Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. AIM: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC. METHODS: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)). RESULTS: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS. CONCLUSION: This study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%. CLINICAL RELEVANCE STATEMENT: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies. TRIAL REGISTRATION: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

Salvage pulmonary resection in stages IIIb-IV lung cancer after treatment with immune checkpoint inhibitors case series and literature review.

BACKGROUND AND OBJECTIVES: The role of salvage thoracic surgery in managing advanced-stage lung cancer following treatment with immune checkpoint inhibitors is currently unclear. We present a series of nine patients with advanced non-small-cell lung cancer who underwent pulmonary resection following treatment with pembrolizumab. METHODS: We performed a single-institution retrospective analysis of pulmonary resection undertaken following treatment with pembrolizumab for advanced-stage lung cancer. Nine patients met the inclusion criteria. RESULTS: In six cases, surgery was indicated for persistent localized disease after treatment, and in three cases for nonresponsive synchronous/metachronous lung nodules while on treatment for stage IV lung cancer. Dense hilar fibrosis was present in all patients. Minimal access surgery was achieved in five cases (video-assisted n = 2, robotic-assisted n = 3). There was no in-hospital mortality. One patient died within 60 days from community-acquired COVID-19 pneumonitis. Seven patients remain free of disease between 5 and 22 months follow-up. CONCLUSIONS: Pulmonary resection is safe and technically feasible following treatment with immune checkpoint inhibitors. Surgical challenges relate to postimmunotherapy fibrosis, but with increased experience and a robotic approach, minimal access surgery is achievable. Further prospective studies are required to assess the surgical impact on disease control and overall survival in this patient cohort.

Tuberculosis associated with Triplet therapy for lung cancer.

We report the first case of TB associated with triplet therapy (chemotherapy and immunotherapy concurrently) for lung cancer, developing just 44 days after treatment initiation. We feel that several important learning points arise from the discussion that are likely to be very relevant to the broad readership of Thorax, and have important clinical and scientific implications. In the three discussion paragraphs, we highlight that: 1) Triplet therapy is now standard first-line treatment for inoperable lung cancer. 2) TB reactivation is increasingly recognised as an adverse effect of immune checkpoint inhibition, but sending diagnostic samples is critical to avoid a missed diagnosis. 3) These insights from novel cancer immunotherapies are challenging the traditional views of the host-pathogen interaction in TB, with wide implications for future control strategies. We propose that the cases reported in the literature are likely to be the tip of the iceberg as most people with lung cancer managed with antiprogrammed death-1 agents who develop new lung lesions will be treated with standard antibiotics and then palliated when they do not respond.

Clinical implementation of pre-treatment DPYD genotyping in capecitabine-treated metastatic breast cancer patients.

PURPOSE: Metastatic breast cancer (mBC) patients with DPYD genetic variants linked to loss of dihydropyrimidine dehydrogenase (DPD) activity are at risk of severe capecitabine-associated toxicities. However, prospective DPYD genotyping has not yet been implemented in routine clinical practice. Following a previous internal review in which two patients underwent lengthy hospitalisations whilst receiving capecitabine, and were subsequently found to be DPD deficient, we initiated routine DPYD genotyping prior to starting capecitabine. This study evaluates the clinical application of routine DPYD screening at a large cancer centre in London. METHODS: We reviewed medical records for consecutive patients with mBC who underwent DPYD genotyping before commencing capecitabine between December 2014 and December 2017. Patients were tested for four DPYD variants associated with reduced DPD activity. RESULTS: Sixty-six patients underwent DPYD testing. Five (8.4%) patients were found to carry DPYD genetic polymorphisms associated with reduced DPD activity; of these, two received dose-reduced capecitabine. Of the 61 patients with DPYD wild-type, 14 (23%) experienced grade 3 toxicities which involved palmar-plantar erythrodysesthesia (65%), and gastrointestinal toxicities (35%); no patient was hospitalised due to toxicity. CONCLUSIONS: Prospective DPYD genotyping can be successfully implemented in routine clinical practice and can reduce the risk of severe fluoropyrimidine toxicities.

