Norman G. Rosenblum

Prevalence and Predictors of Psychological Distress Among Women With Ovarian Cancer

PURPOSE To identify the prevalence of psychological distress among women with ovarian cancer and to examine the association between these symptoms of distress and demographic and medical variables. PATIENTS AND METHODS Participants were 143 women with ovarian cancer. Forty-eight percent of participants had been diagnosed with advanced-stage disease (stage III or IV) and most (80%) were currently receiving treatment. Psychological distress was assessed with the following measures: the Beck Depression Inventory, the Mental Health Inventory, the Impact of Events Scale, and a questionnaire regarding mental health service use. RESULTS Approximately one fifth of women reported moderate to severe levels of distress, and more than half reported high stress responses to their cancer and its treatment. Most participants (60%) were not using any mental health services or psychotropic medications. There was also evidence to suggest that younger patients, patients with more advanced or recurrent disease, and patients who had more recently been diagnosed with ovarian cancer experienced greater psychological distress. CONCLUSION These findings indicate that psychological distress and high stress responses to cancer are prevalent among women with ovarian cancer, suggesting they should be carefully evaluated to determine whether treatment for these symptoms is warranted.

Coping and communication-enhancing intervention versus supportive counseling for women diagnosed with gynecological cancers.

This study compared the efficacy of 2 psychological interventions, a coping and communication-enhancing intervention (CCI) and supportive counseling (SC), in reducing depressive symptoms and cancer-specific distress of women diagnosed with gynecological cancer. Demographic, medical, and psychological moderators of intervention effects were evaluated. Three hundred fifty-three women with gynecological cancer were randomly assigned to 7 sessions of CCI, 7 sessions of SC, or usual care. Intent-to-treat growth curve analyses indicated that participants assigned to CCI and SC reported lower depressive symptoms than participants assigned to usual care at the 6- and 9-month follow-ups. Women with greater than average increases in physician-rated physical symptoms and/or women who were more expressive of positive emotions benefited more from SC than women with lower than average increases in symptom scores and/or women who were less expressive of positive emotions. These findings suggest that both interventions may be effective in treating depressive symptoms among patients with gynecological cancer. Future research should evaluate whether bolstering both psychological interventions with additional intervention sessions and topics in the disease trajectory will result in persistent long-term effects.

Social-cognitive processes associated with fear of recurrence among women newly diagnosed with gynecological cancers

OBJECTIVE This cross sectional study aimed to characterize fears of recurrence among women newly diagnosed with gynecologic cancer. The study also evaluated models predicting the impact of recurrence fears on psychological distress through social and cognitive variables. METHODS Women (N=150) who participated in a randomized clinical trial comparing a coping and communication intervention to a supportive counseling intervention to usual care completed baseline surveys that were utilized for the study. The survey included the Concerns about Recurrence Scale (CARS), Beck Depression Inventory (BDI), Impact of Event Scale (IES), and measures of social (holding back from sharing concerns and negative responses from family and friends) and cognitive (positive reappraisal, efficacy appraisal, and self-esteem appraisal) variables. Medical data was obtained via medical chart review. RESULTS Moderate-to-high levels of recurrence fears were reported by 47% of the women. Younger age (p<.01) and functional impairment (p<.01) correlated with greater recurrence fears. A social-cognitive model of fear of recurrence and psychological distress was supported. Mediation analyses indicated, that as a set, the social and cognitive variables mediated the association between fear of recurrence and both depression and cancer-specific distress. Holding back and self-esteem showed the strongest mediating effects. CONCLUSION Fears of recurrence are prevalent among women newly diagnosed with gynecologic cancer. Social and cognitive factors play a role in womens adaptation to fears and impact overall psychological adjustment. These factors may be appropriate targets for intervention.

Phase I Trial of Multiple Cycles of High-Dose Chemotherapy Supported by Autologous Peripheral-Blood Stem Cells

PURPOSE To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support. PATIENTS AND METHODS Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m(2)) with PBSC and GM-CSF repeated every 28 days. RESULTS Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicities were dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m(2)). The relationship of target AUC to measured AUC was linear (r(2) =. 29; P =.0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks). CONCLUSION Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m(2)) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.

