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.

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.

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.

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.

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.

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.

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.

Efficacy and safety of stereotactic body radiation therapy combined with transarterial chemoembolization for Chinese intermediate-to advanced-stage hepatocellular carcinoma patients: a systematic review and meta-analysis

Aim:According to the current guidelines,transarterial chemoembolization(TACE)remains the first-line therapies for hepatocellular carcinoma(HCC)patients at Barcelona Clinic Liver Cancer(BCLC)B-stage and sorafenib is a small molecule target drug for BCLC C-stage.In clinical practice,clinicians have attempted to use stereotactic body radiation therapy(SBRT)plus TACE for treating intermediate-to advanced-stage HCC.However,the therapeutic effects are still inconsistent.This meta-analysis was conducted to elucidate the validity and safety of the combination therapy of SBRT plus TACE in the patients with intermediate-to advanced-stage HCC.Methods:PubMed,MEDLINE,Web of Science,China Biology Medicine,Chinese Knowledge resources integrated and Chinese Scientific Journal Full-Text Database was searched from their inception date to November 2018.The survival rates(half-year,one-year and two-year)were analyzed and compared between the observation groups and the control groups.The negative conversion rate of AFP and the total effective rate were also assessed.Risk ratios(RR)and 95%CI were calculated to express therapeutic effects. ;Results:A total of 1,210 patients from 13 eligible studies were included.The cooperation of TACE and SBRT notably ameliorated the whole survival rates of half-year,one-year,two-year,the negative conversion rate of AFP,and the total effective rate,compared with TACE or SBRT monotherapy[RR(the total effective rate),1.412,95%CI:1.309-1.523,P<0.001],[RR(half-year survival rate),1.196,95%CI:1.121-1.276,P<0.001],[RR(one-year survival rate),1.327,95%CI:1.236-1.424,P<0.001],[RR(two-year survival rate),1.479,95%CI:1.284-1.703,P<0.001]and[RR(negative conversion rate of AFP),1.756,95%CI:1.502-2.059,P<0.001].Sensitivity analysis supported the above results.Conclusion:Combination therapy of SBRT and TACE provides survival benefits in intermediate-to advanced-stage HCC patients compared to monotherapy of SBRT or TACE.

Comprehending the therapeutic effects of stereotactic body radiation therapy for small hepatocellular carcinomas based on imagings

Surgical resection or radiofrequency ablation(RFA)is considered first-choice treatment for small hepatocellular carcinomas(HCCs).When a patient has a small HCC that is inoperable or unsuitable for RFA,what are alternative treatments?Some oncologists recommend transarterial chemoembolization(TACE),chemotherapy,molecular-targeted therapy,or immunotherapy.However,these treatments have minimally beneficial effects in small HCCs.Stereotactic body radiation therapy(SBRT)is a liver-directed radical therapy for small HCCs,with treatment outcomes similar to those for surgical resection or RFA,but many oncologists do not comprehend its efficacy or accept this therapy.We herein discuss 11 typical patients who received SBRT for various indications:refusal to undergo resection or RFA;surgical resection or RFA considered difficult or unfeasible;residual cancer after surgical resection or RFA or incomplete iodized oil retention after TACE;or tumor recurrence after resection or RFA.We describe each case,including the radiation field,tumor radiation dose,and response to SBRT in both the tumor and liver parenchyma.These clinical data should help readers understand this new therapeutic technique.We also conducted a literature review and found evidence to support survival benefit with SBRT,including good three-and five-year overall survival rates.The purpose of this article is to encourage readers to accept the concept that SBRT is a low-toxicity and effective therapeutic option for patients with small HCCs,which offers substantial local control and improved overall survival,especially for patients with a tumor that is unresectable or unsuitable for RFA,residual tumor after local therapy,or intrahepatic recurrent tumor.

