Average Survival Time Of Patients Research Articles

Prognostic serum markers in malignant pleural mesothelioma: Epidermal growth factor and platelet-derived growth factor

18097 Background: While no previous data has so far shown any difference between the efficacy of serum platelet-derived growth factor (PDGF-AB) and serum epidermal growth factor (EGF) in distinguishing MPM from benign pleural diseases, some pilot studies have shown the potentiality of both these markers in the prognosis of MPM patients. This study investigates this capacity by analyzing survival in a series of MPM patients. Methods: Using an ELISA method, EGF (ng/ml) baseline serum was determined in 83 newly diagnosed MPM patients, and in 62 cases PDGF-AB serum levels were also measured. After a median follow-up time of 11.8 months (range 0.4–52.1 months), the log-rank test was used to compare the survival curves, and Cox’s regression analysis was also performed. Results: Median serum values were 0.56 ng/ml (range 0.09–2.05) for EGF and 43.0 ng/ml (range 0.1–145) for PDGF-AB. Patients with EGF levels higher than the median level of 0.56 ng/ml had an average survival time of 9.4 months (95%CI: 5.7–13.2), while the average survival time of patients with below-median EGF levels was 13.2 months (95%CI: 10.6–15.8); a statistically significant difference (p=0.005). For patients with PDGF-AB levels higher than an assumed cut-off of 49.8 ng/ml, (above 75th percentile of MPM marker concentration) average survival was 7.9 months (95%CI: 4.5–11.3) as against the 14.9 months (95%CI: 10.3–18.7) in patients with below cut-off marker levels, again statistically significant (p=0.02). Cox’s regression analysis was performed on 42 patients in whom data on age, sex, histology, stage and platelet count were available. EGF and PDGF-AB levels higher than the selected cut-offs were confirmed as independent predictors of poor survival (HR=1.49; 95% CI: 1.04–2.13; p=0.03 and HR=1.96; 95% CI: 1.23–3.13; p=0.005, respectively). Conclusions: Our data suggest that circulating PDGF-AB and EGF levels are promising markers for clinical monitoring of MPM patients. No significant financial relationships to disclose.

MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma

Methylation of the DNA-repair gene O6-methylguanine-DNA methyltransferase (MGMT) causes gene silencing. This epigenetic modification has been associated with a favorable prognosis in adult patients with glioblastoma (GBM) who receive temozolomide and other alkylating agents. We explored MGMT promoter methylation in pediatric GBM and its relationship to survival and temozolomide sensitivity. We performed a retrospective study of MGMT promoter methylation in 10 pediatric GBM. The methylation status of the MGMT was determined using a 2-stage methylation specific PCR analysis on DNA extracted from tumor specimens which had been snap frozen at surgery. The relationships between MGMT promoter methylation and patient outcome and response to temozolomide were evaluated. Four of our 10 pediatric patients with GBM were found to have methylation of the MGMT gene promoter. Methylation of the MGMT promoter was shown to correlate (P = 0.0005) with survival. The average survival time for patients with methyltated MGMT was 13.7 months as compared to 2.5 months for the 6 patients with unmethylated MGMT promoter. Of the seven patients that received temozolomide, those patients that had the methylated MGMT gene promoter responded better to treatment (P = 0.007). As in adults, pediatric GBM patients with methylated MGMT promoter benefited from temozolomide. However, a stronger correlation with overall survival, regardless of treatment, was observed in this group of patients. These data suggest that MGMT methylation may be a prognostic factor for survival in pediatric GBM, as well as a marker for temozolomide sensitivity.

TAKING AIM AT MELANOMA

A CLASS OF SMALL MOLEcules called triphenylmethylamides (TPMAs) has been found to induce apoptosis (cell death) in melanoma cells ( J. Am. Chem. Soc. 2005, 127, 8686). The findings could point the way toward potential therapies for malignant melanoma, a particularly deadly form of skin cancer. Currently, a diagnosis of latestage melanoma is practically a death sentence. The average survival time for patients with such a diagnosis is only six months. Paul J. Hergenrother, an assistant professor of chemistry at the University of Illinois, Urbana-Champaign, decided to focus on melanoma after conversations with physicians. was really interested in the most untreatable forms of cancer, he says. As I started reading up on [melanoma], I found that indeed there's only one clinically approved compound, and it has only a 2% efficacy in complete remission. There's really no good treatment. With their discovery of TPMAs, Hergenrother and his coworkers hope to change ...

Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest

Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenylmethylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC(50) approximately 0.5 muM), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor kappa-B (NFkappaB) in the cell; NFkappaB is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NFkappaB and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.

Survival Following Treatment of a Cardiac Malignant Fibrous Histiocytoma

The authors report the successful surgical and chemotherapeutic management of a malignant fibrous histiocytoma with localization in the heart. This rare malignancy has specific morphologic characteristics and is diagnosed in adults when it is already locally aggressive or metastasized. The average survival time for patients with malignant fibrous histiocytoma is < 12 months. Neither clinical nor instrumental signs of recurrence have been detected in this patient after an aggressive surgical resection and a specific therapeutic approach.

Long-Term Results after Surgical Treatment of Organic Hyperinsulinism

43 patients were analyzed for their long-term results after operative treatment of organic hyperinsulinism. The average postoperative observation period totalled 7 years. In the case of solitary adenomas all patients were free of hypoglycemia symptoms and 3 patients required a second operation. In contrast to this only 1 out of 5 patients with multiple insulinomas was free of hypoglycemia symptoms. 1 patient had diabetes mellitus and in the other 3 patients eight operations have been necessary up to now; nevertheless, 1 of the patients had persistent hypoglycemic symptoms. The average survival time of patients with malignant islet cell tumors was 4 years even in cases with metastasis.

Pancreatic cancer. Evaluation of prognostic factors and treatment results.

From 1969 to 1984, 125 patients (49 women and 76 men) with pancreatic cancer were treated at the Department of Radiotherapy at Turku University Central Hospital. The mean age of the patients was 63 years. Surgery was the only treatment in 40 cases, 22 patients received radiotherapy, 27 chemotherapy, and 13 received both radiotherapy and chemotherapy after surgery or as the only treatment; 23 patients received no active therapy. The average survival time was 7.5 months. The mean survival times of patients in the purely surgical group was 8.1 months, in the radiotherapy group 8.7 months, in the chemotherapy group 8.1 months, and in the group which received both radiotherapy and chemotherapy 9.7 months. The average survival time of patients who received neither surgical nor oncological treatment was significantly shorter (3.2 months). Statistically significant factors regarding shorter survival times were metastases at presentation (survival time 3.9 months), and poor general condition (Karnofsky index less than 60; survival time 4.4 months).

TREOSULFAN IN THE TREATMENT OF OVARIAN CARCINOMA

A total of 90 patients has been treated with Treosulfan. The minimum follow-up period was 6 months. Distribution according to age and clinical stages corresponds to what is usually found. The treatment with Treosulfan was given in interrupted causes. The only serious side effect is a depression of the bone-marrow function. Apart from this, Treosulfan is well tolerated and in most cases the treatment can be carried out in the open ward. It is striking that the general condition of the patients very often was improved considerably. Five patients suffering from disseminated cancer apparently were cured. An excellent effect on ascites was seen since a complete disappearance of ascites was seen in 17 out of 27 patients with serous carcinoma and a transient improvement in six. There was hardly any effect of the treatment of the patients in the terminal stage of the disease. In stage III the average survival time for patients who died of the disease was proportional with the degree of response, viz.: Excellent r...

Treosulfan in the Treatment of Ovarian Carcinoma1

A total of 90 patients has been treated with Treosulfan. The minimum follow‐up period was 6 months. Distribution according to age and clinical stages corresponds to what is usually found. The treatment with Treosulfan was given in interrupted causes. The only serious side effect is a depression of the bone‐marrow function. Apart from this, Treosulfan is well tolerated and in most cases the treatment can be carried out in the open ward. It is striking that the general condition of the patients very often was improved considerably. Five patients suffering from disseminated cancer apparently were cured. An excellent effect on ascites was seen since a complete disappearance of ascites was seen in 17 out of 27 patients with serous carcinoma and a transient improvement in six. There was hardly any effect of the treatment of the patients in the terminal stage of the disease. In stage III the average survival time for patients who died of the disease was proportional with the degree of response, viz.: Excellent response: 20.4 months, good response: 15.7 months and no or poor response: 6.0 months.