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Results of chemo-radiotherapy and prognostic factors of small cell lung cancer.

We studied the therapeutic results and prognostic factors in 63 cases of small cell lung cancer (SCLC) experienced in our hospital over the past eight years. In the group initially treated with combination chemotherapy using COMP-VAD, the survival period was significantly prolonged. Use of adjuvant radiotherapy from the beginning had no effect on improvement in the survival period, but the period until local recurrences tended to be prolonged. Prognostic factors influencing survival were analyzed by the log rank test and generalized Wilcoxon test and multivariate analysis by the proportional hazard model of Cox. Statistical significance using univariate analysis was found for six factors (PS, clinical stage, LDH, albumin, treatment protocols, treatment response). The strong prognostic factors determined by multivariate analysis were, in the order of importance, chemotherapy protocol, initial PS, and treatment response.

Adult↗

Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973-1991.

BACKGROUND: A number of prognostic factors for thyroid carcinoma have been identified, including sociodemographic characteristics, such as age and gender, and tumor characteristics, such as histology and stage. The relative importance of these factors as independent predictors of survival for patients with papillary, follicular, anaplastic, and medullary thyroid carcinoma has been extensively studied but remains uncertain. METHODS: The authors used data collected by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute between 1973 and 1991 to investigate prognostic factors for each of the major histologic types of thyroid carcinoma in a population-based patient series and to assess the effect of these factors as predictors of survival. RESULTS: Both tumor and sociodemographic characteristics were independently associated with survival. Patients with papillary carcinoma had the highest 10-year relative survival (0.98), followed by those with follicular carcinoma (0.92) and medullary carcinoma (0.80). Anaplastic tumors had the lowest 10-year relative survival (0.13). Stage at diagnosis and differentiation status were strong independent prognostic factors for each histologic type. Advanced stage at diagnosis was a stronger prognostic factor for medullary carcinoma than for other histologic types. Increasing age was associated with lower relative survival for each histologic type. Gender, marital status, and ethnicity were significant, but weaker, predictors of survival. CONCLUSIONS: Survival varied markedly among patients with different histologic types of thyroid carcinoma. Stage at diagnosis and tumor differentiation were important prognostic factors for each histologic type. Age at diagnosis was a stronger predictor of survival for patients with follicular and medullary carcinoma than for patients with papillary carcinoma.

Adenocarcinoma, Follicular↗

Selective reporting biases in cancer prognostic factor studies.

BACKGROUND: Nonreported and selectively reported information and the use of different definitions may introduce biases in the literature of prognostic factors. We probed these biases in a meta-analysis of a prognostic factor for head and neck squamous cell cancer (HNSCC) mortality that has drawn wide attention--the status of the tumor suppressor protein TP53. METHODS: We compared results of meta-analyses that included published data plus unpublished data retrieved from investigators; published data; and only published data indexed with "survival" or "mortality" in MEDLINE/EMBASE, with or without standardized definitions. We also evaluated whether previously published meta-analyses on mortality predictors for various malignancies addressed issues of retrieval and standardized information. All statistical tests were two-sided. RESULTS: For the 18 studies with 1364 patients that included published and indexed data, we obtained a highly statistically significant association between TP53 status and mortality. When we used the definitions preferred by each publication, the association was stronger (risk ratio [RR] = 1.38, 95% confidence interval [CI] = 1.13 to 1.67; P = .001) than when we standardized definitions (RR = 1.27, 95% CI = 1.06 to 1.53; P = .011). The addition of 13 studies with 1028 subjects that included published but not indexed data reduced the observed association (RR = 1.23, 95% CI = 1.03 to 1.47; P = .02). Finally, when we obtained data from investigators (11 studies with 996 patients) and analyzed it with all other data, statistical significance was lost (RR = 1.16, 95% CI = 0.99 to 1.35; P = .06). Among 18 published meta-analyses of 37 cancer prognostic factors, 13 (72%) did not use standardized definitions and 16 (89%) did not retrieve additional information. CONCLUSIONS: Selective reporting may spuriously inflate the importance of postulated prognostic factors for various malignancies. We recommend that meta-analyses thereof should maximize retrieval of information and standardize definitions.

