How Does Spiritual Well-Being Change Over Time Among US Patients with Heart Failure and What Predicts Change?

Few studies have examined how spiritual well-being changes over time in patients with heart failure. We conducted a secondary analysis of data from the Collaborative Care to Alleviate Symptoms and Adjust to Illness (CASA) trial (N = 314). Spiritual well-being was measured using the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp) at baseline and 12-month follow-up. Of the 165 patients with spiritual well-being data at follow-up, 65 (39%) experienced probable clinically meaningful changes (> 0.5 SD) in spiritual well-being (35 improved, 30 declined). Increased pain (p = 0.04), decreased dyspnea (p < 0.01), and increased life completion (p = 0.02) were associated with improvement in overall spiritual well-being. Exploratory analyses found different predictors for FACIT-Sp subscales.

Preferred Role in Health Care Decision Making Over Time in Patients With Heart Failure: My Decision or My Doctor's Decision?

BACKGROUND: Understanding patients' preferred role in decision making can improve patient-centered care. This study aimed to determine change and the predictors of change in preferred decision-making roles over time in patients with heart failure. METHODS AND RESULTS: During the CASA (Collaborative Care to Alleviate Symptoms and Adjust to Illness) trial, patients' preferred roles in decision making were measured using the Control Preferences Scale (range 1-5; higher = less active; n = 312) at 4 timepoints over 1 year. The effect of the CASA intervention on preferred decision-making roles was tested using generalized linear mixed models. Whether preferences changed over time in the whole population was determined using linear regression. Demographic and health-related factors were examined as predictors of change using multiple linear regression. At baseline, most participants preferred active (score 1-2, 37.2%) or collaborative (score 3, 44.9%) roles. The CASA intervention did not influence preferred decision-making roles (P > 0.1). Preferences significantly changed over 1 year (P < 0.01), becoming more active (82.1%, 84.2%, 89.0%, 90.1% active/collaborative at each timepoint). Among all models and covariates, there were no significant predictors of change (P > 0.1). CONCLUSIONS: Patients' preferred roles in decision making change over time, but changes are not well predicted. Clinicians should frequently and directly communicate with patients about their preferred decision-making roles.

Reliability, Validity, and Responsiveness of the DEG, a Three-Item Dyspnea Measure.

BACKGROUND: Dyspnea is a common and debilitating symptom that affects many different patient populations. Dyspnea measures should assess multiple domains. OBJECTIVE: To evaluate the reliability, validity, and responsiveness of an ultra-brief, multi-dimensional dyspnea measure. DESIGN: We adapted the DEG from the PEG, a valid 3-item pain measure, to assess average dyspnea intensity (D), interference with enjoyment of life (E), and dyspnea burden with general activity (G). PARTICIPANTS: We used data from a multi-site randomized clinical trial among outpatients with heart failure. MAIN MEASURES: We evaluated reliability (Cronbach's alpha), concurrent validity with the Memorial-Symptom-Assessment-Scale (MSAS) shortness-of-breath distress-orbothersome item and 7-item Generalized-Anxiety-Disorder (GAD-7) scale, knowngroups validity with New-York-Heart-Association-Functional-Classification (NYHA) 1-2 or 3-4 and presence or absence of comorbid chronic obstructive pulmonary disease (COPD), responsiveness with the MSAS item as an anchor, and calculated a minimal clinically important difference (MCID) using distribution methods. KEY RESULTS: Among 312 participants, the DEG was reliable (Cronbach's alpha 0.92). The mean (standard deviation) DEG score was 5.26 (2.36) (range 0-10) points. DEG scores correlated strongly with the MSAS shortness of breath distress-or-bothersome item (r=0.66) and moderately with GAD-7 categories (ρ=0.36). DEG scores were statistically significantly lower among patients with NYHA 1-2 compared to 3-4 [mean difference (standard error): 1.22 (0.27) points, p<0.01], and those without compared to with comorbid COPD [0.87 (0.27) points, p<0.01]. The DEG was highly sensitive to change, with MCID of 0.59-1.34 points, or 11-25% change. CONCLUSIONS: The novel, ultra-brief DEG measure is reliable, valid, and highly responsive. Future studies should evaluate the DEG's sensitivity to interventions, use anchor-based methods to triangulate MCID estimates, and determine its prognostic usefulness among patients with chronic cardiopulmonary and other diseases.

Two Factor Structures Possible for the FACIT-Sp in Patients With Heart Failure.

