local therapy for breast cancer in malignant lymphoma survivors

Summary Aims: Breast cancer is the most frequent secondary tumor in young women previously treated with mantle radiation for Hodgkin's disease. Prior therapeutic radiation to the breast region is considered an absolute contraindication to breast conservative surgery, and mastectomy is considered the treatment of choice. We performed a retrospective review to assess the potential of performing breast conservative surgery and intraoperative radiotherapy with electrons (ELIOT), in these patients. Methods and results: Forty-three patients affected by early breast cancer, previously treated with mantle radiation for malignant lymphoma, who underwent breast conservative surgery and ELIOT, were identified in our institution. Median age at diagnosis of lymphoma was 26 years (49% were less than 25). Median interval between lymphoma and breast cancer occurrence was 19 years. A total dose of 21 Gy (prescribed at 90% isodose) in 39 patients (91%), of 17 Gy (prescribed at 100% isodose) in 1 patient and 18 Gy (prescribed at 90% isodose), was delivered. ELIOT was well tolerated in all patients without any unusual acute or late reactions. After a median follow-up of 52 months, local recurrence occurred in 9% of the patients and metastases in 7% patients. Conclusion: In patients previously treated for lymphoma, partial breast irradiation, and in particular ELIOT, permits breast conservative surgery without acute local complications, decreasing the number of avoidable mastectomies

breast conserving surgery in 201 very young patients 35 years

Abstract Introduction Surgical treatment of breast cancer in very young patients ( Patients and Methods We retrospectively evaluated outcome and prognostic factors of 201 consecutive patients treated with breast conservation followed by whole breast irradiation between 1997 and 2004 with special attention paid to local control. The average follow up was 72 months (range 13–133 months). Results The mean age was 32 years (Range 20–34). Invasive ductal carcinoma was found in 175 (87.1%) patients. Two (1%) patients had invasive lobular carcinoma. One-hundred and eighteen patients (58.7%) had tumors of 2 cm or smaller. Sentinel lymph node biopsy was performed in 105 (52.2%) patients. One-hundred and ten (54.7%) patients had node-negative disease, 68 (33.8%) patients had 1–3 positive nodes and 23 (11.4%) +4 positive nodes. Eighteen patients (9.0%) developed a local recurrence, 25 (12.5%) developed distant metastases and 23 patients (11.4%) died during follow up. The 5- and 10-year cumulative incidence of local events were 8.2% and 12,3% respectively. The univariate analysis did not identify any variables affecting local disease-free survival. Conclusions Breast conservation in very young patients achieves an acceptable local control rate. No prognostic factors were associated with local events

The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy

Aims The ageing heart naturally incurs a progressive decline in function and perfusion that available treatments cannot halt. However, some exceptional individuals maintain good health until the very late stage of their life due to favourable gene–environment interaction. We have previously shown that carriers of a longevity-associated variant (LAV) of the BPIFB4 gene enjoy prolonged health spans and lesser cardiovascular complications. Moreover, supplementation of LAV-BPIFB4 via an adeno-associated viral vector improves cardiovascular performance in limb ischaemia, atherosclerosis, and diabetes models. Here, we asked whether the LAV-BPIFB4 gene could address the unmet therapeutic need to delay the heart’s spontaneous ageing. Methods and results Immunohistological studies showed a remarkable reduction in vessel coverage by pericytes in failing hearts explanted from elderly patients. This defect was attenuated in patients carrying the homozygous LAV-BPIFB4 genotype. Moreover, pericytes isolated from older hearts showed low levels of BPIFB4, depressed pro-angiogenic activity, and loss of ribosome biogenesis. LAV-BPIFB4 supplementation restored pericyte function and pericyte-endothelial cell interactions through a mechanism involving the nucleolar protein nucleolin. Conversely, BPIFB4 silencing in normal pericytes mimed the heart failure pericytes. Finally, gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and pericyte coverage. Conclusions We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in the heart’s ageing. These findings open to using LAV-BPIFB4 to reverse the decline of heart performance in older people

The sacral chordoma margin

[Objective]: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. [Background]: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. [Methods]: A multidisciplinary meeting of the “Chordoma Global Consensus Group” was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. [Results]: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. [Conclusion]: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity

Unmet needs in the management of unresectable stage III non-small cell lung cancer: a review after the 'radio talk' webinars

Introduction Stage III non-small cell lung cancer (NSCLC) is a variable entity, encompassing bulky primary tumors, nodal involvement, or both. Multidisciplinary evaluation is essential to discuss multiple treatment options, to outline optimal management, and to examine the main debated topics and critical issues not addressed by current trials and guidelines that influence daily clinical practice. Areas covered From March to 5 May 2021 ,meetings were scheduled in a webinar format titled 'Radio Talk' due to the COVID-19 pandemic; the faculty was composed of 6 radiation oncologists from 6 different Institutions of Italy, all of them were the referring radiation oncologist for lung cancer treatment at their respective departments and were or had been members of AIRO (Italian Association of Radiation Oncology) Thoracic Oncology Study Group. The topics covered included: pulmonary toxicity, cardiac toxicity, radiotherapy dose, fractionation and volumes, unfit/elderly patients, multidisciplinary management. Expert opinion The debate was focused on the unmet needs triggered by case reports, personal experiences and questions; the answers were often not univocal; however, the exchange of opinion and the contribution of different centers confirmed the role of multidisciplinary management and the necessity that the most critical issues should be investigated in clinical trials

Efficacy of the telephone-based Brief Motivational Intervention for alcohol problems in Brazil

Background: The Brief Motivational Intervention (BMI) is an effective treatment for alcohol misuse but has not been adequately tested for use in helplines for alcoholics. The main objective of this study was to evaluate the efficacy of a telephone-based BMI for Brazilians seeking help with alcohol use cessation. Methods: A randomized, controlled trial was performed with Brazilian subjects. Participants were randomly assigned to either the minimal intervention group (i.e., given reference materials) or the BMI group. Alcohol abstinence was evaluated in a 6-month follow-up telephone counseling session. The analysis was based on the intention to treat (ITT). Results: Of the 5,896 drug users who called the helpline, 700 (12%) used alcohol, 637 of whom enrolled in this study. At 6-month follow-up, 70% of the BMI group had stopped consuming alcohol compared to 41% in the control group (odds ratio = 1.5; 95% confidence interval = 1.2-1.9; p = 0.001). Conclusions: A helpline-based BMI helps alcohol users achieve abstinence

Migratory activity of circulating mononuclear cells is associated with cardiovascular mortality in type 2 diabetic patients with critical limb ischemia

OBJECTIVE Prediction of clinical outcome in diabetic patients with critical limb ischemia (CLI) is unsatisfactory. This prospective study investigates if the abundance and migratory activity of a subpopulation of circulating mononuclear cells, namely, CD45dimCD34posCXCR4posKDRpos cells, predict major amputation and cardiovascular death in type 2 diabetic patients undergoing percutaneous transluminal angioplasty for CLI. RESEARCH DESIGN AND METHODS A consecutive series of 119 type 2 diabetic patients with CLI was enrolled. CD45dimCD34posCXCR4posKDRpos cells were assessed by flow cytometry upon isolation and also after spontaneous or stromal cell-derived factor 1α−directed migration in an in vitro assay. The association between basal cell counts and migratory activity and the risk of an event at 18-month follow-up was evaluated in a multivariable regression analysis. RESULTS Time-to-event analysis of amputation (n = 13) showed no association with the candidate predictors. Sixteen cardiovascular deaths occurred during 18 months of follow-up. Abundance of CD45dimCD34posCXCR4posKDRpos cells was not associated with cardiovascular mortality. Interestingly, in vitro migration of CD45dimCD34posCXCR4posKDRpos cells was higher in patients with cardiovascular death compared with event-free subjects (percentage of migrated cells median value and interquartile range, 0.03 [0.02–0.07] vs. 0.01 [0.01–0.03]; P = 0.0095). Multivariable regression model analysis showed that cell migration forecasts cardiovascular mortality independently of other validated predictors, such as age, diagnosed coronary artery disease, serum C-reactive protein, and estimated glomerular filtration rate. In this model, doubling of migrated cell counts increases the cardiovascular death hazard by 100% (P < 0.0001). CONCLUSIONS The new predictor could aid in the identification of high-risk patients with type 2 diabetes requiring special diagnostic and therapeutic care after revascularization