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A New Palliative Prognostic Score: A First Step for the Staging of Terminally Ill Cancer Patients

In recent years, extensive research has been performed to identify prognostic factors that predict survival in terminally ill cancer patients. This study describes the construction of a simple prognostic score based on factors identified in a prospective multicenter study of 519 patients with a median survival of 32 days. An exponential multiple regression model was adopted to evaluate the joint effect of some clinico-biological variables on survival. From an initial model containing 36 variables, a final parsimonious model was obtained by means of a backward selection procedure. The Palliative Prognostic Score (PaP Score) is based on the final model and includes the following variables: Clinical Prediction of Survival (CPS), Karnofsky Performance Status (KPS), anorexia, dyspnea, total white blood count (WBC) and lymphocyte percentage. A numerical score was given to each variable, based on the relative weight of the independent prognostic significance shown by each single category in the multivariate analysis. The sum of the single scores gives the overall PaP Score for each patient and was used to subdivide the study population into three groups, each with a different probability of survival at 30 days: (1) group A: probability of survival at 30 days > 70%, with patient score < or = 5.5; (2) group B: probability of survival at 30 days 30-70%, with patient score 5.6-11.0; and (3) group C: probability of survival at 30 days < 30%, with patient score > 11.0. Using this method, 178/519 (34.3%) patients were classified in risk group A, 205 (39.5%) patients were in risk group B, and 136 (26.2%) patients were in risk group C. The patients classified in the three risk groups had a very different survival experience (logrank = 294.8, P < 0.001), with a median survival of 64 days for group A, 32 days for group B, and 11 days for group C. The PaP Score based on simple clinical and biohumoral variables proved to be statistically significant in a multivariate analysis. The score is valid in this population (training set). An independent validation on another patient series (testing set) is required and is the object of a companion paper.

Successful Validation of the Palliative Prognostic Score in Terminally Ill Cancer Patients

The aim of this work was to validate a previously constructed prognostic score for terminally ill cancer patients in order to determine its value in clinical practice. The Palliative Prognostic Score (PaP Score) was tested on a population of 451 evaluable patients consecutively entered in the hospice programs of 14 Italian Palliative Care Centers. The score subdivided patients into three specific risk classes based on the following six predictive factors of death: dyspnea, anorexia, Karnofsky Performance Status (KPS), Clinical Prediction of Survival (CPS), total white blood count (WBC), and lymphocyte percentage. The performance of the PaP Score index in the training and testing sets was evaluated by comparing mortality rates in the 3 prognostic risk categories. The score was able to subdivide the validation-independent case series into three risk groups. Median survival was 76 days in group A (with a 86.6% probability of 30-day survival), 32 days in group B (with a 51.6% probability of 30-day survival), and 14 days in group C (with a 16.9% probability of 30-day survival). Survival medians were remarkably similar to those of the training set (64 days in group A, 32 days in group B, and 11 days in group C). In the complex process of staging terminally ill patients, the PaP Score is a simple instrument which permits a more accurate quantification of expected survival. It has been validated on an independent case series and is thus suitable for use in clinical practice.

Food groups and risk of colorectal cancer in Italy

The proportion of colorectal cancer attributed to dietary habits is high, but several inconsistencies remain, especially with respect to the influence of some food groups. To further elucidate the role of dietary habits, 1,225 subjects with cancer of the colon, 728 with cancer of the rectum and 4,154 controls, hospitalized with acute non‐neoplastic diseases, were interviewed between 1992 and 1996 in 6 different Italian areas. The validated food‐frequency questionnaire included 79 questions on food items and recipes, categorised into 16 food groups. After allowance for non‐dietary confounding factors and total energy intake, significant trends of increasing risk of colorectal cancer with increasing intake emerged for bread and cereal dishes (odds ratio [OR] in highest vs. lowest quintile = 1.7), potatoes (OR = 1.2), cakes and desserts (OR = 1.1), and refined sugar (OR = 1.4). Intakes of fish (OR = 0.7), raw and cooked vegetables (OR = 0.6 for both) and fruit other than citrus fruit (OR = 0.7) showed a negative association with risk. Consumption of eggs and meat (white, red or processed meats) seemed uninfluential. Most findings were similar for colon and rectum, but some negative associations (i.e., coffee and tea, and fish) appeared stronger for colon cancer. Our findings lead us to reconsider the role of starchy foods and refined sugar in light of recent knowledge on the digestive physiology of carbohydrates and the insulin/colon cancer hypothesis. The beneficial role of most vegetables is confirmed, with more than 20% reduction in risk of colorectal cancer from the addition of one daily serving. Int. J. Cancer 72:56–61, 1997.

Reproducibility of an Italian food frequency questionnaire for cancer studies. Results for specific nutrients

The reproducibility of measures of the intake of total energy and 27 selected nutrients from a quantitative food frequency questionnaire (FFQ) used in a case-control study on cancer of the breast, ovary, and digestive tract was evaluated. The results of two FFQ administrations at an interval of 3 to 10 months (median = 5.4 months) to 452 volunteers (144 males and 308 females; median age = 50 years) from three Italian provinces (Pordenone, Genoa, and Forì) were compared. Pearson correlation coefficients (r) between crude nutrient intake (unadjusted for energy) ranged from 0.50 for vegetable fat to 0.80 for alcohol, with most values falling between 0.60 and 0.70 (median r = 0.67). Adjustment of nutrient intakes for total energy slightly decreased most coefficients (median r = 0.60). The agreement between the two measurements did not differ substantially by sex, age, education, and interval between interviews. The contribution of specific FFQ components (i.e., frequency-only questions, open questions, portion size, and fat intake pattern) was also assessed separately with respect to the performance and reproducibility of nutrient measures, yielding, in general, very similar results. The seven questions concerning individual fat intake pattern, which were used to modulate the composition of various recipes, led, however, to a significant increase in mean daily intake of vegetable fat, oleic acid, and vitamin E, but a reduction of estimated daily intake of linoleic acid and polyunsaturated fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Delirium on the Short Term Prognosis of Advanced Cancer Patients

The objective of this study was to evaluate the impact of delirium on the survival of advanced cancer patients also assessed with a validated prognostic score (the palliative prognostic [PaP] score).

