Showing papers in "Cancer in 1991"

Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms

Abstract: Forty-five patients with metastatic neuroendocrine tumors were treated with a regimen of etoposide 130 mg/m2/d for 3 days plus cisplatin 45 mg/m2/d on days 2 and 3. Both drugs were given by continuous intravenous infusion. Among 27 patients with well-differentiated carcinoid tumors or islet cell carcinomas, only two partial objective tumor regressions were observed (7%). Among 18 patients prospectively classified as having anaplastic neuroendocrine carcinomas, however, there were nine partial regressions and three complete regressions, an overall regression rate of 67%. For anaplastic disease, the median duration of regression was 8 months (range to 21 months). Tumor response was unrelated to primary site, endocrine hyperfunction, or prior therapy experience. The median survival of all patients with anaplastic tumors was 19 months; this seemed favorable when considering the small experiences with these rare tumors reported in the literature. Toxicity, which was severe for most patients, consisted primarily of vomiting, leukopenia, thrombocytopenia, anemia, alopecia, and neuropathy. The anaplastic neuroendocrine tumor is strongly responsive to therapy with combined etoposide and cisplatin. Patients with undifferentiated carcinomas, originating in typical neuroendocrine tumor sites (small and large bowel, pancreas, and stomach) or of unknown origin, who have consistent histologic findings by light microscopy should be evaluated for this possibility with appropriate immune staining or electron microscopy.

MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration.

Abstract: This study reports on the specific expression of the MIC2 gene, a pseudoautosomal gene located on the short arms of the X and Y chromosomes, on Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET) cells. The gene product, a cell membrane protein, is recognized by the newly established monoclonal antibody (MoAb) HBA-71 and the previously described MoAb 12E7 and RFB-1. Furthermore, the reaction pattern of the MIC2 antibodies, especially HBA-71, with normal tissues and a great number of benign and malignant tumors (70 different tumors, 199 tumor samples), as well as the correlation between the specific chromosomal aberrations, i.e., the t(11;22) and the del(22) and the expression of this antigen, are demonstrated. Both ES and pPNET cells express the MIC2 gene in very high amounts, which represents a highly selective and almost unique feature of these cells, making an assignment of these tumors in one entity even more likely. The MIC2 antibodies are of great value for clinical and research purposes.

Thymic carcinoma. A clinicopathologic study of 60 cases.

Abstract: The clinicopathologic features of 60 patients with thymic carcinoma were studied. Patients ranged in age from 10 to 76 years (mean, 46), of whom 24 were females and 36 were males. Overall survival at 1, 3, and 5 years was 56.6%, 40%, and 33.3%, respectively. The following morphologic features were correlated with survival: type of tumor margins; presence or absence of a lobular growth pattern; nuclear atypia; necrosis; mitotic activity; and histologic tumor type and grade. Eighty eight percent of patients with poorly circumscribed/infiltrating neoplasms died of their tumors as compared with 16.6% of patients with well-circumscribed neoplasms (P less than 0.0000). Of patients whose tumors had mitotic counts exceeding 10/10 high-power fields (HPF), 84.3% died, as compared with 21.4% of patients with lower mitotic counts (P less than 0.0000). Of patients whose tumors showed lack of lobular growth pattern, 91.6% died, as compared with 29% of those whose tumors had a lobular growth pattern (P less than 0.0000). Finally, 84.6% of patients whose tumors displayed a high-grade histology (lymphoepithelioma-like carcinoma, small cell/neuroendocrine carcinoma, clear cell carcinoma, sarcomatid carcinoma, and anaplastic/undifferentiated carcinoma) died of tumor, as compared with 0% of patients whose tumors were of low-grade histology (well-differentiated squamous carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma) (P less than 0.0000). Evaluation of the various treatment modalities used to treat these patients did not yield any statistically significant correlations with survival. Two clinically distinct groups of patients were identified: one after a relatively favorable clinical course with long survival, and one after a rapidly fatal outcome. The morphologic features of the tumors in these patients correlated well with their clinical behavior; histologic type (and the grade to which it was assigned) constituted the most reliable and important predictor of prognosis.

Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group.

Abstract: Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characterisitcs and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.

Screening for lung cancer. A critique of the Mayo Lung Project.

Abstract: The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.

