Stereotactic Body Radiotherapy Group Research Articles

Nodal radiotherapy for prostate adenocarcinoma recurrence: predictive factors for efficacy.

Nodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes. This retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event-biochemical or imaging recurrence, or death. A total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p < 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time >6 months, and a Gleason score <8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications. For an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients.

Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer

BackgroundWhether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.MethodsWe conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.ResultsA total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P=0.94).ConclusionsFive-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.)

Stereotactic body radiotherapy versus lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity matching score analysis

Background and objectivesThe purpose of this study was to investigate the survival benefit of Stereotactic Body Radiotherapy (SBRT) versus lenvatinib as first-line therapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).Materials and methods147 HCC patients with PVTT were included in this retrospective study, 70 were treated with SBRT and 77 of were treated with lenvatinib. Propensity score matching (PSM) analysis was employed to balance the differences in baseline characteristics between the two groups. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between the two groups. In addition, the safety of patients in both groups was also evaluated.ResultsAfter PSM, 38 patients were matched in each of the two groups. The median OS was 14.5 (95% CI: 10.1–18.9) and 11.1 (95% CI: 9.3–12.9) months in the SBRT and lenvatinib groups, respectively (P = 0.014). The median PFS was 6.8 (95% CI: 5.1–8.5) and 5.0 (95% CI: 3.0–7.0) months, respectively (P = 0.010). The 1-, 2-years OS rates in the two groups were 65.8% vs. 39.5% and 31.6% vs. 10.5%, respectively. The 6-, 12-months PFS rates in the two groups were 57.9% vs. 44.7% and 28.9% vs. 10.5%, respectively. In addition, the SBRT group had a better ORR than the lenvatinib group (52.6% vs. 23.7%, P = 0.009). Patients with good response to SBRT had better survival. Cox proportional hazard model showed that SBRT was an important prognostic factor for OS and PFS. The incidence of hypertension (34.2% vs. 0%) was higher in the LEN group, however, both treatment modalities were well tolerated in the two groups of patients.ConclusionIn HCC patients with PVTT, SBRT had a better survival benefit than Lenvatinib treatment as first-line therapy.

Comparison of Metastasectomy and Stereotactic Body Radiation Therapy for Pulmonary Oligometastasis From Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis

Although there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. We retrospectively analyzed 209 patients with HCC with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting was used to minimize potential bias between the 2 groups. The median follow-up duration was 39.8 months (range, 2.3-166.9 months). The 2-year rate of freedom from local progression was 98.2% in the metastasectomy group and 97.0% in the SBRT group (P = .197). The 2-year rates of overt systemic progression-free survival (PFS) (51.0% vs 46.1%; P = .274), PFS (26.3% vs 9.1%; P = .074), and overall survival (OS, 74.0% vs 57.6%; P = .006) were higher in the metastasectomy group. After the probability of treatment weighting adjustment, the 2-year rates of overt systemic PFS (50.8% vs 52.7%; P = .396), PFS (23.0% vs 24.7%; P = .478), and OS (72.6% vs 83.0%, P = .428) were not significantly different between the 2 groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status.

Comparison of resection, ablation and stereotactic body radiation therapy in treating solitary hepatocellular carcinoma ≤ 5 cm: a retrospective, multicenter, cohort study.

