Quality of life and survival in advanced cervical cancer: a Gynecologic Oncology Group study

Purpose

To determine associations between pretreatment health-related quality of life subscales with progression-free (PFS) and overall survival (OS) in advanced and recurrent cervical cancer.

Patients and Methods

Patients included those participating in Gynecologic Oncology Group advanced or recurrent cervical cancer phase III treatment trials who completed the Functional Assessment of Cancer Therapy for patients with cervical cancer (FACT-Cx) and a single-item pain scale at study entry. The FACT-Cx includes five domains: physical (PWB), emotional (EWB), social (SWB), functional well being (FWB), and cervix cancer subscale (CCS). A high quality of life (QoL) score reflects better QoL. After stratifying by protocol and adjusting for patient and disease characteristics, a Cox proportional hazards model was fitted for each subscale as a continuous variable. If statistically significant, (p < 0.05), an analysis on mean item scores (MIS) was performed.

Results

Nine-hundred-ninety-one patients were enrolled from 1997 to 2007. The majority (87%) had recurrent disease. After adjustment for covariates and predictors, only the PWB domain (better physical QoL) was associated with improved OS [HR 0.96 95% CI 0.95-0.98; p < 0.001]. When classifying patients based on the MIS of each subscale, the patients with the lowest risk of death were likely to report less compromised QoL (MIS > 3) for PWB [HR 0.44 (0.33-0.58) P < 0.001], FWB [0.49 (0.38-0.62) P < 0.001], and CCS [0.48 (0.38-0.61) P < 0.001].

Conclusion

The pretreatment patient-reported PWB as measured by the PWB subscale of the FACT-Cx, is significantly associated with survival in advanced cervical cancer trials, even after controlling for known prognostic factors.     

Quality of life evaluations in patients with ovarian cancer during chemotherapy treatment

OBJECTIVES: To examine the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. PATIENTS AND METHODS: Over 18 months period, all patients with ovarian cancer receiving chemotherapy at the Saskatoon Cancer Center were recruited. The Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire was used to assess patients' quality of life before each chemotherapy cycle. Platinum-based chemotherapy was used initially or in patients with a platinum-free interval of more than 6 months in a recurrence setting. After progression on the platinum-based regimens, liposomal doxorubicin, topotecan, and cisplatinum/etoposide were used as salvage chemotherapy pending on drug availability and convenience of administration to patients. Regression analysis was used to identify significant disease and treatment-related factors that can significantly affect patients' quality of life measures. RESULTS: Seventy-two patients participated in the study providing 270 separate observations. The mean age was 57.81 years with a standard deviation of 13.40. The median duration of chemotherapy-free interval for patients with recurrent disease was 7 months. All patients had stage 3 or 4 disease. About half (52.2%) of the patients had optimal surgical resection with small (<1 cm) residual cancer masses before primary adjuvant chemotherapy. Seventy percent of the patients had either a first diagnosis or a first recurrence of cancer with the other 30% previously treated with two or more chemotherapy regimens. Sixty-two percent had an initial complete response to platinum-based chemotherapy. Multivariate regression analysis showed the use of topotecan or cisplatinum/etoposide, patients' poor responses to chemotherapy, experience with two or more previous line of chemotherapy treatment, and younger ages were significant predictors of poor quality of life during chemotherapy. CONCLUSION: There were significant differences in side effects of commonly used chemotherapy regimens on patients' quality of life. Quality of life assessments should be routinely incorporated in selecting specific chemotherapy to be used. Future research should be carried out to identify the best strategies to further integrate the results of quality of life assessments in cancer treatment protocols and to examine the long-term effects of cancer and its treatment on patients and their families.     

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study

Objective

To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors.

