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Biomedical subjects

N Wolmark

Publications and source records attributed to N Wolmark.

At least 109 records · Page 6Linked to original sources
PubMed1984

The relationship of depth of penetration and tumor size to the number of positive nodes in Dukes C colorectal cancer.

This study examines the interrelationships of depth of penetration, tumor size, and the number of positive nodes in Dukes C colorectal cancer. The results indicated that depth of tumor penetration was related to both tumor size and the number of positive regional lymph nodes. Tumors with positive nodes which failed to penetrate the muscularis propria (C1) were smaller, and were associated with fewer positive nodes than were tumors penetrating all coats of the bowel (C2). Although tumor penetration was related to tumor size and the number of positive nodes, no correlation was evident between tumor size and the number of positive nodes within the C1 and C2 patient subsets. The data underscore the biological significance of depth of tumor penetration and militate against tumor size as a prognostic discriminant in patients with colorectal cancer. The findings represent a contradiction to the prevailing biological concepts relative to the behavior of solid tumors as reflected in the TNM classification scheme.

Colonic Neoplasms↗
PubMed1984

The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer. Results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials.

This analysis explores the prognostic significance of preoperative carcinoembryonic antigen (CEA) levels in patients with colorectal cancer. The data were derived from 945 patients entered into two randomized prospective clinical trials of the National Surgical Adjuvant Breast and Bowel Project. A strong correlation was evident between preoperative CEA level and Dukes class. The mean CEA progressively increased with each Dukes category and the mean value for each of the four classes was significantly different. This relationship was prevalent whether the data were analyzed for all colorectal lesions regardless of location or specifically for right-sided colon tumors. The prognostic function of preoperative CEA level was independent of the number of positive histologic nodes. Preoperative CEA level correlated with the degree of lumen encirclement by tumor. Tumors that did not encircle more than one half the lumen were associated with significantly lower preoperative CEA levels than those that did. The presence or absence of lumen obstruction was unrelated to the preoperative CEA level. The relative risk of developing a treatment failure was associated with preoperative CEA, in both Dukes B and C patients, demonstrating that the prognostic significance of preoperative CEA was independent of Dukes class.

Carcinoembryonic Antigen↗
PubMed1983

Tumor size and regional lymph node metastasis in colorectal cancer. A preliminary analysis from the NSABP clinical trials.

This study explores the relationships between tumor size and regional lymph node involvement in patients with Dukes' B and C colorectal cancer in the randomized prospective clinical trials of the NSABP. Six-hundred and seventy patients with colon cancer and 236 patients with carcinoma of the rectum were available for analysis. Utilizing cumulative frequency distributions of tumor diameter and tumor volume, comparisons were carried out between Dukes' B and C lesions. The results indicate that there was no correlation between the longest diameter of the primary tumor and the status of regional lymph nodes for either colon or rectal cancer. Moreover, this lack of association was evident throughout the distribution. When tumor volume was analyzed, Dukes' B tumors proved to be consistently larger than Dukes' C lesions. This inverse relationship was statistically significant for carcinoma of the rectum. These findings underscore the unique biological behavior of colorectal cancer and emphasize the function of the current generation of randomized prospective trials in providing natural history information.

Clinical Trials as Topic↗
PubMed1983

Adjuvant chemotherapy in stage-II breast cancer: an overview of the NSABP clinical trials.

Data derived from 1848 patients entered into three adjuvant chemotherapy protocols are presented. The three studies were performed sequentially and were designed to identify patient subsets responding to one, two, or three chemotherapeutic agents. Comparison of disease-free survival in patients receiving L-PAM or placebo disclosed that L-PAM was beneficial in patients less than or equal to 49 years of age, but not in women greater than or equal to 50 years. Further analysis indicated that the subset of patients less than or equal to 49 years with 1-3 positive nodes sustained the greatest increment in disease-free survival with single-agent L-PAM. The addition of 5-FU to L-PAM was superior to L-PAM alone in patients greater than or equal to 50 years of age, particularly those with greater than or equal to 4 positive nodes. The three-drug combination of L-PAM, 5-FU, and methotrexate failed to provide a benefit over and above that achieved by the L-PAM-5-FU combination in all subsets examined. The results underscore the heterogeneous response to chemotherapy demonstrated by patient subsets characterized on the basis of age and nodal status. The implications of the findings relative to the current status of adjuvant therapy are discussed.

