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Implications of extracapsular nodal metastases for treatment and prognosis of breast cancer.

BACKGROUND: Extracapsular extension of nodal metastases from cancer of the breast is a frequent histologic finding, but its significance for prognosis and treatment is unclear. METHODS: One hundred forty-three patients with breast cancer who had metastases to axillary lymph nodes were identified and divided into two groups: those with entirely intracapsular metastases (ICM), and those with extracapsular metastases (ECM). RESULTS: ECM was found in 58.7% of patients. A direct correlation was found between ECM and both the number of metastases and their size. Overall survival was significantly lower in patients with ECM, but an influence on survival independent of node count could be demonstrated only in patients with one to three involved nodes. ECM did not influence the pattern (i.e., locoregional versus distant) of recurrence and was not associated with increased recurrence in the axilla. Radiation therapy reduced locoregional failures in both ICM and ECM groups, but it did not improve survival. CONCLUSIONS: It is concluded that ECM has limited influence on prognosis independent of the number of positive nodes and is not an indication for radiation therapy of the axilla after a complete axillary dissection.

Breast Neoplasms↗

The American Joint Committee on Cancer. Criteria for prognostic factors and for an enhanced prognostic system.

The American Joint Committee on Cancer proposes the following criteria for evaluating putative prognostic factors: they must be (1) significant, (2) independent, and (3) clinically important. Furthermore, we suggest the criteria for selecting a prognostic system that includes TNM and new prognostic factors. These criteria are: (1) easy for physicians to use; (2) provides predictions for all types of cancer; (3) provides the most accurate relapse and survival predictions at diagnosis and for every year lived for each patient; (4) provides group survival curves, where the grouping can be by any variable including outcome and therapy; (5) accommodates missing data and censored patients and is tolerant of noisy and biased data; (6) makes no a priori assumptions regarding the type of data, the distribution of the variables, or the relationships among the variables; (7) can test putative prognostic factors for significance, independence, and clinical importance; (8) accommodates treatment information in the evaluation of prognostic factors; (9) accommodates new putative prognostic factors without changing the model; (10) accommodates emerging diagnostic techniques; (11) provides information regarding the importance of each predictive variable; and (12) is automatic.

Humans↗

Growth patterns of human neuroblastoma xenografts and their relationship to treatment outcome.

BACKGROUND: Several investigators have reported the ability to establish xenografts in nude mice from children with neuroblastomas, but a correlation of prognosis with this establishment and the growth patterns of the neuroblastomas has not been reported. METHODS: Tumor specimens from 58 children with neuroblastomas were heterotransplanted into BALB/c nude mice. In 34 patients, heterotransplantation was done before therapy; in 24 patients, tumors were obtained after at least one course of chemotherapy or radiation therapy. The histology, cytogenetics, and growth characteristics of serial passages of the xenografts were studied. RESULTS: The engraftment rate was 34%. Neuroblastomas with diploid chromosome numbers did not engraft. Chromosomal abnormalities involving 1p were seen in more than 50% of the xenografts. Cytogenetic features were retained between original tumors and resultant xenografts. Xenografts could be established only from tumors with unfavorable histology, as defined by Shimada classification criteria. The histology of each xenograft line was strikingly similar, and each was highly undifferentiated. Engraftment rates, doubling times, and lag times did not vary appreciably between xenografts established from treated tumors compared with xenografts established from untreated tumors. There was no correlation between doubling or lag times and prognosis. Patients whose tumors engrafted had only a 5% 3-year survival rate. CONCLUSIONS: From these results, it appears that successful engraftment is the most important prognostic indicator for patients with neuroblastomas. Because of the commonality of the histologic features and the stability of the tumor clones from patients before and after heterotransplantation, these xenografts may be useful as an in vivo model for studying drug resistance and for designing treatment regimens.

Animals↗

Cancer in older persons. Magnitude of the problem--how do we apply what we know?