BRAF- and MEK-Targeted Small Molecule Inhibitors Exert Enhanced Antimelanoma Effects in Combination With Oncolytic Reovirus Through ER Stress.

Reovirus type 3 (Dearing) (RT3D) infection is selective for cells harboring a mutated/activated RAS pathway. Therefore, in a panel of melanoma cell lines (including RAS mutant, BRAF mutant and RAS/BRAF wild-type), we assessed therapeutic combinations that enhance/suppress ERK1/2 signaling through use of BRAF/MEK inhibitors. In RAS mutant cells, the combination of RT3D with the BRAF inhibitor PLX4720 (paradoxically increasing ERK1/2 signaling in this context) did not enhance reoviral cytotoxicity. Instead, and somewhat surprisingly, RT3D and BRAF inhibition led to enhanced cell kill in BRAF mutated cell lines. Likewise, ERK1/2 inhibition, using the MEK inhibitor PD184352, in combination with RT3D resulted in enhanced cell kill in the entire panel. Interestingly, TCID50 assays showed that BRAF and MEK inhibitors did not affect viral replication. Instead, enhanced efficacy was mediated through ER stress-induced apoptosis, induced by the combination of ERK1/2 inhibition and reovirus infection. In vivo, combined treatments of RT3D and PLX4720 showed significantly increased activity in BRAF mutant tumors in both immune-deficient and immune-competent models. These data provide a strong rationale for clinical translation of strategies in which RT3D is combined with BRAF inhibitors (in BRAF mutant melanoma) and/or MEK inhibitors (in BRAF and RAS mutant melanoma).

Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma.

Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells. An orthotopic model of advanced extremity sarcoma was used to evaluate survival of animals after ILP with combinations of TNF-α, melphalan and GLV-1h68. We investigated the efficiency of viral tumour delivery by ILP compared to intravenous therapy, the locoregional and systemic biodistribution of virus after ILP, and the effect of mode of administration on antibody response. The combination of melphalan and GLV-1h68 was synergistic in vitro. The addition of virus to standard ILP regimens was well tolerated and demonstrated superior tumour targeting compared to intravenous administration. Triple therapy (melphalan/TNF-α/GLV-1h68) resulted in increased tumour growth delay and enhanced survival compared to other treatment regimens. Live virus was recovered in large amounts from perfused regions, but in smaller amounts from systemic organs. The addition of oncolytic vaccinia virus to existing TNF-α/melphalan-based ILP strategies results in survival advantage in an immunocompetent rat model of advanced extremity sarcoma. Virus administered by ILP has superior tumour targeting compared to intravenous delivery. Further evaluation and clinical translation of this approach is warranted.

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway.

BACKGROUND: Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. METHODS: To test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. RESULTS: Correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. CONCLUSIONS: In summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue.

Facilitating healthcare practitioners to deliver self-management support in adult cancer survivors: A realist review.

