Telomeres: a Nobel Prize at the beginning… of the end

The 2009 Nobel Prize for Physiology and Medicine was awarded to Elizabeth H. Blackburn, Carol W. Greider and Jack K. Szostak for their work on telomeres and telomerase. This prize acknowledges their pionneering discoveries on chromosomal extremities. Telomeres are the nucleoproteic complexes that may be found at the ends of linear chromosomes. They are essential for genomic stability and are involved in aging and tumorogenesis.     

The beginning of the end of the lung cancer epidemic in Dutch women?

In some European countries, female lung cancer mortality and incidence have started to decrease or flatten out, whereas they are still rising in The Netherlands. We present recent mortality and incidence trends of lung cancer and smoking trends in The Netherlands to show the end of the lung cancer epidemic in Dutch women. Lung cancer mortality and incidence rates by gender were analyzed for 4 age groups (20-44, 45-49, 50-54 and 55-59), and smoking prevalence rates were examined for women using joinpoint regression and birth cohort analysis. Data on mortality were collected for the period 1960-2006, incidence for the period 1989-2003 and smoking prevalence for the period 1988-2007. Because of decreasing lung cancer mortality and incidence rates among males and dramatically increasing rates among females, rates of young males were surpassed by those of females after the mid-1990s. However, although in young women (20-49) mortality increased with 4-5% per year, it flattened out (no significant in- or decreases) since 1999. Among older women, mortality rates were still increasing markedly. Mortality rates and smoking prevalence tended to decrease in women born after the 1950s. This is the first report suggesting that the lung cancer epidemic in Dutch women is coming to an end. Although the increase in lung cancer incidence and mortality among Dutch women has been one of the most dramatic in Europe, the recent decrease in young women is expected to be followed by a future leveling off or a slight decrease in overall female lung cancer rates.     

Topoisomerase II alpha as a marker predicting the efficacy of anthracyclines in breast cancer: are we at the end of the beginning?

This article attempts to provide the reader with a complete overview of topoisomerase (topo) II alpha as a marker for predicting the efficacy of anthracyclines in patients with breast cancer. In the first section of this article, in vitro data supporting the predictive value of topo II alpha are reviewed. Interestingly, these data suggest that the interaction between HER2 and anthracycline efficacy, which has been hypothesized in several clinical studies performed in the past decade, might depend on the concomitant topo II alpha status. Molecular pathology studies further reinforce the concept that HER2 might not be directly involved in the prediction of response to anthracyclines. They report that topo II alpha gene amplification can be found in 25%-40% of HER2/neu-amplified tumors, while no topo II gene amplification is detected in the absence of HER2/neu gene amplification. In the second part of this article, a series of clinical studies are reviewed and interpreted. These studies have attempted to correlate topo II alpha status with anthracycline efficacy in the adjuvant, neoadjuvant, and metastatic settings. All of the studies evaluating the topo II alpha gene suggest that gene amplification might be associated with an increased efficacy of anthracyclines, and some of the studies evaluating topo II alpha protein find that protein overexpression might correlate with an increased sensitivity to these compounds. Despite these findings, however, the reported studies do not provide the proof of principle needed to authorize the use of topo II alpha as a predictive marker for standard practice. A new generation of research is currently testing the predictive value of topo II alpha. It is hoped that these projects, which are described in the last section of the article, will clarify the role of topo IIa in the prediction of response to anthracyclines.     

Gene therapy: the end of the rainbow?

Background

Papillary carcinoma is the most common differentiated malignant thyroid neoplasm. The biological course of this cancer is typically indolent with a protracted clinical course. Metastases commonly occur in regional lymph nodes, and distant metastasis is a late and rare occurrence. We report a patient who presented with cerebellar metastasis prior to the diagnosis of papillary thyroid carcinoma and review the literature of brain metastasis from papillary thyroid carcinoma.

