Warren W. Lane

Central nervous system metastasis from breast carcinoma autopsy study

Central nervous system (CNS) metastasis was noted in 309 patients of 1044 autopsy cases of breast carcinoma. The brain was involved in 193 cases, and cranial dura in 167 cases. In 82 cases, the cranial dura was the sole site of CNS involvement. Metastasis to the leptomeninges was found in 59 cases, and to the spinal cord and dura in 32 cases. Metastases to the infratentorial portion of the brain was almost as frequent as to the cerebrum. Forty‐two percent of the brain metastasis were single lesions, which is similar to the frequency of solitary metastasis to the brain from malignant tumors as a whole. CNS metastasis occurred more frequently in younger patients than older patients, and the clinical course of these patients was shorter than for those patients without CNS metastasis. CNS metastasis developed in the late stage of the disease, and often was not recognized clinically. Only 31% of the cases were clinically diagnosed or suspected before death. A median survival of these patients after clinical diagnosis of CNS metastasis was 33 days. However, a significant improvement was noted in the clinical diagnosis and median survival in the latter half of the study period. Eleven patients lived for more than 1 year after diagnosis of CNS metastasis. Only 14% of the 309 patients died from CNS failure. Cancer 52:2349‐2354, 1983.

The changing histopathology of lung cancer: a review of 1682 cases.

We have reviewed the histopathology of lung cancer patients seen over the past 13 years at RPMI. Assessment of this data indicates that adenocarcinoma is becoming progressively more prevalent as related to the other forms of lung cancer. Factors which in part may account for this increased prevalence are: 1) changes in criteria for reading histopathology of lung cancer, particularly since 1967; 2) the increased incidence of lung cancer among the female population who have a propensity for adenocarcinoma; and 3) occupational and environmental factors. In 1974 adenocarcinoma for the first time became the most prevalent type of lung cancer at RPMI. Whatever the reason, if our data are truly representative of a national trend, adenocarcinoma will soon become the most prevalent type of lung cancer in the United States. This fact may result in an increasing death rate since the present 18‐month survival rate for adenocarcinoma is substantially less than for squamous cell carcinoma, which has in the past been the prevalent form of the disease. As the smoking habits of women more closely approximate those of men, we expect that the incidence and mortality of lung cancer will prove to be quite similar in both sexes.

Chemotherapy induces regression of brain metastases in breast carcinoma

This study improves treatment options and ultimately survival by using systemic chemotherapy in brain metastases from breast carcinoma, since most of these patients have disseminated disease and a dismal prognosis when treated by conventional brain irradiation alone. One hundred consecutive patients with symptomatic brain metastases documented by radionuclide and/or computerized tomography scan were treated with systemic chemotherapy. Fifty of 100 patients demonstrated an objective response of brain metastases which was similar for extracranial metastases. There were 10 complete responders (CR), 40 partial responders (PR), 9 stable, and 41 nonresponders. Median duration of remission was 10+ months for CR and 7 months for PR (range, 2–72 months). Primary chemotherapy of brain metastases yielded responses in 27 pf 52 patients (52%) treated with Cytoxan (cyclophosphamide) (C), 5‐fluorouracil (F) and prednisone (P); 19 of 35 (54%) receiving CFP‐methotrexate (M) and vincristine (V); 3 of 7 (43%) treated with MVP, and 1 of 6 (17%) receiving Cytoxan plus Adriamycin (doxorubicin) (CA). Thirteen of 35 patients (37%) who subsequently had relapse of brain metastases were retreated successfully with secondary chemotherapy. The median survival for CR and PR was 39.5 months and 10.5 months, respectively, in contrast with nonresponder patients who had a median survival of 1.5 months. Thirty‐one percent of all treated patients survived more than 12 months. These findings suggest that the chemotherapeutic agents used penetrate the blood‐brain barrier inducing regression of brain metastases. This approach offers a significant benefit by simultaneously controlling extracranial disease, improving the response and prolonging survival.

An autopsy study of 1206 acute and chronic leukemias (1958 to 1982).

