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The serum or plasma hyperviscosity syndrome has been described in both monoclonal and polyclonal immunoglobulin disorders. The usefulness of initial and serial plasma viscosity measurements by an automated viscometer technique was evaluated and compared with serum protein electrophoresis data in 107 patients without monoclonal gammopathies and 153 patients with monoclonal gammopathies. In patients without monoclonal gammopathies, plasma viscosity correlated best with the concentration of gamma globulins. In patients with monoclonal gammopathies, plasma viscosity correlated best with the serum monoclonal protein concentration, but individual patient variations in the ratio of plasma viscosity to monoclonal protein concentration made accurate prediction of plasma viscosity difficult without direct measurement. Six of eight patients with plasma viscosity above 5.0 cp had classic symptoms of hyperviscosity syndrome, and four of the six had recurrent episodes. Six other patients with plasma viscosity above 4.0 cp had more subtle presentations of hyperviscosity but responded equally well to therapeutic lowering of plasma viscosity. These patients are part of a larger subset of 27 patients in whom initial plasma viscosity was above 3.0 cp. No patient with an initial plasma viscosity below 3.0 cp subsequently showed hyperviscosity symptoms. Plasma viscosity measured by this technique is a useful tool in screening patients with dysproteinemias to identify and monitor those with and at risk for the hyperviscosity syndrome.

Cystosarcoma phyllodes is an unusual breast neoplasm that rarely metastasizes. Most series report chemotherapy, radiation, and hormonal therapy to be ineffective. Three patients were treated with cisplatin and etoposide combination chemotherapy with effective palliation in two patients. Radiation therapy was effective in controlling symptomatic metastasis in all three patients. Hormonal therapy was ineffective in two patients despite the presence of positive hormone receptors. Chemotherapy and radiotherapy may be more effective in the treatment of this tumor than has been reported, although there is no apparent role for hormonal therapy. Functional hormone receptors are probably not present.

Confusion exists concerning the influence of pregnancy on survival in patients with malignant melanoma. To evaluate this problem a retrospective computer-aided study was performed of women in the child-bearing years treated for Stage I cutaneous melanoma at the Duke University Comprehensive Cancer Center. Fifty-eight women were identified who had melanoma arise during pregnancy (Group 1) and 43 patients were noted who became pregnant within 5 years of diagnosis of their melanoma (Group 2). Appropriate control groups matched for the clinical variables of age, primary site, and stage of disease and the pathologic variables of Clark's Level, tumor thickness, ulceration, and histologic type were selected from the cohort of 2938 melanoma patients seen at Duke. Actuarial survivals for Group 1 and 2 patients did not differ from their respective controls, although the small number of deaths in each group resulted in wide confidence intervals. When actuarial disease-free intervals were plotted, there was a significant difference beween women who had melanoma develop during pregnancy when compared to their controls (P = 0.04). In a multivariate regression analysis, after adjustment for the influence of the more significant prognostic factors for Stage 1 melanoma, including Clark's Level, ulceration, and tumor thickness, the effect of pregnancy on disease-free interval became more apparent (P = 0.02). No difference in actuarial disease-free interval was noted in the melanoma patients who elected to become pregnant within 5 years of diagnosis (P = 0.31). A multivariate regression analysis confirmed this finding. These data indicate that although an intercurrent melanoma during pregnancy has a worse prognosis than the control groups, once a woman has been diagnosed as having a cutaneous melanoma, a subsequent pregnancy has no effect on recurrence rate or survival. Cancer 55:1340-1344, 1985.

Thirty-three patients with newly diagnosed chronic granulocytic leukemia (CGL) were treated with melphalan between 1968 and 1976. Within 3 mo of beginning therapy subjective and objective disease parameters improved. Disease control was easily maintained with this agent until hematologic exacerbation occurred. The median duration of disease control was 25.3 mo, and the median duration of survival was 28.6 mo. Serious side effects were not produced. Thus melphalan appears to be another agent that may be used to control the manifestations of CGL prior to hematologic exacerbation.

In the United States, there are an estimated 5000 to 6000 new patients annually who might be candidates for major hepatic resection to treat their recurrent colon cancer. Since 1971, the program reported here has evaluated various factors that might influence the curative potential of such an approach. Sixty-five patients had a major hepatic resection from March 1971 through May 1982. Using a stepwise proportional hazard analysis, all data that had been stored in CLINFO (a data analysis system by Bolt, Beranek and Newman; Boston, MA) were evaluated for the effect of multiple variables on the survival of patients with resected hepatic metastases. Twenty-seven had a right hepatic lobectomy; 14 had extended right hepatectomy with one having the caudate lobe also removed; ten had left lobectomy, nine had left lateral segmentectomy; and five had a major hepatic resection with three-dimensional wedge excision of a metastatic deposit in the contralateral lobe. The 30-day operative mortality rate was 7% (4/58) for patients undergoing the standard major hepatic resection. It was 14% for seven patients in whom the isolation-hypothermic perfusion technique was used early in the series. In ten patients, wedge excision only was required to remove the tumor. Stage I disease is defined as tumor confined to the resected portion of the liver without invasion of major intrahepatic vessels or bile ducts. Stage II disease is regional spread and Stage III disease is metastasis to lymph nodes or extraregional sites. The 3-year survival estimate was 66% for the 37 patients with Stage I disease. The 3-year survival estimate for 13 patients with Stage II disease was 58%. Five of the nine patients with Stage III disease are presently alive from 3 to 23 months; one of the other four died at 35 months of disease. The stage of liver disease was the most significant variable in this survival analysis (p = 0.02); Dukes' classification of colorectal primary was significant at p less than 0.05. Those factors found not to be significant determinants of survival were: number of metastatic hepatic deposits, site of colon primary, age, sex, preoperative liver function tests, and CEA.