CAncer rehabilitation evaluation system–short form (CARES‐SF). A cancer specific rehabilitation and quality of life instrument

Abstract: The CAncer Rehabilitation Evaluation System (CARES) (CARES Consultants, Santa Monica, CA) a rehabilitation and quality of life instrument with well-documented reliability and validity, has been shortened. This report describes the development and psychometric properties of the new instrument, the CAncer Rehabilitation Evaluation System--Short Form (CARES-SF). The data from four existing samples of cancer patients demonstrate that the CARES-SF is highly related to the CARES (r = 0.98), has excellent test-retest reliability (86% agreement), concurrent validity with related measures, and acceptable internal consistency of summary scales (alpha = 0.85 to 0.61). In a new sample of breast cancer patients evaluated at three points in time (1 month, 7 months, and 13 months after diagnosis) the instrument appears to be sensitive to change and is highly related to the Functional Living Index--Cancer (FLIC), an existing quality of life instrument. The authors conclude that the CARES-SF has excellent potential as a quality of life instrument for use in clinical trials.

Quality of life assessment. An independent prognostic variable for survival in lung cancer.

Abstract: Improved quality of life has long been the goal of cancer treatment, but only recently have investigators begun to include a systematic assessment of quality of life in clinical trials. The major interest for its inclusion in clinical trials has been to assess treatment outcome. An evaluation of the relationship between patient-rated quality of life and survival is reported in a homogeneous sample of patients with advanced metastatic lung cancer participating in a clinical trial. Under the Cox proportional-hazards model (with quality of life, marital status, and their interaction in the model), a statistically significant relationship was observed between initial patient-rated quality of life and subsequent survival. In addition, being married led to a significantly improved survival. These findings suggest that nonmedical factors, such as quality of life assessment and marital status, play a role in survival and that they should be evaluated and described as potential predictors of survival in cancer patients in clinical trials.

The American cancer society national prostate cancer detection project. Findings on the detection of early prostate cancer in 2425 men

Abstract: The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary, multicenter effort to assess the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) assay. By June 1990, 2425 men not previously suspected of having prostate cancer had been examined in ten participating clinical centers according to the project protocol. Three hundred ninety-six men (16.3%) were recommended for biopsy on the basis of TRUS or DRE. An analysis of the results of 330 completed biopsies showed 52 cancers detected by DRE and/or TRUS. Forty-four (84.6%) of the men with cancer had positive TRUS examination results compared with 33 (63.5%) with positive DRE. Five additional cancers were discovered as a result of elevated PSA levels. The overall detection rate was 2.4% and this rate varied by age. The detection rate in men 55 to 60 years of age was 1.3% and this rose to 3.3% in men older than 65 years of age. The estimated sensitivity was significantly greater for TRUS compared with DRE (77.2% versus 57.9%; P less than 0.05). The estimated specificity of DRE was greater than that of TRUS (96.3% versus 89.4%; P less than 0.01). The positive predictive value (PPV) for the tests varied as a function of patient and disease characteristics. The overall PPV was 28.0% for DRE and 15.2% for TRUS. The occurrence of elevated PSA levels significantly increased the PPV of both TRUS and DRE. The majority of cancers detected were at early stages. These preliminary data suggest the feasibility of using these techniques to promote cancer control, but additional data and follow-up are needed to assess the significance of the results.

Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study.

Abstract: Histopathologic examination was done on 18 cases after percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma. In eight cases, the lesion was treated by PEIT alone; in the other ten cases, PEIT was combined with transcatheter arterial embolization. The lesion was completely necrotic in 13 cases, 90% necrotic in four cases, and 70% necrotic in the rest. In addition, PEIT seemed to be effective against intercapsular, extracapsular, and vascular invasions. In the four cases of incomplete necrosis, the viable cancer tissue remained in small tumor nodules around the main tumor, in portions isolated by septa, or along the edge of the lesion. Therefore, ethanol should be injected not only into the center of the lesion, but also into sites close to its edge. Ethanol did not damage noncancerous liver parenchyma distant from injected sites. Local dissemination of the cancer cells was not found in any case. Therefore, PEIT seems to be a valuable therapy and may be an alternative to surgery in some cases.

A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan.