Aged↗

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE: The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA: A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS: Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS: Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiner's Grade 1. CONCLUSIONS: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Algorithms↗

Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs.

The objectives of this study were to determine prognostic factors for response to treatment, freedom-from-relapse (FFR) survival, and overall survival of 737 aggressive malignant lymphoma patients treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, methotrexate with leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH-84) regimen; to construct a prognostic index with factors isolated by multivariate analyses; and to validate this prognostic index with another set of patients. Complete response (CR) was reached in 75% of LNH-84 patients, and 30% of them relapsed. With a median follow-up of 36 months, median FFR survival and median overall survival were not reached. Low serum albumin level, high tumoral mass, weight loss, bone marrow involvement, greater than or equal to 2 extranodal sites, and increased lactic dehydrogenase (LDH) level were associated with a low response rate. Advanced stage, increased LDH level, and nonlarge-cell histologic subtypes (diffuse mixed, lymphoblastic, and small non-cleaved) were statistically associated with a high relapse rate and short FFR survival. Increased LDH level, low serum albumin level, tumoral mass larger than 10 cm, greater than or equal to 2 extranodal sites, advanced stage, and age older than 65 years were statistically associated with short overall survival. Four of these parameters, namely, LDH level, stage, number of extranodal sites, and tumoral mass, were put together to construct a prognostic index. This index partitioned LNH-84 patients into three subgroups of good, intermediate, and poor prognosis (P less than .00001): CR rates of 93%, 83%, and 61%; relapse rates of 12%, 25%, and 45%; 3-year FFR survival of 87%, 73%, and 53%, and 3-year survival of 88%, 71%, and 41%, respectively. This prognostic index was applied to a test set of patients: 155 patients treated on protocols of the Nebraska Lymphoma Study Group. Using this index, these patients had 3-year FFR survival of 70%, 40%, and 22% (P = .0002) and 3-year survival of 79%, 52%, and 31% (P = .005). In patients with aggressive lymphomas, this simple prognostic index could distinguish between patients requiring intensive treatment such as autologous bone marrow transplantation in first complete remission and those who could be treated with standard regimens.

Adolescent↗

Histologic prognostic factors for small-sized squamous cell carcinomas of the peripheral lung.

OBJECTIVE: Although the incidence of peripheral squamous cell carcinomas (SqCCs) of the lung has increased over recent years, histologic prognostic factors for small peripheral SqCCs have not been well established. The aim of this study is to identify clinicopathologic prognostic factors. MATERIALS AND METHODS: We evaluated various clinicopathologic parameters in 101 patients with peripheral lung SqCCs (defined as tumors located in or more peripheral to the fourth branching bronchus), measuring < or = 30 mm in diameter. RESULTS: Multivariate analysis showed that the size of the minimal tumor nest (MTN), a background of usual interstitial pneumonia (UIP) and lymph node metastasis were significant prognostic factors. MTN sizes were defined as large (>6 tumor cells), small (2-5 tumor cells) or single cell. The 5-year disease-free survival rate was significantly worse in patients with single cell nests (50 patients, 69.5%) than in those with small nests (42 patients, 94.1%) (P = 0.0035, log rank test). The MTN size had a significant impact on survival in patients with pathologic stage IA disease and tumors < or = 20 mm in diameter. A background of UIP, which correlated with the presence of a single cell invasive component and pleural involvement, was also a poor prognostic factor, suggesting that peripheral SqCC in UIP is highly malignant even if the tumor is small. CONCLUSION: The MTN size is a useful prognostic factor for small peripheral SqCCs. Tumors with a single cell invasive component appear to be highly malignant, and should be distinguished from invasive cancers with a low malignant potential (tumors with large or small tumor nest components).