Autopsy data on 1,206 children and adult patients with acute myelocytic leukemia (AML) (585), chronic granulocytic leukemia (CGL) (204), acute lymphocytic leukemia (ALL) (308), and chronic lymphocytic leukemia (CLL) (109) obtained from 1958 to 1982 were reviewed. This analysis has shown that, whereas the proportion of patients with residual AML at any anatomic site decreased significantly and uniformly over the entire study period, significant corresponding decreases in patients with CGL and ALL occurred only since 1976 and 1978, respectively. No significant corresponding decreases were noted in patients with CLL at any time. Significant decreases were also noted over time in the rates of extramedullary site involvement by AML, CGL, and ALL. Whereas the lymphoreticular organs, kidneys, adrenals, and pituitary were most often involved at autopsy by CLL, the testes, leptomeninges, dura mater, uterus, large bowel, and pancreas were most often involved by ALL. In general, patients with AML and CGL showed the lowest relative rates of involvement of the various organs by leukemia during the 24‐year period. Whereas patients with AML and ALL showed significant decreases in the rates of involvement of nearly all anatomic sites during the most recent study periods, those with CGL and CLL showed corresponding decreases in only a few organ sites. The lower rates of organ involvement in patients with AML and ALL attest to the more aggressive eradication of leukemic cells by therapeutic regimens in these diseases over time. In particular, the significant decrease in the rate of meningeal involvement by ALL during the most recent period is probably attributable to central nervous system prophylaxis.

Ductal carcinoma in situ with microinvasion. A curable entity using surgery alone without need for adjuvant therapy

Of 408 negative axillary node (NAN) patients surgically treated at Roswell Park Cancer Institute (Buffalo, NY, 1976 through 1987), 36 (8.8%) presented with ductal carcinoma in situ with microinvasion (DCISM). In more than 50% of the patients (20/36) the disease was detected solely by mammography (microcalcifications and/or radiological density less than 1.5 cm). Thirty‐three patients underwent modified radical mastectomy; three had wide excision ± axillary dissection. Residual disease after excisional biopsy was found in 22 of 33 mastectomy specimens (67%): 11 (33%) pure ductal carcinoma in situ, five (15%) DCISM, and six (18%) frankly invasive. Of the 22 incidents of residual disease, 50% (11) were multicentric (one third of all specimens). These findings imply a high likelihood of residual cancer after excisional biopsy in these patients. All patients were free of disease for a mean follow‐up of 57 months (range, 16 to 137). These findings indicate that DCISM is an entirely curable disease when treated by mastectomy alone, without the need for adjuvant therapy, regardless of the status of other prognostic factors such as tumor size, histologic differentiation, age, or steroid receptor status.

Predicting recurrence in axillary-node negative breast cancer patients.

SummaryThis study attempted to identify the risk groups in axillary node negative breast cancer patients using validated first-generation prognostic clinical and pathologic factors. An updated 10-year follow-up in 407 such patients treated by surgery alone at Roswell Park between 1976–1987 showed a 10-year recurrence rate (RR) of 19% (95% confidence interval ±5%). Predictors of outcome were, in order of strength: (1) Tumor size (p= 0.0006); RR at 10 years was 2% ± 4 for tumors ≤ 0.5cm, 6% ± 7 for tumors 0.6-1.0cm, 16% ± 9 for 1.1–2cm, 29% ± 12 for 2.1–5cm, and 40% ± 31 over 5cm; (2) Histologic differentiation (p = 0.017); poorly differentiated/anaplastic (P/A) tumors had a greater RR (24% ± 8) than well or moderately differentiated (W/M) tumors (13% ± 8); (3) Age (p = 0.046); patients < 35 showed a RR of 28% ± 20, pts 35–50, 22% ± 10, and pts > 50, 17% ± 7 (p = 0.046). Cox Model analysis showed tumor size (4 groups) significant at < 0.0001, histologic differentiation (2 groups) significant at < 0.0005 after allowing for size, and age (±50) significant at <0.05 after allowing for size and differentiation.Combining these variables into subgroups enables selecting groups at various risks of recurrence. Groups with low risk are: (1) patients with tumor≤1cm, W/M (0% RR), (2) patients with ductal carcinomain situ with microinvasion (0% RR), and (3) patients with tumors ≤1cm, P/A (8% RR). In a suggestive finding in this last group, those over age 50 achieved a RR of 3% ± 6, while those age 50 or less had RR 14% ± 15. With the exception of this last group, all should be considered highly curable using loco-regional therapy alone, and might be spared the risks and costs of routine systemic adjuvant therapy. Groups with high risk are: (1) patients with tumors > 2cm (RR 32% ± 12), and (2) patients with tumors 1.1–2cm, P/A (RR 21% ± 14). These should receive adjuvant therapy. Groups with intermediate risk are patients with tumor 1.1-2cm, W/M (RR 12% ± 12). In a suggestive finding, those in this group over age 50 had a RR of 11% ± 12, while those up to 50 had a RR of 17% ± 30. These patients should be considered to be prime candidates for clinical trials.Adding second generation factors such as DNA ploidy or S-phase fraction to first generation factors should provide additional information on which to base therapy decisions, particularly in the gray area of intermediate risk. Our study indicates that node-negative breast cancer patients represent a heterogeneous population in terms of risk and prognosis, and that an individualized approach to adjuvant therapy should be taken.

