Median Cancer-specific Survival Time Research Articles

Prospective study of combined treatment with interferon‐alpha and active vitamin D3 for Japanese patients with metastatic renal cell carcinoma

To assess the safety and efficacy of combined therapy with interferon-alpha (INF-alpha) and active vitamin D(3) for metastatic renal cell carcinoma (RCC). Sixteen patients with metastatic RCC were enrolled in this prospective study. All received oral alfacalcidol (1 microg once daily) and INF-alpha (Sumiferon; 3 million units, three times a week). The primary endpoint was the response rate (defined as complete + partial remission). Secondary endpoints were cancer-specific survival and toxicity. The median follow-up period was 17 months (range: 5-49 months). The median age of the patients was 68 years (range: 41-73 years). The sites of metastases were: lung in 13 patients, bone in one, lung and bone in one, and lung, bone, and lymph nodes in one. Four patients (25%) had a partial response (PR), 10 patients (62.5%) showed no change (NC), and two patients (12.5%) had progressive disease (PD). The median cancer-specific survival time was 45 months. One patient had to discontinue vitamin D(3) because of hypercalcemia. Kaplan-Meier survival analysis revealed that metastasis at the time of initial diagnosis and older than average age were significant predictors of poor survival (P < 0.05). Combined treatment with INF-alpha and active vitamin D(3) has shown to be safe and effective for metastatic RCC patients.

METASTECTOMY FOR NON‐COLORECTAL, NON‐NEUROENDOCRINE LIVER SECONDARIES

The role of metastectomy for colorectal and neuroendocrine liver secondaries is well established. Significant palliation and survival have been reported after aggressive surgical resection. However, the role of liver resection for secondaries from other primary tumours is less well defined. In this study, we aim to describe our experience, including indications and selection criteria, operative strategy and clinical outcome of liver resection, for non-colorectal, non-neuroendocrine liver metastases. A review of prospectively collected operative database was conducted and patients who underwent liver resection of secondaries from non-colorectal, non-neuroendocrine primary tumours were studied. Eighteen patients were included in the study. There were 4 men and 14 women with a median age of 48 years (range, 37-78 years). Liver resection was carried out either for cure or for palliation of debilitating symptoms. Selection criteria included: (i) absence of extrahepatic disease and (ii) functional status of the liver and volume of remnant liver after hepatectomy. The median follow up was 24 months (range, 7-81 months) for 17 patients, excluding the one who defaulted after surgery. Cancer-specific survival and recurrence-free interval was calculated from the date of hepatectomy. Liver resection was considered curative in 13 patients. There was no 30-day mortality in this cohort of patients. The median recurrence-free survival time was 13 months (95% confidence interval (CI), 8-18 months). The median follow-up time for the 12 patients was 23.5 months (range, 7-35 months). Only five patients died due to cancer-specific causes and one died from acute myocardial infarction. The median cancer-specific survival time was 30 months (95% CI, 25-35 months). The 2-year survival rate was 77.1% (95% CI, 48.9-100%). The results are encouraging and suggest that with appropriate selection criteria, there is a role for metastectomy of non-colorectal, non-neuroendocrine liver secondaries.

DNA ploidy and S-phase fraction in carcinoma of the gallbladder related to histopathology, number of gallstones and survival.

Gallstones are a risk factor for the development of gallbladder cancer. We studied DNA ploidy and cell cycle composition by flow cytometry in archival specimens from 52 gall bladder carcinomas in relation to histopathological grade, tumour stage, gallstone number and survival. 69% of the gallbladder carcinomas showed aneuploidy. All tumours with single stones (N=11) were aneuploid while only 61% of tumours with multiple stones (N=41) were aneuploid (p=0.002). DNA aneuploidy was related to increase in T‐category (p=0.01), grade (p=0.02), and nuclear pleomorphism (p=0.0005). The distribution of DNA ploidy shifted from tetraploid in low stage towards triploid positions in high stage tumours (p=0.02) combined with higher S‐phase values in triploid tumours (p=0.05). S‐phase fraction increased during development from normal tissue to dysplasia, cancer in situ and cancer in diploid cases (p=0.0002), and further at the change from diploid to aneuploid (p=0.004). At a median cancer specific survival time of four months patients with diploid tumours had a better survival than those with aneuploid tumours (p=0.02). In multivariate analysis of the tumour characteristic, only T‐category and tumour grade were independent prognostic factors. The shift from diploid to aneuploid and the further shift of ploidy within aneuploid tumours are in agreement with the concept of a clonal development of gallbladder cancer. These changes are combined with a stepwise increase in the fraction of S‐phase cells. Low frequency of symptoms in single stone patients may be the reason for detection of malignancy at a late stage of tumour development.

Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival.

Tumor associated macrophages (TAM) influence diverse processes such as angiogenesis, tumor cell proliferation, and metastasis during tumor progression. In a variety of tumor types, the amount of TAM has been associated with prognosis, but their role in prostate cancer has not been elucidated. The purpose of this study was to investigate the role of TAM in a series of 85 cases of prostatic carcinoma, diagnosed at transurethral resection of the prostate between 1975-1983, using immunohistochemistry and morphometrical techniques. Macrophage density was assessed as the maximum number of TAM per field in the three most macrophage dense areas (TAMmax) and as the average volume density of TAM in an estimate of the whole resected tumor. Furthermore, the individual cell profile area of TAM was assessed with an image analyzer. Macrophage variables were thereafter related to histological grade, tumor stage, metastasis as well as to vascular density, tumor cell proliferation and survival. Patients with a volume density of TAM in the fourth quartile had a shorter median cancer specific survival time than patients in the first to third quartile (3.3 vs. 5.9 years, p=0.005). Furthermore, an increased macrophage cell profile area was related to poor clinical outcome (4.6 vs. 5.9 years, p=0.039) whereas TAMmax gave no prognostic information. In a multivariate analysis, metastasis and the volume density of macrophages gave independent prognostic information (p=0.0008, p=0.010). However, when excluding metastasis from the analysis, only Gleason score was an independent predictor of cancer specific survival (p= 0.005). The volume density of TAM, the macrophage cell profile area and TAMmax increased with increasing Gleason score (p=0.001, p=0.0001, p=0.0001 respectively). A correlation was found between the volume density of TAM and tumor cell proliferation (rs=0.44, p=0.001) and an increased macrophage cell profile area was associated to microvessel density (rs=0.42, p=0.0001). Together these results suggest that both the functional state (as reflected by cell size), number and location of the macrophages are of importance for their influence on prostate tumors, but macrophage quantification is not a strong independent prognostic factor.

Prognostic Factors in Patients with Nasopharyngeal Carcinoma

From 1971 to 1985 a total of 122 patients with non-distant metastatic nasopharyngeal carcinoma were treated at the Norwegian Radium Hospital with radiation doses that increased from 50 Gy (at 2 Gy/fractions) to 70 Gy (at 2 Gy/fractions) during the treatment period. Possible relationship between the increase in dose and survival time was investigated. The median cancer-specific survival time was 50 months, and the median crude survival time 38 months. No correlation was found between radiation dose and survival time. In a multivariate analysis histology was found to be the most important prognostic factor for survival with a relative risk of death from cancer of 3.4 and 3.2 for non-keratinizing carcinoma and squamous cell carcinoma respectively compared with undifferentiated carcinoma. When assessed in terms of N category the relative death risk for N2/N3 was 2.1 compared to N0/N1.