Evaluation of the Systemic and Regional Antibiotic Therapy Effectiveness as Part of Complex Therapy in Patients with Locally Spread Breast Cancer

In recent years, breast cancer is the most common oncologic pathology and the most common cause of disability among women in developed countries.The aim of the study. To improve direct and long-term results of treatment in patients with locally spread forms of breast cancer (LSBC) by accelerated regression of perifocal inflammatory changes using selective intraarterial application of antibiotics; improving patients' quality of life.Materials and methods. The main sample consisted of 109 patients.The control group included 65 (61 %) clinical cases of LSBC who were performed series of courses of intravenous systemic polychemotherapy (SPHT) as neoadjuvant therapy accompanied by systemic intravenous antibiotic therapy. The study group consisted of 42 (39 %) patients who were performed selective intraarterial neoadjuvant polychemotherapy course with simultaneous regional use of antibiotic therapy in the intraarterial administration.Results. The regional administration of antibiotics as a part of the complex neoadjuvant therapy, along with the method of selective intraarterial polychemotherapy, has a positive effect on the linear and chronometric regression of perifocal inflammatory changes around the focus of the primary inoperable LSBC, which positively affects the somatic and psychological patient's state and increases the quality of his life.Conclusions. The complex regional impact on the affected organ has a statistically confirmed better effect with bright holistic features, demonstrating the additive synergism of selective techniques.The selective intraarterial antibiotic therapy does not require additional time and material costs while increasing the efficiency of the method. The versatile advanced approach positively affects the somatic and psychological state of the patient

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

Background: Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20–30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.Objectives: To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.Data sources: Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.Review methods: Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.Results: The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of –£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ? 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.Conclusions: There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.Source of funding: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

The role of adjuvant chemotherapy for patients with resected pancreatic cancer: Systematic review of randomized controlled trials and meta-analysis

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3-5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI -4.6 to 10.8%, p > 10.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined. Copyright (C) 2008 S. Karger AG, Basel

How and why systemic inflammation worsens quality of life in patients with advanced cancer

Introduction: The presence of an innate host systemic inflammatory response has been reported to be a negative prognostic factor in a wide group of solid tumour types in both the operable and advanced setting, both local and distant. In addition, this host systemic inflammatory response is associated with both clinician reported patient performance status and self-reported measures of quality of life in patients with cancer. Areas covered: A variety of mechanisms are thought to underlie this, including the influence of the host immune response on physical symptoms such as pain and fatigue, its effect on organ systems associated with physical ability and well being such as skeletal muscle, and bone marrow. Furthermore, this innate inflammatory response is thought to have a direct negative impact on mood through its action on the central nervous system. Expert commentary: It is clear that the host systemic inflammatory response represents a target for intervention in terms of both improving quality of life and prognosis in patients with advanced cancer. Based on this paradigm, future research should focus both on pathways which might be targeted by novel agents, but also on whether existing anti-inflammatory drugs might be of benefit

Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis.

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM

New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials.

Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease

Neoadjuvant therapy for breast cancer

Objective: To evaluate the frequency of neoadjuvant therapy (NT) in women with stage I–III breast cancer in Italy and whether it is influenced by biological characteristics, screening history, and geographic area. Methods: Data from the High Resolution Study conducted in 7 Italian cancer registries were used; they are a representative sample of incident cancers in the study period (2009–2013). Included were 3546 women aged <85 years (groups <50, 50–69, 70–64, and 75+) with stage I–III breast cancer at diagnosis who underwent surgery. Women were classified as receiving NT if they received chemotherapy, target therapy, and/or hormone therapy before the first surgical treatment. Logistic models were built to test the association with biological and contextual variables. Results: Only 8.2% of women (290 cases) underwent NT; the treatment decreases with increasing age (14.5% in age <50 and 2.2% in age 75+), is more frequent in women with negative receptors (14.8%), HER2-positive (15.7%), and triple-negative (15.6%). The multivariable analysis showed the probability of receiving NT is higher in stage III (odds ratio [OR] 3.83; 95% confidence interval [CI] 2.83–5.18), luminal B (OR 1.87; 95% CI 1.27–2.76), triple-negatives (OR 1.88; 95% CI 1.15–3.08), and in symptomatic cancers (OR 1.98; 95% CI 1.13–3.48). Use of NT varied among geographic areas: Reggio Emilia had the highest rates (OR 2.29; 95% CI 1.37–3.82) while Palermo had the lowest (OR 0.41; 95% CI 0.24–0.68). Conclusions: The use of NT in Italy is limited and variable. There are no signs of greater use in hospitals with more advanced care