Howard T. Thaler

The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress

The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology.

Surgical management of renal tumors 4 cm. or less in a contemporary cohort.

PURPOSE We evaluated a patient cohort with renal tumors 4 cm. or less treated with partial or radical nephrectomy. We compared patient and tumor characteristics, and survival in these 2 groups. MATERIALS AND METHODS We retrospectively analyzed the records of 670 patients with a median age of 63 years treated surgically for renal cell carcinoma between July 31, 1989 and July 31, 1997. Renal tumors 4.0 cm. or less were noted in 252 patients (38%) who underwent a total of 262 procedures, including 183 radical (70%) and 79 partial (30%) nephrectomies. Ten patients required 2 operations each because of bilateral renal cell carcinoma. Median followup was 40 months. We compared clinicopathological parameters in the partial and radical nephrectomy groups using chi-square or Wilcoxon analysis as appropriate. Survival analysis was determined by the log rank test and Cox regression model. RESULTS The partial and radical nephrectomy groups were comparable with respect to gender ratio, tumor presentation, histological classification, pathological stage and complication rate. Median tumor size was 2.5 and 3.0 cm. in the partial and radical nephrectomy groups, respectively (p = 0.0001). Resection was incomplete in 1 patient (1.3%) in the partial and none in the radical nephrectomy group. There was no local recurrence after either procedure, and no significant difference in disease specific, disease-free and overall survival (p = 0.98, 0.23 and 0.20, respectively). CONCLUSIONS Patients with a small renal tumor have similar perioperative morbidity, pathological stage and outcome regardless of treatment with partial or radical nephrectomy. Therefore, partial nephrectomy remains a safe alternative for tumors of this size.

Symptom prevalence, characteristics and distress in a cancer population

Despite the importance of symptom control in the cancer population, few studies have systematically assessed the prevalence and characteristics of symptoms or the interactions between various symptom characteristics and other factors related to quality of life (QOL). As part of a validation study of a new symptom assessment instrument, inpatients and out-patients with prostate, colon, breast or ovarian cancer were evaluated using the Memorial Symptom Assessment Scale and other measures of psychological condition, performance status, symptom distress and overall quality of life. The mean age of the 243 avaluable patients was 55.5 years (range 23–86 years); over 60% were women and almost two-thirds had metastatic disease. The Karnofsky Performance Status (KPS) score was≤80 in 49.8% and 123 were inpatients at the time of assessment. Across tumour types, 40–80% experienced lack of energy, pain, feeling drowsy, dry mouth, insomnia, or symptoms indicative of psychological distress. Although symptom characteristics were variable, the proportion of patients who described a symptom as relatively intense or frequent always exceeded the proportion who reported it as highly distressing. The mean (±SD, range) number of symptoms per patient was 11.5±6.0 (0–25); inpatients had more symptoms than outpatients (13.5±5.4 vs. 9.7±6.0, p<0.002) and those with KPS≤80 had more symptoms than those with KPS>80 (14.8±5.5 vs. 9.2±4.9, p<0.0001). The number of symptoms was highly associated with heightened psychological distress and poorer quality of life (for example, r=0.67 for the relationship with the Functional Living Index-Cancer, a QOL measure). These data clarify the prevalence and characteristics of cancer-related symptoms and suggest that the number of symptoms per patient may be a useful quality of life indicator.

Combined modality therapy for primary CNS lymphoma.

PURPOSE Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL. PATIENTS AND METHODS Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.

Phase III Study of Cisplatin With or Without Paclitaxel in Stage IVB, Recurrent, or Persistent Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study

PURPOSE To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

The Measurement of Symptoms in Children with Cancer

The purpose of this study was to determine symptom prevalence, characteristics, and distress in children with cancer. The Memorial Symptom Assessment Scale (MSAS) 10-18, a 30-item patient-rated instrument adapted from a previously validated adult version, provided multidimensional information about the symptoms experienced by children with cancer. This instrument was administered to 160 children with cancer aged 10-18 (45 inpatients, 115 outpatients). To confirm the instruments reliability and validity, additional data about symptoms were collected from both the parents and the medical charts, and retesting was performed on a subgroup of inpatients. Patients could easily complete the scale in a mean of 11 minutes. The analyses supported the reliability and validity of the MSAS 10-18 subscale scores as measures of physical, psychological, and global symptom distress, respectively. Symptom prevalence ranged from 49.7% for lack of energy to 6.3% for problems with urination. The mean (+/- SD) number of symptoms per inpatient was 12.7 +/- 4.9 (range, 4-26), significantly more than the mean 6.5 +/- 5.7 (range, 0-28) symptoms per outpatient. Patients who had recently received chemotherapy had significantly more symptoms than patients who had not received chemotherapy for more than 4 months (11.6 +/- 6.0 vs. 5. 2 +/- 5.1), and those patients with solid tumors had significantly more symptoms than patients with either leukemia, lymphoma, or central nervous system malignancies (9.9 +/- 7.0 vs. 6.8 +/- 5.5 vs. 6.8 +/- 5.0 vs. 8.0 +/- 6.1). The most common symptoms (prevalence > 35%) were lack of energy, pain, drowsiness, nausea, cough, lack of appetite, and psychological symptoms (feeling sad, feeling nervous, worrying, feeling irritable). Of the symptoms with prevalence rates > 35%, those that caused high distress in more than one-third of patients were feeling sad, pain, nausea, lack of appetite, and feeling irritable. Subscale scores demonstrated large variability in symptom distress and could identify subgroups with high distress. The prevalence, characteristics, and distress associated with physical and psychological symptoms could be quantified in older children with cancer. The data confirm a high prevalence of symptoms overall and the existence of subgroups with high distress associated with one or multiple symptoms. Symptom distress is relatively higher among inpatients, children with solid tumors, and children who are undergoing antineoplastic treatment. Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in clinical chemotherapeutic trials. Symptom epidemiology may also provide a focus for future clinical trials related to symptom management in children with cancer.

