How generalizable are the SEER registries to the cancer populations of the USA?

Background

We determined whether the current SEER registries are representative of the nation’s cancer cases or the socio-demographic characteristics.

Methods

We used breast cancer (BC) and colorectal cancer (CRC) cases diagnosed 2004–2009 from the US Cancer Statistics (USCS) database. Cases were classified into groups residing in SEER coverage areas and the other areas. We compared difference between SEER and non-SEER areas in: age–race-specific proportions of late-stage BC or CRC, area demographics and socioeconomic factors, and data quality.

Results

For late-stage CRC diagnosis, SEER areas contained lower proportions of people with other race and higher proportions of Asian and Hispanic females aged <40, than non-SEER areas. For late-stage BC diagnosis, SEER and non-SEER estimates were comparable. SEER areas had lower percentages of whites and higher percentages of young people, were more urban, and had higher percentage of poor, lower educational attainment, and higher unemployment. SEER areas also tended to have a higher percentage of case completeness than non-SEER areas.

Conclusion

Overall, SEER registries were not significantly different from non-SEER areas in terms of average age–race-specific proportions of late-stage BC or CRC, except for estimates of late-stage CRC for other race and young Asian and Hispanic women. Although case completeness was better in SEER areas than non-SEER areas, SEER areas had greater economic disadvantage and greater minority diversity among the population. This study demonstrated a need for caution in using SEER data and discussed advantages of using the more complete USCS database.

     

Cytokine-based Preclinical Approaches to the Therapy of Renal Cancar

Antigen-nonspecific approaches to the use of BRMs for cancer treatment have resulted in only limited success to date. Recent demonstrations of T-Iymphocyte-mediated antigen-specific responses against some human tumors, and the more pronounced effects of these cells in preclinical models have refocusedmuch of responses, the mechanisms by which positive effects are achieved, and the reasons why T Iymphocytes in tumor-bearing mice may not respond as predicted. We have recently found that T-Iymphocytes obtained from tumo-bearing mice exhibit some degree of functional impairment to stimulation through the T cell antigen receptor possibly     

Qualitative meta-synthesis of survivors’ work experiences and the development of strategies to facilitate return to work

Purpose

To review the empirical qualitative literature on cancer survivors’ experiences of the return to work process in order to develop strategies for health and vocational professionals to facilitate return to work.

Methods

A rigorous systematic search of five databases was completed to identify relevant qualitative studies published between Jan 2000 and July 2013. All potentially relevant titles and abstracts were reviewed by two reviewers. For studies that met eligibility, the full-text articles were obtained and assessed for quality. The collected evidence was then synthesized using meta-ethnography methods.

Results

In total, 39 studies met the eligibility criteria and passed the quality assessment. The synthesis of these studies demonstrated that cancer diagnosis and treatment represented a major change in individuals’ lives and often resulted in individuals having to leave full-time work, while undergoing treatment or participating in rehabilitation. Thus, many survivors wanted to return to some form of gainful or paid employment after treatment and rehabilitation. However, there was also evidence that the meaning of paid employment could change following cancer. Return to work was found to be a continuous process that involved planning and decision-making with respect to work readiness and symptom management throughout the process. Nine key factors were identified as relevant to work success. These include four related to the person (i.e., symptoms, work abilities, coping, motivation), three related to environmental supports (i.e., family, workplace, professionals), and two related to the occupation (i.e., type of work/demands, job flexibility). Finally, issues related to disclosure of one’s cancer status and cancer-related impairments were also found to be relevant to survivors’ return to work experiences.

Conclusions

This review reveals that cancer survivors experience challenges with maintaining employment and returning to work following cancer and may require the coordinated support of health and vocational professionals.

Implications for Cancer Survivors

Cancer survivors need integrated support from health and vocational professionals (e.g., assistance with defining work goals, determining work readiness, determining how symptoms may impact work performance, suggesting workplace supports, and accommodations) to maintain and return to work after cancer diagnosis and treatment. These supports need to be provided throughout the recovery and rehabilitation process.     

Does the standardized helmet technique lead to adequate coverage of the cribriform plate? An analysis of current practice with respect to the ICRU 50 report

Purpose: To investigate whether the standardized helmet technique adequately covers the cribriform plate.

Methods and Materials: For 11 patients with acute leukemia or primary intracerebral neoplasms undergoing irradiation with the standardized helmet technique, three-dimensional isodose distributions were evaluated with special respect to the dose to the cribriform plate and the ocular lenses.

