Low Risk Of Distant Metastasis Research Articles

Distant Metastases Following Permenanet Interstitial Brachytherapy for Patients With Clinically Localized Prostate Cancer

Purpose: Recent publications have suggested high risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival than patients receiving definitive external beam radiation therapy. To date, none of these studies have compared distant metastases and cause-specific survival in brachytherapy patients including those with high risk features. In this study, we evaluate such parameters in a consecutive cohort of patients undergoing permanent interstitial brachytherapy. Materials and Methods: Between April 1995 and June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with permanent interstitial brachytherapy. Risk group stratification was as per NCCN guidelines. Six hundred fifty eight, 893 and 289 were assigned to low, intermediate and high risk categories. Median followup was 7.4 years. Biochemical progression-free survival was defined as a PSA ≤0.40 ng/mL after nadir. The median day 0 D90 for all patients was 119.2% of prescription dose. Nine hundred thirty nine patients (51.0%) received supplemental external beam radiation therapy and 670 (36.4%) received androgen deprivation therapy (median duration 4 months). The mode of failure (biochemical, local or distant) was determined for each failed patient. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free and cause-specific survival at 12 years were 98.1% and 98.2%, respectively. When stratified by low, intermediate and high risk groups, the 12-year metastasis-free survival was 99.8%, 98.1% and 93.8% (p < 0.001), respectively. At 12 years cause-specific survival was 99.8%, 98.0% and 95.3% (p < 0.001) for low, intermediate and high risk groups. Biochemical progression-free survival at 12 years was 98.7%, 95.9% and 89.4% for low, intermediate and high risk patients (p < 0.001). In multivariate Cox-regression analysis, metastases-free survival was mostly closely related to Gleason score, while biochemical progression-free survival was associated with Gleason score and year of treatment. Cause- specific survival was most closely related to Gleason score. For biochemically controlled patients, the median post-treatment PSA was <0.02 ng/mL. Conclusions: Excellent cause-specific and metastases free survival are achievable with high quality brachytherapy for low, intermediate and high risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy. In particular, our metastases free survival and cause-specific survival for high risk patients appear superior to published radical prostatectomy and external beam radiation therapy series.

Pathological diagnosis for individualized therapy of colorectal cancer

Pathological diagnosis is essential today for the individualized therapy of colorectal cancer. In the routine analysis of colorectal carcinomas the molecular-pathological detection of a KRAS mutation predicts unresponsiveness to EGFR-targeted antibody therapies. Moreover, the detection of mismatch-repair deficiency or high-degree microsatellite instability indicates unresponsiveness to 5-FU monotherapy. Colorectal carcinomas with high-grade microsatellite instability and their associated morphologic subtypes, such as the medullary carcinoma, exhibit a low risk of distant metastasis and might be considered as carcinomas with low need for adjuvant chemotherapy.

Gene-expression assays: New tools to individualize treatment of early-stage breast cancer

The clinical and economic data for the two currently available gene-expression assays are reviewed. Two gene-expression assays, used to determine the risk of breast cancer recurrence in patients with stage I or II node-negative breast cancer, are currently available. Oncotype DX is an assay performed on RNA extracted from paraffin-embedded tumor tissue. It analyzes the expression of 21 genes: 16 cancer-related genes and 5 reference genes. The results are used to calculate a recurrence score to identify the likelihood of cancer recurrence in patients treated with tamoxifen. The results of two studies evaluating the ability of Oncotype DX to predict the risk of breast cancer recurrence suggest that patients with ER-positive, node-negative breast cancer and a low recurrence score may need only adjuvant treatment with tamoxifen, while intermediate- and high-risk patients may require additional treatment with adjuvant chemotherapy. MammaPrint, an oligonucleotide microassay performed on fresh-frozen tumor samples, analyzes the expression of 70 genes. Studies have found that MammaPrint allows young patients (<61 years) with early-stage breast cancer to be categorized as having a high or low risk of distant metastasis. High-risk patients may then be managed with more aggressive therapy. Two gene-expression assays, Oncotype DX and MammaPrint, have been developed to determine the risk of breast cancer recurrence in patients with stage I or II node-negative breast cancer. In the future, these tests may be useful in determining the need for systemic adjuvant therapy in such patients.

Osteogenic Sarcoma of the Mandible and Maxilla: A Canadian Review (1980–2000)

