Multivariate Prognostic Index Research Articles

Multivariate prognostic index and triplet regimen efficacy predictive index in locally advanced and metastatic gastric cancer: pooled analysis from three clinical trials using individual patient data.

To construct an effective prognostic index to predict overall survival (OS) and triplet regimen efficacy for advanced gastric cancer (AGC) patients treated with platinum-based and fluorouracil-based chemotherapy. Between 2011 and 2021, 679 patients from two randomized phase III trials and one phase II trial were enrolled. We collected 11 baseline clinicopathological and 14 hematological parameters to establish a prognostic index. Univariate and multivariate Cox analyses were used to screen prognostic factors, and a prognostic index nomogram was conducted. Seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic nomogram named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in the low-risk group (median OS, 15.5 versus 8.0 months, p < 0.001). The areas under the curve of the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. A validation and external cohort verified the prognostic value of the FARS index. Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (p = 0.018). The constructed FARS index to predict the OS of AGC patients and the TRIS index to screen out the dominant population for triplet regimens can be used to aid clinical decision-making and individual risk stratification.

A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer.

BackgroundPeople’s Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors.ObjectiveTo compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM) stage in patients undergoing gastric cancer resection.MethodsThe inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic nutritional index (PNI), and prognostic index (PI) were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage.ResultsIn univariate analysis, preoperative serum C-reactive protein (P<0.001), serum albumin (P<0.001), GPS (P<0.001), PLR (P=0.002), NLR (P<0.001), PI (P<0.001), PNI (P<0.001), and TNM stage (P<0.001) were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024), NLR (P=0.012), PI (P=0.001), TNM stage (P<0.001), and degree of differentiation (P=0.002) were independent predictors of gastric cancer survival. GPS and TNM stage had a comparable prognostic value and higher linear trend chi-square value, likelihood ratio chi-square value, and larger area under the receiver operating characteristic curve as compared to other inflammation-based prognostic scores.ConclusionThe present study indicates that preoperative GPS and TNM stage are robust predictors of gastric cancer survival as compared to NLR, PLR, PI, and PNI in patients undergoing tumor resection.

P37 Multivariate prognostic index with emphasis on proliferation adds specificity to standard prognostic factors in operable breast cancer

P37 Multivariate prognostic index with emphasis on proliferation adds specificity to standard prognostic factors in operable breast cancer

P130 Comparison between univariate and multivariate prognostic index to evaluate treatment efficacy in subgroups of patient at different risks of death. Data from a systematic overview

P130 Comparison between univariate and multivariate prognostic index to evaluate treatment efficacy in subgroups of patient at different risks of death. Data from a systematic overview

Syntactic structure analysis in invasive breast cancer: Analysis of reproducibility, biologic background, and prognostic value

The reproducibility, biologic background, and prognostic value of syntactic structure analysis were studied in a group of 94 patients with invasive primary breast cancer. Using an interactive digitizing video overlay system, the centers of malignant breast cancer nuclei were marked in the five (subjectively) most cellular fields of vision for each case at a final magnification of × 1,200, and the corresponding minimum spanning tree was composed for each field. From each minimum spanning tree, 10 syntactic structure features were derived; subsequently, the mean, standard deviation, minimum, and maximum values of the five fields analyzed were calculated for further statistical analysis. Forty statistics thus were available for each case. The reproducibility of repeatedly measuring the same field (independent of nuclearity) and the same patient twice by the same or different observers was good for most of the syntactic structure features. When comparing the statistics of the syntactic structure features with other established prognosticators, correlations were found with (in this order) standard deviation and mean nuclear area (expressing nuclear differentiation), volume percentage epithelium (expressing architectural differentiation), and mitotic activity index. In univariate survival analysis several syntactic structure statistics yielded prognostic significance, the best being the maximum of the number of nuclei with two neighbors ( P = .002; Mantel-Cox test, 12.4). Multivariate analysis revealed that syntactic structure features did not provide additional prognostic values with regard to each other. However, they did show additional prognostic values with regard to the multivariate prognostic index (currently one of the best prognosticators in breast cancer), which combines the mitotic activity index, lymph node status, and tumor size. Measurement of syntactic structure features could therefore contribute to an improved prediction of prognosis of breast cancer patients. In conclusion, syntactic structure analysis is a simple, fast, and highly reproducible technique that shows prognostic value in invasive breast cancer and also has important prognostic value with regard to the well-established and prognostically strong morphometric features. It seems to be a promising new method of analyzing tissue architecture in breast cancer and perhaps in many other tumors.

