Feasibility of marker-less stereotactic body radiotherapy for hepatocellular carcinoma.

BACKGROUND: The feasibility of marker-less stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has not yet been established, and, thus, was examined in the present study. MATERIAL AND METHODS: We retrospectively investigated patients who received marker-less SBRT for locally untreated HCC tumors between July 2005 and December 2018. Radiotherapy planning CT was performed under fixation with vacuum cushions and abdominal compression. The clinical target volume (CTV) was equivalent to the gross tumor volume (GTV). The internal target volume (ITV) margin to CTV was determined from calculations based on the motion of the diaphragm. The planning target volume (PTV) margin to ITV was 5-6 mm. In the set-up, radiotherapy planning CT and linac-integrated cone-beam CT performed in the same imaging and fixation settings were merged by referring to the anatomical components surrounding target tumors. The primary endpoint was the 3-year cumulative local tumor progression rate. The upper limit of the 95% confidence interval for the 3-year cumulative local tumor progression rate was less than 7.0%, which was interpreted as favorable local control and feasible for marker-less SBRT. Local tumor progression was assessed by mRECIST. RESULTS: We reviewed 180 patients treated with 35-40 Gy/5 fractions. The median follow-up time for the local tumor progression of censored tumors was 32.3 months (range, 0.3-104). The 3-year cumulative local tumor progression rate was 3.0% (95% CI, 1.1-6.5%). The 3-year overall survival rate was 71.6% (95% CI, 63.5-78.2%). Regarding acute hematologic toxicities, grade 3 hypoalbuminemia and thrombocytopenia were detected in 1 (0.6%) and 5 (2.9%) patients, respectively. Treatment-related death from SBRT was not observed. SBRT was initiated within 7 days after radiotherapy planning CT for 84% (152/180) of patients. CONCLUSIONS: Marker-less SBRT for HCC achieved favorable local control that fulfilled the threshold. This result suggests that marker-less SBRT with appropriate settings is a feasible treatment strategy.

Hypofractionated radiotherapy for hepatocellular carcinomas adjacent to the gastrointestinal tract.

AIM: Decisions regarding therapeutic plans for inoperable patients with hepatocellular carcinoma (HCC) adjacent to the gastrointestinal (GI) tract are challenging because radiofrequency ablation has the potential risk of thermal injury. Moreover, the response rate of transcatheter arterial chemoembolization is relatively low and stereotactic body radiotherapy (SBRT) is believed to be too toxic. We have applied hypofractionated radiotherapy (HFRT) for such lesions. This study investigated the outcomes and toxicities of this treatment. METHODS: Among consecutive HCC patients treated with radiotherapy with curative intent at our institution between 2015 and 2019, we retrospectively extracted those outside of the indication for SBRT due to exceeding the constraint of the GI tract and who were treated using HFRT with a prescription dose of 42 Gy in 14 fractions and prophylactic proton pump inhibitor administration for 6 months. The oncological outcomes and toxicities were investigated. RESULTS: A total of 66 patients with 73 lesions were eligible. The median follow-up period was 24.0 months. The local recurrence, intrahepatic recurrence, liver-related death, and overall survival rates at 2 years were 11.3%, 50.6%, 15.9%, and 60.4%, respectively. Six (9.1%) patients experienced Child-Pugh score deterioration ≥2 within 6 months following treatment. Two and one patient developed grades 2 and 3 gastroduodenal bleeding, respectively. CONCLUSIONS: HFRT can achieve good local control in patients with HCC adjacent to the GI tract, with low GI toxicity incidence. Our study demonstrated that HFRT can be a potentially curative treatment option for lesions.

Comparison of stereotactic body radiotherapy and radiofrequency ablation for hepatocellular carcinoma: Systematic review and meta-analysis of propensity score studies.