Few studies have focused on the efficacy of stereotactic body radiation therapy (SBRT) in treating early hepatocellular carcinoma (HCC) for curative intention. This study aims to determine the best option among resection, ablation and SBRT in dealing with single HCC no more than 5cm. This multicenter retrospective cohort study included 985 patients from 3 hospitals: 495, 335 and 155 in the resection, ablation and SBRT groups, respectively between January 2014 and December 2021. Subgroup analysis and propensity score matching (PSM) were performed. The SBRT group had unfavorable clinical features including larger tumor size, poorer liver function and more relapsed tumors. The 1-, 3-, and 5-year recurrence free survival (RFS) rates were 84.3%, 66.8% and 56.2% with resection, 73.3%, 49.8% and 37.2% with ablation and 73.2%, 56.4% and 53.6% with SBRT, respectively (P<0.001). The 3-year overall survival (OS) rates were 89.0%, 89.2% and 88.8% in the resection, ablation and SBRT group, respectively (P=0.590). The three modalities resulted in similar RFS and OS after adjusting for clinical factors. Resection provided ideal local tumor control, successively followed by SBRT and ablation. SBRT led to comparable RFS time compared to resection for tumors < 3cm (HR=0.75, P=0.205), relapsed tumors (HR=0.83, P=0.420) and patients with poor liver function (HR=0.70, P=0.330). In addition, SBRT was superior to ablation regarding RFS when tumors were adjacent to intra-hepatic vessels (HR=0.64, P=0.031). SBRT were more minimally invasive, however, gastrointestinal disorders, hepatic inflammation and myelosuppression occurred more frequently. All three approaches could be applied as curative options. Resection remains the best choice for preventing tumor recurrence, and SBRT showed advantages in treating small, recurrent and vascular-type lesions as well as patients with relatively poor liver function.

Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy for Painful Spinal Metastases: A Comparative Analysis of Randomized Trials and Practical Considerations

IntroductionRecent randomized trials have compared the efficacy and safety of stereotactic body radiation therapy (SBRT) with standard conventional external beam radiotherapy (cEBRT) for the treatment of painful spinal metastases. We conducted a composite analysis of these trials in order to inform current practice using pooled outcomes. MethodsData from each randomized trial were abstracted from the final publications with biologically effective doses (BEDs) recalculated for SBRT and cEBRT. Primary outcome measures were overall (OR) and complete pain response (CR) rates at 1, 3, and 6-months, and rates of vertebral compression fracture (VCF). Random effects models were used to estimate primary outcome measures and meta-regression assessed the effect of BED. ResultsFour prospective randomized clinical trials published between 2018 and 2024 were included, with a total of 686 patients (383 and 303 in the SBRT and cEBRT groups, respectively). Dose and fraction (fx) number for the SBRT group ranged from 24 Gy/ 1 fx to 48.5 Gy/ 10 fx (median BED10 50 Gy), and for the cEBRT group from 8 Gy/ 1 fx to 30 Gy/ 10 fx (median BED10 28 Gy). The 1, 3, and 6-month OR rates for SBRT and cEBRT were similar: 53.6%, 52.4%, 58.8% vs. 48.4%, 47.9%, 43.8%, respectively (p>0.05). The 3-month CR rate was significantly higher for SBRT compared to cEBRT (31.9% vs. 14.8%, RR 2.26; 95% CI, 1.48-3.45, p<0.001), but not the 6-month rate (34.4% vs. 16.3% RR 1.83; 95% CI, 0.74-4.53, p=0.194). VCF rates were similar at 17.3% and 18.4% for SBRT and cEBRT, respectively. No significant dose-dependent effect was observed with increasing BED for any efficacy or safety outcomes. ConclusionsOR pain response rates are similar, but CR pain response rates appear higher with SBRT compared to cEBRT, yet no dose-dependent effects were identified despite approximately 1.8x BED dose with SBRT.

Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm

Background & AimsRadiation therapy has been refined with the increasing evidence of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤ 5.0 cm. MethodsPatients with a single HCC lesion ≤ 5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate (CLRR/CDRR), progression-free survival (PFS), overall survival (OS), adverse events (AEs) and subsequent treatments after recurrence were analyzed. ResultsA total of 288 patients received RFA (166) or SBRT (122) were enrolled. The baseline characteristics between the two groups were comparable. The CLRR in the SBRT group was significantly lower than that in the RFA group (HR = 0.30, 95%CI = 0.16 – 0.57, P < 0.001), especially for patients with tumors > 2.0 cm (HR = 0.20, 95% CI = 0.08 – 0.50, P < 0.001) or adjacent to major vessels (HR = 0.29, 95% CI = 0.13 – 0.66, P < 0.001). CDRR, PFS and OS showed no significant differences between the two groups (all P > 0.050). AEs were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and TB increase. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (P < 0.001). ConclusionsBoth RFA and SBRT were effective and safe for HCC with a single lesion ≤ 5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumors > 2.0 cm or adjacent to major vessels. Impact and implicationsStereotactic body radiation therapy (SBRT) may be used as an alternative therapy to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumors > 3 cm and those with 1 to 3 tumors. This study focused on HCC patients with specific tumor burden, a single lesion ≤ 5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumors > 2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting for the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.

Stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) versus TACE and TKIs alone for unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombus (PVTT): A randomized controlled trial.

4102 Background: TKIs-based systemic therapy is a primary treatment option for uHCC. Clinical studies have established the effectiveness and safety of radiotherapy (RT) in patients with PVTT, who typically have a poor prognosis. Previous research has shown that combining TACE and RT can extend survival in HCC patients with PVTT compared to sorafenib treatment. This study aimed to explore the efficacy and safety of combined local therapy (TACE plus SBRT) and TKIs in HCC patients with PVTT. Methods: This single-center, randomized controlled study enrolled patients aged ≥18 years with HCC and PVTT. Additional eligible criteria included ECOG PS 0-1, Child-Pugh score ≤B7, no extrahepatic metastasis on CT scan, and normal liver volume ≥700cc. Patients were randomly assigned to either the SBRT+TACE+TKIs group (Group A) or the TACE+TKIs group (Group B). SBRT was administered at 35-45 Gy in 5 fractions, 3 fractions per week. TKIs (sorafenib 0.4g bid; donafenib 0.2g bid; or lenvatinib 8mg/12mg qd, depending on body weight) were paused during the perioperative period of TACE (up to 4 times). The primary endpoint was the 6-month progression-free survival (PFS) rate, with secondary endpoints including objective response rate (ORR), overall survival (OS), disease control rate (DCR) and treatment-related adverse events (TRAEs). Treatment response was evaluated using mRECIST. Results: A total of 90 patients with uHCC were enrolled from June 2019 to October 2023 in this trial, with baseline characteristics presented in the Table. As of January 5th 2024, the median follow-up time was 14.5 months [IQR, 2.43-55]. The 6-month PFS rate was significantly higher in Group A (78%) compared to Group B (36%, P=0.0245). Group A also showed prolonged median PFS (9.75 vs. 4.89 months, HR=1.703 [95%CI, 1.045-2.777], P=0.0245) and OS (17.93 vs. 9.61 months, HR=1.869 [95%CI, 1.059-3.266], P=0.017). Improved ORR was observed in the SBRT group (74.4% vs. 40.5%, P=0.0015). DCR was 81.4% in Group A and 66.7% in Group B ( P=0.1211). The most common grade 3/4 TRAEs were hypertension (Group A: 17.8%, Group B: 13.3%, P=0.5608), ALT elevation (Group A: 26.7%, Group B: 22.2%, P=0.6237), and AST elevation (Group A: 22.2%, Group B: 15.6%, P=0.4191). There was one treatment-related death in Group B due to liver failure. Conclusions: In uHCC patients with PVTT, the combination of SBRT and TACE-TKIs showed significant survival benefit without the identification of any severe safety concerns. Clinical trial information: ChiCTR1900025300. [Table: see text]

A retrospective study comparing the efficacy of microwave ablation and stereotactic body radiotherapy in colorectal cancer lung metastases.