The Memorial Symptom Assessment Scale Short Form (MSAS-SF)

The Memorial Symptom Assessment Scale Short Form (MSAS‐SF), an abbreviated version of the Memorial Symptom Assessment Scale, measures each of 32 symptoms with respect to distress or frequency alone. A physical symptom subscale (PHYS), psychologic symptom subscale (PSYCH), and global distress index (GDI) can be derived from the Short Form. We validated the MSAS‐SF in a population of cancer patients.

Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes

OBJECTIVE The purpose of this study was to determine whether abnormal placentation (defined as the failure of physiologic transformation of spiral arteries) is present in patients with preterm labor and intact membranes who delivered a preterm neonate. STUDY DESIGN A cross-sectional study was conducted to examine the histopathologic findings in the placental bed and placenta of patients with preterm labor and intact membranes (n=27), preeclampsia (n=43), and healthy pregnant women at term (n=103). Immunohistochemistry studies with cytokeratin 7 and periodic acid-Schiff were used to detect trophoblast and fibrinoid, respectively, and diagnose the failure of physiologic transformation of the spiral arteries. RESULTS The mean percentage of spiral arteries with failure of physiologic transformation in the myometrium was significantly higher in patients with preterm labor and preeclampsia than in normal pregnant women at term (P=.0004 and P<.0001, respectively). Similar findings were observed in the decidual segment of spiral arteries within the placental bed (P=.001 and P<.0001). In contrast, the mean percentage of the spiral arteries with failure of physiologic transformation in the decidua of the basal plate was not significantly different between patients with preterm labor and normal pregnant women (P=.17). CONCLUSION Failure of physiologic transformation of the spiral arteries in the myometrial and decidual segments of the placental bed is frequent in patients with preterm labor and intact membranes.

The undertreatment of pain in ambulatory AIDS patients.

&NA; Pain is highly prevalent in individuals with HIV disease, yet is often overlooked as a symptom requiring clinical intervention. We evaluated the adequacy of analgesic management for pain and identified predictors of pain undertreatment in a sample of 366 ambulatory AIDS patients using a prospective cross‐sectional survey design. Two hundred and twenty‐six of the 366 ambulatory AIDS patients surveyed reported “persistent or frequent” pain over the 2 week period prior to the survey. Adequacy of analgesic therapy was assessed using the Pain Management Index (PMI ‐ a measure derived from the Brief Pain Inventory) and the type and frequency of analgesic medications prescribed for pain. Results indicated that nearly 85% of patients were classified as receiving inadequate analgesic therapy based on the PMI. Less than 8% of the 110 patients who reported “severe” pain were prescribed a “strong” opioid (e.g., morphine), as suggested by published guidelines. Adjuvant analgesic drugs (e.g., antidepressant medications) were prescribed in only 10% of the patients. Women, less educated patients, and patients who reported injection drug use as their HIV transmission risk factor were most likely to have received inadequate analgesic therapy. These results demonstrate the alarming degree of undertreatment of pain in ambulatory patients with AIDS, and indicates the need to improve the management of AIDS‐related pain in this underserved population. Future research should elucidate the factors that impede adequate pain management in order to overcome obstacles to adequate treatment.

The role of postoperative radiotherapy after resection of single brain metastases

To assess the value of whole brain radiotherapy (WBRT) after complete resection of a single brain metastasis we reviewed the records of 98 patients who had elective craniotomy between 1978 and 1985. Seventy-nine patients received postoperative WBRT (Group A) and 19 patients no radiotherapy (RT) (Group B). Neurological relapse was designated as local (i.e., at the site of the original metastasis) or distant (i.e., elsewhere in the brain). Postoperative WBRT significantly prolonged the time to any neurological relapse (P = 0.034) with a 1-year recurrence rate of 22% in Group A and 46% in Group B patients; however, it did not specifically control either local or distant cerebral recurrence. Recurrence of metastatic brain disease was not affected by location of the original lesion; however, meningeal relapse occurred in 38% of cerebellar lesions, but only in 4.7% of supratentorial metastases (P = 0.003). The total radiation dose or fractionation scheme of RT did not affect survival nor time to neurological relapse. The median survival was 20.6 and 14.4 months for Groups A and B, respectively (not statistically different). Forty-eight percent of Group A and 47% of Group B patients survived for 1 year or longer; however, 11% of patients who had received RT and survived 1 year developed severe radiation-induced dementia. All patients with radiation-related cerebral damage received hypo-fractionated RT with high daily fractions as commonly designed for rapid palliation of macroscopic brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)