Advanced-stage Cancer Patients Research Articles

Decisional conflict of physicians during the decision-making process for a simulated advanced-stage cancer patient: an international longitudinal study with German and Belgian physicians

BackgroundDecision making with advanced cancer patients is often associated with decisional conflict regarding treatment outcomes. This longitudinal multicenter study investigated German physicians’ course of decisional conflict during the decision-making process for a Simulated advanced-stage cancer Patient (SP). Results were compared to a matched sample of Belgian physicians.MethodsGerman physicians’ (n = 30) decisional conflict was assessed with the Decisional Conflict Scale (DCS) at baseline (t1) and after the four steps of a decision-making process: after reviewing the SP chart (t2), after viewing an assessment video interview with the SP (t3), after reviewing the team recommendations (t4), and after conducting the patient-physician decision-making interview (t5). The results were compared to those of a Belgian matched sample (n = 30).ResultsDecisional conflict of German physicians decreased during the Decision-Making process (M = 53.5, SD = 11.6 at t2 to M = 37.8, SD = 9.6 at t5, p < 0.001). This was similar to the pattern in the Belgian sample (M = 53.5, SD = 12.5 at t2 to M = 34.1, SD = 10.9 at t5, p < 0.001). There was no significant difference between the two groups for Decisional conflict end scores (p = 0.171). At the end of the Decision-making process, in both groups, still 43.3% of the physicians among each group (n = 13) reported a high Decisional Conflict (DCS > 37.5).ConclusionsPhysicians’ decisional conflict decreases during the decision-making process for an advanced cancer SP, though it remains at a high level. Culture, language and different health care systems have no influence on this process. The results emphasize the influence of psychosocial factors. We conclude that this issue should be considered more intensively in future research and in clinical care.

Factors Related to Advanced Stage of Cancer Presentation in Botswana

Botswana, an upper-middle income country in southern Africa, faces unique challenges in controlling cancer incidence and mortality. Despite universal access to free health care, the majority of Botswana cancer patients present at advanced stages. This study was designed to quantify cancer care-related delays and explore the patient-level and clinical factors related to advanced stage at presentation in Botswana. Two hundred and fourteen patients attending an oncology clinic between December 2015 and January 2017 at the Princess Marina Hospital in Gaborone, Botswana completed a questionnaire on sociodemographic and clinical factors, as well as the cancer-related fears, attitudes, beliefs, and stigmas. Odds ratios were calculated to identify factors significantly associated with advanced stage (stage III/IV) at diagnosis. Of the 214 patients, 40 (18.7%) were male and 174 (81.3%) were female. The median age of diagnosis was age 46, with a total of 146 (71.9%) patients older than 40 years. The most commonly represented cancers included cervical (42.3%), breast (16%), head and neck (15.5%), vulvar (7%), and Kaposi sarcoma (6.6%). Cancer stages represented in the study group included 17 (8.4%) Stage I, 39 (19.2%) Stage II, 49 (24.1%) Stage III, 24 (11.9%) Stage IV, and 74 (36.4%) with unknown stage. There were no significant differences in any of the cancer care delay intervals between early and advanced stage cancer patients. Most of the early and advanced stage patients held appropriate fears, attitudes, and beliefs regarding cancer and its treatment options. Patients who presented at advanced stages were significantly more likely to not be afraid of having cancer (OR=3.48; p<0.05), believe that their family would not care for them if they needed treatment (OR=6.35; p=0.05), and that they cannot afford to get cancer (OR=2.73; p<0.05). Male gender, non-female specific cancers, and the perception that symptoms were less serious were also significantly related to advanced stage diagnosis (p<0.05). Future cancer mortality reduction efforts should emphasize cancer symptom awareness and early detection through routine cancer screening, as well as increasing the acceptability of care seeking among male patients.

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced-stage cancer treated with immunotherapy.

Optimal prognostic and predictive biomarkers for patients with advanced-stage cancer patients who received immunotherapy (IO) are lacking. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), are readily available. The authors investigated the association between these markers and clinical outcomes of patients with advanced-stage cancer who received IO. A retrospective review was conducted of 90 patients with advanced cancer who received treatment on phase 1 clinical trials of IO-based treatment regimens. NLR, MLR, and PLR values were log-transformed and treated as continuous variables for each patient. Overall survival (OS), progression-free survival (PFS), and clinical benefit were used to measure clinical outcomes. For univariate associations and multivariable analyses, Cox proportional-hazards models or logistic regression models were used. The median patient age was 63 years, and most were men (59%). The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). High baseline NLR, MLR, and PLR values were associated significantly with worse OS and PFS (P < .05) and a lower chance of benefit (NLR and PLR; P < .05). Increased NLR, MLR, and PLR values 6 weeks after baseline were associated with shorter OS and PFS (P ≤ .052). Baseline and early changes in NLR, MLR, and PLR values were strongly associated with clinical outcomes in patients who received IO-based treatment regimens on phase 1 trials. Confirmation in a homogenous patient population treated on late-stage trials or outside of trial settings is warranted. These values may warrant consideration for inclusion when risk stratifying patients enrolled onto phase 1 clinical trials of IO agents.