The purpose of the present study was to assess and compare the efficacy of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) in the treatment of lung metastases from patients with colorectal cancer (CRC) and to identify the preferable treatment modality based on patient and tumor characteristics. Records of 118 patients with CRC with a total of 307 lung metastases who underwent SBRT or MWA between January 2015 and December 2022 were retrospectively analyzed, including the essential clinicopathological information on patients (age, sex and underlying diseases), diagnosis and treatment information [primary tumor site, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9], imaging data [diameter of lung metastasis, location of the metastasis (i.e., whether or not the tumor was adjacent to the vessel or bronchus) and internal features] and follow-up data (postoperative therapy, complications or adverse effects and survival outcomes). For statistical analysis of the local tumor progression (LTP), disease-free survival and overall survival (OS) rates, Cox regression analysis, along with the Kaplan-Meier method adjusted using inverse probability of treatment weighting (IPTW), were performed. The median follow-up duration in the present study was 31.5 months. Multivariable Cox regression analysis revealed that the CEA level, metastasis diameter and internal features were independent predictors of OS. In the IPTW-adjusted analysis, no significant difference in the 1-year OS rate was observed between the SBRT and MWA groups (92.9 vs. 93.9%; P=0.483); however, a notable discrepancy in the treatment modalities was noted, leading to significant differences in the 2- and 3-year OS rates (65.9 vs. 57.6%, P=0.001, and 44.7 vs. 36.4%, P<0.001, respectively). A significant interaction effect for the treatment modality was observed for LTP (P=0.021). In conclusion, the present study revealed that SBRT and MWA have similar therapeutic effects in terms of prolonging the survival of patients with CRC with lung metastases; however, regarding the local control of lung metastases, MWA is associated with a number of significant advantages.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p=.02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Comparison of outcomes following surgical resection, percutaneous ablation or stereotactic body radiation therapy in early-stage, solitary and small (≤3 cm) treatment-naïve hepatocellular carcinoma.

Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment-naïve, solitary HCCs ≤3 cm. This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were treatment-related clinical toxicity rates and local control (LC) rates. There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow-up was 23 months (range, 3-60 months) from diagnosis. The 3-year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3-year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3-year LC rate for the entire cohort was 98%. In patients with treatment-naïve, early-stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients.

Stereotactic body radiotherapy compared to conventionally fractionated radiotherapy for locally advanced or oligometastatic pancreatic cancer.

677 Background: Pancreatic cancer, particularly in its locally advanced and oligometastatic forms, poses a formidable therapeutic challenge. Radiotherapy remains an important treatment in an attempt to gain local control, however there is no consensus on whether stereotactic body radiotherapy (SBRT) is appropriate as compared to conventionally fractionated radiotherapy (CFRT). Herein, we report our experience. Methods: We conducted a retrospective analysis of patients with locally advanced and oligometastatic pancreatic cancer who received definitive radiotherapy at our institution between January 2010 and March 2023 with SBRT 30-50 Gy in 3-5 fractions or CFRT 50-60 Gy in 25-30 fractions. We excluded all patients with resectable disease who underwent surgery. Clinicopathological data, treatment regimens, and radiation parameters were collected and analyzed. Results: A total of 51 patients (17 females, 34 males; median age: 67.9 years). 24 patients (47.1%) were treated with CFRT, and 27 patients (52.9%) were treated with SBRT. Median time of follow-up for the entire cohort was 14.4 months. A total of 13 patients (25%) experienced a Local failure (LF) at a median time of 18.5 months, with no difference observed between CFRT and SBRT groups. Cancer-specific mortality (CSM) was statistically significant with a lower mortality rate in SBRT (37%) vs CFRT group (63%) (p&lt;0.004). Several treatment characteristics and dosimetric factors such as sex, age, receipt of chemotherapy, type of chemotherapy, use of elective nodal irradiation, GTV size, biologically equivalent dose (BED) corrected prescribed dose, minimum dose to GTV, or max dose to GTV did not predict local failure. There was no difference in QOL and toxicity between the two groups. Conclusions: In our cohort, local failure rates remain high and were similar between patients treated with SBRT compared to those treated with conventionally fractionated radiotherapy. We were unable to identify any specific predictors for local recurrence in this patient population. Our observation of a lower CSM rate among patients who received SBRT needs further study. The findings underscore the need to further improve radiotherapeutic approaches in an attempt to improve local control in locally advanced disease.

Comparing resection and stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion: A propensity score matched study.