Aged↗

[Comparative study on prognostic factors in young and old lung cancer patients under chemo-radiotherapy].

OBJECTIVE: To investigate the differences in prognostic factors between the young and old lung cancer patients treated by chemo-radiotherapy. METHODS: The clinical data were collected from 70 young patients (< 40 years old, the study group) and 82 randomly selected old patients (> or = 40 years old, the control group) treated by chemo-radiotherapy. Survival analysis was done by the Kaplan-Meier method, univariate analysis by Log rank test and multivariate analysis by Cox proportional hazard model, respectively. RESULTS: Median survival time was 10 months in the study group and 12 months in the control group. The 2-year survival rate was 11.1% versus 23.1% and the 5-year survival was 3.1% versus 5.4%, respectively. Univariate analyses demonstrated that symptom duration time, mis-diagnosis duration time, clinical stage, chemo-radiation regimen, radiation dose, DDP dose, weight loss and Karnofsky performance status were associated with the prognosis of the study group, and symptom duration time, clinical stage, radiation dose, DDP dose, weight loss and Karnofsky performance status were associated with that of the control group. Multivariate analyses showed that clinical stage, weight loss and Karnofsky performance status were independent prognostic factors for both groups, but DDP dose only for the study group. CONCLUSION: The overall survival was similar in young and old patient groups; There was some difference in prognostic factors between the two groups; DDP dose was an independent prognostic factor for young lung cancer patients which might bear dose-response relationship.

Adenocarcinoma↗

Metastatic urothelial cancer: evaluation of prognostic factors and change in prognosis during the last twenty years.

OBJECTIVE: This study was designed to establish prognostic factors for survival of patients with locally advanced or metastatic urothelial cancer. We have furthermore investigated changes in patient characteristics and treatment strategies during the last 20 years. PATIENTS AND METHODS: Between 1992 and 1997, a total of 156 patients with newly diagnosed recurrent locally advanced disease (nonresectable, radioresistant) and/or metastatic transitional cell carcinoma of the urothelial tract were included in a protocol evaluating clinical and laboratory prognostic factors at baseline. The relationship between these characteristics and survival was analyzed using univariate and multivariate methods. The results were compared to the survival results of similar patients treated previously from 1976 to 1991. RESULTS: Median survival after diagnosis of recurrent locally advanced or metastatic disease was 5.8 months. Multivariate analysis showed that good performance status (PS), normal alkaline phosphatase (AP), absence of liver metastases and chemotherapy were independent prognostic factors for long survival. An increase in survival was found when comparison was made with 240 patients treated in the period from 1976 to 1991, but the period of treatment had no independent importance in multivariate analysis. CONCLUSION: PS, AP and liver metastases are the major important prognostic factors in metastatic urothelial cancer. Stage migration and increased use of chemotherapy may have contributed to improved median survival during the last 20 years.

Carcinoma, Transitional Cell↗

Prognostic factors for patients with spinal metastases from lung cancer.

STUDY DESIGN: We conducted a retrospective study to identify prognostic factors of patients with spinal metastases from lung cancer. OBJECTIVE: To provide clinical data with strong association to the prognosis and to propose criteria determining indication of operation for spinal metastases. SUMMARY OF BACKGROUND DATA: To make a proper selection of patients for whom surgery is indicated, forecasting short-time survival after spinal metastases is very important. In the past, there has been no report of prognostic factors of patients with such metastases from this cancer. METHODS: This study included 114 patients with spinal metastases of lung cancer. Tumors were histologically categorized as non-small cell lung cancer (NSCLC) in 94 patients and small cell lung cancer (SCLC) in 20 patients. We investigated prognostic factors after spinal metastases using Cox comparative hazard model and a preoperative prognostic score proposed by Tokuhashi. We also investigated the patients who underwent operation for spinal metastases from lung cancer in our hospital. RESULTS: Multivariate analysis showed that the significant prognostic factors for survival after spinal metastases from NSCLC were performance status (PS), Ca, Alb. Among SCLC patients, Ca, Alb, and a history of chemotherapy were significant (P < 0.05) in univariate analysis. The score of Tokuhashi was not correlative to the survival period. Among the operated patients, postoperative PS was significant for the period of postoperative survival. CONCLUSION: PS, Ca, and Alb in NSCLC and Ca, Alb, and a history of chemotherapy in SCLC are useful for determining an indication of operation for spinal metastases from lung cancer.