BACKGROUND: Supporting cancer survivors in self-management can empower them to take an active role in managing the long-term physical and psychosocial consequences of cancer treatment. Healthcare practitioners are key to supporting patients to self-manage, however, they do not routinely engage in these discussions. This review aimed to establish what works for whom and in what circumstances in relation to facilitating healthcare practitioners to provide self-management support in people living with long-term consequences of cancer treatment. METHODS: The review follows five steps: define the review's scope, develop initial programme theories, evidence search, selection and appraisal, and data extraction and synthesis. Database searches of Medline, EMBASE, CINAHL, Scopus, PsycINFO, ERIC and AMED databases, to September 2019 were supplemented with practitioner surveys. Insights into the mechanisms that operate in particular contexts to produce successful outcomes were illustrated using realist programme theories, developed using the Theoretical Domains Framework. Data selection was based on relevance and rigour. Data were extracted and synthesised iteratively to illuminate causal links between contexts, mechanisms and outcomes. RESULTS: Five programme theories were identified from 20 included articles and seven practitioner surveys: practitioners will engage patients in discussions about self-management if they have appropriate (1) knowledge and (2) consultations skills, (3) a clear understanding of their self-management support role and responsibilities, and if (4) organisational strategies and (5) health system configuration enable integration into routine care. The mechanisms facilitating practitioners to support self-management were practitioner confidence, mutual trust and shared responsibility between practitioners and cancer survivors, organisational prioritisation and ease of delivery of self-management support. CONCLUSION: The findings articulate the necessary components for embedding self-management support into routine cancer care. Operationalisation of these components into effective self-management support interventions will require reconfiguration of pathways and adaptation for local context, using strategies such as quality improvement and co-design to guide intervention development, implementation and evaluation.

Non-Small Cell Lung Cancer (NSCLC) in Young Adults, Age < 50, Is Associated with Late Stage at Presentation and a Very Poor Prognosis in Patients That Do Not Have a Targeted Therapy Option: A Real-World Study

(1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011−2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results: Of 248 NSCLC patients, median age was 46 years, 50% (n = 125) female, 58% (n = 145) white, 18% (n = 45) black and 4% (n = 10) Asian ethnicity. Amongst patients with a documented smoking history, 30% (n = 64) were never-smokers. Most patients had adenocarcinoma (77%, n = 191) and presented with metastatic disease (67%, n = 166). Only 31% (n = 76) had treatment with curative intent. In patients who presented or developed metastatic non-squamous NSCLC (n = 179), EGFR mutation status was known in 88% (n = 157) and mutation present in 19% (n = 34), ALK was known in 66% (n = 118) with a translocation in 10% (n = 18), ROS1 status was known in 57% (n = 102) with a translocation in 4% (n = 8), and KRAS status was known in 66% (n = 119) with a mutation in 12% (n = 22). Overall, 76% (n = 152) patients with metastatic NSCLC received first-line systemic anti-cancer therapy. Median overall survival in metastatic NSCLC was 9.0 months (95% CI 6.5−11.6 months), with superior median overall survival in those with a targeted therapy option (28.7 months) compared to those without (6.6 months; p < 0.001). (4) Conclusion: Young patients contribute a significant proportion of those presenting with lung cancer. They present with advanced stage at diagnosis and have a poor prognosis. Identification of a targeted therapy option is associated with improved survival. However, most patients do not have a known genomic driver, which is in part due to limited testing, particularly in the early years of this study period. These findings highlight the particular importance of rapid-turnaround comprehensive genomic profiling in this age group and the need to identify strategies to facilitate earlier diagnosis in young NSCLC patients.

Realist review protocol for understanding the real-world barriers and enablers to practitioners implementing self-management support to people living with and beyond cancer.

INTRODUCTION: Self-management support can enable and empower people living with and beyond cancer to take an active role in managing long-term consequences of cancer treatment. Healthcare professionals are key to promoting patients to self-manage, however, they do not routinely engage in these discussions. This review aims to understand what works for whom and in what circumstances in relation to practitioners engaging with supporting people living with and beyond cancer to self-manage long-term consequences of systemic anticancer treatment. METHODS AND ANALYSIS: We will follow five steps for undertaking the realist review: (1) define the review scope, (2) develop initial programme theories, (3) evidence search, (4) selection and appraisal and (5) data extraction and synthesis. We will combine an informal literature search with a theory-based approach, using the theoretical domains framework, and stakeholder feedback to develop initial programme theories. We will search Medline, EMBASE, CINAHL, Scopus, PsycINFO, ERIC and AMED databases to September 2019, and supplement this with citation tracking, grey literature and practitioner surveys. Data selection will be based on relevance and rigour. Data will be extracted and synthesised iteratively, and causal links between contexts, mechanism and outcomes illuminated in the process. The results will be reported according to the Realist And Meta-narrative Evidence Syntheses: Evolving Standards quality and publication standards. ETHICS AND DISSEMINATION: We have received ethical approval through the Research Ethics Committee, Faculty of Medicine and Health Sciences, University of East Anglia (ref 2 01 819-124). We will disseminate to the research community through conference presentations and a peer-reviewed journal article. We will work with healthcare organisations, cancer charities and patients to agree a strategy for disseminating to these groups. PROSPERO REGISTRATION NUMBER: CRD42019120910.

Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol.

BACKGROUND: We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more. PATIENTS AND METHODS: Data from 52 patients with HSRs were analyzed according to the Common Toxicity Criteria for Adverse Events (CTCAE), v3.0. Three patients were chosen for the desensitization protocol. After determining the starting point for desensitization, we applied the standard protocol for parenteral desensitization to b-lactam antibiotics. Oxaliplatin treatment was then carried out with serial 10-fold dilutions in sufficient volume to administer the total dose. A total of 52 patients (24.2%) were recorded as having an allergic reaction to oxaliplatin. RESULTS: Hypersensitivity reactions were recorded after a mean of 6.5 (SD +/- 4.5) cycles. Only 4 patients (4 of 215; 1.8%) developed CTCAE grade 3/4 HSRs. Hypersensitivity reactions were seen more likely in patients receiving second-line or more of chemotherapy compared with chemotherapy-naive patients. No other correlations were seen (the presence of atopic disease, positive skin prick test). The 3 patients, having completed the parenteral desensitization protocol, completed their treatment uneventfully as well. CONCLUSION: Hypersensitivity reactions from oxaliplatin respond quickly to the discontinuation of the drug and appropriate support. Premedication and an increased infusion time could allow for readministration. The desensitization protocol we developed can provide a reliable alternative to permanent discontinuation of oxaliplatin.

Erlotinib-induced skin rash in patients with non-small-cell lung cancer: pathogenesis, clinical significance, and management.

The human epidermal growth factor receptor (EGFR) signaling is overexpressed in many solid malignancies, making it an appealing target for biologic agents. A number of agents that target this receptor are in use or in development. A specific adverse effect common to this class of agents is an acneiform-like skin rash that has been related to EGFR inhibition in the skin. Little is known about the etiology of this rash, and there are no clear evidence-based management recommendations. Findings suggest that there is a relationship between the development of rash and response and/or survival, making rash a potential surrogate marker of activity. This review summarizes and updates the current knowledge of the clinical presentation, etiology, and predictive and prognostic value of erlotinib-induced skin rash and establishes a treatment strategy to help treat dermatologic adverse events and allow patients to continue therapy without dose interruption or drug discontinuation.

Therapy-induced toxicity of the lungs: an overview.

UNLABELLED: Pulmonary toxicity induced by novel antineoplastic agents has not been well characterized because of the simultaneous or sequential use of drugs and a multimodality therapeutic approach. To further investigate this topic, relevant studies were identified through Medline. The generic names of novel antineoplastic agents and the key words pulmonary toxicity, dyspnea and pneumonitis were used for the search. References from the articles identified were also reviewed for additional sources. Most novel antineoplastic drugs may induce pulmonary toxicity. The most recognized patterns of lung toxicity consist of unspecified dyspnea and interstitial lung disease (ILD). Exclusion diagnosis of possible underlying diseases is necessary. Genetic predisposition, autoimmune conditions or superimposed disease may also be involved in the development of lung toxicity. CONCLUSION: Clinicians should be aware of potential pulmonary toxicity as a complication in the treatment of cancer and focus on its early detection or prediction.

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.

The significance of leptin, adiponectin, and resistin serum levels in non-small cell lung cancer (NSCLC).

