Impact of biologic therapies on risk of adverse cardiovascular events in patients with Ankylosing Spondylitis or Psoriatic Arthritis: A systematic literature review.

BACKGROUND: Recent evidence highlights increased mortality and morbidity due to cardiovascular disease (CVD), especially within the two major forms of Spondyloarthropathies (SpAs), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Healthcare professionals and patients in these populations should be alerted regarding the high risk of cardiovascular (CV) events and thus, customize the treatment strategy accordingly. OBJECTIVE: This systematic literature review aimed to determine the effects of biological therapies on serious CV events in AS and PsA. METHODS: Screening for the study was carried out using PubMed and Scopus databases from the database's inception to the 17th of July 2021. The literature search strategy for this review is based on the Population, Intervention, Comparator, Outcomes (PICOs) framework. Randomized controlled trials (RCTs) of biologic therapies for the treatment of AS and/or PsA were included. The primary outcome measure was the number of serious CV events reported during the placebo-controlled phase. RESULTS: 4,422 articles were generated from keywords, eligibility criteria, and databases. Following the screening, we retained 13 studies for analysis: 3 in AS and 10 in PsA. Meta-analysis of results was not feasible due to the small number of the identified studies, the heterogeneity of the biologic treatment and the included populations, as well as the infrequently reported requested endpoint. According to our review, biologic treatments are safe options as for CV risk in patients with PsA or AS. CONCLUSION: Further and more extensive trials in AS/PsA patients at high risk of CV events are needed before firm conclusions can be drawn.

Serum and Pleural Soluble Cell Adhesion Molecules in Mesothelioma Patients: A Retrospective Cohort Study.

Mesothelioma, a malignant neoplasm of mesothelial cells, has overall poor prognosis. Cell adhesion molecules (CAMs) are proteins that contribute to the immune response. In this study the clinical utility and prognostic significance of serum and pleural fluid soluble CAM (sCAM) levels were assessed in patients with mesothelioma. Mesothelioma patients were retrospectively recruited (2016-2020). Clinical characteristics, serum and pleural sCAM levels (sE-cadherin, sE-selectin, intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1)) and histopathological characteristics were gathered. A total of 51 healthy controls were also recruited for a secondary cross-sectional analysis. 92 mesothelioma patients were analyzed (mean age 64.5 years, 87% males, performance status 0-2). Patients with increased pleural sE-cadherin had higher risk for disease progression (adjusted HR 1.11 (1.02, 1.20), p = 0.013). Serum and pleural sE-selectin were decreased in patients with high-grade mesothelioma. Patients with increased serum or pleural sE-selectin levels had lower risk for death (adjusted HR 0.88 (0.81, 0.96), p = 0.003; 0.90 (0.82, 0.99), p = 0.039, respectively). Serum sE-cadherin, sE-selectin and sICAM-1 levels were significantly increased in mesothelioma patients compared to healthy controls. Further studies are needed to indicate the clinical utility of serum and pleural sCAMs in mesothelioma patients.

Use of oral glutamine in radiation-induced adverse effects in patients with thoracic and upper aerodigestive malignancies: Results of a prospective observational study.