Activities of Daily Living↗

Prognostic Factors for Node-negative Breast Cancers: Results of a Study Program by the Japanese Breast Cancer Society.

BACKGROUND: Prognostic factors for predicting the recurrence of node-negativebreast cancers have been controversial. The present study was performed to elucidate practically useful prognostic factors using formalin-fixed paraffin sections. METHODS: This was a case-controlled multi-institutional study that composed 40 patients with recurrent node-negative breast cancer and 80 patients with node-negative breast cancer but without recurrence after radical surgery. Tumors weresmaller than 3 cm in diameter and were treated surgically between January 1, 1985 and December 31, 1990. The recurrent and non-recurrent cases were matched with regard to their age, adjuvant chemotherapy and the year in which surgery was performed. Fourteen immunohistochemical factors and 8 histological factors of theprimary tumor were studied on formalin-fixed, paraffin-embedded sections by immunohistochemical and histochemical analyses. RESULTS: According to univariate analysis, factors such as progesterone receptor (PgR), MIB-1, CD44v6, CD44v9 and platelet-derived endothelial cell growth factor (PDECGF) were significantly different between the recurrent and non-recurrent groups (p &ly; 0.1; Wilcoxon-Mann-Whitney analysis). Chi-squared test showed significant differences in MIB-1, cdc2 and stromal plasminogen activator receptor (suPAR). Histologically, mitotic count was also significantly different between the two groups (p < 0.005). Multivariate analysis revealed that positivity for cdc2 (p=0.01), high mitotic count (p=0.04) and negativity for CD44v9 (p=0.02)were independent prognostic factors among variables selected by univariate analysis, and that positivity for MIB-1 (p=0.03) and cdc2 (p =0.01), and negativity for CD44v9 (p =0.03) were independent prognostic factors among the immunohistochemical markers examined. CONCLUSION: Our results indicated that positivity for MIB-1 and cdc2, high mitotic count and negativity for CD44v9 could serve as independent factors for predicting the recurrence of node-negative breast cancer.

Journal Article↗

Prognostic factors of thin cutaneous melanoma: an analysis of the central malignant melanoma registry of the german dermatological society.

PURPOSE: The increasing number of thin cutaneous melanomas (CM) with tumor thickness up to 1 mm demands a detailed analysis of prognostic factors for the classification and grading of these tumors. The aim of the present study was to identify prognostic factors in thin CM. PATIENTS AND METHODS: A series of 12,728 patients with thin incident primary invasive CM and follow-up data recorded between 1976 and 2000 by the German-based Central Malignant Melanoma Registry was analyzed using the multivariate Cox proportional hazard model to evaluate prognostic factors, and classification and regression trees analysis (CART) to define prognostic groups. RESULTS: Multivariate analysis found tumor thickness, sex, age, body site, and histopathologic subtype to be significant prognostic factors of thin CM. Ulceration and regression did not affect prognosis significantly. Prognostic classification based on the results of CART analysis resulted in three groups defined by tumor thickness, age, and sex. Ten-year survival rates of these groups varied between 91.8% and 98.1%, with improved classification as compared with subgroups by tumor thickness alone. CONCLUSION: Classification by tumor thickness identified prognostic subgroups with highest significance in thin CM, and the classification was improved by the introduction of age and sex. However, neither ulceration nor the level of invasion included in the new American Joint Committee on Cancer TNM system classification, revealed statistical significance as prognostic factors in thin CM.

Adult↗

DNA ploidy as a prognostic factor in rhabdomyosarcoma. Analysis of 35 cases with image cytometry.