Research in animal and human cell cultures has shown that some chemotherapeutic agents, cisplatin in particular, have cytotoxicity that is significantly potentiated at elevated temperatures. Concurrent administration of systemic cisplatin and local hyperthermia in human patients has not been previously reported. A phase I/II study was undertaken to assess the systemic and local toxicities and activity of concurrently administered local hyperthermia and systemic cisplatin in human tumours. Nine patients with histologically proven malignant tumours have been treated from March 1985 to July 1987. Their histologies were: breast, four; SCC of head and neck, two; SCC of skin, one; malignant melanoma, one; synovial cell sarcoma, one. Once-weekly hyperthermia was administered for 60 min by external microwave devices in an attempt to achieve minimum intratumoral temperatures of 42 degrees C. Plastic catheters were placed intratumorally under CT guidance for thermometry purposes. Cisplatin 40-60 mg/m2 was given over 60 min when steady-state heating was achieved. A total of 44 treatments are available for analysis. All nine patients had minimum intratumoral temperatures below the desired goal of 42 degrees C, and only two patients achieved average intratumoral temperatures of 42 degrees C or greater. Two of the responding patients sustained significant thermal injury consisting of blistering and necrosis. Three patients required transfusion and delay of weekly treatment because of anaemia and leukopenia. Four patients had partial response (PR) and one patient had minor response (MR) within the heated treatment volume. Three of these five patients experienced significant subjective palliation. This combination of treatment modalities can be delivered safely.(ABSTRACT TRUNCATED AT 250 WORDS)

The maximum percent change (MPC) of plasma carcinoembryonic antigen (CEA) and gross cystic disease fluid protein (CDP) were correlated with response to therapy in 92 metastatic breast carcinoma patients. In patients treated with hormone therapy MPC values were significantly different between patients with disease progression (Prog) and regression (Reg): MPC-CEA for Reg = -72 +/- 7%, for Prog = 396 +/- 150%; MPC-CDP for Reg = -86 +/- 6%, for Prog = 702 +/- 330%, P less than 0.001 in a one-way ANOVA for CEA and CDP. Similar differences were noted in patients treated with chemotherapy. Decreased (greater than 50%) plasma CEA levels were observed in 24/29 (83%) of Reg, 18/35 (51%) stable and 0/49 (0%) of Prog; decreased (greater than 50%) plasma CDP levels were noted in 19/24 (79%) of Reg, 21/28 (75%) of stable and 2/35 (6%) of Prog. Patients with plasma marker decreases greater than 50% had significantly longer responses to therapy (14.2 months for CEA, 14.1 months for CDP) compared to patients with less than 20% decrease (2.0 months for CEA, 0.8 months for CDP), P less than 0.001 in a one-way ANOVA. Decreasing marker levels during the initial six weeks of therapy (negative slope) accurately identified Reg or stable patients: the predictive value of a negative slope was 92% for CEA and 86% for CDP. Rising marker values correctly identified treatment failures (Prog): the predictive value of a positive slope was 90% for CEA and 76% for CDP. These data indicated that changes in plasma CEA and CDP levels reflected increasing or decreasing tumor burden during hormone or chemotherapy treatment of metastatic breast carcinoma. Criteria have been established to predict therapeutic outcome based on the slope of CEA or CDP after six weeks of treatment.U

The cytosolic estrogen receptor (CER) content of 1037 primary breast carcinomas was evaluated by sucrose density gradient analysis. Tumor specimens from premenopausal patients had significantly lower levels of CER (14.6 +/- 1.5 (mean +/- SEM) 8S binding fmole/mg protein) compared with carcinomas from postmenopausal patients (57.5 +/- 3.9 fmole/mg protein; p less than 0.001). The proportion of specimens with CER levels above threshold values of 3, 7, or 10 fmoles/mg protein were significantly higher for postmenopausal patients (72%, 63%, 59%, respectively) than for premenopausal patients (56%, 42%, 36%, p less than 0.001). When compared within half-decades, no statistically significant differences between premenopausal and postmenopausal patients were observed for mean, median, or rank sums of CER levels (p greater than 0.3). When patients were compared by half-decades, both mean and ranked sums of CER levels were significantly different (p less than 0.001). The proportion of specimens that demonstrated CER levels above a threshold value of 10 fmole/mg protein increased sequentially from a low of 13/51 (26%) for patients less than 35 years to a high of 60/81 (74%) for patients greater than 75 years.

