Freedom From Local Progression Research Articles

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy : Aretrospective study.

Hepatocellular carcinoma (HCC) poses aunique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as apromising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child-Pugh score (CPS) progression was also explored. SBRT demonstrated 93.4% freedom from local progression (FFLP) at 12months. Notably, anear minimum dose (D98%) below 61 Gy as an equivalent dose in 2‑Gy fractions with α/β 10 Gy (EQD2α/β10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed adose-response relationship for FFLP and D98% with 95% and 98% probability of FFLP at adose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1year and 34.3% at 3years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked amean EQD2α/β3-8 dose to the liver (12.8-12.6) with a10% likelihood of ncRILD. SBRT offers acompelling option for achieving high local control and promising survival outcomes in HCC. The study supports aradiation dose range of 61-73.1 Gy, coupled with amean liver dose under 12.6-12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Hypofractionated Radiotherapy for Hematologic Malignancies during the COVID-19 Pandemic and Beyond.

Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6-17 fractions/2.67-5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort and 100, 87 (95% CI: 56.4-96.5%), and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9-90.5%) and 100, 66.1 (95% CI: 36.4-84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. HFRT in HM provides excellent local control to be validated in a larger prospective study.

Hypofractionated Radiotherapy for Hematological Malignancies during COVID-19 Pandemic and Beyond.

Conventionally fractionated radiotherapy (RT) has shown to have excellent local control in hematological malignancies (HM). Up to date there is none or scant literature about the use of hypofractionated radiotherapy (HFRT) for the treatment of HM, this single institution study analyzed the efficacy of HFRT in HM. We hypothesized that HFRT in HM will result in a similar local tumor control that has been reported with standard fractionated RT. In this retrospective study, we analyzed the data from patients within the provincial cancer registry diagnosed with HM treated with a curative intent using HFRT regimens suggested by International Lymphoma Radiation Oncology Group between 2020-2022 during the COVID-19 pandemic. Primary outcome of the study was overall response rate (ORR), measured as complete response (CR), partial response (PR) or stable disease (SD) within the irradiated field determined radiologically or clinically post completion of RT. Secondary end point was freedom from local progression (FFLP), calculated from the date of initiation of RT to the first date among in-field progression, death, and last follow-up. Summary statistics were used to describe cohort and treatment characteristics. FFLP was calculated by 1 minus cumulative incidence accounting for competing risk (i.e., death). Of the 36 patients included for analysis, 18 were aggressive non-Hodgkin lymphoma (NHL), 9 were indolent NHL, 6 were Hodgkin lymphoma (HL) and 3 were other HM. Among them 25 had consolidation RT and 11 had definitive RT. HFRT daily dose per fraction ranged from 2.67 Gy to 5 Gy and total dose regimens ranged from 18 Gy to 42.5 Gy in 6 - 17 fractions and median equivalent dose in 2 Gy fractions (EQD2) for alpha/beta = 10Gy was 36 Gy (±7.5). ORR for the entire cohort was 94.4%. With a median follow up of 13.2 months, FFLP at one year for the entire cohort was 91.5% and death without infield progression was 8.7%. Among the 4 patients who had in radiation field recurrence, 2 had aggressive NHL and 2 had HL. No grade 3 or 4 acute toxicities were reported. This retrospective study using HFRT showed an ORR and FFLP comparable to historical studies using standard fractionation. Further long-term follow-up is warranted to confirm these findings.

