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.

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Background. The individualization of prognostic factors in the various stages of cancer facilitates the planning of a therapeutic assistance program aimed at various subsets of patients. The prognostic factors for survival in patients terminally ill with cancer have been investigated in case studies that are often retrospective, monocentric and/or include a mixture of patients in advanced disease stages. The aim of this prospective multicentric study was to verify those clinical factors predictive of survival in a population of patients with terminal cancer. Methods. This prospective and multicentric study was performed on 540 patients with solid tumors in the disseminated phase, no longer subject to specific therapy. Patients were evaluated at study entry and every 4 weeks thereafter. The analysis was performed for 23 clinical parameters. Results. Of 530 assessable patients with a median survival of 32 days, 15 factors were found to be statistically significant prognostic factors. By univariate analysis, 13 factors were found to be indicators of a worse survival: age older than 65 years (P = 0.05); palliative corticosteroid treatment (P < 0.001), anorexia (P < 0.001); dry mouth (P < 0.001); dysphagia (P < 0.001); hospitalization (P < 0.001); transfusion (P < 0.001); weight loss greater than or equal to 10% (P = 0.001); dyspnea (P = 0.01); pain (P = 0.006); increasing amount of pain‐killer treatment (P = 0.01); increasing number of symptoms (P < 0.001); and worse clinical prediction of survival (P < 0.001). Two factors that correlated with a better survival rate were palliative progestin treatment (P = 0.03) and a higher Karnofsky performance status (P < 0.001). Multiple regression.

To examine the prevalence of depressive symptoms and its relationship with quality-of-life domains in home-care cancer patients at an advanced stage of illness, 86 patients were given psychological tests for depression (Hospital Anxiety Depression Scale) (HAD) and quality of life (EORTC-QLQ-C30) 1 week after admission to the home-care program. Using a proper cut-off score on the HAD-Depression subscale, depressive symptoms were reported by 45% of the patients. The quality of life of depressed patients was more affected than non-depressed patients in the social, emotional, cognitive, and physical domains. Significant correlations were found between depression scores and impairment in most quality-of-life areas. These findings support the importance of depression and quality-of-life evaluation in patients with advanced cancer who are followed in a home-care setting. This evaluation is needed to provide patients, their families, and caregivers with appropriate psychosocial interventions.

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.

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.

Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.

Aims-To determine cell proliferation in infiltrating breast carcinomas. Methods-Using the MIB-1 monoclonal antibody, the proliferation index was measured in paraffin wax sections of 871 breast cancers. The MIB-1 proliferation index was compared with other markers of disease progression: size, lymph node status, histotype, oestrogen and progesterone receptor status, expression of p53 and Neu, and DNA ploidy. AUl parameters were measured using image analysis. In 347 tumours, the MIB-1 and Ki-67 proliferation indexes were compared. Follow up data were available for 170 cases (median 66.5 months). Results-Of the tumours, 314 (36%) had a high proliferation index. The MIB-1 proliferation index was correlated directly with size, nodal status, overexpression of p53 and Neu, and the DNA index; and inversely with oestrogen and progesterone receptor status. The correlation between MIB-1 and Ki-67 proliferation indexes was statistically significant. In patients with pT1 tumours, a low proliferation index correlated with a longer relapse-free interval and overall survival; node negative patients with a low proliferation index had a longer overall survival. Conclusions-The MIB-1 proliferation index is a reliable, practical and useful method ofmeasuring proliferative activity and is an important predictor of clinical behaviour. ( Clin Pathol 1996;49:926-930) Keywords: breast cancer, MIB-1, proliferative activity, image analysis, overall survival.Use of immunocytochemistry to measure tumour proliferation preserves both cytological and architectural features and can be used to detect proliferation related nuclear antigens, one of the most important of which is Ki-67. The Ki-67 nuclear antigen is expressed by dividing cells in all phases of the cell cycle except Go 1 and has been established as an independent prognostic marker in breast cancer. Unfortunately, detection of Ki-67 is limited to frozen tissue only. However, several antibodies are available for quantifying cell proliferation in paraffin wax embedded specimens, including antibodies directed against proliferating cell nuclear antigen (PCNA) and the Ki-Sl and MIB-1 monoclonal antibodies."'' MIB-1, in particular, recognises Ki-67 nuclear antigen, permitting the assessment of growth fraction on small tumours, formalin fixed tissue and retrospective studies on archival material.The aim of the present study was to measure the MIB-1 proliferation index in 871 infiltrating breast carcinomas. The results were compared with other markers of prognosis: oestrogen and progesterone receptor status, overexpression of c-erbB-2/Neu and p53, the DNA index, and the Ki-67 proliferation index. The clinical usefulness of the MIB-1 proliferation index was also evaluated in 170 patients (median follow up 66.5 months). MethodsParaffin wax blocks of 871 infiltrating primary breast cancers were retrieved from the archives. The clinicopathological details of the patients studied are presented in table 1. The mean age of the patients was 61 years; 277 (31.8%) were pre-menopausal and 507...