AIM: Stereotactic body radiotherapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC) and has shown excellent local control (LC), as has radiofrequency ablation (RFA). As no randomized controlled trial has compared SBRT and RFA for HCC, data from a propensity score matched study (PSMS) are valuable. However, the results varied greatly and depended on composing factors of Barcelona Clinic Liver Cancer staging (BCLC-factors) adjusted. Therefore, we undertook a systematic review and meta-analyses of the studies focusing on BCLC-factors matching. METHODS: We systematically searched PubMed, the Cochrane database, EMBASE, and Web of Science to identify studies comparing RFA and SBRT using propensity scores. The hazard ratios (HRs) of overall survival (OS) and LC from BCLC-factor-matched and -unmatched PSMS were pooled. Heterogeneity between the data from these studies was assessed. RESULTS: Three BCLC-factor-matched studies were identified. Stereotactic body radiotherapy led to comparable OS (HR, 0.89; 95% CI, 0.74-1.08; p = 0.24; I2  = 0%; p for heterogeneity, 0.56) and significantly better LC (HR, 0.39; 95% CI, 0.30-0.51; p < 0.001; I2  = 0%; p for heterogeneity, 0.67). We also identified three additional BCLC-factor-unmatched studies (HR of OS, 1.41; 95% CI, 1.21-1.65; p < 0.0001; I2  = 0%; p for heterogeneity, 0.63). However, considerable heterogeneity was observed for HR of OS between BCLC-factor-matched and -unmatched studies (I2  = 92.6%; p for heterogeneity, 0.0002). CONCLUSIONS: When BCLC-factors were properly adjusted, the results of the meta-analysis revealed equivalent OS and better LC for SBRT compared with RFA. Stereotactic body radiotherapy could be an alternative treatment option for HCC.

Multicenter prospective study of stereotactic body radiotherapy for previously untreated solitary primary hepatocellular carcinoma: The STRSPH study.

AIM: To prospectively evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for patients with previously untreated solitary primary hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria included the following: (1) primary solitary HCC; (2) no prior treatment for HCC; (3) Child-Turcotte-Pugh score of seven or less; and (4) unsuitability for or refusal of surgery and radiofrequency ablation (RFA). The prescribed dose of SBRT was 40 Gy in five fractions. The primary endpoint was 3-year overall survival (OS); the secondary endpoints included local progression-free survival (LPFS), local control (LC), and adverse events. The accrual target was 60 patients, expecting a 3-year OS of 70% with a 50% threshold. RESULTS: Between 2014 and 2018, 36 patients were enrolled; enrollment was closed early because of slow accrual. The median tumor size was 2.3 cm. The median follow-up at the time of evaluation was 20.8 months. The 3-year OS was 78% (95% confidence interval [CI]: 53%-90%). The 3-year LPFS and LC proportion were 73% (95% CI: 48%-87%) and 90% (95% CI: 65%-97%), respectively. Grade 3 or higher SBRT-related toxicities were observed in four patients (11%), and grade five toxicities were not observed. CONCLUSIONS: This study showed acceptably low incidence of SBRT-related toxicities. LC and OS after SBRT were comparable for previously untreated solitary HCC for patients unfit for resection and RFA. Although a definitive conclusion cannot be drawn by this study, the promising results indicate that SBRT may be an alternative option in the management of early HCC.

Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis.

Potentially curative treatments for early-stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early-stage HCC. Consecutive patients with ≤3 early-stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3-year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7-9.2; versus 12.9%, 95% CI, 9.9-16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3-year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2-77.7; and 70.4%; 95% CI, 58.5-79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well-compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.

Local control by salvage stereotactic body radiotherapy for recurrent/residual hepatocellular carcinoma after other local therapies.