Quality of life in long-term survivors of ovarian germ cell tumors: a Gynecologic Oncology Group study

PURPOSE: This report describes the strength and significance of the association between antecedent and mediating variables across four categories of quality of life (QOL) outcomes in 132 disease free women with ovarian germ cell survivors. METHODS: Survivors (n=132) participated in a mailed questionnaire and computer-assisted telephone survey. Participants in four prospective GOG protocols were contacted their treating physician for verbal consent to be approached by investigators at the Indiana University Cancer Center about a quality of life study. Similar patients treated at the MD Anderson Cancer Center were also included. If women verbally consented after being contacted by investigators at Indiana University, an informed consent and questionnaire packet was sent via mail. After return of the written informed consent and background questionnaire, a trained research assistant scheduled a computer-assisted interview to complete data collection. RESULTS: Median follow-up from diagnosis was 10.2 years. Mediating variables of self-efficacy or social support played a significant role (p=0.05 to p=0.001) in all four QOL categories: physical functioning, psychological functioning, sexual functioning, and spiritual functioning. Being a younger age at diagnosis and married were positively related to sexual functioning (p=0.05). Menstrual and gynecological symptoms were inversely related. IMPLICATIONS: Results indicate that clinicians may want to be especially sensitive to identifying a survivor's social support and confidence (self efficacy) in handling issues evolving from treatment since these skills may be related to overall quality of life outcomes.     

Bevacizumab improves overall survival in platinum refractory ovarian cancer patients: A retrospective study

Objective

The objective of this study was to determine the effectiveness of bevacizumab (BV) in combination with chemotherapeutic regimens for prolonging progression-free survival (PFS) as well as overall survival (OS) in patients with platinum-refractory ovarian cancer.

Cognitive function and quality of life in ovarian cancer

Objectives

As advances in treatment have prolonged survival for many patients with ovarian cancer, there has been growing interest in assessing the adverse effects of disease and treatment. The aim of this study was to review the literature on cognitive function and quality of life (QOL) in this population.

Methods

A review of published studies including formal assessment of neurocognitive functions and self-reported domains of quality of life, with an emphasis on cognitive function, was performed.

Results

The small number of studies including formal evaluations of neurocognitive function suggests that many ovarian cancer patients experience cognitive difficulties associated with their disease and treatment. Several studies described declines in self-reported cognitive function that may impact QOL, but the results were not consistent across studies.

Conclusions

Adequately powered longitudinal studies including formal neurocognitive and QOL assessments are needed to advance our understanding of the incidence of cognitive dysfunction and its impact on functional ability and QOL in ovarian cancer patients. These research efforts may ultimately contribute to treatment decision-making through the identification of vulnerable patients, and to the development of appropriate intervention strategies to improve cognitive function and QOL.     

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

Objective

To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer.

Methods

A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts.

Results

Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented.

Conclusions

Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken.     

The effect of sleep disturbance on quality of life in women with ovarian cancer

Objective

To estimate the prevalence of sleep disturbances, and to determine if there is an association between sleep disturbances with quality of life (QOL), depression or clinical demographic variables.

Methods

Patients diagnosed with ovarian, fallopian tube or primary peritoneal cancer during the last 5 years completed questionnaires regarding sleep patterns and disturbances [Pittsburgh Sleep Quality Index (PSQI)], depression [Beck Depression inventory (BDI)], and QOL [The Functional Assessment of Cancer Therapy-Ovarian (FACT-O), fatigue module (− F)]. Data were analyzed by Student's t-test or Pearson correlation coefficient to determine if there were differences between PSQI score with QOL, depression or clinical demographic variables.

Results

86/275 (31% response) of patients returned the surveys. Mean age was 58.1 (SD = 14.6) years and 70% had advanced disease at diagnosis. Thirty-six percent had current disease of which 81% were receiving chemotherapy. Sixty-seven percent of patients had a PSQI score ≥ 5 corresponding to overall poor sleep quality and 46% of patients reported using sleep medication at least once during the prior month. PSQI score was significantly inversely correlated with all QOL domains (physical: r = −.599, p < .001, functional: r = −.692, p < .001, social: r = −.212, p < .001, emotional: r = −.379, p < .001, fatigue; r = −.655 p < .001) and with depression (r = .539, p < .001). PSQI was not correlated with age, time since diagnosis, number of previous chemotherapy regimens. PSQI score did not differ by current disease or chemotherapy status.

Conclusions

Sleep disturbances reduce QOL, a prognostic indicator for survival, in ovarian cancer patients. These patients should undergo routine screening and would benefit from interventions that aim to promote restful sleep.     