Efficacy and Safety of Image-Guided Hypofractionated Radiotherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

To evaluate the efficacy and safety of image-guided 10-fraction hypofractionated radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Between 2016 and March 2022, 69 HCC with PVTT patients received RT (40-50Gy/10fx) in our institutions. The median prescribed dose of 50 Gy (range, 40-50 Gy, BED10; 56-75 Gy10) was delivered in 10 fractions in all patients. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main portal vein. Response evaluation was performed using response evaluation criteria in solid tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. In this cohort, 4.3% of patients had Vp1 PVTT, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. The median PTV volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy in 10 fractions. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 18.5 months, and 1-year FFLP, PFS, and OS rates were 84.8%, 26.9%, and 62.2% respectively. At 3 months after RT, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, AFP ≥ 600 IU/ml (HR 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and modified Union for International Cancer Control (mUICC) stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.8%) cases of grade ≥3 toxicity: grade 3 AST/ALT elevation (n = 1), and acute cholangitis (n = 1). Hypofractionated RT demonstrated promising local PVTT control with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED10 = 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.

Favorable Survival after Definitive Ablative RT in Surgically Resectable Pancreatic Cancer Patients

Surgical resection has been considered the only curative option for patients with pancreatic adenocarcinoma (PDAC). Ablative RT ≥100Gy BED10 (A-RT) is associated with favorable survival in patients with locally advanced unresectable disease. We sought to evaluate A-RT outcomes in patients with technically resectable disease who did not undergo surgery. Our prospectively maintained database of patients treated with A-RT was queried for consecutive patients with radiographic T1/T2 resectable PDAC. Patients were treated with a standardized technique within a large academic cancer center regional network. Ablative RT using several hypofractionated regimens was delivered on either standard Linacs with respiratory motion management, CBCT image guidance and selective adaptive replanning or MR-Linac with compression belt and daily on-line adaptive replanning. Freedom from local progression (FFLP), distant metastasis-free and overall survival (DMFS and OS, respectively) were analyzed using the Kaplan Meier estimates. Between 2016 and 2022, 28 patients (54% male) with radiographically resectable PDAC received definitive A-RT. Median age was 80 (interquartile range, 77-84) years and 23 (82.1%) had KPS of 80 or below. Eighteen patients (64.3%) had T2 cancer, 5 (17.9%) were node positive, and 23 (82.1%) had head location. Median size was 2.6 (range, 1.6-4.0) cm with a median carbohydrate antigen 19-9 (CA19-9) of 160.5 (0-1823) U/mL. Twenty patients (71.4%) received induction chemotherapy for a median of 2.4 (0-6.2) months. RT regimens delivered on conventional Linacs unless otherwise indicated included 75Gy in 25 fractions (n = 15), 67.5Gy in 15 fractions (n = 10), 50Gy in 5 (N = 2, MR Linac), 60Gy in 10 (n = 1). 24-month FFLP and DMFS were 78.8% (52.3-91.7%) and 17.7% (95% CI, 5.8%-34.8%), respectively. 24-month and 48-month rate of OS from A-RT were 49.1% (95% CI, 27.53-67.5%) and 36.3 (95%16.0-57.1%). Grade 3 acute and late GI toxicity was noted in 3 and 1 patients, respectively, including 2 bleeding events treated with transfusions. There were no ≥ grade 4 events. In patients with surgically resectable PDAC we found that definitive A-RT following multiagent induction therapy was associated with oncologic outcomes similar to resection with minimal toxicity.

MR-Guided Stereotactic Ablative Body Radiotherapy for Pancreatic Oligometastases from Renal Cell Carcinoma

Patients with pancreatic metastases from renal cell carcinoma (RCC) have been reported to have an unusually favorable prognosis. Traditionally, treatment for these pancreatic oligometastases comprises either surgical resection or systemic therapy. However, stereotactic ablative body radiotherapy (SAbR) may be an effective, non-invasive alternative strategy, provided that it shows acceptable toxicity and high local control rates among treated patients. We reviewed all patients treated with MR-guided SABR for pancreatic oligometastases from renal cell carcinoma at a single institute. We explored adverse events (AE), freedom from local progression (FFLP), progression-free survival (PFS), and freedom from start of systemic therapy (FFST) among treated patients. The Kaplan-Meier method was used to describe the time-to-event endpoints. From June 2019 to September 2022, we identified 11 patients treated with MR-guided SAbR to 31 pancreatic oligometastases from RCC. Patients had a mean age of 65.6 years (±6.8) and had a median of 3 irradiated pancreatic metastases (range 1-7). Metastases were treated with 5 fractions of 7 Gy (n = 1 metastasis) or 8 Gy (n = 30 metastases) per fraction. One grade 3 adverse event (bleeding) was observed. At a median follow-up of 10.5 months (range 5-46 months), estimated FFLP at 1 year was 100%. 1y-PFS was 83% (95% CI 58-100%), and 1y-FFST was 91% (95% CI 75-100%). First exploration of MR-guided SAbR to pancreatic oligometastases from RCC indicates that it can be an effective and safe treatment option. Moreover, MR-guided SAbR may facilitate deferral of systemic therapy initiation in this select group of patients with favorable prognosis.