Mediators of a Coping and Communication-Enhancing Intervention and a Supportive Counseling Intervention among Women Diagnosed with Gynecological Cancers

The authors evaluated mechanisms of change for a coping and communication-enhancing intervention (CCI) and supportive counseling (SC). They proposed that the effects of CCI on depressive symptoms would be mediated by psychological processes targeted by CCI, namely increases in the following: positive reappraisal, acceptance, planful problem solving, attempts to understand emotional reactions to cancer, emotional expression, seeking of emotional and instrumental support, and self-esteem. The authors hypothesized that the effects of SC on depressive symptoms would be mediated by the processes encouraged by SC, in this case increases in the following: expression of emotions, attempts to understand emotional reactions to cancer, and self-esteem. Three hundred fifty-three women were randomized to a CCI, SC, or usual care control group and completed measures at preintervention and 3, 6, and 9 months later. The effects of CCI were fully mediated by positive reappraisal, problem solving, and self-esteem and partially mediated by emotional expression. The effects of SC were partially mediated by positive reappraisal. These findings provide support for hypothesized mediators for CCI. The authors were less able to identify mediators for SC. Future research might benefit from identifying SC mediators.

Perceived stress is associated with impaired T-cell response to HPV16 in women with cervical dysplasia.

BackgroundInfection with high-risk subtypes of human papillomavirus (HPV) is a central factor in the development of cervical neoplasia. Cell-mediated immunity against HPV16 plays an important role in the resolution of HPV infection and in controlling cervical disease progression. Research suggests that stress is associated with cervical disease progression, but few studies have examined the biological mechanisms that may be driving this association.PurposeThis study examines whether stress is associated with immune response to HPV16 among women with cervical dysplasia.MethodsSeventy-four women presenting for colposcopy completed measures of health behaviors, stressful life events and perceived stress. A blood sample was obtained to evaluate proliferative T-cell response to HPV16, and a cervical sample was obtained during gynecologic exam for HPV-typing.ResultsMore than 55% tested positive for one or more HPV subtypes. Women who did not show proliferative responses to HPV (i.e. non-responders) were more likely to be HPV+ compared to women who had a response (i.e. responders). Consistent with study hypotheses, logistic regression revealed that higher levels of perceived stress were associated with a non-response to HPV16, controlling for relevant covariates. Stressful life events were not associated with T-cell response to HPV.ConclusionsHigher levels of perceived stress are associated with impaired HPV-specific immune response in women with cervical dysplasia, suggesting a potential mechanism by which stress may influence cervical disease progression.

Long-term Trajectories of Psychological Adaptation Among Women Diagnosed With Gynecological Cancers

Objective: Women diagnosed with gynecological cancers may cope with a difficult treatment regimen that includes multiple abdominal surgeries and courses of chemotherapy and/or radiation. Little attention has been paid to identifying what factors place women at risk for long-term problems with psychological adaptation. The goal of the present study was to identify a set of demographic, medical, and predisposing factors as well as cognitive and social processing strategies that predict the trajectory of psychological distress and well-being among women diagnosed with gynecological cancer. Methods: One hundred thirteen women on active treatment for gynecological cancer completed measures at baseline, 3, 6, and 9 months afterward. Results: Women with poorer physician-rated performance status and self-reported functional impairment, women who were Caucasian, women who have received previous psychological treatments, women who were less expressive of positive emotions, women who had unsupportive friends and family, and women who were less able to find something positive in the cancer experience reported poorer adaptation. Conclusions: This study identified a set of risk factors for poor long-term psychological adaptation among women diagnosed with gynecological cancers. Healthcare professionals working with these women can use these risk factors to screen for patients who may require additional psychological services. ECOG = Eastern Cooperative Oncology Group.

