Non-localized Disease Research Articles

Pediatric cancer: analysis of hospital records

To analyze pediatric cancer hospital records regarding the occurrence of new cases; to verify the relation between sex, age, race, origin and the disease clinical extension; to describe the mortality of children with cancer; to explore the association of new cases with proposed demographic variables, disease clinical extension and vital status. Observational, descriptive, longitudinal study in children up to 14 years old, from Santa Catarina. Three hundred and seventy-one new cases of cancer were treated in a regional reference outpatient clinic (1994-98) and recorded according to the International Classification of Childhood Cancer. Multiple Correspondence Analysis was applied to evaluate the categorical variables. Three-hundred and seventy-one new cases of cancer were recorded with constant distribution in each year. Cancer affected preschoolers (41.5%) and males (55.8%). Leukemia was observed in 36.6% of the cases. Non-localized stage on the diagnosis occurred in 55.7%. The death occurred in 55.7% of the cases with non-localized disease and 16.3% with localized disease. At the end of the study 58.8% of the children were alive. We observed more cases of cancer at pre-school age and among male subjects. Leukemia is the most frequent type of cancer. Non-localized disease predominates on the diagnosis. The death frequency is higher in the group with non-localized disease. There is direct association with non-localized disease, living vital status, school age, adolescent age, female, and for non-localized disease with death vital status, infant age, pre-school age and male.

The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer

Purpose : Some prostate cancers may have molecular alterations that render them less responsive to radiation therapy; identification of these alterations before treatment might allow improved treatment optimization. This study investigated whether p53, a potential molecular determinant, could predict long-term radiation therapy outcome in a restricted group of relatively favorable-risk prostate cancer patients treated uniformly with irradiation alone. Methods and Materials : This study included 53 patients previously treated with radiotherapy for favorable-to-intermediate-risk prostate cancer. These patients were selected for relatively low pretreatment PSAs (≤21 ng/mL) and Gleason scores (≤7) to decrease the likelihood of nonlocalized disease, because disease localization was necessary to examine the efficacy of localized radiation therapy. The status of p53 was immunohistochemically assessed in paraffin-embedded pretreatment biopsy specimens, along with appropriate controls. This marker was selected based upon a usable mutation prevalence in early-stage prostate cancer and its potential linkage with radiation response via cell cycle, DNA repair, and cell death pathways. Correlation between p53 mutation and clinical outcome was analyzed in univariate and multivariate fashion and included conventional prognosticators, such as stage, grade, and PSA. Freedom from biochemical failure was determined using American Society for Therapeutic Radiology and Oncology criteria. Limitations of prior studies were potentially avoided by requiring adequate posttreatment follow-up (median follow-up in nonfailing patients of 5.1 years), as well as pretreatment PSA and Gleason scores that suggested localized disease, and uniformity of treatment. Results : The total group of 53 favorable-to-intermediate-risk patients demonstrated an actuarial biochemical failure rate of 35% at 5 years. Forty percent of all specimens had a greater than 10% labeling index for p53 mutation, and actuarial biochemical control was found to strongly and independently correlate with p53 status. Patients with higher p53 labeling indices demonstrated significantly higher PSA failure rates ( p < 0.001). In contrast, p53 status did not correlate with pretreatment PSA, grade, or tumor stage. Similarly, pretreatment PSA (log-rank 0.22), Gleason score (log-rank 0.93), and T stage (log-rank 0.15) were not prognostic for outcome in this group of patients selected for their relatively favorable clinical characteristics. Conclusions : ( 1) p53 status in pretreatment biopsies strongly predicted for long-term biochemical control after radiation therapy in favorable-to-intermediate-risk prostate cancer patients. ( 2) If validated in other independent clinical data sets, p53 status should be considered as a stratification factor in future clinical trials and could be useful in guiding treatment. Abnormal p53 status might favor surgical management, aggressive dose escalation, or p53-targeted therapy.

Usefulness of cardiopulmonary bypass in reconstruction of inferior vena cava occupied by renal cell carcinoma tumor thrombus.