Abstract: In Japan, hepatocellular carcinoma (HCC) is one of the most prevalent cancers, with a reported fatality rate showing a consistent and significant increase in the last decade. At most, only 25% of HCC cases are positive for the hepatitis B surface antigen (HBsAg). To investigate a potential role for hepatitis C virus (HCV) in the development of HCC, sera from 105 HBsAg-negative HCC patients were collected from five districts of Japan and assayed for antibody to HCV antigen (HCVAb). A large number of these patients (76.2%) were found to be positive for the HCVAb in comparison with the reported prevalence in sera from blood donors (1.1%). A history of blood transfusion was found in 39.6% of the cases positive for HCVAb, which was significantly different to the lower rate (4.7%) observed in HCC patients who were both positive for HBsAg and negative for HCVAb (P less than 0.001).

Mammographic densities and risk of breast cancer.

Abstract: To determine the relation of mammographic densities to subsequent breast cancer risk, a case-control study was undertaken using prediagnostic mammograms of screening program participants. Mammograms of cases (n = 266) and controls (n = 301) were blindly assessed for mammographic densities, which were measured by planimetry. The odds of breast cancer increased steadily with increasing breast density (test for trend, P less than 0.0001). Breast cancer odds was 1.7 for densities between 5% and 24.9%, 2.5 for 25% through 44.9%, 3.8 for 45% through 64%, and 4.3 for densities of 65% and greater (referent = less than 5% densities). Odds ratios also increased with increasing densities among women with the P2 and DY mammographic patterns. These findings suggest that the percentage of mammographic densities in the breast can predict breast cancer risk more accurately than a qualitative assessment of mammographic patterns.

Primary adenocarcinoma of the urinary bladder: A clinicopathologic analysis of 72 cases

Abstract: Adenocarcinomas account for approximately 2% of primary epithelial malignancies of the urinary bladder. The clinicopathologic features of 72 cases treated at one institution are reported; 22 cases were evaluated immunohistochemically. Twenty-four tumors were urachal and 48 nonurachal. The cases were analyzed according to their stage at presentation, histologic type, and mucin staining; they were tested immunohistochemically to determine their reaction to carcinoembryonic antigen, Leu-M1, prostate-specific antigen, and prostatic acid phosphatase. Tumor stage was a highly significant predictor of outcome (P = 0.001). Nonurachal tumors tended to have a worse outcome than urachal, but the difference was not statistically significant (P = 0.07). Histologic type was not a significant predictor of outcome (P = 0.10). For adenocarcinoma of the urinary bladder, stage was the most significant predictive factor; separating urachal from nonurachal tumors was important, but mucin histochemistry and immunohistochemistry did not help in this distinction. On occasion, a few tumors may react with some polyclonal antibodies to prostate-specific antigen; thus these results must be interpreted with caution. In these instances, the possibility of using highly sensitive and specific monoclonal antibodies such as the one employed in this study should be considered.

Psychosocial adjustment in women with breast cancer.

Abstract: There is a plethora of studies investigating psychosocial adjustment in women with breast cancer, its correlates, clinical course, and prognosis. These studies have been conducted with varying degrees of methodologic rigor. An assessment has been made of the quality of this existing evidence to identify from the best evidence the factors which predict the adjustment status of women with breast cancer. Studies have been reviewed, using methodologic standards for the critical appraisal of studies on prognosis, developed by Sackett and colleagues in the Department of Clinical Epidemiology and Biostatistics at McMaster University (Hamilton, Ontario, Canada). Few of the studies investigating psychosocial adjustment of women with breast cancer meet all of the criteria for reviewing studies of clinical course and prognosis. This review focuses the direction and methodologic rigor required in future investigations. In particular, studies are needed that employ prospective designs and that deliberately measure or control for the extraneous prognostic variables that may affect adjustment. Future investigations need to incorporate adequate precision in measurement so that measures of the psychosocial variables are objective, reliable, and valid.

Primary cutaneous B-cell lymphoma: a unique type of low-grade lymphoma. Clinicopathologic and immunologic study of 83 cases.