Background: To clarify local control by salvage stereotactic body radiotherapy (SBRT) for recurrent/residual hepatocellular carcinoma (HCC) compared with initial definitive SBRT for local treatment-naïve HCC.Material and methods: We retrospectively investigated HCC patients that received SBRT between July 2005 and December 2017. We classified HCC tumors as the initial definitive SBRT group (Arm-1; initial definitive SBRT, Arm-2; initial definitive planned SBRT following transarterial chemoembolization (TACE)) and salvage SBRT group (Arm-3; salvage SBRT for recurrent/residual tumors after TACE, Arm-4; salvage SBRT for recurrent/residual tumors after radiofrequency ablation (RFA), Arm-5; salvage SBRT for recurrent/residual other than Arm-3 or Arm-4). Local control was evaluated by mRECIST.Results: We reviewed 389 HCC tumors of 323 patients treated by 35-40 Gy/5 fr. The median follow-up time for local recurrence of tumors was 34.8 months (range, 6.5-99.2). The cumulative local recurrence rates at 3 years of Arm-1-5 were 1.4% (95% CI, 0.3-4.4%), 5.0% (95% CI, 1.6-11.5%), 12.4% (95% CI, 5.7-21.9%), 14.8% (95% CI, 3.3-34.3%) and 7.3% (95% CI, 1.9-18.0%), respectively. The cumulative local recurrence rates at 3 years of initial definitive treatment and salvage treatment groups were 2.8% (95% CI, 1.1-5.6%) and 11.1% (95% CI, 6.3-17.3%), respectively (p=.004). On multivariate analysis, salvage treatment and the tumor diameter were significant risk factors of local recurrence (p = .02, p < .001 respectively). Estimated overall survival at 3 years for all patients in initial definitive treatment and salvage treatment groups were 71.5% (95% CI, 63.4-78.1%) and 66.1% (95% CI, 56.4-74.2%), respectively (p = .20). No treatment-related death caused by SBRT was observed.Conclusions: This analysis showed local control of salvage SBRT for recurrent/residual HCC was significantly worse than that of initial definitive SBRT for local treatment-naïve HCC. However, local control of salvage SBRT was relatively good, and salvage SBRT is one of the favorable treatment options for recurrent/residual HCC.

Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation.

BACKGROUND: Curative treatment options for patients with early stage hepatocellular carcinoma (HCC) include resection, liver transplantation, and percutaneous ablation therapy. However, even patients with solitary HCC are not always amenable to these treatments. The authors prospectively investigated the clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) for solitary HCC. METHODS: A phase 2 study involving SBRT and optional transarterial chemoembolization (TACE) was conducted in patients with Child-Pugh grade A or B and underlying, solitary HCC (greatest tumor dimension, ≤4 cm) who were unsuitable candidates for resection and radiofrequency ablation. The prescription dose was 35 to 40 grays in 5 fractions. The primary endpoint was 3-year local tumor control. RESULTS: From 2007 to 2012, 101 patients were enrolled, and 90 were evaluable with a median follow-up of 41.7 months (range, 6.8-96.2 months). Thirty-two patients were treatment-naïve, 20 were treated for newly diagnosed intrahepatic failure, and 38 were treated for residual or recurrent HCC as salvage therapy. Thirty-two patients did not receive TACE, 48 received insufficient TACE, and 10 attained full lipiodol accumulation. The 3-year local control rate was 96.3%, the 3-year liver-related cause-specific survival rate was 72.5%, and the overall survival rate was 66.7%. Grade 3 laboratory abnormalities were observed in 6 patients, and 8 patients had Child-Pugh scores that worsened by 2 points. CONCLUSIONS: SBRT achieved high local control and overall survival with feasible toxicities for patients with solitary HCC, despite rather stringent conditions. SBRT can be effective against solitary HCC in treatment-naive, intrahepatic failure, residual disease, and recurrent settings, taking advantage of its distinctive characteristics. Cancer 2016;122:2041-9. © 2016 American Cancer Society.

Local control correlates with overall survival in radiotherapy for early-stage non-small cell lung cancer: A systematic review.

PURPOSE: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC). MATERIALS AND METHODS: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated. RESULTS: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307-1.199; p < 0.001), 0.360 (95% CI: 0.128-0.593; p = 0.002), 0.766 (95% CI: 0.489-1.044; p < 0.001), and 0.574 (95% CI: 0.275-0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254-0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030-0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468-0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000-0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%). CONCLUSIONS: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively.

Role of stereotactic body radiotherapy in multidisciplinary management of liver metastases in patients with colorectal cancer.

In the treatment of colorectal cancer patients with distant metastases, the development of new anticancer agents has considerably prolonged progression-free survival. Such survival benefits attributed to chemotherapy have increased the relative significance of local therapy in patients with limited metastases. The liver is recognized as the most common site of metastasis of colorectal cancer because of the intestinal mesenteric drainage to the portal veins. Hepatic resection of isolated liver metastases of colorectal cancer is the only option for a potential cure. However, hepatic metastases are resectable in only approximately 20% of the patients. For remaining patients with high-risk resectable liver metastases or those who are unfit for surgery, less invasive, local therapies including radiation therapy (stereotactic body radiation therapy, SBRT) may have a potential role in treatment. Although the local control rate of SBRT for colorectal liver metastases has room for improvement, its less-invasive nature and broad indications deserve consideration. Future research should include SBRT dose escalation or the selection of patients who benefit from local ablative therapies. SBRT may offer an alternative, non-invasive approach for the treatment of colorectal liver metastases in a multidisciplinary treatment strategy.