To determine factors that influence survival in patients with osteogenic sarcoma of the jaws. Multicentre retrospective clinical pathologic study of 35 patients with osteogenic sarcoma of the jaws by the Canadian Society of Otolaryngology-Head and Neck Surgery Oncology Study Group. Clinical charts and pathology results were reviewed on 35 patients treated between 1980 and 2000 for osteogenic sarcoma of the maxilla or mandible. Records were acquired from several major Canadian cancer registries. The following variables were examined for the effect on survival: age, gender, tumour site, grade and subtype, margins, and method of treatment. The average age of patients was 40 years (range 14-76 years). The sex distribution was similar, with 18 males and 17 females. The primary site was the mandible in 20 patients and the maxilla in 15 patients. The overall survival was 79 +/- 7% at 2 years and 57 +/- 9% at 5 years. Local recurrence (41%) was more common than distant metastases (17%). Positive margins were the factor most strongly associated with poor prognosis on multivariate analysis (hazard ratio = 3.5, p < .04). Disease-free survival dropped to zero by 3 years for those with positive margins (n = 7). For those who were resected with clear margins (n = 25), 5-year disease-free survival remained greater than 50% and the overall survival rate was almost 80%. Tumour site, grade, and subtype did not correlate with prognosis. There was a trend toward better prognosis in those who received chemotherapy in addition to surgery. Osteogenic sarcoma of the jaws is an aggressive disease with a high mortality rate despite a relatively low risk of distant metastases. Negative margins are paramount for optimizing survival rate. Chemotherapy, although contentious, should be considered given the data from long bone studies and the trend toward better survival in several studies, including ours.

Does histologic grade have a role in the management of head and neck cancers?

High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

Cmyc, p53 and bcl2, apoptosis‐related genes in infiltrating breast carcinomas: Evidence of a link between bcl‐2 protein over‐expression and a lower risk of metastasis and death in operable patients

Apoptosis is an important physiological process controlled by multiple genes, including c-myc, p53 and bcl-2, and its inhibition may lead to the development of human cancers. In this study, we analyzed expression of the c-myc gene using Northern blot and of the p53 and bcl-2 proteins by immuno-histochemistry in 175 breast tumor specimens obtained from patients with operable breast cancer. We evaluated the relation between expression of these 3 genes and (i) the main usual prognostic factors (tumor size, histo-prognostic grade, hormone receptors and number of positive nodes); (ii) the risk of death and relapse, taking into account these 4 factors, after a mean period of follow-up of 9.5 years (SD 2 years). Over-expression of c-myc, p53 and bcl-2 was observed in 35%, 23% and 63% of tumors, respectively. Over-expression of c-myc was strongly linked to the number of positive nodes (p = 0.0005). p53 protein expression was associated with both high-grade (p = 0.0001) and hormone receptor-negative (p = 0.0001) tumors. In contrast, bcl-2 protein over-expression was associated with the main favorable prognostic factors and, more particularly, with hormone receptor-positive tumors (p = 0.0001). Multivariate analysis, using the Cox model, showed that only 2 factors were independently linked to the risk of death: number of positive nodes, which increased the risk (p = 0.0001), and bcl-2 protein over-expression, which decreased the risk (p = 0.008). When bcl-2 over-expression was studied in relation to nodal status, hormone receptor status and chemo- and hormone therapy, no significant difference was observed between different subgroups of patients. bcl-2 expression was also associated with a significantly lower risk of distant metastasis (p = 0.04). In conclusion, bcl-2 expression characterizes a particular phenotype of breast cancer with a favorable prognosis, and it may therefore be used as a marker of long-term survival. Int. J. Cancer (Pred. Oncol.) 84:562–567, 1999. © 1999 Wiley-Liss, Inc.

C-myc, p53 and bcl-2, apoptosis-related genes in infiltrating breast carcinomas: evidence of a link between bcl-2 protein over-expression and a lower risk of metastasis and death in operable patients.

Apoptosis is an important physiological process controlled by multiple genes, including c-myc, p53 and bcl-2, and its inhibition may lead to the development of human cancers. In this study, we analyzed expression of the c-myc gene using Northern blot and of the p53 and bcl-2 proteins by immuno-histochemistry in 175 breast tumor specimens obtained from patients with operable breast cancer. We evaluated the relation between expression of these 3 genes and (i) the main usual prognostic factors (tumor size, histo-prognostic grade, hormone receptors and number of positive nodes); (ii) the risk of death and relapse, taking into account these 4 factors, after a mean period of follow-up of 9.5 years (SD 2 years). Over-expression of c-myc, p53 and bcl-2 was observed in 35%, 23% and 63% of tumors, respectively. Over-expression of c-myc was strongly linked to the number of positive nodes (p = 0.0005). p53 protein expression was associated with both high-grade (p = 0.0001) and hormone receptor-negative (p = 0.0001) tumors. In contrast, bcl-2 protein over-expression was associated with the main favorable prognostic factors and, more particularly, with hormone receptor-positive tumors (p = 0.0001). Multivariate analysis, using the Cox model, showed that only 2 factors were independently linked to the risk of death: number of positive nodes, which increased the risk (p = 0.0001), and bcl-2 protein over-expression, which decreased the risk (p = 0.008). When bcl-2 over-expression was studied in relation to nodal status, hormone receptor status and chemo- and hormone therapy, no significant difference was observed between different subgroups of patients. bcl-2 expression was also associated with a significantly lower risk of distant metastasis (p = 0.04). In conclusion, bcl-2 expression characterizes a particular phenotype of breast cancer with a favorable prognosis, and it may therefore be used as a marker of long-term survival. Int. J. Cancer (Pred. Oncol.) 84:562-567, 1999.