Results: The average dose received by 95% of the cribriform plate with the standardized helmet technique was 85% of the prescribed dose. To enclose the cribriform plate by the 95% isodose (according to the ICRU 50 report) with a 10-mm safety margin allowing for deviations during treatment planning and delivery, the eye block had to be moved in the ventrocaudal direction with an average vector length of 13.6 mm. Consequently, the mean dose received by 5% of the lenses rose from 18% to 91% of the prescribed total dose.

Conclusion: Sufficient lens shielding is usually not compatible with safe irradiation of the frontobasis by the standardized helmet technique.     

Does the professional image of the social worker in oncology correspond to the current challenges of the job? Apropos of a survey of patients and care professionals

Care professionals (physicians and nurses), administrative staff and hospitalised patients were interviewed to find out the necessary qualities for social workers in oncology, as well as the roles and tasks that they must fulfil. On the one hand, the results of this study show that the needs of the interested parties are indeed met by social service from an empirical perspective of psychosocial support and expert advice. On the other hand, they bring to light the fact that the current status of the social worker is hardly recognized. Confronted with new occupational challenges, the social worker should rethink his/her profession and reevaluate his/her practice. Furthermore, he/she should develop professional links intra- and extramural and participate in social research programs whose aim is to improve the rehabilitation of patients and their families.     

Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?

Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC....     

Correlation between the Sensitivity to TRAIL and the Expression Level of DR5 on the Surface of Tumor Cells

OBJECTIVE To investigate the correlation between the sensitivity to the tumor necrosis factor- related apoptosis inducing ligand (TRAIL) and the level of expression of the death receptor 5 (DR5) on the surface of tumor cells.METHODS Anti-DR5 mAbs were used to directly detect the level of expression of DR5 on the surface of tumor cells. Using a TRAIL apoptosis kit and flow cytometry, the sensitivity of the tumor cells to TRAIL-induced apoptosis was determined and the correlation between DR5 expression and sensitivity to TRAIL analyzed.RESULTS The expression level of DR5 on the surface of different tumor cells was as follows: 97.9% in U937 cells, 95.1% in Jurkat cells, 93.8% in SW480 cells, 86.2% in HCT116 cells, 64.2% in HL-60 cells, 46.6% in Hela cells and 13.1% in K562 cells. The TRAIL-induced apoptotic rate was 72.6% in U937 cells, 85.2% in Jurkat cells, 78.6% in SW480 cells, 70.2% in HCT116 cells,60.1% in HL-60 cells, 45.4% in Hela cells and 12.3% in K562 cells. Statistical analysis showed there was a significant positive correlation (r=0.997, P<0.001) between DR5 expression and sensitivity to TRAIL.CONCLUSION The sensitivity of tumor cells to TRAIL is related to the level of expression of DR5 on the surface of tumor cells. These results confirm the importance of DR5 expression for induction of apoptosis by TRAIL.     

The relevance of the TGF-β Paradox to EMT-MET programs

The role of transforming growth factor-β (TGF-β) during tumorigenesis is complex and paradoxical, reflecting its ability to function as a tumor suppressor in normal and early-stage cancers, and as a tumor promoter in their late-stage counterparts. The switch in TGF-β function is known as the “TGF-β Paradox,” whose manifestations are intimately linked to the initiation of epithelial-mesenchymal transition (EMT) programs in developing and progressing carcinomas. Indeed, as carcinoma cells emerge from EMT programs stimulated by TGF-β, they readily display a variety of acquired phenotypes that provide a selective advantage to growing carcinomas, including (i) enhanced cell migration and invasion; (ii) heightened resistance to cytotoxic agents, targeted chemotherapeutic, and radiation treatments; and (iv) boosted expansion of cancer-initiating and stem-like cell populations that underlie tumor metastasis and disease recurrence. At present, the molecular, cellular, and microenvironmental mechanisms that enable post-EMT and metastatic carcinoma cells to hijack the oncogenic activities of TGF-β remain incompletely understood. Additionally, the molecular mechanisms that counter EMT programs and limit the aggressiveness of late-stage carcinomas, events that transpire via mesenchymal-epithelial transition (MET) reactions, also need to be further elucidated. Here we review recent advances that provide new insights into how TGF-β promotes EMT programs in late-stage carcinoma cells, as well as how these events are balanced by MET programs during the development and metastatic progression of human carcinomas.     

Immune approaches to the treatment of breast cancer,around the corner?

