Stereotactic Body Radiotherapy for Various Cancers: Recent Advances and Future

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 17981

Special Issue Editor


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Guest Editor
Department of Radiology, School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 4093898, Japan
Interests: stereotactic body radiotherapy; respiratory organ motion management; hypo-fractionated radiotherapy; image guidance; lung cancer; liver cancer; kidney cancer; prostate cancer; oligo-metastases; abscopal effect; Immune effect

Special Issue Information

Dear Colleagues,

Stereotactic body radiotherapy (SBRT) has been established as a definitive treatment for Stage I non-small cell lung cancer (NSCLC), prostate cancer, hepatocellular carcinoma, kidney cancer, spinal metastases, and oligometastases. Considering the effectiveness of SBRT in these tumors, indication of SBRT may be expanded to include malignant tumors of other organs or cancer status. The strong points of SBRT are high radicality, minimum invasiveness, short treatment term with ultra-hypofractionation, and probably immunological enhancement.  Recently, abscopal effect of radiation has been come into the spotlight according to appearance of SBRT and immune-checkpoint inhibitors. In spite of these topics, SBRT has not been reasonably popularized. Therefore, the aim of this special issue is to explore expanding the role of SBRT for more patients including not only medically inoperable, aged, or high risk operable but toward clearly operable patients. Original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: to demonstrate the current status in various cancers or disease status, recent advances in irradiation technique, and future possibilities or problems of SBRT.

I look forward to receiving your contributions.

Dr. Hiroshi Onishi
Guest Editor

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Keywords

  • stereotactic body radiotherapy
  • SBRT
  • stereotactic ablative radiotherapy
  • SABR
  • lung
  • liver
  • spine
  • prostate
  • kidney
  • adrenal
  • pancreas
  • breast
  • lymph node
  • oligometasetases
  • abscopal effect
  • immune reaction

Published Papers (9 papers)

