Molecular Evidence Demonstrating Local Treatment Failure is the Source of Distant Metastases in Some Patients Treated for Breast Cancer

2008 ◽  
Vol 71 (3) ◽  
pp. 689-694 ◽  
Author(s):  
Frank A. Vicini ◽  
Neal S. Goldstein ◽  
Michelle Wallace ◽  
Larry Kestin
2005 ◽  
Vol 103 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Sharad Goyal ◽  
Dheerendra Prasad ◽  
Frank Harrell ◽  
Julie Matsumoto ◽  
Tyvin Rich ◽  
...  

Object. The goal of this study was to evaluate the effectiveness and limitations of gamma knife surgery (GKS) in the treatment of intracranial breast carcinoma lesions. Methods. A retrospective analysis of the GKS database at the University of Virginia Health System identified 43 patients with a total of 84 lesions who were treated between 1989 and 2000. All patients who received treatment were included in this study. Imaging studies were available in 35 patients with 67 treated lesions. The overall duration of median survival was 13 months (95% confidence interval [CI] 7–16 months) after radiosurgery. A univariable Cox regression analysis revealed that a single lesion (p = 0.035), a high Karnofsky Performance Scale (KPS) score (p = 0.019), and a high Score Index for Radiosurgery (SIR) in Brain Metastases (p = 0.036) were associated with a significantly lengthened time to local treatment failure. The median duration of survival for patients grouped according to the SIR as low, middle, and high was 3, 8, and 21 months, respectively (p = 0.00033). A multivariable analysis showed that a high KPS score (p = 0.006), a high SIR (p = 0.014), and advanced age (0.038) were predictive of survival. The 1-, 2-, 3-, and 5-year survival rates were 49, 23, 12, and 2%, respectively. The overall median time to local treatment failure was 10 months (95% CI 6–14 months) after GKS. A univariable analysis demonstrated that a single lesion, higher KPS score, and a higher SIR were associated with a significantly longer time until local treatment failure. A multivariable analysis showed that a higher KPS score and SIR and patients who had received chemotherapy were associated with a significantly longer time to local treatment failure. Neuroimaging scores given for the enhancement pattern (ring-enhancing, heterogeneous, and homogeneous signal), amount of necrosis (none, < 50%, and > 50%), and mass effect (none, mild, moderate, and severe) of each treated lesion did not correlate with survival or local treatment failure. Conclusions. The SIR and the KPS score are prognostic factors in patients whose intracranial breast cancer metastases are treated with GKS. The SIR, which includes the KPS score, patient age, systemic disease status, largest lesion volume, and number of lesions, can be used to identify those patients with breast cancer metastasis who would benefit from GKS better than KPS score alone. The contribution of whole-brain radiation therapy to GKS with regard to local tumor control or survival could not be identified.


Author(s):  
Francisco Pimentel Cavalcante ◽  
Eduardo Camargo Millen ◽  
Felipe Pereira Zerwes ◽  
Guilherme Garcia Novita

AbstractThe present paper reports on the local treatment of breast cancer from a historical perspective. A search for articles written in English was made in the Medline and EMBASE databases, and 40 papers were selected. Over the past 10 years, various randomized, controlled clinical trials on the local treatment of breast cancer indicated that patients with the same molecular subtype may receive different individualized surgical treatments aimed at optimizing systemic adjuvant therapy. With a view to retaining the gains made in disease-free and overall survival, surgical techniques have advanced from radical surgery to conservative mastectomies, thus reducing sequelae, while adjuvant and neoadjuvant therapies have contributed toward controlling the disease, both distant metastases and local recurrence. Current studies evaluate whether future breast cancer therapy may even succeed in eliminating surgery to the breast and axilla altogether.


Author(s):  
Vinzenz Völkel ◽  
Tom A. Hueting ◽  
Teresa Draeger ◽  
Marissa C. van Maaren ◽  
Linda de Munck ◽  
...  

Abstract Purpose To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases (DM) using updated follow-up data and the best suitable statistical approaches. Methods Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (n = 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples. Results Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74–0.76) and SP (0.67, 95%CI: 0.65–0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77–0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created. Conclusions INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.


Author(s):  
Aleksandra Ledwon ◽  
Ewa Paliczka-Cieślik ◽  
Aleksandra Syguła ◽  
Tomasz Olczyk ◽  
Aleksandra Kropińska ◽  
...  

Abstract Objective In patients with differentiated thyroid carcinoma (DTC), serum thyroglobulin levels measured at the time of remnant ablation after thyroid hormone withdrawal were shown to have prognostic value for disease-free status. We sought to evaluate serial thyroglobulin measurements at the time of recombinant human thyroid-stimulating hormone (rhTSH)-aided iodine 131 (131I) adjuvant treatment as prognostic markers of DTC. Methods Six hundred-fifty patients with DTC given total/near-total thyroidectomy and adjuvant radioiodine post-rhTSH stimulation were evaluated. Thyroglobulin was measured on day 1 (Tg1; at the time of the first rhTSH injection), day 3 (Tg3; 1 day after the second, final rhTSH injection), and day 6 (Tg6; 3 days post-radioiodine administration). Treatment failure was defined as histopathologically confirmed locoregional recurrence, or radiologically-evident distant metastases (signs of disease on computer tomography (CT) or magnetic resonance imaging (MRI), or abnormal foci of radioiodine or [18F] fluorodeoxyglucose ([18F]FDG) uptake. Results In univariate analysis, Tg1 (p < 0.001) and Tg3 (p < 0.001), but not Tg6, were significantly associated with structural recurrence. In multivariate analysis of the overall cohort, only Tg3 was independently associated with structural recurrence. In multivariate analysis of the subgroup (n = 561) with anti-Tg antibodies titers below the institutional cut-off, 115 IU/mL, Tg1 was an independent prognostic marker. Tg1 and Tg3 cutoffs to best predict structural recurrence were established at 0.7 ng/mL and 1.4 ng/mL, respectively. Conclusions Tg1 and Tg3, measurements made after rhTSH stimulation but before radioiodine treatment, independently predict a low risk of treatment failure in patients with DTC. Levels measured post-radioiodine application (e.g., Tg6) are highly variable, lack prognostic value, and hence can be omitted.


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