Immunotherapy for the treatment of breast cancer can be categorized as either (a) specific stimulation of the immune system by active immunization, with cancer vaccines, or (b) passive immunization, such as tumor-specific antibodies (including immune modulators) or adoptive cell therapy that inhibit the function of, or directly kill, tumor cells. We will present the current information and the future perspectives of immunotherapy in patients with breast cancer, including the prognostic role of tumor infiltrating lymphocytes, immune signatures, targeted therapies modulating the immune system, and tumor antigen cancer vaccines. Active immunotherapy in breast cancer and its implementation into clinical trials have been largely a frustrating experience in the last decades. The concept that the immune system regulates cancer development is experiencing a new era of interest. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. Also, the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape. Major topics in the field of immunology deserve a response: what do we know about tumor immunogenicity, and how might we therapeutically improve tumor immunogenicity? How can we modulate response of the immune system? Is there any gene signature predictive of response to immune modulators? The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signaling pathways that regulate immune responses in the tumor microenvironment.     

Application of Proteomics to the Study of Hepatocellular Carcinoma and Some Related Diseases

Hepatocellular carcinoma is a malignant tumor causing one of the highest death rates in the world. Viral hepatitis, hepatic fibrosis and hepatocirrhosis etc. Are some of the most important causes of hepatocellular carcinoma. With the advent of the post-genomic age, studying carcinoma and some related diseases using the developing technology of proteomics has become a major focus of researchers. This article is a review of the application of proteomics to study hepatocellular carcinoma and some related diseases.     

Is Response to Radiotherapy in Patients Related to the Severity of Pretreatment Pain?

PURPOSE: The primary objective of this study was to determine whether there is a relationship between the severity of pretreatment pain and response to palliative radiotherapy (RT) for painful bone metastases. METHODS AND MATERIALS: The database for patients with bone metastases seen at the Rapid Response Radiotherapy Program at the Odette Cancer Center from 1999 to 2006 was analyzed. The proportion of patients with mild (scores 1-4), moderate (scores 5-6), or severe (scores 7-10) pain at baseline who experienced a complete response, partial response, stable response, or progressive response after palliative RT was determined according to International Bone Metastases Consensus definitions. RESULTS: During the 7-year study period 1,053 patients received palliative radiation for bone metastases. The median age was 68 years and the median Karnofsky performance status was 70. Of the patients, 53% had a complete or partial response at 1 month, 52% at 2 months, and 54% at 3 months post-RT. CONCLUSIONS: There was no significant difference in terms of the proportion of responders (patients with complete or partial response) and nonresponders in terms of painful bone metastases among patients presenting with mild, moderate, or severe pain. Patients with moderate pain should be referred for palliative RT.     

What has the meta-analysis contributed to today's standard of care in the treatment of thoracic malignancies?

Meta-analyses dealing with the treatment of thoracic malignancies (non-small cell lung cancer, small cell lung cancer and mesothelioma) are reviewed including those performed in the context of a systematic review of the literature or based on individual patients data. Their results have been used as an effective tool for resolving various clinical questions, providing more reliable evidence for some clinical practice: (neo)adjuvant chemotherapy after surgery for resectable NSCLC, radiochemotherapy for patients with unresectable limited NSCLC and limited SCLC, advantage of chemotherapy for advanced NSCLC and identification of the most active drugs. However, it is important to understand the limits of their methodology in order to avoid inappropriate interpretations.     

Optimal design of trials to demonstrate the utility of?genomically‐guided therapy: Putting Precision Cancer?Medicine to the test

The new age of Precision Cancer Medicine, with specific biomarkers being used to direct targeted agents, generally concerns only a subset of patients within a certain histopathologically defined tumor type. This paradigm is challenged by the need to perform widespread molecular screening in certified laboratories, with results available to clinicians within reasonable timeframe. Tumor heterogeneity and clonal evolution must be considered in the decision making process. Adaptive and innovative clinical trial designs exploring predictive algorithms and reconsideration of traditional efficacy endpoints are required to rapidly translate scientific discoveries into patient care. Furthermore, international collaboration in cancer research and open discussions on the availability of investigational agents will likely redefine the drug development and approval process in the coming years.     