P1.02-08 Hope for People Living with Metastatic Lung Cancer

As in any developing countries state of West Bengal in India has a huge burden of metastatic lung cancer patients in advanced stage coming from rural area where awareness regarding the usefulness of palliative care in rather poor. Our goal is to give a pain free good quality of life in these advanced stage lung cancer patients. Objective of this study is to identify the main difficulties in achieving the above goal in a rural village setting in India. Advanced lung cancer patients in need of palliative care in various villages in of rural India were selected for this study. Their symptoms and managements in that rural surroundings were evaluated by an NGO (under the guidance of a senior palliative care specialist) working in that area. An attempt was made to identify the main obstacles in getting proper palliative care in a rural setting. Pain, fatigue, respiratory distress are the main symptoms effecting these patients. In most patients pain and other symptoms control were grossly inadequate due to lack of properly trained manpower in the rural India. However regular homecare visits by a group of social workers were of immense help in the last few months of life. NGO team was well guided by a palliative care specialist. There is a wide gap of trained manpower in this filled in rural areas of India. Dedicated groups from rural area itself need encouragement, repeated home visit, awareness built up, proper training to home care giver, so that difficult symptoms can be managed locally along with necessary social and psychological support to these patients.

1221P - Sites of metastasis and association with clinical outcome (CO) in advanced stage cancer patients (pts) treated with immunotherapy (IO)

1221P - Sites of metastasis and association with clinical outcome (CO) in advanced stage cancer patients (pts) treated with immunotherapy (IO)

133P - Sarcopenia and inflammation predicts survival in advanced stage cancer patients (pts) treated with immunotherapy (IO)

133P - Sarcopenia and inflammation predicts survival in advanced stage cancer patients (pts) treated with immunotherapy (IO)

The Role of “Liquid Biopsy” Repositories in Cancer Care in Low to Middle–Income Countries

Background and context: Translation of underlying individual genomic heterogeneity in cancer into precision medicine practice requires annotated cancer biorepositories. The potential for practice of precise medicine is also coupled to saving vital resources in low to middle–income countries. An overview of experience and outcomes from a tertiary level cancer center in a high-income country for liquid biobank established since 2009 is presented. Aim: To understand the challenges of building economically viable biorepositories that can be used for molecular diagnostics while delivering cancer care. Strategy/Tactics: An institutional ethics–approved prospective liquid biorepository was established in September of 2009 for advanced cancer patients. Informed consent–approved collection of 29.5 mL blood/urine was performed serially on enrolled patients and clinical annotation was obtained during follow-up including previous, current and future treatments and their outcomes. All specimens were processed using a uniform protocol in which extraction of germline DNA from buffy coats; serum for proteomics; platelet-poor and platelet-rich plasma (in citrate and EDTA anticoagulants) for microRNA and cell-free DNA extractions; and extraction of PAXgene RNA/DNA from whole blood was performed. Processing was done within 45 minutes of sample acquisition and storage in −80°C freezers with no freeze–thaw cycles. Program/Policy process: Biobanking for cancer care. Outcomes: Between September of 2009 and January of 2015, 535 advanced-stage prostate cancer patients in hormone-sensitive and castrate-resistant stage; 250 advanced kidney cancer patients; 110 testicular cancer patients were enrolled and 1550 collections were performed serially. This generated &gt;60,000 plasma/serum/DNA/RNA aliquots. Nucleic acids (DNA/RNA) from buffy coats and whole blood of 500-1000 ng volume each were also extracted. Cell-free DNA for somatic mutational and copy number analysis; single nucleotide profiling from germline DNA; RNA expression profiling from whole blood and microRNA analysis in plasma has been performed from this cohort along with proteomics using tandem mass spectrometry. By 2017, this has resulted in &gt;35 scientific publications; 5 patents; multiple national and international grant awards and enhanced precision cancer care for patient care. The cost burden for establishing the infrastructure was highly economical. What was learned: In our experience, liquid biopsy repositories can augment clinical cancer globally, but do not find this discussed in low to middle–income nations. Advancing and applying molecular oncology and team science to prospectively collected and retrospectively annotated biobanks can be a cost-efficient resource in a global cancer healthcare delivery system and a useful tool for scientific and economic opportunities and collaborations.

