Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Treatment Outcomes of Proton Beam Therapy for Esophageal Squamous Cell Carcinoma at a Single Institute.

Recently, proton beam therapy (PBT) has gathered attention for improving outcomes and reducing toxicities in various cancers; however, the evidence for esophageal squamous cell carcinoma (ESCC) is lacking. Our study retrospectively evaluated the outcomes of PBT for ESCC patients at a single institute. The patients treated with PBT between November 2015 and February 2022 were included in the study, excluding those with distant metastases or those that had undertaken prior treatment for esophageal cancer (EC). The 3 year overall survival (OS) and progression-free survival (PFS) rates were calculated based on stage grouping. The patterns of failure, salvage treatment outcomes, and toxicity profiles were analyzed. The median follow-up was 35.1 months, and 132 patients were analyzed. The 3 year OS and PFS rates for the stages I, II, and III disease cases were 81.0%, 62.9%, and 51.3%; and 70.6%, 71.8%, and 39.8%, respectively. Nineteen patients presented isolated local progression, ten patients underwent appropriate salvage procedures, and nine were successfully salvaged. One patient with isolated regional progression was also salvaged. No cases of grade ≥ 4 lymphopenia were observed. One patient had grade 4 pericardial effusion and esophageal fistula. For the patients with ESCC, PBT is an effective treatment in terms of the survival outcomes and toxicities.

Efficacy of Prophylactic Cranial Irradiation According to the Risk of Extracranial Recurrence in Limited-Stage Small Cell Lung Cancer.

PURPOSE: We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for "early brain metastasis", which occurs before extracranial recurrence (ECR), and "late brain metastasis", which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors. RESULTS: The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026). CONCLUSION: PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

Analysis of Once-Daily Thoracic Radiotherapy Dose According to the Underlying Lung Disease in Patients with Limited-Stage Small Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy.

PURPOSE: In the treatment of concurrent chemoradiotherapy (CCRT) in limited-stage small cell lung cancer, the optimal once-daily radiotherapy (RT) dose/fractionation remain unclear although it is the most frequently used. Therefore, this study aimed to compare the treatment outcomes and toxicities of modest dose RT (≤ 54 Gy) with those of standard dose RT (> 54 Gy) and investigate the benefit of the high dose based on patient factors. MATERIALS AND METHODS: Since 2004, our institution has gradually increased the thoracic RT dose. Among the 225 patients who underwent CCRT, 84 patients (37.3%) received > 54 Gy. Because the patients treated with RT > 54 Gy were not randomly assigned, propensity score matching (PSM) was performed. RESULTS: The proportion of patients treated with > 54 Gy increased over time (p=0.014). Multivariate analysis revealed that the overall tumor stage and dose > 54 Gy (hazard ratio, 0.65; p=0.029) were independent prognostic factors for overall survival (OS). PSM confirmed that thoracic RT doses of > 54 Gy showed significantly improved progression-free survival (3-year, 42.7% vs. 24.0%; p < 0.001) and OS (3-year, 56.2% vs. 38.5%; p=0.003). Sensitivity analysis also showed that 60 Gy resulted in better survival than 54 Gy. However, in patients with underlying lung disease, OS benefit from > 54 Gy was not observed but considerable rates of severe pulmonary toxicities were observed (p=0.001). CONCLUSION: Our analysis supports that the 60 Gy RT dose should be considered in the once-daily regimen of CCRT for limited-stage small cell lung cancer without underlying lung disease, but RT dose > 54 Gy did not seem to benefit for patients with chronic obstructive pulmonary disease or interstitial lung disease. Further study is needed to validate these results.

Correlation between 3D scanner image and MRI for tracking volume changes in head and neck cancer patients.

INTRODUCTION: We investigated the correlation between optical surface imaging using a three-dimensional (3D) scanner and magnetic resonance imaging (MRI) for suggesting feasibility in the clinical process of tracking volume changes in head and neck patients during radiation treatment. METHODS: Ten patients were divided into two groups depending on the location of their tumor (i.e., right or left side). With weekly imaging data, the change in volume based on MRI was evaluated during the treatment course. Four volumes of interest (VOIs) were calculated on the 3D surface image of the facial and cervical areas using an optical 3D scanner, and the correlation between volumetric parameters were analyzed. RESULTS: The target volume changed significantly overall for both groups. The changes parotid volume reduced by up to 3.8% and 28.0% for groups A (right side) and B (left side), respectively. In Group A, VOI 1 on the facial area and VOI 3 on the cervical area decreased gradually during the treatment course by up to 3.3% and 10.7%, respectively. In Group B, only VOI 4 decreased gradually during the treatment course and reduced by up to 9.2%. In group A, the change in target volume correlated strongly with right-side parotid, VOI 1, and VOI 3, respectively. The parotid also showed strong correlations with VOIs (P < 0.01). The weight loss was strongly correlated with either PTV or parotid without statistical significance (P > 0.05). In group B (left side), the change in target volume correlated strongly with each volumetric parameter, including weight loss. For individual patient, PTV showed more correlation with VOIs on the cervical area than VOIs on the facial area. CONCLUSIONS: An optical 3D scanner can be applied to track changes in volume without radiation exposure during treatment and the optical surface image correlated with MRI.

