Number Of New Metastases Research Articles

P03.09.B LOW DOSE BATH FROM RADIOSURGERY TO SURROUNDING NORMAL BRAIN IN TREATMENT OF BRAIN METASTASES COULD STERILIZE BRAIN AND INHIBIT RECURRENCES

Abstract BACKGROUND Stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) are standard treatments for brain metastases. Each SRS/fSRT plan has a low-dose penumbra outside the high dose area, which multiplies if multiple metastases are irradiated and results in a low-dose bath in healthy brain tissue. We hypothesize that a certain dose of the low-dose bath can sterilize brain tissue and prevent local recurrences. We present first data of an ongoing project. MATERIAL AND METHODS Data of fifty-three patients with brain metastases treated with single fraction SRS or fractionated fSRT at our institute between 2020 and 2022 were reviewed retrospectively. All patients with at least one cranial follow-up MRI after 3 months were evaluated. Follow-up MRI scans were fused to the original treatment plans. New metastases in the isodose-volumes of 10 Gy-, 8 Gy-, 6 Gy-, 4 Gy-, and 2 - Gy were identified and evaluated. Mean doses, on the site of the new lesions, received from SRS/fSRT were tabulated summarized and analyzed. RESULTS Six of the 53 patients met the inclusion criteria. Five patients developed recurrent brain metastases out-of-field within 2-4 months of follow-up. One metastasis was observed outside the irradiation field. One patient developed no new metastases. With decreasing isodose levels an increasing number of new metastases were observed: In the reconstructed volume of 10Gy (V10Gy), V8Gy and V6Gy two metastases each, no metastases in the V4Gy and 5 metastases in the V2Gy. No toxicities were observed. CONCLUSION Our data suggest a trend towards a benefit that the low-dose bath as part of the penumbra of stereotactic radiotherapy sterilizes brain tissue. Especially, brain regions receiving doses of 4 Gy or more had fewer new lesions compared to regions that received less than 4 Gy. This should be further validated prospectively in larger patient populations, in clinical trials with combination of CNS-accessible immunotherapy like Osimertinib. Indications for whole brain radiotherapy could be further reduced. Low dose spillage with manageable risks might be sufficient to treat microscopic brain metastases in the future.

Initial Brain Metastasis Velocity: Does the Rate at Which Cancers First Seed the Brain Affect Outcomes?

Brain metastasis velocity (BMV) is a novel metric used to describe the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). BMV, as defined in a previous publication, is a valuable tool to help guide the decision for WBRT vs SRS for salvage therapy. A limitation in the application of BMV is that it requires the number of metastases at time of treatment failure after initial SRS. By investigating patient characteristics at time of first SRS, we developed initial brain metastasis velocity (iBMV), a new metric that takes into account factors that influence the BMV prior to treatment failure. Particularly, it incorporates the rate at which cancer seeds the brain from time of initial cancer diagnosis. We retrospectively reviewed patients with BM treated at our institution from 2000-2013 with upfront SRS without WBRT. BMV for each patient was calculated as the cumulative number of new metastases from initial SRS divided by units of years. We defined iBMV, a new metric for patients who were diagnosed with BM after their primary cancer diagnosis. iBMV was calculated as the number of BM at the time of initial SRS over the unit of years from initial diagnosis to first SRS. Thus, representing a rate that the primary cancer seeded the brain. We performed a linear regression to assess the relationship of iBMV to BMV and overall survival (OS) after first SRS to death and other oncologic outcomes. iBMV was not calculated for patients who presented with stage IV disease with BM or for patients who developed BM <2 months from initial diagnosis. From 2000-2013, 736 patients were treated at our institution with upfront SRS without WBRT. Median OS was 8.6 mos (IQR 7.9-9.6). The presence or absence of BM at initial cancer diagnosis was not predictive of survival after first SRS, neurologic death, or BMV and the median number of BM at first SRS was similar (median BM = 1.0, IQR = 1-3, P = 0.71). Four hundred forty-three (60%) patients developed BM ≥2 months after initial diagnosis. In these 443 patients, the median time to first SRS from time of initial diagnosis was 27.2 mos (IQR = 24.7-31.4). Median iBMV was 0.73 (IQR = 0.30-1.74). Lung histology was associated with a higher iBMV compared to breast (β = 0.09 SE = 0.02, P < 0.001). Renal cell, melanoma, and other histologies did not have significantly different iBMV rates compared to breast. The iBMV was predictive of both BMV after treatment (β = 23.87, SE 6.92, P<0.001) and OS (HR = 1.11; CI: 1.03-1.20, P = 0.006). The iBMV was not significant for predicting neurologic death (HR = 1.07; CI 1.00-1.15 P = 0.07) or time to WBRT (P = 0.18). The iBMV ≥4 metastases/year was predictive of distant brain failure per Gray’s test (P = 0.02). The iBMV is a metric that predicts for BMV and OS. A higher iBMV was associated with a worse OS and numerically higher BMV. Lung histology was associated with a higher iBMV than breast. The presence or absence of BM at time of initial cancer diagnosis was not predictive for survival, as calculated from time of first SRS to death.