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients. Between March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33-66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed. The median follow-up duration after RT was 14.2 months (range, 10.0-18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6-4.5) and 14.8% (95% CI, 12.5-17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8-76.2), 0%, and 85.7% (95% CI, 75.9-95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient. The addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.

Efficacy and Dose-Response Relationship of Stereotactic Body Radiotherapy for Abdominal Lymph Node Metastases from Hepatocellular Carcinoma.

The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC). Between 2010 and 2020, data of 148 patients with HCC with abdominal LNM, including 114 who underwent SBRT and 34 who received conventional fractionation radiation therapy (CFRT), were collected. A total radiation dose of 28-60 Gy was delivered in 3-30 fractions, with a median biologic effective dose (BED) of 60 Gy (range, 39-105 Gy). Freedom from local progression (FFLP) and overall survival (OS) rates were analyzed. With a median follow-up of 13.6 months (range, 0.4-96.0 months), the 2-year FFLP and OS rates of the entire cohort were 70.6% and 49.7%, respectively. Median OS of the SBRT group was longer than the CFRT group (29.7 vs. 9.9 months, P = .007). A dose-response relationship was observed between local control and BED in either the entire cohort or the SBRT subgroup. Patients who received SBRT with a BED ≥60 Gy had significantly higher 2-year FFLP and OS rates than those who received a BED <60 Gy (80.1% vs. 63.4%, P = .004; 68.3% vs. 33.0%, P < .001). On multivariate analysis, BED was an independent prognostic factor for both FFLP and OS. SBRT achieved satisfactory local control and survival with feasible toxicities in patients with HCC with abdominal LNM. Moreover, the findings of this large series suggest a dose-response relationship between local control and BED.

Clinical Efficacy of Hypofractionated Proton Beam Therapy for Intrahepatic Cholangiocarcinoma.

Forty-seven patients with intrahepatic cholangiocarcinoma (IHCC) who received proton beam therapy (PBT) were analyzed to evaluate the clinical efficacy and safety of hypofractionated PBT in patients with inoperable or recurrent IHCC. The median prescribed dose of PBT was 63.3 GyE (range: 45-80 GyE) in 10 fractions, and the median duration of follow-up in all the patients was 18.3 months (range: 2.4-89.9 months). Disease progression occurred in 35 of the 47 (74.5%) patients; local, intrahepatic, and extrahepatic progression occurred in 5 (10.6%), 20 (42.6%), and 29 (61.7%) patients, respectively. The 2-year freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS) rates, and median time of OS were 86.9% (95% confidence interval [CI], 74.4-99.4%), 16.8% (95% CI, 4.3-29.3%), 42.7% (95% CI, 28.0-57.4%), and 21.9 months (95% CI, 16.2-28.3 months), respectively; grade ≥ 3 adverse events were observed in four (8.5%) patients. In selected patients with localized disease (no viable tumors outside of the PBT sites), the median time of OS was 33.8 months (95% CI, 5.4-62.3). These findings suggest that hypofractionated PBT is safe and could offer a high rate of FFLP and promising OS in patients with inoperable or recurrent IHCC.

What is appropriate target delineation for MRI-based brachytherapy for medically inoperable endometrial cancer?