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Research

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13 pages, 1547 KiB  
Article
Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer
by Hiroshi Onishi, Yoshiyuki Shioyama, Yasuo Matsumoto, Yukinori Matsuo, Akifumi Miyakawa, Hideomi Yamashita, Haruo Matsushita, Masahiko Aoki, Keiji Nihei, Tomoki Kimura, Hiromichi Ishiyama, Naoya Murakami, Kensei Nakata, Atsuya Takeda, Takashi Uno, Takuma Nomiya, Hiroshi Taguchi, Yuji Seo, Takafumi Komiyama, Kan Marino, Shinichi Aoki, Masaki Matsuda, Tomoko Akita and Masahide Saitoadd Show full author list remove Hide full author list
Cancers 2023, 15(17), 4382; https://doi.org/10.3390/cancers15174382 - 01 Sep 2023
Viewed by 1833
Abstract
Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage [...] Read more.
Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48–70 Gy in 4–10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients. Full article
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10 pages, 803 KiB  
Article
Impact of Systemic Autoimmune Diseases on Treatment Outcomes and Radiation Toxicities in Patients with Stage I Non-Small Cell Lung Cancer Receiving Stereotactic Body Radiation Therapy: A Matched Case-Control Analysis
by Zhe Chen, Hotaka Nonaka, Hiroshi Onishi, Eiji Nakatani, Mitsuhiko Oguri, Masahide Saito, Shinichi Aoki, Kan Marino, Takafumi Komiyama, Kengo Kuriyama, Masayuki Araya, Licht Tominaga, Ryo Saito, Yoshiyasu Maehata and Ryoji Shinohara
Cancers 2022, 14(23), 5915; https://doi.org/10.3390/cancers14235915 - 30 Nov 2022
Viewed by 1274
Abstract
We aimed to evaluate the impact of systemic autoimmune diseases (SADs) on treatment outcomes and radiation toxicities following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We queried an institution-based database on patients with SADs treated with SBRT [...] Read more.
We aimed to evaluate the impact of systemic autoimmune diseases (SADs) on treatment outcomes and radiation toxicities following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We queried an institution-based database on patients with SADs treated with SBRT for lung cancer between 2001 and 2016 (SAD group). Each patient was matched to three controls without SADs. The primary outcomes of interest were the overall survival (OS) and local control rate (LCR). The secondary outcomes were radiation toxicities of grades ≥2 (≥G2). Twelve patients with SADs were matched to 36 controls. The median follow-up duration was 3.6 years. There was a significant intergroup difference in the OS (hazard ratio [HR]: 4.11, 95% confidence incidence [CI]: 1.82–9.27, p < 0.001) and LCR (HR: 15.97, 95% CI: 2.89–88.29, p < 0.001). However, there were no significant intergroup differences in the odds of acute (odds ratio [OR]: 0.38, 95% CI: 0.02–8.91, p = 0.550) and late (OR: 2.20, 95% CI: 0.32–15.10, p = 0.422) ≥G2 radiation pneumonitis. No other ≥G2 toxicities were identified. In conclusion, although radiation toxicities are not enhanced by SADs, SADs are risk factors of poor prognosis following SBRT for stage I NSCLC. Full article
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11 pages, 1261 KiB  
Article
Palliative Efficacy of High-Dose Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Painful Non-Spine Bone Metastases: A Propensity Score-Matched Analysis
by Kei Ito, Kentaro Taguchi, Yujiro Nakajima, Hiroaki Ogawa and Keiko Nemoto Murofushi
Cancers 2022, 14(16), 4014; https://doi.org/10.3390/cancers14164014 - 19 Aug 2022
Cited by 3 | Viewed by 1790
Abstract
(1) Background: The superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) in terms of pain palliation for bone metastases remains controversial. (2) Methods: This propensity score-matched study compared the overall pain response (OR) 3 months after radiotherapy among patients [...] Read more.
(1) Background: The superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) in terms of pain palliation for bone metastases remains controversial. (2) Methods: This propensity score-matched study compared the overall pain response (OR) 3 months after radiotherapy among patients with painful (≥2 points on a 0-to-10 scale) non-spine bone metastases. Patients with lesions that were treated with SBRT or cEBRT and whose pain scores were evaluated 3 months after radiotherapy were included in this study. Pain response was evaluated according to the International Consensus Criteria. (3) Results: A total of 234 lesions (SBRT, n = 129; cEBRT, n = 105) were identified in our institutional database. To reduce the confounding effects, 162 patients were selected using a propensity score-matched analysis (n = 81 for each treatment). The OR rate at 3 months after SBRT was significantly higher than that after cEBRT (76.5% vs. 56.8%; p = 0.012). A noteworthy finding of our study is that the same trend was observed even after 6 months (75.9% vs. 50.0%; p = 0.011). The 1-year local failure rates after SBRT and cEBRT were 10.2% and 33.3% (p < 0.001), respectively. (4) Conclusions: Our findings suggest that SBRT is superior to cEBRT for pain palliation in patients with non-spine bone metastases. Full article
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11 pages, 1079 KiB  
Article
Stereotactic Radiosurgery for Lung Cancer with a Risk-Adapted Strategy Using the Volumetric Modulated Arc Therapy Technique: A Single Arm Phase II Study
by Takaya Yamamoto, Yu Katagiri, Yoko Tsukita, Haruo Matsushita, Rei Umezawa, Yoshiyuki Katsuta, Noriyuki Kadoya, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Keita Kishida, So Omata, Eisaku Miyauchi, Ryota Saito and Keiichi Jingu
Cancers 2022, 14(16), 3993; https://doi.org/10.3390/cancers14163993 - 18 Aug 2022
Cited by 1 | Viewed by 1566
Abstract
Purpose: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start [...] Read more.
Purpose: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. Materials and Methods: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1–5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. Results: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3–22.2%), 20.1% (95% CI: 6.0–40.2%), 59.2% (95% CI: 34.4–77.3%), and 78.2% (95% CI: 51.4–91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. Conclusions: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity. Full article
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12 pages, 656 KiB  
Article
Establishment of a Prediction Model for Overall Survival after Stereotactic Body Radiation Therapy for Primary Non-Small Cell Lung Cancer Using Radiomics Analysis
by Subaru Sawayanagi, Hideomi Yamashita, Yuki Nozawa, Ryosuke Takenaka, Yosuke Miki, Kosuke Morishima, Hiroyuki Ueno, Takeshi Ohta and Atsuto Katano
Cancers 2022, 14(16), 3859; https://doi.org/10.3390/cancers14163859 - 10 Aug 2022
Cited by 3 | Viewed by 1682
Abstract
Stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) leads to recurrence in approximately 18% of patients. We aimed to extract the radiomic features, with which we predicted clinical outcomes and to establish predictive models. Patients with primary non-metastatic NSCLC [...] Read more.
Stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) leads to recurrence in approximately 18% of patients. We aimed to extract the radiomic features, with which we predicted clinical outcomes and to establish predictive models. Patients with primary non-metastatic NSCLC who were treated with SBRT between 2002 and 2022 were retrospectively reviewed. The 358 primary tumors were randomly divided into a training cohort of 250 tumors and a validation cohort of 108 tumors. Clinical features and 744 radiomic features derived from primary tumor delineation on pre-treatment computed tomography were examined as prognostic factors of survival outcomes by univariate and multivariate analyses in the training cohort. Predictive models of survival outcomes were established from the results of the multivariate analysis in the training cohort. The selected radiomic features and prediction models were tested in a validation cohort. We found that one radiomic feature showed a significant difference in overall survival (OS) in the validation cohort (p = 0.044) and one predicting model could estimate OS time (mean: 37.8 months) similar to the real OS time (33.7 months). In this study, we identified one radiomic factor and one prediction model that can be widely used. Full article
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13 pages, 1137 KiB  
Article
Ultrahypofractionated Radiotherapy versus Conventional to Moderate Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer
by Hideya Yamazaki, Gen Suzuki, Norihiro Aibe, Daisuke Shimizu, Takuya Kimoto, Koji Masui, Ken Yoshida, Satoaki Nakamura, Yasutoshi Hashimoto and Haruumi Okabe
Cancers 2022, 14(1), 195; https://doi.org/10.3390/cancers14010195 - 31 Dec 2021
Cited by 1 | Viewed by 1575
Abstract
The purpose of this study was to compare the toxicity (first endpoint) and efficacy (second endpoint) of ultrahypofractionated radiotherapy (UHF) and dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT) for clinically localized prostate cancer. We compared 253 patients treated with UHF and 499 patients [...] Read more.
The purpose of this study was to compare the toxicity (first endpoint) and efficacy (second endpoint) of ultrahypofractionated radiotherapy (UHF) and dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT) for clinically localized prostate cancer. We compared 253 patients treated with UHF and 499 patients treated with DeRT using multi-institutional retrospective data. To analyze toxicity, we divided UHF into High-dose UHF (H-UHF; equivalent doses of 2 Gy per fraction: EQD2 > 100 Gy1.5) and low-dose UHF (L-UHF; EQD2 ≤ 100 Gy1.5). In toxicity, H-UHF elevated for 3 years accumulated late gastrointestinal and genitourinary toxicity grade ≥ 2 (11.1% and 9.3%) more than L-UHF (3% and 1.2%) and DeRT (3.1% and 4.8%, p = 0.00126 and p = 0.00549). With median follow-up periods of 32.0 and 61.7 months, the actuarial 3-year biochemical failure-free survival rates were 100% (100% and 100% in the L-UHF and H-UHF) and 96.3% in the low-risk group, 96.5% (97.1% and 95.6%) and 94.9% in the intermediate-risk group, and 93.7% (100% and 94.6%) and 91.7% in the high-risk group in the UHF and DeRT groups, respectively. UHF showed equivocal efficacy, although not conclusive but suggestive due to a short follow-up period of UHF. L-UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy. Full article
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Review