Reproducibility of mitosis counting in 2,469 breast cancer specimens: Results from the Multicenter Morphometric Mammary Carcinoma Project

The Multicenter Morphometric Mammary Carcinoma Project is a prospective study on the reproducibility and prognostic value of routine quantitative assessments, especially the mitotic activity index (MAI), the multivariate prognostic index (MPI; a combination of MAI, tumor size, and lymph node status), the mean nuclear area, and DNA ploidy assessments in patients with invasive breast cancer. Fourteen pathology laboratories providing routine services to 35 hospitals throughout The Netherlands are participating in this project. In this article, the reproducibility of MAI and MPI assessments is described. Assessment of the MAI was, according to a strict protocol, first performed in the participating laboratories; thereafter, slides were transferred to the coordination center in Amsterdam for quality control. Analysis of the reproducibility of the assessments in 2,469 patients showed correlation coefficients between 0.81 and 0.96 (mean, 0.91) for the MAI and between 0.91 and 0.97 (mean, 0.96) for the MPI. The reproducibility was fairly constant in time, although it showed a slight drop in the middle of the 2-year intake period. A prognostically relevant discrepancy in MPI (caused by differences in MAI) between the original and quality control assessments was found in only 7.2% of the cases. When analyzing the reasons for these discrepancies, a plausible explanation could be found in all cases: bad tissue processing and ignorance of or negligence in following the protocol guidelines for selection of the counting area or in the process of counting were the most important flaws. Since these errors are largely controllable, an even lower discrepancy rate is theoretically achievable. In conclusion, in a routine setting it can be learned, within a reasonable time, to perform mitosis counting in a highly reproducible way if a strict protocol is carefully followed. This opens the way for a wider application of the MAI and MPI in breast cancer patients. Motivation is, however, an important factor to obtain reproducible results, and ongoing quality control is essential to guarantee the reproducibility of the assessments.

Further evaluation of the prognostic value of morphometric and flow cytometric parameters in breast‐cancer patients with long follow‐up

The added prognostic value of cellular DNA content compared with single and combined morphometric factors and classical parameters such as tumor size, nodal status, histologic grade and estrogen receptor (ER) content was investigated in 225 consecutive breast-cancer patients with long follow-up. Of all features investigated, the MPI (multivariate prognostic index) had the strongest prognostic value [Mantel-Cox (MC) = 48.2, p less than 0.00005]. The results further showed that neither age nor ER content had significant prognostic value, but the DNA index (DI) as a single parameter had (though weak) prognostic significance (MC = 5.9, p = 0.015); a similar result was obtained with the percentage of S-phase cells (MC = 6.1, p = 0.013). The DI had (restricted) additional prognostic value to the morphometric features (MPI plus DI Mantel-Cox 53.0, p less than 0.0001). The percentage of S-phase cells had no additional prognostic value over the MPI. On the other hand, the additional value of the DI over tumor size and nodal status was much more impressive (MC = 41.0 and 40.7), although it did not reach the prognostic significance of the MPI. Prediction of disease outcome with a linear combination of quantitative microscopical parameters of the primary tumor alone [MAI (mitotic activity index), DI and mean nuclear area] was very accurate, even without considering lymph-node status (MC 30.8, p less than 0.0005). Grade had no additional value to the MPI at all (p = 0.76). This could be especially important for lymph-node-negative patients in whom the prognostic value of the MPI and the MAI are confirmed.

The Multicenter Morphometric Mammary Carcinoma Project (MMMCP): A Nationwide Prospective Study on Reproducibility and Prognostic Power of Routine Quantitative Assessments in the Netherlands

The Multicenter Morphometric Mammary Carcinoma Project (MMMCP) has been set up to investigate prospectively the prognostic value and reproducibility of routine assessments of the morphometric Multivariate Prognostic Index (MPI) and other quantitative parameters in comparison with classical prognosticators and steroid receptors in breast cancer patients. In this project, 34 hospitals participate, divided over six geographically different regions. Of each patient entering in the study, multiple clinical and classical pathological parameters (including tumor size and lymph node status) as well as several quantitative parameters such as mean nuclear area, DNA index and mitotic activity index will be evaluated. Of all patients, the MPI will be assessed with tumour size, lymph node status and mitotic activity index. The quantitative assessments are performed in all consecutive breast cancers which enter the participating pathology laboratories, and all measurements are controlled in Amsterdam. The patient intake time will be from January 1, 1988 until January 1, 1990. It is expected that 3000 patients will enter in this study. Follow up data will be gathered up to 10 years. However, two to five years after the initiation of the Project, a first evaluation of the reproducibility and prognostic significance of routine MPI and other assessments in breast cancer patients will be possible. A detailed description of this project is given.

