Oligo- and Polymetastatic Progression in Lung Metastasis(es) Patients Is Associated with Specific MicroRNAs

Rationale: Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy.Methods: We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤5 initial metastases resected with curative intent.Results: Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset.Conclusion: Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.</p

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation

<p>Abstract</p> <p>Background</p> <p>Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.</p> <p>Design</p> <p>Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.</p> <p>Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.</p> <p>Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.</p> <p>Discussion</p> <p>The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01392586">NCT01392586</a>.</p

Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study

Purpose: To study the capacity of an internally cooled radiofrequency (RF) bipolar applicator to create sufficiently deep thermal lesions in hepatic tissue. Materials and methods: Three complementary methodologies were employed to check the electrical and thermal behaviour of the applicator under test. The experimental studies were based on excised bovine (ex vivo study) and porcine liver (in vivo study) and the theoretical models were solved by means of the finite element method (FEM). Results: Experimental and computational results showed good agreement in terms of impedance progress and lesion depth (4 and 4.5 mm respectively for ex vivo conditions, and approximately 7 and 9 mm respectively for in vivo conditions), although the lesion widths were overestimated by the computer simulations. This could have been due to the method used to assess the thermal lesions; the experimental lesions were assessed by the white coagulation zone, whereas the tissue damage function was used to assess the computational lesions. Conclusions: The experimental results suggest that this applicator could create in vivo lesions to a depth of around 7mm. It was also observed that the thermal lesion is mainly confined to the area between both electrodes, which would allow lesion width to be controlled by selecting a specific applicator design. The comparison between the experimental and computational results suggests that the theoretical model could be usefully applied in further studies of the performance of this device. © 2012 Informa UK Ltd All rights reserved.This work received financial support from the Spanish Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion TEC2011-27133-C02-(01 and 02), from Universitat Politecnica de Valencia (INNOVA11-01-5502; and PAID-06-11 Ref. 1988). A. Gonzalez-Suarez is the recipient of grant VaLi+D (ACIF/2011/194) from the Generalitat Valenciana. The proof-reading of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paper.González Suárez, A.; Trujillo Guillen, M.; Burdío Pinilla, F.; Andaluz Martínez, AM.; Berjano Zanón, E. (2012). Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study. International Journal of Hyperthermia. 28(7):663-673. https://doi.org/10.3109/02656736.2012.716900S663673287Topp, S. A., McClurken, M., Lipson, D., Upadhya, G. A., Ritter, J. H., Linehan, D., & Strasberg, S. M. (2004). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 239(4), 518-527. doi:10.1097/01.sla.0000118927.83650.a4Gnerlich, J. L., Ritter, J. H., Linehan, D. C., Hawkins, W. G., & Strasberg, S. M. (2009). Saline-Linked Surface Radiofrequency Ablation. 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An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation

BACKGROUND PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. METHODS Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. RESULTS In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. CONCLUSIONS The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer

Survival Impact of Primary Tumor Resection in De Novo Metastatic Breast Cancer Patients (GEICAM/El Alamo Registry)

The debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach's outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990-2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study's criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results

Younger age as a prognostic indicator in breast cancer: A cohort study

<p>Abstract</p> <p>Background</p> <p>The debate continues as to whether younger women who present with breast cancer have a more aggressive form of disease and a worse prognosis. The objectives of this study were to determine the incidence of breast cancer in women under 40 years old and to analyse the clinicopathological characteristics and outcome compared to an older patient cohort.</p> <p>Methods</p> <p>Data was acquired from a review of charts and the prospectively reviewed GUH Department of Surgery database. Included in the study were 276 women diagnosed with breast cancer under the age of forty and 2869 women over forty. For survival analysis each women less than 40 was matched with two women over forty for both disease stage and grade.</p> <p>Results</p> <p>The proportion of women diagnosed with breast cancer under the age of forty in our cohort was 8.8%. In comparison to their older counterparts, those under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p < 0.001) and higher <it>HER2 </it>over-expression (p = 0.002); there was no statistical difference as regards tumour size (p = 0.477). There was no significant difference in overall survival (OS) for both groups; and factors like tumour size (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p = 0.031) and <it>HER2 </it>(p = 0.002) status and treatment received were independent predictors of OS</p> <p>Conclusion</p> <p>Breast cancer in younger women has distinct histopathological characteristics; however, this does not result in a reduced survival in this population.</p