38 research outputs found
Prospective randomized clinical studies involving reirradiation: update of a systematic review
BACKGROUND
Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation of methodological strengths and weaknesses, practice-changing results, and open questions.
MATERIAL AND METHODS
Systematic review of trials published between 2015 and February 2023.
RESULTS
We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma. Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites.
CONCLUSION
Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation
Prospective randomized clinical studies involving reirradiation: update of a systematic review
Background Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or
symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous
review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation
of methodological strengths and weaknesses, practice-changing results, and open questions.
Material and methods Systematic review of trials published between 2015 and February 2023.
Results We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The
median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses
varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma.
Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local
control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred
option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity
remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites.
Conclusion Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care
for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy
and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort
ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation
How we treat octogenarians with brain metastases
Biologically younger, fully independent octogenarians are able to tolerate most oncological treatments. Increasing frailty results in decreasing eligibility for certain treatments, e.g., chemotherapy and surgery. Most brain metastases are not an isolated problem, but part of widespread cancer dissemination, often in combination with compromised performance status. Multidisciplinary assessment is key in this vulnerable patient population where age, frailty, comorbidity and even moderate additional deficits from brain metastases or their treatment may result in immobilization, hospitalization, need for nursing home care, termination of systemic anticancer treatment etc. Here, we provide examples of successful treatment (surgery, radiosurgery, systemic therapy) and best supportive care, and comment on the limitations of prognostic scores, which often were developed in all-comers rather than octogenarians. Despite selection bias in retrospective studies, survival after radiosurgery was more encouraging than after whole-brain radiotherapy. Prospective research with focus on octogenarians is warranted to optimize outcomes
Personalized treatment of brain metastases: Evolving survival prediction models may benefit from evaluation of serum tumor markers (narrative review)
Treatment of a limited number of brain metastases (oligometastases) might include complex and sometimes invasive approaches, e.g. neurosurgical resection followed by post-operative stereotactic radiotherapy, and thus, correct identification of patients who are appropriate candidates is crucial. Both, staging procedures that visualize the true number of metastastic lesions and prognostic assessments that identify patients with limited survival, who should be managed with less complex, palliative approaches, are necessary before proceeding with local treatment that aims at eradication of all oligometastases. Some of the prognostic models, e.g. the LabBM score (laboratory parameters in patients with brain metastases), include blood biomarkers believed to represent surrogate markers of disease extent. In a recent study, patients with oligometastases and a LabBM score of 0 (no abnormal biomarkers) had an actuarial 5-year survival rate of 27% after neurosurgical resection and 39% after stereotactic radiotherapy. Other studies have tied serum tumor markers such as carcinoembryonic antigen (CEA) to survival outcomes. Even if head-to-head comparisons and large-scale definitive analyses are lacking, the available data suggest that attempts to integrate tumor marker levels in blood biomarker-based survival prediction models are warranted
Personalized treatment of brain metastases: Evolving survival prediction models may benefit from evaluation of serum tumor markers (narrative review)
Treatment of a limited number of brain metastases (oligometastases) might include complex and sometimes invasive approaches, e.g. neurosurgical resection followed by post-operative stereotactic radiotherapy, and thus, correct identification of patients who are appropriate candidates is crucial. Both, staging procedures that visualize the true number of metastastic lesions and prognostic assessments that identify patients with limited survival, who should be managed with less complex, palliative approaches, are necessary before proceeding with local treatment that aims at eradication of all oligometastases. Some of the prognostic models, e.g. the LabBM score (laboratory parameters in patients with brain metastases), include blood biomarkers believed to represent surrogate markers of disease extent. In a recent study, patients with oligometastases and a LabBM score of 0 (no abnormal biomarkers) had an actuarial 5-year survival rate of 27% after neurosurgical resection and 39% after stereotactic radiotherapy. Other studies have tied serum tumor markers such as carcinoembryonic antigen (CEA) to survival outcomes. Even if head-to-head comparisons and large-scale definitive analyses are lacking, the available data suggest that attempts to integrate tumor marker levels in blood biomarker-based survival prediction models are warranted.
Keywords: biomarkers; brain metastases; prognostic model; score; tumor marker
Personalized radiotherapy of brain metastases: survival prediction by means of dichotomized or differentiated blood test results?
Background and objectives: The validated LabBM score (laboratory parameters in patients with brain metastases) represents a widely applicable survival prediction model, which incorporates 5 blood test results (serum lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin, platelets and hemoglobin). All tests are classified as normal or abnormal, without accounting for the wide range of abnormality observed in practice. We tested the hypothesis that improved stratification might be possible, if more granular test results are employed.
Methods: Retrospective analysis of 198 patients managed with primary whole-brain radiotherapy in one of the institutions who validated the original LabBM score.
Results: For two blood tests (albumin, CRP), discrimination was best for the original dichotomized version (normal/abnormal). For two others (LDH, hemoglobin), a three-tiered classification was best. The number of patients with low platelet count was not large enough for detailed analyses. A modified LabBM score was developed, which separates the intermediate of originally 3 prognostic groups into 2 statistically significantly different strata, resulting in a 4-tiered score.
Conclusion: This initial proof-of-principle study suggests that granular blood test results might contribute to further improvement of the score, or alternatively development of a nomogram, if additional large-scale studies confirm the encouraging results of the present analysis
Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative
The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively
A virtual audit system for intensity-modulated radiation therapy credentialing in Japan Clinical Oncology Group clinical trials: A pilot study
PURPOSE
The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data.
METHODS
We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2).
RESULTS
The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively.
CONCLUSION
This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system
NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics
BACKGROUND
Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable.
METHODS
A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed.
RESULTS
IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed.
CONCLUSION
NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others
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NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics.
BACKGROUND
Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable.
METHODS
A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed.
RESULTS
IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed.
CONCLUSION
NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others