Cell blocks in cytopathology: An update.

The cell block (CB) offers many advantages over other cytological preparations, particularly for immunocytochemical and molecular testing. However, inconsistent cellularity remains the most common reason for dissatisfaction among cytopathologists. In recent years, there has been a surge in the demand for CBs imposed by the increasing number of minimally invasive procedures performed to obtain material for diagnostic, prognostic and predictive purposes from advanced stage cancer patients. However, routine preparation of CBs significantly increases laboratory work load, operating cost and sample turn-around time. The objectives of our review were to: (a) identify scenarios where a CB is likely to improve diagnostic yield; (b) optimise CB preparatory methods; and (c) understand the factors influencing the success and validity of ancillary testing on various types of CBs. We performed an extensive literature search on CBs in cytology on internet search engines using the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. New CB methods, improvisations of previous CB methods, their utility for diagnosis, immunocytochemistry and molecular testing, and role in predictive biomarker testing are discussed in this review. CBs of good quality and cellularity outperform other cytology preparations in their reliability and versatility for ancillary testing. With many CB methods described in the literature, each with specific advantages and limitations, laboratories may choose to use one or more of the methods depending upon their infrastructure, expertise and workload.

A tree ensemble-based two-stage model for advanced-stage colorectal cancer survival prediction

Classification techniques have widely been applied to cancer survival prediction for predicting survival or death of patients. However, little attention has been paid to patients who are predicted to die. In this work, we consider survival prediction as a two-stage task, where the first stage is to predict whether the outcome is survival or not, and the second stage is to predict the remaining lifespan for patients whose predicted outcome is death. To this end, we propose a two-stage machine learning model to enhance cancer survival prediction. At the first stage, a tree-based imbalanced ensemble classification method is proposed for classification of the survivability of advanced-stage cancer patients. At the second stage, a selective ensemble regression method is proposed for survival time prediction, where a priori knowledge is adopted for feature selection and the mean proportion of error interval is proposed for selecting base learners. Extensive computational studies performed on colorectal cancer data from SEER database demonstrate that the proposed two-stage model can achieve a more accurate prediction compared to the one-stage regression model. The results show that the proposed classification approach can effectively handle the imbalanced survivability data, and the proposed regression method outperforms several state-of-the-art regression models.

Effects of whole-body electromyostimulation combined with individualized nutritional support on body composition in patients with advanced cancer: a controlled pilot trial

BackgroundPhysical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment.MethodsIn a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests.ResultsTwenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks.ConclusionsSupervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment.Trial registrationClinicalTrials.gov NCT02293239 (Date: November 18, 2014).

Metastatic Colorectal Cancer to the Peritoneum: Current Treatment Options.

Peritoneal metastases (PM) are common in advanced-stage colorectal cancer (CRC) patients representing the second most common metastatic site of CRC. In the past, this clinical situation was treated with palliative intent. The introduction of new chemotherapeutic and targeted biologic agents has improved the prognosis of patients with metastatic colorectal cancer. However, the inclusion of treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as inherent components of a multidisciplinary treatment was evolving for the management of these patients. Notably, the surgical approach of CRS/HIPEC has been effective offering a prolonged survival with curative intent in patients with colorectal PM. This article reviews and highlights the recent evidence of CRS and HIPEC as well as current research going on in this form of locoregional treatment in the setting of peritoneal metastases of colorectal cancer.

Prospective administration of anti–nerve growth factor treatment effectively suppresses functional connectivity alterations after cancer-induced bone pain in mice

Cancer-induced bone pain is abundant among advanced-stage cancer patients and arises from a primary tumor in the bone or skeletal metastasis of common cancer types such as breast, lung, or prostate cancer. Recently, antibodies targeting nerve growth factor (NGF) have been shown to effectively relieve neuropathic and inflammatory pain states in mice and in humans. Although efficacy has been shown in mice on a behavioral level, effectiveness in preventing pain-induced functional rearrangements in the central nervous system has not been shown. Therefore, we assessed longitudinal whole-brain functional connectivity using resting-state functional magnetic resonance imaging in a mouse model of cancer-induced bone pain. We found functional connectivity between major hubs of ascending and descending pain pathways such as the periaqueductal gray, amygdala, thalamus, and cortical somatosensory regions to be affected by a developing cancer pain state. These changes could be successfully prevented through prospective administration of a monoclonal anti-NGF antibody (mAb911). This indicates efficacy of anti-NGF treatment to prevent pain-induced adaptations in brain functional networks after persistent nociceptive input from cancer-induced bone pain. In addition, it highlights the suitability of resting-state functional magnetic resonance imaging readouts as an indicator of treatment response on the basis of longitudinal functional network changes.