Aggressive surgical treatment in renal cell carcinoma is still controversial. The aim of this paper is to assess inferior vena caval (IVC) reconstruction for suprahepatic vena caval renal cell carcinoma (RCC) tumor thrombus. Twelve patients with suprahepatic vena caval thrombus from renal cell carcinoma who underwent surgical repair with cardiopulmonary bypass were evaluated. The vena caval defect was reconstructed by direct suture, patch repair, or graft replacement. Of 12 patients undergoing partial cardiopulmonary bypass, tumor thrombus extended to the junction of the hepatic vein in three patients and to the right atrium in one. Tumor thrombus was removed manually or with balloon catheter. Tumor thrombus in the right atrium was removed during electrical ventricular fibrillation. Repair of the IVC was performed by direct suture of the IVC wall in two patients, patch repair with expanded polytetrafluoroethylene (EPTFE) graft in seven, and graft replacement with an EPTFE graft in three. There were no operative deaths and the only postoperative complication was one patient death from pulmonary emboli. The four patients with nonlocalized disease died within 2 years, but four patients lived for more than 3 years postoperatively. Survival was 37.5% at 3 years and 18.8% at 5 years by the Kaplan-Meier's method. (1) Partial cardiopulmonary bypass is useful for the control of bleeding when tumor thrombus in the IVC extends to the junction of the hepatic vein. (2) Nephrectomy with tumor thrombectomy of the IVC is valuable, and long-term survival is possible in patients without distant metastases or regional lymph node metastases.

Expression of the MDR1 gene product P-glycoprotein in childhood neuroblastoma.

In cancer treated with chemotherapy, multidrug resistance is characterized by increased genetic expression of P-glycoprotein (P-gp), which acts as an ATP-dependent drug-efflux pump. However, the clinical significance of the expression of the multidrug resistance gene (MDR1) product P-gp in neuroblastoma (NB) is still a matter of debate. In this study, the role of the expression of P-gp in NB was evaluated. NB tumor imprints and NB positive bone marrow smears from 23 children before and after multidrug chemotherapy were examined for P-gp expression by antialkaline phosphatase immunocytochemical analysis. Before chemotherapy, only 10% of the NB samples showed positivity for P-gp. At diagnosis, no difference in P-gp expression was found between primary tumor cells and NB cells from metastases to bone marrow. P-gp positivity was only observed in patients with nonlocalized disease. P-gp positivity was never found in tumor cells that were histologically well differentiated. No clear correlation of P-gp positivity with poor prognostic parameters, such as chromosome 1p deletion or MYCN amplification, were found. Multidrug chemotherapy did not induce enhanced expression of P-gp in the neuroblasts. However, at clinical recurrence, P-gp expression was found in the metastatic NB cells of five of seven bone marrow samples examined. The prognostic relevance of P-gp expression in NB was not clear from the results of this study. To resolve the uncertainties, a standardization of the methodology and more prospective studies are needed to determine whether routine analysis of P-gp is worth adding to the other prognostic parameters that are evaluated in NB patients. The finding that metastatic cells are capable of expressing MDR1, in contrast to the NB cells of the primary tumor, would certainly be an interesting topic for further study as work directed at understanding the progression to metastasis continues.

Use of hospital services by breast cancer patients by stage of the disease: implications on the costs of cancer control.

The use of resources for breast cancer during the first five years after diagnosis by different stages of disease was evaluated on the basis of all breast cancer patients (555) diagnosed in the Tampere University hospital district (Finland). All outpatient visits or inpatient-days of these patients in any hospital of the district were recorded and the average costs of hospital-day and of outpatient visit were applied to quantify the total use of resources. During the first five years of follow-up 535 breast cancer patients had 8206 follow-up visits and spent 18472 days in hospital. The stage II-IV patients had more than twice as many outpatient visits and inpatient-days as the stage I patients. The number of hospital-days/patient-year was 2.4-fold for stage II patients and 4.1-fold for stage III-IV patients as compared to stage I patients. The overall use of resources/patient for those with nonlocalized disease was twice as high as the use for stage I patients, while the use of resources/person-year was 2.3-fold for stage II patients and 3.6-fold for stage III-IV as compared to stage I patients. Our study in an unselected patient population during the first five years of follow-up shows that breast cancer patients diagnosed in the early stage (stage I) require far fewer health care resources than if diagnosed in advanced stages. The results can be directly transformed into costs of breast cancer control by stage of breast cancer.