Non-cancer life stressors contribute to impaired quality of life in ovarian cancer patients

Objectives

Diagnosis and treatment for a life threatening illness such as cancer are known to be psychologically impactful. However, little is known about the influence that non-cancer life stressors have on the quality of life (QOL) of ovarian cancer patients. The goal of the present study was to examine associations between non-cancer life stressors and QOL in 123 women with invasive epithelial ovarian cancer who were followed prospectively and longitudinally for one year.

Methods

Mixed models for repeated measures were used to examine the relationship between life stressors and QOL pre-surgery and one year later, while adjusting for age, cancer stage, depressive symptoms, anxiety, and chemotherapy status (at one year). Prospective associations between QOL pre-surgery and one-year QOL were also examined.

Results

Number and severity of life stressors were unrelated to QOL of participants before surgery. At one year, however, participants experiencing a greater number of life stressors reported poorer concurrent physical well-being (PWB) (p = 0.015), functional well-being (FWB) (p < 0.0001), social well-being (SWB) (p = 0.0003), and total QOL (p < 0.0001). Similar effects were found for life event severity. Finally, experiencing a greater number of life stressors pre-surgery predicted poorer overall QOL one year post-diagnosis (p < 0.0001).

Conclusions

Non-cancer life stressors can substantially impact long-term QOL of ovarian cancer patients, adjusting for medical variables such as chemotherapy and cancer stage, thus highlighting the importance of evaluating the stress burden of patients in ongoing cancer care.     

A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer

Objective

Although overall survival is the ultimate goal of cancer therapy, many clinical and health economic decisions are taken when only progression free survival (PFS) data are available. This study evaluates the relationship between PFS and post progression survival (i.e. the time between disease progression and death) to estimate how many months a new drug for ovarian cancer might add to overall survival if the number of months the drug added to PFS (relative to a standard drug) was already known.

Methods

A literature search was conducted over Medline for randomised controlled trials published between January 1990 and July 2010 that evaluated the effect of a drug treatment in comparison to alternative drug treatment in patients with either advanced stage primary or recurrent ovarian cancer. A systematic review of progression free and post progression survival (PPS) was performed. The relationship between PFS and PPS was evaluated by a graphical method and standard statistical tests.

Results

Thirty-seven trials involving 15,850 patients met the inclusion criteria. The review found that increases in median PFS generally lead to little change in post-progression survival. Percentage gains in PFS are generally associated with no percentage gains or with very slight percentage gains or losses in post-progression survival

Conclusion

If the effect of a new drug treatment for ovarian cancer is to extend median PFS by x months, then it is reasonable to estimate that the treatment will also extend median overall survival by x months. This information will be useful for individual and collective decision making.     

Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: An exploratory study of the Gynecologic Oncology Group

Objective

To determine whether chemotherapy-induced neutropenia (C-iN) is associated with improved survival in a population of primary advanced ovarian cancer and peritoneal carcinoma patients treated with a carboplatin plus paclitaxel chemotherapy backbone.

Methods

A post-hoc exploratory analysis of Gynecologic Oncology Group (GOG) protocol 182 was performed. Landmark analysis was conducted on all patients with progression-free survival > 18 weeks from the time of study entry. Neutropenia was defined as the absolute neutrophil count < 1000 mm³. The occurrence of C-iN was analyzed according to demographic, clinicopathologic, and therapeutic intent, including age, body surface area, and treatment arm. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The Cox proportional hazards model was used to evaluate independent prognostic factors and to estimate their effects on PFS and OS.

Results

Neutropenic data was available for 3447 patients. Neutropenic (n = 3196) and non-neutropenic groups (n = 251) were similar in demographic and clinicopathologic characteristics. Neutropenic patients experienced significantly improved survival compared to non-neutropenic patients with the adjusted hazard ratio (HR) for death being 0.86 (95% confidence interval 0.74–0.99; p = 0.041). There was no survival benefit associated with any of the treatment arms among patients with C-iN.

Conclusion

These data suggest that C-iN may represent a clinical biomarker associated with a survival advantage for patients with untreated advanced ovarian cancer. The absence of C-iN may indicate under-dosing and ultimately attenuated anti-neoplastic effect in vulnerable populations.     