Combining Radiomics and Blood Test Biomarkers to Predict the Response of Locally Advanced Rectal Cancer to Chemoradiation.

BACKGROUND/AIM: A noninvasive method for predicting a patient's response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer would be useful because this would help determine the subsequent treatment strategy. Two types of noninvasive biomarkers have previously been studied, based on radiomics and based on blood test parameters. We hypothesized that a combination of both types would provide a better predictive power, and this has not previously been investigated. PATIENTS AND METHODS: Data from 135 patients with locally advanced rectal cancer who underwent nCRT were retrospectively allocated into training and validation cohorts in a 2:1 ratio. Sixty-five radiomics features were extracted from tumors segmented on T2-weighted magnetic resonance images. An elastic net was applied to generate four models for discerning the patients with good responses to nCRT based on radiomics features (model R), blood biomarkers (model B), both (model RB), and a linear combination of models R and B (model R+B). RESULTS: Among 65 radiomics features, 17 were selected as robust features for model development. The AUC values of model R, model B, model RB, and model R+B achieved 0.751, 0.627, 0.785, and 0.711 in the training cohort (n=90), and 0.705, 0.603, 0.679, and 0.705 in validation cohort (n=45), respectively. In the entire cohort, models RB and R+B demonstrated a significantly better performance than model B but not R. There was no correlation between the scores of models R and B (p=0.76). Radiomics features had a greater influence than blood biomarkers on models RB and R+B. CONCLUSION: A non-redundancy between radiomics features and blood-based biomarkers was observed. Furthermore, radiomics features are more valuable in terms of predicting response to nCRT. The importance of combining non-invasive biomarkers in future investigations is highlighted.

Three-dimensional versus four-dimensional dose calculation for breast intensity-modulated radiation therapy.

OBJECTIVE: To analyze the effect of intra- and interfractional motion during breast intensity modulated radiation therapy (IMRT) by calculating dose distribution based on four-dimensional computed tomography (4DCT). METHODS: 20 patients diagnosed with left breast cancer were enrolled. Three-dimensional CT (3DCT) along with 10 phases of 4DCT were collected for each patient, with target volumes independently delineated on both 3DCT and all phases of 4DCT. IMRT plans were generated based on 3DCT (43.2 Gy in 16 fractions). The plan parameters for each segment were split into phases based on time duration estimates for each respiratory phase, with phase-specific dose distributions calculated and summated (4D-calculated dose). The procedure is repeated for 16 fractionations by randomly allocating starting phase using random-number generation to simulate interfractional discrepancy caused by different starting phase. Comparisons of plan quality between the original and 4D-calculated doses were analyzed. RESULTS: There was a significant distortion in 4D-calculated dose induced by respiratory motion in terms of conformity and homogeneity index compared to those of the original 3D plan. Mean doses of the heart and the ipsilateral lung were significantly higher in the 4D-calculated doses compared to those of the original 3D plan (0.34 Gy, p = 0.010 and 0.59 Gy, p < 0.001), respectively). The mean internal mammary lymph node (IMN) dose was significantly greater in the 4D-calculated plan, compared to the original 3D plan (1.42 Gy, p < 0.001). CONCLUSIONS: IMN doses should be optimized during the dose-calculation for the free-breathing left breast IMRT. ADVANCES IN KNOWLEDGE: The interplay effect between respiratory motion and multileaf collimator modulation caused discrepancies in dose distribution, particularly in IMN.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer.

PURPOSE: To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). MATERIALS AND METHODS: Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. RESULTS: Median follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). CONCLUSION: Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended.

Delta-radiomics signature predicts treatment outcomes after preoperative chemoradiotherapy and surgery in rectal cancer.