OBJECTIVE: To correlate DNA ploidy in rhabdomyosarcoma (RMS) with other prognostic factors and patient survival and to search for possible reasons for inconsistent conclusions in similar, published studies. STUDY DESIGN: DNA content was measured in archival specimens obtained from 35 patients (23 children and 12 adults) with RMS. Cell suspensions were prepared by the modified Hedley technique, stained by the modified Feulgen-thionin method and analyzed by automated high-resolution image cytometry. DNA ploidy was assessed on the basis of DNA index values. We used the chi 2 test to correlate DNA ploidy with other prognostic factors, Kaplan-Meier procedure to estimate overall survival in terms of individual prognostic factors, log-rank test to calculate differences in survival between groups and Cox multivariate regression analysis to determine the independence of variables in relation to survival. RESULTS: A statistically significant correlation was found only between DNA ploidy and histologic subtype of RMS, patient sex and patient age. A hyperdiploid DNA pattern predominated among patients with embryonal RMS, and a tetraploid pattern dominated among patients with alveolar RMS. The highest 5-year survival rate was seen among patients with hyperdiploid RMS, followed by those with diploid, tetraploid and hypertetraploid RMS. Although DNA ploidy was a significant prognostic factor in univariate analysis, it did not retain its independent prognostic value in multivariate analysis, in which patient age, tumor size and histologic subtype were the only significant factors. We found 12 articles reporting on the association between DNA ploidy and survival of patients with RMS: 6 found a correlation, and 6 did not. The main reasons for the discrepancies seem to be the inclusion of chemotherapy-treated and nontreated patients, low number of patients and differences in grouping DNA histograms. CONCLUSION: The precise prognostic value of DNA ploidy in RMS remains equivocal. Larger, cooperative studies could give statistically more reliable results.

Adolescent↗

The time-related changes of the importance of prognostic factors in breast cancer. A sequential multivariate analysis of 1423 Japanese patients.

The value of individual prognostic factors may change dependent on the length of the follow-up period, if some factors have their greatest prognostic potential immediately after operation. It is not clear how long these factors keep their prognostic relevance. We retrospectively examined data on 1423 surgically treated Japanese patients with primary breast cancer between 1983 and 2002. Survival analysis was done starting at 2.5-yearly intervals after operation and follow-up in the first analysis started at the time of the operation. The changing importance of the prognostic factors during different follow-up periods was investigated by univariate and multivariate analysis. Based on multivariate analysis, tumor size retained its prognostic value even up to 7.5 years after operation, whereas the age, vascular involvement, ER and PgR showed a changing influence on prognosis dependent on the length of the follow-up period. The prognosis of patients some years after operation is necessarily different from the initial prognosis established after operation. Detecting the changing importance of prognostic factors could provide new biological insights that might otherwise be missed, and may help determine the most appropriate clinical use of various factors.

Adult↗

The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up.

We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer (SCLC) patients included in a prospective multicenter study with a minimum 5-year follow-up. Pretreatment clinical and laboratory parameters were registered. Possible prognostic factors were evaluated by univariate analysis (log rank test) and by the Cox multivariate regression model. In the univariate analysis of all patients, only age, nodal metastasis, and skin metastasis were not associated with survival. The multivariate Cox model identified gender, extent of disease, performance status (PS), weight loss, platelet count, LDH, and NSE as independent prognostic factors. In subset multivariate analyses according to extent of disease, we found haemoglobin level, PS, NSE, and total WBC as significant prognostic indicators for survival in limited-stage disease (LD-SCLC), while PS, weight loss, LDH, number of metastases, liver metastases, and brain metastases were identified as independent prognostic factors in extensive-stage disease (ED-SCLC). There was a significant correlation between serum LDH and NSE levels. In conclusion, gender, extent of disease, PS, weight loss, haemoglobin, WBC count, platelet count, LDH, and NSE were all found to be independent prognostic factors for SCLC survival. However, the prognostic value of these factors depends highly on whether all or subsets of SCLC patients are studied.