Impact of Local Recurrence on Cause-Specific Death After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: Dynamic Prediction Using Landmark Model.

PURPOSE: The purpose of this study was to assess the impact of local recurrence (LR) on cause-specific death (CSD) in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). A dynamic prediction model that incorporated LR as a time-dependent covariate was used. METHODS AND MATERIALS: This study included 535 stage I (cT1-T2aN0M0) NSCLC patients treated with SBRT from two institutions. We developed a landmark dynamic prediction model to estimate the probability of a CSD. This model determined the probability of surviving for an additional 3 years at different prediction time points during follow-up, given the history of recurrence status. The baseline covariates included in the model were age, sex, T stage, and histology, while the time-dependent covariates were LR and regional and/or distant recurrence (RDR) status. RESULTS: Overall, 137 patients (25.6%) died of lung cancer within a median follow-up of 4.1 years. Of the 195 patients who developed recurrence, 28, 125, and 42 patients had LR only, RDR only, and both, respectively. The landmark model showed that older age, advanced T stage, LR, and RDR were significantly associated with an increased risk of subsequent CSD. Among these covariates, LR (odds ratio [OR], 8.5; 95% confidence interval [CI], 6.0-12.0; P < .001) and RDR (OR, 11.6; 95% CI, 9.1-14.9; P < .001) demonstrated strong effects on CSD within 3 years after the prediction time points. The dynamic prediction provided information on the probability of future CSD according to individual recurrence status during follow-up. CONCLUSIONS: Dynamic prediction using the landmark model showed that LR had a substantial impact on subsequent CSD, which was comparable to that of RDR. This result supports the notion that strategies to improve local control are reasonable.

Relationship between Dose Prescription Methods and Local Control Rate in Stereotactic Body Radiotherapy for Early Stage Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis.

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

CT Findings and Treatment Outcomes of Ground-Glass Opacity Predominant Lung Cancer After Stereotactic Body Radiotherapy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been rapidly evolving and increasingly performed in patients with ground-glass opacity (GGO) predominant lung cancer (GGOp-LC). PURPOSE: To evaluate early-phase CT findings of GGOp-LC after SBRT. MATERIALS AND METHODS: Patients with GGOp-LC staged as cTis-2bN0M0 treated with SBRT were retrospectively identified. The CT images were analyzed using radiologists' interpretation and CT-density histograms. Long-term treatment outcomes were also assessed. RESULTS: This study evaluated 126 patients with 133 cases of GGOp-LC, comprising GGOp-LC with pure GGO (pureGGO-LC) (n = 31) and part-solid tumors (partsolid-LC) (n = 102). The median follow-up duration was 64.3 months (range, 10.8-178.9 months). Most GGOp-LC cases were interpreted as stable disease at 1 and 3 months after SBRT (96% [125/130] and 85% [62/73], respectively). However, the solid component was often interpreted as progressive disease (42% [34/82] and 60% [29/48], respectively). The GGO component was interpreted as denser in 47% (61/130) and 86% (63/73) of cases, respectively. For 25 evaluable pureGGO-LC cases at 3 months, the median tumor density values increased over time (P < .001). For 48 evaluable partsolid-LC cases at 3 months, the median areas of CT-density ≥ -160 HU increased over time (P < .001). The 5-year overall survival for GGOp-LC patients was 78.0%. No local or regional recurrence were observed. CONCLUSION: Clinical outcomes of SBRT for GGOp-LC were excellent, without local or regional recurrence. In the interpretation of early-phase follow-up CT scans of GGOp-LC after SBRT, it should be noted that most GGOp-LC remains stable disease, solid component increases in size, and GGO component is denser.

Applying Artificial Neural Networks to Develop a Decision Support Tool for Tis-4N0M0 Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy.

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

Three Cases of Hepatocellular Carcinoma With Massive Macrovascular Invasion Successfully Treated With Radiotherapy.

