Long-term Survivors Of Ovarian Cancer Research Articles

Abstract A095: Long-term ovarian cancer survivors: spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface

Abstract Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. Reports to date have not fully established the heterogeneity of the tumor microenvironment (TME) in ovarian cancer and its association with clinical outcomes. The TME, which is composed primarily of fibroblasts, endothelial cells, lymphocytic infiltrates, and extracellular matrix proteins, can directly affect cancer cell growth, migration, and differentiation, and thus presents a unique opportunity for cancer diagnosis and treatment. To investigate the stromal heterogeneity of the TME in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival in patients with advanced HGSC. Spatial transcriptomics and single-cell RNA sequencing data were integrated to distinguish tumor and stroma regions, and a computational method was developed to investigate spatially resolved ligand-receptor interactions between various tumor and CAF subtypes in the TME. Our spatial transcriptomics analysis demonstrated the presence of different tumor clusters represented by different transcriptome signatures within a tumor tissue, suggesting high levels of heterogeneity not only among different HGSC samples but also within single HGSC samples. Moreover, our spatial transcriptomics analysis of treatment-naïve STS and LTS samples demonstrated high levels of both intra- and inter-stromal heterogeneity among HGSCs. Annotated stroma clusters, which were identified predominantly in STS samples, had high levels of both periostin and CD36 expression as well as high levels of COL1A1 expression. Furthermore, a specific subtype of CAFs expressing αSMA, VIM and PDGFRβ and its spatial location relative to a particular ovarian cancer cell subtype in the TME correlated with long-term survival in advanced HGSC patients. We also characterized region-specific ligand-receptor interactions by analyzing crosstalk signaling in neighboring spots at the stroma-tumor interface. Using this method and subsequent validation studies by multiplex immunohistochemistry we found that increased APOE-LRP5 crosstalk occurred at the stroma-tumor interface in tumor tissues from STS compared to LTS. These findings suggest that a strong crosstalk signaling network between tumor-derived LRP5 and CAF-derived APOE may confer a more aggressive phenotype of the HGSC, which contribute to poorer patient survival rates. Further studies to confirm whether such crosstalk plays a role in modulating the malignant phenotype of HGSC and could serve as a predictive biomarker of patient survival are warranted. Citation Format: Sammy Ferri-Borgogno, Ying Zhu, Jianting Sheng, Jared K. Burks, Javier A. Gomez, Kwong Kwok Wong, Stephen TC Wong, Samuel C. Mok. Long-term ovarian cancer survivors: spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A095.

Side Effects from Cancer Therapies and Perspective of 1044 Long-Term Ovarian Cancer Survivors-Results of Expression VI-Carolin Meets HANNA-Holistic Analysis of Long-Term Survival with Ovarian Cancer: The International NOGGO, ENGOT, and GCIG Survey.

The aim of this survey was to increase the knowledge on the characteristics and health concerns of long-term survivors (LTS; survival > 5 years) after ovarian cancer in order to tailor follow-up care. This international survey was initiated by the NOGGO and was made available to members of ENGOT and GCIG. The survey is anonymous and consists of 68 questions regarding sociodemographic, medical (cancer) history, health concerns including distress, long-term side effects, and lifestyle. For this analysis, 1044 LTS from 14 countries were recruited. In total, 58% were diagnosed with FIGO stage III/IV ovarian cancer and 43.4% developed recurrent disease, while 26.0% were receiving cancer treatment at the time of filling in the survey. LTS who survived 5-10 years self-estimated their health status as being significantly worse than LTS who survived more than 10 years (p = 0.034), whereas distress also remained high 10 years after cancer diagnosis. Almost half of the cohort (46.1%) reported still having symptoms, which were mainly lymphedema (37.7%), fatigue (23.9%), pain (21.6%), polyneuropathy (16.9%), gastrointestinal problems (16.6%), and memory problems (15.5%). Almost all patients (94.2%) regularly received follow-up care. Specialized survivorship care with a focus on long-term side effects, lifestyle, and prevention should be offered beyond the typical five years of follow-up care.

