Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy.
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ABSTRACT:
SUBMITTER: Huang BT
PROVIDER: S-EPMC4676016 | biostudies-other | 2015 Dec
REPOSITORIES: biostudies-other
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Project description:BackgroundThe optimal dose and fractionation scheme of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) remains unclear due to different tolerated liver volumes and degrees of cirrhosis. In this study, we aimed to verify the dose-survival relationship to optimize dose selection for treatment of HCC.MethodsThis multicenter retrospective study included 602 patients with HCC, treated with SBRT between January 2011 and March 2017. The SBRT dosage was classified into high dose, moderate dose, and low dose levels: SaRT (BED10 ≥ 100 Gy), SbRT (EQD2 > 74 Gy to BED10 < 100 Gy), and ScRT (EQD2 < 74 Gy). Overall survival (OS), progression-free survival (PFS), local control (LC), and intrahepatic control (IC) were evaluated in univariable and multivariable analyses.ResultsThe median tumor size was 5.6 cm (interquartile range [IQR] 1.1-21.0 cm). The median follow-up time was 50.0 months (IQR 6-100 months). High radiotherapy dose correlated with better outcomes. After classifying into the SaRT, SbRT, and ScRT groups, three notably different curves were obtained for long-term post-SBRT survival and intrahepatic control. On multivariate analysis, higher radiation dose was associated with improved OS, PFS, and intrahepatic control.ConclusionsIf tolerated by normal tissue, we recommend SaRT (BED10 ≥ 100 Gy) as a first-line ablative dose or SbRT (EQD2 ≥ 74 Gy) as a second-line radical dose. Otherwise, ScRT (EQD2 < 74 Gy) is recommended as palliative irradiation.
| S-EPMC8058965 | biostudies-literature
Project description:Lung tumors are often associated with a poor prognosis although different schedules and treatment modalities have been extensively tested in the clinical practice. The complexity of this disease and the use of combined therapeutic approaches have been investigated and the use of high dose-rates is emerging as effective strategy. Technological improvements of clinical linear accelerators allow combining high dose-rate and a more conformal dose delivery with accurate imaging modalities pre- and during therapy. This paper aims at reporting the state of the art and future direction in the use of radiobiological models and radiobiological-based optimizations in the clinical practice for the treatment of lung cancer. To address this issue, a search was carried out on PubMed database to identify potential papers reporting tumor control probability and normal tissue complication probability for lung tumors. Full articles were retrieved when the abstract was considered relevant, and only papers published in English language were considered. The bibliographies of retrieved papers were also searched and relevant articles included. At the state of the art, dose-response relationships have been reported in literature for local tumor control and survival in stage III non-small cell lung cancer. Due to the lack of published radiobiological models for SBRT, several authors used dose constraints and models derived for conventional fractionation schemes. Recently, several radiobiological models and parameters for SBRT have been published and could be used in prospective trials although external validations are recommended to improve the robustness of model predictive capability. Moreover, radiobiological-based functions have been used within treatment planning systems for plan optimization but the advantages of using this strategy in the clinical practice are still under discussion. Future research should be directed toward combined regimens, in order to potentially improve both local tumor control and survival. Indeed, accurate knowledge of the relevant parameters describing tumor biology and normal tissue response is mandatory to correctly address this issue. In this context, the role of medical physicists and the AAPM in the development of radiobiological models is crucial for the progress of developing specific tool for radiobiological-based optimization treatment planning.
| S-EPMC5766682 | biostudies-literature
Project description:Background and purposeSpinal stereotactic body radiotherapy (SBRT) involves large dose gradients and high geometrical accuracy is therefore required. The aim of this work was to assess residual intra-fraction error with a tracking robotic system for non-immobilized patients. Shifts from the first alignment (i.e. mimicking the unavailability of tracking) were also quantified.Materials and methodsForty-two patients treated for spinal metastasis (128 fractions, 4220 images) were analyzed. Residual error was quantified as the difference between translations/rotations referring to consecutive x-ray images during delivery (tracking) and to the initial set-up (no-tracking). The error distribution for each fraction/patient and the entire population was assessed for each axis/rotation angle. The impact of lesion sites, fractionation and patient's pain (VAS score) were investigated. Finally, the dosimetric impact of residual motion was quantified in the four most affected fractions.ResultsMean overall errors (OE) were near 0 (SD < 0.1 mm). Residual translations/rotations >1 mm/1° were found in less than 1.5%/1% of measurements. Lesion site and fractionation showed no impact. The dosimetric impact in the most affected fractions was negligible. For "no-tracking", mean OE was <1 mm/0.5°; less than 2% of displacements were >2 mm/1° within 10 min from the start of treatment with an increasing probability of shifts >2 mm over time. A significantly higher fraction of OE ≥ 2 mm was found for patients with pain in case of no-tracking.ConclusionsSpine tracking with a latest-generation robotic system is highly efficient for non-immobilized patients: residual error is time independent and close to 0. For delivery times >7-8 min, tracking should be considered as mandatory for non-immobilized patients.
