| Background and Objective:Stereotactic Body Radiation Therapy(SBRT)is widely used in clinical practice,playing a significant role in controlling metastatic lesions and providing curative treatment.This study aims to assess the feasibility and efficacy of SBRT in the treatment of adrenal gland metastases(AGM)from liver cancer,oligometastatic prostate cancer(omPCa),and localized prostate cancer(PCa).Regarding the control of metastatic lesions,multiple studies have demonstrated the benefits of SBRT for AGM,showing a high local control rate and low toxicity.The role of SBRT for AGM in patients with liver cancer has not been well-discussed before.Therefore,we report our two-institution experience to further elaborate on the feasibility and effectiveness of SBRT in treating AGM from liver cancer.SBRT can be utilized in the treatment of metastatic lesions and even primary tumors in patients with PCa.Rare studies explore the role of curative radiotherapy for both primary and metastatic lesions in the treatment of low-burden omPCa.The second part of this study aimed to investigate the potential survival benefits of this approach.Moreover,this is the first study to report the outcomes of curative radiotherapy for both local and distant metastatic lesions in patients with omPCa from China.SBRT is widely used in the curative treatment of localized PCa,but there remains a debate over the optimal dosage.The third part of this study aims to compare the safety and efficacy of high-dose biologically effective dose(BED)and standard-dose regimens in SBRT for localized PCa using propensity score matching(PSM)analysis.High-Risk/Very High-Risk Prostate Cancer(HR/VHR-PC)is a subtype found among patients with localized PCa characterized by highly invasive and malignant potential.According to NCCN guidelines,both radiation therapy and surgery are treatment options for patients with HR/VHR-PC.However,radical prostatectomy(RP)often entails a high recurrence rate.There is currently limited research on SBRT treatment for HR/VHR-PC patients.We aim to compare the oncological outcomes of SBRT and RP in HR/VHR-PC patients across multiple institutions.Methods:Part Ⅰ:Two-institution results of SBRT for treating AGM from liver cancerA total of 23 liver cancer patients(19 males,4 females)with 24 AGMs treated by SBRT from July 2006 to April 2021 were retrospectively included in this part of the study.Toxicity was assessed based on clinical adverse events using the Common Terminology Criteria for Adverse Events(CTCAE)version 5.0.Effectiveness was assessed based on local control(LC),progression-free survival(PFS),and overall survival(OS),which were calculated using the Kaplan-Meier method.Univariate analyses were performed using the log-rank test.Relevant covariates were evaluated using Cox proportional hazards models.Part Ⅱ:Curative Radiotherapy for Local and Metastatic Lesions in omPCaA retrospective analysis was conducted on patients with 33 omPCa patients who received curative radiotherapy for the primary site and metastatic lesions between July 2012 and June 2022.The inclusion criteria mandated fewer than five oligometastases,excluding regional lymph nodes by imaging examinations,with no prior radiotherapy or RP for omPCa.OS was the primary endpoint,while biochemical progression-free survival(bPFS)and radiological progression-free survival(rPFS)were secondary endpoints.Survival analysis was conducted using the Kaplan-Meier method,followed by univariate analysis using the log-rank test.Subsequently,multivariate analysis was performed using the Cox proportional hazards regression model.Part Ⅲ:Analysis of Standard vs Dose-Escalated SBRT in Localized PCa:A PSM Comparative Evaluation of Survival OutcomesBetween June 2012 and February 2022,patients with localized prostate cancer treated with SBRT were selected from two medical institutions.The high-dose group(n=12)received a high dose of BED1.5(>250Gy),and the control group(n=119)followed the NCCN guidelines(35-37.5 Gy/5f,BED1.5 198.3-225Gy).PSM was utilized to eliminate confounding variables,taking into account NCCN prognostic grading,Gleason pathological grading,TNM staging,age,and Prostate-Specific Antigen(PSA)levels.The R 4.3.1 software was employed for 1:4 nearest neighbor matching,resulting in 12*4 matched samples.Kaplan-Meier analysis was conducted using SPSS v26.0 to assess differences in OS,Prostate Cancer-Specific Survival Rate(CSS),bPFS,LC,and Distant Metastasis-Free Survival(DMFS).Log-rank