Fear of recurrence, emotional well-being and quality of life among long-term advanced ovarian cancer survivors

ObjectiveAlthough advanced stage epithelial ovarian cancer is widely considered life-threatening, 17% of women with advanced disease will survive long-term. Little is known about the health-related quality of life (QOL) of long-term ovarian cancer survivors, or how fear of recurrence might affect QOL. Methods58 long-term survivors with advanced disease participated in the study. Participants completed standardized questionnaires to capture cancer history, QOL, and fear of recurrent disease (FOR). Statistical analyses included multivariable linear models. ResultsParticipants averaged 52.8 years at diagnosis and had survived >8 years (mean:13.5); 64% had recurrent disease. Mean FACT-G, FACT-O, and FACT-O-TOI (TOI) scores were 90.7 (SD:11.6), 128.6 (SD:14.8), and 85.9 (SD:10.2) respectively. Compared to the U.S. population using T-scores, QOL for participants exceeded that of healthy adults (T-score (FACT-G) = 55.9). Overall QOL was lower in women with recurrent vs. non-recurrent disease though differences did not reach statistical significance (FACT-O = 126.1 vs. 133.3, p = 0.082). Despite good QOL, high FOR was reported in 27%. FOR was inversely associated with emotional well-being (EWB) (p < 0.001), but not associated with other QOL subdomains. In multivariable analysis, FOR was a significant predictor of EWB after adjusting for QOL (TOI). A significant interaction was observed between recurrence and FOR (p = 0.034), supporting a larger impact of FOR in recurrent disease. ConclusionQOL in long-term ovarian cancer survivors was better than the average for healthy U.S. women. Despite good QOL, high FOR contributed significantly to increased emotional distress, most notably for those with recurrence. Attention to FOR may be warranted in this survivor population.

Spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface in long-term ovarian cancer survivors.

Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. To investigate the stromal heterogeneity of the tumor microenvironment (TME) in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival in patients with advanced HGSC. Spatial transcriptomics and single-cell RNA sequencing data were integrated to distinguish tumor and stroma regions, and a computational method was developed to investigate spatially resolved ligand-receptor interactions between various tumor and CAF subtypes in the TME. A specific subtype of CAFs and its spatial location relative to a particular ovarian cancer cell subtype in the TME correlated with long-term survival in advanced HGSC patients. Also, increased APOE-LRP5 crosstalk occurred at the stroma-tumor interface in tumor tissues from STS compared to LTS. These findings were validated using multiplex immunohistochemistry. Overall, this spatial transcriptomics analysis revealed spatially resolved CAF-tumor crosstalk signaling networks in the ovarian TME that are associated with long-term survival of HGSC patients. Further studies to confirm whether such crosstalk plays a role in modulating the malignant phenotype of HGSC and could serve as a predictive biomarker of patient survival are warranted.

46P Long-term residual chemotherapy-induced peripheral neuropathy (CIPN) and relationship with single nucleotide polymorphisms (SNPs) in ovarian cancer patients free of disease in the GINECO Vivrovaire study

Paclitaxel and carboplatin remains a backbone treatment of ovarian cancer (OC) inducing peripheral neuropathy in a significant proportion of patients. Meanwhile, long term survival of OC has dramatically increased with the recent therapeutic progress. Predictive factors for long-term CIPN are needed considering the impact on quality of life (Qol) of patients. We investigated the link between the incidence of CIPN and selected genetic polymorphisms in a cohort of ovarian cancer survivors. Vivrovaire is a French multi-center long-standing cohort of ovarian cancer patients free of disease 3 years after the end of the primary treatment. Long-term analysis of Qol in linked with neuropathy was performed including peripheral neuropathy assessed by the FACT/GOG-Ntx4 self-questionnaire. CIPN scores were correlated with SNPs in the selected CYP2C8, CYP3A4, ERCC1 and XPC genes. 130 patients were included with a median time from the end of chemotherapy of 63 months [35-180]. Median CIPN score was 37 [18-44] with 35 patients (27 %) having a severe score (< 33). SNPs (homozygotous/heterozygotous) were identified as follows: CYP2C8 [n=32 (24.6%)/ n=99 (76%)]; CYP3A4 [n=0 (0%)/ n=8 (6.1%)], ERCC1 [n=21 (16.1%)/ n=57 (43.8%)] and XPC [n=45 (34.6%)/ n=66 (50.8%)]. In univariate analysis, homozygous SNP (ho SNP) in any of the selected genes was associated with CIPN score as a continuous variable (p=0.045) but not with severe score (< 33) (OR: 1.66; 95% CI [0.74-3.88], p=0.22). Patients with CYP2C8_rs1934951 SNP tend to have CIPN score <33, (OR: 2.22; 95% CI [0.98-5.02], p=0.057). In multivariate analyses including age, interval from the end of chemotherapy, type and number of chemotherapy courses, identification of homozygotous or heterozygotous CYP2C8_rs1934951 SNP was associated with a severe CIPN score (OR: 2.41; 95% CI [1.02-5.70], p=0.043). Our study shows that residual CIPN is a frequent concern for ovarian cancer survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in long-term survivors of ovarian cancer.