Abstract: The clinical presentation and course, and the morphoimmunologic features of primary cutaneous B-cell lymphoma (CBCL) were investigated in a series of 83 patients. Fifty-one patients were male and 32 were female (male-to-female ratio of 1.6:1); CBCL primarily involved the elderly (median age, 58 years). A locoregional extension of the disease was quite frequent (86.7%). The neoplastic cells showed a range of appearances reminiscent of the whole spectrum of follicular/parafollicular cells. The antigenic phenotype of tumor cells (CD19+, CD20+, CD22+, CD28+, CD10-, CD5-, MB2+, CD74+/-, CDw75+/-, MT2+/-, surface immunoglobulin + monoclonal/-) plus the presence of admixed CD14- dendritic reticulum cells suggest a mantle-zone nature for CBCL. The nonaggressive clinical behavior with a substantial tendency to remain localized to a limited area of the skin, the quite good response to nonaggressive treatment, and the dichotomy existing between the enhancement of morphoimmunologic atypism--which parallels the increasing age and growth rate of lesions--and the constant benign overall prognosis on long-term follow-up make CBCL a unique type of lymphoma of low-grade malignancy. Proper recognition of CBCL is mandatory to avoid possible undertreatment or overtreatment of the patients affected.

Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index

Abstract: Survival rates for 22,616 cases of breast cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were stratified on outcome according to the histologic grade and stage of disease. Two different staging systems, "local, regional, and distant" and a modified American Joint Committee on Cancer (AJCC) system adopted for SEER were used. Relative survival rates were calculated at 5 and 10 years. Patients who were assigned Stage II, Grade 1 had the same survival as those assigned Stage I, Grade 3. Their survival was better than patients assigned Stage I, Grade 4. The 5-year relative survival rate for patients listed as Stage I, Grade 1 was 99% and for patients listed as Stage I, Grade 2, it was 98%. At 10 years, the survival rate of patients assigned Stage I, Grade 1 was 95%. Patients with histologic Grade 1 tumors less than 2 cm in size and with positive axillary lymph nodes had a 5-year survival rate of 99%. As breast tumors increased in size, the histologic grade also increased. The results suggest that in linking histologic grade with stage of disease, the staging system should also be considered. Histologic grade when used in conjunction with stage of disease can improve the prediction of outcome. Our results also indicate that a prognostic index can be created for breast cancer using a combination of stage of disease and histologic grade. The data suggest that only three grades are needed for breast cancer.

Ki-67 immunostaining in human breast tumors and its relationship to prognosis.

Abstract: Ki-67 labeling was quantified in 37 nonmalignant breast tissues and in 63 breast carcinomas by counting ten random high-power fields each in three section planes (RC) or by evaluation of the area with the highest labeling density (HDC). Both procedures proved to be highly correlated (rs = 0.94). Ki-67-positive fractions of the nonmalignant tissues (mean, 2.1% for RC and 4.1% for HDC) were significantly lower as compared with the carcinomas (mean, 14.5% for RC and 17.5% for HDC). In carcinomas the Ki-67 labeling was significantly associated with pT stage, axillary lymph node status, and tumor grading and inversely related to progesterone receptor status. Using the medians of both counting methods (12% for RC and 17% for HDC) as cutoff points, significantly different curves for overall and disease-free survival (median follow-up, 37 months) were obtained. However, Cox multivariate analysis failed to demonstrate an independent effect of Ki-67 labeling. In contrast, Ki-67 reactivity seems to be of independent prognostic value if a higher cutoff level was selected.

Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma. Preliminary results

Abstract: Cryosurgery, the in situ freezing of cancer, has been proposed in the past as a possible treatment for unresectable hepatic tumors. Its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection, allowing treatment of multiple lobes. Because cryosurgery does not affect large vessels, tumors in difficult locations, such as adjacent to the inferior vena cava (IVC), can be treated. With the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process, 18 patients with unresectable metastatic colon carcinoma confined to the liver were treated. Of the 18 patients treated, 4 (22%) are in complete remission as determined by computed tomography (CT) scans and carcinoembryonic antigen (CEA) levels, with a mean follow-up of 28.8 months. Four patients (22%) were not adequately treated at the time of cryosurgery. The number of lesions frozen in each patient ranged from 1 to 12, with a mean of 6 lesions. Fourteen patients had bilobar disease; three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery, and one patient had unilobar disease. Mean survival of the 14 cases with recurrence was 21.4 months, with 2 of the 14 still alive. Ultrasound-guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable (including patients with bilobar and multiple lesions). These preliminary results indicate that the procedure warrants further study.

Immunohistochemical study of androgen receptors in metastatic prostate cancer. Comparison of receptor content and response to hormonal therapy.

