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Multivariate analysis of prognostic factors in patients with ovarian cancer stage I and II.

OBJECTIVE: To evaluate prognostic factors such as surface capsular invasion, rupture of the capsule and intraperitoneal cytology in patients with stage I or II ovarian cancer. METHOD: Multivariate analysis was performed using 11 clinicopathologic prognostic factors obtained from 183 cases of stage I and II ovarian cancer, which had been surgically treated between 1983 and 1993. RESULTS: Significant prognostic factors determined by the Kaplan-Meier method were rupture and invasion of the capsule in stage II ovarian cancer. Multivariate analysis showed that spontaneous rupture of the capsule was the only significant factor, and intrapelvic cytology was an important factor without significance. Although capsular rupture caused by the surgeon showed poor prognosis by the Kaplan-Meier method, no significance was observed for this factor by multivariate analysis. CONCLUSION: Multivariate analysis showed that capsular rupture caused by the surgeon did not affect the prognosis in stage I and II ovarian cancer.

Adenocarcinoma↗

Laryngeal carcinoma--multivariate analysis of prognostic factors in 1252 consecutive patients treated with primary radiotherapy.

Multivariate analyses of prognostic factors were carried out in 1252 consecutive patients with laryngeal squamous cell carcinoma treated with primary radical radiotherapy. Ten percent of patients had positive neck nodes Most of the patients were in stage I (48%), the remainder in stage II (24%), III (18%) and IV (10%). Of these patients, 746/1 252 (60%) were controlled by primary treatment but 506/1 252 (40%) had residual tumor or recurrent disease. The larynx was preserved in 62% of patients. The 5-year actuarial values for disease-specific and overall survival were 78% and 60%, respectively. The results of a univariate analysis showed multiple significant prognostic factors, and in a Cox proportional hazards model it was found that gender and T-classification were significant for T-failure, locoregional failure, death from cancer and death from all causes. The region of origin, nodal involvement, differentiation and pretreatment hemoglobin value were significant for several of the above-mentioned endpoints. Laryngeal carcinoma is curable when treated with primary radiotherapy, and this treatment confers a high degree of organ preservation. Independent prognostic factors in the multivariate analyses were gender, region of origin, T-stage, nodal involvement, differentiation and hemoglobin.

Adolescent↗

The value of prognostic factors in prostatic cancer.

Several prognostic parameters of prostatic carcinoma needed to help guide treatment in individual patients are discussed. Tumour volume, nodal and bone metastases, grading, prostate-specific antigen and DNA ploidy have been correlated with prognosis. Recent studies have analysed tumour volume in detail. However, currently there is no single prognostic factor which can predict tumour aggressiveness on an individual patient basis to rationalize decisions. Multivariate analyses are therefore in progress to determine independent prognostic variables.

Humans↗

Erythrocyte sedimentation rate as a tumor marker in human prostatic cancer. An analysis of prognostic factors in 300 population-based consecutive cases.

BACKGROUND: The natural history of prostatic cancer is variable. Our knowledge of prognostic factors is limited; therefore, research is needed. METHODS: The cases of 300 population-based consecutive patients with a diagnosis of cancer of the prostate were analyzed regarding different prognostic factors (but with special reference to the erythrocyte sedimentation rate [ESR]). RESULTS: After a mean observation time of 100 months, M category, ESR, grade, performance status, hemoglobin level, and T category were found to correlate with disease-specific death using multivariate analysis. The variables correlating with progression in the multivariate model were M category, ESR, T category, grade, treatment, and age. Patients treated with estrogen had a significantly lower risk (relative hazard, 0.3) of relapse. ESR was highly statistically significant (P less than 0.0001) as a prognostic factor. With the variable in linear form, a 20-mm/h higher level suggested a 29% increased risk, on average, for dying of prostatic cancer (using a best-fit multivariate model). However, the relationship was not linear. After correcting for the effect of other factors, the risk for dying of prostatic cancer was lowest when the ESR was 40-50 mm/h and highest when its values were highest. CONCLUSIONS: ESR is an indicator of increased risk of progression and death in prostatic cancer. Other prognostic factors such as M and T categories, grade, performance status, hemoglobin level, and age currently are more important when planning treatment. It is possible that the ESR reflects aspects of tumor-host relationship and that both a low and high ESR are markers for patients with receding host defence mechanism.