Palliative Sedation in End-of-Life Care and Survival: A Systematic Review

PURPOSE Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival. METHODS A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed. RESULTS Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival. CONCLUSION Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting, palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.

Palliative sedation therapy does not hasten death: Results from a prospective multicenter study

BACKGROUND Palliative sedation therapy (PST) is indicated for and used to control refractory symptoms in cancer patients undergoing palliative care. We aimed to evaluate whether PST has a detrimental effect on survival in terminally ill patients. METHODS This multicenter, observational, prospective, nonrandomized population-based study evaluated overall survival in two cohorts of hospice patients, one submitted to palliative sedation (A) and the other managed as per routine hospice practice (B). Cohorts were matched for age class, gender, reason for hospice admission, and Karnofsky performance status. RESULTS Of the 518 patients enrolled, 267 formed cohort A and 251 cohort B. In total, 25.1% of patients admitted to the participating hospices received PST. Mean and median duration of sedation was 4 (standard deviation 6.0) and 2 days (range 0-43), respectively. Median survival of arm A was 12 days [90% confidence interval (CI) 10-14], while that of arm B was 9 days (90% CI 8-10) (log rank = 0.95, P = 0.330) (unadjusted hazard ratio = 0.92, 90% CI 0.80-1.06). CONCLUSION PST does not shorten life when used to relieve refractory symptoms and does not need the doctrine of double effect to justify its use from an ethical point of view.

Cisplatin, Dacarbazine With or Without Subcutaneous Interleukin-2, and Interferon Alfa-2b in Advanced Melanoma Outpatients: Results From an Italian Multicenter Phase III Randomized Clinical Trial

PURPOSE Phase II and III studies have shown that the addition of interleukin-2 (IL-2) and interferon alpha-2b (IFN alpha-2b) in multiagent chemotherapy (CT) for advanced melanoma increases overall response (OR), albeit without clear evidence of an improvement in overall survival (OS). Treatment with high-dose IL-2 can cause severe toxicity and is normally administered in an inpatient setting. We conducted a multicenter prospective randomized clinical trial in outpatients with metastatic melanoma to compare CT with biochemotherapy (bioCT) using immunomodulant doses of IL-2 and IFN alpha-2b. PATIENTS AND METHODS One hundred seventy-six eligible patients with advanced melanoma were randomized to receive CT (cisplatin and dacarbazine with or without carmustine every 21 days) or bioCT comprising the same CT regimen followed by low-dose subcutaneous IL-2 for 8 days and IFN alpha-2b three times a week, both for six cycles. RESULTS At a median follow-up of 18 (CT) and 16 (bioCT) months, median OS was 9.5 versus 11.0 months (P =.51), respectively. In the 89 CT-arm patients, 18 ORs (20.2%) (three complete responders [CRs] and 15 partial responders [PRs]) were observed according to World Health Organization criteria. In the 87 bioCT-arm patients, 22 ORs (25.3%) (three CRs and 19 PRs) (P =.70) were recorded. Treatment-related toxicity was fairly similar in both arms. CONCLUSION The addition of low-dose immunotherapy did not produce a statistically significant advantage in OS, time to progression, or OR. However, the 11-month median OS in the bioCT arm does not differ greatly from the best results with high-dose IL-2-containing regimens reported in the literature. Furthermore, our treatment schedule was carried out on outpatients and had an acceptable level of toxicity.

Biological indices predictive of survival in 519 Italian terminally Ill cancer patients

The knowledge of prognostic factors capable of subdividing cancer patients into groups having homogenous survival times is useful even in very advanced stages of illness. This prospective multicenter study assessed these prognostic factors in 530 terminal patients with solid tumors who were undergoing only palliative care. Thirteen hematological and urinary parameters were assessed on admission and every 28 days thereafter. In 519 assessable patients with a median survival of 32 days, six biological parameters demonstrated a statistically significant predictive prognosis. A poor prognosis was predicted by high total white blood count (WBC) (P < 0.0001), high neutrophil percentage (P < 0.0001), low lymphocyte percentage (P < 0.0001), low serum albumin level (P = 0.0015), low pseudocholinesterase level (P < 0.0001), and high proteinuria (P = 0.0064). Multiple regression analysis showed that only WBC, lymphocyte percentage and pseudocholinesterase level were independent predictors of survival. The individualization of biological parameters having an independent prognostic capacity is a useful step in the attempt to identify subsets of patients with a homogeneous prognosis. The biological factors needed are easily detected by means of a simple blood test and do not require invasive operations on patients who are already debilitated.

Duration of Chemotherapy for Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PURPOSE To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS). METHODS We searched literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques. RESULTS We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio [HR], 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy. CONCLUSION Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.