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Biomedical subjects

R D Gelber

Publications and source records attributed to R D Gelber.

At least 163 records · Page 9Linked to original sources
PubMed1989

Comparison of adjuvant therapies using quality-of-life considerations.

The benefit for patients with operable breast cancer treated with adjuvant systemic therapy is small, if reduction of early mortality within the context of randomized control trials is used for treatment comparison. One might consider that the 75%-85% of patients who die despite treatment are overtreated, as are patients who remain alive even without therapy within a given time frame. Larger treatment benefits in terms of avoided or delayed breast cancer relapse have been demonstrated even at early phases of follow-up in the vast majority of adjuvant trials. Exposure of all patients to adjuvant therapy at a time at which no symptoms of disease are present is detrimental in terms of quality of life. Based on our assumption that the quality of life of the patient is typically altered both by subjective toxic effects of adjuvant treatment and by the appearance of relapse, we developed a method of comparing treatment effects in terms of time without symptoms of disease and toxicity of treatment (TWiST). Because the impact of treatment on relapse rates appears earlier than survival effects in all adjuvant therapy trials, and because the value of time without relapse in terms of the quality of life of the patients is as yet poorly defined, we have generalized our method of comparing treatment attitudes to include individual qualitative judgment values. The experience gained from integrating quality-of-life issues into clinical trials for breast cancer might also be applied to other diseases characterized by a chronic course, toxic treatments, and gains in periods of relative or absolute freedom from toxic effects and progressive disease.

Attitude to Health↗
PubMed1989

Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis.

The use of adjuvant chemotherapy for postmenopausal patients with early breast cancer remains controversial because the potential benefits in terms of prolongation of disease-free survival (DFS) and overall survival (OS) must be balanced against the toxicity of treatment. Following mastectomy, 463 evaluable postmenopausal women with node-positive breast cancer were randomized to receive either chemoendocrine therapy for 1 year, or endocrine therapy alone for 1 year, or no adjuvant therapy (Ludwig Trial III). At 7-years median follow-up, OS was longer for the chemoendocrine-treated patients compared with controls (P = .04) and compared with the adjuvant endocrine therapy-alone group (P = .08). In order to balance this therapeutic advantage against the toxic effects of treatment, OS time was divided into time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after systemic relapse (REL). TOX and REL were weighted by coefficients of utility relative to TWiST and the results added to give a period of quality-adjusted survival (Q-TWiST). Benefits measured by Q-TWiST generally favored chemoendocrine therapy. For example, if TOX and REL were both given utility coefficients of 0.5 relative to 1.0 for TWiST, then by 7 years the average Q-TWiST for chemoendocrine therapy was 6.7 months longer than for no-adjuvant therapy (P = .05) and 4.1 months longer than for endocrine therapy alone (P = .20). Quality-adjusted survival analysis is recommended in assessing costs and benefits of toxic adjuvant therapy. In this example, it supports the use of chemoendocrine therapy in postmenopausal node-positive patients for a wide range of relative values assigned to periods with symptoms and toxicity.

Antineoplastic Agents↗
PubMed1989

Autologous bone marrow transplantation for acute lymphoblastic leukemia.

Forty-four children with acute lymphoblastic leukemia (ALL) who had relapsed (N = 43) or had refractory disease (N = 1) were intensively treated with combination chemotherapy, had remission bone marrow (BM) harvested and purged in vitro with monoclonal antibodies specific for leukemia-associated antigens, underwent postharvest ablative chemotherapy and radiotherapy and subsequently were infused with their autologous marrow. Of the 44 patients treated between November 1980 and January 1988, 19 relapsed, 10 died of complications, and 15 remained in complete remission for a median of 28.5 months (range, 10+ to 94+). Event-free survival (EFS) (+/- SE) at 5 years after autologous transplantation was 29 +/- 8%. For the 26 patients whose initial remission was greater than 2 years, event-free survival was 51 +/- 10%. These results compare favorably with allogeneic transplantation and chemotherapy trials for patients with relapsed ALL, and provide an alternative transplantation option for children without histocompatible donors.

Adolescent↗
PubMed1989

A quality-of-life-oriented endpoint for comparing therapies.

An endpoint, time without symptoms of disease and toxicity of treatment (TWiST), is defined to provide a single measure of length and quality of survival. Time with subjective side effects of treatment and time with unpleasant symptoms of disease are subtracted from overall survival time to calculate TWiST for each patient. The purpose of this paper is to describe the construction of this endpoint, and to elaborate on its interpretation for patient care decision-making. Estimating the distribution of TWiST using actuarial methods is shown by simulation studies to be biased as a result of induced dependency between TWiST and its censoring distribution. Considering the distribution of TWiST accumulated within a specified time from start of therapy, L, allows one to reduce this bias by substituting estimated TWiST for censored values and provides a method to evaluate the "payback" period for early toxic effects. Quantile distance plots provide graphical representations for treatment comparisons. The analysis of Ludwig Trial III evaluating toxic adjuvant therapies versus a no-treatment control group for postmenopausal women with node-positive breast cancer illustrates the methodology.