Aged↗

Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors.

PURPOSE: The purpose of this study was to analyze the prognostic value of baseline hemoglobin levels before radiotherapy in patients with head and neck tumors. PATIENTS AND METHODS: In a retrospective study with a median follow-up of 43 months, we analyzed the results of 214 patients irradiated for head and neck cancer between January 1, 1990 and January 1, 1998 (180 men and 34 women; median age 58 years). The treatment concept consisted in adjuvant radiotherapy in 58 patients, 77 patients received definitive radiochemotherapy, 42 patients definitive radiotherapy, and 37 patients reirradiation for in-field recurrence. Baseline hemoglobin values were divided in four groups of the same patient number (quartiles). Several known prognostic factors like sex, age, tumor stage, histologic grading, performance status, and treatment scheme were analyzed for their influence on overall and event-free survival and correlated with pretreatment hemoglobin values (Kaplan-Meier method). In addition, univariate und multivariate logistic regression analyses were carried out to evaluate the effect of baseline hemoglobin on response rates. RESULTS: The median survival (event-free survival) of all patients amounted to 15 months (10 months). 25%, 50%, and 75% of patients had hemoglobin values < 11.2 g/dl, < 12.7 g/dl, and < 13.9 g/dl, respectively. In the univariate analysis, the following variables were significant prognostic factors for overall/event-free survival (log-rank test): treatment concept (p < 0.001/p < 0.001), tumor stage (p < 0.001/p < 0.001), general condition (p < 0.001/p < 0.001), and pretreatment hemoglobin (p = 0.014/p = 0.05). Multivariate analysis (Cox) proved these parameters to be independent of each other. In addition, response rate after radiation showed a strong association between hemoglobin and local control probability (p = 0.02). CONCLUSION: In this retrospective analysis, baseline hemoglobin level was shown to be an independent significant prognostic factor in radiotherapy of head and neck cancer patients. Therefore, the value of tumor anemia as a prognostic factor should be emphasized more.

Adult↗

Comparison of DNA ploidy and S-phase fraction with prognostic factors in gastric cancer.

OBJECTIVE: To assess the value of DNA ploidy and S-phase fraction (SPF) as prognostic factors in gastric cancer. STUDY DESIGN: DNA ploidy and SPF were analyzed in 289 gastric cancer cases using flow cytometry and compared with the clinical and histopathologic features of the tumors. RESULTS: Aneuploidy was found in 36% of the patients; it was more frequent in the intestinal type of cancer (56%) as compared to the diffuse type (15%). Aneuploidy was also related to advanced TNM stage, cardiac location and high mitotic activity. In univariate survival analysis, TNM stage and tumor size were the most important prognostic factors. High SPF was significantly related to inferior survival rates, but DNA ploidy did not have any significant correlation with survival when all patients were analyzed together. However, in diffuse-type cancer, both DNA ploidy and SPF were significant prognostic factors. In multivariate analysis, DNA ploidy proved to be an independent predictor of survival in gastric cancer. CONCLUSION: The results indicate that in addition to TNM stage, flow cytometric analysis of DNA ploidy and SPF are important prognostic factors in gastric cancer.

Adenocarcinoma↗

Prognostic factor analysis for plaque psoriasis.

BACKGROUND: Little is known about the long-term prognostic factors which affect clinical outcomes after the diagnosis of psoriasis. OBJECTIVE: To identify the prognostic factors which predict long-term outcomes after diagnosis. METHODS: Patients' clinical characteristics at diagnosis were associated with long-term prognosis using the logistic regression method for 169 psoriasis patients (median follow-up time 11.6 years). RESULTS: The factors age > or =40 [odds ratio 0.27, 95% confidence interval (CI) 0.10-0.72, p = 0.0091], male (odds ratio 2.67, 95% CI 1.02-7.00,p = 0.0459) and BMI > or =25 (odds ratio 2.74, 95% CI 1.01-7.42, p = 0.0480) had significant effects on long-term prognosis after diagnosis. A simple prognostic index based on these factors was proposed. CONCLUSIONS: Three major prognostic factors were identified. The proposed index may be useful in the design of future clinical trials for psoriasis and in the selection of appropriate therapeutic approaches for individual patients.

Adolescent↗

[Multivariate analysis of prognostic factors in Philadelphia chromosome-positive chronic granulocytic leukemia].

