Tuesday, July 19, 2016
OhioLINK ETD: Stories of Teal: Women's Experiences of Ovarian Cancer (Ohio/Michigan)
OhioLINK ETD: Tetteh, Dinah A
Stories of Teal: Women's Experiences of Ovarian Cancer
2016, Doctor of Philosophy (Ph.D.), Bowling Green State University, Communication Studies.
This
dissertation explores the lived experiences of ovarian cancer. I used
feminist ethnographic methods of in-depth interviews and focus groups to
collect data from 28 ovarian cancer survivors in Northwest Ohio and
Southern Michigan. The concepts of social support, uncertainty in
illness, and intersectionality are used to understand women’s
experiences of the disease and their quality of life post-treatment. My
grounded theory analysis shows the ovarian cancer experience as a
process involving three phases including (not)making sense, owning the
experience, and becoming a survivor. The phases are neither linear nor
distinct, and each presents unique challenges to survivors, helping
shape how they make meaning and communicate about their experiences. I
identify managing uncertainty as the core variable in the ovarian cancer
experience; uncertainty is high at diagnosis, plateaus during
treatment, heightens again at the end of treatment, and remains in the
backgrounds of women’s lives as they navigate treatment aftereffects
and/or recurrences. The ovarian cancer experience is influenced by
women’s age, religion, socioeconomic status, level of available social
support, stage of disease, and treatment protocol. These factors work
through and with each other to impact women’s meaning making about the
disease. This research helps demystify the ovarian cancer experience and
puts human faces on the disease. It also provides a deeper
understanding about the factors that influence women’s experiences of
ovarian cancer and the communicative strategies they use to determine
their experiences.
Sandra Faulkner, Ph. D. (Advisor)
Apollos Nwauwa, Ph. D. (Other)
Radhika Gajjala, Ph. D. (Committee Member)
Lisa Hanasono, Ph. D. (Committee Member)
Apollos Nwauwa, Ph. D. (Other)
Radhika Gajjala, Ph. D. (Committee Member)
Lisa Hanasono, Ph. D. (Committee Member)
152 p.
Files
Full text release has been delayed at the author's request until June 01, 2020
open access: Regional and temporal heterogeneity of epithelial ovarian cancer tumor biopsies: implications for therapeutic strategies
open access:
Regional and temporal heterogeneity of epithelial ovarian cancer tumor biopsies: implications for therapeutic strategies
Article Tools
Supplementary Files
Stage III/IV epithelial ovarian cancer (EOC) is a
systemic disease. The clonal relationship among different tumor lesions
at diagnosis (spatial heterogeneity) and how tumor clonal architecture
evolves over time (temporal heterogeneity) have not yet been defined.
Such knowledge would help to develop new target-based strategies, as
biomarkers which can adjudge the success of therapeutic intervention
should be independent of spatial and temporal heterogeneity.
The
work described in this paper addresses spatial and temporal
heterogeneity in a cohort of 71 tumor biopsies using targeted NGS
technology. These samples were taken from twelve high grade serous (HGS)
and seven non HSG-EOC, both at the time of primary surgery when the
tumor was naïve to chemotherapy and after chemotherapy.
Matched
tumor lesions growing in the ovary or at other anatomical sites show
very different mutational landscapes with branched tumor evolution.
Mutations in ATM, ATR, TGFB3, VCAM1 and COL3A1 genes were shared across all lesions. BRCA1 and BRCA2
genes were frequently mutated in synchronous lesions of non HGS-EOC.
Relapsed disease seems to originate from resistant clones originally
present at the time of primary surgery rather than from resistance
acquired de novo during platinum based therapy.
Overall
the work suggests that EOC continues to evolve. More detailed mapping
of genetic lesions is necessary to improve therapeutic strategies.
A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer
Abstract
A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer
Menopausal
estrogen-alone therapy (ET) is a well-established risk factor for serous
and endometrioid ovarian cancer. Genetics also plays a role in ovarian
cancer, which is partly attributable to 18 confirmed ovarian cancer
susceptibility loci identified by genome-wide association studies. The
interplay among these loci, ET use, and ovarian cancer risk has yet to
be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid
cases, and 4,051 controls across 10 case-control studies participating
in the Ovarian Cancer Association Consortium (OCAC). Conditional
logistic regression was used to determine the association between the
confirmed susceptibility variants and risk of serous and endometrioid
ovarian cancer among ET users and non-users separately and to test for
statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (pint=0.013).
ET users carrying the T allele had a 51% increased risk of disease
(OR=1.51, 95% CI 1.19-1.91), which was stronger for long-term ET users
of 10+ years (OR=1.85, 95% CI 1.28-2.66, pint=0.034).