Results

A 75-year old female presented at the emergency room with progressive dizziness, headache and vomiting, where a brain CT and MRI showed a posterior cerebellar tumor. Surgical resection revealed papillary carcinoma consistent with thyroid origin. Subsequent ultrasound and CT-scan revealed a thyroid nodule, after which the patient underwent total thyroidectomy. Pathologic evaluation was consistent with papillary thyroid carcinoma.

Conclusion

Brain metastasis may rarely be the initial presentation of papillary thyroid carcinoma. Solitary brain metastasis can completely be resected with better prognosis.     

Searching for leukemia stem cells--not yet the end of the road?

Defining the characteristics of leukemia stem cells is critical in order to better understand both the genesis of leukemic disease and strategies by which such cells may be eradicated. In this issue of Cancer Cell, Somervaille and Cleary describe studies in which the properties of malignant stem cells are elucidated in a mouse model of leukemia induced by expression of the MLL-AF9 translocation. Biological features of leukemia stem cells in this system challenge previous thinking in several ways and suggest an unexpected degree of heterogeneity among stem cells in various forms of leukemia.     

Treating high grade gliomas in the elderly: the end of ageism?

Introduction Treating high grade gliomas in the elderly is a challenge for multidisciplinary teams. Most studies on this topic exclude patients aged >65 and a Karnofsky Performance Status (KPS) score of <70, a group most likely to have a poor outcome. We undertook this study to analyze the outcomes in a cohort of patients which included such patients. Methods Ours was a retrospective cohort study. About 71 consecutive patients with high grade gliomas, who were seen in the neurooncology clinic in 2004, were included. The case records of these patients were scrutinized for the demographic, clinical data, follow-up and survival. The cohort was divided into two groups; Age ≥65 and age <65 for analysis. The factors influencing survival were analyzed using the Cox’s proportional hazards model in each group. Results In the age group ≥65 years, patients treated with a radical resection ± adjuvant therapy had a lower risk of death (hazard ratio 0.14, 95%CI 0.04–0.51, P = 0.003) when compared to patients undergoing a biopsy ± adjuvant therapy and palliative treatment. In the group <65 years, the greater the age, greater was the risk of death (hazard ratio 2.05, 95%CI 1.13–3.73, P = 0.01). The median survival was 12 months in the group <65 years and 5 months in age ≥65 years (P = 0.001). In the group ≥65 years, those patients who had radical resection ± adjuvant treatment had a median survival of 7 months as compared to 3 months in the patients who had biopsy ± adjuvant treatment (P = 0.003). KPS, presence of co-morbidities, duration of symptoms, location of the lesion and sex were not found to be significant independent predictors of survival in our study. Conclusions Age is an important predictor of survival in younger patients, however in the elderly treatment matters most. Elderly patients undergoing radical surgery ± adjuvant treatment had a longer median survival as compared to the elderly patients undergoing a biopsy ± adjuvant treatment. KPS was not found to be a significant independent predictor of survival probably because of underrepresentation of patients with poor KPS. Radical treatment should not be denied to elderly patients who are deemed fit as the outcome is significantly better.     

Chemotherapy at the end of life: up until when?

Aim

The aim of this study is to analyze the use of CT in terminal stage cancer and the percentage of patients who received UCPD in 2009 and 2010 on the Medical Oncology and Palliative Home Care integrated service (UCPD) ward of the Marqués de Valdecilla University Hospital.

Method

Retrospective analysis of death rate registered on the Medical Oncology ward for 2009 and 2010 and the recorded date of the last CT given. The data are analyzed using the SPSS version 15.0 statistic package. Data were obtained from the Database Minimum Set for oncology admissions.

Results

The death rate on the Medical Oncology ward is 22?C24?%. Total number of cases studied is 303. 47?% of patients are aged 60 or younger. 81.8?% (248) received active cancer treatment; of these, 138 (55.6?%) in the last month, and 84 (33.8?%) in the last 2?weeks. Only 66 patients out of those who died on the ward (21?%) were previously sent to the UCPD.