OBJECTIVE: To investigate the prognostic factors of the patients with Philadelphia chromosome-positive chronic granulocytic leukemia (CGL). METHODS: Clinical and laboratory parameters of 209 CGL patients at diagnosis were analyzed in relation to survival. COX regression analysis were used to identify the statistically significant prognostic factors. RESULTS: The median survival time was 57 (3 - 179) months, and 5 year survival rate was 48%. From the COX regression model, the four main poor prognostic factors were as follows: percentage of bone marrow blasts (>or= 0.04), percentage of peripheral blood blasts and promyelocytes and presence of erythroid precursors in peripheral blood. According to the prognostic scores, three groups of CGL were identified. The low-risk group was with a median survival time of 76 months, the intermediate-risk group with 56 months, and the high-risk group with 31.5 months (P < 0.01). The 5 year survival rate was 70.42%, 46.30% and 18.18% (P < 0.01), respectively. CONCLUSIONS: A prognostic scoring system suitable for Chinese CGL patients was proposed.

Adolescent↗

Analysis and validation of prognostic factors for CML. German CML Study Group.

The analysis and validation of prognostic factors is a decisive prerequisite with regard to the development and application of risk-adjusted therapies. Among others, the Sokal index 1 and Kantarjian's new staging system 2 were scores set up to assess the survival of every patient individually. By means of 504 Ph- and/or bcr-abl-positive patients of the German CML study I, we tried to validate both scores mentioned above. Whereas Kantarjian's staging system provided rather unsatisfactory results, the discrimination of different risk groups was more promising with respect to the Sokal index. Still, concerning the differentiation between risk groups for the interferon-alpha (IFN-alpha) treated patients of the German study I, the Sokal index also failed. Hence, we applied Cox stepwise regression technique and identified three prognostic factors for the IFN-alpha treated patients, i.e. eosinophils, erythroblasts (both in peripheral blood), and extramedullary manifestations. We developed our own score and found an encouraging 5-y survival rate of 90% (95% confidence interval (CI) 76-100%) for a certain low-risk group of 41 out of 120 IFN-alpha treated patients. With the need to validate our score and, if possible, not only to confirm the above result but also to identify other particular patient groups, we launched the European Prognostic Factors Project (E.P.F.P.). Within this project, our special interest will be dedicated to patient groups who might also benefit from a bone marrow transplantation.

Adolescent↗

Carcinoma of the tonsil: prognostic factors.

OBJECTIVES: This study was conducted to provide a review of the prognostic factors of tonsillar carcinoma. DESIGN: A retrospective analysis. SETTING/PATIENTS: Patients with squamous cell carcinoma of the tonsil, treated in Northern Alberta, at the Cross Cancer Institute from 1975 to 1995 were analyzed using a population-based, head and neck cancer registry. There were 102 patients, 73 male and 29 female, ranging in age from 35 years to 83 years, with a mean of 60 years. The clinical stages were T1: 5 patients; T2: 27 patients, T3: 33 patients; T4: 11 patients; and Tx: 3 patients. The nodal stages were N0: 33 patients, N1: 26 patients; N2: 34 patients, N3: 7 patients; Nx: 2 patients. METHOD: The patients were treated with various modalities: surgery alone: 2 patients; surgery plus radiation: 26 patients; radiation treatment alone: 61 patients; and others: 13 patients. Patients were classified according to the UICC TNM 1992 criteria. The overall 5-year Kaplan-Meier survival in our series was 39%. The cause-specific 4-year survival was 57%. Various prognostic factors and their impact on survival were studied. RESULTS: On univariate analysis, the following factors were found to be significant. Age < 50 vs. > 50 (p = .02); endophytic growth pattern vs. exophytic growth of the primary (p = .01); ulcerated lesions vs. nonulcerated lesions (p = .000); various T stages (p = .003); clinical extension vs. no extension of primary disease (p = .02); combined modality of treatment (surgery and radiation treatment) had the best chance of survival compared to radiation treatment alone (p = .03). Nodal stages N0 vs. N+ disease (p = .2); sex of the patient, female vs. male (p = .83); and dose of radiation treatment < 5000 cGy vs. > 5000 cGy (p = .41) were found not to be significant. When the above significant factors were stratified according to the stage of the disease, only two were significant; ulcerated lesions vs. nonulcerated lesions (p = .04), and the modality of treatment chosen (e.g., radiation alone vs. radiation plus surgery) (p = .02). CONCLUSIONS: In this series of patients, combined-modity approach using surgery and radiation treatment was found to be the best way to treat carcinoma of the tonsil. However, each treatment strategy should be individualized taking into account various prognostic factors.