Non-users showed essentially no association (OR=1.08, 95% CI 0.96-1.21).
Two additional genomic regions harboring rs7207826 (C allele) and
rs56318008 (T allele) also had significant interactions with ET use for
the endometrioid histotype (pint=0.021 and pint=0.037,
respectively).
Hence, a total of three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci.
Hence, a total of three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci.
The pro-inflammatory effect of obesity on high grade serous ovarian cancer
abstract
CONCLUSION:
In HGSC, pro-inflammatory cytokines are influenced by obesity, as differing inter-cytokine correlations were observed based on BMI, possibly due to dysregulation between cytokines in the setting of obesity. Differences in survival and platinum sensitivity were not noted. Future studies are warranted to determine whether obesity may be a modifiable risk factor for poorer outcomes due to differing immune response.The influence of age and other prognostic factors associated with survival of ovarian immature teratoma
abstract:
The influence of age and other prognostic factors associated with survival of ovarian immature teratoma - A study of 1307 patients
OBJECTIVE:
To determine impact of age and other prognostic factors on the survival of ovarian immature teratoma (IT) patients.METHODS:
Data obtained from the SEER database between 1973 and 2012. Kaplan-Meier methods and multivariate Cox regression models were used for statistical analyses.RESULTS:
Of 1307 patients (median: 24years; range: 0-93), 78%, 5%, 13%, 4% were stages I, II, III and IV, respectively. 25%, 35%, and 40% had grades 1, 2, and 3. Whites were less likely to be diagnosed, and Asians had a nearly 3-fold higher proportion of IT compared to the proportion of Asians in the U.S. census. The 5-year disease-specific survival (DSS) was 91.2%. Those with stages I, II, III and IV disease had survivals of 99.7%, 95%, 81%, and 71.8% (p<0.001) and grades 1, 2, and 3 had DSS of 98.7%, 95.8%, and 91% (p<0.001), respectively. Of those who underwent fertility-preserving surgery, the DSS was 98.8%. Over time from 1973 to 1986, to 1987-1999, to 2000-2012, the survivals were 76.4%, 92.8%, and 94.7% (p<0.001). Of stage I patients, no patient <18years (n=214, used as adult cutoff) and 2 of 283 patients >18years died of cancer, with corresponding 5years DSS of 100% vs. 99.6% (p>0.05). Older age (by year, HR: 1.05; 95% CI: 1.04-1.06; p<0.0001) and higher stage (HR: 11.52; 95% CI: 4.08-32.48; p<0.0001) were independent factors indicating poorer survival.CONCLUSION:
The outcome of patients with stage I disease was excellent at 99.7%, with children and adults having corresponding survivals of 100% and 99.6%.Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation, Progression, and Metastasis
abstract
Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation, Progression, and Metastasis: A Critical Systematic Review of In Vivo Preclinical Data
P
A
major objective of the emerging field of exercise–oncology research is
to determine the efficacy of, and biological mechanisms by which,
aerobic exercise affects cancer incidence, progression, and/or
metastasis. There is a strong inverse association between self-reported
exercise and the primary incidence of several forms of cancer;
similarly, emerging data suggest that exercise exposure after a cancer
diagnosis may improve outcomes for early-stage breast, colorectal, or
prostate cancer. Arguably, critical next steps in the development of
exercise as a candidate treatment in cancer control require preclinical
studies to validate the biological efficacy of exercise, identify the
optimal “dose”, and pinpoint mechanisms of action. To evaluate the
current evidence base, we conducted a critical systematic review of in vivo
studies investigating the effects of exercise in cancer prevention and
progression. Studies were evaluated on the basis of tumor outcomes
(e.g., incidence, growth, latency, metastasis), dose–response, and
mechanisms of action, when available. A total of 53 studies were
identified and evaluated on tumor incidence (n = 24), tumor growth (n = 33), or metastasis (n
= 10). We report that the current evidence base is plagued by
considerable methodologic heterogeneity in all aspects of study design,
endpoints, and efficacy. Such heterogeneity precludes meaningful
comparisons and conclusions at present. To this end, we provide a
framework of methodologic and data reporting standards to strengthen the
field to guide the conduct of high-quality studies required to inform
translational, mechanism-driven clinical trials. Cancer Res; 76(14); 4032–50. ©2016 AACR.
