International meeting on cancer vaccines: how can we enhance efficacy of therapeutic vaccines?

The major aims of the International Meeting on Cancer Vaccines were to review the state-of-the-art research on cancer vaccines, to compare different experimental approaches of therapeutic vaccination and to discuss critical issues and perspectives. The results from recent clinical trials in patients treated with different types of cancer vaccines were presented. Reasons for the limited response and possible modalities for enhancing efficacy of therapeutic vaccines were subjects of major discussion. A consensus was achieved on the need of combining cancer vaccines with other anticancer treatments. Of note, evidence stemming from studies in animal models pointed out new rationales for a selective combination of cancer vaccines with chemotherapy. In addition, some main presentations focused on new adjuvants (CpG oligonucleotides) and on the role of cytokines (i.e., type I IFN, interleukin 12, and interleukin 15) in promoting an antitumor immune response to vaccines. A considerable attention was given to regulatory T cells and to strategies for suppressing their function, thus enhancing vaccine efficacy. An entire session was devoted to the use of dendritic cells for the development of cancer vaccines. The results of clinical studies and the advantages of using new modalities for preparing dendritic cell-based vaccines were discussed.     

Is England closing the international gap in cancer survival?

Background:

We provide an up-to-date international comparison of cancer survival, assessing whether England is ‘closing the gap'' compared with other high-income countries.

Methods:

Net survival was estimated using national, population-based, cancer registrations for 1.9 million patients diagnosed with a cancer of the stomach, colon, rectum, lung, breast (women) or ovary in England during 1995–2012. Trends during 1995–2009 were compared with estimates for Australia, Canada, Denmark, Norway and Sweden. Clinicians were interviewed to help interpret trends.

Results:

Survival from all cancers remained lower in England than in Australia, Canada, Norway and Sweden by 2005–2009. For some cancers, survival improved more in England than in other countries between 1995–1999 and 2005–2009; for example, 1-year survival from stomach, rectal, lung, breast and ovarian cancers improved more than in Australia and Canada. There has been acceleration in lung cancer survival improvement in England recently, with average annual improvement in 1-year survival rising to 2% during 2010–2012. Survival improved more in Denmark than in England for rectal and lung cancers between 1995–1999 and 2005–2009.

Conclusions:

Survival has increased in England since the mid-1990s in the context of strategic reform in cancer control, however, survival remains lower than in comparable developed countries and continued investment is needed to close the international survival gap.     

Connecting mitotic instability and chromosome aberrations in cancer--can telomeres bridge the gap?

Gross mitotic disturbances are often found in malignant tumours, but not until recently have the molecular causes and the genomic consequences of these abnormalities started to become known. One potential source of mitotic instability is chromosomes with dysfunctional telomeres, giving rise to a high rate of chromatin bridges at anaphase. These bridges could lead either to structural chromosome rearrangements through chromatin fragmentation or to whole-chromosome losses through kinetochore-spindle detachment. Statistical meta-analyses have recently revealed that tumours with high rates of anaphase bridging, such as ovarian, head and neck, and pancreatic carcinomas, are characterised by multimodal distributions of genomic imbalances, consistent with a dramatically increased rate of chromosome rearrangements. In contrast, tumours without gross cell division disturbances are characterised by a monotonously decreasing distribution of genomic changes. This distribution follows a power-law, best described by a preferential attachment model in which the tolerance for chromosomal changes increases steadily with tumour growth. Even though many common cancers, such as breast, colorectal, and renal cell carcinomas adhere to this simple power-law dynamics, the underlying molecular mechanisms remain elusive.     

How will lung cancer be treated in the future?

Lung cancer is still considered the leading cause of cancer-related deaths in industrialized countries. Despite improvements in cancer diagnosis and therapy, the present 5-year survival rate of 14% is only slightly higher than the survival rate of 8% in the early 1960s. At present, a survival plateau has been reached by the current management of lung cancer, including surgery, chemo- and radiotherapy. Although prevention and early diagnosis are undoubtedly important, more innovative treatment approaches and new agents that affect alternate mechanisms in tumor cells are needed. Since molecular targets of tumorigenesis and metastasis are currently the focus of lung cancer research, this review will summarize the most important molecular approaches and clinical trials of novel therapeutics.     

FDG-PET in staging lung cancer: how does it change the algorithm?