BACKGROUND: To develop and compare delta-radiomics signatures from 2- (2D) and 3-dimensional (3D) features that predict treatment outcomes following preoperative chemoradiotherapy (CCRT) and surgery for locally advanced rectal cancer. METHODS: In total, 101 patients (training cohort, n = 67; validation cohort, n = 34) with locally advanced rectal adenocarcinoma between 2008 and 2015 were included. We extracted 55 features from T2-weighted magnetic resonance imaging (MRI) scans. Delta-radiomics feature was defined as the difference in radiomics feature before and after CCRT. Signatures were developed to predict local recurrence (LR), distant metastasis (DM), and disease-free survival (DFS) from 2D and 3D features. The least absolute shrinkage and selection operator regression was used to select features and build signatures. The delta-radiomics signatures and clinical factors were integrated into Cox regression analysis to determine if the signatures were independent prognostic factors. RESULTS: The radiomics signatures for LR, DM, and DFS were developed and validated using both 2D and 3D features. Outcomes were significantly different in the low- and high-risk patients dichotomized by optimal cutoff in both the training and validation cohorts. In multivariate analysis, the signatures were independent prognostic factors even when considering the clinical parameters. There were no significant differences in C-index from 2D vs. 3D signatures. CONCLUSIONS: This is the first study to develop delta-radiomics signatures for rectal cancer. The signatures successfully predicted the outcomes and were independent prognostic factors. External validation is warranted to ensure their performance.

Impact of Tumor Regression Grade as a Major Prognostic Factor in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Proposal for a Modified Staging System.

There is ongoing debate regarding the significance of complete or near-complete response after neoadjuvant chemoradiotherapy (CRT) for rectal cancer. This study assessed the prognostic value of the Dworak tumor regression grade (TRG) following neoadjuvant CRT and surgery primarily in patients with pathological stage (ypStage) II and III rectal cancer. The records of 331 patients who underwent neoadjuvant CRT followed by total mesorectal excision between 2004 and 2015 were retrospectively reviewed. Patients were categorized as having a good response (GR, TRG 3/4, n = 122) or a poor response (PR, TRG 1/2, n = 209). At a median follow-up of 65 months, five-year disease-free survival (DFS) was higher in the GR group than in the PR group (91.3% vs. 66.6%, p < 0.001). Patients with a GR and ypStage II disease had a five-year DFS that was indistinguishable from that of patients with ypStage 0⁻I disease (92.3% vs. 90.7%, p = 0.885). Likewise, patients with a GR and ypStage III disease had a five-year DFS similar to those with ypStage II disease (76.0% vs. 75.9%, p = 0.789). A new modified staging system that incorporates grouped TRG (GR vs. PR) was developed. The prognostic performance of this modified stage and the ypStage was compared with the Harrell C statistic. C statistic of the modified stage was higher than that of the ypStage (0.784 vs. 0.757, p = 0.012). The results remained robust after multivariate Cox regression analyses. In conclusion, a GR to neoadjuvant CRT is an independent predictor of good DFS and overall survival and further stratifies patients so as to estimate the risk of recurrence and survival among patients with ypStage II and III rectal cancer.

Benefit of volumetric-modulated arc therapy over three-dimensional conformal radiotherapy for stage I-II extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue in the stomach: a dosimetric comparison.

PURPOSE: To retrospectively analyze dosimetric parameters of volumetric-modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3D-CRT) delivered to extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma) to find out advantages of VMAT and conditions for definite benefits of VMAT. MATERIALS AND METHODS: Fifty patients with stage I-II gastric MALT lymphoma received VMAT (n = 14) or 3D-CRT (n = 36) between December 2005 and April 2018. Twenty-seven patients were categorized according to whether the planning target volume (PTV) overlaps kidney(s). Dosimetric parameters were analyzed by dose-volume histogram. RESULTS: Radiation dose to the liver was definitely lower with VMAT in terms of mean dose (p = 0.026) and V15 (p = 0.008). The V15 of the left kidney was lower with VMAT (p = 0.065). For those with PTV overlapping kidney(s), the left kidney V15 was significantly lower with VMAT. Furthermore, the closer the distance between the PTV and kidneys, the less the left kidney V15 with VMAT (p = 0.037). Delineation of kidney(s) by integrating all respiratory phases had no additional benefit. CONCLUSIONS: VMAT significantly increased monitor units, reduced treatment time and radiation dose to the liver and kidneys. The benefit of VMAT was definite in reducing the left kidney V15, especially in geometrically challenging conditions of overlap or close separation between PTV and kidney(s).