Conclusions

Even when it is known that the majority of cancer patients become resistant to CT at the end of their lives, it is often given to patients of all ages. The request for palliative care is rare and often late.     

Hormone therapy in breast cancer: the end of tamoxifen?

The rise of aromatase inhibitors changes our habits in hormonal treatment in breast cancer. In premenopausal women tamoxifen with ovarian suppression remains reference treatment although the succession of the two treatments has not been explored as far as treatment duration is concerned. In post menopausal women the use of AI in the first line treatment gives a greater chance of response and a longer response duration than tamoxifen with a good tolerance profile. When both treatments are used, total duration of endocrine therapy (time to chemotherapy) is significantly longer for patients who receive AI in first line than for patients who receive tamoxifen first. In adjuvant treatment, tamoxifen and ovarian suppression remain references in premenopausal patients; therefore trials using aromatase inhibitors with LH-RH agonists are running. In post menopausal women aromatase inhibitors are challenging tamoxifen. Three large trials proved their superiority over tamoxifen. In the adjuvant setting AI may represent a beneficial approach, they can be used up front or in sequence with tamoxifen. The ideal combination or sequence of therapies requires investigations. At last duration of hormonal treatment remains an open deal.     

Age-period-cohort analysis of oral cancer mortality in Europe: the end of an epidemic?

Over the last decade, mortality from oral and pharyngeal cancer has been declining in most European countries, but it had been increasing substantially in Hungary, Slovakia and a few other countries of central Europe, reaching rates comparable to those of lung cancer in several western European countries in males. To update trends in oral cancer mortality and further analyse the recent epidemic in central Europe, official death certifications for oral and pharyngeal cancer for 37 European countries were derived over the period 1970-2007, and an age-period-cohort model was fitted for selected countries. Male oral cancer mortality continued to decline in most European countries, including the Russian Federation, and, more importantly, it also started to decline in some of the countries with the highest male rates, i.e. Hungary and Slovakia; persisting rises were, however, observed in Belarus, Bulgaria and Romania. Oral cancer mortality rates for women were lower than in men and showed no appreciable trend over recent periods in the EU overall. Estimates from the age-period-cohort analysis for most selected countries showed a fall in effects for the cohorts born after the 1950s. For the period effect displayed a rise for the earlier periods, an inversion in the 1990 s and a continuous fall up to the last studied period. Only some former non-market economy countries, like Romania, Ukraine and Lithuania, had rising cohort effect trends up to most recent generations. The major finding of this updated analysis of oral cancer mortality is the leveling of the epidemic for men in most European countries, including Hungary and other central European countries, where mortality from this cancer was exceedingly high. These trends essentially reflect the changes in alcohol and tobacco consumption in various populations.     

Cancer patient survival in Sweden at the beginning of the third millennium – predictions using period analysis

Estimates of cancer patient survival made using traditional, cohort-based, methods can be heavily influenced by the survival experience of patients diagnosed many years in the past and may not be particularly relevant to recently diagnosed patients. Period-based survival analysis has been shown to provide better predictions of survival for recently diagnosed patients and earlier detection of temporal trends in patient survival than cohort analysis. We aim to provide predictions of the long-term survival of recently diagnosed cancer patients using period analysis. The period estimates are compared with the latest available cohort-based estimates. Our results, based on period analysis for the years 2000–2002, suggest an improvement in survival for many forms of cancer during recent years. For all sites combined the 5-, 10-, 15-, and 20-year relative survival ratios were 62, 53, 48, and 47 for males and 67, 62, 60, and 59, for females. These estimates were 3–14 units higher than those obtained using the latest available cohorts with the respective lengths of follow-up. The interval-specific relative survival stabilised for males at 97 after 8years of follow-up and for females at 98 after 7years for both period and cohort analyses.