Thirty-nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x-ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexatefolinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P< .006). All patients who failed methotrexate-folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P= .03), but the total number of courses of chemotherapy was not significantly different (P= .06). No life-threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x-ray are predictive of an increased risk of methotrexate-folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate-folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease.(Obstet Gynecol 68:348, 1986)

One of the most controversial areas in the management of malignant melanoma concerns the efficacy of prophylactic lymph node dissection. During a retrospective computer-aided data review of over 3000 melanoma patients referred to the Duke University Cancer Center, 613 patients with complete staging along with surgical and pathologic data, having trunk and extremity melanoma, were identified with Breslow thickness in the range of 0.76 to 4.0 mm. One hundred eighty-seven of these clinically node-negative patients received an elective lymph node dissection (WLE/ND). The remaining patients were treated only with an initial wide local excision (WLE) at the time of diagnosis of their melanomas. There was no difference in age at diagnosis or male-female ratio between the treatment groups. A higher percentage of the WLE/ND group (36% vs. 31%) showed ulceration of their primary lesions and a greater mean tumor thickness (1.81 +/- 0.80 mm vs. 1.60 +/- 0.73 mm) than the WLE patients. Despite the force of these two adverse prognostic factors in the WLE/ND group, only ten deaths (5%) have occurred in the elective lymph node group compared to 51 (12%) in the control group. Using a multifactorial analysis to control for the prognostic contribution of the two most informative variables in stage I melanoma, Breslow thickness and ulceration, WLE/ND had an independent favorable effect on survival (p = 0.01). There was no apparent additional benefit to lymph node dissection in patients whose primary lesion measured less than 0.76 mm or greater than 4.0 mm in thickness. The surgeon may use survival estimates with and without elective node dissection based on a prognostic equation ("prognostigram") as a quantitative aid to treatment planning.

Eighty-eight patients with hormone-resistant Stage IV prostate cancer were treated with a five-drug chemotherapy program. Patient demographic data, prior therapy, symptoms, extent of disease, and laboratory studies were analyzed statistically to evaluate the association of these parameters with survival from the onset of chemotherapy. Factors associated with short survival included age greater than 65, severe bone pain, poor performance status, presence of soft tissue metastases, anemia, elevation of serum LDH, SGOT, alkaline and acid phosphatases, and prolactin, and hypoalbuminemia. Race, stage at initial diagnosis, prior radiation therapy, prior orchiectomy, and elevation of CEA had no prognostic association. We suggest that clinical trials of new therapies of hormone-resistant prostate cancer take into account the presence of these prognostic factors in the analysis of the results of therapeutic programs.

We have reviewed the clinical experience in the treatment of medulloblastoma with radiotherapy at Duke University Medical Center One hundred and twenty-seven patients treated between January 1, 1940 and December 31, 1983 were evaluated. The irradiation technique was reviewed and all irradiation doses were recalculated as minimum tumor doses in Gray (Gy). The mean follow-up was 24.4 years and the median follow-up was 26.5 years. The energy of the treatment machine was known in 102 cases. Sixty patients were treated with orthovoltage equipment and 42 patients were treated with megavoltage equipment. As a gross assessment of the impact of the details of radiotherapy treatment upon outcome, patients were grouped into excellent, good, fair, and poor treatment groups. Patients undergoing cranio-spinal axis (CSA) irradiation and receiving ≥52 Gy to the posterior fossa and ≥30 Gy to the clinically uninvolved remainder of the CSA were classified as having "excellent" technique. Patients undergoing CSA irradiation and receiving 40 to 52 Gy to the posterior fossa and ≥20 Gy to the remainder of the CSA were classified as "good." Patients receiving 20 to 40 Gy to the posterior fossa and ≥ 10 Gy to the spinal axis with or without prophylactic cranial irradiation were designated "fair." Any patient not fulfilling the above minimum criteria was categorized as "poor." The actuarial 5-year survival for the entire population was 33%. The 10-year survival was 21%. In 93 patients for whom records were detailed enough to allow categorization of treatment technique, 5-year actuarial survivals were: Excellent 37% (n = 17), Good 55% (n = 13), Fair 35% (n = 23), Poor 20% (n = 40). A complete surgical resection was not correlated with improved disease-free survival (DFS) in the excellent and good groups, but was correlated with an improved DFS in the fair and poor groups. The posterior fossa accounted for 62% of the failures in the 55 patients completing irradiation where the initial site of failure was known. An examination of patterns of failure in the spinal canal failed to demonstrate a dose response relationship above 10 Gy for spinal canal prophylactic irradiation. No patient developed recurrence beyond their period of risk as defined by "Collins' Law." In multivariable analysis, three factors were found to be independently associated with freedom from relapse: Radiation technique ( p = 0.02, good/excellent > fair > poor), extent of resection ( p = = 0.04, total > subtotal or biopsy), and Chang T stage ( p = 0.03, Stage IV > Stage III > Stage II). The last finding ran counter to expectation and indicates the inadequacy of staging patients retrospectively. The decade of treatment and the treatment machine energy were highly correlated with the treatment technique quality and were eliminated as independent factors in the multivariable analysis. We conclude: (a) Survival appears to be partially correlated with improved radiotherapy technique. (b) Spinal cord prophylaxis with irradiation in standard risk patients will need to be examined by prospective randomized trials to assess whether this dose can be lowered and thus decrease morbidity. (c) The period of risk for recurrence as defined by "Collins' Law" was valid in our population.