| S-EPMC7807594 | biostudies-literature
Project description:Stereotactic body radiotherapy is the technique of accurately delivering high doses of radiotherapy to small volume targets in a single or small number of sessions. The high biological effective dose of this treatment is reflected in the high rates of local control achieved across multiple tumour sites. Toxicity of the treatment can be significant and ongoing prospective trials will help define the utility of this treatment as an alternative to surgery in treating primary tumours and oligometastatic disease. Longer follow-up and survival data from prospective trials will be essential in determining the value of this resource-intensive treatment. The opportunity to combine this treatment with systemic therapies and its potential synergy with immunotherapy opens up interesting avenues for research in the future.
| S-EPMC6316669 | biostudies-other
Project description:BACKGROUND:In most clinical trials, gold fiducial markers are implanted in the prostate to tune the table position before each radiation beam. Yet, it is unclear if a cone-beam computed tomography (CBCT) should be performed before each beam to monitor a possible variation of the organs at risk (OARs) fullness, especially in case of recto-prostatic spacer implantation. The present study aimed at assessing the inter- and intra-fraction movements of prostate, bladder and rectum in patients implanted with a hyaluronic acid spacer and undergoing prostate stereotactic body radiotherapy (SBRT). METHODS:Data about consecutive patients undergoing prostate SBRT were prospectively collected between 2015 and 2019. Inter-and intra-fraction prostate displacements and volume variation of organs at risk (OARs) were assessed with CBCTs. RESULTS:Eight patients were included. They underwent prostate SBRT (37.5Gy, 5 fractions of 7.5Gy) guided by prostate gold fiducial markers. Inter-fraction variation of the bladder volume was insignificant. Intra-fraction mean increase of the bladder volume was modest (29?cc) but significant (p?<?0.001). Both inter- and intra-fraction variations of the rectum volume were insignificant but for one patient. He had no rectal toxicity. The magnitude of table displacement necessary to match the prostate gold fiducial marker frequently exceeded the CTV/PTV margins (0.4?cm) before the first (35%) and the second arc (15%). Inter- and intra-fraction bladder and rectum volume variations did not correlate with prostate displacement. CONCLUSION:Major prostate position variations were reported. In-room kV fiducial imaging before each arc seems mandatory. Intra-fraction imaging of the OARs appears unnecessary. We suggest that only one CBCT is needed before the first arc. TRIAL REGISTRATION:NCT02361515, February 11th, 2015.
| S-EPMC7168857 | biostudies-literature
Project description:Prostate cancer remains the most common and second most deadly cancer diagnosed amongst U.S. men. External beam radiotherapy is a standard-of-care definitive treatment option for localized prostate cancer and historically constituted an 8-9-week treatment course comprised of 39-45 doses of 1.8-2.0 Gy each (conventional fractionation, CF). Based on the notion that prostate cancer may respond favorably to a higher dose per day, considerable research efforts have been focused on characterizing the safety and efficacy profile of shorter and shorter radiation courses. Ultrahypofractionation (UHF) involves condensing the radiation course into just 5-7 treatments of 6-8 Gy each. When utilizing modern techniques that allow the precise sculpting of a dose distribution that delivers high doses to the prostate and lower doses to surrounding normal tissues over five or fewer treatments, this treatment is called stereotactic body radiotherapy (SBRT). Two randomized trials (HYPO-RT-PC and PACE-B) have compared UHF to longer radiation courses. The former demonstrated that UHF and CF have similar long-term toxicity and efficacy, while the latter demonstrated that modern SBRT has equivalent short-term toxicity as well. A separate report from a consortium of studies data provides prospective, albeit nonrandomized, data supporting the longer-term safety and efficacy of SBRT specifically. Thus, mounting high-level evidence suggests that SBRT is an acceptable standard care of option for men with localized prostate cancer.