BACKGROUND: In patients with lung cancer, positron emission tomography (PET) using fluor-18-fluorodesoxyglucose (FDG) may be used both to detect extrathoracic metastases (ETM) and for mediastinal lymph node staging (MLS), potentially reducing the need for mediastinoscopy. We assessed the added value of FDG-PET in detecting ETM and focused on the reliability of FDG-PET and mediastinoscopy for MLS. PATIENTS AND METHODS: In 72 consecutive patients with non-small cell lung cancer, the impact of adding FDG-PET to full conventional clinical staging was prospectively analyzed. The predictive value of FDG-PET findings and tumor location for pathologic mediastinal lymph node status were assessed in a logistic regression analysis. RESULTS: Unexpected extrathoracic metastases were detected by FDG-PET in 15% of patients. In MLS overall negative and positive predictive values were 71 and 83% for FDG-PET, and 92 and 100% for mediastinoscopy. However, the negative predictive value of FDG-PET was only 17% in case of FDG-PET positive N1 nodes and/or a centrally located primary tumor, whereas it was 96% in case of FDG-PET negative N1 nodes and a non-centrally located primary tumor. CONCLUSION: By incorporating FDG-PET in clinical staging, 15% of patients with lung cancer are upstaged due to unexpected extrathoracic metastases. In case of a negative mediastinal FDG-PET, mediastinoscopy can only be omitted in the presence of a non-centrally located primary tumor and without FDG-PET positive N1 nodes.     

Thromboembolism in lung cancer – An area of urgent unmet need

Introduction

Thromboembolism is common in lung cancer. Current thromboprophylaxis guidelines lack specific recommendations for appropriate strategies in this high thrombotic risk patient cohort. We profiled lung cancer patients receiving anti-cancer therapy. Thromboembolism incidence and thromboembolism-related mortality rates are reported and we explored patient, disease, and treatment-related risk factors associated with higher thrombotic rates.

Methods

Retrospective review of lung cancer patients referred to a Comprehensive Cancer Centre between 01/07/2011 and 30/06/2012 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records.

Results

After a median follow up of 10 months (range: 0.03–32 months), 24/222 patients (10.8%) had developed radiologically confirmed thromboembolism; 131 events per 1000 person-years (95%CI 87–195). Thromboembolism occurred equally in patients with non-small cell and small cell lung cancer (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell carcinoma (14.7% and 5.3% respectively). Chemotherapy-treated patients experienced thromboembolism more often than patients who did not receive chemotherapy (HR 5.7 95%CI 2.2–14.8). Radiotherapy was also associated with more frequent thromboembolism (HR 5.2 95%CI 2.0–13.2). New lung cancer diagnosis, presence of metastatic disease, second primary malignancy and Charlson Index ≥5 were also associated with higher rates of thromboembolism. Importantly, pharmacological thromboprophylaxis (P-TP) was not routinely or systematically prescribed for ambulant lung cancer patients during any treatment phase, at this institution. The majority (83%) of thromboembolic events occurred in the ambulatory care setting.

Conclusion

Morbidity and mortality from thromboembolism occurs frequently in lung cancer. Thromboprophylaxis guidelines should be developed for the ambulatory care setting.     

Has lung cancer in the elderly different characteristics at presentation?

Lung cancer is the first cause of cancer death for males aged > or =35 years, and the second for females aged between 35 and 70 years. Elderly patients seem to have the worst performance status (PS) and earlier stage of disease at diagnosis. We analyzed data concerning 1,035 patients with lung cancer referred to the National Cancer Institute of Naples. The variables considered in the analysis were: gender; type of cancer [small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC)]; ECOG (Eastern Cooperative Oncology Group) PS, the stage of disease at diagnosis, the histological type, age at diagnosis. In order to better assess the relevance of age at diagnosis in lung cancer patients we categorized the age into two groups (young < or =70; old >70 years). The statistical analyses were performed using chi2 trend test with corresponding p-value and odds ratios (OR) for the examined variables, with a corresponding 95% confidence interval. These were derived using multiple logistic regression, fitted by the maximum likelihood method. For all the 1035 patients the risk between the age at diagnosis and the performance status was not statistically significant (OR=1.1, 95%CI 0.8-1.5). We repeated the same risk distinguishing the histological type and we analyzed the performance status for the SCLC (OR=1.0, 95%CI 0.4-2.5) and the stage at diagnosis (OR=1.0, 95%CI 0.4-3.0), without any significant difference. Our study showed that elderly patients with lung cancer do not seem to have different characteristics at presentation, particularly related to stage of disease, PS and histology, as compared to their younger counterpart. Other characteristics such as type and number of co-morbidities and organ function differ in the two groups of populations.