血小板增多与上皮性卵巢癌临床病理及生存预后的相关性研究

目的:研究术前血小板(PLT)与卵巢癌临床病理和预后的相关性。方法:回顾分析2009年1月至2013年3月于同济大学附属第一妇婴保健院行手术治疗的171例卵巢癌、218例卵巢良性上皮性肿瘤和59例交界性肿瘤患者的临床资料,分析PLT计数与患者年龄、病理类型、临床分期、细胞分级、CA125水平等临床病理因素之间的关系,同时分析比较卵巢癌伴或不伴PLT增多以及化疗后PLT变化对患者生存的影响。结果:卵巢癌患者术前PLT计数平均值为248.0×109/L,显著高于良性及交界性肿瘤(188.3×109/L和206.9×109/L,P0.0001)。171例卵巢癌患者中20例(11.7%)合并血小板增多(PLT≥350×109/L),卵巢癌合并PLT增多的患者中晚期比例高(P=0.030),更易发生大网膜(P=0.006)、腹膜(P=0.016)、膈下腹膜(P=0.018)转移,达到满意肿瘤减灭术比例较低(P=0.010)。卵巢癌患者的术前PLT与CA125值呈正相关(P=0.049)。患者术前PLT计数分别为≥232.2×109/L、208.5×109/L和327.5×109/L时,可依次最大程度预测卵巢癌减灭手术不满意、疾病处于晚期及总体预后不良。卵巢癌合并PLT增多及术前PLT与3周期化疗后PLT比值大于2的患者的生存时间明显缩短(P0.0001,P=0.006)。结论:卵巢癌患者术前PLT计数显著高于良性及交界性卵巢肿瘤。合并PLT增多的患者晚期肿瘤及多脏器转移比例显著增高,满意肿瘤减灭术比例低。PLT增多及化疗后PLT较术前显著下降是卵巢癌的不良预后指标。     

Ovarian stimulation for oocyte vitrification does not modify disease-free survival and overall survival rates in patients with early breast cancer

Research questionDoes ovarian stimulation for oocyte vitrification affect disease-free survival and overall survival rates in women with early breast cancer?DesignThis cohort study included 259 patients with early breast cancer; 148 patients underwent ovarian stimulation, whereas 111 patients did not. Patients were treated between January 2008 and December 2016. To calculate the disease-free survival time and overall survival rate, the time of definitive surgery was defined as the starting point. The follow-up was conducted up to 5 years.ResultsExposed and non-exposed groups were comparable in tumour, node and metastases classification, Nottingham grade, hormonal receptor status, tumour molecular phenotype, histology and pathology stage. The exposed group was younger than the non-exposed. Recurrences occurred in 9/148 women (6.1%) in the exposed group and 15/111 women (13.5%) in the non-exposed group, with no significant difference. The mean disease-free survival time was 63.9 months (95% confidence interval [CI]: 61.5–66.4) in the exposed group and 60.6 months (95% CI: 56.9–64.2) in the non-exposed, with no significant difference (log-rank [Mantel–Cox] test). Overall survival rates were comparable; 2/148 (1.4%) and 4/111 (3.6%) patients died, in exposed and non-exposed groups, respectively, during the period analysed. Mean overall survival times were 67.2 months (95% CI: 66.2–68.2) in the exposed group and 65.9 months (95% CI: 64.0–67.9) in the unexposed, with no significant difference (log-rank [Mantel–Cox] test).ConclusionsThis study suggests that ovarian stimulation in patients with early-stage breast cancer is safe in the long term.     

Quality of life assessments in epithelial ovarian cancer patients during and after chemotherapy

To study the immediate and long-term effects of chemotherapy on quality of life (QoL) of advanced ovarian cancer patients. All consecutive patients undergoing chemotherapy for metastatic ovarian cancer and those presenting for follow-up post chemotherapy were recruited. Participants were asked to fill out a short QoL questionnaire (Functional Assessment Cancer Therapy-Ovarian) during each clinic visit. Two-factor analysis of variance analyses were used to examine the effects of chemotherapy treatment and current disease status on QoL scores. Ninety-four patients on chemotherapy and 159 follow-up patients participated. Patients on chemotherapy for recurrent disease had a significantly worsened overall, emotional, and ovarian cancer-specific concerns QoL scores compared to those receiving first-line chemotherapy. There were favorable significant differences between those on follow-up compared to those on chemotherapy in the mean overall QoL scores and in the means of physical, functional, and concern scores. There were significant differences favoring patients with complete response compared to those with partial response or progressive disease in the mean overall QoL scores as well as the physical, emotional, functional, and concern domains mean scores. There were improvements in most QoL measures after completion of chemotherapy. Complete disease remission remained important in maintaining improved QoL.     