521 Background: Macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor. Current guidelines endorse systemic therapy for MVI. Local therapies present a potential for obliteration of MVI and improved survival. Surgery has been the standard local therapy at our institution, and stereotactic body radiotherapy (SBRT) has emerged as an alternative local therapy for this patient population. Methods: In this retrospective study, one-to-one optimal pair propensity score matching was used to compare outcomes of HCC patients with MVI who underwent surgery or received SBRT. Matching was done based on sex, age, ECOG, cirrhosis presence, Child-Pugh class, number of tumours, tumour volume, alpha-fetoprotein level, ALBI score, Japanese Classification of portal vein invasion, and hepatic vein invasion. Overall survival was estimated using the Kaplan-Meier method and between group differences determined using the log-rank test. The cumulative incidence of recurrence, accounting for the competing risk of death, was compared using Gray’s test. Results: Ninety of 193 patients were included after matching (45 patients in both the surgery and SBRT groups) (Table). The SBRT group had a median OS of 15 months (95% CI: 10-38), while in the surgery group it was 24 months (95% CI: 11-81). Comparing the 12-, 36-, and 60-month overall survival (OS) rates between the SBRT group (57%, 33%, 15%) and the surgery group (58%, 37%, 34%), there was no statistically significant differences (p=0.16); the 5-year OS was double in the surgical resection group. The 12-, 36-, and 60-month cumulative incidence of HCC recurrence in the SBRT group (47%, 73%, 75%) was comparable to the surgery group (69%, 69%, 69%) (p=0.89). Conclusions: Long term survival is possible in patients with HCC and MVI in a substantial minority of patients with HCC and MVI treated with local therapies. There was no statistical difference in outcomes; however, surgical resection resulted in numerically longer survival outcomes compared to SBRT after propensity score adjustment. There is rationale for investigating both local therapies with systemic therapies in future clinical trials. [Table: see text]

Incorporating stereotactic body radiation therapy for inoperable pancreatic cancer.

656 Background: The management of inoperable pancreatic cancer (PC) is controversial. We sought to compare local progression (LP) for inoperable PC managed with chemotherapy (CHT) and/or stereotactic body radiation therapy (SBRT). Methods: This single-institution retrospective review analyzed 94 patients diagnosed with locally advanced (LA), medically inoperable, or metastatic PC between 2014 and 2022. Patients received CHT alone, sequential (seq) CHT + SBRT, or SBRT alone. The primary endpoints were LP and intervention due to local progression (ILP) from start of treatment. Obstructive symptoms needing intervention, percutaneous endoscopic gastrostomy tube, gastrojejunostomy, or bleeding needing transfusion were considered ILP. Primary tumor growth on imaging or ILP were defined as LP. Fine-Gray regression models with treatment received considered a time-varying covariate were used to compare ILP and LP between treatment groups where death without LP was treated as a competing risk adjusting for ECOG, stage, age and year of diagnosis. In the subgroup of patients who received SBRT, patients were stratified at the median time between diagnosis and receipt of SBRT, and risk of ILP and LP was compared between the groups using cause-specific cumulative incidence functions. Results: Of 94 patients, 51 had CHT alone, 21 received seq CHT + SBRT, and 22 had SBRT alone. The median year of diagnosis was 2019 (range, 2014 - 2022). The median ECOG was 1 with worse ECOG in SBRT alone and seq CHT + SBRT groups (p = 0.012). There were more LA or metastatic cases in the CHT (78%) and seq CHT + SBRT groups (67%) compared to the SBRT group (23%) [p &lt; 0.001]. The median SBRT dose was 36Gy (range, 25 – 40Gy) in 5 fractions. Rates of LP and ILP were higher for CHT alone (68.6%, 39.2%) compared to seq CHT + SBRT (42.9%, 38.1%) or SBRT alone (18.2%, 4.5%) [p &lt; 0.001; p = 0.004]. Higher rate of ILP associated with an increasing year of diagnosis (HR = 2.03, p &lt; 0.005) and younger age of diagnosis (HR = 0.922, p = 0.011). The median time to SBRT was 116 days. Early (&lt; 116 days) vs late SBRT LP rates differed (ILP: 4.8% vs 30%, LP: 14.3% vs 40%). Cause-specific cumulative incidence functions showed that death without LP favored early vs late SBRT (p = 0.009). Additionally, death without ILP favored early vs late SBRT (p=0.011). Conclusions: LP rates are high among patients with inoperable PC. SBRT for inoperable PC provides reasonable local control. Early SBRT reduces the need for ILP before death compared with late SBRT. Further investigation into the role of SBRT for inoperable PC is necessary. [Table: see text]

Contribution of neoadjuvant chemotherapy and radiation therapy (intensity-modulated radiation therapy with concurrent chemotherapy versus stereotactic body radiation therapy alone) on tumor volume regression in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma: A single institution experience.