Cancer growth in host tissues features glutamine (gln) depletion over time, decreasing epithelial cells' optimal functioning. In addition, radiotherapy (RT) and/or chemotherapy (CT) cause damage to normal tissues, probably enhanced by this depletion. The present study prospectively examined the effect of gln supplementation on 72 patients with thoracic and upper aerodigestive malignancies (T&UAM) treated with sequential or concurrent RT-CT or RT alone. All patients received prophylactic gln powder 15 g bid for the full duration of treatment. The severity of acute radiation toxicities was graded according to the RT Oncology Group/European Organization for Research and Treatment of Cancer criteria. Primary endpoints were the incidence of grade >2 toxicities, weight loss and requirement for analgesics, and the secondary endpoint was the association of the length of irradiated esophagus from treatment planning with the use of opioids. The incidence of adverse effects was as follows: Grade >2 stomatitis, 25.0%; esophagitis, 60.5%; dysphagia, 54.2%; pain, 25.4%; mycosis, 40.8%. Stomatitis grade >2 was more frequent in patients with head and neck tumors (P<0.001) and in those with prior surgery (P<0.001). Esophagitis (P=0.020) and dysphagia (P=0.008) grade >2 were more frequent in patients with concurrent RT-CT. Regarding analgesics, 9.9% of patients received no pain treatment, 56.3% received simple analgesic therapy and 33.8% opioids. Patients on opioid therapy had a greater mean length of irradiated esophagus (P=0.024) or length >12 cm (P=0.018). In 54.2% of patients, weight loss was observed, particularly with concurrent RT-CT (P=0.007). Thus, the use of oral gln may have an important role in reducing acute radiation toxicities and weight loss, and in lowering the requirement for analgesics in patients with T&UAM. Further randomized trials are required to identify the appropriate gln dose, duration of treatment and precise radiation dosimetric parameters in this group of patients. The present clinical trial was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System (registration no. NCT05054517/22-09-2021).

Modern radiopharmaceuticals for lung cancer imaging with positron emission tomography/computed tomography scan: A systematic review.

INTRODUCTION: In this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed tomography. METHODS: We conducted review of the current literature at PubMed/MEDLINE until February 2020. The search language was English. RESULTS: The most widely used radiopharmaceuticals are the following:Experimental/pre-clinical approaches: (18)F-Misonidazole (18F-MISO) under clinical development, D(18)F-Fluoro-Methyl-Tyrosine (18F-FMT), 18F-FAMT (L-[3-18F] (18)F-Fluorothymidine (18F-FLT)), (18)F-Fluoro-Azomycin-Arabinoside (18F-FAZA), (68)Ga-Neomannosylated-Human-Serum-Albumin (68Ga-MSA) (23), (68)Ga-Tetraazacyclododecane (68Ga-DOTA) (as theranostic agent), (11)C-Methionine (11C-MET), 18F-FPDOPA, ανß3 integrin, 68Ga-RGD2, 64Cu-DOTA-RGD, 18F-Alfatide, Folate Radio tracers, and immuno-positron emission tomography radiopharmaceutical agents.Clinically approved procedures/radiopharmaceuticals agents: (18)F-Fluoro-Deoxy-Glucose (18F-FDG), (18)F-sodium fluoride (18F-NaF) (bone metastases), and (68)Ga-Tetraazacyclododecane (68Ga-DOTA). The quantitative determination and the change in radiopharmaceutical uptake parameters such as standard uptake value, metabolic tumor volume, total lesion glycolysis, FAZA tumor to muscle ratio, standard uptake value tumor to liver ratio, standard uptake value tumor to spleen ratio, standard uptake value maximum ratio, and the degree of hypoxia have prognostic and predictive (concerning the therapeutic outcome) value. They have been associated with the assessment of overall survival and disease free survival. With the positron emission tomography/computed tomography radiopharmaceuticals, the sensitivity and the specificity of the method have increased. CONCLUSION: In terms of lung cancer, positron emission tomography/computed tomography may have clinical application and utility (a) in personalizing treatment, (b) as a biomarker for the estimation of overall survival, disease free survival, and (c) apply a cost-effective patient approach because it reveals focuses of the disease, which are not found with the other imaging methods.

The clinical significance of serum markers of bone turnover in NSCLC patients: surveillance, management and prognostic implications.