PURPOSEFor medically inoperable endometrial cancer (MIEC), the volumetric target of image-guided brachytherapy (IGBT) techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. METHODS AND MATERIALSFor all MIEC patients receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution, BT dose was prescribed to HRCTV defined as GTV plus endometrial cavity with a planning goal of a summed EQD2 D90 of ≥85 Gy. Freedom from local progression (FFLP) and overall survival (OS) were estimated via Kaplan Meier method. RESULTSThirty two MIEC patients received EBRT followed by MRI-based IGBT between December 2015 and August 2020. Median follow up was 19.8 months. A total of 75% of patients had FIGO stage I/II disease, 56% endometrioid histology, and 50% grade 3 disease. OS was 73.6% (95% CI 57.8%–89.3%) at 12 months and 65.8% (95% CI 48.4%–83.2%) at 24 months. FFLP was 93.8% (95% CI 85.3%–100%) at 12 months and 88.8% (95% CI 86.6%–91.0%) at 24 months. 23 (72%) patients experienced no RT-related toxicity, while 2 of 32 patients (6%) experienced late grade 3+ toxicities (grade 3 refractory vomiting; grade 5 GI bleed secondary to RT-induced proctitis). CONCLUSIONSPatients with MIEC receiving definitive EBRT followed by MRI-based IGBT prescribed to the MRI-defined HRCTV demonstrated favorable long-term local control with an acceptable toxicity profile.

Multi-Institutional Comparison of Ablative Radiation Therapy in 5 Versus 15-25 Fractions for Locally Advanced Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Ablative RT doses ∼100Gy BED₁₀ are associated with improved overall survival (OS) in patients with locally advanced unresectable pancreatic cancer (LAPC), but the optimal fractionation scheme remains unknown. <h3>Materials/Methods</h3> We performed a retrospective analysis of consecutive LAPC patients treated at 2 high-volume institutions with either 50 Gy in 5 fractions using a 0.35T MR Linac and online adaptive replanning between 2018-2021 or 67.5-75 Gy in 15-25 fractions using CBCT guidance and selective offline adaptive replanning between 2016-2019. All were treated with breath hold or gating. Elective nodal coverage was used in 94%. Clinical characteristics between the groups were compared using Fisher's exact test. Freedom from local progression (FFLP) by RECIST and OS were estimated from time of RT with the Kaplan-Meier method. Log-rank test and Cox proportional hazards regression model were used for univariate (UVA) and multivariate (MVA) analyses. <h3>Results</h3> 183 patients were evaluated including 62 (34%) treated with 50 Gy in 5 fractions, 23 (123%) treated with 67.5 Gy in 15 fractions, and 98 (54%) treated with 75 Gy in 25 fractions. Median age was 67 years (range 35 to 91), 53% were male, 72% had a head tumor location, 81% were T3/4 with a median tumor size of 3.8 cm (range 1.4-7.4 cm) and 38% were lymph node positive. Patients receiving 5 fractions were more likely to be N0 than patients receiving 15-25 fractions (69.3% vs 44.6%, p=0.0219), and there were no other clinical differences between the groups. 98% received induction chemotherapy for a median of 3.9 months (FOLFIRINOX 61%, Gemcitabine/Nab-paclitaxel 29%, other 10%). Median follow-up was 38 months. Median FFLP and OS were 31 and 18 months, with 2-yr FFLP and 2-yr OS of 62.9% (95%CI 47.9 – 69.3%) and 36.2% (26.0 – 40.9%), respectively. There were no significant differences in FFLP (HR= 1.493, 95%CI 0.8030 – 2.775, p=0.1598) or OS (HR=1.321, 95%CI 0.8835 – 1.974, p=0.1580) between patients receiving 5 vs 15-25 fractions, respectively, on UVA. Likewise, after adjusting for T stage, nodal status, tumor size, chemotherapy type and duration, there were no significant differences in OS between the groups on MVA (HR=1.234, 95%CI 0.8151 – 1.833, p=0.3070). The rate of grade 3+ GI bleeding was 4.8% and 8% (p=0.5476) in patients receiving 5 vs 15-25 fractions, respectively. <h3>Conclusion</h3> In appropriately selected LAPC patients, ablative RT (BED₁₀ ∼100 Gy) in 5 fractions delivered with MR guidance and online adaptive replanning or 15-25 fractions delivered with CT guidance and selective offline adaptive replanning both appear to achieve excellent efficacy and minimal severe toxicity. Choice of fractionation scheme should be based on anatomical considerations and available technology.