All 86 patients with squamous cell carcinoma of the oral cavity and oropharynx treated with fast neutrons at the Mid-Atlantic Neutron Therapy facility at the Naval Research Laboratory (MANTA) from its inception in 1976 until closing in 1979, are reported. Patients generally had advanced disease or have failed or were failing conventional treatment prior to being treated at MANTA. The fixed horizontal beam parameters were suboptimal. Patients were treated by either neutrons alone or various combinations of neutrons and photons. In patients with T3 or T4 primary carcinomas treated with less than 2100 neutron rad, only 37% (3/11) had a complete response at the primary compared to 57% (24/42) treated to a higher dose. However, there was a significant evidence of radiation related complication. The latter was expected in a phase I/II trial of a new modality such as fast neutrons. Isocentric hospital based cyclotrons should offer some hope of improvement in the future.

Errors in urine testing were studied using 119 health professionals who tested simulated urine specimens from six hypothetical patients. A record of the hypothetical patients' test results for 2 previous days accompanied each specimen. Five of the six records were loaded high or low to investigate testers' biases as a result of their knowledge of previous values. Testers demonstrated an aversion to extreme readings. At the lower concentration, 83% of erroneous readings were higher than the correct value. At the higher concentration, 70% of errors were below the true value. The results also revealed that readings were influenced by knowledge of past records. A higher reading for the sample with the biased-high record occurred 50% more often than a lower reading. Differences in error were nonsignificant for different educational levels and past experiences of the testers. Urine testing accuracy appears to be affected by a tendency toward avoidance of extremes and knowledge of previous results.

A time-dependent statistical model is employed to represent changes in 88 advanced prostate cancer patients' prognosis. Prognosis is based on whether serum alkaline and acid phosphatase are above or below respective cutoffs of 120 units and 2 units. It is estimated that a patient is over eight times as likely to die within 3 months if both his phosphatase measurements are high than if both are low (p ⪡ 0.001). This finding takes on added importance since the patients spent over two-thirds of their time in these two states. The model lends itself to investigation of questions regarding the dynamics of the disease, including changes in the probability of death and changes in prognosis. Three-month mortality rates, standardized according to prognostic state, are 0.13 for the first 90 days, 0.24 for days 91–270 and 0.13 for days beyond 270 (p < 0.05 for each comparison; missing data excluded). This initial increase, followed by a decrease in the state-standardized death rate, is consistent with either a treatment effect or individual differences between patients on the basis of relevant variables not included in the analysis.

Breast cancer is one of the most common serious health problems for elderly women. The study of age-related differences in breast cancer provides useful insights into its pathophysiology. New strategies for treatment, including adjuvant systemic therapy and less aggressive therapy for primary lesions, add new dimensions to a complex and variable disease.

A monoclonal antibody (H222) prepared against purified estrogen receptor has been demonstrated to be highly specific and sensitive in an immunohistochemical assay for the detection and quantification of estrogen receptor in human breast carcinoma biopsy specimens. To evaluate the clinical applicability of this assay in cytologic specimens, response to therapy in 12 patients with recurrent breast cancer was correlated with H222 antibody localization in specimens obtained by fine needle aspiration biopsy. All 7 patients with positive H222 responded to hormone therapy (1 complete and 3 partial remissions and 3 stable disease), while 1 of 5 patients with negative H222 responded (1 stable disease). This experience suggests a role for immunohistochemical estrogen receptor determinations in prediction of response to hormonal therapy in patients whose tumor is accessible only to aspiration biopsy. Special care in the handling and interpretation of specimens is essential to optimal application of this method.

The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.

A total of 143 patients underwent radical prostatectomy. Surgical specimens were evaluated with respect to local extent of disease, Gleason grade of the primary and relative nuclear roundness of the surgical specimen. The probability of disease control in the total population was 88 per cent at 5 years. Only 8 per cent of the patients who had disease confined to the specimen failed compared to 14 per cent of those who demonstrated extension outside of the surgical margins. The incidence of failure increased as a function of seminal vesicle involvement. Seminal vesicle involvement was greatest among patients with a Gleason grade greater than 7. Postoperative radiation did not offer any apparent advantage in patients with positive margins.

Patients with hormonally unresponsive prostatic adenocarcinoma were subjected to a five-drug chemotherapy program using bleomycin, 5-fluorouracil, methotrexate, vincristine, and prednisone. Analysis of survival curves indicated that deletion of an alkylating agent from this five-drug program reduced survival when patients with equal risk factors were compared. Bleomycin was poorly tolerated by this aged population.

The clinical course of 75 males subjected to radical prostatectomy after pelvic lymphadenectomy were compared with that of 29 males receiving radical prostatectomy without lymphadenectomy. The adverse survival impact of positive pelvic nodes and the impact of pelvic lymphadenectomy are discussed.

