Showing papers in "Cancer in 1988"

Grading of astrocytomas: A simple and reproducible method

Abstract: This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)

The intergroup rhabdomyosarcoma study‐I. A final report

Abstract: The results of treatment of 686, previously untreated patients younger than 21 years with rhabdomyosarcoma or undifferentiated sarcoma, who were entered on Intergroup Rhabdomyosarcoma Study-I (IRS-I) were analyzed after a minimum potential follow-up time of 7 years. Patients in Clinical Group I (localized disease, completely resected) were randomized to receive either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC + radiation. At 5 years, approximately 80% of patients given either treatment were still disease-free and there was no significant difference between treatments in the overall percentages of patients surviving of 93% and 81%, respectively (P = 0.67). Patients in Clinical Group II (regional disease, grossly resected) were randomized to receive either vincristine and dactinomycin (VA) + radiation or VAC + radiation. At 5 years, 72% and 65% of the patients, respectively, were disease-free and there was no evidence of a difference between treatments (P = 0.46). The overall survival percentage at 5 years was approximately 72% for both treatments. Patients in Clinical Groups III (gross residual disease after surgery) and IV (metastatic disease) were randomized to receive either "pulse" VAC + radiation or "pulse" VAC + Adriamycin (doxorubicin) + radiation. The complete remission (CR) rate was 69% in Clinical Group III and 50% in IV, with no statistically significant difference in CR rates between treatments in either group. Those who achieved a CR had a nearly 60% chance of staying in remission for 5 years in Clinical Group III compared with approximately 30% in Clinical Group IV. The overall survival percentage at 5 years was 52% in Clinical Group III compared to 20% in Clinical Group IV (P less than 0.0001). The 5-year survival percentage for the entire cohort of 686 patients was 55%. Survival after relapse was poor, being 32% at 1 year and 17% at 2 years. The risk of distant metastasis was much greater than the risk of local recurrence within each clinical group, and there was no evidence of differing types of relapses between treatments. Primary tumors of the orbit and genitourinary tract carried the best prognosis, whereas tumors of the retroperitoneum had the worst prognosis. The authors conclude that for the therapeutic regimens evaluated there was no therapeutic advantage to including radiation in the treatment of Clinical Group I disease, or cyclophosphamide given as a daily low-dose oral regimen in the treatment of Clinical Group II disease or Adriamycin in the treatment of Clinical Groups III and IV diseases.

Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan

Abstract: Most patients with metastatic prostate cancer will have metastasis to bone. Such patients are best monitored by serial radionuclide bone scans. One hundred sixty six men with bone metastasis from prostate cancer who received androgen deprivation therapy had their pretreatment bone scans reviewed using a semiquantitative grading system based upon the extent of disease (EOD) observed on the scan. The EOD on the scan correlated with survival. The 2-year survival rates for EOD I to IV were 94%, 74%, 68%, and 40%, respectively. The survival of patients in categories EOD I and IV significantly differed from the other categories. Men with metastatic prostate cancer entered into trials designed to evaluate the impact of treatment on survival should be stratified based upon the EOD on the bone scan. This analysis also indicates that patients in the EOD IV category have a particularly poor prognosis and may be candidates for alternative treatments.

Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy.

Abstract: One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.

Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial.

Abstract: The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewing's Sarcoma Study (CESS 81) using a four-drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease-free. Using the Kaplan-Meier life table analysis, the estimated disease-free survival (DFS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty-one of 93 patients (23%) had local failure, 18 of 93 patients (19%) developed systemic metastases. The local failure rate was particularly high in patients treated with radiation and was reduced when radiation planning was centralized within the study based upon the extent of disease at diagnosis. Cox regression analysis of prognostic factors showed that tumor volume was a significant factor influencing prognosis. The estimated 3-year DFS rate was 80% for patients with small tumors (volume less than 100 ml) compared to 31% for patients with large tumors (volume greater than or equal to 100 ml). In patients who had surgery for local control, the histologic response to chemotherapy was analyzed on the surgical specimen and had a strong influence on survival: 79% DFS at 3 years for patients with less than 10% viable tumor (good responders) compared to 31% DFS for patients with more than 10% viable tumor (poor responders). Tumor load and responsiveness to chemotherapy are the two major factors influencing prognosis in patients with primary Ewing's sarcoma of bone.