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18 pages, 570 KiB  
Review
The Current Role of Stereotactic Body Radiation Therapy (SBRT) in Hepatocellular Carcinoma (HCC)
by Tomoki Kimura, Toshiki Fujiwara, Tsubasa Kameoka, Yoshinori Adachi and Shinji Kariya
Cancers 2022, 14(18), 4383; https://doi.org/10.3390/cancers14184383 - 08 Sep 2022
Cited by 17 | Viewed by 3207
Abstract
The role of stereotactic body radiotherapy (SBRT), which can deliver high radiation doses to focal tumors, has greatly increased in not only early-stage hepatocellular carcinoma (HCC), but also in portal vein or inferior vena cava thrombi, thus expanding this therapy to pre-transplantation and [...] Read more.
The role of stereotactic body radiotherapy (SBRT), which can deliver high radiation doses to focal tumors, has greatly increased in not only early-stage hepatocellular carcinoma (HCC), but also in portal vein or inferior vena cava thrombi, thus expanding this therapy to pre-transplantation and the treatment of oligometastases from HCC in combination with immune checkpoint inhibitors (ICI). In early-stage HCC, many promising prospective results of SBRT have been reported, although SBRT is not usually indicated as a first treatment potion in localized HCC according to several guidelines. In the treatment of portal vein or inferior vena cava tumor thrombi, several reports using various dose-fraction schedules have shown relatively good response rates with low toxicities and improved survival due to the rapid advancements in systemic therapy. Although SBRT is regarded as a substitute therapy when conventional bridging therapies to transplantation, such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), are not applicable or fail in controlling tumors, SBRT may offer advantages in patients with borderline liver function who may not tolerate TACE or RFA, according to several reports. For oligometastases, the combination of SBRT with ICI could potentially induce an abscopal effect in patients with HCC, which is expected to provide the rationale for SBRT in the treatment of oligometastatic disease in the near future. Full article
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Other