Thirty-one patients with metastatic breast carcinoma refractory to standard hormonal and chemotherapy were treated with cisplatin 100 mg/m2 per course and etoposide 300 mg/m2 per course divided over 5 days. Courses were repeated at 3-6-week intervals, depending on the speed of recovery from myelosuppression. Of 29 evaluable patients, three had complete responses, eight had partial responses, eight had stable disease, and 10 had progressive disease. Nausea, emesis, anorexia, weakness, and easy fatigability were common but tolerable side effects. Myelosuppression was frequent and occasionally profound but there were no deaths from hemorrhage or infection. No significant renal toxicity was encountered. The combination of cisplatin and etoposide has sufficient antitumor activity with acceptable toxicity in heavily pretreated patients to justify its further study in breast cancer.

The most effective immunization historically has been active immunization against a specific disease process. We report here the results of specific active immunization of 719 patients with invasive melanoma. The patients were sequentially immunized with approximately 2.5 × 107 x-irradiated, neuraminidase treated melanoma cells and BCG was used for its adjuvant effect. The sites of primary tumor location included trunk (42%), extremity (35%), head and neck (15%), unknown (3%), eye (2%) and mucocutaneous (1%). Two hundred thirty-six Clark's Level III patients with Stage I disease experienced an 88% survival ar four years while 47 Stage II patients had an observed survival of 82% during this same lime period. Very similar statistics were observed for 124 State I Clark's Level IV patients and 70 Stage II patients. Nineteen and 26 Clark's Level V patients with Stage I and Stage II disease realized a 100% and 55% observed survival at four years respectively. Fifty-two patients with either an unknown primary and metastatic disease prior to immunotherapy or mucous membrane primaries with metastatic disease prior to immunization were observed to have a 65% survival at four years while invasive ocular primary patients without metastatie disease prior to immunotherapy had a 70% four year survival in the 19 patients evaluable. The largest number of patients fall in the first two years of follow-up, therefore, the degree of confidence concerning the survival statistics for years 3 and 4 is broad at this point in time. Further follow-up with careful evaluation will be required before definition statements can be made and comparisons can be elicited. The overall survival statistics do, however, encourage continued evaluation of specific active immunotherapy for patients with invasive melanoma with both Stage I and Stage II disease.

This prospective randomized study in nonhormonally responsive adenocarcinoma of the prostate shows that response rates to melphalan vs cyclophosphamide groups were virtually identical.

In a series of 1341 patients with histologically proven malignant melanoma seen at Duke University Medical Center from 1968 to 1978, 107 patients developed central nervous system (CNS) metastases. These patients were evaluated on the basis of which factors were associated with the development of CNS metastases. Male patients, patients with invasive primary lesions as measured by Clark's system, and patients with primary lesions of the head/neck or oral mucosa had higher incidences of CNS metastasis. Age and race were not significant factors. Clinically, single CNS metastases were seen in 48.8% of the patients; multiple cerebral lesions were seen in 37.2% of the patients. In 22% of the patients there was CNS metastasis alone, in 41% a second organ was involved, and in 20% three organs were involved.

The Gompertz equation has emerged as the most useful model for tumor growth analysis but lacks a demonstrable relationship between its parameters and biological growth regulatory mechanisms. A new model for tumor growth analysis is developed based upon a class of mechanisms considered most likely to be responsible for control of the growth of normal and neoplastic tissues. The resulting differential equation is not soluble in closed form for cell number as a function of time. A technique related to quasi linearization is developed to allow fitting the model to data and estimating the parameters from the dataset. A comparison is made on animal tumor data between the new model and the Gompertz model. The fit obtained with the new model appears at least as good, if not better, than the Gompertz. The ability to obtain parameter estimates relating to biologically important characteristics of the tumor with the new model more than offsets the more complex computations involved in fitting. This model is an attractive alternative to the Gompertz equation as the basis for analysis of tumor growth data.

Data management problems in clinical medicine frequently require organization and analysis of data over the dimension of time, particularly in chronic disease such as cancer. Manual methods share the disadvantages of being cumbersome to modify and allowing only casual subjective interpretation. We have developed a schema-driven, time-oriented record for oncology (TORO) on a minicomputer for storage, retrieval, and analysis of cancer patient data. This system features interactive data entry and editing, simple schema development, and tabular and graphical outputs of analyzed and retrieved data in formats the physician uses in his manual records. A series of statistical tests, most importantly those relevant to response and survival analysis, operate directly on TORO patient files in response to interactive requests from a medical investigator. TORO combines the ability to manage individual patient data for clinical purposes with the ability to perform rapid cross-patient analyses for research purposes. Furthermore, space utilization is quite efficient and transportability of the system has been demonstrated.

The Southeastern Cancer Study Group performed a Phase II study of teniposide in previously treated patients with metastatic breast cancer. No responses were observed in 11 evaluable patients who received teniposide 60 mg/m2 by IV infusion for five consecutive days every three weeks. Toxicity was primarily gastrointestinal and hematologic and was frequently severe. This study demonstrated no therapeutic activity for teniposide when given in this dose and schedule to patients with heavily pretreated metastatic breast cancer.

