Obesity and cancer outcome : The Lancet
Sunday, April 15, 2012
Obesity and cancer outcome : The Lancet
12 million Americans are cancer survivors and a staggering two-thirds of Americans are currently considered overweight or obese. On April 3, the National Cancer Policy Forum of the US Institute of Medicine released a welcome report entitled The Role of Obesity in Cancer Survival and Recurrence. Many epidemiological studies have identified obesity as a factor in cancer risk and prognosis. Obesity is associated with higher cancer incidence, recurrence, progression, and death. The report emphasises how little is still known about the precise cellular mechanisms that link obesity with cancer.
Adipose tissue can behave as an endocrine organ by generating hormones, growth factors, and cytokines that can disrupt regulation of cell growth and survival—the hallmark of malignancy. Knowing the precise cellular targets involved in this interplay could lead to targeted therapeutic approaches for controlling both cancer and obesity. For example, appropriate animal models could allow investigation of mechanisms of obesity and diabetes in precise genetic models of human cancers.
What is not yet known is whether weight management changes the prognosis and outcome in different cancers. The simple solution of tracking individuals' BMI and bodyweight during clinical trials to analyse effect on cancer outcomes needs to become standard practice. Another area of clinical controversy is related to proper chemotherapy dosing in obese cancer patients. Total body-surface area is used to calculate the chemotherapy dose, which does not take into account the body's composition (such as an individual's fat percentage). This approach often leads to suboptimum doses of chemotherapy.
But the most important lesson of this report comes from the basic science of obesity-associated cancer risk. Our population-level responses—which have largely failed—are based on a far too simplistic understanding of how obesity contributes to cancer. To address this challenge demands not more poorly thought out intervention trials.
Instead, we need greater understanding of the biological mechanisms underpinning cancer and obesity.
Genetic Variations in Stem Cell-Related Genes and Colorectal Cancer Prognosis:
Many properties of cancer cells are reminiscent of those in normal stem cells. Genes important to stem cell development have been significantly implicated in the etiology and clinical outcome of colorectal cancer (CRC). However, the associations of genetic variations in these genes with CRC prognosis have not yet been elucidated.
The most significant finding was related to rs879882, a variant in the 5′ region of POU5F1 gene which encodes a protein essential for embryonic stem cell self-renewal and pluripotency, and induced pluripotent stem cell reprogramming. The variant-containing genotypes of rs879882 were associated with an increased risk of recurrence (hazard ratio [HR] = 2.10, 95 % confidence interval [CI] 1.17–3.76, P = 0.01). In chemotherapy-stratified analysis, the association remained borderline significant in patients receiving chemotherapy (HR = 1.97, 95 % CI 0.89–4.34, P = 0.09). In addition, a nonsynonymous SNP of APC gene was also significantly associated with recurrence risk in chemotherapy-treated patients (HR = 2.63, 95 % CI 1.14–6.06 P = 0.02). Further analyses showed a combined effect of the two SNPs in predicting CRC recurrence in patients receiving chemotherapy (P = 0.04) but not in those without chemotherapy (P = 0.43). Moreover, an exploratory multivariate assessment model indicated that these two variants enhanced the power to predict recurrence after chemotherapy.
abstract: Therapy-related myelodysplasia and acute myeloid leukemia following paclitaxel- and carboplatin-based chemotherapy in an ovarian cancer patient: a case report and literature review
Blogger's Note: treatment-related secondary leukemia is a known adverse effect and previously reported in ovarian cancer; data shows risk ~1-5%; as in all treatment modalities, it is a risk vs benefit decision; this abstract is dated 2008 but a timely reminder
Therapy-related myelodysplasia and acute myeloid leukemia following paclitaxel- and carboplatin-based chemotherapy in an ovarian cancer patient: a case report and literature review:
Alkylating agents have strong leukemogenic potential. There are a number of recent acute myeloid leukemia (t-AML) cases related to previous paclitaxel exposure. These leukemias tend to be of aggressive subtypes with long-latency periods. Unlike previously reported cases, the present case was of the secondary acute megakaryoblastic myeloid leukemia (AML M7) subtype. Additionally, it did not harbor a translocation in chromosome 19. A 73-year-old woman was diagnosed with t-AML M7 with antecedent myelodysplasia. Leukemia followed a second induction of paclitaxel- and carboplatin-based chemotherapy for recurrent ovarian cancer. Her second induction began 25 months after completion of her first course of chemotherapy. The increased incidence of postpaclitaxel leukemia suggests a probable role for paclitaxel as a leukemogenic agent. It highlights the importance of assessing for leukemia risk factors prior to beginning paclitaxel therapy.
Serous borderline ovarian tumors in long-term culture: phenotypic and genotypic distinction from invasive ovarian carcinomas
Serous borderline ovarian tumors in long-term culture: phenotypic and genotypic distinction from invasive ovarian carcinomas:
Serous borderline ovarian tumors (SBOTs) are differentiated, slow growing, noninvasive, and have a better prognosis than their invasive counterparts, but recurrence and progression to invasive carcinomas are common, and unlike high-grade serous carcinomas, they tend to be nonresponsive to chemotherapy. However, due to a lack of culture systems and animal models, information about the properties of SBOT and their changes with neoplastic progression is extremely limited. Our objective was to establish a cell culture model for SBOTs and to characterize their phenotype and genotype..............In conclusion, we have established the first permanent SBOT cell line, which provides a new model to elucidate the undefined relationship of SBOTs to invasive ovarian carcinomas.