The elderly experience the major impact of cancer. The incidence rate for those aged 65 and older is 2085.3 per 100,000 as compared with 193.9 per 100,000 for those younger than 65. Overall, 58% of all cancer incidence is in the older segment of the population. Cancer mortality in the elderly now accounts for 67% of all cancer deaths. Data from the National Cancer Institute Surveillance, Epidemiology, and End Results program for 1985-1989 reveal many salient facts. Older persons have a risk of developing cancer 10 times greater than that for individuals younger than 65. This paper outlines the magnitude of the major cancers that affect the elderly. Incidence and mortality data are presented according to individual tumors (colon, rectum, lung/bronchus, pancreas, stomach, urinary bladder, breast, ovary, and prostate). Demographic data from the U.S. Bureau of the Census focus on the expanding elderly population in the United States and projections for the future. Needs for cancer care and treatment for the elderly, already great, are likely to increase. It is imperative that older persons receive special attention for cancer prevention, early diagnosis, and treatment efforts, especially because there is almost always an overlay of other chronic diseases and age-associated declines concurrent with the diagnosis of cancer in the elderly. This paper highlights issues unique to older persons as individuals at high risk for cancer and suggests research strategies that should be made in anticipation of the even greater cancer burden for the elderly as this subset of the population expands.

Aged↗

Prognostic factors for survival in patients treated in phase I clinical trials.

BACKGROUND: Patients with advanced or metastatic cancer treated in Phase I clinical trials are considered to have a poor prognosis. Survival from first treatment in a Phase I trial was determined for 349 patients. Univariate and multivariate survival analyses were performed to determine whether potential prognostic factors and distinct risk groups could be identified. METHODS: Patients were identified retrospectively from a large data base of patients with advanced or metastatic cancer treated in Phase I clinical trials at the University of Chicago between February 1987 and October 1991. RESULTS: With a median follow-up of 29 months, 10% of patients were alive at the time of analysis. Twenty-nine percent were alive 1 year after the initiation of Phase I chemotherapy, and the median survival from first treatment in a Phase I study was 6.5 months. Multivariate analysis indicated that a better pretreatment performance status, a higher pretreatment serum albumin concentration, a lower pretreatment platelet count, no prior cisplatin chemotherapy, and a genitourinary or gynecologic cancer diagnosis were predictive of better survival. Three risk groups incorporating these five variables were identified, with median survivals of 12.7, 7.4, and 3.5 months for the good, intermediate, and poor risk groups, respectively. CONCLUSION: Patients treated in Phase I clinical trials have a median survival of 6.5 months, even though some patients have been treated at early (subtoxic and potentially subtherapeutic) dose levels. The results of this study may allow the identification of patients who are likely to survive long enough to contribute information on acute and cumulative drug-related toxicities and, possibly, tumor response.

Adult↗

The multicentric occurrence of squamous epithelial dysplasia and squamous cell carcinoma in the esophagus.

BACKGROUND: The biologic significance of esophageal dysplasia has not yet been completely elucidated, especially regarding the process of multiple occurrences of squamous cell carcinoma. METHODS: The multiplicity of dysplasia in 73 patients with solitary carcinoma of the esophagus (Group I) and 21 with multiple carcinomas (Group II) was compared in surgically resected specimens. RESULTS: Thirty-nine second carcinomas were identified in 13 patients of Group II, and all were superficial. The incidences of five or more isolated dysplasias in cases without continuity to a carcinomatous lesion, was 6.8% and 66.7% in Groups I and II, respectively (P < 0.01). In a case with three or more carcinomas, the incidence increased to 84.6%. The coexistence of all grades of isolated dysplasias was observed in 10 patients (47.6%) in Group II but in only 6 patients (8.2%) in Group I (P < 0.01). CONCLUSIONS: These findings suggest that various degrees of evolving biologically related lesions, such as dysplasia and carcinoma, can occur multicentrically in the same esophagus.

Carcinoma in Situ↗

The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma.

BACKGROUND: Prostate carcinoma poses a significant public health problem. Although a minority of men with newly diagnosed prostate carcinoma manifest bone metastases or skeletal abnormalities, a significant proportion of men will develop these complications over the course of their lives. Patients at highest risk for bone metastases include those with high grade, high stage neoplasms, those who fail primary curative therapies such as radical prostatectomy or radiation therapy, and those who develop biochemical recurrence after hormonal therapy. METHODS: The relative risks and prognostic factors for bone metastases in each of these settings will be reviewed. RESULTS: In comparison with men without prostate carcinoma, benign skeletal complications (osteopenia and fractures) occur at significantly increased rates among men with untreated prostate carcinoma. Moreover, the incidence rate of these conditions increases dramatically among those men who are receiving endocrine therapy. The duration and intensity of the endocrine therapy may be associated with the incidence rate and severity of skeletal complications. CONCLUSIONS: Given the significant incidence rate and quality of life implications of skeletal complications and bone metastases, there is an urgent need to identify effective preventive therapies and treatments. Bisphosphonates may have a role in preventing osteopenia and, potentially, bone metastases among men with prostate carcinoma.