Twenty-six patients with known or suspected medullary thyroid carcinoma (MTC) and 21 normal control subjects were tested intravenously on four separate days with calcium gluconate (CG), 2 mg Ca(++)/kg/1 min.; pentagastrin (P), 0.5 ug/kg/ 5 sec.; calcium chloride (CC), 3 mg Ca(++)/kg/10 min.; and a combination of calcium gluconate and pentagastrin (CG + P). Calcitonin (CT) levels were determined by radioimmunoassay on plasma collected before and immediately following each test infusion. In none of the 21 control subjects was there a clear increase in CT above 200 pg/ml following any of the four provocative tests. Conversely, in all 26 patients with known or suspected MTC, plasma CT levels were markedly increased (>300 pg/ml) following the combined infusion of CG + P. The peak CT response was greater with CG + P than with a) CG alone (22 of 24 patients, p < 0.002), b) P alone (25 of 26 patients, p < 0.002), or c) CC alone (17 of 17 patients, p < 0.002). Of 12 MTC patients with undetectable basal calcitonin levels, all had peak responses greater than 300 pg/ml following CG + P, whereas such responses occurred less often following CG alone (8 of 12) or P alone (8 of 12). The results demonstrate that the combined administration of pentagastrin and calcium gluconate constitutes a more effective and reliable stimulus for CT secretion from MTC cells than the use of either agent alone, and appears the most useful single screening test for the detection of occult MTC.

• A retrospective search of the Duke University Melanoma Clinic patients identified 399 cases with primary malignant melanoma located in the head and neck region. Ninety-five percent of the deaths in this series were from metastatic melanoma. Various clinical and pathological data were examined and their effects on survivability and disease-free intervals were evaluated. The characteristics noted included sex, age, depth of the invasion, thickness, site of the lesion, histologic type, and nodal status. A multivariate regression analysis identified the following factors as having a negative effect on survival: nodular histologic type, scalp primary, increasing Clark level, and male sex. In comparing head and neck, extremity, and truncal primary sites, the median survival for patients with head and neck malignant melanomas was notably less. These differences correlated with a higher incidence for male patients, for patients with thicker lesions, and for patients with an increased frequency of nodular histologic type. ( Arch Otolaryngol 1983;109:803-808)

Let me start by putting the proper time frame on this discussion. I brought my daughter home from boarding school yesterday. She is seventeen years old. She was born one year after our first meeting on the subject of EFT. So, EFT is not something that’s been around for just a few years.

APPROPRIATE description and classification of the clinical features of the patient with cancer are important prerequisites to clinical management and interpretation of treatment results. Classification serves at least three important functions. First, it is used to provide a prognosis for the individual patient, to establish a basis on which the patient, his family, and the physician may discuss the anticipated course of the disease. A second related use of classification is to guide the physician in his choice of therapy and assist the patient in understanding the potential benefits and risks of alternate forms of treatment. Finally, classification facilitates the use of stratification techniques prior to treatment allocation in clinical trials so that relatively homogeneous subgroups are available for comparison on alternative treatments. A classification system should be chosen according to its ability to fulfill these functions. Drawbacks of Staging Systems Staging, or classification according to the anatomical extent of

In a prospective study of 211 outpatients undergoing cosmetic surgical procedures under local anesthesia supplemented with intravenous diazepam and morphine, patient pain response to the local anesthetic infiltration was graded and the recall of the operative experience was assessed. One hundred and fifty-five patients (73%) had either no pain response or a mild response, 41 (19%) had a moderate response, and 15 (7%) had a severe response. One hundred and eighty-seven patients (88%) had total amnesia for the local anesthetic infiltration and the operative procedure, and 183 (87%) could not recall pain, but had recall of events during surgery. There were no untoward drug reactions nor episodes of cardiorespiratory depression. We conclude that intravenous diazepam with or without intravenous morphine following triazolam, morphine, and premethazine premedication is a safe and effective regimen, for outpatient surgery.

To evaluate age-related differences in the current patterns of presentation and clinical management of breast cancer patients, the authors reviewed 1795 patients referred to a university hospital for their initial treatment. No age-related differences were found with respect to laterality and anatomic site. Age-related differences were seen with respect to histology, with mucinous (colloid) carcinoma being relatively more common with increasing age and medullary and inflammatory carcinoma being more common among young patients. Patients over age 55 presented with more advanced extent of disease, but the proportion did not further increase above age 65. Patients age 75 and older were nearly twice as likely to have surgery as their sole treatment as patients under age 45. The difference in treatment was specifically associated with the differential use of adjuvant chemotherapy between age groups. Sixty percent of patients under 45 with regional node involvement received adjuvant chemotherapy compared with only 27% of those 65 and older. Despite their similar characteristics in regard to laterality, anatomic site, and histology, elderly patients are less frequently given adjuvant chemotherapy in stage II breast cancer.

Transcutaneous oxygen monitoring during rhytidectomy surgery under local anesthesia was evaluated in 18 patients. Blood gas analysis of samples of arterial blood obtained from the superficial temporal arteries during rhytidectomy was compared with transcutaneous PO2 values. Simple linear regression analysis indicated that the transcutaneous PO2 correlates strongly with arterial PO2. Transcutaneous PO2 monitoring could be a reliable, inexpensive, and continuous method of assessing gradual or sudden changes in arterial PO2, provided the sensor is fastidiously maintained and properly applied, elements which are critical to relying on this particular device. However, this instrument has no advantages over the digital pulse oximeter.