Consensus document of the Italian Association of Medical Oncology and the Italian Society of Palliative Care on early palliative care.

A consensus document on early palliative care was produced by a committed Working Group of the Italian Society of Medical Oncology and the Italian Society of Palliative Care to improve the early integration of palliative care in medical oncology and to stimulate and guide the choices of those who daily face the problems of advanced stage cancer patients. The simultaneous administration of antineoplastic treatments and early palliative care was shown to be beneficial in metastatic cancer pathway outcomes. Patients who could benefit from early palliative care are those with an advanced cancer at presentation, a compromised PS for cancer, and/or morbidities, and who are too frail to receive treatment. According to the Bruera practice models, in which the combination of cancer management with early palliative care can be offered, three groups of patients needing simultaneous care were identified and three different models of the delivery of palliative care were proposed. In patients with good prognosis and low need of simultaneous care, the solo practice model and the request for consultations were suggested, while in patients with poor prognosis disease with high need of simultaneous care and in conditions with high need of simultaneous care, regardless of cancer prognosis, the integrated care approach should be offered. Palliative care consultation services are seldom accessible in the majority of Italian hospitals; thus the application of various practice models depends on available resources, and a shared care model with the structures of palliative care operating in the area is often required.

Bevacizumab with dose-dense paclitaxel/carboplatin as first-line chemotherapy for advanced ovarian cancer

Phase III trials have shown improved survival in ovarian cancer patients when the anti-vascular endothelial growth factor (VEGF) therapy bevacizumab is added to first-line chemotherapy. However, further evidence is needed regarding bevacizumab when used with dose-dense paclitaxel/carboplatin chemotherapy in advanced ovarian cancer patients. This single-arm trial enrolled 184 advanced-stage (III–IV) epithelial ovarian cancer patients following primary debulking. Enrollees were treated with dose-dense paclitaxel/carboplatin chemotherapy with bevacizumab administered on the first day of cycles 2 through 6. Thereafter, maintenance bevacizumab was continued for 12 months in patients exhibiting persistent disease. The primary endpoint was the tumor response rate. The secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse effects. VEGF-associated serum markers and VEGFA/B lymphoma Mo-MLV insertion region 1 homolog (BMI1) pathway proteins in tumor-derived ovarian epithelial cancer cells were analyzed. Of the enrollees with residual disease that completed at least four cycles, 56.6% had a complete response and 3.7% had a partial response. OS and PFS were significantly different between optimally debulked and suboptimally debulked patients (P < 0.05). The most common grade 3/4 adverse event was neutropenia. Patients with progressive disease showed greater basal serum VEGFA and ovarian VEGFA/BMI1 pathway protein expression relative to patients with stable disease and responsive disease (P < 0.05). In conclusion, bevacizumab plus dose-dense paclitaxel/carboplatin shows efficacy and tolerability in advanced ovarian cancer patients, especially in those having received optimal resection. Our evidence also suggests a prognostic relationship between serum VEGFA levels and a worse prognosis in ovarian cancer patients with measurable disease.

Early change in blood-based biomarkers and association with clinical outcome (CO) in advanced stage cancer patients (pts) treated with immunotherapy (IO).

e15022Background: Ideal biomarkers for cancer pts receiving IO are currently lacking. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR...

Randomized trial comparing a web-mediated follow-up via patient-reported outcomes (PRO) vs. routine surveillance in lung cancer patients: Final results.