Dose Response of Bulky Tumors in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

<h3>Purpose/Objective(s)</h3> This study sought to assess whether there is a radiotherapy (RT) dose response for bulky tumors in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). <h3>Materials/Methods</h3> Patients with r/r DLBCL (age ≥18 years) treated with salvage- or palliative-intent RT (2008-2020) at a single institution were included. Course-level data were examined to assess in-field responses of index lesions. Courses used for either post-therapy consolidation, CNS or skin disease, and TBI conditioning were excluded. Index lesion size ≥7.5 cm was considered bulky. EQD2s (α/β = 10) were calculated to accurately compare biologic effective doses between conventional and hypofractionated (≥2.5 Gy/fraction) schemes. Post-treatment responses of index lesions were classified using Lugano Criteria. Objective response rates (ORR), defined as achieving either CR or PR, were compared between non-bulky and bulky tumors using Fisher's exact test. Freedom from local progression (FFLP) and overall survival (OS, patient-level data) from RT start date were recorded. Bulky disease impacts on FFLP and OS were assessed using Kaplan-Meier and multivariable-adjusted Cox proportional hazard regression analyzes. <h3>Results</h3> 151 r/r DLBCL patients underwent 183 RT courses (median follow-up time: 6 months, IQR: 2-17 months). Median age at RT was 67 years (IQR: 56-72 years) with a male/female ratio of 55%/45%. Non-bulky and bulky tumors were treated in 109 (60%) and 74 (40%) cases, respectively. Intent was classified as salvage or palliative in 68 (37%) and 115 (63%) cases, respectively. Median EQD2 was 33 Gy (IQR: 23-39 Gy) with hypofractionation used in 84 (46%) cases. Of those with post-RT imaging (n = 146, 80%), there was a trend towards lower ORR for bulky vs. non-bulky tumors (50% vs. 65%, p = 0.087; CR: 21% vs. 42%, PR: 29% vs. 23%, SD: 28% vs. 14%, PD: 22% vs. 22%). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (≤30 Gy vs. >30 Gy: 27% vs. 64%, p = 0.014), whereas a lower EQD2 cut-off was sufficient for non-bulky tumors (<20 Gy vs. ≥20 Gy: 38% vs. 73%, p = 0.0076). In all courses, bulky tumors were significantly associated with shorter FFLP (median: 5.6 months vs. not reached, HR = 2.30, 95% CI: 1.24-4.26, p = 0.0079) and OS (median: 3.7 vs. 10.1 months, HR = 1.66, 95% CI: 1.06-2.58, p = 0.025). Amongst bulky tumors, there was a trend towards improved FFLP with RT regimens with higher EQD2s (20-30 Gy vs. <20 Gy - median: 4.2 vs. 2.3 months, HR = 0.38, 95% CI: 0.09-1.62, p = 0.19; >30 Gy vs. <20 Gy - median: not reached vs. 2.3 months, HR = 0.34, 95% CI: 0.11-1.01, p = 0.053). <h3>Conclusion</h3> In this study, bulky r/r DLBCL tumors were associated with less favorable outcomes in salvage and palliative settings. If durable local control of bulky tumors is needed, RT regimens using higher EQD2s (>30 Gy) should be considered, including cases where shortened, hypofractionated courses are opted for such as during the SARS-CoV-2 pandemic, bridging to CAR-T cell infusion, or prior to allogeneic stem cell transplantation.