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer.

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer.

Long-Term Survival Among Histological Subtypes in Advanced Epithelial Ovarian Cancer: Population-Based Study Using the Surveillance, Epidemiology, and End Results Database.

BackgroundActual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported.ObjectiveThis study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC.MethodsWe performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan–Meier analysis, and multivariate Cox proportional hazards model for the analyses.ResultsWe included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P<.001), mucinous (HR 0.454, P<.001), and clear cell (HR 0.563, P<.001) subtypes showed better ovarian cancer-specific survival than those with the serous subtype. Similar results were found regarding overall survival. However, ovarian cancer–specific survival and overall survival were comparable among those with endometrioid, clear cell, and mucinous tumors.ConclusionsOvarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.

Attributions of survival and methods of coping of long-term ovarian cancer survivors: a qualitative study

BackgroundOnly 8–23% of advanced epithelial ovarian cancer patients survive for 10 years or longer. Given the need for targeted interventions to improve survival, we interviewed this relatively rare survivor population to gain personalized insights into the reasons for their survival. The aim of this study was to characterize subjective attributions of survival and specific coping mechanisms long-term survivors of ovarian cancer.MethodsTwenty-two semi-structured, qualitative interviews assessing survival attributions and coping strategies were conducted from April to November 2014. Data were analyzed in a multistep process using ATLAS.ti.8: codes were identified during review of the transcripts and refined with literature review; the frequency of codes and code co-occurrence was calculated, and codes were grouped into themes. Resulting themes were checked by a national leader of an ovarian cancer advocacy organization and compared against available literature.ResultsThematic analysis found that participants credited their long-term survival to a variety of factors including medical, social, religious/spiritual, and lifestyle/personal characteristics. Some participants rejected these same attributions, concluding that the reason for survival was due to luck or unknowable. Several of Carver et al.’s theoretical dimensions of coping were evident in our sample: planning, positive reinterpretation, social support, religion and acceptance whereas three relatively new strategies were uncovered: conserving emotional energy, value-based activity coping, and self-care.ConclusionsLong-term survivors’ perspectives were largely consistent with those of newly diagnosed ovarian cancer patients and ovarian cancer survivors of shorter duration. However, the long-term survivors were also willing to reject conventional attributions for survival and recognized the importance of disciplined self-preservational coping strategies.

Gynecologic Cancers: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner.

Laura Doherty, FNP-BC, AOCNP®, of Women &amp; Infants Hospital of Rhode Island/Brown University, interprets data on adjuvant chemotherapy for locally advanced cervical cancer, bevacizumab for advanced ovarian cancer, a new treatment option for platinum-resistant ovarian cancer patients, and side effects that long-term ovarian cancer survivors experience. Reporting by The ASCO Post.

Secondary malignancies in long-term ovarian cancer survivors: results of the ‘Carolin meets HANNA’ study

ObjectiveTo evaluate the rate of secondary malignancies in long-term survivors with ovarian cancer.MethodsLong-term survivors with ovarian cancer (survival ≥8 years after initial diagnosis) with multiple malignancies were identified within the...

