Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference

Application of generic and specific measures of health status and quality of life to different diseases, conditions, states, and populations is increasing. Four strategies for using these measures are separate generic and specific measures, modified generic measures, disease-specific supplements, and batteries. The preferred strategy depends on project aims, methodological concerns, and practical constraints. Generic measures are necessary to compare outcomes across different populations and interventions, particularly for cost-effectiveness studies. Disease-specific measures assess the special states and concerns of diagnostic groups. Specific measures may be more sensitive for the detection and quantification of small changes that are important to clinicians or patients. Comparison studies are needed of the validity, reliability, and responsiveness of generic and disease-specific measures in the same population and in minority and age-specific groups.

Generic and disease-specific measures in assessing health status and quality of life.

Context.—Cancer pain can be relieved with pharmacological agents as indicated
by the World Health Organization (WHO). All too frequently pain management
is reported to be poor.Objective.—To evaluate the adequacy of pain management in elderly and minority
cancer patients admitted to nursing homes.Design.—Retrospective, cross-sectional study.Setting.—A total of 1492 Medicare-certified and/or Medicaid-certified nursing
homes in 5 states participating in the Health Care Financing Administration's
demonstration project, which evaluated the implementation of the Resident
Assessment Instrument and its Minimum Data Set.Study Population.—A group of 13625 cancer patients aged 65 years and older discharged
from the hospital to any of the facilities from 1992 to 1995. Data were from
the multilinked Systematic Assessment of Geriatric Drug Use via Epidemiology
(SAGE) database.Main Outcome Measures.—Prevalence and predictors of daily pain and of analgesic treatment.
Pain assessment was based on patients' report and was completed by a multidisciplinary
team of nursing home personnel that observed, over a 7-day period, whether
each resident complained or showed evidence of pain daily.Results.—A total of 4003 patients (24%, 29%, and 38% of those aged ≥85 years,
75 to 84 years, and 65 to 74 years, respectively) reported daily pain. Age,
gender, race, marital status, physical function, depression, and cognitive
status were all independently associated with the presence of pain. Of patients
with daily pain, 16% received a WHO level 1 drug, 32% a WHO level 2 drug,
and only 26% received morphine. Patients aged 85 years and older were less
likely to receive either weak opiates or morphine than those aged 65 to 74
years (13% vs 38%, respectively). More than a quarter of patients (26%) in
daily pain did not receive any analgesic agent. Patients older than 85 years
in daily pain were also more likely to receive no analgesia (odds ratio [OR],
1.40; 95% confidence interval [CI], 1.13-1.73). Other independent predictors
of failing to receive any analgesic agent were minority race (OR, 1.63; 95%
CI, 1.18-2.26 for African Americans), low cognitive performance (OR, 1.23;
95% CI, 1.05-1.44), and the number of other medications received (OR, 0.65;
95% CI, 0.5-0.84 for 11 or more medications).Conclusions.—Daily pain is prevalent among nursing home residents with cancer and
is often untreated, particularly among older and minority patients.

https://jamanetwork.com/journals/jama/articlepdf/187650/joc71977.pdf

Management of Pain in Elderly Patients With Cancer

The role of health care providers and significant others in evaluating the quality of life of patients with chronic disease: A review

Background: The vital role played by family caregivers in supporting dying cancer patients is well recognized, but the burden and economic impact on caregivers is poorly understood. We prospectively examined the psychosocial, occupational and economic impact of caring for a person with a terminal illness. Methods: We studied 89 caregivers of women with advanced breast cancer receiving care at either the Ottawa or Hamilton regional cancer centres in Ontario. Patients were followed until their death or study completion at 3 years. Patients identified a principal caregiver to participate in the study. The Karnofsky Performance Status (KPS) index, the Medical Outcomes Study 36-item Short Form (SF-36), the Hospital Anxiety and Depression Scale, the Zarit Burden Inventory, FAMCARE and the Medical Outcomes Study Social Support Survey were administered during follow-up. Economic data were collected by means of a questionnaire administered by an interviewer. Assessments were conducted every 3 months during the palliative period (KPS score > 50) and every 2 weeks during the terminal period (KPS score ≤ 50). Results: Over half of the caregivers were male (55%) and the patient9s spouse or partner (52%), with a mean age of 53 years. At the start of the palliative period, the caregivers9 mean physical functioning score was better than the patients9 (51.3 v. 35.1, 95% confidence interval [CI] 13.3–20.0); there were similar mean mental functioning scores (46.6 and 47.1 respectively); similar proportions were depressed (11% and 12%); and significantly more caregivers than patients were anxious (35% v. 19%, p = 0.009). More caregivers were depressed (30% v. 9%, p = 0.02) and had a higher level of perceived burden (26.2 v. 19.4, p = 0.02) at the start of the terminal period than at the start of the palliative period. Burden was the most important predictor of both anxiety and depression. Of employed caregivers, 69% reported some form of adverse impact on work. In the terminal period 77% reported missing work because of caregiving responsibilities. Prescription drugs were the most important component of financial burden. Interpretation: Caregivers9 depression and perceived burden increase as patients9 functional status declines. Strategies are needed to help reduce the psychosocial, occupational and economic burden associated with caregiving.