Aged↗

[Evolution and prognostic factors of adenocarcinomas of the prostate metastasizing at diagnosis].

OBJECTIVES: In 30-40% patients, prostate adenocarcinoma is diagnosed already in the metastatic phase, a percentage that will depend on the number of patients with localized cancer that we are unable to detect. Hormonal suppression is the most widely accepted therapeutical option, although there are doubts on the value of rescue treatment after the hormone-refractive stage. This paper analyses those parameters as well as the main prognostic factors in a series of 135 patients with metastatic prostate cancer at diagnosis. MATERIAL AND METHODS: Between 1983 and 1996, 414 patients were diagnosed with prostate adenocarcinoma in the Urology Unit. Móstoles Hospital, 135 of which (32.6%) were metastatic at the time of diagnosis and were managed as follows: 113 (84%) were treated with maximum androgenic blockade (MAB). 13 (9.6%) with orchiectomy and antiandrogens, 5 (3.7%) with various treatments, and only 4 received symptomatic treatment. Of those treated with MAB, 97 (72%) continued treatment after the hormone-refractive stage and 16 (12%) were given stramustine phosphate instead of the antiandrogen. Response monitoring was done basically by means of serial PSA determination. The parameters analyzed included survival and the following potential prognostic factors: age, performance status, metastatic bone pain, tumour diagnosis based on number of metastasis, prior PSA level, Gleason, local stage, M1 type at diagnosis based on the 1992 TNM classification, and response to the various treatment applied. RESULTS: Mean age: 72 years. Over an average of 25 (0-127) months, 80 (59%) patients have died; mean follow-up of patients alive at end of study: 24 months (3-111). Lost to follow-up: 6 patients (4.4%). Up to 1991, the proportion of patients with metastasis was 48%; since 1992, 24%. Percentage of patients diagnosed due to clinical manifestations of the metastasis (25 patients) over these two periods increased, mean age decreased and the proportion of patients with highly aggressive tumours increased. Mean overall survival, 26 months: influential prognostic factors: diagnosis due to metastasis and Gleason greater than 7; very poor prognosis for those receiving no hormonal therapy, with no differences between drug versus surgical treatment. Tumour-dependent mean survival, 32 months; influential prognostic factors: performance status, metastatic bone pain, diagnosis due to metastasis and Gleason greater than 7; very poor prognosis for those receiving no hormonal therapy. Progression-free interval, 19 months; influential prognostic factors: metastatic bone pain, PSA higher or lower than 90. Gleason greater than 7 and local stage: no differences between treatments. Mean survival after progression, 6 months; influential prognostic factors: diagnosis due to metastasis, M1b versus M1c patients: increased survival in patients rescued with stramustine phosphate. CONCLUSIONS: The proportion of prostate adenocarcinomas with metastasis at diagnosis shows a trend to decrease, although the percentage of patients who are diagnosed by the sings and symptoms of their metastasis is increasing. These patients should be treated with pharmacological or surgical hormone-suppression. Rescue treatment with stramustine phosphate prolongs survival. Influential prognostic factors: Gleason greater than 7, metastatic bone pain, tumour extent and previous PSA.

Adenocarcinoma↗

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.

PURPOSE: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. METHODS AND MATERIALS: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). RESULTS: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011). CONCLUSION: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

Adult↗

Prognostic factors for clinically localized prostate carcinoma: analysis of 938 patients irradiated in the prostate specific antigen era.