Adult↗

Conformal high dose rate brachytherapy improves biochemical control and cause specific survival in patients with prostate cancer and poor prognostic factors.

PURPOSE: To improve outcome for patients with prostate cancer with poor prognostic factors higher than conventional radiation doses are required. To achieve this outcome a brachytherapy boost was given. We report the results of the first high dose rate dose-escalation brachytherapy trial. MATERIALS AND METHODS: Between 1991 and 2000, 207 patients were prospectively enrolled in a dose escalation trial including pelvic radiotherapy and conformal high dose rate prostate brachytherapy boost. The dose was increased from 5.5 to 11.5 Gy. per implant. Patient eligibility for the study included pretreatment prostate specific antigen 10 or greater, Gleason 7 or greater or clinical stage T2b or higher. No patient received hormonal therapy. The American Society for Therapeutic Radiology and Oncology consensus panel definition of biochemical failure was applied. RESULTS: Median patient age was 69 years. Mean followup was 4.7 years (range 0.6 to 10.4). The 5-year actuarial biochemical control rate was 74%. The 5-year biochemical control was 85% for 1 poor prognostic factor, 75% for 2 and 50% for all 3 (p = 0.001). On Cox regression multivariate analysis lower brachytherapy dose, and higher Gleason and nadir value were associated with biochemical failure. The 5-year actuarial overall survival was 92%, cause specific survival 98% and disease-free survival 68%. The 5-year actuarial rates of complications were 8% and 0% for grades 3 and 4 genitourinary, and 0.5% and 0.5% for grades 3 and 4 gastrointestinal, respectively. The 5-year actuarial impotence rate was 51%. CONCLUSIONS: For patients with poor prognostic factors external beam radiation therapy with conformal high dose rate brachytherapy boost improved biochemical control, resulting in a high cause specific survival rate with low toxicity. Another important advantage is that the patient is not radioactive after the high dose rate implant.

Actuarial Analysis↗

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

BACKGROUND: The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. METHODS: The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. RESULTS: Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. CONCLUSIONS: Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value.

Adult↗

Prognostic factors and scoring system for survival in colonic perforation.

BACKGROUND/AIMS: No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. METHODOLOGY: Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. RESULTS: The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. CONCLUSIONS: Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

APACHE↗

Prognostic factors of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are rare neoplasms of unknown etiology and pathogenesis. Their clinical behavior is very unpredictable and a reliable prognostic factor is lacking. The aim of this study was to analyze some prognostic factors and estimate which one is the most reliable. Thirty-eight biopsy specimens of GIST were immunolabeled for PCNA, CD34, vimentin, NSE and actin. The greatest diameter, histological grading, mitotic count, DNA-index and S-phase were estimated for each case. All patients were followed-up for at least 24 months or to death. The data were analysed by univariate and multivariate statistical analysis using a computer program. The results showed that greatest diameter, tumor grade, mitotic count and PCNA-index are prognostic factors in univariate analysis. In multivariate analysis only the greatest diameter is a useful prognostic factor for planning further therapy.

Adult↗

Immunologic parameters as significant prognostic factors in lung cancer.