Increasing incidence of primary brain lymphoma in the US.

Abstract: There have been a number of clinical reports suggesting an increasing incidence of primary brain lymphoma unrelated to acquired immune deficiency syndrome (AIDS) and organ transplantation. To investigate this issue, the US incidence of this rare lymphoma was assessed using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program (1973 through 1984). Never-married men, a relatively high risk group for AIDS, were excluded from the analyses. Brain lymphoma incidence increased from 2.7 in 1973 through 1975 to 7.5 cases per ten million population in 1982 through 1984 (chi-square trend, 15.25; P less than 0.001), and it increased among both men (chi-square trend, 6.74; P = 0.009) and women (chi-square trend, 10.48; P = 0.001). Increases in incidence also were observed among persons younger than 60 years of age (chi-square trend, 4.10; P = 0.04) and persons 60 years of age and older (chi-square trend, 9.16; P = 0.002). This increased incidence of brain lymphoma appears to be real: It antedates the AIDS epidemic and does not appear to be related to organ transplantation, another cause of increased risk of brain lymphoma. Although part of the increase may be an artifact of improvements in diagnostic technology and practice, most of the observed increase antedates the widespread use of such technologies. Finally, the increase in incidence of brain lymphoma does not appear to be related to overall trends in the incidence of brain tumors and non-Hodgkin's lymphoma, and it is not related to time trends in nosology.

Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial.

Abstract: To assess the efficacy and safety of Adriamycin (Adria Laboratories, Columbus, OH) in inoperable hepatocellular carcinoma (HCC), 60 patients were randomized to receive Adriamycin 60 to 75 mg/m2 at 3-week intervals and 46 patients to receive no antitumor therapy. The median survival rate of the Adriamycin group was 10.6 weeks; that of the group receiving no antitumor therapy was 7.5 weeks (P = 0.036). Adriamycin induced tumor regression of 25% to 50% in 5% of patients and of over 50% in only 3.3% of patients. It caused fatal complications (septicemia and cardiotoxicity) in 25% of patients. The severity of neutropenia leading to septicemia for a particular dose was unpredictable. Four of eight patients who developed cardiotoxicity received less than 500 mg/m2 of Adriamycin. We conclude that Adriamycin is not an ideal drug for the treatment of inoperable HCC.

Aneurysmal bone cyst. A review of 123 cases including primary lesions and those secondary to other bone pathology.

Abstract: A group of 639 bone lesions was reviewed in order to study the features of the aneurysmal bone cyst and its association with other conditions. A diagnosis of primary aneurysmal bone cyst not associated with any other bone lesion was made in 87 patients. In 36 additional patients the gross and microscopic changes of aneurysmal bone cyst were identified as part of some other solid bone lesion. Fourteen of these additional cases were associated with giant cell tumor (96 cases studied), six with chondroblastoma (41 cases studied), three with chondromyxoid fibroma (45 cases studied), two with nonossifying fibroma (68 cases studied), four with osteoblastoma (61 cases studied), one with fibrosarcoma (50 cases studied), three with fibrous histiocytoma (45 cases studied), two with osteosarcoma (100 cases studied), and one with fibrous dysplasia (42 cases studied). The age, site, and sex distribution of the cases associated with another lesion compares closely with that of the solid lesion concerned, supporting the concept that the aneurysmal bone cyst component is secondary.