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10 pages, 1144 KiB  
Commentary
The Evolving Interplay of SBRT and the Immune System, along with Future Directions in the Field
by Mihailo Miljanic, Steven Montalvo, Maureen Aliru, Tidie Song, Maria Leon-Camarena, Kevin Innella, Dragan Vujovic, Ritsuko Komaki and Puneeth Iyengar
Cancers 2022, 14(18), 4530; https://doi.org/10.3390/cancers14184530 - 19 Sep 2022
Cited by 6 | Viewed by 1892
Abstract
In this commentary, we describe the potential of highly ablative doses utilizing Stereotactic Body Radiation Therapy (SBRT) in single or few fractions to enhance immune-responsiveness, how timing of this approach in combination with immune-checkpoint inhibitors may augment treatment-effect, and whether Personalized Ultrafractionated Stereotactic [...] Read more.
In this commentary, we describe the potential of highly ablative doses utilizing Stereotactic Body Radiation Therapy (SBRT) in single or few fractions to enhance immune-responsiveness, how timing of this approach in combination with immune-checkpoint inhibitors may augment treatment-effect, and whether Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy (PULSAR) is an avenue for future advancement in the continued endeavor to foster a systemic effect of therapy beyond the radiation treatment field. The ablative potential of SBRT may support an increase in tumor-antigen presentation, enhancement of immune-stimulatory components, and an improvement in tumor-microenvironment immune cell infiltration. Furthermore, the latest advancement of ablative radiation delivery is PULSAR-based therapy, whereby ablative doses are delivered in pulses of treatment that may be several weeks apart, combined with adaptive treatment to tumor changes across time. The benefits of this novel approach include the ability to optimize direct tumor control by assessment of tumor size and location via dedicated imaging acquired prior to each delivered pulse, and further potentiation of immune recognition through combination with concurrent immune-checkpoint blockade. Full article
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12 pages, 1769 KiB  
Systematic Review
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
by Takahisa Eriguchi, Atsuya Takeda, Takafumi Nemoto, Yuichiro Tsurugai, Naoko Sanuki, Yudai Tateishi, Yuichi Kibe, Takeshi Akiba, Mari Inoue, Kengo Nagashima and Nobuyuki Horita
Cancers 2022, 14(15), 3815; https://doi.org/10.3390/cancers14153815 - 05 Aug 2022
Cited by 7 | Viewed by 1989
Abstract
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 [...] Read more.
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. Full article
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