In clinical practice, the treatment approach for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) is determined on a case-by-case basis. The common management options include systemic and local therapies, although the former is the more widely accepted approach. We present three cases of HCC with MVI successfully treated with radiotherapy. The first patient was a 62-year-old man with Child-Pugh A cirrhosis who had a 5.7-cm treatment-naïve HCC invading the bilateral branches of the portal vein. Stereotactic body radiotherapy (SBRT) was administered, with no evidence of recurrence observed at the 24-month follow-up. The second patient was an 81-year-old man with Child-Pugh A cirrhosis who had a 3.8-cm HCC invading the inferior vena cava (IVC). Transcatheter chemoembolization performed one month earlier had been ineffective, and the tumor had grown rapidly. SBRT was administered, and no evidence of recurrence was observed up to his death from pneumonia 24 months after the treatment initiation. The third patient was a 72-year-old man with Child-Pugh A cirrhosis who had a 6.7-cm treatment-naïve HCC with portal vein tumor thrombosis (PVTT) from the main trunk to the secondary branches of both lobes. PVTT was treated with hypofractionated radiotherapy, while the primary HCC and intrahepatic recurrent lesions were subsequently treated with hepatic arterial infusion chemotherapy (HAIC) and five rounds of ablation. Six months after the last ablation (48 months after initial therapy), no evidence of recurrence was observed. Our cases illustrate that radiotherapy leads to the successful treatment of HCC with MVI.

Development and validation of a prognostic model for non-lung cancer death in elderly patients treated with stereotactic body radiotherapy for non-small cell lung cancer.

This study sought to develop and validate a prognostic model for non-lung cancer death (NLCD) in elderly patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients aged ≥65 diagnosed with NSCLC (Tis-4N0M0), tumor diameter ≤5 cm and SBRT between 1998 and 2015 were retrospectively registered from two independent institutions. One institution was used for model development (arm D, 353 patients) and the other for validation (arm V, 401 patients). To identify risk factors for NLCD, multiple regression analysis on age, sex, performance status (PS), body mass index (BMI), Charlson comorbidity index (CCI), tumor diameter, histology and T-stage was performed on arm D. A score calculated using the regression coefficient was assigned to each factor and three risk groups were defined based on total score. Scores of 1.0 (BMI ≤18.4), 1.5 (age ≥ 5), 1.5 (PS ≥2), 2.5 (CCI 1 or 2) and 3 (CCI ≥3) were assigned, and risk groups were designated as low (total ≤ 3), intermediate (3.5 or 4) and high (≥4.5). The cumulative incidences of NLCD at 5 years in the low, intermediate and high-risk groups were 6.8, 23 and 40% in arm D, and 23, 19 and 44% in arm V, respectively. The AUC index at 5 years was 0.705 (arm D) and 0.632 (arm V). The proposed scoring system showed usefulness in predicting a high risk of NLCD in elderly patients treated with SBRT for NSCLC.

Stereotactic Body Radiation Therapy With a High Maximum Dose Improves Local Control, Cancer-Specific Death, and Overall Survival in Peripheral Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: We investigated whether delivery of a high biologically effective dose (BED) to primary tumors affects systemic outcomes of cancer-specific death (CSD) and overall survival (OS) rates after stereotactic body radiation therapy (SBRT) in patients with early-stage non-small cell lung cancer (ES-NSCLC). METHODS AND MATERIALS: Among consecutive ES-NSCLC patients treated with SBRT between 2005 and 2019, we retrospectively identified patients who received a prescription of 50 to 60 Gy in 5 fractions with maximum doses of 62.5 to 100 Gy. Patients were categorized by maximum BED within the planning target volume with a threshold dose of 200 Gy. Outcomes were analyzed in all and matched patients. RESULTS: Overall, 433 patients were eligible, and 262 and 171 patients were categorized into HighBED and LowBED groups, respectively. After propensity score matching, pairs of 154 patients were selected. Median follow-up times for the HighBED and LowBED groups were 52.3 months (range, 0.8-107.2 months) and 121.6 months (range, 3.0-162.8 months), respectively. The local recurrence rate in the HighBED group was significantly lower than that in the LowBED group (5-year rate, 1.3% and 7.2%; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.03-0.65; P = .011). Rates of any recurrence and CSD in the HighBED group were significantly lower (5-year any recurrence: 18.1% and 32.1%; HR, 0.52; 95% CI, 0.33-0.83; P = .0058; 5-year CSD: 9.5% and 21.8%; HR, 0.38; 95% CI, 0.20-0.70; P = .002), and OS in the HighBED group was significantly better compared with the LowBED group (5-year rate: 61.7% and 51.8%; HR, 0.71; 95% CI, 0.50-1.00; P = .047). CONCLUSION: In patients with peripheral ES-NSCLC, SBRT with a high maximum dose may improve not only local control, but also any recurrence, CSD, and OS rates without increased toxicity. Further trials designed to evaluate whether higher intensity SBRT increases local control rates and contributes to improved CSD and OS outcomes are anticipated.