Abstract: A longstanding goal has been to determine whether androgen receptor (AR) levels could be used to predict the clinical response of metastatic prostate cancer to androgen withdrawal therapy. A major limitation of previous studies was the use of homogenized tissue, which yields an average AR content for all cells. By AR immunohistochemical study using an antibody specific for AR the authors assessed nuclear AR content specifically in the malignant epithelial cells of prostate needle biopsy specimens of 17 patients with Stage D prostate cancer. The authors found that prostate cancer contains AR-positive and AR-negative malignant cells before androgen withdrawal therapy, but the percentage of AR-positive cells did not predict the time to tumor progression after therapy. There was no significant correlation between the percentage of AR-positive malignant cells and the time to tumor progression. When patients were divided into two groups based on the median time to progression, the percentage of AR-positive nuclei was not significantly different in poor responders versus good responders. When patients were divided into two groups based on the median percentage of receptor-positive nuclei, Kaplan-Meier estimates of the progression-free interval revealed no significant difference between the group of patients with AR-poor tumors and patients with AR-rich tumors. Potential explanations for these results are discussed. The authors conclude that the percentage of AR-positive nuclei is not a sufficient criterion to predict tumor behavior.

Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.

Abstract: This study determines, within the frame of current therapeutic possibilities, the impact of chronic nonleukemic myeloproliferative disorders on expected survival. The survival data for 1067 patients (454 with polycythemia vera, 247 with essential thrombocythemia, and 366 with idiopathic myelofibrosis) were collected from 38 Spanish institutions. The actuarial survival probability of each group of patients was compared with that of the age-matched and sex-matched control population. The survival of the patients with polycythemia vera and essential thrombocythemia did not differ from that of the control population (P = 0.92 and, 0.22, respectively), whereas the survival of the patients with idiopathic myelofibrosis was strikingly reduced with respect to the control population (P = 0.0000000007). Thus, in terms of survival, current therapeutic procedures may be considered as quite satisfactory in patients with polycythemia vera and essential thrombocythemia. On the other hand, due to poor survival of patients with idiopathic myelofibrosis, new therapeutic approaches for this condition are clearly needed.

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas

Abstract: From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Human immunodeficiency virus‐related lymphoma. Prognostic factors predictive of survival

Abstract: In an attempt to determine factors predictive of survival in patients seropositive for human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS)-related lymphoma, the authors studied 60 such patients, all of whom were treated with curative intent. Eleven patients presented with lymphoma primary to the brain (P-CNS); the remaining 49 had systemic AIDS-related lymphoma. Patients with P-CNS lymphoma had more severe underlying HIV-related disease than did patients with systemic lymphoma as evidenced by a higher incidence of AIDS before the diagnosis of lymphoma (73% versus 37%; P = 0.04), and lower median number of CD-4-positive lymphocytes in peripheral blood at diagnosis of lymphoma (30/dl versus 189/dl; P = 0.005). Median survival of such patients was 2.5 months versus 6.0 months for patients with systemic lymphoma (P = 0.04). Forty patients with systemic AIDS-related lymphoma have died; three factors were strongly associated with shorter survival: (1) Karnofsky performance status (KPS) of less than 70% (multivariate relative survival risk [RSR] = 3.1); (2) history of AIDS before the diagnosis of lymphoma (multivariate RSR = 3.0 for opportunistic infection plus Kaposi's sarcoma); and (3) bone marrow involvement (RSR = 3.1)). All three factors (KPS of less than 70%, prior AIDS diagnosis, and marrow involvement) were associated with early demise attributed to AIDS, whereas death attributed to lymphoma per se was associated with only two factors (KPS of less than 70% and marrow involvement). In the absence of all three risk factors, a "good prognosis" group of 17 patients was defined, with a median survival of 11.3 months; the median survival of the remaining patients ("poor prognosis") was 4.0 months (P = 0.0002). Attainment of complete response to therapy (CR) was strongly related to prolonged survival in the patients in the good prognosis group (17.8 months in patients with CR versus 5.0 months in those with less than CR); however, such meaningful prolongation of survival was not seen in patients with poor prognosis who attained CR (6.3 months versus 3.4 months). The patients with poor prognosis may be unable to tolerate the insult of multiagent chemotherapy, experiencing low CR rates (25%) and death caused by lymphoma and AIDS. However, patients in either prognostic category who attained CR remained at risk for dying of AIDS while the lymphoma was in remission. Thus, it is apparent that meaningful prolongation of survival in the patient with AIDS-related lymphoma will require not only effective antineoplastic intervention, but also control of the underlying HIV infection. In addition, future therapeutic trials should stratify patients based upon the prognostic factors defined here in an attempt to clarify the results obtained.