The Multivariate Prognostic Index and nuclear DNA content are independent prognostic factors in primary breast cancer patients.

The predictive value of a previously described Multivariate Prognostic Index (which incorporates weighted values of the mitotic activity index, tumor size, and the axillary lymph node status), and the nuclear DNA content (DNA) was evaluated in 156 patients with primary invasive ductal breast cancer, diagnosed between 1980 and 1983. The results were analysed with respect to the occurrence of distant recurrence and survival of the patients after at least 3 yr of follow-up (range 36-73 months; median 44 months). Known prognostic factors such as lymph node status, tumor size, and the mitotic activity index correlated independently with distant recurrence. Furthermore, in respect to survival, the investigated prognostic factors (except DNA content) were significantly correlated. The results indicate that the predictive value of the Multivariate Prognostic Index (MPI) is stronger (P less than 0.001) than of the nuclear DNA content (P less than 0.005) with respect to distant recurrence. In a Cox multivariate regression analysis DNA ploidy turned out to be an independent prognostic factor once the MPI was selected. Furthermore, in Cox's analysis, DNA ploidy was the fourth selected variable after lymph node status, mitotic activity index, and tumor size in individual parameter analysis. The results of this study indicate that, with respect to breast cancer screening programs, it seems worthwhile to integrate morphometric features, the MPI, and DNA ploidy in a new prognostic model.

The value of morphometry to classic prognosticators in breast cancer.

In 271 breast cancer patients with adequate follow-up for at least 5.5 and maximally 12 years, the value of morphometry to classic prognosticators of breast cancer (tumor size and axillary lymph node status) was assessed. Previous studies had indicated the value of this quantitative microscopic technique. Apart from quantitative microscopic features, subjective qualitative features such as nuclear and histologic grade were assessed as well. Univariate life-table analysis showed the significance (p less than 0.001) of several features such as lymph node status, tumor size, nuclear and histologic grade, and several morphometric variables (mitotic activity index, mean and standard deviation of nuclear area). Cellularity index was also significant (p = 0.02). Survival analysis with Cox's regression model, using a stepwise selection as well as backwards elimination, pointed to three features: mitotic activity index, tumor size, and lymph node status. Mitotic activity was the most important prognostic feature, but the combination of these three features in a multivariate prognostic index had even more prognostic significance. Kaplan-Meier curves showed that the 5-year survival of lymph node-negative patients (n = 146) is 85%, versus 93% in patients with a "good prognosis index" (n = 150). For lymph node-positive patients (n = 125), 5-year survival was 55%, compared with 47% in the "high index" (poor prognosis) patients (n = 121). Logistic discriminant analysis with 5.5-year follow-up as a fixed endpoint (191 survivors and 80 nonsurvivors) essentially gave the same results. Application of two instead of one decision threshold (e.g., numerical classification probability 0.60 and 0.40) decrease the number of false-negative and false-positive outcomes, however, with a number of patients falling in the class "uncertain." Thus, in agreement with other studies, morphometry significantly adds to the prognosis prediction of lymph node status and tumor size. Mitotic activity index is the best single predictor of the prognosis. An additional index advantage is that the multivariate model results in a continuous index variable that can be subdivided in many classes with an increasing risk of recurrence, so that more refined clinical therapeutic decision making is possible in individual patient care. The morphometric techniques are inexpensive and fairly simple and therefore can be applied in most pathology laboratories.

Multivariate prognostic index from exercise test after acute myocardial infarction

Multivariate prognostic index from exercise test after acute myocardial infarction

Multivariate Prognostic Index in Acute Myocardial Infarction for Individual Duration of Hospitalization

To estimate the feasibility of an early and individualized discharge of acute myocardial infarction patients, a new prognostic index was constructed from Cox's regression model for survival analysis. From the first 5 d in the coronary care unit the significant prognostic variables in the index were heart failure (definite objective signs of congestive heart failure and/or definite cardiomegaly and/or pulmonary vascular enlargement on chest x ray in upright position), cardiogenic shock, atrioventricular block, and age. From the index the individual patient's probability of survival up to day 36 after admission could be directly predicted. The more positive the index, the higher was the probability of death. The prognostic efficacy was good, with two unexpected deaths from 149 patients in the lowest risk group. With a selected mortality risk of 5% from the day of discharge until day 30 after admission, 134 patients (52%) could be discharged on day 6. To have the risk of less than or equal to 5% after discharge another 54 patients (21%) would have to stay in the hospital for 24 d. Following this system of early and individualized discharge there were few serious post-discharge complications (one cardiac arrest and one ventricular tachycardia). Reinfarctions could not be predicted. This model could save around 2000 hospitalization days per year in this hospital.