707 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a minority of patients (pts) eligible for curative resection. Pts with borderline resectable or locally advanced (BR/LA) PDAC frequently receive neoadjuvant chemotherapy (NAC) +/- radiation therapy (RT) to improve resectability. Here, we report the individual contribution of NAC and RT (either intensity modulated RT + concurrent chemotherapy (IMRT+CC) or stereotactic body RT (SBRT) alone) on tumor regression by measuring tumor volumes. Methods: We performed a single institution retrospective review of PDAC pts who underwent resection between 2011-2021 and were part of a tumor biobank registry. Tumor measurements were performed at baseline, post-NAC, and post-RT by five independent, blinded abdominal radiologists. Analyses were performed using paired t-tests, two-proportion z-tests, log-rank tests, and Mann-Whitney U test. Results: We identified 49 BR/LA pts who received NAC followed by RT who had complete pre- and post-treatment imaging. Fifteen pts received IMRT+CC and 28 received SBRT. The effect of NAC on tumor volumes (-29.2% vs -26.3%, p=0.66; mean percent change) and maximum diameter (-9.2% vs -12.0%, p=0.58) was similar within the IMRT+CC and SBRT groups. Both IMRT+CC (-7.12 cm3, p=0.003) and SBRT (-2.70 cm3, p=0.001) resulted in significant tumor regressions. IMRT+CC achieved a significantly greater overall mean percent change in tumor volume (-53.4% vs -28.8%, p=0.024) and maximum diameter (-30.4% vs -16.2%, p=0.020) compared to SBRT. Pts receiving IMRT+CC or SBRT had similar tumor volumes (10.88 vs 11.74 cm3, p=0.87, respectively) and maximum diameter (3.45 vs 3.17 cm, p=0.48) prior to RT. IMRT+CC resulted in improved tumor volume response (&gt;30% regression; 80.0% vs 46.4%; p=0.033) but not an improved response rate by RECIST criteria (46.7% vs 21.4%; p=0.085). Mean resected tumor volumes (by pathological review) for those receiving IMRT+CC (n=9) and SBRT (n=23) were 4.34 vs 13.1 cm3 (p=0.049). The R0 (86.7% vs 85.7%, p=0.93) and N0 (73.3% vs 53.6%, p=0.21) resection rates between the two groups were similar. Compared to SBRT, IMRT+CC resulted in an improved recurrence free survival (RFS; 2.36 vs 1.31 years; p=0.026), but did not meet statistical significance for an overall survival benefit (mOS; 2.85 vs 2.03 years, p=0.19). Conclusions: We found that IMRT+CC yielded superior radiographic volumetric regression and improved RFS but did not significantly impact mOS. Correspondingly, resected tumors from patients treated with IMRT+CC were smaller than those obtained from patients treated with SBRT. The role of IMRT+CC and SBRT in PDAC remains to be clearly defined.

SBRT with ipilimumab and nivolumab to metastatic MSS colorectal and pancreatic cancer: A pooled analysis of four prospective phase II trials.