Postirradiation sarcoma. Analysis of a nationwide cancer registry material.

Abstract: Thirty-three cases of postirradiation sarcoma (PIS) from the files of the Finnish Cancer Registry were analyzed. The most frequent first primary tumors were cancers of the breast (seven cases) and female reproductive organs (13 cases). Five patients had a childhood cancer. The median total radiation dose at the site of the PIS was 3600 cGy (1600 cGy to 11200 cGy). The median interval from start of radiation therapy to detection of PIS was 13.2 years (3.4 to 22.8 years). The PIS was of soft tissue origin in 25 of 33 cases. The most frequent histologic types were osteosarcoma (ten cases, including four extraskeletal tumors), malignant fibrous histiocytoma (ten cases), and fibrosarcoma (six cases). The overall crude 5-year survival rate was 29% (calculated from the start of treatment for PIS), and for patients initially treated with either radical surgery or combined marginal surgery and postoperative irradiation it was 67%. The authors conclude that there is a chance for cure for radically treated patients with postirradiation sarcoma that emphasizes the importance of regular long-term follow-up of cancer patients.

Mucin-producing tumor of the pancreas.

Abstract: A new pancreatic tumor, called mucin-producing tumor, has received great attention in Japan. These tumors are found inside the pancreatic duct and produce large quantities of copious mucus. The authors examined 22 cases of these tumors histologically and histochemically. In 12 malignant cases, the tumors inside the ducts consisted of cancerous lesions over small areas along with papillary or atypical hyperplasia. Tumors in ten benign cases mainly consisted of papillary hyperplasia. Except for three patients with carcinoma in situ, cancerous tumors infiltrated the pancreatic parenchyma and, in some cases, were observed invading the bile duct or duodenum. A mucous histochemical study showed evidence of sialomucin in malignant cases; neutral mucin was dominant in benign cases. Characteristics of this disease were also compared with 13 cases of mucinous cystic neoplasm. From the results, it was concluded that these two diseases can be classified into the same conceptual category.

Acromegaly and gastrointestinal cancer.

Abstract: A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow-up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat.

Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation.

Abstract: The growth rates of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLTX) were estimated by calculating the tumor doubling time (TDT) in 20 patients. The mean TDT, calculated by multiple measurement of tumor size, was 44.3 +/- 11.3 days (mean +/- standard error) in 12 patients with pulmonary metastasis (range, 10 to 161 days) and 37.6 +/- 8.9 days (range, 7 to 65 days) in 5 patients with liver allograft recurrence. The TDT as estimated by serum alpha-fetoprotein (AFP) levels in 6 patients was 37.3 +/- 10.0 days (range, 12 to 84 days). The mean TDT obtained from 5 control subjects with HCC who were treated with liver resection (without immunosuppression) was 273.8 +/- 79.1 days (range, 82 to 560 days). The disease-free period and survival time after OLTX both correlated well with the TDT (r = 0.546 and r = 0.701, respectively). The patients with fibrolamellar HCC had a greater TDT and a longer survival time than those with nonfibrolamellar HCC. Despite a wide range of TDT in patients who received transplants, their recurrent HCC tumors grew significantly faster than those of patients with the same disease who did not receive transplants. The factors involved in this accelerated growth rate may include the use of immunosuppressive drugs and the consequent suppression of host immunity against the growth of micrometastasis.

Methodologic issues in assessing the quality of life of cancer patients.

Abstract: Although quality of life assessments have been employed successfully in descriptive and evaluative studies in oncology, their use in cancer clinical trials has, to date, been limited. A range of issues have impeded the conduct of clinical trial-based quality of life investigations. These include: the absence of theoretical models to guide the development of quality of life measures; over-reliance on ad hoc approaches to quality of life assessment; and insufficient attention to the practical constraints operating in clinical research settings. Of primary importance is the need to develop multidimensional quality of life instruments that are brief and psychometrically robust. It is suggested that future work on instrument development focus on refining currently available generic or cancer-specific measures, and on developing new diagnostic-specific questionnaire modules. This psychometric work should be guided by appropriate theoretical models of the relationship among health-related quality of life domains. Although it is widely accepted that the patient represents the most appropriate source of quality of life data, it is suggested that efforts also be directed toward improving the validity and reliability of physician-generated assessments of patients' performance status and of treatment toxicities, and toward determining the feasibility of employing family members as proxy raters of the psychologic and social health status of patients who are unwilling or unable to provide such information. Additional attention should be paid to the many logistical problems that arise in clinical trial-based quality of life investigations. In particular, research designs and data collection procedures should be selected that minimize patient, medical staff, and institutional burden.