Progression of bone metastases in patients with prostate cancer - automated detection of new lesions and calculation of bone scan index

BackgroundThe objective of this study was firstly to develop and evaluate an automated method for the detection of new lesions and changes in bone scan index (BSI) in serial bone scans and secondly to evaluate the prognostic value of the method in a group of patients receiving chemotherapy.MethodsThe automated method for detection of new lesions was evaluated in a group of 266 patients using the classifications by three experienced bone scan readers as a gold standard. The prognostic value of the method was assessed in a group of 31 metastatic hormone-refractory prostate cancer patients who were receiving docetaxel. Cox proportional hazards were used to investigate the association between percentage change in BSI, number of new lesions and overall survival. Kaplan-Meier estimates of the survival function were used to indicate a significant difference between patients with an increase/decrease in BSI or those with two or more new lesions or less than two new lesions.ResultsThe automated method detected progression defined as two or more new lesions with a sensitivity of 93% and a specificity of 87%. In the treatment group, both BSI changes and the number of new metastases were significantly associated with survival. Two-year survival for patients with increasing and decreasing BSI from baseline to follow-up scans were 18% and 57% (p = 0.03), respectively. Two-year survival for patients fulfilling and not fulfilling the criterion of two or more new lesions was 35% and 38% (n.s.), respectively.ConclusionsAn automated method can be used to calculate the number of new lesions and changes in BSI in serial bone scans. These imaging biomarkers contained prognostic information in a small group of patients with prostate cancer receiving chemotherapy.

One should not just read what one believes: the nearly irresolvable issue of producing truly objective, evidence-based guidelines for the management of differentiated thyroid cancer

summary of some of the cited publications introduces eachrecommendation; comprehensive tabular overviews ofsupporting data are not given. The reader therefore cannoteasily assess the thoroughness with which the literatureregarding controversial topics was considered. In particular,the ATA guidelines’ summaries often fail to mentionevidence against the recommendation.Further, whether greater weight is accorded to publishedmeta-analyses such as those by Sawka et al. [12, 13] than tosingle-centre observational studies is not specified in theguidelines’ methodology description. Meta-analyses ofcourse may show effects that individual studies are toosmall to detect; for example, the meta-analysis by Sawka etal. [13] regarding the effect of RRA on recurrence anddisease-specific mortality considered six studies addressingrecurrence at distant sites. None of the studies individuallyincluded enough distant recurrences for a 95% confidenceinterval (CI) for risk reduction that excluded the zero value.However, pooling the results from all six studies, the riskreduction was 2% and the 95% CI 4–1%. A significantlylower number of new metastases over the course of thedisease after

Timing and risk factors for new brain metastasis formation in patients initially treated only with Gamma Knife surgery

Stereotactic radiosurgery has been shown to afford a reasonable chance of local tumor control. However, new brain metastasis can arise following successful local tumor control from radiosurgery. This study evaluates the timing, number, and risk factors for development of subsequent new brain metastasis in a group of patients treated with stereotactic radiosurgery alone. One hundred seventeen patients with histologically confirmed metastatic cancer underwent Gamma Knife surgery (GKS) to treat all brain metastases demonstrable on MR imaging. Patients were followed clinically and radiologically at approximately 3-month intervals for a median of 14.4 months (range 0.37-51.8 months). Follow-up MR images were evaluated for evidence of new brain metastasis formation. Statistical analyses were performed to determine the timing, number, and risk factors for development of new brain metastases. The median time to development of a new brain metastasis was 8.8 months. Patients with 3 or more metastases at the time of initial radiosurgery or those with cancer histologies other than non-small cell lung carcinoma were found to be at increased risk for early formation of new brain metastasis (p < 0.05). The mean number of new metastases per patient was 1.6 (range 0-11). Those with a higher Karnofsky Performance Scale score at the time of initial GKS were significantly more likely to develop a greater number of brain metastases by the last follow-up evaluation. The timing and number of new brain metastases developing in patients treated with GKS alone is not inconsequential. Those with 3 or more metastases at the time of radiosurgery and those with cancer histology other than non-small cell lung carcinoma were at greater risk of early formation of new brain metastasis. Frequent follow-up evaluations, such as at 3-month intervals, appears appropriate in this patient population, particularly in high-risk patients. When detected early, salvage treatments including repeat radiosurgery can be used to treat new brain metastasis.

Combined vindesine and razoxane shows antimetastatic activity in advanced soft tissue sarcomas

Razoxane and vindesine were shown to suppress distant metastasis in animal systems. Both drugs affect main steps of the metastatic cascade. Therefore, a pilot study was performed to study the influence of these drugs on the dynamics of metastasis in advanced soft tissue sarcomas (STS). This study was now updated. Twenty-three patients with unresectable (n = 7) and oligometastatic STS (n = 16) received a basic treatment with razoxane and vindesine supported by radiotherapy and occasionally by surgery. Long-term treatment was intended in patients with metastatic disease. The cumulative number of new metastases after 6 and 9 months were determined. Thirty-six patients with comparable stages of STS treated with contemporary chemotherapy served as non-randomized, retrospective controls. The prognostic parameters of the groups were comparable. In patients receiving razoxane and vindesine, the median number of new metastases after 6 months was 0 (range, 0-40) and after 9 months likewise 0 (0-70). The corresponding numbers in the control group were 4.5 (range, 0-40) and 9 (0->100) (P < 0.001). The progression-free survival at 6 months was 74% in the study group and 23% in the controls. The median survival time from the occurrence of the first metastasis or the time of unresectability was 20+ months (range, 8-120+) versus 9 months (range, 2-252) (P < 0.001). The combined treatment was associated with a low to moderate toxicity. Trimodal treatment with razoxane, vindesine, and radiotherapy is feasible in patients with unresectable primaries and early metastatic STS. The combination inhibits the development of remote metastases in a majority of the patients and prolongs survival.

Modeling Growth Kinetics and Statistical Distribution of Oligometastases

Modeling Growth Kinetics and Statistical Distribution of Oligometastases