752 Background: The role of immunotherapy (IO) in microsatellite stable (MSS) pancreatic and colorectal cancer is limited. Stereotactic body radiation therapy (SBRT) is increasingly used in the limited metastatic setting, however its use with IO remains an area of investigation for both target response and overall systemic response. Here we evaluate the local failure rate of irradiated target lesions with and without IO. Methods: We pooled four prospective phase II single-arm studies of patients with metastatic MSS colorectal or pancreatic cancer treated with SBRT alone or with IO. Those in the first study (NCT01239381) received ablative liver SBRT to a maximum biologically effective dose (BED) of 48-100 Gy. Patients in the remaining studies received low dose SBRT to liver, lung, or nodal metastases with 24 Gy in 3 fractions to a BED of 43.2 Gy in combination with Ipilimumab and Nivolumab during the first (NCT04361162, NCT04575922) or second (NCT03104439) cycles. Local failure rates at the time of first progression were estimated by the cumulative incidence with non-target progression only and death as competing risks and compared using Gray’s test. The best response at the target was measured with the RECIST 1.1 criteria using the largest reduction in target size during follow up. Fisher’s exact test was used to compare objective response (ORR) and disease control rates (DCR), while the Wilcoxon rank sum test was performed to compare target size and percentage of tumor reduction. Results: Across all four studies there were 154 evaluable patients including 50 who received ablative SBRT and 104 patients who received low dose SBRT with IO. There were 92 patients with colorectal and 62 with pancreatic cancer. Median target size was 3.7 cm in the ablative SBRT group and 2.8 cm in the IO group (P=0.04). The 6-month, 1-year, and 2-year local failure rates were 10%, 18%, and 20% respectively following ablative SBRT and 24%, 25%, and 26% following low dose SBRT with IO (P=0.32). The ORR was 50.0% with SBRT alone and 23.1% with the addition of IO (P=0.001). There was no significant difference in the DCR (80.0% vs. 68.3%, P=0.18). The percent decrease in size was significantly higher in those with ablative SBRT (median -53.0% vs. -10.6%, p=0.02). There was no difference in the percent tumor response with respect to primary tumor type (P=0.13), KRAS (P=0.11) or TP53 (P=0.27) status. Conclusions: Despite the use of low dose SBRT with immune checkpoint inhibitors, there was no significant difference in local failure rates compared to ablative SBRT. Ablative SBRT dosing yielded a significantly higher depth of response. As clinical and preclinical studies suggest liver metastases are less responsive to IO, understanding dose and fractionation schemas for optimal local control is critical. Further studies are needed to explore the radiation dose with regards to local control when delivered with IO.

Early stereotactic body radiation therapy improves progression-free survival of first-generation EGFR tyrosine kinase inhibitors in EGFR-mutated lung cancer: an observational cohort study.

Stereotactic body radiation therapy (SBRT) in treating non-small-cell lung cancer (NSCLC) exhibits a remarkable therapeutic efficacy. However, its effectiveness in overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced EGFR mutations (EGFRm) NSCLC remains uncertain. We aimed to analyze the effect of SBRT on patients with first-line EGFR-TKIs. Eligible patients with advanced NSCLC initially diagnosed with EGFRm were enrolled. Patients in the EGFR-TKIs group received only the first-generation EGFR-TKIs until disease progression or death, while the others in the EGFR-TKIs + SBRT group received EGFR-TKIs and early SBRT (dose of 40-60 Gy/5-8 F) targeting the primary lung tumor at 1 month after EGFR-TKIs. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were treatment-related adverse effects, overall survival (OS), and sites of initial failure. A total of 184 advanced NSCLC patients with EGFRm were enrolled, including 39 patients in the EGFR-TKIs + SBRT group and 145 patients in the EGFR-TKIs group. The median PFS was 15.50 months in the EGFR-TKIs + SBRT group compared to 9.33 months in the EGFR-TKIs group (p = 0.0020). However, the median OS was 29.10 months in the EGFR-TKIs + SBRT group and 26.33 months in the EGFR-TKIs group, with no significant difference observed (p = 0.22). SBRT is an independent positive prognostic factor for PFS in advanced EGFRm NSCLC. EGFR exon 19 deletion mutation (16.33 vs 11.55 months, p = 0.0087) and fewer metastases (0-5) (31.94 vs 9.59 months, p = 0.0059) were associated with improved PFS in EGFR-TKIs + SBRT versus EGFR-TKIs. Combination therapy increased radiation pneumonitis mainly in Grades 1-2 (89.74% vs 0.0%). The EGFR-TKIs + SBRT group mainly had new site failure (57.10% vs 32.10%) rather than the original site failure. Early SBRT for primary lung tumors may overcome targeted resistance in advanced EGFRm NSCLC patients combined with EGFR-TKIs without serious toxicities, especially for EGFR exon 19-del. ChiCTR-OIN-17013920.