Adult↗
PubMed1983

The prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Findings from the NSABP clinical trials.

The present study examines the prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Data were obtained from 1021 patients entered into two randomized prospective clinical trials of the NSABP. Tumor location proved to be a strong prognostic discriminant. Lesions located in the left colon demonstrated the most favorable prognosis. Tumors of the rectosigmoid and rectum had the worst prognosis with the relative risk of treatment failure for the latter being over three fold that of the left colon. When the relative risks associated with tumor location were adjusted for nodal imbalances, the left colon continued to demonstrate the most favorable prognosis. The presence of bowel obstruction also strongly influenced the prognostic outcome. Examination of the data without considering tumor location disclosed that patients with bowel obstruction were at greater risk for treatment failure than those without obstruction. The effect of bowel obstruction was influenced by the location of the tumor. The occurrence of bowel obstruction in the right colon was associated with a significantly diminished disease-free survival, whereas obstruction in the left colon demonstrated no such effect. This phenomenon was independent of nodal status and tumor encirclement, the latter two factors proving to be of prognostic significance independent of tumor obstruction. A multivariate analysis in which the covariate effects of sex, age, nodal status, tumor obstruction, encirclement, and tumor location were adjusted underscored the role of tumor location and obstruction as prognostic discriminants. The results indicate that the definition of prognostic factors can identify patient subsets with unique characteristics.

Carcinoma↗
PubMed1983

Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.

In 1977 the National Surgical Adjuvant Breast and Bowel Project initiated a prospectively randomized clinical trial for women with primary operable breast cancer and positive axillary nodes. In this study 1891 patients were randomized to receive L-phenylalanine mustard and 5-fluorouracil (PF) either with or without tamoxifen (T). In this interim report findings are presented concerning disease-free survival (DFS) and survival as related to age and to estrogen receptor (ER) and/or progesterone receptor (PR) content of the tumor. The median follow-up time is 3 yr. Patients 50 yr of age or older with either 1-3 or more than 3 positive axillary nodes had a markedly longer disease-free survival on PFT than did those receiving PF adjuvant therapy (p less than 0.001). The effectiveness of PFT was related to the levels of tumor receptors. Patients 50 yr old or more with both tumor ER and PR levels of 10 fmole or more ("high") displayed the greatest benefit in disease-free survival from PFT (p = 0.004). Analyses by age indicated that it is more appropriate to divide patients of 50 yr or older into two age groups, 50-59 and 60-70 yr old. In the former the survival results were poorer on PFT when tumor PR was low, whereas, regardless of receptor levels, those 60-70 yr old experienced an advantage on PFT. In women under 50 yr of age, there was no difference in disease-free survival (p = 0.64), but survival results favored the PF over the PFT treated (p = 0.06). Patients under 50 yr with tumor ER and PR levels under 10 fmole ("low") had a poorer survival when given PFT (p = 0.003). Those whose tumors demonstrated a high ER and a low PR also had a shorter survival on PFT (p = 0.01). The observation of no benefit in younger patients when both receptor levels were high, but a benefit in older patients with receptor-poor tumors, indicates that, at least according to the conditions of this study, the difference between the two age groups cannot be explained by the association of age with receptor content. Multivariate analyses considered the effects of the number of positive nodes, age, ER, and PR. They support the conclusion that, while nodes and ER exert strong prognostic influences in both PF- and PFT-treated patients, the PR content of tumors is a stronger predictor of the effectiveness of PFT therapy than is ER content.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1981

Findings from NSABP Protocol No. B-04: comparison of radical mastectomy with alternative treatments. II. The clinical and biologic significance of medial-central breast cancers.

Findings from 1665 women with primary breast cancer, treated at 34 NSABP institutions in Canada and the United States, have failed to demonstrate that patients with medial-central tumors had a greater probability of developing distant metastases or dying than did those with lateral tumors despite the greater incidence of internal mammary (IM) node involvement when tumors are medial-central in location. A comparison of patients with similar clinical nodal status and tumor location who were treated either by radical mastectomy (RM) or by total mastectomy plus radiation therapy (TM + RT) failed to indicate that radiation of IM nodes reduced the probability of distant treatment failure (TF) or mortality. When findings from patients having equivalent clinical nodal status and tumor location treated by TM alone or TM + RT were compared, it was found that the addition of RT failed to alter the probability of the occurrence of a distant TF or of death. This was despite the fact that in the nonradiated group two putative sources of further tumor spread, i.e., positive axillary and IM nodes, were left unremoved and untreated. The findings provide further insight into the biologic significance of the positive lymph node and confirm our prior contention that positive regional lymph nodes are indicators of a host-tumor relationship which permits the development of metastases and that they are not important investigators of distant disease.