Positron emission tomography in patients with glioma a predictor of prognosis

Abstract: Positron emission tomography (PET) studies have been performed using 18-F-fluorodeoxyglucose in 29 adult subjects with primary brain tumors. Seventy-two percent of the patients were treated previously. The glucose metabolic state in the lesions was increased in 16 patients, and was normal or decreased in 13 patients. The hypermetabolic tumors tended to behave in a more malignant fashion. Patients with hypermetabolic tumors had a median survival of 7 months after PET scan, compared to 33 months for those with hypometabolic lesions. Among the high-grade glioma patients, the PET results separated them into a good prognosis group (hypometabolic, with 78% 1-year survival) and a poor prognosis group (hypermetabolic, with a 29% 1-year survival after PET). These results suggest that glucose metabolic studies may provide an independent measure of the aggressiveness of a brain tumor, and may supplement pathologic grading.

Postradiation soft tissue sarcomas. An analysis of 53 cases.

Abstract: The clinicopathologic features of 53 cases of postradiation soft tissue sarcoma (PRS) were correlated with the physical characteristics of the administered radiation. All but three patients received radiation for malignant processes. Of the secondary sarcomas, malignant fibrous histiocytoma (MFH) accounted for 36 cases (68%), followed by seven extraskeletal osteosarcomas (13%), six fibrosarcomas (11%), two malignant Schwannomas (4%), one extraskeletal chondrosarcoma, and one angiosarcoma. The sex incidence, age of the patient at time of diagnosis, and location of the PRS correlated only with the clinical characteristics of the initial treated condition. The latency period (mean 10 years) showed an indefinite relationship to patient survival but no definite relationship to the patient's age at the time of the initial radiation. There was no difference between patients treated with megavoltage radiation (39 patients) and with orthovoltage radiation (seven patients) in the type of sarcoma, location, or survival, although the orthovoltage group received a lower mean radiation dose (3880 rads) than the megavoltage group (4446 rads). Megavoltage radiation, however, produced deeper tissue radiation changes and was associated with a shorter latency period. Most PRS were poorly differentiated, produced abundant collagen, and had a dismal prognosis.

Urokinase‐plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report

Abstract: Plasminogen activator is a serine protease which exists in two forms, known as tissue-type plasminogen activator and urokinase-type plasminogen activator. Here, we show that urokinase-type plasminogen activator activity in primary breast carcinomas correlates with both size of tumor and number of axillary nodes with metastases. Patients with primary carcinomas containing high levels of urokinase-type plasminogen activator activity had a significantly shorter disease-free interval than patients with low levels of activity. It is concluded that urokinase-plasminogen activator may be a new prognostic marker in breast cancer.

Pleuropulmonary blastoma the so-called pulmonary blastoma of childhood

Abstract: The authors studied 11 pediatric intrathoracic neoplasms that share clinicopathologic features and constitute a specific tumor in children. These neoplasms were intrapulmonary, mediastinal, or pleural-based masses. A common histologic feature was the presence of small, primitive cells with blastematous qualities separated by an uncommitted stroma. Focal rhabdomyosarcomatous, chondrosarcomatous, and liposarcomatous differentiation was observed. Epithelial components had bland cytologic features and probably represented entrapped benign epithelium and/or mesothelium. The prognosis for these patients was grave; seven patients died of their disease 5 months to 2 years after diagnosis. Two patients have survived disease-free for 10 and 12 years after diagnosis. Two recent cases are alive 14 and 32 months after diagnosis. This neoplasm constitutes a distinct entity which has been reported in the literature as pulmonary blastoma in children. It differs from pulmonary blastoma in adults because of its variable anatomic location, primitive embryonic-like blastema and stroma, absence of a carcinomatous component, and potential for sarcomatous differentiation. The designation of pleuropulmonary blastoma is suggested by the authors for these intrathoracic neoplasms of childhood rather than pulmonary blastoma for histogenetic and anatomic reasons. The clinicopathologic features, immunophenotypic and ultrastructural characteristics, possible histogenesis, and differential diagnosis of these neoplasms from other thoracopulmonary tumors in children serve as the basis for this report.

DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens

Abstract: Breast cancer proliferative capacity as determined by the DNA thymidine labeling index, along with estrogen and progesterone receptor status, is highly predictive for risk of relapse and overall survival. Recently, DNA ploidy and proliferative capacity (S-phase fraction [SPF]) as determined by flow cytometry have also shown significant prognostic value. The authors have developed a technique which allows a 50 to 100 mg aliquot of the same frozen breast tumor specimen routinely employed in steroid receptor assays, to be assayed for both DNA ploidy and SPF by flow cytometry. Of the 1331 tumors examined, DNA histograms were evaluable for ploidy in 89% (1184) of specimens examined; 57% of these were aneuploid. Adapting a trapezoidal model to estimate SPF in both diploid and aneuploid tumors, the authors found 81% (1084) to be evaluable for SPF, with a median SPF of 5.8% for the entire population. The median SPF was significantly lower in diploid tumors (2.6%) than in aneuploid tumors (10.3%, P less than 0.0001). Both aneuploidy and high SPF were strongly associated with absence of steroid receptors. Aneuploid tumors showed more striking differences in the frequency of high S-phase values with respect to receptor status and age or menopausal status, whereas diploid but not aneuploid tumors showed lower SPF in node-negative versus node-positive patients. Because it is particularly important to identify the high-risk minority of node-negative patients, the authors examined the node-negative group separately. High SPF subgroups appeared in each category of receptor status and age or menopausal status within the node-negative group, suggesting that SPF will be an independent prognostic factor. With the DNA flow cytometric methods used here, it is now practical to determine ploidy and SPF for nearly every breast cancer patient. These factors, which show associations with established prognostic factors, such as receptor status can now be fully evaluated for their prognostic significance in broad patient populations.

Characteristics of accelerated disease in chronic myelogenous leukemia.

Abstract: Determination of the characteristics of accelerated disease in chronic myelogenous leukemia (CML) helps in individual prognostication, and in the introduction and analysis of investigative approaches based on risk-benefit ratios. The outcome of 357 patients with Philadelphia chromosome-positive CML was analysed from the time of development of suspected features of accelerated disease. Median survivals shorter than 18 months were associated with the appearance of any of the following: cytogenetic clonal evolution; extramedullary disease; peripheral blasts greater than or equal to 15%, peripheral blasts and promyelocytes greater than or equal to 30%, or peripheral basophils greater than or equal to 20%; platelet count less than 1.0 X 10(5)/microliters; marrow blasts greater than or equal to 15%, marrow blasts and promyelocytes greater than or equal to 30%, or marrow basophils greater than or equal to 20%. Relative hazard ratios, or risk of death per unit time, were calculated based on the relative survivals of patients who did or did not develop the particular feature of accelerated disease, after accounting for the time to development of the characteristic. Further analysis identified five features that have additive independent prognostic importance: cytogenetic clonal evolution; peripheral blasts greater than or equal to 15%; peripheral basophils greater than or equal to 20%; peripheral blasts and promyelocytes greater than or equal to 30%; and thrombocytopenia. By providing an objective estimate of prognosis in accelerated disease, the model identifies patients in need of different therapeutic interventions before the development of blastic crisis.

Dietary habits and past medical history as related to fatal pancreas cancer risk among adventists

Abstract: Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.

Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis.

Abstract: The clinicopathologic features of 56 cases of ovarian serous borderline tumors (SBT) associated with peritoneal implants were reviewed. Data from 368 person-years of follow-up (median follow-up, 6.0 years) were analyzed to investigate the possibility that the histologic features of implants of this type of tumor may correlate with the prognosis. Eighty-five percent of the 56 patients were clinically free of tumor at the time of death or at last contact. Thirteen percent of the patients died of tumor, and one patient (2%) was alive with widespread progressive tumor. The product-limit estimate of the probability of death from tumor (+/- standard error) was 4% (+/- 3%) at 5 years and 23% (+/- 9%) at 10 years. The following three histologic features of the implants correlated with an adverse prognosis: (1) invasion (P = 0.0004), (2) severe cytologic atypia in both invasive and noninvasive implants (P = 0.0008) and in noninvasive implants alone (P = 0.02), and (3) the presence of mitotic activity in both types of implants (P = 0.02) and in noninvasive implants alone (P = 0.02). The only other feature that correlated with the prognosis was the presence of residual tumor postoperatively as assessed by the surgeon (P = 0.01). The product-limit estimate of death of tumor in patients with at least one of these four adverse prognostic factors was 56% (+/- 20%) at 10 years. Whether or not the patients received radiation therapy, chemotherapy, or both had no statistically significant effect on the outcome. These data and the results of a stratified analysis suggest that patients may benefit from additional therapy if adverse prognostic factors are present, especially invasiveness or severe cytologic atypia. It is unlikely that additional therapy is necessary in patients without adverse prognostic features, because no deaths occurred in this group.

Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients.

Abstract: Cyclophosphamide is an alkylating agent used intravenously or orally in the treatment of both malignant and nonneoplastic diseases. A known adverse effect of such treatment is hemorrhagic cystitis. A series of 100 patients with hemorrhagic cystitis induced by cyclophosphamide was studied. Major symptoms were gross hematuria (78%) and irritative voiding symptoms (45%). Microhematuria developed in 93% of patients. Hemorrhagic cystitis developed at significantly lower doses and shorter durations of therapy in patients treated intravenously than in patients treated orally. Cystectomy was required in nine patients and bladder cancer developed in five. Urine cytologic study, urinalysis, and cystoscopy are important in the diagnosis of hemorrhagic cystitis, and these studies plus periodic excretory urography are important for surveillance. In addition, new methods of protecting against the urotoxicity are available.

A population-based case-control study of childhood leukemia in Shanghai.

Abstract: A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patient's prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio [OR] = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children.

Distant metastases in papillary thyroid cancer. A review of 91 patients

Abstract: Of 731 patients with papillary thyroid cancer, 91 had metastases outside regional lymph nodes. The most common site was intrathoracic, occurring in 73 of the 91 patients. Miliary, micronodular pulmonary metastases, with iodine 131 (I-131) uptake and “curable” by I-131 treatment were encountered in seven patients. It has not been established whether this was a transient stage in additional patients. In 38 patients rounded, macrohodular pulmonary metastases were found. Another 21 patients had unilateral pulmonary infiltration and mediastinal enlargement. Pulmonary infiltrations may be hematogenic, or may possibly occur via regional, mediastinal lymph nodes. Mortality within 1 year of the diagnosis of distant metastases exceeded 50%. Occurrence of distant metastases showed a slight but highly significant association with male sex, advanced age, and advanced local tumor stage. Better prognostic determinants are, however, required if adequate treatment of the individual patient with papillary thyroid cancer is to be achieved.

Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C.

Abstract: Continuous hyperthermic peritoneal perfusion (CHPP) with a solution that contains mitomycin C (CHPP-M) has been clinically introduced as a prophylactic treatment for peritoneal recurrence of gastric cancer with serosal invasion. Two studies, each with a treated and a control group, were performed. In the historical control study the postoperative 3-year survival rate of patients (73.7%) in the treated group (n = 38) was significantly higher than the survival rate (52.7%) of those in the control group (n = 55) (P less than 0.04). In the random control study the survival rate (83%) of patients in the treated group (n = 26) was also higher than that (67.3%) of those in the control group (n = 21) in the 30 months that followed gastric surgery. However, there was no significant difference. In the historical control study with respect to the postoperative complications, anastomotic leak was observed in 8.5% of patients who were given CHPP-M and 12.8% patients who did not have CHPP-M. In the random control study anastomotic leak was observed in 3.1% of patients who had CHPP-M and 7.1% of patients who did not have CHPP-M. The incidence of adhesive ileus in patients having CHPP-M did not increase in historical or random control groups. Postoperative prolonged intestinal paresis or chemical peritonitis were not induced by CHPP-M. These results indicate that CHPP-M is a simple, safe, and readily available prophylactic therapy for peritoneal recurrence that may follow gastric cancer surgery.