| S-EPMC7278320 | biostudies-literature
Project description:BackgroundFurther analysis of phase I trial of the KEYNOTE-001 has shown that previous radiotherapy improves the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab treatment, possibly explained by the radiation-induced specific anti-cancer immunity with a memory effect. In this study, we aimed to investigate the peripheral memory and naïve T cells as predictors of early response in lung metastases post-stereotactic body radiotherapy (SBRT).MethodsSixty-six lung metastases patients with NSCLC who received SBRT were enrolled in this study. Analyses of peripheral memory CD4+ T, memory CD8+ T, naive CD4+ T, and naive CD8+ T in NSCLC patients were performed by flow cytometry. Evaluations of the link between immune cells and early radiation response a month after SBRT were carried out via logistic regression analyses.ResultsHigher levels of memory CD4+ T, memory CD8+ T, and lower levels of naïve CD4+ T, CD4+ naïve/memory ratio, and CD8+ naïve/memory ratio were shown in responders compared with non-responders (all P?<?0.05). Logistic regression analyses of univariate and multivariate revealed that peripheral memory CD4+ T (OR: 0.14, 95% CI 0.04-0.50, P?=?0.003; OR: 0.17, 95% CI 0.05-0.66, P?=?0.010), memory CD8+ T (OR: 0.11, 95% CI 0.01-0.87, P?=?0.037; OR: 0.11, 95% CI 0.01-0.97, P?=?0.047), naïve CD4+ T (OR: 16.25, 95% CI 3.17-83.13, P?=?0.001; OR: 12.67, 95% CI 2.26-71.18, P?=?0.004) and CD4+ naïve/memory ratio (OR: 11.27, 95% CI 2.67-47.58, P?=?0.001; OR: 8.50, 95% CI 1.90-38.14, P?=?0.005) were independent predictors for tumor response to SBRT in the lung metastases of NSCLC patients.ConclusionsThe tumor response of lung metastases a month after SBRT independently correlated with peripheral memory CD4+ T, memory CD8+ T, naïve CD4+ T, and CD4+ naïve/memory ratio. These findings could be helpful in incorporating additional treatments to improve clinical outcomes in the case of poor responders.
| S-EPMC6505218 | biostudies-literature
Project description:Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low ?/? ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come.
| S-EPMC6069023 | biostudies-literature
Project description:The aim of the present study was to evaluate the toxicity and investigate the prognostic factors of stereotactic body radiotherapy (SBRT) for peripheral stage I lung cancer in patients with poor pulmonary function. Data from 95 patients with stage I lung cancer with poor pulmonary function treated using SBRT at Osaka Rosai Hospital were retrospectively analyzed. Poor pulmonary function was defined as the forced expiratory volume %/sec (FEV1/FVC) <70% or percentage of vital capacity (%VC) <80% during pretreatment spirometry testing. The median FEV1/FVC and %VC of the patients were 59.1 and 78.8%, respectively. The most commonly prescribed dose of SBRT was 50 Gy in four fractions (68 patients, 72%). The median follow-up period was 34 months. Four patients developed adverse effects of grade ?3, one patient developed grade 5 radiation pneumonitis, one grade 5 hemoptysis, one grade 3 radiation pneumonitis and one grade 3 chest wall pain. The 3-year local control and overall survival (OS) rates were 78.8 and 59.9%, respectively. Univariate analysis revealed that Karnofsky performance status (KPS) significantly predicted OS (P=0.037). Thus, SBRT in patients with stage I lung cancer with poor pulmonary function may be effective with acceptable toxicity. A KPS score ?80 indicated good prognosis.
| S-EPMC7039104 | biostudies-literature
Project description:Background and purposePhoton Stereotactic Body Radiotherapy (SBRT) for primary and metastatic tumors of the liver is challenging for larger lesions. An in silico comparison of paired SBRT and Stereotactic Body Proton Therapy (SBPT) plans was performed to understand the potential advantages of SBPT as a function of tumor size and location.Methods and materialsTheoretical tumor volumes with maximum diameter of 1-10 cm were contoured in the dome, right inferior, left medial, and central locations. SBRT and SBPT plans were generated to deliver 50 Gy in 5 fractions, max dose <135%. When organs-at-risk (OAR) constraints were exceeded, hypothetical plans (not clinically acceptable) were generated for comparison. Liver normal tissue complication probability (NTCP) models were applied to evaluate differences between treatment modalities.ResultsSBRT and SBPT were able to meet target goals and OAR constraints for lesions up to 7 cm and 9 cm diameter, respectively. SBPT plans resulted in a higher integral gross target dose for all lesions up to 7 cm (mean dose 57.8 ± 2.3 Gy to 64.1 ± 2.2 Gy, p < 0.01). Simultaneously, SBPT spared dose to the uninvolved liver in all locations (from 11.5 ± 5.3 Gy to 8.6 ± 4.4 Gy, p < 0.01), resulting in lower NTCP particularly for larger targets in the dome and central locations. SBPT also spared duodenal dose across all sizes and positions (from 7.3 ± 1.1 Gy to 1.1 ± 0.3 Gy, p < 0.05).ConclusionThe main advantages of SBPT over SBRT is meeting plan goals and constrains for larger targets, particularly dome and central locations, and sparing dose to uninvolved liver. For such patients, SBPT may allow improvements in tumor control and treatment safety.
| S-EPMC7807648 | biostudies-literature