Prognostic factors in gastric cancer: the value of vascular invasion, mitotic rate and lymphoplasmacytic infiltration.

A retrospective analysis of 321 gastric cancer patients was made to assess the prognostic value of TNM classification, tumour differentiation, Laurén classification, proliferative rate, inflammatory reaction and tumour invasion in vascular or neural structures of the gastric wall. The TNM classification showed the strongest correlation with survival in univariate and multivariate analyses (P < 0.0001). The invasion in lymphatic or vascular system and Laurén classification were also independent prognosticators in multivariate analysis (P < 0.05). In univariate analysis, the WHO-grade, the size and the location of the tumour and perinueral invasion were significant prognostic factors (P < 0.01), as were the infiltration of lymphocytes and plasma cells in the tumour (P < 0.05). On the other hand, the mitotic indices reflecting the proliferative activity of the tumour cells showed no significant correlation with the prognosis. The results indicate that the prognostic power of the TNM classification can be further increased by assessment of the above special histological features in gastric cancer.     

Prognostic factors in invasive cutaneous malignant melanoma: a population-based study and review

A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6-2.1), increasing Clark level (OR 1.8, 95% CI 1.6-2.0), ulceration (OR 1.8, 95% CI 1.6-2.0), nodular melanoma (OR 1.5, 95% CI 1.3-1.6) and increasing age (continuous variable, P < 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2-1.7) and ulceration (OR 1.4, 95% CI 1.2-1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P = 0.04), as did age at diagnosis (P = 0.005).     

Prognostic factors in cutaneous desmoplastic melanoma

BACKGROUND:

Desmoplastic melanoma (DM) is a rare subtype of melanoma that is characterized by malignant spindle cells separated by prominent, fibrocollagenous stroma. Primary melanomas either may be entirely desmoplastic or almost entirely desmoplastic (pure DM [pDM]) or may exhibit a desmoplastic component admixed with a nondesmoplastic component (combined DM [cDM]).

METHODS:

Patients who were diagnosed between 1993 and 2007 at a single institution with clinically localized, primary cutaneous melanoma (PCM) that contained a desmoplastic component and who underwent sentinel lymph node (SLN) biopsy were identified. Clinical and pathologic features of the primary tumors were correlated with DM type, SLN status, and patient outcome.

RESULTS:

Two hundred fifty‐two patients (167 men, 85 women) were identified (median age, 61 years). The median tumor thickness was 2.0 mm. One hundred twenty‐three patients (48.8%) had pDM, and 129 patients (51.2%) had cDM. Overall, 17 patients (6.7%) had positive SLN status, including 12 patients with cDM and 5 patients with pDM. Because of the low SLN‐positive rate, a statistically significant difference in SLN status between patients with cDM (8.5%) and patients with pDM (4.9%; P = .25) could not be demonstrated. Older patient age, being a man, positive SLN status, and increasing tumor thickness were associated significantly with poorer disease‐free survival (P < .05), although only the latter 2 variables were independently predictive. In addition, cDM type (P = .017) was associated significantly and independently with a shorter time to recurrence.

CONCLUSIONS:

In this largest study to date of patients with DM who underwent SLN biopsy, the SLN‐positive rate in patients with DM was lower than that in patients with conventional melanoma. The results indicated that DM type is associated significantly and independently with the time to recurrence and should be evaluated routinely in all patients with PCM. Cancer 2010. © 2010 American Cancer Society.     

Prognostic factors in thin cutaneous malignant melanoma

A small subset of patients with thin (less than 0.76 mm thick) primary cutaneous malignant melanomas develop metastases. Features that may help differentiate higher and lower risk lesions in this thickness range are reported to include the patient's age and sex, anatomic site and diameter of the primary lesion, Clark level of invasion, development of a vertical growth phase, the mitotic index, ulceration, regression, and cellular aneuploidy. In this report, we review the literature regarding the significance of these factors on the patient's prognosis.     

Prognostic factors for cutaneous malignant melanoma in Vaud,Switzerland

We considered, by means of a multivariate approach, trends in survival from cutaneous malignant melanoma in relation to patient and tumor characteristics, using data from the Cancer Registry of the Swiss Canton of Vaud. Between 1980 and 1994, 1,229 cases of incident cutaneous malignant melanoma were registered. There was a decline in the proportion of neoplasms in the head and neck and lower limbs, and a rise in those of the trunk and upper limbs, an increase in superficial spreading melanoma and in tumors of limited thickness, mostly in females. Five-year crude survival was 0.68 for males and 0.82 for females, and relative survival of 0.79 for males and 0.89 for females, corresponding to a multivariate hazard ratio (HR) of 0.63 for females vs. males. Survival was inversely related to age, with 5-year relative survival of 0.92 at age 15–44 years, 0.85 at age 45–64 years, and 0.79 at age ≥65 years. With reference to histological type, no significant difference was observed in males, but in females nodular melanoma showed reduced survival. Compared with melanoma of the limbs, the HR was 1.46 for melanoma of the trunk, and 1.23 for those in the head and neck, and the difference was greater in females. A strong relation, in both sexes, was observed between survival and tumor thickness, with an HR of 3.96 for tumors ≥4 mm vs. those <1.50 mm. After allowance for all other factors considered, most recent calendar period of diagnosis was associated with improved survival in both sexes (HR = 0.72), but mostly in females. Although differences in survival tended to be larger during the first 2 years after diagnosis, the pattern was similar for most prognostic factors considered up to 10 years after diagnosis. Int. J. Cancer 78:315–319, 1998.© 1998 Wiley-Liss, Inc.     