Combined transarterial chemoembolization and stereotactic body radiation therapy as a bridge therapy to liver transplant for hepatocellular carcinoma

Liver transplant(LT)is the curative treatment for patients with hepatocellular carcinoma(HCC).Bridge therapies are local treatments given to patients on the LT waitlist,to prevent tumor progression and to reduce the dropout rate.Case presentation:We reported a 40-year-old man diagnosed with Barcenola-Clinic Liver Cancer BCLC intermediate stage HCC and Child-Pugh A5 hepatitis B virus cirrhosis who underwent combined bridge therapies to LT.Firstly,the patient received transarterial chemoembolization(TACE)for two times and showed a partial response.Then he underwent stereotactic body radiation therapy(SBRT)with a total dose of 45 Gy in 3 fractions.Three months later,the tumor size and serum protein induced by Vitamin K absence or antagonists-II,alpha fetoprotein levels decreased gradually.In June 2019 a suitable donor was found and his LT was successfully performed.Conclusion:We propose that a combination of TACE and SBRT was feasible as bridge therapy for HCC patients on the LT waitlist.

Stereotactic body radiation therapy for the management of HCC

Hepatocellular carcinoma(HCC)is a common malignant tumor in China.After years of efforts,there has been great progress in the management of liver cancer,but overall,it is still not ideal.At present,there are many therapies for liver cancer,including surgical resection,transcatheter arterial chemoembolization(TACE),ablation,molecular targeted therapy,stereotactic body radiation therapy,chemotherapy,immunotherapy,and so on.Studies have reported that TACE combined with radiotherapy can shrink the tumor,and some of the remainder will be resectable,resulting in cure.For HCC with tumor thrombus,the tumor thrombus was reduced and then resected after neoadjuvant radiotherapy.The survival time of the patients with portal vein tumor thrombus was significantly longer than that of the patients without neoadjuvant radiotherapy.Large liver cancer will be reduced to small liver cancer after comprehensive treatment,which can be transformed into stereotactic radiotherapy or radiofrequency ablation,and can also be palliative to radical treatment.Individualized and multidisciplinary therapy for liver cancer is the direction of future development.More clinical evidence-based level of radiotherapy treatment of liver cancer should be done in the future.

Stereotactic body radiation therapy for primary liver tumors with adverse factors

Aim:To test the efficacy and safety of liver stereotactic body radiation therapy(SBRT)in patients who harbor adverse factors.Methods:We retrospectively evaluated the outcomes of liver SBRT in a single cancer center.We invented criteria consisting of two physical factors and two tumor factors to measure the treatment difficulty in each case.The clinical outcomes and toxicity were evaluated by stratification of the harboring factors.Results:A total of 24(23 hepatocellular carcinoma and 1 intrahepatic cholangiocarcinoma)patients were eligible for this study,with a median follow-up duration of 18 months.Of all eligible patients,21 patients(88%)had one or more factors.The local control,progression-free survival,and overall survival rates for all patients at 2 years were 89%,42%,and 76%respectively.In the patients with physical and tumor adverse factors,local control/progression-free survival/overall survival rates at 2 years were 100%/42%/69%and 80%/23%/78%,respectively.The subgroup of 11 patients with 2 or more factors showed comparable local control rate at 2 years to the subgroup of 13 patients with 0 to 1 factors(100%vs.86%,P=0.59).One patient(4.2%)experienced a decline in the Child-Pugh score by 2 points at 3 months after the treatment.Grade 2 to 3 gastrointestinal toxicity was observed in three patients.Conclusion:SBRT showed a high local control rate with acceptable toxicity for the group of liver cancer patients harboring both physical and tumor adverse factors as long as conducted following patient selection and dose constraints that were used in this study.

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.

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.

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).

Autosegmentation of cardiac substructures in respiratory-gated,non-contrasted computed tomography images