Perioperative morbidity of intracavitary gynecologic brachytherapy

PURPOSE To define the incidence and severity of perioperative morbidity and its subsequent management with standard tandem and ovoid insertions and to evaluate pretreatment and treatment factors associated with an increased risk of perioperative morbidity. METHODS AND MATERIALS Ninety-five tandem and ovoid insertions were performed at the Fox Chase Cancer Center between 1985 and 1992 for cervical (n = 91) and endometrial (n = 4) cancer. Patients were placed on antibiotics in 19%, usually for a positive routine preoperative urine culture, but no patient was given prophylactic antibiotic therapy. Deep-vein thrombosis prophylaxis was practiced for 70% of implants and included subcutaneous heparin (40%), graduated compression elastic stockings (16%), and external pneumatic calf compression (14%). All patients were placed on prophylactic diphenoxylate hydrochloride, with doses ranging from three to eight tablets/day. RESULTS Intraoperative complications were seen in 3% of implants and included two perforations and a vaginal laceration in two patients. Twenty-four percent of implants (16 patients) developed temperatures of > 100.5 (range 100.6 to 103), although only one patient required implant removal because of fever. Management of fever included antibiotics in 35% and acetaminophen only in 65%. Five implants (5%) were removed emergently secondary to presumed sepsis (n = 1), exacerbation of chronic obstructive pulmonary disease, hypotension, change in mental status (n = 3), and myocardial infarction/congestive heart failure (n = 1). No patient developed a deep-vein thrombosis, pulmonary embolism, gastrointestinal obstruction, or died of a postoperative complication. Univariate analysis of pretreatment and treatment factors revealed older age (p < 0.005) and spinal/epidural anesthesia (p < 0.02) to be associated with increased perioperative morbidity, and older age (p < 0.05) and higher ASA classification (p < 0.02) to be associated with severe complications requiring removal of implant. Multivariate analysis revealed only older age (p < 0.01) to be significantly related to perioperative morbidity. CONCLUSIONS Fever of > 100.5 was seen in 24% of implants and can be managed successfully without removal of the implant in 96% of cases. Use of antibiotics preoperatively and intraoperatively did not reduce the risk of perioperative temperature elevation. Use of routine diphenoxylate hydrochloride prophylaxis was tolerated without ileus or gastrointestinal obstruction clinically. Although routine deep-vein thrombosis prophylaxis is reasonable, our data would support a low risk of deep-vein thrombosis for untreated patients. Severe perioperative morbidity necessitated premature implant removal in only 5% of cases and was related to older age in multivariate analysis.

Phase I Trial of Multiple Cycles of High-Dose Carboplatin, Paclitaxel, and Topotecan With Peripheral-Blood Stem-Cell Support as Front-Line Therapy

PURPOSE To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell (PBSC) support. PATIENTS AND METHODS Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with either filgrastim alone or in combination with cyclophosphamide and paclitaxel. Patients then received three or four cycles of high-dose carboplatin (area under the concentration-time curve [AUC] 16), paclitaxel (250 mg/m(2)), and topotecan (10-15 mg/m(2)), with the latter two agents administered as 24-hour infusions and supported with PBSC and filgrastim. Cycles were repeated every 28 days. RESULTS Twenty patients were enrolled onto the trial and were assessable for toxicity and clinical outcome. Dose-limiting toxicities were stomatitis and prolonged hematopoietic recovery. The maximum-tolerated dose of topotecan was 12.5 mg/m(2) when given with high-dose carboplatin and paclitaxel for three cycles. Four cycles were able to be given with a dose of topotecan of 10 mg/m(2). The pharmacokinetics of each compound were not affected by the other agents. Eleven (85%) of 13 patients with assessable disease responded. CONCLUSION Multiple cycles of high-dose carboplatin, paclitaxel, and topotecan can be safely administered with filgrastim and PBSC support. The recommended doses for phase II study are carboplatin AUC 16, paclitaxel 250 mg/m(2), and topotecan 10 mg/m(2). Trials are currently being conducted with this regimen as front-line treatment in patients with advanced ovarian cancer and extensive small-cell carcinoma. This approach remains experimental and should be used only in the context of a clinical trial.

Intraperitoneal cisplatin and etoposide in peritoneal mesothelioma: favorable outcome with a multimodality approach

Ten patients with histologically documented peritoneal mesothelioma were treated with intraperitoneal cisplatin 200 mg/m2, sodium thiosulfate rescue and etoposide 65–290 mg/m2 every 4 weeks for a maximum of six cycles. All had epithelial or mixed epithelial-fibrous histology. Toxicity was tolerable, with 50% sustaining grade 3 or 4 granulocytopenia. There was one episode of neutropenic fever. Grade 2 peripheral neuropathy occurred in one patient, grade 1 in five patients. Complete remission occurred in one of five patients with measurable disease. Median survival for patients whose tumors were surgically debulked to <2 cm residua prior to treatment was 22 months, while it was 5 months for those with measurable, surgically inaccessible disease (P=0.0731 by Cox regression proportional hazard model). These data suggest that patients who present with resectable disease may benefit from an aggressive adjuvant approach. This possibility warrants prospective testing in a randomized clinical trial.