Stereotactic body radiation therapy versus radiofrequency ablation in hepatocellular carcinoma: an up-date meta-analysis.

Radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) are available locoregional curative treatments for nonsurgical Hepatocellular carcinoma (HCC) patients. We aimed to compare the clinical efficacy and safety of SBRT versus RFA for HCC. A computerized bibliographic search was performed using PubMed, Embase, the Cochrane Library and Web of Science to identify comparative studies. The primary outcome was overall survival (OS), and the secondary outcomes were freedom from local progression (FFLP) and treatment-related complications. In total, there were 17 trials involving 22,180 patients. Patients receiving RFA showed significantly better 1-, 2- year OS (OR 0.69, 95% CI 0.50-0.96, P = 0.141,OR 0.69, 95% CI 0.53-0.89, P = 0.082), whereas SBRT resulted in significantly better 1-, 2-, 3- year FFLP (OR 2.19, 95% CI 1.44-3.34, P = 0.303; OR 1.57, 95% CI 1.12-2.19, P = 0.268; OR 2.22, 95% CI 1.70-2.90, P = 0.470). There were no significant differences for 3-, 5- year OS in both groups (OR 0.94, 95% CI 0.65-1.38, P = 0.001; OR 0.98, 95% CI 0.68-1.34, P = 0.016). The overall treatment-related complication rate did not differ significantly between the two treatment arms, while SBRT was significantly associated with Child-Pugh worsening. Though SBRT has excellent FFLP, RFA yields superior short-term survival for HCC. But the discrepancy between FFLP and OS requires further investigation.

Efficacy of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma by Underlying Liver Disease Etiology

<h3>Purpose/Objective(s)</h3> The use of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has been steadily increasing. Recently, it was reported that patients with HCC have a differential response to immune-checkpoint inhibitor based on the background liver disease etiology. Whether outcomes of SBRT are affected by underlying liver disease etiology is currently unknown. We therefore reviewed outcomes of SBRT with special focus on tumor size, BED, and underlying liver disease etiology. <h3>Materials/Methods</h3> This study is a retrospective review of HCC patients treated with SBRT at one institution between 2009 and 2021. Patients with tumor thrombus or extrahepatic disease were excluded. Kaplan-Meier curves and Cox regression models were used to describe freedom from local progression (FFLP) and overall survival (OS) rates and examine potential prognostic factors. <h3>Results</h3> One-hundred and sixty-four patients met study entry criteria. Median gross tumor volume (GTV) size was 9.3 cc (range 0.3 to 762.4 cc). 67% of patients had a history of hepatitis C, and 9% had a history of hepatitis B. 71% of patients received our institutional standard SBRT dose of 50 Gy in 5 fractions (biological effective dose [BED] 100 Gy). Other patients received lower doses ranging from 30 to 47.5 Gy in three to five fractions (BED range 48 to 93 Gy) if necessary to preserve normal liver tissue. Median follow-up time was 43 months (interquartile range [IQR] 36 to 52 months). Seventeen in-field failures and 67 deaths have occurred. 3- and 5-year FFLP rates were 84% and 75%, and 3- and 5-year OS rates were 65% and 48%, respectively. History of hepatitis C was associated with better FFLP (HR=0.36 (95% CI:0.14, 0.94), p=0.038). Treatment with 50 Gy was associated with better FFLP compared to treatment with lower doses for patients with hepatitis C (HR=0.15 (95%CI: 0.04, 0.63), p=0.01) but not for other patients (HR=3.1 (95%CI: 0.38, 24.7), p=0.29). <h3>Conclusion</h3> SBRT for HCC yields excellent local control, particularly for patients with hepatitis C. In hepatitis C patients, dose escalation beyond a BED of 100Gy may be more important for local control than in non-hepatitis C patients. More studies are necessary to better understand if HCC etiology should be considered when planning SBRT.