The purpose of this study was to investigate various serum markers of bone turnover in non-small cell lung cancer patients (NSCLC) in the presence or absence of bone metastasis. Our retrospective study included 79 newly diagnosed NSCLC patients. Group A included 51 patients with bone metastasis and group B included 28 patients that never developed bone metastasis. The measurement of bone formation markers, bone resorptive markers and osteoclastogenesis markers as well as routine biochemical analysis was determined. Patients with bone metastasis had an increase in receptor activator of nuclear factor kappaB ligand, osteopontin and osteoprotegerin. Patients who later developed bone metastasis had decreased osteocalcin and tartrate-resistant acid phosphatase isoform 5b levels (TRACP-5b). We also found an unusually low TRACP-5b/RANKL ratio for patients who have or later developed metastasis. In patients that never developed bone metastases, cross-linked carboxy-terminal telopeptide of type I collagen was increased. Positive correlations were found between osteopontin and TRACP-5b, and also between bone alkaline phosphatase with osteocalcin and TRACP-5b. In conclusion, serum markers of bone turnover may be able to determine the time-to-tumor progression, metastatic potential and overall survival of the NSCLC patient. In addition, they may contribute to a more accurate follow-up and tailored treatment options.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) detection in cancer patients: a prognostic marker for lung metastases from solid malignancies.

UNLABELLED: The aim of the study was to evaluate the serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in breast, lung and colorectal cancer patients in correlation with clinical variables. PATIENTS AND METHODS: A total of 59 patients with a median age of 64 years and histologically confirmed breast 14, colorectal 15 or lung cancer 30 were evaluated. Five patients with breast cancer, 7 patients with colorectal cancer and 8 patients with lung cancer had lung metastases. Blood was collected upon enrolment, centrifuged and the serum kept at -80 degrees C until assayed for sTREM-1. The estimation of sTREM-1 was performed by a crude enzyme immunoabsorbent assay. RESULTS: High levels of sTREM-1 were observed in 50% of breast cancer, 33.3% of Small Cell Lung carcinoma (SCLC), 26.7% of colorectal cancer and 13.3% of Non Small Cell Lung Carcinoma (NSCLC) patients. sTREM-1 expression showed a correlation to the site of metastases. Higher concentrations were observed in the absence of lung metastases (p=0.019). DISCUSSION: The novel mediator sTREM-1 may be a prognostic marker for the detection of lung metastases in metastatic and locally advanced solid tumors.

Safety and efficacy of zoledronic acid rapid infusion in lung cancer patients with bone metastases: a single institution experience.

Zoledronic acid (Zometa, Novartis, Basel, Switzerland) is a new generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast and prostate cancer patients with bone metastases. The safety and efficacy of intravenous zoledronic acid in lung cancer patients was assessed. In 86 patients with newly diagnosed non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) and bone metastases, 4 mg of zoledronic acid was administered with rapid 15-minute intravenous infusion every 3-4 weeks. A total of 414 infusions were administered over a 24-month period during which a statistically significant decrease in serum calcium levels (p = 0.03) was observed. Serum alkaline phosphatase (ALP) also decreased but not significantly. With regard to clinical efficacy, 55 of our patients stabilized or reduced their need for analgesic treatment. No significant side-effects, including fever, hemodynamic instability and renal dysfunction, were seen. We conclude that the rapid infusion of zoledronic acid is safe and convenient for lung cancer patients even after the 3rd and 6th months follow-up.

A phase II study of sequential docetaxel and gemcitabine followed by docetaxel and carboplatin as first-line therapy for non-small cell lung cancer.

Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for inoperable NSCLC. Twenty-six chemo-naïve patients aged less than 75 years with histologically or cytologically confirmed unresectable stage IIIB, IV or relapsed post-operative metastatic NSCLC were included in the study. Gemcitabine 1,250 mg/m(2) was administered and was followed by docetaxel 65 mg/m(2). Treatment was administered on days 1 and 14 in a 28-day cycle for three consecutive cycles. If patients had no progressive disease after three cycles of chemotherapy, they received another three cycles of docetaxel 65 mg/m(2) followed by carboplatin AUC5 on day 1 in a 21-day cycle. Recombinant human granocyte colony-stimulating factor (rhG-CSF) was given prophylactically. In addition, all patients received standard pre- and post- treatment with oral dexamethasone. Response rates at three cycles were: 19% achieved a partial response (PR), 46% had stable disease (SD) and 23% had progressive disease. At six cycles, 8% of the patients maintained PR, 19% showed SD and 35% had progressive disease. The median time-to-disease progression was 6 months. The median survival time of patients was 10 months while, at the end of the first year, the patients who managed to get through the complete therapy (20 patients) had a survival rate of 38%. This detailed analysis of 20 patients showed that 80% of the patients survived for up to 6 months, 38% up to 12 months and 19% for more than a year. The only risk factor associated with the hazard of death among the factors studied was the performance status of the patients. Patients with PS=0 presented a median survival time of 13 months and those with PS=1, it was only 9 months. Non-haematological and haematological toxic effects were generally mild to moderate and entirely manageable.

The use of radiolabeled somatostatin analog scintigraphy in the staging of small cell lung cancer patients.

OBJECTIVES: The prognosis of patients with small cell lung cancer (SCLC) is dismal with a median survival not exceeding 18 months. For the fact that the tumor stage remains the most significant prognostic factor, efforts have been made to improve its accuracy. We evaluated the role of somatostatin receptor scintigraphy (SRS) in the diagnosis and initial staging of SCLC in comparison with the conventional staging procedure. METHODS: We administered radiolabeled somatostatin analog Indium 111 (111In)-diethylenetriamine pentaacetic acid (also known as Indium In-111 pentetreotide or OctreoScan) in 32 newly diagnosed patients with SCLC, 19 of which of had limited disease and 13 of which had extensive disease. All patients had been previously examined with other imaging modalities, specifically CT and/or MRI. RESULTS: Staging with 111In-OctreoScan successfully located the primary tumor site with a sensitivity of 92%. Although detection of mediastinal lymph node dissemination was also relatively high (83%), the SRS failed to detect most of the metastatic lesions outside the thorax (9 of 36, 25%), while its sensitivity for the detection of malignant lesions in the liver, adrenals, and bones, was 56%, 33% and 17%, respectively. CONCLUSIONS: Although 111In-OctreoScan may be used in addition to current SCLC staging methods, there are insufficient data for maintaining that SRS may replace conventional staging.

Report of two cases of endobronchial metastases secondary to colorectal cancer.

Two cases of endoluminar/endobronchial metastases (EEM) from a secondary extrathoracic tumour are reported. The patients, eight years after the curative treatment of colorectal adenocarcinoma, were examined exhibiting pulmonary symptoms with radiological findings in the chest and endobronchial lesions as an initial presentation. The use of fiberoptic bronchoscopy of endoluminar/endobronchial lesions may help in diagnosing the origin of metastatic spread in the presence or absence of a primary tumour.

Pegylated Liposomal Doxorubicin HCL (Caelyx) in combination with Sandostatin LAR as salvage therapy in patients with small-cell lung cancer.

BACKGROUND: The aim of the present study was to evaluate the efficacy of Pegylated Liposomal Doxorubicin (Caelyx) combined with Sandostatin LAR as salvage treatment of small cell lung cancer (SCLC) in platinum-pretreated patients. PATIENTS AND METHODS: Nine pretreated patients (median age 53.5 years, PS: 0-1) with histologically confirmed SCLC were treated with Caelyx 40 mg/m2 (i.v.) on day 1 and Sandostatin LAR 30 mg (i.m.) on day 1 every 28 days. Four (44%) out of the nine patients had received two prior regimens and five (55%) were refractory to front-line chemotherapy. RESULTS: No complete or partial responses were observed. Disease stabilization was obtained in two (22%) patients. The median overall survival was 18.7 months and the median time to progression was 9.1 months. CONCLUSION: The combination of Caelyx and Sandostatin LAR was inactive as salvage treatment in this poor prognosis group of patients with relapsed SCLC. However, the combination would merit further investigation in patients pretreated with one prior regimen.