CONTEXT: The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp) is a 12-item measure of spiritual well-being in chronic illness originally developed in patients with cancer. The overall scale, a two-factor model (meaning/peace, faith), and a three-factor model (meaning, peace, faith) have been proposed for the FACIT-Sp, and consensus on the best factor structure has not been reached. In addition, the factor structure of the FACIT-Sp has not been considered in patients with heart failure. OBJECTIVES: To examine the factor structure of the FACIT-Sp in heart failure patients. METHODS: A confirmatory factor analysis framework was used to test three competing models on 217 patients with heart failure using data from the CASA (Collaborative Care to Alleviate Symptoms and Adjust to Illness) trial. The overall scale (single factor), two-factor, and three-factor models were tested using baseline data, then confirmed with 12-month data. Model modifications were made based on empirical inspection of baseline data and replicated using 12-month data. Cronbach's alpha and correlations with measures of quality of life and psychological health were examined. RESULTS: All three models had strong factor loadings on all items except the negatively worded items. The two-factor and three-factor models fit reasonably well after modifications, but the single factor did not fit well (1/2/3-factor: RMSEA 0.14/0.09/0.06, CFI 0.85/0.93/0.97, SRMR 0.09/0.05/0.04). Internal consistency was sufficient for all factors. CONCLUSION: The two-factor and three-factor models were supported in heart failure patients. The three-factor model demonstrated better statistical fit but was not more interpretable. KEY MESSAGE: This study investigated the factor structure of the FACIT-Sp in patients with heart failure. The two-factor and three-factor models were supported, but the single factor model was not. Negatively worded items did not perform well.

Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies.

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism.

Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer.

p53 tumour suppressor gene alterations are one of the most frequent genetic events in lung cancer. A subset of patients with p53 mutation and cancer exhibited circulating serum anti-p53 self-antibodies (p53-Ab). The prevalence of these antibodies in lung cancer is currently being analysed in a multicentric study. In a group of homogeneous SCLC patients, p53-Ab were detected in 20/97 (20.6%) individuals. In this group of patients, Cox's multivariate analysis identified disease extent (p = 0.022), WHO initial performance status greater than 0 (p = 0.005), and the absence of a complete response after 6 months of treatment (p < 0.0001) as independent prognostic variables, with p53-Ab being of borderline significance (p = 0.051). In the subset of limited-stage SCLC patients, Cox's multivariate analysis found p53-Ab (p = 0.033), WHO initial performance status greater than 0 (p = 0.028), and absence of a complete response (p < 0.001) to be independent prognostic variables. Thus, actuarial analysis showed that patients with limited-stage SCLC and p53-Ab had a median survival time of 10 months, whereas limited-stage SCLC patients without p53-Ab had a 17-month median survival time (p = 0.014).Therefore, serum assay of p53-Ab could help to identify a population of SCLC patients with an especially poor prognosis. This population could represent patients with tumours harboring aggressive p53 mutations.

Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment.

Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.

Detection and monitoring of serum p53 antibodies in patients with colorectal cancer.

BACKGROUND: Detection of p53 antibodies in serum might be an effective indirect procedure to detect alterations of the p53 gene. AIMS: To assess the prevalence and the variation under treatment of p53 antibodies in patients with colorectal cancer. PATIENTS AND METHODS: Fifty four patients with colorectal cancer (26 men and 28 women, mean age 65, range 33-90 years) and 24 patients with non-malignant digestive disease were tested for p53 antibodies by enzyme linked immunosorbent assay (ELISA), and for the carcinoembryonic antigen and carbohydrate antigen 19.9. Immunohistochemical detection of p53 protein tumour overexpression was performed in 38 cases. RESULTS: Fourteen patients (26%) with colorectal cancer but none of those with non-malignant disease displayed p53 antibodies. Overexpression of p53 was shown by immunohistochemistry in 22 patients (58%), 10 of whom also had p53 antibodies. The antibodies were present in four patients with high carcinoembryonic antigen and three patients with high carbohydrate antigen 19.9 concentrations, but also in 10 patients (33.3%) with normal values of these markers. The ratio of p53 antibodies decreased in 11 of 13 patients after tumour resection. In two patients variations in p53 ratio strongly correlated with tumour relapse or progression. CONCLUSION: Testing for serum p53 antibodies constitutes a useful technique for assessing alterations in p53 and may help physicians to follow up patients with colorectal cancer.

Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers.