Axilla↗
PubMed1981

Disease-free survival at intervals during and following completion of adjuvant chemotherapy: the NSABP experience from three breast cancer protocols.

Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) trials evaluating three different regimens of adjuvant chemotherapy (L-PAM, L-PAM + 5-FU, L-PAM + 5-FU + MTX) in patients with primary breast cancer and positive axillary nodes indicate that each regimen has significantly contributed toward achieving the initial goal of such therapy, namely to diminish or prevent treatment failure in all or major subsets of patients during the first two years following operation when women are at greatest risk for a recurrence. Because of this hazard, chemotherapy was administered in all protocols for two years. Findings were examined at the end of the first year of therapy and at the termination of the second year for those who entered that year of therapy disease-free in order to determine whether the second year of treatment contributed a benefit beyond that achieved from the first year of therapy. A reduction in the incidence of treatment failure was evident in every subgroup of patients at completion of the first year of therapy. There was evidence of added improvement during the second year of treatment in patients aged 49 years or younger but not in those aged 50 years or older. Despite the finding, it is not possible from these studies to be absolutely certain that a second year of therapy is or is not advantageous. Findings obtained to date from the three studies indicate that patients completing two years of chemotherapy who are disease-free display a subsequent treatment failure rate that is no greater than that observed in untreated patients who survived two years without recurrence. Consequently, any advantage in disease-free survival observed at completion of therapy has been subsequently sustained for several years, suggesting this represents a real decrease rather than a postponement of treatment failure.

Age Factors↗
PubMed1981

Treatment of primary breast cancer with chemotherapy and tamoxifen.

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were greater than or equal to 10 fmol. Among patients greater than or equal to 50 years old treatment failure was significantly reduced (P less than 0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients less than or equal to 49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients greater than or equal to 50 years old whose levels are low.

Age Factors↗
PubMed1981

Surgery in the primary treatment of breast cancer.

Information available from NSABP protocols has contributed to an altered biological perception of breast cancer. The results of these studies lend support to a hypothesis which postulates that alterations in the loco-regional treatment of primary breast cancer will not change the natural history of the disease relative to distant metastasis and survivorship. Data from NSABP Protocol B-04 indicate that radical mastectomy provides no advantage over total mastectomy in clinically node-negative patients. Since 39% of this population had histologically positive nodes it may be concluded that leaving histologically positive nodes untreated results in no disadvantage. NSABP Protocol B-04 made available the scientific rationale for the study of breast-preserving operations in which the clinical significance of multicentricity will be determined. Although there is a sound scientific basis for the consideration of segmental mastectomy, there are no data available to justify the utilization of the procedure outside the context of a clinical trial. With the increased popularity and implementation of breast-preserving operations without the necessary supporting data, a potentially dangerous situation has been created which threatens to undermine the clinical trial process.

Axilla↗
PubMed1980

Laminated Marlex-methyl methacrylate prosthesis for massive chest wall resection.

Room temperature-curing methyl methacrylate has been sandwiched between two layers of Marlex mesh and molded in the operating room to achieve chest wall stability following an extensive anterolateral resection. Reliable coverage with latissimus dorsi myocutaneous flap has made this simple, aesthetically pleasing, and firm reconstruction practical, even in a patient who received high-dose irradiation.

Breast↗
PubMed1980

Cellular cytotoxicity in tumor-bearing mice after transfer of normal or tumor-sensitized lymphoid cells.

The present investigations are a continuation of those indicating that the administration to normal inbred C3HeB/-FeJ mice of syngeneic tumor-sensitized cells or cells from F344 Mai rats (xenogeneic) sensitized to mouse tumor imparted "information" that resulted in the production of tumor-specific cytotoxic cells by recipients. Current findings revealed that normal but not tumor-sensitized spleen cells when transferred to syngeneic tumor-bearing recipients enhanced the cytotoxicity ofrom F344 Mai rats (xenogeneic) sensitized to mouse tumor imparted "information" that resulted in the production of tumor-specific cytotoxic cells by recipients. Current findings revealed that normal but not tumor-sensitized spleen cells when transferred to syngeneic tumor-bearing recipients enhanced the cytotoxicity of lymphoid cells in the recipients. This enhanced cytotoxicity was specific for the immunizing tumor. Inoculation of normal or tumor-sensitized lymph node cells failed to produce such an effect. Our present and previous findings suggested that in the presence of a tumor, uncommitted cells that reside in the spleen and that are available for recruitment and "instruction" may become depleted, whereas no comparable deficit may exist in cells that are capable of information transfer.