A phase II trial of hypofractionated high-dose proton beam therapy for unresectable liver metastases

Background and purposeProton beam therapy (PBT) is an effective treatment option for primary malignant liver disease. However, evidence regarding liver metastasis is insufficient. We aimed to investigate the efficacy and safety of hypofractionated high-dose PBT in the treatment of metastatic liver disease. Materials and methodsFrom January 2019 to January 2021, patients with unresectable liver metastases were enrolled. For PBT, the dose schemes of 60 Gy relative biological effectiveness (GyRBE) in 5 fractions (fx) (biologically effective dose [BED] 132 GyE) or 70 GyRBE in 10 fx (BED 119 GyE) were used. Either a passive scattered beam or pencil beam scanning (PBS)-based intensity-modulated proton therapy (IMPT) was performed with proper respiratory management. The primary endpoint of the study was 6-month freedom from local progression (FFLP) rate; and the Kaplan–Meier method was used to calculate the FFLP and survival rates. ResultsOf the 49 liver metastases in 46 patients, the colorectum accounted for 60% of the primary cancer sites, followed by the gastrointestinal organs and pancreas/biliary tract. Forty patients presented only 1 liver metastasis, while the other 6 patients had 2 to 4 metastases. The Six-month FFLP rate was 95.2%. The 1-year FFLP rate in patients with <3 cm liver metastasis was 87.4%, while that was 74.1% in patients with > 3 cm group (p = 0.087). With regard to systemic treatment, the 1-year FFLP rate after PBT was better (94.1%) than that without systemic treatment (75.8%; p = 0.051). Regarding PBT-related toxicity, one patient developed a grade 2 gastric ulcer, while none of the patients developed grade ≥3 toxicities. ConclusionsHypofractionated PBT with a BED > 100 GyRBE for liver metastasis is safe and effective, given the high rate of 6-month FFLP without grade ≥3 treatment-related toxicities. However, further improvements are required for larger tumors and/or those without prior systemic therapy.

Proton Beam Therapy for Treatment-Naïve Hepatocellular Carcinoma and Prognostic Significance of Albumin-Bilirubin (ALBI) Grade.

Simple SummaryProton beam therapy (PBT) has not been generally recommended as an initial treatment for hepatocellular carcinoma (HCC) due to the insufficiency of data on PBT for treatment-naïve HCC until now, and albumin-bilirubin (ALBI) grade has been shown to be an effective assessment of liver dysfunction and more discriminatory for survival than the Child–Pugh classification. This study evaluated the efficacy of PBT as first-line treatment in treatment-naïve HCC and assessed the prognostic significance of ALBI grade in these patients. Our findings showed that PBT could result in comparable local tumor control and survival outcomes in treatment-naïve HCC patients to those of other recommended first-line treatments, with a safe toxicity profile compared to our institutional cohort data and previous other studies, and ALBI grade and tumor stage were independent predicting factors for overall survival.To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2–64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7–100.7), 43.3% (95% CI, 28.2–58.4), and 69.2% (95% CI, 54.9–83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.

Stereotactic radiosurgery for the treatment of brainstem metastases: a multicenter retrospective study