tests were utilized to compare differences between different treatment groups.Part Ⅳ:Comparison of SBRT and RP in High-Risk/Very High-Risk Prostate Cancer:A Large Multi-Center Comparative Analysis Using PSMOur study retrospectively reviewed data from three medical centers between 2007 and 2021,encompassing a total of 316 patients with high-risk(HR)/very high-risk(VHR)prostate cancer(PC).The study participants were all aged 18 years or older,pathologically diagnosed with prostate adenocarcinoma,meeting the criteria for high-risk or very high-risk patients according to NCCN guidelines,including Gleason pathological scores of 8-10,pathological grade group 4 or higher,PSA>20 ng/mL,or clinical stage ≥T3.The initial definitive treatment methods were RP or SBRT.Among them,119 patients received SBRT as the primary definitive treatment,while 197 patients underwent RP.PSA levels were monitored monthly during the follow-up period.Study endpoints included bPFS,PFS,OS,and CSS.Statistical analysis was conducted using R 4.3.1,matching PSM baseline characteristics through binary logistic regression models and maintaining balance between the two groups using one-to-one optimal matching.Survival curves were estimated using the Kaplan-Meier method.Multivariable Cox regression analysis was employed to assess factors influencing biochemical control and disease progression in PCa patients.Results:Part Ⅰ:Among 23 patients with liver cancer,the median dose was 40 Gy delivered in 5 fractions,yielding a corresponding median biological effective dose(BED10,α/β=10Gy)of 72 Gy.The median overall follow-up time was 15.4 months(range:4.2-70.6 months).The complete response(CR),partial response(PR),stable disease(SD)and progressive disease(PD)rates were 25.0%,20.8%,33.3%,and 20.8%,respectively.All 6 patients with AGM accompanying symptoms had varying degrees of alleviation after SBRT.The 0.5-,1-year,and 2-year LC rates were 87.5%,77.8%,and 77.8%,respectively.The 0.5-,1-year and 2-year OS rates were 95.5%,66.8%,and 41.1%,respectively.The treatments were all tolerated with only one patient reporting a grade-3 hepatic injury.The univariate analysis concluded that only gross tumor volume(GTV)<34.5 ml(p=0.039)was associated with a favorable LC rate.Multivariate analysis revealed favorable predictors associated with OS,including GTV<34.5 ml(p=0.043),systemic therapy(p=0.017),and absence of distant metastasis after SBRT(p=0.009).Part Ⅱ:A total of 33 patients,including 31 de novo oligometastatic hormone-sensitive prostate cancer(omHSPC)patients and 2 oligometastatic castration-resistant prostate cancer(omCRPC)patients,were enrolled in the study.The median follow-up was 38.8 months(range:4.2-70.6 months).The median OS was 127.7 months(2yr:100%,5yr:81.2%).The median bPFS was 58.9 months,and the median rPFS was 55.3 months.Factors associated with poorer survival were pre-radiotherapy Castration-Resistant Prostate Cancer(CRPC)status,symptomatic lesions,and transurethral resection of the prostate(TURP)before radiotherapy.Multivariate analysis indicated potential associations:external beam radiation therapy(EBRT)synchronized with androgen deprivation therapy(ADT)/chemotherapy,pre-radiotherapy hormone-sensitive status,and higher pre-radiotherapy prostate-specific antigen(PSA)levels were possibly linked to longer rPFS.The simultaneous presence of lymph node and bone metastases increased the risk of biochemical recurrence.No acute adverse reactions of grade 3 or higher were observed;the incidence of chronic grade 3 reactions was 3.03%.Part Ⅲ:In contrast to the control group,the high-dose group had a higher percentage of patients(75%)in the high or very high-risk categories,with 33%of patients concurrently receiving combined hormonal therapy.The median follow-up period extended to 74.0 months(range:5.3-117.0 months).The 5-year OS for the high-dose group was 88.9%,and the 7-year OS was 66.7%,while the control group had a 5-year OS of 92.5%and a 7-year OS of 83.4%(p=0.402).The overall CSS for all patients in the study was 95.9%at 5 years and 89.9%at 7 years,with a median CSS of 111.17 months(range:105.63-116.70).The high-dose group displayed a 5-year CSS rate of 88.9%and a 7-year CSS rate of 88.9%,whereas the control group’s 5-year CSS was 97.4%and 7-year CSS was 90.5%(p=0.480).Regarding biochemical control,the high-dose group demonstrated a 5-year bPFS rate of 91.7%and 7-year bPFS rate of 91.7%,whereas the control group displayed a 5-year bPFS rate of 82.1%and a 7-year