Florodeoxyglucose imaging: A method to assess the proliferative activity of human cancer in vivo. Comparison with DNA flow cytometry in head and neck tumors

Abstract: Thirteen patients with malignant head and neck tumors were studied before they were treated with (18F) fluorodeoxyglucose (FDG) imaging and DNA flow cytometry (FCM). The nuclear DNA content and the percentage of proliferative cells (S + G2/M) were compared with the FDG uptake; FDG was retained in the primary tumor and/or neck metastasis in all patients. The accumulation of FDG did not correlate with histologic grade of the tumors, but there was a clear correlation (r = 0.86, P less than 0.001) between the proportion of the cells in S + G2/M phases of the cell cycle and the intensity of FDG accumulation. The uptake of FDG by the tumor also correlated with the percentage of S-phase cells (r = 0.82, P less than 0.001). The result suggests that enhanced glucose metabolism, measured by FDG uptake, is associated with the proliferative activity of the tumor. Thus, imaging with FDG may offer a new method to assess the aggressiveness of human cancer growth in vivo.

AIDS-related lymphoid neoplasia. The Memorial Hospital experience.

Abstract: The clinical features and laboratory results of 63 patients with or at risk for AIDS with lymphoid neoplasias seen from November 1980 through November 1986 are reviewed. Forty-three had systemic non-Hodgkin's lymphoma (NHL), nine had primary large cell lymphomas of the brain, 11 had Hodgkin's disease (HD), and one had plasmacytoma evolving to myeloma. Those with systemic NHL included 40 (93%) with intermediate or high-grade histologies, 35 (81%) with advanced stage (III, IV), and 28 (65%) with extranodal disease at presentation (predominantly marrow and meninges). Overall survival was short (median, 10.5 months from diagnosis) with the majority of deaths attributable to AIDS-related opportunistic infections (OI). However, 17 patients with diffuse NHL achieved a complete clinical remission, and nine now have been disease-free for more than 1 year (median follow-up, 28 months; range, 12 to 73 months). Early stage and lack of systemic symptoms were features associated with prolonged disease-free survival. Primary brain NHL was a uniformly lethal manifestation of AIDS, being diagnosed at postmortem in seven of nine severely immunosuppressed homosexual men. As with NHL, a propensity towards advanced disease and extranodal involvement was also observed in HD, suggesting that the atypical clinical behavior of HD may be an additional epiphenomenon of AIDS. This experience tends to argue for the use of intensive therapy in at least some patients with AIDS-related systemic NHL since it has resulted in a proportion of long-term disease-free survivors.

Renal cell carcinoma. Prognostic significance of morphologic parameters in 121 cases.

Abstract: Morphologic parameters were correlated with survival in 121 renal cortical neoplasms including 116 carcinomas and five oncocytomas. An increasing nuclear grade was generally correlated with a significant decrease in disease-free survival although no statistical difference was found between nuclear Grade 1 and 2 tumors. Similarly, a higher stage at diagnosis predicted a shorter disease-free survival. Renal vein invasion adversely affected prognosis only for high nuclear grade carcinomas. Papillary and spindled carcinomas, independent of nuclear grade, were associated with a significant decrease in disease-free survival compared to tumors with a solid pattern. Patients with large neoplasms (greater than 10 cm) had a significantly worse disease-free survival than patients with tumors 10 cm or less. The prognostic significance of tumor cell type is less clear. Patients with oncocytomas had the best disease-free survival compared with patients with tumors of other cell types. However, the difference in survival was not statistically significant for low-grade tumors, suggesting that nuclear grade rather than cell type may be the more important determinant.