One hundred endometrial carcinoma specimens were analyzed for estrogen receptor content and histologic composition. Benign tissue elements were identified in the majority of tissue sections. Histologic control of endometrial carcinoma specimens submitted for steroid receptor analysis is critical, because biochemical assays of whole tissue homogenates cannot determine receptor localization among tissue components.

Endometrial adenocarcinomas from 96 patients were studied for their biochemical estrogen receptor content as well as immunohistochemical localization of estrogen receptor. A well-characterized specific monoclonal antihuman estrogen receptor antibody (H222 sp gamma) as amplified by peroxidase/antiperoxidase techniques was used for immunohistologic localization. Immunohistochemical evaluation incorporated both the intensity and distribution of staining into a semiquantitative analysis (HSCORE). The total HSCORE was the sum of the relative contributions of the four histologic components: benign epithelium, malignant epithelium, stroma, and myometrium. These results were compared with clinicopathologic features of the tumors. Excellent sensitivity (91.5%) and specificity (93.1%) were observed for immunohistochemical analyses as compared with the biochemical analysis of estrogen receptor for these tissues. The cancer component HSCORE correlated better with grade than did the biochemical estrogen receptor determination. Correlation was also observed between surgical stage and estrogen receptor content. Decreasing biochemical estrogen receptor content predicted advanced surgical stage (p = 0.0003), as did the total HSCORE (p = 0.003); however, the HSCORE of the cancer component only did not correlate with advanced surgical stage (p = 0.11). Although immunohistochemical analyses predicted biologic differentiation better than did the biochemical technique, stage correlated better with biochemical estrogen receptor analysis and total HSCORE than did the cancer component HSCORE. The HSCORE of the cancer component may better predict biologic behavior and therefore identify cancers more likely to respond to hormonal therapy.

In patients with hormone-resistant, Stage D adenocarcinoma of the prostate histologic grading using the Gleason classification allowed stratification of a subgroup of patients in whom response to chemotherapy could be predicted from the growth pattern of the original prostatic tumor. Sixteen of 30 patients (53 per cent) with Gleason sums of 6 or 7 demonstrated a response to chemotherapy. Conversely, only 4 of 21 patients (19 per cent) with elevated Gleason sums of 8, 9, or 10 achieved a response to chemotherapy (P

Some of the most substantive recent developments regarding malignant melanoma involve the elucidation of prognostic factors in the disease. Formerly, melanoma had the well-justified reputation of being a capricious, unpredictable neoplasm. The advances in prognostic classification are largely due to pathological microstaging guidelines formulated by Clark et al. and Breslow [1, 2]. Their criteria have made it possible to precisely predict which patients have almost certainly been cured by wide local excision alone, which patients are likely to have occult distant metastases with a high risk for recurrence and which patients have occult metastasis confined to regional lymph nodes. Several of the long-standing issues in treating melanoma, such as the efficacy of prophylactic lymph node dissections and the role of various modalities of adjuvant therapy, should be readily resolvable with well-designed studies involving a practical number of subjects now that it is possible to form subgroups of patients with uniform prognostic features.

• Twenty-two patients with inflammatory breast carcinoma received preoperative chemotherapy consisting of weekly administration of cyclophosphamide, doxorubicin hydrochloride, fluorouracil, and vincristine sulfate for six weeks. Postoperative therapy consisted of 22 weeks of biweekly administration of these drugs. Regional radiotherapeutic consolidation followed chemotherapy. Nineteen patients completed therapy. Twelve of these patients remain disease free (median, 15 months; range, four to 32 months). Median disease-free survival for all 22 patients is 13 months or more (range, zero to 32 months). Median overall survival is 18 months or more (range, one to 33 months). This regimen compares favorably with prolonged adjuvant and maintenance chemotherapy for inflammatory breast carcinoma. ( Arch Surg 1987;122:1329-1332)

Advancing age is associated with poorer prognosis in malignant melanoma. We studied 3,872 cases of malignant melanoma to evaluate whether the effect of age could be analyzed relative to sex, tumor depth, primary site, and other clinical and pathologic variables. The sex distribution by age shows a slight female predominance in the early and late decades but male predominance in the middle years. The percentage of patients with metastatic disease at initial diagnosis did not vary with age, despite greater diameter and depth of lesions in the older patients. In fact, in the older age groups, initial nodal metastasis occurred slightly less frequently. Trunk primaries decreased in frequency with increasing age, while extremity lesions remained relatively constant, and face, nose, and ear lesions increased. This was in part related to the histopathologic type, as lentigo maligna lesions increased in frequency with age, superficial spreading lesions were somewhat less frequent in the older age group and nodular types were fairly constant. On the basis of both Clark's level and Breslow thickness, there was an increasing proportion of deeper penetrating lesions in the older age group. The mean diameter of these lesions on the skin surface was also greater for the older patients. This would suggest that lesions in the older individual remain confined to the local site longer, penetrate and spread, but do not necessarily metastasize more rapidly. Cox model regression analysis of survival time within stage showed that age was highly significant as a poor prognostic factor. Though the adverse relation of advancing age with survival was partially explained by predominance of other unfavorable factors, such as primary site, depth of lesion, or histologic type, age remained an independent poor prognostic factor (chi 2 = 5.3; P = .02) for death due to melanoma.