BACKGROUND Radiation dose to specific cardiac substructures can have a significant on treatment related morbidity and mortality,yet definition of these structures is labor intensive and not standard.Autosegmentation software may potentially address these issues,however it is unclear whether this approach can be broadly applied across different treatment planning conditions.We investigated the feasibility of autosegmentation of the cardiac substructures in four-dimensional(4D)computed tomography(CT),respiratory-gated,non-contrasted imaging.AIM To determine whether autosegmentation can be successfully employed on 4DCT respiratory-gated,non-contrasted imaging.METHODS We included patients who underwent stereotactic body radiation therapy for inoperable,early-stage non-small cell lung cancer from 2007 to 2019.All patients were simulated via 4DCT imaging with respiratory gating without intravenous contrast.Generated structure quality was evaluated by degree of required manual edits and volume discrepancy between the autocontoured structures and its edited sister structure.RESULTS Initial 17-structure cardiac atlas was generated with 20 patients followed by three successive iterations of 10 patients using MIM software.The great vessels and heart chambers were reliably autosegmented with most edits considered minor.In contrast,coronary arteries either failed to be autosegmented or the generated structures required major alterations necessitating deletion and manual definition.Similarly,the generated mitral and tricuspid valves were poor whereas the aortic and pulmonary valves required at least minor and moderate changes respectively.For the majority of subsites,the additional samples did not appear to substantially impact the quality of generated structures.Volumetric analysis between autosegmented and its manually edited sister structure yielded comparable findings to the physician-based assessment of structure quality.CONCLUSION The use of MIM software with 30-sample subject library was found to be useful in delineating many of the heart substructures with acceptable clinical accuracy on respiratory-gated 4DCT imaging.Small volume structures,such as the coronary arteries were poorly autosegmented and require manual definition.

Commissioning of the TrueBeam STx 6 MV FFF Beam in the RayStation Treatment Planning System for SRS and SBRT Treatments

Purpose: The purpose of this study is to provide technical information on commissioning the TrueBeam STx 6 MV flattening-filter free (FFF) beam in the RayStation treatment planning system (TPS) for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) treatments. Methods: For beam modeling, percent depth dose curves, profiles and output factors for jaw-collimated fields and stereotactic cones as well as X-jaws transmission were measured. For multi-leaf collimator (MLC) modeling, MLC model parameters such as offset, gain, curvature, leaf tip width, tongue and groove and transmission were determined and output factors for MLC-collimated fields were measured. Absolute dose calibration was also performed. For beam model and MLC model validation, the American Association of Physicists in Medicine Task Group-119 plans, clinical SRS and SBRT plans and end-to-end testing were performed. Results: Beam characteristics of the 6 MV FFF beam agreed well with those in the literature. Validation results showed that our beam model and MLC model were acceptable for SRS and SBRT treatments. Conclusions: The technical information and dosimetric data provided in this study will be a useful reference for other clinics/institutions which will commission the same machine energy in the RayStation TPS.

Stereotactic ablative radiotherapy for hepatocellular carcinoma

Patients with hepatocellular carcinoma(HCC)often present with underlying liver disease and significant comorbidities,limiting treatment tolerance.With the development of improved toxicity models and highly conformal radiation delivery systems,external beam radiotherapy has become a valuable treatment option for liver cancer.Using cutting edge technology,stereotactic ablative radiotherapy(SABR)allows for the delivery of ablative doses in few fractions while sparing uninvolved liver tissue.This approach permits dose escalation and precise tumor targeting with minimal risk of radiation induced liver disease.This review clarifies SABR's role alongside liver-directed treatments such as radiofrequency ablation,transarterial radioembolization,and transarterial chemoembolization in the management of HCC.It also examines the promising potential of SABR combined with immunotherapy to treat advanced HCC.

Hepatocellular carcinoma clinical update: Current standards and therapeutic strategies

Hepatocellular carcinoma(HCC)accounts for the vast majority of primary hepatic malignancies.The overall incidence of this disease has always been significant,but in recent years it has continued to rise,now making HCC one of the leading causes of cancer deaths worldwide.Fortunately,research into the mechanisms of carcinogenesis and treatment options for this disease has also been progressing rapidly.Although the future for new insights and therapies appears more promising than ever,it also remains important to understand both the nature of HCC and the current state-of-the-art for treating affected patients.Although surgery is often considered to be a first choice,many patients present with extensive disease and are therefore not operative candidates.Fortunately,significant clinical advances over the last decade have contributed a number of new or improved treatment options.Many of these treatments require expertise from a variety of different clinical subspecialties.Indeed,managing patients with HCC has rapidly become a multi-modality,multi-disciplinary endeavor in which the details of each in-dividual’s circumstance can greatly impact outcomes,and strategies can be quite nuanced.The purpose of this review is to provide a perspective on the disease itself,the patients who become afflicted,the spectrum of currently available treatment options,and the strategies for their optimal implementation.Such knowledge can be critically important as new data become available on the research front.