Abstract A26: Molecular analysis of short- vs. long-term ovarian cancer survivors

Abstract Background: High-grade serous ovarian carcinomas (HGSOC) comprise the majority of ovarian cancer cases and usually present at diagnosis with late stages of disease. Despite having similar histology, patients with HGSOC often experience highly variable outcomes. The underlying determinants for long-term (LT- ≥10 years) versus short-term (ST- &amp;lt;3 years) survival are largely unknown. The present study sought to identify molecular predictors of LT survival for women with HGSOC. To achieve this, we used deep molecular analysis of tumors from LT and ST survival patients of HGSOC. Methods: For the discovery tumor cohort, RNA sequencing was conducted on twenty-four (24) frozen samples HGSOC tumors (12 from LT and 12 from ST survivors). A validation cohort included 29 samples (15 from LT and 14 from ST survivors). In vitro studies were carried out using OVCAR8 and SKOV3 cell lines. Results: From RNAseq analysis, a total of 11 genes were differentially expressed between ST and LT survivors (fold change &amp;gt;2, p &amp;lt; 1 × 10-5, FDR &amp;lt;0.01). A secondary screen was used to eliminate genes that were expressed below threshold levels (fold change &amp;gt;2). Three genes were overexpressed in LT survivors; one had sufficient expression for future therapeutic benefit—TMEM62. In the subsequent validation cohort, TMEM62 had the most significant result of the initial genes of interest, with qRT-PCR data demonstrating an average 3.0-fold higher expression of TMEM62 mRNA in LT versus ST survivors. Next, OVCAR8 and SKOV3 ovarian cancer cells were transfected with TMEM62 using a bacterial plasmid; increased expression of TMEM62 led to decreased proliferation (OVCAR8 73%; SKOV3: 33%), invasion (OVCAR8: 73%; SKOV3: 33%), and a slight decrease in migration (about 2%) in both cell lines. Using a protein array, a decrease in chemokines in SKOV3 cells (MIF, Serpin E1, IL6, CXCL7, IL8, Midkine, and CXCL1) was observed, suggesting that increased TMEM62 expression may lead to reduced tumor inflammatory markers. Conclusion: Our results demonstrate that TMEM62 may be a novel treatment target for HGSOC given its much higher expression in those patients who achieve long-term survival. These findings may have implications for biomarker and intervention strategies to help improve patient outcomes. Citation Format: Elaine Stur, Graziela Zibetti Dal Molin, Sherry Wu, Keith Baggerly, Shelley Tworoger, Douglas Levine, Beth Karlan, Kathleen Moore, Susan Lutgendorf, Anil Sood. Molecular analysis of short- vs. long-term ovarian cancer survivors [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A26.

Abstract IA06: The Long-Term Ovarian Cancer Survivor Project: A Department of Defense initiative

Abstract In 2019 there will be 22,500 new cases of ovarian cancer, resulting in approximately 14,000 deaths. Ovarian cancer remains the highest case fatality rate of any gynecologic cancer. Despite significant improvement in the surgical and chemotherapeutic managements of ovarian cancer patients, the overall survival has not changed in 30 years. However, these new therapies have resulted in a significant improvement in median survival, resulting in increasing numbers of patients surviving greater than 10 years with disease. The clinical and molecular features of these unique patients remain uncharacterized. The Department of Defense Ovarian Cancer Research Program (DOD OCRP) funded the creation of our interdisciplinary Long-term Survivor Consortium (LTSC), composed of 6 research sites including MDACC, UAB, IU, UCI, Ludwig Cancer Research, and University Hospitals of Canton Vaud (CHUV) and INOVA, a bioinformatic center at DFCI, and administrative centers at UCI and UAB. The purpose of the consortium is to identify characteristics and predictors of long-term survival in advanced ovarian cancer patients. The consortium is overseen by both a scientific and advocacy advisory board to guide direction and efforts. 285 specimens of advanced-stage high-grade serous ovarian cancers with full clinical annotation including greater than 12 years of follow-up were analyzed for this project. In addition, 340 early-stage high-grade ovarian cancers were available for one of the AIMs of the project. These latter samples were obtained through the creation of an international consortium funded by the DOD OCRP. All specimens were first reviewed for tumor context by H&amp;E staining to determine percentage of tumor. The scientific platforms include whole transcriptome, microRNAs, global proteomics, immune profiling, and methylation. All specimens were analyzed on each individual platform and the results will be integrated in a global process. In parallel with these efforts, a systematic analysis of quality of life of patients at the time of diagnosis and later during the course of their disease based upon patient-reported outcome surveys has been undertaken. These data will also be integrated with genomic results to produce signatures that can further characterize long-term survivors of ovarian cancer. Citation Format: Michael J. Birrer, Lari Wenzel, Austin Miller, Heather Lankes, Nilsa Ramirez, Giovanni Parmigiani, Samuel Mok, Kenneth Nephew, Thomas Conrads, George Coukos, George L. Maxwell, Giulia Fulci, Mary Scroggins. The Long-Term Ovarian Cancer Survivor Project: A Department of Defense initiative [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA06.

Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer

Fatigue is a challenge in ovarian cancer survivorship and greatly impacts quality of life. In other cancer populations, fatigue has been associated with abnormal diurnal cortisol patterns. However, little is known about biological and behavioral factors in 5+-year ovarian cancer survivors and potential mechanisms underlying persistent fatigue have not been investigated in this population. Moreover, relationships between neuroendocrine and psychosocial factors in 5+-year ovarian cancer survivors have not been studied. We addressed these issues by examining relationships between diurnal cortisol rhythms, fatigue, life stress, and social support in 30 survivors of ovarian cancer who were assessed at least 5 years (mean=6.20years) following their primary diagnosis. Flatter diurnal cortisol slopes were associated with higher levels of fatigue, suggesting a role for HPA-axis dysregulation in sustained fatigue experienced by survivors. Moreover, greater cumulative lifetime stressor exposure (p=0.023) and stressor severity (p=0.004) were associated with flatter diurnal cortisol slopes, while higher social attachment (p=0.001) was associated with steeper diurnal cortisol slopes. These findings suggest that ovarian cancer survivors with greater lifetime stress exposure or lower social attachment may be at increased risk for circadian rhythm disruption, which in turn is associated with fatigue. Future research should examine relationships of clinical stage and inflammatory cytokines to cortisol rhythms and fatigue in long-term ovarian cancer survivors, as well as investigating the clinical significance of abnormal diurnal cortisol profiles in this population.

Quality of life among long-term ovarian cancer survivors.

e21570Background: A consortium of multi-disciplinary investigators and patient advocates was assembled to address key questions related to outcomes of long-term (LT) survivors with ovarian cancer (...

Long-term mortality among women with epithelial ovarian cancer

ObjectivesPatients with solid tumors are at greatest risk for dying from their cancers in the five years following diagnosis. For most malignancies, deaths from other chronic diseases begin to exceed those from cancer at some point. As little is known about the causes of death among long-term survivors of ovarian cancer, we examined causes of death by years from diagnosis. MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with ovarian cancer between 1988 and 2012. We compared causes of death by stage, age, and interval time after diagnosis. ResultsA total of 67,385 women were identified. For stage I neoplasms, 13.6% (CI, 13.0–14.2%) died from ovarian cancer, 4.2% (CI, 3.8–4.5%) from cardiovascular disease, 3.6% (CI, 3.3–3.9%) from other causes and 2.6% (CI, 2.4–2.9%) from other tumors; ovarian cancer was the leading cause of death until 7years after diagnosis after which time deaths are more frequently due to other causes. For those with stage III–IV tumors, 67.8% (CI, 67.3–68.2%) died from ovarian cancer, 2.8% (CI, 2.6–2.9%) from other causes, 2.3% (CI, 2.2–2.4%) from cardiovascular disease and 1.9% (CI, 1.7–2.0%) from other cancers; ovarian cancer was the most frequent cause of death in years 1–15 after which time deaths were more commonly due to other causes. ConclusionsThe probability of dying from ovarian cancer decreases with time. Ovarian cancer remains the most common cause of death for 15years after diagnosis in women with stage III–IV tumors.

Prospective assessment of quality of life in long‐term ovarian cancer survivors

The objective of our study was to compare prospectively the QoL in long-term ovarian cancer survivors with short-term survivors and to explore discriminating variables between short-term and long-term survival. Thirty-three patients were included, 22 died within 5 years post diagnosis and 11 survived beyond 10 years. QoL data were collected pre-treatment (baseline), 1-year post diagnoses and for long-term survivors 10 years post-treatment using the EORTC QLQ-C30. At baseline, there was no difference in terms of FIGO stage, residual tumor and adjuvant chemotherapy. Significantly, more short-term survivors (96%) had intra operative ascites as compared to long-term survivors (55%) (p = 0.01). Before treatment, short-term survivors had clinically significantly lower QoL scores on the physical functioning (mean 75.45) and role functioning scale (mean 68.94) compared to long-term survivors (mean 68.94 and 84.85, respectively). They also reported higher levels of symptoms. One year post-diagnosis, QoL scores were comparable in most domains. Long-term survivors had a significantly better global QoL but more insomnia. Emotional functioning and global QoL/health status improved significantly from baseline to 1-year post-diagnosis and remained relatively stable at the 10-year follow-up. The presence of intra operative ascites and a supporting social network were identified as significant variables that discriminated between short-term and long-term survival. Compared to a reference sample, long-term survivors showed similar QoL scores but more dyspnoea. Although ovarian cancer patients do not belong to the most prevalent survivor populations, we found that long-term survivors have QoL scores similar to females without a history of cancer.