Medulloblastoma: Long-term results for patients treated with definitive radiation therapy during the computed tomography era

Purpose : We performed a retrospective evaluation of the patterns of failure and outcome for medulloblastoma patients treated with craniospinal irradiation therapy during the conputed tomography (CT) era. Materials and Methods : The records of 100 patients treated at Memorial Sloak-Kettering Cancer Center between 1979 and 1994 were reviewed. CT scans or magnetic resonance imaging were used to guide surgical intervention and evaluated the extent of resection postoperatively. All patients were treated with conventional fractionation (1.8 Gy/day) and the majority received full-dose neuraxis radiation therapy and > 50 Gy to the primary site. Results : With a median follow-up of 100 months, the median, 5-year, and 10-year actuarial overall survival for the entire group were 58 months, 50%, and 25%, respectively. The median, 5- and 10-year actuarial disease-free survivals were 37 months, 41%, and 27%, respectively. Patients with localized disease (no evidence of disease beyond the primary site) had significantly improved overall ( p < 0.02) and disease-free ( p < 0.02) survivals compared to those with nonlocalized disease. For patients with localized disease, the 5- and 10-year overall survival rates were 59% and 13%, whereas the disease-free survivals were 49% and 31%, respectively. Disease-free and overall survivals at similar intervals for patients with nonlocalized disease were 29% and 30% (5 years), and 29% and 20% (10 years), respectively. Sixty-four of 100 patients failed treatment. Local failure as any component of first failure occurred in 35% of patients or 55% (35 of 64) of all failures and as the only site of first failure in 14% or 22% (14 of 64) of all failures. For patients presenting with localized disease ( n = 68, local failure as any component of first failure occurred in 32% (22 of 68) and in 18% (12 of 68) as the only site. A multivariate analysis showed that M stage was the only prognostic factor to influence overall survival. For disease-free survival, M stage and the extent of resection were prognostic factors. Ventriculoperitoneal shunting and the use of chemotherapy were associated with a poor outcome; however, these results were confounded by the positive impact of chemotherapy in decreasing the risk of extraneural metastases and the use of these therapies in the more advanced patients.

Body mass and breast cancer. Relationship between method of detection and stage of disease.

Obesity is associated with advanced stage breast cancer at diagnosis and a poorer prognosis. Stage of breast cancer at diagnosis is also strongly influenced by the method of cancer detection. The objective of this study was to determine the relationship between body mass index (BMI) and breast cancer disease stage, taking into account the method of cancer detection (i.e., self-detection, screening mammography, and clinical breast examination [CBE]). From 1988 to 1990, 2863 patients with invasive breast cancer were identified through a statewide, population-based, cancer reporting system and were interviewed as part of a larger study of breast cancer etiology. Stage of disease was classified as either localized or nonlocalized (regional and distant disease combined). The relation between BMI and disease stage was examined by using multiple logistic regression adjusting for age, education, race, year of diagnosis, and prior mammography use. Thirty-eight percent (1092 of 2863) of the women had nonlocalized breast cancer. A strong dose-response relationship was observed between increased BMI and the likelihood of nonlocalized disease (P < 0.001). However, this association was present only among the 55% of women (1585 of 2863) who self-detected their tumors. The odds ratios for nonlocalized cancer increased from 1.0 for the lowest quintile of BMI to 1.3, 1.6, 1.7, and 1.8 for the second through fifth quintiles, respectively, for this group. Greater body mass was associated with nonlocalized breast cancer; however, this association was restricted to women who detected their own cancer. No association was found between BMI and stage of disease among cases detected by either mammography or CBE.