Mammary angiosarcoma: The prognostic significance of tumor differentiation

Abstract: Mammary angiosarcoma appears to be a heterogeneous group of neoplasms morphologically, in which growth pattern or grade is an important prognostic factor. In this report, 63 patients whose slides were seen in consultation and/or who were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) are described. Included are 32 MSKCC patients from an earlier study (with additional follow-up for 15 who are alive) and 31 new cases. Twenty-five (40%) patients had low-grade (Type I) lesions (including the only man in the series), 12 (19%) patients had intermediate-grade (Type II) tumors, and 26 (41%) patients had high-grade (Type III) angiosarcomas. Because prognosis is significantly related to the type of angiosarcoma, the lesion should be thoroughly studied microscopically to establish tumor type. Estimated probabilities of disease-free survival 5 years after initial treatment were as follows: Type I: 76%; Type II: 70%; and Type III: 15%. The median length of disease-free survival also was related to tumor type (Type I: greater than 15 years; Type II: greater than 12 years; and Type III: 15 months). Pretreatment duration of the lesion and primary tumor size were not significantly related to the risk of recurrence or to survival. Total mastectomy is recommended for most mammary angiosarcomas. Adjuvant chemotherapy was used in 31 of 63 (49%) patients and, in this group, recurrences developed in 14 (45%) patients. Among 32 (51%) patients not treated with adjuvant chemotherapy, 18 (56%) had recurrences. Whereas the few long-term survivors with Type III tumors received adjuvant chemotherapy, recurrences developed in most patients with comparable lesions who were given this treatment. Because Type III angiosarcoma has a poor prognosis, such treatment may be appropriate for these patients. We were unable to demonstrate that adjuvant chemotherapy significantly improved prognosis for patients with Type I and Type II tumors, although recurrences tended to be less frequent among treated patients.

Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation

Abstract: One thousand three hundred seventy-nine nasopharyngeal carcinoma (NPC) patients were treated from March 1958 to December 1978. Twenty-two percent had stage I or II and 78% Stage III or IV had lesions. Two hundred twenty-Kv radiographs were used before 1960; and telecobalt was used from 1961 to 1978. Factors influencing the 5-year survival rate favorably are youth of patient, being female, pathologic condition (poorly differentiated carcinoma, 45.1% versus adenocarcinoma, 13%), stage (Stage I, 86%, Stage II, 59.5%; Stage III, 45.8%; Stage IV, 29.2%), decade admitted for treatment in the past (31% in the 1950s, 48.6% in the 1970s), total dose delivered to the nasopharynx (40 to 49 Gy, 46%; 70 to 79 Gy, 54.1%; 90 Gy or more, 64%) and prophylactic radiation to the neck regions (with prophylactic irradiation, 53.8%, without prophylactic irradiation, 23%). This implies that prophylactic radiation of the neck is crucial even without positive clinical metastasis. For those who have a residual tumor in the primary site when 70 Gy has been delivered, the total dose may be boosted to more than 90 Gy with the cone-down technique or on basis of adding 20 Gy to the dose at which the primary lesion disappeared grossly. The common postirradiation complications are: radiation myelitis, trismus, and otitis media. Because disease recurred in some patients after the fifth year, NPC patients should be followed for at least 10 years.

Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S‐phase fraction: A proposed classification of DNA histograms in breast cancer

Abstract: To optimize the prognostic value of DNA flow cytometry in breast cancer the authors calculated several parameters from the DNA histogram, including the DNA index, the size and number of aneuploid peaks as well as S-phase and G2/M-phase cell cycle fractions. Of these, DNA index and S-phase fraction (SPF) proved to be the most valuable prognostic indices. DNA aneuploidy was associated with a three-fold risk of death as compared to DNA diploidy (P less than 0.0001). The highest risk of death was associated with hypertetraploid (greater than 2.20) DNA index, whereas a tetraploid DNA index (1.80-2.20) was associated with a relatively low risk. The SPF had significant additional prognostic value in both DNA diploid (P = 0.0002) and DNA aneuploid (P = 0.02) tumors. By combining DNA index and SPF the authors defined three types of DNA histograms, which were associated with favorable, intermediate, and poor prognosis of the patients. DNA diploidy together with low (less than 7%) SPF (type I DNA histogram) was associated with very favorable prognosis, whereas DNA aneuploidy with high DNA index (greater than 2.20) or high (greater than 12%) SPF (type III DNA histogram) was related to the worst prognosis with approximately eight-fold relative risk of death. In a Cox multivariate regression analysis the type of DNA histogram was an independent and most powerful prognostic indicator in breast cancer. The other independent factors in the Cox analysis were primary tumor size, nodal status, and progesterone receptor status.