Monday, July 18, 2016
Articles/Correspondence: Weekly vs. Every-3-Week Paclitaxel for Ovarian Cancer
NEJM
Correspondence
Weekly vs. Every-3-Week Paclitaxel for Ovarian Cancer
- Article
- Metrics
To the Editor:
Chan et al. (Feb. 25 issue)1 found a marginal benefit of dose-dense (weekly) chemotherapy over standard chemotherapy in a group of 112 women with ovarian cancer who did not receive bevacizumab, a subgroup that represents a mere 16% of the whole. The use of progression-free survival, instead of overall survival, in trials of ovarian-cancer therapies will exaggerate the benefit of a therapy that delays progression but has no effect on survival. The degree of exaggeration is greatest for trials, such as this one, in which the overall survival is poor, because the worse the survival is, the farther the hazard ratio associated with the intervention will fall below unity. In the present study, the 4-year survival rate was 44%; the high mortality can be attributed to the low rate of acceptance of neoadjuvant chemotherapy (13%) and the far lower rate of microscopic residual disease than gross residual disease (24% vs. 63%) after surgery. These two treatment factors are of far greater importance than is any minor modification to the chemotherapy regimen,2 and improving these should be our goal.Steven A. Narod, M.D.No potential conflict of interest relevant to this letter was reported.
Women’s College Research Institute, Toronto, ON, Canada
steven.narod@wchospital.ca
2 ReferencesTo the Editor:
Chan et al. report that weekly paclitaxel and carboplatin, as compared with paclitaxel and carboplatin administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. During the design of the study, the Gynecologic Oncology Group (GOG) completed protocol 218, and 84% of the patients received bevacizumab. Among patients who opted to receive bevacizumab, progression-free survival was similar in the two groups. However, among patients who opted not to receive bevacizumab, weekly paclitaxel was associated with a median progression-free survival that was 3.9 months longer than that observed with paclitaxel every 3 weeks. The Japanese Gynecologic Oncology Group (JGOG) 3016 trial1 showed significant benefit in progression-free survival and overall survival with the use of dose-dense paclitaxel and carboplatin as compared with conventional paclitaxel and carboplatin.
Given the high cost and toxic effects of bevacizumab, the lack of improvement in overall survival, and the similar progression-free survival rates with weekly paclitaxel without bevacizumab (14.2 months) and with weekly or every-3-week paclitaxel with bevacizumab (14.9 months and 14.7 months, respectively) that were observed in the GOG-0262 trial, it may be premature to adopt bevacizumab as the treatment of choice. In our opinion, using dose-dense treatment as in the JGOG 3016 trial is an excellent option, especially in developing countries.Laís Pimenta, M.D.No potential conflict of interest relevant to this letter was reported.
Monica Dornelas, M.D.
Loureno Cezana, M.D.
Hospital Santa Rita de Cássia, Vitória, Brazil
laisguedes@yahoo.com.br
1 ReferenceThe authors reply: As stated by Narod, there was a benefit noted for weekly paclitaxel over standard chemotherapy in the subgroup of patients who did not receive bevacizumab. We included bevacizumab as a prespecified stratification factor in the treatment randomization process with knowledge of its clinical activity. A secondary analysis was performed to assess the assumption of homogeneity of the treatment effect across the strata. We also believe that weekly paclitaxel does not provide a mere marginal benefit, because the magnitude of improvement (hazard ratio for disease progression or death, 0.62) in our trial was similar to that in the JGOG trial (hazard ratio for disease progression or death, 0.71), which resulted in an overall survival advantage.1
Narod also asserts that progression-free survival exaggerates the therapeutic benefit of a treatment for which there is no overall survival advantage, particularly in trials involving patients with poor overall survival. Although overall survival is an important end point, progression-free survival is widely regarded as a valid and clinically relevant end point for clinical trials involving women with advanced-stage ovarian cancer.2 The high mortality observed in this trial is due to the selection of high-risk patients with incompletely resected stage III or any stage IV epithelial cancers, as required in the initial eligibility criteria of our trial. To the contrary, our trial does not minimize the importance of primary cytoreductive surgery. Clinicians seldom change their practice on the basis of the results of a single trial. However, the findings from this current trial add supporting evidence about the benefit of weekly paclitaxel that is consistent with the findings of the JGOG ovarian-cancer trial and previous breast-cancer trials.
We appreciate the comments by Pimenta et al. on the financial advantages of weekly paclitaxel. Comparative effectiveness studies have shown that weekly paclitaxel with carboplatin has an advantage over every-3-week treatment and bevacizumab.3,4 Now, more than ever, we have many options to personalize ovarian-cancer treatments for our patients in order to improve their outcomes.
John K. Chan, M.D.Since publication of their article, the authors report no further potential conflict of interest.
California Pacific–Palo Alto Medical Foundation, San Francisco, CA
chanjohn@sutterhealth.org
Mark F. Brady, Ph.D.
Roswell Park Cancer Institute, Buffalo, NY
Bradley J. Monk, M.D.
University of Arizona Cancer Center, Phoenix, AZ
4 References
Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer/Rectosigmoid Cancer
abstract:
Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer.
CONCLUSIONS:
The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.
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