Cancer-testis antigen expression in primary cutaneous melanoma has independent prognostic value comparable to that of Breslow thickness, ulceration and mitotic rate

To determine the effect of Cancer-Testis Antigen (CTAg) expression on the natural history of primary cutaneous melanoma we compared its impact on prognosis with that of known prognostic factors and its relationship with other clinicopathologic characteristics.The immunohistochemical expression of three CTAgs (MAGE-A1, MAGE-A4 and NY-ESO-1) in 348 cases of stage I and stage II primary cutaneous melanoma was analysed and correlated with clinicopathologic characteristics, relapse free survival (RFS) and overall survival (OS). A Cox proportional hazards regression model was used to analyse factors which independently predicted RFS.All three CTAgs were significantly co-expressed with each other (p < 0.001). The median RFS for patients with CTAg-negative tumours and CTAg-positive tumours was 72 months and 45 months, respectively, (P = 0.008). Univariate analysis demonstrated that the impact of CTAg expression on RFS was comparable in magnitude to that of Breslow thickness, ulceration and tumour mitotic rate. Multivariate Cox regression analysis indicated that CTAg expression was a powerful independent predictor of RFS (risk ratio (RR) = 1.715, 95% confidence interval (CI) = 0.430-0.902, P = 0.010). In contrast, CTAg expression was demonstrated to have no prognostic impact on overall survival.This study demonstrates that CTAg expression in primary cutaneous melanoma is a strong independent predictor of RFS and it is comparable to other known important prognostic factors. CTAg expression has no relationship with overall survival, suggesting anti-melanoma immunity directed towards CTAg expression may contribute to the natural history of the disease. In view of these results, further investigation of the function of CTAgs and their potential use in therapeutic targeting is warranted.     

Prognostic factors of myxofibrosarcomas: implications of margin status, tumor necrosis, and mitotic rate on survival

BACKGROUND: Myxofibrosarcomas (MFS) are characterized by tumor progression with increased metastases after local recurrences (LR). Few series had appropriately addressed what parameters independently affect prognosis. METHODS: Seventy primary localized MFS were analyzed for local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS). Follow-up was obtained in 61 cases. RESULTS: Thirty-eight males and 32 females had primary tumors ranging from 1.5 to 24 cm. Thirty and 40 tumors were superficial and deep, respectively, with 26 cases (38%) having positive margins. The 5-year LRFS-, MeFS-, and DSS-rates were 30%, 60%, and 73%. Positive margins (P = 0.0003) were the only inferior LRFS predictor. High grade (FNCLCC 2 and 3) was a negative factor of both MeFS (P = 0.0078) and DSS (P = 0.0174), and high stage (AJCC stage 3) was predictive of MeFS (P = 0.0470). However, both grading and staging were not prognostically independent. In multivariate analyses, mitoses >or=20/10 HPF (P = 0.0009, RR = 9.71) and positive margins (P = 0.0203, RR = 4.27) were independent adverse DSS predictor. However, tumor necrosis >or=10% (P = 0.0092, RR = 3.91) independently correlated with worse MeFS, together with mitoses >or=20/10 HPF (P = 0.0176, RR = 3.80) and positive margins (P = 0.0121, RR = 3.41). CONCLUSIONS: Margin status and histologic property both affect the prognosis of MFS. The former correlates with improved LRFS and translates into final survival benefits.     

Prognostic information in soft tissue sarcoma using tumour size,vascular invasion and microscopic tumour necrosis-the SIN-system

We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5-27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers' grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.     

Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma

The prognostic relevance of blood vessel invasion (BVI) in non-small cell lung carcinoma (NSCLC) remains controversial, as is the question of whether its finding should influence therapeutic decisions after an R0 resection. One hundred and twelve cases of NSCLC were included in the study. All had been treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. In all cases, lymphatic metastatic spread was at its earliest stage and only one regional lymph node was involved, 27.0+/-8.9 nodes per patient being examined histologically. Most of the cases were pT2 (75.9%) and pN1 (81.3%), and all were MX/M0 and R0. 62.5% were at stage IIB, 25.9% at stage IIIA, and 9.8% at stage IIA. BVI was found in 45.5% of the tumors (V1), and 18.8% exhibited both lymphatic invasion and BVI (L1V1). Local recurrence occurred in 10.7% of the patients, distant metastasis in 24.1%, and both forms of tumor progression simultaneously in a further 7.1%. Thus 31.2% of the patients developed distant metastases by hematogenous spread (to the brain, bones, lung, adrenal, and liver, in descending order of frequency), mostly within two years of surgery. Late metastasis is not typical of NSCLC. Adenocarcinomas showed a strong tendency to be associated with a poorer prognosis than squamous cell carcinomas, probably because of their more frequent involvement of blood vessels. Five-year survival (Kaplan-Meier method) was significantly lower in V1 cases (37.2%) than in V0 cases (56.0%; p = 0.0249). Adjuvant mediastinal radiation in node-positive cases of NSCLC may prevent local recurrence but is unlikely to influence the development of distant metastases. The histological detection of BVI is of prognostic relevance and should be considered for inclusion in the staging criteria and indications for adjuvant chemotherapy.     

Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma

This study aimed to test the hypothesis that lymphovascular invasion adds prognostic information to histological grade and tumour size in node-negative invasive carcinoma of the breast. Lymphovascular invasion was assessed in haematoxylin and eosin tumour sections from 2760 patients with node-negative invasive breast carcinoma treated with definitive surgery. Patients were divided into two groups: 990 in the no adjuvant therapy series (diagnosed in 1974-1988) with median follow-up of 13 years; and 1765 in the selective adjuvant therapy series (1988-2000) with median follow-up of 6.8 years. Lymphovascular invasion was identified in 19% of tumours and was associated with larger tumour size, higher histological grade and younger age. Overall, survival was associated on multivariate analysis with lymphovascular invasion, histological grade and tumour size in both patient series, and with histological type in the no adjuvant therapy series. In conclusion, lymphovascular invasion is an independent prognostic factor in node-negative breast cancer and should be considered in decisions about adjuvant treatment in this group of women.     

Identification of risk in cutaneous melanoma patients: Prognostic and predictive markers

New therapeutic modalities for melanoma promise benefit in selected individuals. Efficacy appears greater in patients with lower tumor burden, suggesting an important role for risk-stratified surveillance. Robust predictive markers might permit optimization of agent to patient, while low-risk prognostic markers might guide more conservative management. This review evaluates protein, gene, and multiplexed marker panels that may contribute to better risk assessment and improved management of patients with cutaneous melanoma.     

Prognostic factors in patients with thick cutaneous melanoma (> 4 mm)

BACKGROUND: The current study was conducted to examine the role of multiple clinical and histologic factors in the prognostic assessment of patients with thick primary melanoma (> 4 mm, classified as T4). METHODS: A retrospective analysis was performed in 329 patients with T4 cutaneous melanomas who were seen at the University of California at San Francisco Melanoma Center between 1978 and 2000. Fourteen histopathologic features were recorded prospectively by a single dermatopathologist. In addition, 9 clinical factors were analyzed. RESULTS: Several histologic factors were found to have a significant impact on the survival of patients with T4 melanoma. On univariate analysis, tumor thickness, ulceration, mitotic rate, microsatellites, vascular involvement, and histogenetic type of the primary tumor all were found to have a significant impact on the overall survival rate. Regional lymph node involvement reduced the overall survival of T4 patients dramatically. The 5-year overall survival of patients with lymph node-negative T4 disease was 61%, compared with 30% for those with lymph node-positive disease. When lymph node status was taken into account, tumor thickness, vascular involvement, and ulceration all remained independent predictors of overall survival on multivariate Cox regression analysis. Neither age, gender, nor anatomic location appeared to affect the recurrence-free or overall survival rates. CONCLUSIONS: Patients with thick primary cutaneous melanomas (> 4 mm) comprise a heterogeneous group. The presence or absence of lymph node involvement, vascular involvement, and ulceration appears to result in significantly divergent overall survival rates in this patient cohort. Consideration of these factors has important implications in the management of patients with T4 melanoma.     

Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy

A retrospective study was made of the results of high dose radiotherapy (≥50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971–April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with >65 Gy, the two year local control was 35%. If treated with <65 Gy the one year local control was ≤40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was <100 cm², the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis were found.     

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.     

Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study

BACKGROUND AND OBJECTIVES: Depth of invasion and stage of the disease are established prognostic indicators in cutaneous malignant melanoma. The role of other parameters is still an open problem. METHODS: In 93 consecutive patients with cutaneous malignant melanoma, the level of invasion, tumor thickness, ulceration, vascular invasion, lymphoplasmocytic infiltrates, and mitotic index were evaluated by histology. Expression of Ki-67 and PCNA proliferative antigens together with vimentin, S100, and HMB 45 proteins were assessed by immunohistochemistry. RESULTS AND CONCLUSIONS: Disease-free and overall survival were correlated with tumor stage, tumor thickness, level of invasion, macroscopic pattern, ulceration, vascular invasion, expression of HMB 45, PCNA, and Ki-67/MIB1. Stage, HMB 45, and PCNA were independent prognostic factors for disease-free survival, whereas tumor stage, tumor thickness, and expression of both proliferative antigens influenced overall survival independently. The variables studied demonstrated reciprocal correlation; therefore, analysis of many prognostic parameters in malignant melanoma could be recommended.