Cognitive functions in long-term survivors of ovarian cancer

Background Women diagnosed with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about the incidence of cognitive adverse effects of chemotherapy in survivors of this disease. This cross-sectional study assessed neuropsychological functions in long-term survivors of ovarian cancer who were either in complete remission or with evidence of recurrent disease. Methods Forty-eight women diagnosed with ovarian cancer 5 to 10 years prior to study enrollment underwent a brief neuropsychological evaluation; 22 patients were disease free and without history of recurrence (Group 1), and 26 patients had recurrent disease and were receiving treatment with chemotherapy or hormonal therapy (Group 2). Results There were no statistically significant differences between the two patient groups on tests of attention, memory, and executive functions. Group mean cognitive test scores were within the average range on all tests; however 28% of patients met criteria for cognitive impairment, a significantly higher frequency (p = 0.03) than reported in healthy populations. Conclusions In this study, neuropsychological test performance did not differ significantly between ovarian cancer survivors who were in remission and patients with recurrent disease and receiving treatment. Cognitive impairment was evident in a subset of patients, although group means test scores were within the average range. Additional research using prospective longitudinal designs is needed to clarify the contribution of disease, chemotherapy, hormonal therapy, and other risk factors to cognitive outcome in this clinical population.

Patterns of Gene Expression That Characterize Long-term Survival in Advanced Stage Serous Ovarian Cancers

A better understanding of the underlying biology of invasive serous ovarian cancer is critical for the development of early detection strategies and new therapeutics. The objective of this study was to define gene expression patterns associated with favorable survival. RNA from 65 serous ovarian cancers was analyzed using Affymetrix U133A microarrays. This included 54 stage III/IV cases (30 short-term survivors who lived <3 years and 24 long-term survivors who lived >7 years) and 11 stage I/II cases. Genes were screened on the basis of their level of and variability in expression, leaving 7,821 for use in developing a predictive model for survival. A composite predictive model was developed that combines Bayesian classification tree and multivariate discriminant models. Leave-one-out cross-validation was used to select and evaluate models. Patterns of genes were identified that distinguish short-term and long-term ovarian cancer survivors. The expression model developed for advanced stage disease classified all 11 early-stage ovarian cancers as long-term survivors. The MAL gene, which has been shown to confer resistance to cancer therapy, was most highly overexpressed in short-term survivors (3-fold compared with long-term survivors, and 29-fold compared with early-stage cases). These results suggest that gene expression patterns underlie differences in outcome, and an examination of the genes that provide this discrimination reveals that many are implicated in processes that define the malignant phenotype. Differences in survival of advanced ovarian cancers are reflected by distinct patterns of gene expression. This biological distinction is further emphasized by the finding that early-stage cancers share expression patterns with the advanced stage long-term survivors, suggesting a shared favorable biology.

Terminal restriction fragments of telomere are detectable in plasma and their length correlates with clinical status of ovarian cancer patients.

Free plasma DNA was extracted and terminal restriction fragment (TRF) sequences were amplified by polymerase chain reaction in 32 patients with stage 3 and stage 4 ovarian cancer and 45 healthy controls. Three peaks of TRF were identified and the size of the largest peak (peak 1) correlated with cancer telomere length in cancer patients. Average size of peak 1 in cancer patients was significantly shorter than in controls. When plasma TRF peak 1 was tested pre- and post-treatment, the average pre-treatment size was 8.7 +/- 0.5 Kb, lengthening significantly post-treatment. In long-term survivors of ovarian cancer (10-year disease-free survival), plasma TRF length was the same as in normal controls. The results suggest that the plasma TRF in ovarian cancer patients is of tumour origin. Its determination may reflect tumour cell viability in the host.