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Lung Cancer (Amsterdam, Netherlands) Aug 2023Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location... (Meta-Analysis)
Meta-Analysis
Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines.
BACKGROUND
Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).
METHODS
We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes.
RESULTS
602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events.
CONCLUSION
SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design.
Topics: Humans; Lung Neoplasms; Radiosurgery; Retrospective Studies; Lung; Dose Fractionation, Radiation; Observational Studies as Topic
PubMed: 37393758
DOI: 10.1016/j.lungcan.2023.107281 -
Progress in Brain Research 2022New understandings of the biology of radiosurgery are considered. Differences from the radiobiology of fractionated radiotherapy are outlined. It is noted DNA damage...
New understandings of the biology of radiosurgery are considered. Differences from the radiobiology of fractionated radiotherapy are outlined. It is noted DNA damage alone is insufficient to account for the tissue changes which occur. Changes in blood vessels and immunological mechanisms are also involved. Tissue repair is more rapid than previously thought so that dose rate (the rate of delivery of radiation to the tissues) has been seen to be more important. The value of fractionation is examined. The effect of radiosurgery on normal brain (so called functional radiosurgery) is considered. The desired effects may be achieved by a focal stable destruction of brain from a high radiation dose. They may also be achieved using a lower dose which acts through the mechanism known as radiosurgical neuromodulation.
Topics: Brain; Dose Fractionation, Radiation; Humans; Radiobiology; Radiosurgery
PubMed: 35074083
DOI: 10.1016/bs.pbr.2021.10.024 -
Clinical Cancer Research : An Official... Feb 2021Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit...
PURPOSE
Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses.
EXPERIMENTAL DESIGN
Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT.
RESULTS
The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor-bearing animals after the delivery of large neurotoxic single dose or hypofractionated regimens.
CONCLUSIONS
The present results show that FLASH-RT delivered with hypofractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT..
Topics: Animals; Brain; Brain Neoplasms; Cognitive Dysfunction; Electrons; Female; Glioblastoma; Humans; Mice; Organs at Risk; Radiation Dose Hypofractionation; Radiation Injuries, Experimental; Radiotherapy Dosage; Reactive Oxygen Species
PubMed: 33060122
DOI: 10.1158/1078-0432.CCR-20-0894 -
Journal of Thoracic Oncology : Official... Jul 2021Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial...
INTRODUCTION
Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity.
METHODS
Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea.
RESULTS
A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0-10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the "hottest" 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage.
CONCLUSIONS
On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions).
Topics: Dose Fractionation, Radiation; Humans; Lung; Lung Neoplasms; Prospective Studies; Radiosurgery; Radiotherapy Dosage
PubMed: 33823286
DOI: 10.1016/j.jtho.2021.03.019 -
Journal For Immunotherapy of Cancer May 2021Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck...
Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma.
BACKGROUND
Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone.
METHODS
The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Eligible patients were treated with neoadjuvant SBRT at a total dose of either 40 Gy in 5 fractions or 24 Gy in 3 fractions, delivered in a 1-week timespan, with or without nivolumab, prior to definitive surgical resection. Patients were then planned for treatment with adjuvant nivolumab for 3 months. The primary safety endpoint was unplanned delay in surgery considered to be at least possibly related to neoadjuvant treatment. The primary efficacy endpoints included pathological complete response (pCR), major pathological response (mPR), and the rate of clinical to pathological downstaging after neoadjuvant treatment.
RESULTS
Twenty-one patients underwent neoadjuvant treatment, which was well tolerated and did not delay surgery, thus meeting the primary endpoint. Tissue responses were characterized by robust inflammatory infiltrates in the regression bed, plasma cells and cholesterol clefts. Among the entire study group, the mPR and pCR rate was 86% and 67%, respectively. Clinical to pathological downstaging occurred in 90% of the patients treated.
CONCLUSION
These data demonstrate that radiation delivered only to the gross tumor volume combined with immunotherapy was safe, resulted in a high rate of mPR and should be further evaluated as a locally focused neoadjuvant therapy for patients with head and neck cancer.
TRIAL REGISTRATION NUMBER
This study is registered with clinicaltrials.gov (NCT03247712) and is active, but closed to patient accrual.
Topics: Aged; Dose Fractionation, Radiation; Female; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nivolumab; Oregon; Programmed Cell Death 1 Receptor; Radiosurgery; Radiotherapy, Adjuvant; Squamous Cell Carcinoma of Head and Neck; Time Factors; Treatment Outcome
PubMed: 33963014
DOI: 10.1136/jitc-2021-002485 -
Reports of Practical Oncology and... 2022This paper describes how to select the most appropriate stereotactic radiotherapy (SRT ) dose and fractionation scheme according to lesion size and site, organs at risk... (Review)
Review
This paper describes how to select the most appropriate stereotactic radiotherapy (SRT ) dose and fractionation scheme according to lesion size and site, organs at risk (OARs) proximity and the biological effective dose. In single-dose SRT, 15-34 Gy are generally used while in fractionated SRT 30 and 75 Gy in 2-5 fractions are administered. The ICRU Report No. 91, which is specifically dedicated to SRT treatments, provided indications for dose prescription (with its definition and essential steps), dose delivery and optimal coverage which was defined as the best planning target volume coverage that can be obtained in the irradiated district. Calculation algorithms and OAR s dose constraints are provided as well as treatment planning system characteristics, suggested beam energy and multileaf collimator leaf size. Finally, parameters for irradiation geometry and plan quality are also reported.
PubMed: 35402033
DOI: 10.5603/RPOR.a2021.0139 -
Cancer Radiotherapie : Journal de La... 2022We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the...