Weight loss and Cachexia in lung cancer

Abstract Incidence, timing and severity of weight loss were studied in 479 patients with lung cancer. A phase of early weight loss, associated with a ∼ 50% reduction in survival, was identified. Food consumption was studied in normal individuals and in patients with and without weight loss. In these patients, anorexia failed to account for the weight loss. We discuss the possibility that weight loss results from interference by cancer with the metabolism of the host.

The prognosis of Hodgkin's disease in older adults.

This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkins disease. The clinical course of Hodgkins disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkins disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkins disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkins disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkins disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates.

Should all patients with node‐negative breast cancer receive adjuvant therapy? Identifying additional subsets of low‐risk patients who are highly curable by surgery alone

This study, which used combined first‐generation prognostic factors (tumor size, histologic differentiation, and age) on 408 patients with axillary node‐negative (ANN) breast cancer treated by surgery alone without systemic adjuvant therapy between 1976 and 1987 at the Roswell Park Cancer Institute, discerned four subsets of low‐risk patients with a 7‐year relapse rate of 6% or better. The first subset consisted of 48 patients (12% of the population) with tumors 1 cm or less in diameter that were well or moderately differentiated. These patients had a disease‐free rate (DFR) of 100% (95% confidence interval [CI], 94% to 100%). The second subset consisted of 35 patients (9% of the population) with tumors less than or equal to 1 cm that were poorly differentiated or anaplastic. These patients older than 50 years of age had a DFR of 97% (95% CI, 91% to 100%). The third subset consisted of 36 patients (9% of the population) with tumors 1.1 to 2 cm that were well or moderately differentiated. These patients were older than 50 years of age and had a DFR of 94% (95% CI, 85% to 100%). The fourth subset consisted of 36 patients with ductal carcinoma in situ with microscopic invasion. These patients had a DFR of 100% (95% CI, 87% to 100%). Twenty‐two of these patients, not in the other subsets mentioned, comprised 5% of the total population. These patients at low risk of recurrence, who comprise one third of the entire node‐negative population, are highly curable by local therapy alone and may be spared the risks and costs of routine adjuvant systemic therapy (AST). Patients with tumors larger than 2 cm (152 patients; 37% of the population) are at high risk of recurrence (26% with a DFR of 74% [95% CI, 64% to 84%]) and should routinely receive systemic adjuvant therapy. Patients with tumors up to 2 cm who are not in the low‐risk groups fall in a gray area (recurrence, 15% to 21%; DFR, 79% to 85%). For these groups, combining second‐generation prognostic factors such as DNA ploidy, S‐phase fraction, or cathepsin D should give the physician additional information to aid in making decisions regarding adjuvant therapy.

Oral contraceptive use has no adverse effect on the prognosis of breast cancer

This study evaluates the possible effect of OC use on the prognosis of established breast cancer. Three hundred forty‐seven patients with primary invasive breast carcinoma age 50 and under treated from 1971 to 1981 are included in this study. There were 112 OC Users (U) and 235 Non‐Users (NU). Separate retrospective analysis were done for a group of 154 patients (59 U and 95 NU) under age 35 (Group A) and for 193 patients (53 U and 140 NU) age 35 to 50 (Group B), in order to pay particular attention to relationship of duration, recency and latency of OC usage. Both subsets of U and NU presented similar clinical characteristics regarding menstrual, reproductive, family history, histology, receptor status. Users presented with a similar extent of disease as Non‐Users. No significant differences were found between U and NU in disease‐free interval (Gr A p = .41; Gr B p = .81), metastatic period (Gr A p = .66; Gr B p = .41) or survival (Gr A p = .54; Gr B p = .79), either alone or when adjusted for extent of node involvement. Users of less than two years (78 patients) had a similar survival (Gr A = .54; Gr B p = .36) as those of longer duration (33 patients). Recent OC users within a year of diagnosis had a similar survival as other users who stopped the pills more than one year (Gr A p = .86; Gr B p = .14). No significant differences were noticed in survival between the patients who began the use 10 years or more before diagnosis from those beginning more recently (Gr A p = .82; Gr B p = .69). Our data suggests no adverse effect of OC on the outcome of breast cancer, regardless the duration of use, latency or recency period.