/pdf/family-caregiver-burden-results-of-a-longitudinal-study-of-177xci05nd.pdf

Family caregiver burden: results of a longitudinal study of breast cancer patients and their principal caregivers

The Karnofsky Performance Status Scale (KPS) is widely used to quantify the functional status of cancer patients. However, limited data exist documenting its reliability and validity. The KPS is used in the National Hospice Study (NHS) as both a study eligibility criterion and an outcome measure. As part of intensive training, interviewers were instructed in and tested on guidelines for determining the KPS levels of patients. After 4 months of field experience, interviewers were again tested based on narrative patient descriptions. The interrator reliability of 47 NHS interviewers was found to be 0.97. The construct validity of the KPS was analyzed, and the KPS was found to be strongly related (P less than 0.001) to two other independent measures of patient functioning. Finally, the relationship of the KPS to longevity (r = 0.30) in a population of terminal cancer patients documents its predictive validity. These findings suggest the utility of the KPS as a valuable research tool when employed by trained observers.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819840501%2953%3A9%3C2002%3A%3AAID-CNCR2820530933%3E3.0.CO%3B2-W

The Karnofsky Performance Status Scale. An examination of its reliability and validity in a research setting.

Total and filterable platinum in plasma were monitored for seven courses (five patients, 25 mg/m2/day) using continuous 5-day infusions and one 30-minute infusion at a similar dose level (120 mg/m2). Maximum filterable (non-protein-bound) platinum levels (0.1-0.3 mg/L) for the extended infusions were ten to 40 times lower than that for the short-term infusion (4.0 mg/L). Filterable drug exposure as measured by the area under the [Pt]filterable-time curve is greater for the extended infusions (9.6 mg X hr/L) than that for the short-term infusion (4.8 mg X hr/L). Renal excretion of cisplatin (% of dose excreted/24-hour period after the beginning of the infusion) was measured for four courses of continuous 5-day infusions and for the 30-minute infusion. Urine excretion rates were lower for the continuous infusion (5%-8% of dose/24-hour period during the infusion) compared to the short-term infusion (33% of dose/24-hour period after the beginning of the 30-minute infusion).

Cisplatin administered as a continuous 5-day infusion: plasma platinum levels and urine platinum excretion.

Analgesic use in terminal cancer patients: report from the National Hospice Study.

Treatment with continuous infusions of cisplatin results in increased filterable drug exposures as measured by the area under the curve (AUC) of nonprotein-bound plasma platinum levels. To determine the dose-limiting toxicity and optimal method of administration, 24 patients were treated with continuous infusions of cisplatin at a dose rate of 25 mg/M2/day in a limited Phase I trial. A total of 47 courses were given. Nine patients received 13 courses of 4 days duration, 19 received 29 courses of 5 days duration, and five received courses of 6 or 7 days duration. Dose-limiting toxicity was found to be leukopenia: 42% of patients receiving the 5-day treatment developed a nadir count of less than 3000 cells/mm3. Nausea and vomiting were easily controlled. Minimal nephrotoxicity occurred in five patients and was associated with daily volume expansion with 2 l of 0.9% NaCl solution in four patients. All other patients were given 3 l of daily volume expansion during treatment. Responses were seen in 6 of 22 evaluable patients (27%). It is concluded that continuous infusion cisplatin at a dose rate of 25 mg/M2/day can be given safely for 5 days as a single agent if concomitant volume expansion with at least 3 l of 0.9% NaCl solution is given daily. Phase III comparative trials with a conventional bolus and newer high-dose regimens for response and toxicity are indicated. Cancer 59:15–18, 1987.

A phase I trial of continuous infusion cisplatin.

The rate of nucleoside transport decreased profoundly in human promyelocytic leukemia HL-60 cells after myeloid differentiation was induced by 5-6 days of exposure to 08% N,N-dimethylformamide (DMF) The facilitated diffusion of 100 microM radiolabeled adenosine and 2'-deoxyadenosine, measured by rapid transport assays, decreased 10- to 20-fold The transport of 2 microM coformycin or 2'-deoxycoformycin, which is mediated by the same mechanism and was monitored by the adenosine deaminase titration assay, decreased 29-fold The reduction in nucleoside transport capacity after DMF treatment was confirmed by a 19-fold decrease in the number of specific binding sites per cell (from 24-30 X 10(4) to 12-17 X 10(4)) for [3H]-6-p-nitrobenzylthioinosine, a nucleoside transport inhibitor The binding affinity of 6-p-nitrobenzylthioinosine was not altered significantly and nucleoside transport remained sensitive to the transport inhibitors, 6-p-nitrobenzylthioinosine, dipyridamole, and dilazep after DMF-induced maturation Time-dependence studies showed that the rate of 100 microM deoxyadenosine transport was unchanged for the first 24 h of exposure to DMF but fell to about 36% of control rates at 24-26 h and then gradually decreased further to about 4-5% of control rates after 5-6 days In contrast, transport rates of the purine bases were reduced only 2- to 3-fold in HL-60 cells after 5 days of DMF treatment The rates of adenosine and deoxyadenosine transport were unchanged or reduced by no more than 2-fold after 5-6 days of exposure to 08% DMF in the following human tumor cell lines that are not inducible with DMF: ARH-77 (multiple myeloma), KG-1 (acute myelogenous), and K-562 (chronic myelogenous) Thus, changes in nucleoside transport may serve as an early, membrane-associated marker of differentiation of the HL-60 cell line

Michael C. Wiemann

Papers

The Karnofsky Performance Status Scale. An examination of its reliability and validity in a research setting.

Cisplatin administered as a continuous 5-day infusion: plasma platinum levels and urine platinum excretion.

Analgesic use in terminal cancer patients: report from the National Hospice Study.

A phase I trial of continuous infusion cisplatin.

Changes in nucleoside transport of HL-60 human promyelocytic cells during N,N-dimethylformamide induced differentiation.