bPFS rate of 67.4%(p=0.497).In univariate analysis,a notable finding indicated that an elevated Gleason score was linked to impaired biochemical control(p=0.028).Additionally,in alignment with prognostic stratification,patients with more adverse classifications,showed suboptimal biochemical control(p=0.028).In the context of local control,the high-dose group achieved 7-year LC rates of 100%,while the control group had 7-year LC rates of 95.1%(p=0.569).The high-dose group had a 5-year and 7-year DMFS rate of 91.7%and 91.7%,while the control group had rates of 97.6%and 81.6%respectively(p=0.918).Univariate analysis revealed that patients with underlying health conditions were less likely to experience distant metastasis than those without such conditions(p=0.047).The majority of patients exhibited good tolerability to SBRT,with no Grade 3 or higher adverse reactions observed in any of the patients.Part Ⅳ:This part of this study retrospectively reviewed patient data from three large hospitals between 2007 and 2021,including 316 HR/VHR-PC patients who met the NCCN guidelines for high-risk or very high-risk criteria.Among them,119 patients were treated with SBRT and 197 with RP.Using 1:1 PSM,238 matched cases were included.The median follow-up time was 69.04 months(range:7.57-161.57 months).The biochemical recurrence rate was 41.18%for RP patients and 23.53%for SBRT patients.The median biochemical progression-free survival(bPFS)was 84.17 months(range:53.8-218.1 months)after RP and 126.93 months(not reached)after SBRT.The 3-year,5-year,and 7-year bPFS rates were 67.9%,58.2%,and 54.6%for RP,compared to 92.8%,80.5%,and 72.1%for SBRT(p<0.001).Factors associated with bPFS in the overall patient cohort included Gleason score(HR=1.564(1.199-2.041),p=0.001),local prostate treatment after initial treatment(HR=3.242(1.862-5.645),p<0.001),and post-treatment ADT(HR=2.780(1.703-4.537),p<0.001).Cox analysis for RP patients indicated that factors associated with bPFS included the presence of comorbidities(HR=6.972,95%CI:1.667-29.159,p=0.008),postoperative Gleason score grouping(HR=2.257,95%CI:1.460-3.489,p<0.001),and pathological evidence of capsular invasion(HR=4.734,95%CI:1.375-16.230,p=0.014).For SBRT patients,Cox analysis showed that subsequent radiation or surgery(HR=5.580,95%CI:2.009-15.496,p=0.001)and Gleason score gradegroup(HR=1.956,95%CI:1.332-2.872,p=0.001)were associated with bPFS.Among the 119 RP patients,33(27.73%)experienced disease progression,recurrence,or non-regional lymph node or distant metastasis.18 SBRT patients(15.13%)experienced disease progression.The 3-year,5-year,and 7-year PFS rates were 88.7%,75.8%,and 60.2%for RP,compared to 95.5%,89.3%,and 79.9%for SBRT(p=0.002).The 3-year,5-year,and 7-year CSS rates for the RP group were 100%,97.5%,and 88.9%,while for the SBRT group,they were 99.1%,95.9%,and 91.7%(p=0.954).The median OS was 130.81 months(range:119.768-141.851 months)for SBRT and 135.55 months(range:126.506-144.600 months)for RP.The 3-year,5-year,and 7-year OS rates for the RP group were 99.2%,96.7%,and 83.5%,compared to 98.2%,90.0%,and 75.2%for SBRT(p=0.081).Notably,the RP group exhibited a higher proportion of postoperative adjuvant/salvage treatments compared to the SBRT group after definitive treatment.Conclusions:In summary,SBRT is feasible,effective,and well-tolerated in the treatment of liver cancer with AGM,omPCa with low metastatic burden,and localized PCa.When treating distant metastases,SBRT is a safe and effective technique for liver cancer AGM,particularly for patients with smaller GTV volumes(<34.5 ml).Additionally,smaller metastatic lesion volumes,fewer distant metastatic lesions,and systemic therapy interventions are more likely to improve OS.Furthermore,SBRT can be used for radical radiotherapy of both primary and metastatic sites in omPCa patients.Curative radiotherapy for local and metastatic lesions with an optimistic bPFS and rPFS may enhance the OS of omHSPC and omCRPC patients.In the treatment of localized PCa,the use of high biologically effective dose with SBRT compared to standard dosage does not significantly improve tumor control or survival rates.Among HR/VHR-PC patients,the rate of adjuvant or salvage therapy was higher in the RP group compared to the SBRT group,but the SBRT group showed a trend towards better PFS and biochemical control.Both groups maintained high levels of CSS and OS with no significant differences. |
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