comparisons.Modifications were proposed according to the survival comparisons.A cohort from the SEER database was used for external validation of the modified staging system.Results:A total of 683 patients were included.Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition.The survival of patients with(PV±PVTT)was comparable to that of patients with T4 tumors.The concordance index of the seventh and eighth editions,and the modified staging system was 0.744(95%CI:0.718—0.769),0.750(95%CI:0.725—0.775),and 0.788(95%CI:0.762-0.813),respectively.For external validation,the concordance index was 0.744(95%CI:0.718-0.770),0.750(95%CI:0.724-0.776),and 0.788(95%CI:0.762-0.814),respectively.Conclusions:The modified staging system is suggested to have the m ost accurate prognostic value.Hence,PV土PVTT should be added to the definition of T4 tumors regardless of tumor size.Patients with N2 or N1 in different T stages could be regrouped into different substages.Additionally,stage III should be subclassified into IIIA(T3N 2 and T4N 0)and IIIB(T4N 1-2).