A snapshot of microarray-generated gene expression signatures associated with ovarian carcinoma:
It was hypothesized that analysis of global gene expression in ovarian carcinoma can identify dysregulated genes that can serve as molecular markers and provide further insight into carcinogenesis and provide the basis for development of new diagnostic tools as well as new targeted therapy protocols................From these genes, merely three were identified in at least two different studies. This snapshot of available gene expression data not only provides independently described potential diagnostic and therapeutic targets for ovarian carcinoma but also emphasizes the drawbacks of the current state of global gene expression analyses in ovarian cancer.
Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma
It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible on the basis of only histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty and 3 fellows) but who were trained in its use by referring to a website designed for the purpose. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (≥4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/reactive was achieved in 76% of the lesions, with no consensus in 24%. Combining diagnoses into 2 categories (STIC versus non-STIC) resulted in an overall consensus of 93% and no consensus in 7%. The κ value for STIC versus non-STIC among all 6 observers was also high at 0.67 and did not significantly differ, whether for faculty (κ=0.66) or fellows (κ=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it to routine clinical practice, the algorithm should be evaluated by general surgical pathologists in a community setting.
abstract: Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type.
Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type [Am J Surg Pathol. 2012]
AbstractThe role of endometriosis in ovarian cancer, disease progression, and survival is a subject of active investigation. A series of 144 ovarian cancers with clear cell or endometrioid histology or associated endometriosis, all classified on the basis of strict histologic criteria, was evaluated to further explore the relationship between endometriosis-associated ovarian cancer and age at presentation, FIGO stage, histology, presence of synchronous primary disease elsewhere in the mullerian tract, and survival.
Patients with endometrioid carcinomas were significantly younger (mean, 52 y) in comparison with patients with either clear cell carcinoma (mean, 55 y) or mixed tumors (mean, 59 y; P=0.002).
Clear cell carcinoma presented as low-stage disease (FIGO I) in 33% of cases compared with endometrioid carcinomas in 97% of cases and mixed carcinomas in 27% of cases. Endometriosis was associated with 53% of clear cell carcinomas, 33% of endometrioid carcinomas, and 45% of mixed tumors (P<0.001). Synchronous primary tumors, observed in 31% of endometrioid tumors, 5% of mixed tumors, and in 2% of clear cell tumors (P<0.001), were unlikely to be associated with endometriosis (P=0.04). Univariate analysis of the aggregate cohort demonstrated that the single best overall predictor of disease-free survival was FIGO stage at presentation (P<0.001), followed by histologic subtype (P=0.003).
Endometriosis did not have a significant relationship with disease-free survival (P=0.7). We conclude that the link between endometriosis and ovarian cancer is much stronger for clear cell carcinoma than for other histologic subtypes (P<0.001). Furthermore, when uniform histologic criteria are applied, true mixed endometrioid and clear cell carcinomas are uncommon; most endometriosis-associated mixed tumors are heterogenous mixtures of endometrioid, mucinous, and serous histology with areas of clear cell cytoplasm. Endometriosis per se does not appear to predict prognosis in clear cell and endometrioid tumors, with the possible exception of tumors with mixed histology. Until more data are collected, pathologists should classify ovarian tumors with mixed histology as a separate and potentially unique biological and prognostic group.
open access: Survivorship care plans in research and practice - Apr 2012 - CA: A Cancer Journal for Clinicians
Blogger's Note: while the focus here is breast/colorectal cancers, research background included gyn cancer
Survivorship care plans in research and practice - 2012 - CA: A Cancer Journal for Clinicians
The Institute of Medicine (IOM) recommends the use of survivorship care plans (SCPs) for all cancer survivors. Developing useful SCPs requires understanding what survivors and their providers need and how SCPs can be implemented in practice. Published studies investigating the perspectives of stakeholders (survivors, primary care providers, and oncology providers) were reviewed regarding the content and use of SCPs. All National Cancer Institute (NCI)-designated cancer centers were surveyed concerning the extent to which SCPs for survivors of breast and colorectal cancers are in use, their concordance with the IOM's recommendation, and details about SCP delivery. Survivors and primary care providers typically lack the information the IOM suggested should be included in SCPs. Oncology providers view SCPs favorably but express concerns about the feasibility of their implementation. Fewer than one-half (43%) of NCI-designated cancer centers deliver SCPs to their breast or colorectal cancer survivors. Of those that do, none deliver SCPs that include all components recommended by the IOM. Survivors' and providers' opinions about the use of SCPs are favorable, but there are barriers to implementation. SCPs are not widely used in NCI-designated cancer centers. Variation in practice is substantial, and many components recommended by the IOM framework are rarely included.
abstract: Researchers find discordance between standard human epidermal growth factor receptor 2 (HER2) testing and HER2 status reported on Oncotype DX - CA: A Cancer Journal for Clinicians
Researchers find discordance between standard human epidermal growth factor receptor 2 (HER2) testing and HER2 status reported on Oncotype DX - 2012 - CA: A Cancer Journal for Clinicians