SUMMARY: Adipose tissue secretes adipokines with proinflammatory and anti-inflammatory properties. Our aim was to assess the role of adipose tissue in generalized inflammatory state of advanced NSCLC patients and the possible use of leptin, adiponectin and resistin as diagnostic and prognostic markers. Correlation of adipose tissue with weight loss in advanced NSCLC patients was also studied. Fasting serum levels of leptin, adiponectin and resistin were determined in 101 advanced NSCLC patients (76 without weight loss and 25 with weight loss) and 51 healthy volunteers using commercially available ELISA. Adipokine serum levels were determined at diagnosis, at the end of first-line chemotherapy and at the time of disease progression for those who responded to treatment. Epidemiological, anthropometrical and laboratory data were assessed. Serum leptin and adiponectin levels presented no differences. Serum resistin levels were significantly increased in NSCLC patients after adjustment for age, sex and BMI. Multivariate analysis showed that these adipokines at diagnosis could not be used as predictive factors for overall survival or time to progression. Only serum resistin levels were associated with weight loss. Despite no direct involvement of leptin and adiponectin, resistin as a proinflammatory cytokine may play a role in the pathogenesis of weight loss in NSCLC patients.

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.

Serological diagnosis of Chlamydophila pneumoniae infection in Greek COPD patients by microimmunofluorescence and ELISA.

BACKGROUND: The possible role of Chlamydophila pneumoniae infection in episodes of acute exacerbation of COPD (AECOPD) was described in 4-34% of COPD patients, but never in Greece. The possible association of chronic C. pneumoniae infection with disease severity is under study, with a diversity of results reported. MATERIAL/METHODS: Seventy-five Greek patients with AECOPD were tested for serum C. pneumoniae antibodies using the microimmunofluorescence (MIF) test and ELISA during the first day of their hospitalization and 30 days after enrollment. Serological diagnosis of acute and past C. pneumoniae infection was determined and the sensitivities, specificities, and predictive values of both methods were evaluated. Chronic C. pneumoniae infection was also estimated in both the patient group and a control group. RESULTS: Seven patients (9.3%) had serological evidence of acute C. pneumoniae infection. Although ELISA and MIF produced equal results for the diagnosis of acute C. pneumoniae infection, the sensitivity and negative predictive value of ELISA for the diagnosis of past C. pneumoniae infection was low when MIF was used as the gold-standard method. Chronic C. pneumoniae infection was more common in COPD patients than in the control group and was even more common in patients with FEV(1)<50%. CONCLUSIONS: Acute C. pneumoniae infection is associated with AECOPD in Greece. ELISA may currently be a valuable diagnostic tool for the diagnosis of acute C. pneumoniae infection, but not for the diagnosis of past infection. The possible role of chronic C. pneumoniae infection in COPD progression needs further investigation.

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.

Rapid infusion of ibandronate in lung cancer patients with bone metastases.

BACKGROUND: The high prevalence of bone metastases in stage IV non-small cell lung cancer (NSCLC) patients contributes substantially to the burden of the disease by resulting in significant skeletal morbidity. Ibandronate is a new generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast and prostate cancer patients with bone metastases. PATIENTS AND METHODS: In 32 patients with newly diagnosed NSCLC and bone metastases, 4 mg of ibandronate were administered, as a rapid 20-minute intravenous infusion every 3-4 weeks. RESULTS: A total of 189 infusions were administered over a 24-month period, during which a statistically significant decrease in calcium serum levels (p=0.03) was observed. The serum levels of alkaline phosphatase (ALP) were also decreased, but not significantly. With regard to clinical efficacy, 24 of our patients stabilized or reduced their need for analgesic treatment. The reduced time of infusion (20 min vs. 2 h) did not correlate with any side-effects, including vital sign deterioration and renal dysfunction. CONCLUSION: The rapid infusion of ibandronate in lung cancer patients with bone metastases is a safe and convenient procedure that may be administered in a day-clinic setting.

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.