Immunologic prognostic factors in lung cancer have not been fully clarified. We report the results of a prospective study undertaken to clarify the correlation between various cellular immunologic parameters and the survival of lung cancer patients. A total of 287 lung cancer patients were enrolled in this study. Representative in vitro cellular immune activities including lymphoblastogenesis and natural killer cell activities, in addition to the percentage of main lymphocyte subsets (CD3, CD4, CD8, HLA-DR, and Fc gamma R III on T cells) in the peripheral blood were evaluated before the initiation of therapy. The immune factors that influence the prognosis were analyzed by the log rank test and a multivariate analysis using the Cox proportional hazards model. Univariate analysis of the survival curves revealed a significant difference with regard to disease stage (P<0.0001), age (P=0.007), gender (P=0.0037), and HLA-DR (%) (P=0.048), when all the non-small cell lung cancer (NSCLC) patients (n=257) were analyzed together. This analysis, based on the histologic type, revealed that HLA-DR (%) was a significant predictor of survival in squamous cell carcinoma (P=0.0013) and small cell carcinoma (P=0.0025). A decreased CD4/CD8 ratio in small cell carcinoma (P=0.0062) and male gender in adenocarcinoma (P=0.0086) were factors associated with a worse prognosis. Multivariate analysis identified a significant correlation between survival and disease stage (P<0.0001) and gender (P=0.0243) in adenocarcinoma, disease stage (P<0.0001), age (P=0.0436) and HLA-DR (%) (P=0.0142) in squamous cell carcinoma, and HLA-DR (%) (P=0.0212) and CD4/CD8 (P=0.0112) in small cell carcinoma, suggesting independent prognostic significance. A variety of immunologic indices have prognostic significance for the different types of lung cancer. Among these, the HLA-DR (%) in the peripheral blood is the most reliable factor for squamous cell carcinoma and small cell carcinoma.

Adenocarcinoma↗

Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer.

In order to identify the prognostic factors that significantly influence the disease-free survival rate after surgical resection of primary breast cancers, we determined tumour and lymph node grades, and immunohistochemical staining for estrogen and progesterone receptors (ER and PR), c-erbB-2, p53, bcl-2, bax and PCNA in 76 patients. Univariate analysis showed that increased grade of tumour and lymph nodes, negative immunostaining for ER, positive immunostaining for c-erbB-2, and a high PCNA index (> or = 30%) negatively influenced the disease-free survival rate, but PR, p53, bcl-2 and bax had no predictive value. Although p53 was not an independent prognostic factor by itself, the combination of p53, bcl-2, and bax proved to correlate with the disease-free survival, with the best prognosis noted in tumours negative for p53 and positive for both bcl-2 and bax, intermediate prognosis in tumours negative for p53 and positive for either bcl-2 or bax and worst prognosis in tumors negative for p53 as well as bcl-2 and bax. Tumour grade correlated positively with PCNA index, while positive staining for ER correlated negatively with tumour grade as well as with PCNA index, although this was statistically insignificant. Immunostaining of breast cancers for bcl-2 correlated negatively with tumour grade and PCNA index. Immunostaining for c-erbB-2 correlated positively with PCNA but not with tumour grade. Immunostaining for p53 tended to correlate positively with PCNA, but not with tumour grade. Immunostaining for PR and bax did not correlate with tumour grade and PCNA index. These results suggest that in addition to tumour size and lymph node involvement, immunostaining for ER, c-erbB-2, and a high PCNA index are important prognostic factors in human breast cancer. Wild-type p53 with preserved bcl-2 and bax gene products is also a favorable prognostic factor indicating breast cancer at an early stage of cancer progression.

Adult↗

Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. MATERIALS AND METHODS: The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. RESULTS AND CONCLUSIONS: Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

Biomarkers, Tumor↗

Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers.

PURPOSE: To evaluate prospectively the prognostic value of SF2 for local control and survival in patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS: Following informed consent tumor specimens were obtained from 156 patients with primary carcinomas of the head and neck region. The specimens were assessed for the ability to grow in vitro (colony forming efficiency, CFE) and inherent radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft-agar clonogenic assay. Patients were treated mainly with neoadjuvant chemotherapy plus radiation therapy usually as a combination of accelerated external beam and interstitial radiotherapy. The probabilities of local control and survival were analyzed by univariate, bivariate and Cox multivariate analyses. RESULTS: Successful growth was achieved in 110/156 specimens and SF2 values were obtained from 99/156. Eighty four out of these patients underwent radical treatment. The median SF2 value for the 84 tumors was 0.40. At a mean follow-up time of 25 months (range 7-65) the median SF2 value of tumors from 14 patients who developed local recurrence was 0.53, which was significantly higher than the median of 0.38 for tumors from 70 patients without local recurrence (p = 0.015). Tumor SF2 was a significant prognostic factor for local control (p = 0.036), but not for overall survival (p = 0.20). Tumor SF2 was an independent prognostic factor for local control within bivariate and Cox multivariate analyses. CONCLUSIONS: This study has shown that tumor radiosensitivity measured as SF2 is a significant prognostic factor for local control in head and neck cancers.

Adult↗