Bone Neoplasms↗

Primary treatment of cystosarcoma phyllodes of the breast.

BACKGROUND: Cystosarcoma phyllodes is a rare sarcoma of the breast. Although surgical removal is the mainstay of treatment, the extent of surgery required (excision vs. mastectomy) and the need for additional local therapy, such as radiotherapy, are unclear. The current study evaluated the rate of local and distant failure, as well as potential prognostic factors, to better define appropriate treatment strategies. METHODS: One hundred one patients treated primarily for cystosarcoma phyllodes of the breast were evaluated. These tumors were classified histologically into benign (58%), indeterminate (12%), and malignant (30%) based on well defined criteria. Stromal overgrowth (29%) was considered separately. Surgery was comprised of local excision with breast conservation (47%) or mastectomy (53%). Microscopic surgical margins were negative in 99% of cases. Six patients received adjuvant radiotherapy. RESULTS: Overall survival for the 101 patients was 88%, 79%, and 62% at 5, 10, and 15 years, respectively. For patients with nonmalignant (benign or indeterminate) and malignant cystosarcoma phyllodes, the overall survival was 91% and 82%, respectively, at 5 years, and 79% and 42%, respectively, at 10 years. Similar rates were observed based on the presence or absence of stromal overgrowth. Local recurrence occurred in 4 patients, with an actuarial 10-year rate of 8%. Eight patients developed distant metastases, with an actuarial 10-year rate of 13%. Multivariate analysis using Cox proportional hazards regression revealed stromal overgrowth to be the only independent predictor of distant failure. CONCLUSIONS: Local failure in this group of largely margin negative patients with cystosarcoma phyllodes of the breast was low, showing that breast-conserving surgery with appropriate margins is the preferred primary therapy. The current study data do not support the use of adjuvant radiotherapy for patients with adequately resected disease. Patients with stromal overgrowth, particularly when the tumor size was > 5 cm, were found to have a high rate of distant failure; such patients merit consideration of a trial that examines the efficacy of systemic therapy.

Adult↗

Metabolic activity and clinical features of primary ganglioneuromas.

BACKGROUND: Ganglioneuroma (GN) is considered by most to be a benign tumor of neural crest origin. It may evolve from differentiating neuroblastoma or may be diagnosed as primary ganglioneuroma. The rarity of this tumor and the lack of understanding of its biology often lead to inaccurate diagnosis and treatment. METHODS: The authors analyzed clinical features and biologic behavior of primary ganglioneuroma in 49 patients who were registered with but were not part of the national neuroblastoma trials. Data included age and symptoms at diagnosis, gender, tumor localization and size, (123)I-metaiodobenzylguanidine (mIBG) scintigraphy, secretion of catecholamines, histology, treatment, and outcome, whenever available. RESULTS: Patients with primary ganglioneuroma were significantly older than patients with neuroblastoma. Median age at diagnosis was 79 months compared with 16 months (P < 0.0001). Ganglioneuroma were equally distributed between males and females (1.13:1). A preference of thoracic (41.5%) and abdominal, nonadrenal tumors (37.5%) was observed compared with adrenal GN (21%). At diagnosis, thoracic tumors appeared larger than nonthoracic ones. Local lymph node metastases occurred in two patients. One ganglioneuroma had metastasized to soft tissues. (123)I-mIBG scintigraphy detected mIBG uptake at tumor site in 57% of the GN tumors. Levels of catecholamines in plasma and/or urine were increased in 39%. Slight immaturity of ganglion cells was observed in 93% of all ganglioneuroma tumors. None of the 22 tumors analyzed exhibited MYCN gene alterations. Although 12 patients had macroscopic residuals, no tumor progression or recurrence was observed in a median follow-up of 25 months. CONCLUSIONS: Ganglioneuroma may present with metabolic activity such as increased secretion of catecholamines and/or mIBG uptake. There are no specific diagnostic signs or symptoms discriminating ganglioneuroma and neuroblastoma tumors. Therefore, ganglioneuroma requires tissue investigation for diagnosis. Prognosis after surgical resection without further therapy seems to be excellent.