Aerosol delivery of liposomal all-trans -retinoic acid to the lungs

Purpose: To optimize the delivery of all-trans-retinoic acid (ATRA) to lung tissue, we determined the potential of vehiculating the drug in liposomes (L-ATRA) and delivering it via aerosol. Liposomes may provide a means to prevent local irritation of lung tissue and reduce pulmonary toxicity, prolong therapeutic levels and generate high drug concentrations at the tumor sites. Cumulatively, this would result in reduced systemic toxicity and enhanced drug efficacy. Methods: Previous studies have shown that liposomes can serve as excellent carriers for otherwise poorly soluble ATRA. Delivery of ATRA to the lung tissue of mice was accomplished by nebulization of L-ATRA. The liposomes in the aerosol were relatively uniform (309 ± 138 nm), stable, and retained the drug well. Results: The drug was effectively delivered at high concentrations (10 ± 2 μg/g of tissue) to the lungs of mice and was retained for at least up to 96 h after a single exposure to L-ATRA aerosol. No appreciable levels of ATRA were detected in the blood or the liver of treated mice. The aerosol-delivered ATRA was biologically active as demonstrated by its ability to induce the expression of tissue-type transglutaminase. Conclusion: Aerosol delivery of L-ATRA offers an effective way to deliver high levels of ATRA to the lung without apparent pulmonary toxic effects. Received: 17 February 1998 / Accepted: 21 July 1998     

Did earthworms contribute to the parasitic evolution of dermatophytes?

The survival of dermatophyte species in the gut of four species of earthworms was studied by feeding the fungi to the earthworms. Recovery of the dermatophyte species in culture from the guts was only possible for Microsporum gypseum and Chrysosporium keratinophilum. In the light of these findings, we presume that earthworms could have influenced the parasitic evolution of certain dermatophytes.     

Should the diagnosis of cancer be communicated to patients? Evaluation of a sample opinion survey of the Spanish population

The aim of this paper is to determine the opinion of healthy individuals among whom might be future cancer patients, about communicating the diagnosis of this disease to the patients. An inquiry was performed on a representative sample of the spanish population. It covered 2493 persons over the age of 18. Two questions were asked: 1) "If you suffered from cancer would you prefer your physician to tell you or not?" 2) "If the cancer patient were a very near relative of yours (parent, etc.), would you wish the physician to inform the patient or not?" 69% gave a positive reply to the first question and 23% answered in the negative. The number of affirmative answers was significantly higher among the following groups: men (76%); young persons (82%); individuals with a high cultural level (79%; the unemployed (80%); and non-believers (86%). 42% answered "yes" to the second question and 44% answered "no". The number of affirmative answers was significantly higher among the following: men (48%); young people (54%); non-believers (65%); it was significantly lower among housewives (33%). The conclusion is that the diagnosis of cancer should not be communicated indiscriminately to the patient in all cases. The future problem lies in determining which persons should be informed of the diagnosis.     

The Effect of the MDM2-p53 Loop on the Sensitivity of Ovarian Cancer Cells to Cisplatin

OBJECTIVE To explore whether MDM2 transfection can alter the MDM2-p53 autoregulatory feedback loop so as to change the sensitivity of ovarian cancer cell lines to cisplatin. METHODS The ovarian cancer cell line A2780 expressing wild-type P53 and the ovarian cancer cell line SKOV-3 with the p53 null type were stably transfected with pCMV-MDM2 or pCMV as a control. The blocked expression of P53 was determined by Western blots. Cytotoxicity was assessed using the MTT assay and the trypan blue exclusion assay. Flow cytometry was used to detect changes in the cell cycle and removal of platinum -DNA adducts was measured by atomic absorption spec-troscopy. RESULTS (1) Parental A2780 and A2780-V cells (IC50= 15.14±1.39 μmol) have similar cisplatin sensitivities, whereas sensitivity to cisplatin in A2780-M cells (IC50=7.98±1.32 μmol) was 2 to 3 fold greater (P=0.001). The trypan blue exclusion assay demonstrated that cisplatin killed a higher percentage of A2780-M cells compared to A2780-V cells. There was no significant change following MDM2 transfection in SKOV-3 cells. (2) After cisplatin treatment, A2780-M cells showed a pronounced S-phase arrest, however, A2780 cells with the intact wild-type P53, arrested primarily at the G2/M transition. (3) Platinum uptake was similar for all of the A2780 cell lines after ciaplatin treatment, but the removal of plat-inum-DNA adducts was reduced in the A2780-M cells compared with A2780-V cells. CONCLUSION MDM2 increases cisplatin cytotoxicity in ovarian cancer cells by blocking the expression of p53 through the MDM2-p53 autoregulatory feedback loop.