Comparison of Treatment Outcomes Between Thoracoscopic Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

Objective: To compare the risk of death, tumor recurrence, metastasis, and disease progression in early-stage non-small cell lung cancer (NSCLC) patients treated with thoracoscopic surgery and stereotactic body radiotherapy (SBRT). Methods: Patients who underwent radical surgery and SBRT for NSCLC between April 2010 and November 2021 were retrospectively analyzed. Continuous and categorical variables were compared using the Mann-Whitney U and Chi-square test, respectively. Kaplan-Meier curves were used to evaluate the survival outcomes of each patient group. Cox proportional hazard regression analyses were performed to estimate the risk of death, tumor recurrence, metastasis, and disease progression. Results: A total of 167 patients were enrolled, of whom 75 and 92 underwent SBRT and surgery, respectively. The median follow-up was 45 months (range, 4-105 months). SBRT patients were observed to be significantly older (median, 76.0 vs 67.0 years; P < .001), and associated with significantly higher mortality rate (42.7% vs 26.1%, P = .024). However, no significant difference in overall survival duration was seen between the SBRT and surgery groups (45.0 vs 41.0 months; P = .199). SBRT patients demonstrated significantly lower rates of metastasis (12.0% vs 30.4%, P = .004), and significantly longer metastasis-free survival (39.0 months vs 35.5 months, P = .020). The remaining outcomes, including tumor recurrence and disease progression rates, were similar between the groups. Compared to surgery, SBRT did not significantly associate with death, recurrence, or disease progression. Kaplan-Meier curves showed significant differences in overall, tumor recurrence-free, and disease progression-free survival between the groups (log-rank P < .05). Conclusions: SBRT demonstrated similar overall survival compared to radical surgery, and associated with significantly reduced risk of tumor metastasis. Our study thereby suggests SBRT as the best treatment option for patients with inoperable NSCLC.

Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study

Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete. From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0-4·5) for patients in the standard-of-care group versus 7·2 months (4·5-10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35-0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2-not reached] vs 2·2 months [95% CI 2·0-4·5]; HR 0·41, 95% CI 0·22-0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5-8·7] vs 4·2 months [1·8-5·5]; 0·78, 0·43-1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. National Cancer Institute.

Hyperfractionated Accelerated Radiotherapy Versus Stereotactic Body Radiotherapy in the Treatment of Limited-Stage Small Cell Lung Cancer: A Matched-Pair Analysis.

Concurrent chemoradiotherapy based on hyperfractionated accelerated radiotherapy (HART) is the first-line recommended regimen for the treatment of small-cell lung cancer (SCLC). However, Stereotactic Body Radiotherapy (SBRT) is also regarded as an effective treatment for limited-stage (LS) SCLC, and the efficacy and safety of HART versus SBRT stay controversial. In this study, 188 LS-SCLC patients were retrospectively divided into two groups receiving chemotherapy combined with either HART or SBRT. In HART group, patients received 4500 cGy in 30 fractions, administered twice daily for 3 weeks. Whereas in the SBRT group, a total radiation dose of 4000-4500 cGy was delivered in 10 fractions over 2 weeks. Thirty-three pairs of patients were finally included for next analysis. The estimated objective response rates were 63.6 % (21/33) and 78.8 % (26/33) in HART group and SBRT group, respectively (P = 0.269). Furthermore, there was no significant difference between HART and SBRT groups in overall survival (26 months vs. 29 months, P = 0.362) and progression free survival (11 months vs. 15 months, P = 0.223). As for the adverse events, toxicity of both groups is similar and slight that no grade 4 event was observed. Grade 3 pneumonitis cases were all occurred in the HART group (9.1%, 3/33, P = 0.238), and grade 3 esophagitis cases were all occurred in the SBRT group (6.1%, 2/33, P = 0.492). Compared with HART, SBRT could be another effective treatment with satisfactory safety for the concurrent chemoradiotherapy in patients with LS-SCLC.