BackgroundBrainstem metastases (BSM) are associated with a poor prognosis and their management represents a therapeutic challenge. BSM are often inoperable and, in absence of randomized trials, the optimal radiation treatment of BSM remains to be defined. We evaluated the efficacy and toxicity of linear accelerator (linac)-based stereotactic radiosurgery (SRS) and hypofractionated steretotactic radiotherapy (HSRT) in the treatment of BSM in a series of patients treated in different clinical centers.MethodsWe conducted a multicentric retrospective study of patients affected by 1–2 BSM from different histologies who underwent SRS/HSRT. Freedom from local progression (FLP), cancer-specific survival (CSS), overall survival (OS), and treatment-related toxicity were evaluated. In addition, predictors of treatment response and survivals were evaluated.ResultsBetween 2008 and 2021, 105 consecutive patients with 111 BMS who received SRS or HSRT for 1–2 BSM were evaluated. Median follow-up time was 10 months (range 3–130). One-year FLP rate was 90.4%. At the univariate analysis, tumor volume ≤ 0.4 cc, and concurrent targeted therapy were associated with longer FLP, with combined treatment that remained a significant independent predictor [0.058, HR 0.139 (95% CI 0.0182–1.064]. Median OS and CSS were 11 months and 14.6 months, respectively. At multivariate analysis, concurrent targeted therapy administration was significantly associated with longer OS [HR 0.514 (95%CI 0.302–0.875); p = 0.01]. Neurological death occurred in 30.4% of patients, although this was due to local progression in only 3 (2.8%) patients.ConclusionLinac-based SRS/HSRT offers excellent local control to patients with BSM, with low treatment-related toxicity and no apparent detrimental effects on OS. When treated with ablative intent, BSM are an uncommon cause of neurological death. The present results indicates that patients with BSM should not be excluded a priori from clinical trials.

Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients

Breast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients. Retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall survival (OS). One-hundred fifty-three (153) metastases in 79 oligoprogressive breast cancer patients were treated with SBRT. Median follow-up 24months. Median NEST 8months. Predictive factor of NEST at the multivariate analysis (MVA) was the number of treated oligometastases (HR 1.765, 95%CI 1.322-2.355; p = < 0.01). Systemic treatment after SBRT was changed in 29 patients for polymetastatic progression and in 10 patients for oligometastatic progression < 6months after SBRT. The 2-year FLP in the overall population was 86.7%. A biological effective dose (BED) > 70Gy10 was associated with improved FLP (90% versus 74.2%). The median tPMC was 10months. At the MVA the only factors significantly associated with tPMC were the number of oligometastases (HR 1.172, 95%CI 1.000-1.368; p = 0.03), and the local control of the treated metastases (HR 2.726, CI95% 1.108-6.706; p = 0.02). SBRT can delay the switch to a subsequent systemic treatment, however patient selection is necessary. Several predictive factors for treatment tailoring have been identified.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases

PurposeRandomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and MaterialsThe RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. ResultsNinety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. ConclusionsTo our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

Stereotactic Body Radiation Therapy versus Concurrent Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Propensity Score-Matched Analysis.

Simple SummaryIn the lack of direct comparative evidence of stereotactic body radiation therapy, we reviewed one of the largest locally advanced pancreatic cancer cohort homogeneously treated in a tertiary cancer center. Our propensity score–matched analysis shows comparable outcomes between stereotactic body radiation therapy and concurrent chemoradiotherapy in terms of survival, local control, and treatment-related toxicities. Considering the advantages of SBRT such as short treatment duration, better tolerance, easy combination with systemic treatment, and the potential for dose escalation, further investigation of the feasibility of SBRT as an alternative to CCRT in treating locally advanced pancreatic cancer is required.In locally advanced pancreatic cancer (LAPC), stereotactic body radiation therapy (SBRT) has been applied as an alternative to concurrent chemoradiotherapy (CCRT); however, direct comparative evidence between these two modalities is scarce. The aim of this study was to compare the clinical outcomes of SBRT with CCRT for LAPC. We retrospectively reviewed the medical records of patients with LAPC who received SBRT (n = 95) or CCRT (n = 66) with a concurrent 5-FU-based regimen between January 2008 and July 2016. The clinical outcomes of freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS), and toxicities were analyzed before and after propensity score (PS) matching. After a median follow-up duration of 15.5 months (range, 2.3–64.5), the median OS, PFS, and FFLP of the unmatched patients were 17.3 months, 11 months, and 19.6 months, respectively. After PS matching, there were no significant differences between the SBRT and CCRT groups in terms of the 1-year rates of OS (66.7% vs. 80%, p = 0.455), PFS (40.0% vs. 54.2%, p = 0.123), and FFLP (77.2% and 87.1%, p = 0.691). Our results suggest SBRT could be a feasible alternative to CCRT in treating patients with LAPC.