BACKGROUND: Pretreatment serum prostate specific antigen (PSA) level is a powerful prognostic factor for clinically localized prostate carcinoma. The traditional prognostic factors, T classification and Gleason score, appear to have been relegated to a minor position. This study was conducted to evaluate the relative prognostic roles of PSA, T classification, and Gleason score in a large cohort of men irradiated in the PSA era. METHODS: The authors analyzed the outcome for a group of 938 men with T1-T4, N0 or NX, M0 prostate carcinoma who received definitive external beam radiation therapy as their only initial treatment during the period 1987-1995. The T classifications were as follows: T1, 283 (30%); T2, 360 (38%); T3/T4, 295 (31%). Gleason scores were as follows: Gleason 2-6, 580 (62%); Gleason 7, 224 (24%); Gleason 8-10, 122 (13%). Pretreatment PSA levels (ng/mL) were as follows: PSA < or = 4, 167 (18%); PSA 4 to < or = 10, 363 (39%); PSA 10 to < or = 20, 259 (28%); PSA > 20, 149 (16%). At a mean follow-up of 43 months (range, 6-106 months), disease outcome specified as relapse/rising PSA, local recurrence, or metastasis was analyzed using univariate and multivariate techniques. RESULTS: The 6-year actuarial incidences of relapse/rising PSA, local recurrence, and metastases were 48%, 27%, and, 6%, respectively. In multivariate regression, pretreatment PSA level, T classification, and Gleason score were each independently highly significantly (P < 0.001) correlated with every endpoint. Pretreatment PSA level was the most significant variable for rising PSA and local recurrence, and T classification was the most significant variable for metastatic relapse. Using relapse/rising PSA as the endpoint, the authors formulated a highly significant 6-tier prognostic grouping based on PSA, T classification, and Gleason score, as follows: Category I: T1/T2, PSA < or = 4, and Gleason 2-6 (relapse rate, 6%); Category II: T1/T2, PSA < or = 4 and Gleason 7-10, or PSA 4 to < or = 10 and Gleason 2-7 (relapse rate, 30%); Category III: T1/T2, PSA 4 to < or = 10 and Gleason 8-10, or PSA 10 to < or = 20 and Gleason < 8 (relapse rate, 40%); Category IV: T3/T4, PSA < 10 (relapse rate, 46%); Category V: T3/T4, PSA 10 to < or = 20, and Gleason < 8 (relapse rate, 57%); Category unfavorable: any T, PSA > 20 and any Gleason, or PSA 10 to < or = 20 and Gleason 8-10 (relapse rate, 88%). CONCLUSIONS: The establishment of T classification and Gleason score as independent prognostic factors bridges an apparent gap between an older era and the current PSA era. PSA has supplemented, rather than supplanted, the utility of the traditionally established prognostic factors for clinically localized prostate carcinoma.

Aged↗

Preoperative CA 125: an independent prognostic factor in patients with stage I epithelial ovarian cancer.

OBJECTIVE: To evaluate the prognostic importance of preoperative CA 125 levels in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer in comparison with the established prognostic factors: degree of differentiation, FIGO substage, and age. METHODS: In a retrospective analysis, the traditional prognostic factors and CA125 levels (cutoff value 65 U/mL) were studied in 201 patients who were treated in five centers during 1984-1993. Patients with borderline tumors or non-epithelial ovarian carcinomas were excluded, as were women in whom CA 125 had not been determined preoperatively. RESULTS: In univariate analysis (Mantel test), overall survival decreased significantly in patients positive for CA 125 (P < .001). Substage (P = .004) and histologic grade (P = .01) also significantly influenced survival prognosis. When the effects of preoperative CA 125 levels were correlated with histologic grade, all three subgroups with CA 125 levels equal to or greater than 65 U/mL were associated with a decreased survival probability (grade 1, P = .04; grade 2, P = .003; grade 3, P = .01). Multivariate analysis (Cox model) identified preoperative CA 125 as the most powerful prognostic factor for survival (P < .001), the risk of dying of disease being 6.37 times higher (95% confidence interval 2.39-16.97) in CA 125-positive patients. Although FIGO substage retained its significant influence on survival (P = .03), histologic grade and age were not prognostically important. CONCLUSION: Randomized trials investigating the efficacy of adjuvant treatment in patients with FIGO stage I epithelial ovarian cancer should also include stratification by preoperative CA 125 levels.

Age Factors↗