A comparison of primary intraperitoneal chemotherapy to consolidation intraperitoneal chemotherapy in optimally resected advanced ovarian cancer

Objective

To compare survival outcomes for patients with advanced epithelial ovarian cancer (EOC) who received primary intravenous/intraperitoneal (IV/IP) chemotherapy to those who received IV followed by consolidation (treatment given to patients in remission) IP chemotherapy.

Methods

Data were analyzed and compared for all patients with stage III–IV EOC who underwent optimal primary cytoreduction (residual disease ≤ 1 cm) followed by cisplatin-based consolidation IP chemotherapy (1/2001–12/2005) or primary IV/IP chemotherapy (1/2005–7/2011).

Results

We identified 224 patients; 62 (28%) received IV followed by consolidation IP chemotherapy and 162 (72%) received primary IV/IP chemotherapy. The primary IP group had significantly more patients with serous tumors. The consolidation IP group had a significantly greater median preoperative platelet count, CA-125, and amount of ascites. There were no differences in residual disease at the end of cytoreduction between both groups. The median progression-free survival (PFS) was greater for the primary IP group; however, this did not reach statistical significance (23.7 months vs 19.7 months; HR 0.78; 95% CI, 0.57–1.06; p = 0.11). The median overall survival (OS) was significantly greater for the primary IP group (78.8 months vs 57.5 months; HR 0.56; 95% CI, 0.38–0.83; p = 0.004). On multivariate analysis, after adjusting for confounders, the difference in PFS was not significant (HR 0.78; 95% CI, 0.56–1.11; p = 0.17), while the difference in OS remained significant (HR 0.59; 95% CI, 0.39–0.89; p = 0.01).

Conclusions

In our study, primary IV/IP chemotherapy was associated with improved OS compared to IV followed by consolidation IP chemotherapy in patients with optimally cytoreduced advanced EOC.     

Surgical and survival outcomes of laparoscopic staging surgery for patients with stage I ovarian cancer

Objective

To assess the feasibility and survival outcomes of laparoscopic staging for patients with stage I ovarian cancer.

Caring for women with ovarian cancer in the last year of life: A longitudinal study of caregiver quality of life,distress and unmet needs

Purpose

Caregiver burden, quality of life (QOL) and unmet needs are poorly understood, particularly at the end of life. We explored these issues in caregivers of women with ovarian cancer.

Patients and methods

The Australian Ovarian Cancer Study (AOCS) is a prospective population-based study of women newly diagnosed with primary epithelial ovarian cancer. Ninety-nine caregivers of women participating in the AOCS QOL sub-study (88% response rate) rated their QOL (SF-12), psychological distress (HADS), optimism (LOT), social support (Duke) and unmet needs (SCNS-carers), and patients rated their QOL (FACT-O), every three months for two years. This analysis included measurements in the patient's last year of life.

Results

Caregivers had significantly lower mental and physical QOL than population norms (p < 0.01). Mean distress (p = 0.01) and unmet needs increased over time, however social support remained constant. In linear mixed models, (using scores for each psychosocial variable over time), optimism (p < 0.0001), social support (p < 0.0001), higher unmet needs (p = 0.008), physical wellbeing (p < 0.0001), and time to death (p < 0.0001) but not patient QOL, predicted caregiver mental well-being and distress. Highest unmet needs in the last 6 months related to managing emotions about prognosis, fear of cancer spread, balancing one's own and the patient's needs, impact of caring on work and making decisions in the context of uncertainty.

Conclusions

Aspects of caregiver functioning, rather than patient quality of life, predict caregiver quality of life and distress. Caregivers need help with managing emotions about prognosis, balancing their own and the patient's needs, work, and decision-making when there is uncertainty.