Prognosis of pregnancy-associated breast cancer.

Abstract: The survival of patients with pregnancy-associated (PA) breast cancer is difficult to predict for two reasons: The combination is very rare, and the natural history of breast cancer that is not associated with pregnancy is intricate and varies among individuals. Valid data collection and analysis is problematic given that studies gather patients over many years. The charts of 56 women with Stages I, II, and III breast cancer, who were pregnant or within 1 year postpartum at the time of breast cancer diagnosis between 1960 and 1980, were analyzed. Patients with PA breast cancer were compared to nonpregnant women of comparable ages, who were treated at the same hospital, by the same physicians, and during the same period. Four patients were lost before 5-year follow-up, and one patient before 10-year follow-up. These five patients had distant metastases at the time they were lost to follow-up, and are considered to have died within that time. Across stages, patients with PA breast cancer have survival not significantly different from those patients with non-pregnancy-associated (non-PA) breast cancer.

Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome.

Abstract: This study describes the inheritance of a defect in pyrimidine catabolism and its association with drug-induced toxicity in a patient receiving 5-fluorouracil (FUra) as adjuvant chemotherapy for breast carcinoma. The study population included the affected patient (proband), nine of her blood relatives, and seven healthy volunteers. The activity of dihydropyrimidine dehydrogenase (DPD), the initial enzyme of pyrimidine (and FUra) catabolism, in peripheral blood mononuclear cells was measured in each subject by a specific radiometric assay using FUra as the substrate. The proband had no detectable DPD activity. When enzyme levels in the proband and relatives were compared with that in controls, an autosomal recessive pattern of inheritance was demonstrated. This is the third patient with severe FUra toxicity secondary to an alteration in pyrimidine catabolism and the second from our clinic population suggesting that the frequency of this genetic defect may be greater than previously thought. Monitoring DPD activity may be important in the management of patients experiencing severe toxicity secondary to FUra chemotherapy.

Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. A gynecologic oncology group study of second‐line therapy in 105 patients

Abstract: One hundred five patients with Stage III or IV epithelial ovarian cancer whose disease had persisted or recurred after primary surgery and first-line chemotherapy were given tamoxifen (20 mg orally twice daily) and evaluated for response. Eighteen percent of the patients responded: 10% demonstrated a complete response (CR) and 8% showed a partial response (PR). Thirty-eight percent of the patients had short-term disease stabilization. CR had a median duration of 7.5 months, with the longest lasting 17 months. For patients with PR or stable disease, the median duration of response was 3 months (maximum duration, 9 months). When estrogen receptors of tumor tissue from patients demonstrating CR were evaluated, eight of nine (89%) had elevated estrogen receptor levels. This contrasts with patients who had stable or progressive disease as only 59% of them had measurable estrogen receptors (P = 0.16).

Endocrine therapy for desmoid tumors.

Abstract: Two female patients with desmoid tumors (aggressive fibromatosis) showed tumor regression after endocrine therapy. In one patient, tumor response to tamoxifen has been maintained over several years of treatment. In the second patient, who had inoperable mesenteric fibromatosis, the tumor progressed on tamoxifen but regressed after treatment with Zoladex (goserelin acetate, ICI, Melbourne, Australia) and medroxyprogesterone acetate (MPA). To the authors' knowledge this is the first report of the use of Zoladex in the treatment of desmoid tumors. This review of the literature reveals that the biology of this disease is related to the endogenous hormonal environment and that estrogen receptors have been documented in desmoid tumors. Thirty-five cases are identified where endocrine agents have been employed, with a response rate of 51%. Furthermore, tumors may respond to second-line hormonal therapy after failing to respond to initial endocrine treatment. Endocrine treatments have also been used in other disorders of fibroblastic origin. The authors recommend that endocrine treatment be employed in inoperable desmoid tumors or where there has been postsurgical recurrence. In addition, the role for endocrine therapy in other soft tissue neoplasms should be determined.