We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the gold standard treatment for hypopharynx cancers. Early T1 and T2 tumors could be treated by exclusive radiotherapy or surgery followed by postoperative radiotherapy in case of high recurrence risk. For locally advanced tumours requiring total pharyngolaryngectomy (T2 or T3) or with significant lymph nodes involvement, induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy were possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on initial primary tumour treatment. In non-surgical procedure, for 35 fractions, curative dose is 70Gy (2Gy per fraction) and prophylactic dose are 50 to 56Gy (2Gy per fraction in case of sequential radiotherapy or 1.6Gy in case of integrated simultaneous boost) radiotherapy; for 33 fractions, curative dose is 69.96Gy (2.12Gy per fraction) and prophylactic dose is 52.8Gy (1.6Gy per fraction in integrated simultaneous boost radiotherapy or 54Gy in 1.64Gy per fraction); for 30 fractions, curative dose is 66Gy (2.2Gy per fraction) and prophylactic dose is 54Gy (1.8Gy per fraction in integrated simultaneous boost radiotherapy). Doses over 2Gy per fraction could be done when chemotherapy is not used regarding potential larynx toxicity. Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria, 60 to 66Gy for R1 resection and 54 to 60Gy for complete resection in bed tumour; 50 to 66Gy in lymph nodes areas regarding extracapsular spread. Volume delineation were based on guidelines cited in this article.
Topics: Chemoradiotherapy; Dose Fractionation, Radiation; France; Humans; Hypopharyngeal Neoplasms; Induction Chemotherapy; Laryngectomy; Lymphatic Irradiation; Pharyngectomy; Radiation Oncology; Radiotherapy, Intensity-Modulated
PubMed: 34953703
DOI: 10.1016/j.canrad.2021.10.006 -
Cancer Radiotherapie : Journal de La... 2022This article reviews the various treatment options, by primary or postoperative external radiotherapy and by brachytherapy for the p16-negative oropharyngeal squamous... (Review)
Review
This article reviews the various treatment options, by primary or postoperative external radiotherapy and by brachytherapy for the p16-negative oropharyngeal squamous cell carcinoma. Dose levels, fractionation and association with systemic treatments are presented. The need for neck node dissection post local treatment is discussed, as well as specificities for the management of p16-positive tumours. Guidelines for target volume selection and delineation are thoroughly elaborated. Last, the management by radiotherapy of locoregional recurrences is discussed.
Topics: Brachytherapy; Cyclin-Dependent Kinase Inhibitor p16; Dose Fractionation, Radiation; France; Humans; Induction Chemotherapy; Neck Dissection; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Radiation Oncology; Retreatment; Societies, Medical; Squamous Cell Carcinoma of Head and Neck
PubMed: 34953693
DOI: 10.1016/j.canrad.2021.10.002 -
Clinical Breast Cancer Apr 2021For early-stage breast cancer, partial breast irradiation (PBI) allows for reduction in the irradiated volume of normal tissues by confining the radiation target to the... (Review)
Review
For early-stage breast cancer, partial breast irradiation (PBI) allows for reduction in the irradiated volume of normal tissues by confining the radiation target to the area surrounding the lumpectomy cavity after breast-conserving surgery. This approach has been supported by phase 2 data. However, widespread adoption of PBI has awaited the results of randomized controlled trials. This review discusses the results of randomized controlled trials comparing whole breast irradiation to PBI, including the recently published National Surgical Adjuvant Breast and Bowel Project (NSABP) B39/Radiotherapy Oncology Group (RTOG) 0413, and the Canadian RAPID trials. PBI techniques, dose/fractionation schedules, and patient selection are also reviewed.
Topics: Brachytherapy; Breast Neoplasms; Dose Fractionation, Radiation; Female; Humans; Mastectomy, Segmental; Neoadjuvant Therapy; Organ Sparing Treatments; Radiotherapy; Radiotherapy Planning, Computer-Assisted
PubMed: 32448706
DOI: 10.1016/j.clbc.2020.04.003 -
Physics in Medicine and Biology Sep 2022In online adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. This allows for...
In online adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. This allows for a planning target volume margin that does not need to be constant over the whole course of treatment, as is the case in conventional radiotherapy. This work aims to introduce an approach to update the margins each fraction based on the per-patient treatment history and explore the potential benefits of such adaptive margins.We introduce a novel methodology to implement adaptive margins, isotropic and anisotropic, during a treatment course based on the accumulated dose to the CTV. We then simulate treatment histories for treatments delivered in up to 20 fractions using various choices for the standard deviations of the systematic and random errors and homogeneous and inhomogeneous dose distributions. The treatment-averaged adaptive margin was compared to standard constant margins. The change in the minimum dose delivered to the CTV was compared on a patient and a population level. All simulations were performed within the van Herk approach and its known limitations.The population mean treatment-averaged margins are down to 70% and 55% of the corresponding necessary constant margins for the isotropic and anisotropic approach. The reduction increases with longer fractionation schemes and an inhomogeneous target dose distribution. Most of the benefit can be attributed to the elimination of the effective systematic error over the course of treatment. Interpatient differences in treatment-averaged margins were largest for the isotropic margins. For the 10% of patients that would receive a lower than prescribed dose to the CTV this minimum dose to the CTV is increased using the adaptive margin approaches.Adaptive margins can allow to reduce margins in most patients without compromising patients with greater than average target motion.
Topics: Dose Fractionation, Radiation; Humans; Margins of Excision; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided
PubMed: 36096130
DOI: 10.1088/1361-6560/ac9175