A Multi-Institutional Retrospective Study of Repeated Stereotactic Body Radiation Therapy for Intrahepatic Recurrent Hepatocellular Carcinoma.

PURPOSE: Through this multi-institutional study, we aimed to retrospectively evaluate the safety and efficacy of repeated stereotactic body radiation therapy (SBRT) for intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Between 2005 and 2017, 709 patients with 835 HCCs underwent SBRT; those treated with repeated SBRT were eligible. The median prescribed dose was 40 Gy in 5 fractions. RESULTS: Eighty-one patients with 189 tumors underwent repeated SBRT (≥ 2 courses [median 2 times; range, 2-5 times]). The median follow-up periods from the first to the second SBRT were 41.5 (range, 12-99) and 20 (range, 1-81) months, respectively. The median interval between the first and second SBRT was 18 (range, 3-74) months. The 5-year local recurrence rate was 6.3% (95% confidence interval [CI], 2.3%-13.4%). The 5-year overall survival (OS) and liver-related death rates from the first SBRT were 60.4% (95% CI, 47.0%-73.8%) and 32.9% (95% CI, 20.3%-46.0%), respectively, and the 3-year rates from the second SBRT were 61.0% (95% CI, 49.9%-75.2%) and 34.5% (95% CI, 20.6%-48.9%), respectively. The frequency of grade 3 toxicity was not significantly different between the first and second SBRT (first: 11% [95% CI, 5.2%-20%]; second: 15% [95% CI, 7.9%-24%]; P = .48). Among 39 patients with no intrahepatic recurrence for 1 year after the first and second SBRT, the deterioration in liver function after the first and second SBRT was not significantly different; the albumin-bilirubin score increased 1 year after the first versus second SBRT (first, 0.143 ± 0.23; second, 0.195 ± 0.38; P = .48). Multivariate analysis revealed that the intrahepatic recurrence-free interval was the only significant factor for OS. CONCLUSIONS: Repeated SBRT for intrahepatic recurrent HCC resulted in high local control with safety and a satisfactory OS comparable with that of other curative local treatments for patients with well-preserved liver function.

Pleural contact decreases survival in clinical T1N0M0 lung cancer patients undergoing SBRT.

BACKGROUND: Clinical staging, as used for patients treated with stereotactic body radiotherapy (SBRT) for early-stage lung cancer, inadequately accounts for pleural invasion, which is a pathologic criteria. Considering the current situation, we analyzed effects of relationships between tumors and the pleura on treatment outcomes of SBRT for early-stage lung cancer. MATERIALS AND METHODS: Among consecutive patients treated with SBRT between 2006 and 2017, we retrospectively identified non-small cell lung cancer patients with primary tumor diameters ≤4 cm and N0M0. The relationships between tumors and the pleura were investigated. The effects of these findings on treatment outcomes were analyzed. RESULTS: We identified 386 patients which met the inclusion criteria. Among these patients, 323 patients were with tumors of 0.1-3.0 cm (T1-size), and 63 patients were with tumors of 3.1-4.0 cm (T2a-size). Among patients with T1-size tumors, 120, 134, and 23 had findings of pleural contact, pleural indentation, and pleural thickening, respectively. When we divided T1-size patients into 2 groups based on pleural contact (contact- or contact+), the 3-year cause-specific mortality and overall survival in patients with T1-size & contact+ were significantly worse than those in patients with T1-size & contact- (17.6% (95% confidence interval (CI), 10.7-25.9%) vs. 6.6% (95% CI, 3.5-11.1%), p < 0.01), and 58.2% (95% CI, 47.6-67.5%) vs. 77.6% (95% CI, 70.5-83.2%), p < 0.01). Local recurrence, regional recurrence, pleural cavity recurrence, and distant metastasis were associated with worse cause-specific mortality and overall survival. On multivariate analysis, pleural contact was associated with cause-specific mortality (hazard ratio (HR), 1.96; 95% CI, 1.09-3.52; p = 0.03) and overall survival (HR, 1.59; 95% CI, 1.08-2.34; p = 0.02). CONCLUSION: Pleural contact in clinical T1N0M0 lung cancer patients was associated with significantly worse survivals.