Tumor grade and stage as prognostic variables in upper tract urothelial tumors.

Abstract: Clinical and pathologic data of 54 patients with clinically localized transitional cell tumors of the upper urinary tract were reviewed to determine the significance of tumor grade and stage on patient survival. There were 43 tumors of the renal pelvis (one bilateral) and 11 tumors of the ureter. The primary tumor was staged by the new TNM classification into low stage (Ta: limited to mucosa; T1: lamina propria invasion) and high stage (T2: muscularis invasion; T3; invasion beyond the muscularis). Tumors were low stage (Ta/T1) in 28 cases (51.8%) and advanced (T2/T3) in 26 cases (48.2%). Twenty-five of 54 (46.3%) of the patients had low grade (Grades 1 and 2) and 29 of 54 (53.7%) had high grade (Grades 3 and 4) tumors. Median survival for all patients from date of diagnosis was 31 months, with a 5-year survival rate of 45.8%. Grade (low/high) matched stage (low/high) in 45 of 54 patients (83%). Median survival for patients with low grade tumors was 66.8 months compared to 14.1 months in patients with high grade tumors. Median survival for low stage tumors was 91.1 months and for high stage tumors was 12.9 months. These differences in survival related to both tumor stage (P = 0.001) and grade (P = 0.004) were statistically significant by log-rank test. Fourteen of the 54 patients (25.9%) developed local recurrence and 29 (53.7%) developed distant metastases. The lung was the most common site of metastasis. Eighteen patients (33.3%) had or developed transitional cell carcinoma of the bladder, which preceded the diagnosis of transitional cell carcinoma of the upper tract in seven cases and developed subsequently in 11 cases. Primary tumor stage by the new TNM classification is a better predictor of prognosis than tumor grade, although both variables are strongly predictive of patient course and survival. The advantages of the new TNM classification are discussed.

Histopathologic classification of small cell lung cancer. Changing concepts and terminology.

Abstract: Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.

Significance of systemic mast cell disease with associated hematologic disorders.

Abstract: A clinical and hematopathologic review of 66 patients with systemic mast cell disease (SMCD) was undertaken to investigate the frequency and the clinical significance of associated hematologic disorders. Twenty-two patients were found to have a second hematologic disorder, 19 of which involved the myeloid cells (ten dysmyelopoietic syndromes, five myeloproliferative disorders, three acute nonlymphocytic leukemias, and one chronic neutropenia), and three of which involved the lymphoid cells (three malignant lymphomas). A chromosome analysis of the bone marrow revealed abnormalities characteristic of neoplastic myeloid disorders in four patients. Five-year survival for patients with hematologic disorders was 28% compared with 61% for other SMCD patients (P = 0.004). Patients with hematologic disorders differed significantly from other SMCD patients in that they were about 7 years older (P = 0.039), and they presented more commonly with anemia (P less than 0.001) and constitutional symptoms (P = 0.007). These patients also had less frequent skin symptoms (P = 0.003) and urticaria pigmentosa (P = 0.018). By definition, patients with hematologic disorders had a greater percent of hematopoiesis (P less than 0.001) and decreased fat cells (P = 0.011) on bone marrow biopsies. A multivariate model demonstrated that the following independent variables were associated with the presence of hematologic disorders: low hemoglobin (P = 0.001), the absence of hepatomegaly (P = 0.016), high leukocyte count (P = 0.021), and the presence of pathologic fractures (P = 0.051). The frequent coexistence of SMCD with dysplastic and neoplastic disorders of myeloid cells is consistent with the concept that SMCD itself is a disorder of myeloid cells and that the mast cell may be myeloid in origin.