Animals↗
PubMed1980

Cellular cytotoxicity and serum inhibition in normal mice following transfer of syngeneic tumor-sensitized cells.

Investigations were performed to elucidate changes in normal syngeneic recipients after they received tumor-sensitized cells. Transfer of regional or nonregional lymph node cells or spleen cells from tumor-bearing inbred C3HeB/FeJ mice to normal syngeneic recipients caused the recipients to produced bone marrow, which mediated in vitro cytolysis of immunizing tumor target cells. This finding was not entirely limited to transfer of lymphoid cells. The transfer of myeloid cells, granulocytes, and cultured macrophages from tumor-bearing mice also produced cytotoxic cells. The extent of cytotoxicity following cell transfer was related to the duration of tumor growth in cell donors, to the degree of cytotoxicity, and to the number of cells transferred. Both the iv and ip routes were equally effective. Treatment of cells before transfer with trypsin or pronase, mitomycin C, or sublethal irradiation failed to prevent development of cytotoxicity in cells of the recipient, whereas freeze-thawing abolished this event. Serum from the cell recipient could inhibit the cytotoxicity demonstrated by lymphoid cells derived from the recipient or from a tumor-bearing animal. The findings indicate that "information" transferred to normal animals not previously exposed to a tumor results in production of tumor-specific cytotoxic cells in these animals.

Animals↗
PubMed1978

Preliminary observations on the use of Corynebacterium parvum in patients with primary intracranial tumors: effect on intracranial pressure.

It has been observed that patients with metastatic brain lesions developed neurologic symptoms when given Corynebacterium parvum. To obtain more information in patients with intracranial mass lesions, intracranial pressures (ICP) were measured or observed in six patients undergoing C. parvum therapy. All patients except two (one previously shunted, one recently operated) demonstrated a profound increase in ICP. It is presumed that either edema is formed within brain and tumor tissue (inasmuch as neurologic deterioration has not been observed in patients without an intracranial lesion) or transient increases in cerebral blood flow adversely alter an already compromised intracranial volume. Surgical decompression of tumor volume or use of Lasix may abort this response to C. parvum infusion.

Adolescent↗
PubMed1976

Observations following Corynebacterium parvum administration to patients with advanced malignancy. a phase I study.

There has been increasing interest regarding the use of Corynebacterium parvum (CP) with other modalities in the management of primary cancer. Due to the paucity of specific information available relative to CP toxicity, a Phase I study was carried out in patients with advanced disease. The purpose of the investigation was not to evaluate the effect of CP on tumor growth. from 273 injections of CP in 40 patients it was observed that following intravenous (i.v.) infusion of CP: a) a febrile response and chills of considerable severity occured in almost all patients and did not appreciably diminish in intensity following repetitive administrations; b) nausea, vomiting, headache, and confusion were not infrequent; c) a "flu-like" syndrome lasting 24 to 48 hours occurred following almost all courses of CP; d) blood pressure elevations occurred on occasion and were related to the severity of other-side-effects; hyper- or hypo- tension was not a problem; e) ther were no anaphalactic reactions. Pretreatment with a single administration of 100 mg of hydrocortisone prior to CP infusion markedly and in some instances dramatically diminished the toxicity and made acceptable the use of i.v. CP on an outpatient basis. The use of i.v. CP in patients with cerebral metasteses may be hazardous. Subcutaneously administered CP resulted in a significant number of undesirable local reactions. Evaluation of delayed cutaneous hypersensitivity response, immunoglobulins, complement, and E- and EAC-rosette-forming cells during CP administration failed to demonstrate significant change from injection values. Results were similar whether hydrocortisone pretreatment was or was not employed. From the standpoint of toxicity it now seems appropriate to use i.v. CP, particularly following pretreatment with hydrocortisone, in a controlled clinical trial to evaluate its therapeutic effectiveness in the management of primary cancer.

Acute Kidney Injury↗