Stereotactic body radiotherapy for patients with non-small-cell lung cancer using RapidArc delivery and a steep dose gradient: prescription of 60% isodose line of maximum dose fitting to the planning target volume.

We retrospectively investigated outcomes, including pulmonary toxicities, of stereotactic body radiation therapy using RapidArc and a risk-adapted 60% isodose plan for early-stage non-small-cell lung cancer patients. We evaluated patients staged as cT1a-2bN0M0 between 2011 and 2017 and treated with a total dose of 40-60 Gy in five fractions to the 60% isodose line of the maximum dose encompassing the planning target volume with curative intent. Comorbidities and age were rated using an age-adjusted Charlson comorbidity index (AACCI). Factors associated with overall survival (OS) were investigated. A total of 237 patients with 250 lesions were eligible. The median follow-up was 28.0 months. The local recurrence rate at 3 years was 0.8%; none of the patients developed isolated local recurrence. OS, deaths from lung cancer, and deaths from intercurrent disease at 3 years were 72.7%, 8.2% and 19.1%, respectively. On multivariate analysis for correlating factors with OS, AACCI and maximal standardized uptake value on [18F]-fluorodeoxyglucose positron emission tomography/computed tomography remained significant. Grade ≥3 toxicities were limited to radiation pneumonitis in six (2.4%) patients (Grade 3 in four patients and Grade 5 in two patients). Among those, three patients had idiopathic interstitial pneumonia. The total dose was unrelated to the incidence of Grade ≥3 radiation pneumonitis (P = 0.69). Using the 60% isodose prescription and RapidArc, maximal local control was achieved with acceptable toxicities. Although the OS may depend on patient background, dose escalation aiming at higher local control can be beneficial for medically inoperable patients.

Stereotactic body radiotherapy for primary non-small cell lung cancer patients with clinical T3-4N0M0 (UICC 8th edition): outcomes and patterns of failure.

The evidence for stereotactic body radiotherapy (SBRT) is meagre for patients with clinical T3-4N0M0 non-small cell lung cancer (8th Edition of the Union for International Cancer Control (UICC)). This study retrospectively investigated clinical outcomes following SBRT for such patients. Among consecutive patients treated with SBRT, patients staged as cT3-4N0M0 by all criteria were examined, most of whom were unsuitable to chemoradiotherapy due to their fragile characters. Clinical outcomes were evaluated and factors associated with outcomes were investigated. Between 2005 and 2017, 70 eligible patients (T3: 58, T4: 12; median age 81 (63-93) years) were identified. Median follow-up duration was 28.6 (1.0-142.5) months. No adjuvant chemotherapy was administered. The 3-year local recurrence rates were 15.8% and 16.7% in T3 and T4 patients, respectively, and they were significantly lower in the high-dose group (3.1% vs 28.6%, P < 0.01). Multivariate analyses showed that the dose-volumetric factor was the significant factor for local recurrence. The 3-year regional and distant metastasis rates, cancer-specific mortality, and overall survival in T3 and T4 patients were 22.7% and 25.0%, 26.5% and 33.3%, 32.2% and 41.7%, and 39.5% and 41.7%, respectively. Only age was correlated with overall survival. Radiation pneumonitis ≥grade 3 and fatal hemoptysis occurred in 3 and 1 patients, respectively. SBRT for cT3-4N0M0 lung cancer patients achieved good local control. Survival was rather good considering that patients were usually frail, staged with clinical staging, and were not given adjuvant chemotherapy, and it may be comparable to surgery. To validate these outcomes following SBRT, a prospective study is warranted.