6500 Background: In a previous interim analysis, we found a 7-month median overall survival (OS) benefit (p = 0.002) associated with web-based monitoring to detect recurrence in lung cancer patients after initial treatment, vs. scheduled imaging. We hypothesized that benefit was due to earlier detection of symptoms and relapses, prompting earlier treatment and supportive care. Final results with 2-year follow-up is presented. Methods: Advanced-stage lung cancer patients without evidence of disease progression after initial treatment were randomly assigned to compare a web-mediated follow-up (experimental arm) based on weekly self-scoring of 13 common patient symptoms with a routine follow-up (control arm) with 3-6 months repeated CT-scans. In the experimental arm, an alert email was sent to the oncologist when self-scored symptoms matched predefined criteria. The IRB protocol-specified primary outcome was OS. After a pre-planned interim analysis in which OS improvement was observed, the IDMC suggested a cessation of further recruitment in 1-2016 and recommended to offer eligible patients in the control arm to cross over to the intervention. Results: From 6-2014 to 1-2016, 121 patients were included in the intent-to-test survival (ITT) analysis. Ten out of 34 living patients in the control arm were eligible to cross over following the interim analysis. With 2 years of follow-up and 70 deaths observed, the median OS was 23.0 months in the experimental arm and 14.8 months without adjustment for crossover in the control arm (HR 0.62, 95% CI 0.39 to 0.995, p= 0.048). Censoring crossover resulted in a hazard ratio of 0.53 (95% CI 0.33 to 0.85, p = 0.009) with consistent results also observed based on a rank-preserving structural failure time model (psi = -0.55, 95% CI -1.09 to -0.03). Conclusions: With a longer follow-up and although eligible patients from the control arm crossed over to receive intervention after the preplanned interim analysis, the OS remained significantly larger with the web-mediated follow-up based on PRO than with routine disease follow-up by CT scans alone. This is the first study to show the benefits of PROs during surveillance in cancer patients. Clinical trial information: NCT02361099.

Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells.

Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor-1 PAI-1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI-1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells. We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa-activity and thrombin generation as indicators for the procoagulant activity of EV. Double-tagged proteinase-activated receptor 1(PAR-1) expressed in CHO cells to assess its activation by EV. The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI-1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR-1, which was evident by the truncation of tagged-PAR-1. The active oncogene EGFRvIII increases the concentration of TF and PAI-1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR-1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Decreased expression of microRNA-26b in locally advanced and inflammatory breast cancer

Advanced-stage breast cancer patients comprise a smaller proportion of breast cancer patients than do early stage patients and are more likely to experience a poor outcome. Understanding the underlying molecular mechanisms and identifying new biomarkers for treatment in this subgroup of patients is paramount. With the aim of identifying microRNAs that are regulated in advanced-stage breast cancer, we found lower expression of miR-26b, a member of the miR-26 family, in inflammatory breast cancer and noninflammatory locally advanced breast cancer tissue than in normal breast tissue, by quantitative real-time polymerase chain reaction and in situ hybridization. Quantitative real-time polymerase chain reaction (but not in situ hybridization) also revealed lower miR-26b expression in inflammatory breast cancer than in noninflammatory locally advanced breast cancer. Furthermore, lower expression of miR-26b was correlated with shorter distant metastasis-free survival and overall survival in univariate analysis, and with shorter overall survival in multivariate analysis. The expression of miRNA-26b was inversely associated with EZH2 protein expression in several breast cancer cell lines, and overexpression and knockdown of miR-26b caused corresponding changes in EZH2 expression. Our study shows that miR-26b may regulate EZH2 expression in breast cancer and may be useful as a therapeutic target for inflammatory breast cancer and noninflammatory locally advanced breast cancer.

Case Study in International Cooperation: Cuba's Molecular Immunology Center and Roswell Park Cancer Institute

In 1961, the USA severed diplomatic relations with Cuba, and in 1962 an embargo was imposed on trade and financial relations with that country. It was not until five decades later that the USA and Cuba would reestablish relations. This opened the way for the New York State Trade Mission to Cuba in April 2015, during which Cuba's Molecular Immunology Center and Buffalo, New York's Roswell Park Cancer Institute signed a formal agreement that would set in motion biotechnology research collaboration to address one of the most important causes of death in both countries. Significant research from Cuba led to this groundbreaking collaboration. The purpose of this paper is to discuss the development of this cooperation, from the Molecular Immunology Center's initial investigations, through the opening of a phase I clinical trial at Roswell Park Cancer Institute with therapies developed at the Center. This cooperation was responsible for the first clinical trial for CIMAvax-EGF involving advanced-stage non-small cell lung cancer patients in the USA. A license was also approved by the US Department of the Treasury's Office of Foreign Assets Control authorizing a commercial partnership for development of biotechnology products, combining the cancer research efforts of both institutions. This unusual collaboration between Cuba and the USA-the US economic embargo and travel restrictions not withstanding-opens good prospects for expanded medical research between the two countries. While political and logistical challenges remain, the shared mission and dedication of these Cuban and US scientists points the way towards relationships that can lead to development, testing, approval and use of promising new therapies for cancer patients. KEYWORDS Biotechnology, clinical trials, cancer vaccines, cancer immunotherapy, non-small cell lung cancer, NSCLC, Cuba, USA.