BACKGROUND: In the UK EPIC validation studies, the accuracy of several methods was assessed by comparison with to-day weighed records and the biomarkers, 24-hour urine nitrogen (N) and potassium (K), plasma carotenoids and plasma vitamin C. METHODS: Comparisons between methods were made on 156 women, studied over 1 year at 3-monthly intervals at home. On each of four occasions, volunteers completed 4 days of weighed records and provided two 24-hour urine collections and a fasting blood sample. RESULTS: In comparison with the 16 days of weighed records, a food frequency questionnaire (FFQ) yielded higher values mainly due to greater reported consumption of milk and of vegetables. A 24-hour recall was as good as the FFQ in placing individuals in the distribution of habitual diet from weighed records. Results obtained from a 7-day estimated record were closest to those obtained from the weighed record. Correlations between 24-hour urine excretion and dietary N intake from weighed records were high (0.78-0.87) as were those with estimated food diaries (0.60-0.70). Correlations between urine N and the FFQ and 24-hour recall were lower (0.10 to 0.27), but improved by energy adjustment using residuals for N and K which are correlated with total energy intake. Comparisons between dietary estimates and urinary K and serum carotenoids and vitamin C showed broadly similar results. Limited biomarker information amongst 200 UK EPIC participants supported the findings of the validation study. CONCLUSIONS: UK EPIC uses three methods (the 7-day diary, an improved FFQ, and the 24-hour recall) to assess diet. 93% of first food diaries are returned completed by participants. Repeated diaries are the main dietary assessment method for nested case-control analyses.

Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma.

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Analysis of p53 antibody response in patients with squamous cell carcinoma of the head and neck.

p53 alterations are the most common alteration found in human cancer. Protein p53 was studied in 102 patients with early lesions or advanced squamous cell carcinoma of the head and neck (SCCHN). Biopsies and sera samples were collected before the initiation of treatment. Protein p53 expression was evaluated by immunohistochemistry using Pab 1801, Pab 240, DO7 and CM1 antibodies on paraffin-embedded sections. Antibodies specific for p53 protein were analysed in the sera of these patients by an ELISA procedure. We demonstrated that p53 protein overexpression (> or = 20% positive cells) was an early event in the carcinogenesis of SSCHN and correlated to the progression of carcinogenesis. Overexpression of protein p53 was frequent (56.5%) in advanced tumors. No correlation was found with clinical stage or the differentiation status of the tumor, but we demonstrated differences in protein p53 expression according to the initial localisation of the tumor, with high expression in hypopharynx (67%) and oropharynx (65%) versus larynx (12%). The prevalence of p53 antibodies was high (44%) and was correlated with the rate of p53 overexpression (> or = 30% positive cells) in tumors (p < 0.0001 chi square test). These results suggest that the humoral response is an indicator of the presence of squamous cell carcinoma with immunogenic mutant p53 protein. Therefore the detection of anti-p53 antibodies could be used as a precocuous marker of p53 alteration and a prognostic marker, in order to screen for patients with a better prognosis.

[P53 antibodies: a new method for the analysis of alterations of the p53 gene: application to breast cancer]. / Les anticorps anti-p53: une nouvelle méthode d'analyse des altérations du gène p53: application au cancer du sein.

Alterations in the p53 gene are found in 20% to 40% of breast cancers and are generally associated with factors of adverse prognostic significance. In most instances, point mutations modify the confirmation of p53, causing the gene to accumulate in the nuclei of tumor cells. These alterations can be detected via molecular analysis or immunohistochemical methods. More recent studies have demonstrated that accumulation of the p53 protein in tumor cells may induce an immune response with presence of anti-p53 antibodies in the serum of cancer patients. Assaying serum anti-p53 antibody is a new approach to investigation of the status of the p53 gene in a tumor.

p53 antibodies in patients with various types of cancer: assay, identification, and characterization.

Alteration of the p53 gene is the most frequent genetic alteration in human cancer and leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasia have p53 antibodies in their sera which could be used as an indirect diagnostic procedure for p53 alteration. Using a new ELISA, we have analyzed the sera from more than 1000 patients with various types of cancer and from healthy blood donors. We demonstrate that p53 antibodies are detected mainly in cancer patients and are strictly proportional to the occurrence of p53 mutations. Using various immunological approaches, these antibodies were unambiguously demonstrated to be directed toward the human p53 protein. Isotyping analysis of these antibodies strongly suggested that they correspond to a humoral response to the p53 protein which accumulates in the tumor cell. This finding suggests that serological analysis, combined with histochemistry, is suitable for assessing the integrity of the p53 gene in cancer patients.

Serum p53 antibodies as early markers of lung cancer.