Prostate cancer: trends in mortality and stage-specific incidence rates by racial/ethnic group in Los Angeles County, California (United States)

Between 1976 and 1988 in the United States, the secular trends to age-adjusted incidence rates of prostate cancer were significantly different by racial/ethnic group (P < 0.001), and increased significantly only among non-Hispanic Whites at a rate of 2.7 percent (95 percent confidence interval [CI] = 2.3-3.1%) annually. While incidence rates of regional disease increased significantly (7.7 percent to 11.3 percent annually) among all racial/ethnic groups during this period, localized disease increased significantly only among non-Hispanic Whites, by 1.8 percent (CI = 1.4-2.3%) annually. Prostate cancer mortality in Los Angeles County (California) remained constant among Hispanics, non-Hispanic Whites, and Asians, but increases 1.6 percent (CI = 0-3.2%) annually among Blacks. While the increase in localized disease rates of non-Hispanic Whites may be due to increased detection of asymptomatic disease, this apparently has not occurred among other racial/ethnic groups in Los Angeles County. The secular increase in regional disease rates among all racial/ethnic groups without a concurrent increase in mortality (except Blacks), suggests increased accuracy of staging rather than a true increase in incidence may account for these trends. Adjusted for socioeconomic status, year and age at diagnosis, Black and Hispanic men were at significantly higher risk of being diagnosed with non-localized disease (odds ratio = 1.39 and 1.24, respectively) than were non-Hispanic Whites.

Determinants of breast cancer detection among Wisconsin (United States) women, 1988-90.

Early detection is advocated widely as the best method to reduce the high rate of breast cancer mortality in women. The purpose of this study was to describe the detection histories of women with breast cancer and to identify factors related to the method of detection. During the period 1988-90, 3,197 women with invasive breast cancer, identified through the Wisconsin (United States) tumor registry, were interviewed. The method of cancer detection (classified as self, screening mammography, or clinical breast examination [CBE]) was analyzed using polychotomous logistic regression. Fifty-five percent (1,754/3,197) of the women found their own cancers, while 35 percent (1,122/3,197) were detected by screening mammography. Compared with self-detection, the likelihood of non-localized disease was significantly lower for tumors detected by mammography (odds ratio [OR] = 0.3, 95 percent confidence interval [CI] = 0.2-0.4) and CBE (OR = 0.6, CI = 0.4-0.7). The likelihood of cancer being detected by screening mammography increased with increasing age, education, number of prior mammograms, family history, and body mass index (weight/height2) (BMI). Women in the highest BMI quintile were 2.3 times (CI = 1.7-3.0) more likely than women in the lowest BMI quintile to have their cancers diagnosed by mammography. This association most likely results from breast tumors being more difficult to palpate in heavier women.

Survival and prognostic factors of patients with skin melanoma. A regression-model analysis based on nationwide cancer registry data.

Survival and prognostic factors of skin melanoma patients were studied using a regression analysis of relative survival rates based on nationwide cancer registry data. The material consisted of 4980 cases of melanoma of the skin diagnosed in Finland in 1953 to 1981 and reported to the Finnish Cancer Registry. In the last diagnostic period, 1974 to 1982, the 5-year relative survival rate for male patients was 61.1% and that for female patients 76.6%. The analysis included variables sex, age, stage, year of diagnosis, follow-up year, and site of the tumor. All of them were needed to explain the differences in survival. The patients had the greatest relative risk of dying from skin melanoma during the second year from diagnosis. However, the difference in death risk due to melanoma by stage was most remarkable during the first follow-up year: the risk of patients with nonlocalized disease was over 12 times that of others. The male-female ratio in the risk of dying from skin melanoma was (to a marked extent) attributable to differences in the distributions of stage and site of the tumor. In all site groups males did worse than females but risk ratio varied from 1.15 (trunk) to 1.89 (limbs). The effect of some important prognostic factors on survival could be quantified with ample material and with a method taking into account the competing causes of death. The results suggest a difference either in biological behavior of skin melanoma or in a patient's delay between males and females.

Combined chemotherapy in 76 children with non-Hodgkin's lymphoma excluding Burkitt's lymphoma.

