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M Goodyear

Publications and source records attributed to M Goodyear.

12 recordsLinked to original sources

When is a prognostic factor useful? A guide for the perplexed.

Traditionally, a number of variables have been used to predict outcome in patients with early-stage breast cancer. These tests are simple to perform and relatively inexpensive. Recently, a number of new factors, eg, tumor proliferative index, nuclear DNA content, and amplification or overexpression of growth-promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer. There is now increasing pressure to introduce such tests into routine clinical practice. How does a clinical practitioner identify which test, or group of tests, best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone? The aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not. The prognostic usefulness of a test can be expressed in terms of relative risk (RR), which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative. Methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following: (1) Was an inception cohort assembled? (2) Was the referral pattern described? (3) Were laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried out? (6) Were appropriate statistical methods used? An approach is suggested to help the clinician choose the test, or combination of tests, likely to discriminate between "high-" and "low-risk" patients in his/her own practice. The decision regarding what particular threshold value (risk) defined by a prognostic test (or series of tests) warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient.

Breast Neoplasms

Addition of verapamil and tamoxifen to the initial chemotherapy of small cell lung cancer. A phase I/II study.

Based on experimental observations that verapamil and tamoxifen reverse multiple drug resistance, the authors investigated the feasibility of combining both agents with the initial chemotherapy of extensive small cell lung cancer. Overall, in a consecutive series of 58 patients the most important toxicity was myelosuppression, and there was a 24% rate of severe infections. Therapeutic results included 24% complete and 34% partial response rates, median time to disease progression of 32 weeks, and median survival of 46 weeks. In three consecutive cohorts of patients the dose of either tamoxifen or verapamil were escalated by 25% and 33%, respectively. The cohort of patients receiving verapamil 360 mg/day and tamoxifen 100 mg/day (level 2) had slightly more toxicity but also more responses than the other groups. Therefore, the authors recommend that these doses be used in controlled trials to confirm the promising results of their study.

Antineoplastic Combined Chemotherapy Protocols

The relationship between anti-factor Xa level and clinical outcome in patients receiving enoxaparine low molecular weight heparin to prevent deep vein thrombosis after hip replacement.

Studies in experimental animals have demonstrated that there is a relationship between levels of low molecular weight (LMW) heparin and both bleeding and inhibition of thrombosis. The relationship between these outcomes and ex vivo anti-factor Xa levels has been examined in 163 patients undergoing total hip replacement who were given prophylaxis once daily with a LMW heparin (enoxaparine). Fifty patients received 60 mg of enoxaparine and 113 received 40 mg, both regimens being administered subcutaneously once daily. Blood samples for anti-factor Xa levels were collected 12 hours after the injection on the day of surgery and on days 1, 3 and 6, postoperatively. The incidence of wound hematoma was 5.3% when the maximum anti-factor Xa level was less than or equal to 0.2 units per ml, but increased to 24.5% when the anti-factor Xa level exceeded 0.2 units per ml, P = 0.0008. The incidence of postoperative thrombosis was low (6.3%) if the minimum anti-factor Xa level exceeded 0.1 units per ml, but increased to 14.6% when less than or equal to 0.1 units per ml, and to 18.8% if the anti-factor Xa level was less than or equal to 0.05 units per ml. Regression analysis revealed that there was a statistically significant relationship between anti-factor Xa level and wound hematoma, P = 0.002 and anti-factor Xa level and thrombosis, P = 0.03. These findings suggest that when enoxaparine is administered as a once daily subcutaneous injection, the 12 hour anti-factor Xa level should not exceed 0.2 units per ml to minimize bleeding and levels greater than 0.05 units per ml should be obtained to optimize efficacy.

Factor Xa Inhibitors

Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer.

Studies were analyzed to show the correlation of response with dose intensity of single-agent 5-fluorouracil (5-FU) against colorectal cancer, multiagent CMF (cyclophosphamide, methotrexate, 5-FU) regimens against advanced breast cancer, and adjuvant therapy in stage II breast cancer. In colorectal cancer studies, subgroups in which 5-FU was given by intravenous (IV) bolus, infusion, and orally were analyzed. One study reported delivered dose levels after reductions for toxicity. This allowed calculations of received dose intensity for the three dose levels, and comparison with projected dose intensities. The data suggest that the dose-intensity response line is steep, once a threshold dose intensity has been surpassed. An increase of only 100 mg/m2/wk of received dose intensity of 5-FU increased the response rate from 20% to 29%, which in relative terms was an increase of almost 50%. Received dose intensity may correlate with response, not only in groups of patients, but also in individual patients, and this may, in fact, be the most important application of the concept of dose intensity.

Antineoplastic Combined Chemotherapy Protocols

Arthroscopy.

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Endoscopy

Extra-osseous localization of 99Tcm-Sn pyrophosphate.

99Tcm-Sn pyrophosphate bone scans of 250 patients referred for skeletal metastatic survey were analysed to determine the frequency of abnormal extra-osseous localization and the various pathological causes. Twenty-six patients demonstrated abnormal extra-osseous concentration. There were three false positives. Sixty-five per cent of the extra-osseous lesions concentrating pyrophosphate were malignant (carcinoma of lung and breast, metastatic hepatic carcinoma, chondrosarcoma) and the remainder were benign lesions, e.g. sarcoidosis, soft-tissue calcification, post-surgical and irradiation sites. An incidental finding was the unusual frequency of accumulation of pyrophosphate in various joints, especially the knees and shoulders in asymptomatic patients above 70 years of age.

Age Factors

Cobalt-labeled bleomycin--a new radiopharmaceutical for tumor localization. A comparative clinical evaluation with gallium citrate.

The efficacy of 57Co-labeled bleomycin as a tumor-scanning agent was evaluated in 50 patients with malignant tumor. In terms of sensitivity, labeled bleomycin was found to be a superior agent for malignant tumor detection when compared with 67Ga-citrate (p less than or equal to 0.005). Maximum sensitivity (96%) was found in epidermoid carcinomas. Because of rapid blood clearance and rapid excretion by the kidneys, interpretation of 57Co-bleomycin scans is facilitated.

Adenocarcinoma

Gallium-67 citrate in cerebral infarction.

Cerebral scans were obtained on 30 "stroke" patients first with 99mTc pertechnetate and subsequently with 67Ga citrate. Of the 26 patients with abnormal 99mTc static scans, 17 (65%) showed the same abnormality in gallium citrate scans also. In 4 patients with positive technetium flow studies but negative static scans, no abnormality was seen in the scans obtained after gallium citrate injection. In none of the patients was the relative concentration of radioactivity in the lesion greater in the gallium image than in the technetium image. This study proves the nonspecificity of gallium citrate and thus its inability to differentiate cerebral tumor from cerebral infarction just on the basis of localization of gallium.

Aged