The p53 alteration is the most common alteration found in human cancer. It usually involves missense mutations that stabilize the p53 protein, which in turn accumulates, reaching levels detectable by immunohistochemistry. We and others have demonstrated that this overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. This result was assessed by the presence of p53 antibodies in sera of patients with various types of cancers, whereas normal populations do not exhibit such antibodies. In lung cancer, the prevalence of p53 antibodies is high (30%) and is correlated with a very high rate of p53 mutations in this cancer (60-70%). We show that these antibodies are always present at the time of diagnosis, but never appear during tumour development, an observation strengthened by the fact that these antibodies are mostly IgG, corresponding to a secondary immune response. These results suggest that the humoral response is an early event and that p53 antibodies can be used as a precocious marker of p53 alteration before clinical manifestation of the disease.

p53 antibodies in the sera of lung cancer patients: comparison with p53 mutation in the tumour tissue.

This study examined the sensitivity and specificity of serum auto-antibodies to p53 protein as a non-invasive marker of p53 genetic alterations or protein accumulation in lung cancer cases. A sensitive ELISA to detect serum p53 antibodies was developed and used to examine sera from 186 patients undergoing pulmonary surgery for a suspected lung cancer. Target antigens in ELISA were wild-type p53 protein and 5 peptides covering the N- and C-terminal parts of the protein. Sixteen sera were positive for serum p53 antibodies in both ELISAs and all were among the 136 patients with confirmed primary lung carcinoma. Of 50 patients with other pulmonary diseases, none had p53 antibodies. In 92 cancer patients exons 5 to 8 of the p53 gene were examined for mutations by denaturing gradient gel electrophoresis and direct sequencing of PCR products. Forty-seven tumours had a p53 mutation and 7 (15.2%) of these were positive for p53 antibodies. Two patients had serum antibodies but no detectable mutation in exons 5 to 8. Frequencies of p53 mutations and serum antibodies were higher in squamous cell carcinoma patients than in adenocarcinoma. Accumulation of p53 protein in tumour tissue was observed in 32 patients, but only 5 were positive for p53 antibodies. In conclusion, serum p53 antibodies were detected only in a proportion of lung cancer cases, but the majority were specifically associated with a detectable p53 mutation in the tumour.

Primary proliferative T cell response to wild-type p53 protein in patients with breast cancer.

Mutations in the p53 tumor suppressor gene are the most frequent genetic alterations found in human tumors. There are mainly point mutations that lead to single amino acid substitutions. The mutated proteins have a longer half-life than wild-type p53 and accumulate in the nucleus of tumor cells. Anti-p53 antibodies have been found in sera of patients with several types of cancers including breast cancer. This report describes a T cell immune response in three patients with breast tumors who had mutated p53 gene and accumulated p53 protein. All showed a humoral response to p53 protein and the T cells of these patients recognized the wild-type p53 protein and proliferated in response to it. The data reported here are relevant to the immune processes leading to autoimmunity and have a bearing on anti-p53 vaccine development in tumor immunology.

Antibodies against p53 protein in serum of patients with benign or malignant pancreatic and biliary diseases.

Specific markers for pancreatic or biliary cancer have been developed in the past few years. Ca 19-9 has a good sensitivity but it is also increased in benign cholestasis. Mutations in the p53 gene are commonly reported in pancreatic cancer and can be detected by a serological analysis. The aim of this work was to find out the sensitivity and specificity of this new assay in diagnosing cancer of the pancreas or of the bile ducts. The presence of antibodies against p53 was determined by an enzyme linked immunosorbent assay (ELISA) in 29 patients with pancreatic cancer, 33 with biliary tract cancer, and 33 with benign biliary or pancreatic diseases as controls. p53 Antibodies were detected in eight of 29 patients with pancreatic cancer (28%), in five of 33 patients with biliary tract (15%), and in one patient (3%) with stones of the common bile duct. The sensitivity and the specificity for the diagnosis of malignant biliary or pancreatic diseases were 21% and 96% respectively. It is concluded that the presence of p53 antibodies in the serum of patients with pancreatic and biliary diseases is specific for malignancy and independent from the presence of cholestatic disease.

Prognostic significance of circulating P53 antibodies in patients undergoing surgery for locoregional breast cancer.

P53 mutations can lead to the production of P53 antibodies in serum of cancer patients. Here we studied the prognostic value of P53 antibodies in 353 primary breast cancer patients. P53 antibodies were detected in 42 cases (12%) and were negatively related to oestradiol and progesterone receptors. The median duration of follow-up for live patients was 5.3 years. In actuarial analyses, overall survival was worse in patients with P53 antibody (p < 0.0005); in Cox's multivariate analysis, P53 antibody was an independent prognostic variable. Thus plasma assay of P53 antibody would be useful to select rapidly and easily a population of patients with poor prognosis.

In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: cell characterization and correlations with local control and overall survival.

PURPOSE: To determine whether in vivo parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome. METHODS AND MATERIALS: Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay. RESULTS: Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610(-3). Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9-47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy-1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values about the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years). CONCLUSION: These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.