From January 1983 to December 1986 seventy-six previously untreated children with non-Hodgkin's lymphoma (NHL) were treated by combination chemotherapy. Burkitt's lymphoma patients were ineligible. The treatment regimens include intermittent chemotherapy and for non-localized patients, prophylactic central nervous system chemotherapy. Intrathoracic non-Hodgkin's lymphoma patients also had cranial prophylactic radiotherapy. Sixty-six patients (86.8%) achieved complete remission. Two year failure-free survival rate was 82.1% for localized (stage I and II) NHL and 53.3% for non-localized (stage III and IV) NHL patients. Failure-free survival did not differ significantly for the two major histologic diagnoses, but two year survival rate was lower in diffuse poorly differentiated lymphoblastic than undifferentiated non-Burkitt's lymphoma (50% versus 66.8% respectively). Failure-free survival rate was 53.7% in mediastinal disease and, 73.2% in abdominal disease at 24 months. Relapse rate was higher in mediastinal cases (46.1%) than primary abdominal cases (24.3%) at 24 months. Eleven (13.5%) died of treatment related sepsis. Although the overall survival rate was 72.4% at 2 years we need novel or more intensive programmes for mediastinal and non-localized disease.

Effect of peptichemio in nonlocalized neuroblastoma.

PTC, a mixture of oligopeptides of m-L-sarcholysin, acting primarily as an alkylating agent, was utilized as initial therapy following diagnosis in 80 children with nonlocalized neuroblastoma. Of the 67 evaluable patients (21 Stage III, 41 Stage IV and five Stage IV-S), 51 had measurable lesions allowing to evaluate PTC activity; objective tumor responses to the drug were recorded in 45 of these 51 cases (88.2%); 5/5 Stage III, 37/41 Stage IV, 3/5 Stage IV-S. Complete responses were obtained in seven patients (13.7%), partial responses in 32 (62.7%), objective improvement in six (11.8%). Four patients (7.8%) had either no tumor change, or tumor progression. There have been two early drug-related deaths (3.9%). Stage III and IV patients responding to PTC were then treated by irradiation + VCR, followed by cycles of a combination of ADriamycin, vincristine, and cyclophosphamide. Stage IV-S patients received no further therapy. Thirteen of 21 Stage III (61.9%), five of 41 Stage IV (12.2%) and four of five Stage IV-S (80%) are presently alive from 19-48 months (median, 27 months). PTC is an effective agent in advanced neuroblastoma. However, the results of this report do not indicate that its addition to a "standard" treatment, at least in the schedule adopted in this protocol, has improved the final outcome of children with nonlocalized disease.

Recent trends in the incidence and mortality of cancer of the uterine corpus in Connecticut

Incidence rates for invasive cancer of the uterine corpus (including cancer of the uterus, not otherwise specified) have been calculated according to stage of disease (localized, nonlocalized) based on cases reported to the Connecticut Tumor Registry between 1960 and 1975. 1960–1964 and 1965–1969 rates were very similar for both disease stages. However, in 1970–1975 the incidence of localized corpus cancer was 26% higher than in either of the preceding quinquennia, while the rate of nonlocalized disease remained about the same as previously. Women aged 50–59 experienced the largest increase in localized disease, although all other age groups over 50 also had higher rates in the most recent period of diagnosis. No increases were evident in women under 50 years of age. In addition, the frequency of the diagnosis of carcinoma in situ of the endometrium increased gradually over the 16-year period, and mortality from corpus cancer declined slightly. The possible effects of increasing exogenous estrogen use by menopausal and postmenopausal women, changes in diagnostic practices leading to earlier diagnosis, diagnostic criteria, and decreasing numbers of women with intact uteri as a result of increasing hysterectomy rates are considered in the interpretation of these recent trends in the incidence and mortality of cancer of the uterine corpus in Connecticut.

Carcinoma of the pancreas: Results from the vermont tumor registry

1. 1. Approximately 90 per cent of patients with ductal adenocarcinoma of the pancreas on the Vermont Tumor Registry presented with tumor extending outside of the pancreas. 2. 2. Only 3.4 per cent of patients with histologically proved adenocarcinoma of the pancreas had surgical resection for cure. 3. 3. Two of three patients with apparently localized tumor did not undergo resection and had a median survival of nine months. The patients who did not undergo resection averaged fourteen years older than the patients who had resection. Patients with nonlocalized disease had a median survival of two to three months. 4. 4. Seven patients had resection for cure: one, distal pancreatic resection and six, pancreaticoduodenal resection. Two of the six patients having pancreaticoduodenal resection for ductal adenocarcinoma of the pancreas are alive and apparently free of tumor at five and seven years.

Triethylene Melamine in the Treatment of Neoplastic Disease

Triethylene Melamine in the Treatment of Neoplastic Disease