3-Iodobenzylguanidine↗

Bilateral carcinoma of the breast.

Among the 911 cases of carcinoma of the breast treated between 1969 and 1978 there were 39 cases of bilateral primary cancer. Of these, 17 were synchronous tumours defined as cancers diagnosed and treated during the same primary hospital admission. The remaining 22 patients had tumours that were diagnosed separately (metachronous tumours), with a mean time interval of 5 years and 8 months between presentation of first and second primaries (range 6 months to 20 years). Of the metachronous tumours, 20 had presented within 7 years of the diagnosis of the first primary (2.2 per cent of all patients). The patients with synchronous disease fared badly, but patients in the metachronous group had a good prognosis. This is due, at least in part, to the inherent selection of patients in the metachronous group who have to survive the first primary tumour in order to develop the second. However, careful follow-up after the first primary may also account for the relatively good prognosis of this group. We therefore recommend continuing regular out-patient follow-up, with careful examination of the second breast, for all patients having undergone treatment for cancer of the breast.

Aged↗

Pre-operative or postoperative colonic examination for synchronous lesions in colorectal cancer.

A review of 130 consecutive large bowel examinations at which a cancer of the colon or rectum was diagnosed has been undertaken. Of 50 patients examined by colonoscopy, the whole colon was seen in only 21 (42 per cent) and almost half of these had a tumour in the caecum or ascending colon. In most cases, an incomplete examination was the result of narrowing of the lumen by the tumour preventing passage of the endoscope. Of 80 patients examined by double contrast barium enema, the entire length of the colon was visualized in 83 per cent but the quality of the examination was sufficient to confidently exclude synchronous neoplastic lesions in only 51 per cent. The incidence of synchronous cancer in this series was within the expected range, although two such cancers were not detected until laparotomy, but the incidence of synchronous adenomas was two-thirds of the expected number in colonoscopy patients and one-third in those examined by barium enema. It is concluded that, in patients with known colorectal cancer, preoperative investigation is unreliable for the detection of all synchronous neoplasia and that patients should have postoperative colonoscopy.

Adult↗

A clinicopathological study of synchronous multiple gastric cancer.

In a 7 1/2-year period (from 1 January 1980 to 30 June 1987), 997 patients with gastric cancer underwent gastric resection at the Department of Surgery, Matsuyama Red Cross Hospital, Japan. We studied clinicopathologically 83 patients (182 lesions) with synchronous multiple gastric cancer and compared them with patients who had solitary cancers only in the same period. We found that elderly men had a relatively high incidence of multiple gastric cancer, and that early cancer of the elevated well differentiated type was the most common. Of the 182 lesions, as many as 42 (23.1 per cent) were missed in the preoperative examination. Eighteen of these 42 lesions were found only with the aid of a microscope in sections almost incidentally excised. Small flat lesions tended to be missed. We should always be conscious that other gastric lesions may be present when treating patients with gastric cancer.

Female↗

Carcinoid tumour of the appendix.

BACKGROUND: Appendiceal carcinoid tumours are found in 0.3-0.9 per cent of patients undergoing appendicectomy. Controversy exists over the management following appendicectomy, especially with regard to the role of right hemicolectomy in patients with tumours smaller than 2 cm in diameter. METHODS AND RESULTS: The literature pertaining to the behaviour of appendiceal carcinoids was reviewed in order to formulate indications for right hemicolectomy. Metastatic disease from appendiceal carcinoids is a rare occurrence, but is more common when lesions are larger than 2 cm in diameter. The risk-benefit balance of right hemicolectomy needs to be better defined, and an improved understanding of tumour cell biology may aid prognostic accuracy and decision-making. CONCLUSION: There is limited evidence on which to base clear indications for right hemicolectomy in patients with a diagnosis of appendiceal carcinoid. Acceptable indications are carcinoids larger than 2 cm in size, any high-grade malignant carcinoid (including those with a high mitotic index), mesoappendiceal invasion, lesions at the base of the appendix with tumour-positive margins, and goblet cell adenocarcinoid tumours.

Appendiceal Neoplasms↗