Cancer patients report numerous adverse symptoms associated with their disease and treatment including cognitive dysfunction, fatigue, and affective distress. Cognitive dysfunction is ubiquitous in ...patients with primary central nervous system (CNS) cancer and recent evidence has documented similar deficits in patients with non-CNS cancer as well. Both the cancer itself and treatments including chemotherapy, biological response modifiers, and hormonal therapies have been demonstrated to adversely impact cognitive and neurobehavioral function. Neuroimaging and neurophysiological investigations have likewise revealed alterations in brain function that are helping to account for the nature of these cognitive disorders. Similarly, preclinical animal research is assisting to identify the pathophysiological mechanisms that underlie treatment-related neurotoxicities. The coalescence of multidisciplinary clinical and research efforts hold promise for the development of interventions that may offer neuroprotection in addition to currently available symptomatic therapies and cognitive rehabilitation techniques.
Chemotherapy-induced cognitive dysfunction in patients with breast carcinoma has been described previously. However, those studies only assessed patients' postchemotherapy cognitive functioning and ...were not able to determine the relation between cognitive function and other treatments, such as surgery and radiotherapy, that often precede systemic chemotherapy.
Eighty-four women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before receiving adjuvant therapy for nonmetastatic primary breast carcinoma.
Before the start of systemic therapy, 35% of women in the current cohort exhibited cognitive impairment. Verbal learning (18%) and memory function (25%) were impaired significantly more frequently relative to normative expectations. Although the impairments were not significant in the women who were examined, nonverbal memory (17%), psychomotor processing speed and attention (13%), confrontational naming (13%), visuoconstruction (13%), and upper-extremity fine motor dexterity (12%) were impaired more frequently than was expected. Affective distress was related significantly to cognitive impairment (Pearson chi-square = 9.90; P = 0.002). Given the conservative statistical approach employed, extent of surgery, hormone replacement therapy history, and current menopausal status failed to achieve statistical significance, but these variables did exhibit provocative trends with respect to cognitive impairment.
Cognitive impairment frequently is observed before the administration of systemic chemotherapy. Thus, investigations purporting to measure chemotherapy-induced cognitive dysfunction must employ study designs that incorporate prechemotherapy baseline assessments to accurately detect changes in cognitive function that are attributable to chemotherapy.
Cognitive impairment is a common symptom in patients with brain metastasis, and significant cognitive dysfunction is prevalent in a majority of patients who are still able to engage in basic ...self-care activities. In the current study, the neurocognitive performance of 32 patients with brain metastasis and 32 demographically-matched controls was examined using a battery of standardized neuropsychological tests, with the goal of comprehensively examining the cognitive functioning of newly diagnosed brain metastasis patients. The cognition of all patients was assessed within 1 week of beginning treatment for brain metastasis. Results indicated impairments in verbal memory, attention, executive functioning, and language in relation to healthy controls. Performance in relation to appropriate normative groups was also examined. Overall, cognitive deficits were prevalent and memory was the most common impairment. Given that cognitive dysfunction was present in this cohort of patients with largely minimal functional impairment, these results have implications for patients, caregivers and health care providers treating patients with brain metastasis.
Cancers and cancer treatments produce multiple symptoms that collectively cause a symptom burden for patients. These symptoms include pain, wasting, fatigue, cognitive impairment, anxiety, and ...depression, many of which co-occur. There is growing recognition that at least some of these symptoms may share common biologic mechanisms.
In November 2001, basic and clinical scientists met to consider evidence for a cytokine-immunologic model of symptom expression along with directions for future research.
The characteristics of cytokine-induced sickness behavior in animal models have much in common with those of symptomatic cancer patients. Sickness behavior refers to a set of physiologic and behavioral responses observed in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines. In some cases, these responses can be prevented by cytokine antagonists. A combination of animal and human research suggests that several cancer-related symptoms may involve the actions of proinflammatory cytokines.
Based on the similarities between cancer symptoms and sickness behavior, the authors discussed approaches to further test the implications of the relationship between inflammatory cytokines and symptoms for both symptom treatment and symptom prevention.
To study the incidence of depression among patients undergoing surgery for high-grade glioma, document factors associated with the presence of depression, and examine the relationship between ...depression and patient outcome.
Physician and patient reports of depression were analyzed immediately postoperatively and again 3 and 6 months after surgery for high-grade glioma. Physician-reported depression was defined according to the Diagnostic and Statistical Manual of Mental Disorders, ed 4. Patient self-assessment of depression was based on responses to questions contained in two validated functional status surveys. Concordance of physician- and patient-reported depression was examined, along with the extent of use of pharmacological treatment for depression. Additional outcomes examined included quality of life, survival, patient satisfaction, and posttreatment complications.
Data from 598 patients were analyzed. In the early postoperative period, physicians reported depression in 15% of patients, whereas 93% of patients reported symptoms consistent with depression. The incidence of patient self-reported depression remained similar at 3- and 6-month follow-up, whereas physician reported depression increased from 15% in the early postoperative period to 22% at both 3- and 6-month follow-up. Concordance between physician recognition of depression and treatment of depression was low initially (33%) and increased at 3 and 6 months (51 and 60%, respectively). As compared with patients who were not depressed, survival was shorter and complications were more common among depressed patients.
Symptoms of depression were common immediately after surgery for glioma, and they increased throughout the 6-month period after surgery. These findings support the hypothesis that clinically important depression is a common complication in patients with high-grade glioma. Concordance between physician recognition of depression and self-reports of depression by patients was low. Concordance between physician recognition of depression and initiation of pharmacological antidepressant therapy was fair in the early postoperative period and improved somewhat over the subsequent 6-month period; however, within the 6-month period after surgery for glioma, antidepressant therapy was provided for only 60% of patients in whom the physician recognized depressive symptoms and in only 15% of patients who self-reported symptoms of depression. Findings from this observational study suggest the need for a controlled trial that is designed to test the hypothesis that more attention to the identification of postoperative depression and aggressive treatment of depressive symptoms can improve the quality of life and survival of patients after surgery for high-grade glioma.
To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma ...(SCC) among patients with aggressive skin SCC.
Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation.
At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio HR, 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities.
Results of this phase III trial do not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.
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