A quantitative assessment of the long-term prognostic value and clinical usefulness of recall antigen reactions in patients with malignant melanoma is not available. The authors evaluated longitudinal observations of survival made in 846 patients over a 12-year period. Each patient was initially studied with Mantoux-type recall antigen skin tests. The patients were categorized with respect to the following: high (> 5 mm) or low (≤ 5 mm) averaged skin test reaction diameters at 48 hr; Clark level; tumor stage (I=localized tumor, 11=local extension and/or region lymph node metastasis, III=systemic metastasis); ulceration; site of primary; histologic type; age; and sex. The percentage of high reactors in Stages I, II, and III were 44.3%, 37.4%, and 25%, respectively. Survival was evaluated with the Cox- Mantell hazard function model and the Cox regression model. The significant (chi-squared; probability) risk factors detected were tumor stage (94.58; ≤ 0.0001), Clark level (19.37; ≤ 0.0001), sex (16.97; ≤ 0.0001), and skin test reactivity (7.48; ≤ 0.0062). A significant relationship also was detected between skin test reactor status and the tumor stage (p≤0.0330). When evaluated within each stage of disease, skin test reactivity predicted survival only in Stage II patients (p ≤ 0.0080). Five-year survival estimates among Stage II patients were 58% among high reactors and 38% among low reactors. Despite this interesting difference, the amount of independent information about survival provided by recall skin tests was small in comparison to the other clinically available risk factors. This suggests that recall antigen skin tests are not likely to be helpful in the evaluation of the individual patient.

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969–1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III 2 received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach.

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)

Of 44 patients with clinically localized prostatic adenocarcinoma and regional lymphatic metastases proved by staging pelvic lymphadenectomy 11 were treated by radical prostatectomy, 20 received extended field radiationand 13 were assigned to delayed hormonal therapy. The median survival for the entire group was 39.5 months. None of the3 treatments appeared superior in prolonging survival. Furthermore, no enhancement of disease control could be demonstrated in either treatment group. Patients with prostatic adenocarcinoma and positive nodes appear to have equivalent adverse biologic potential and should be considered candidates for treatments designed to produce systemic effect.

Immediate reconstruction of a breast removed for treatment of carcinoma can be accomplished without altering the cancer-ablative surgical procedure. The theoretical possibility that reconstruction might compromise the cure rate has tempered enthusiasm for this approach. To test this issue, the relapse-free survival of 101 patients who underwent breast reconstruction in the immediate postmastectomy period was compared with that of 377 patients with breast cancer who underwent mastectomy without immediate reconstruction. This comparison was accomplished using multivariable statistical techniques to correct for baseline inequalities between the patient groups. After adjustment for the relevant prognostic factors, no significant difference remained between the two groups. We conclude that immediate reconstruction has no discernible adverse influence on the natural history of surgically treated breast carcinoma.

The prognostic significance of immunocytochemical methods for estrogen (ER) and progesterone (PgR) receptor analyses was studied in 257 patients with primary breast cancer followed up to ten years. H222 antibody was used for ER and JZB39 used for PgR. ER positive (>10 fmol/mg prot) tumors using ligand assays showed disease free interval (DFI) advantage for 3 years but none after three years. H222 positive tumors were associated with survival advantage throughout the ten year period (p=0.004). PgR (by ligand analysis) advantage was only seen in the first 3.5 years. JZB39 positive tumors showed significant survival advantage through the ten year period (p=0.04). Both ER and PgR correlated with nuclear grade and histologic grade. Within histologic graDe S ER positive DFI advantage was observed only among HG II lesions (p=0.04). While separation within lymph node groups was observed in the initial period in each category, only the 1–3 node positive subgroup had distinct advantage throughout the period of follow-up. The data indicate that semi-quantitative immunocytochemical ER and PgR analyses contributes to the separation of prognostic groups among specific subgroups of primary breast cancer.

Malignant melanoma, a type of cancer that accounts for 1% to 3% of all malignant neoplasms is 20 times more frequent in the American white than black population. During a computer-aided retrospective chart review of more than 2,500 patients with melanoma being followed up at the Duke University Comprehensive Cancer Center, 31 blacks have been identified. Primary lesions of the foot were predominant in blacks with melanoma, and a high percentage of these were classified pathologically as acral lentiginous primary lesions. Black patients had a more advanced stage of disease at first presentation and a more deeply invasive primary lesion than their white counterparts. Five-year survival for the total black population was 23%. Blacks had a significantly worse prognosis than the white population when a comparison with the total group was made that was controlled for sex, age, site of primary lesion, stage of disease at presentation, and Clark level of primary melanoma lesion. This emphasizes the aggressive nature of this disease in the American black. (JAMA1982;248:1856-1859)