Antineoplastic Agents↗
PubMed1988

Treatment of recurrent respiratory papillomatosis with human leukocyte interferon. Results of a multicenter randomized clinical trial.

Recurrent respiratory papillomatosis is a relentless disease of viral origin in which squamous papillomas frequently obstruct the respiratory tract of children and young adults. No therapy has been proved to be curative for this process. Recent reports have suggested that interferon may cure or dramatically control airway papillomatosis. We evaluated the efficacy of human leukocyte interferon in the treatment of respiratory papillomatosis. One hundred twenty-three patients were randomly assigned to receive treatment with either surgery plus interferon or surgery alone. Interferon (2 X 10(6) IU per square meter of body-surface area) was given daily for one week, then three times per week for one year; treatment was followed by a year of observation, without the drug. Both study groups underwent serial endoscopy to remove papillomas and to document the efficacy of treatment during the two years of study. During the first six months, the growth rate of papillomas in the interferon group was significantly lower than in the control group (P = 0.0007). This difference diminished during the second six months and was no longer statistically significant (P = 0.68). Our data do not show that interferon is either curative or of substantial value as an adjunctive agent in the long-term management of recurrent respiratory papillomatosis. The initial benefit of interferon is not sustained.

Child, Preschool↗
PubMed1988

Ophthalmic evaluation of survivors of acute lymphoblastic leukemia.

Eighty-two survivors of acute lymphoblastic leukemia (ALL) had prospective eye evaluations to determine the ocular sequelae of the disease and its treatment. All patients had completed or nearly completed a 25- to 31-month protocol which included either 3.4 or 10.2 g of systemic prednisone/m2 per year and cranial irradiation (total 1800-2800 rad). The mean interval from the end of treatment to the eye examination was 32 months. Only one patient had reduced vision attributable to the ALL. Ocular morbidity attributed to the treatment only included posterior subcapsular cataracts (PSCs) which occurred in 52% of patients. Posterior subcapsular cataracts (PSCs) developed in none of the 15 survivors of acute myelogenous leukemia (AML) examined who had received neither long-term systemic prednisone nor irradiation (P = 0.0006). Eyes with PSC had a median visual acuity of 20/20 (range, 20/15-20/50). The authors conclude that the ocular morbidity from antileukemia treatment programs at our institutions is minimal.

Cataract↗
PubMed1988

Relapse of breast cancer after adjuvant treatment in premenopausal and perimenopausal women: patterns and prognoses.

Eight hundred eighteen premenopausal or perimenopausal breast cancer patients with axillary node metastases were treated with adjuvant chemotherapy (CMF) with or without endocrine treatment (prednisone, oophorectomy) in two concurrent prospective trials. Three hundred fifty-two (43%) had recurrent disease at a median follow-up time of 6 years. The 2-year survival percentages from time of first relapse were 16% for patients with initial metastases in visceral or multiple sites (including bone and soft tissue), 41% for those with regional metastases or skeletal relapse alone and 70% for patients with isolated local recurrence or contralateral breast cancer. The features that most influenced prognosis within the categories defined by site of first relapse were disease-free interval (less than 24 months v greater than or equal to 24 months), and estrogen receptor content in the primary tumor. These features had clinical importance (identifying patients with at least a 50% 2-year survival percentage) only in those patients with local, contralateral breast, regional, or bony disease alone. The treatment of individual patients after relapse must be directed toward optimized palliation. The results of this study are important for defining groups of patients who relapse after CMF for whom the subsequent therapeutic approach might be differentiated (eg, experimental treatments for dire prognosis, accent on minimal side effect treatment for intermediate prognosis, and investigation of adjuvant systemic therapy for isolated local recurrence).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Association of DNA index and S-phase fraction with prognosis of nodes positive early breast cancer.

DNA index and S-phase fraction of 490 primary breast carcinomas were measured by flow cytometry, using paraffin-embedded tissue as a starting point. All patients had involvement of axillary lymph nodes and all were randomized onto one of the Ludwig Breast Cancer Trials I-IV between July 1978 and August 1981. The presence of an abnormal DNA stemline correlated with involvement of four or more axillary lymph nodes (P = 0.09), postmenopausal status (P = 0.008), estrogen receptor negativity (P = 0.03), and high tumor grade (P = 0.0005). Disease-free and overall survival for these patients was worse than for those with tumors of normal DNA content, but DNA aneuploidy did not have independent prognostic significance when allowance was made for its correlation with other prognostic features. The percentage of cells in S phase, which is an index of cell proliferation, was also analyzed in 285 DNA histograms considered to be capable of giving a valid estimate. Disease-free survival for 154 patients with S phase less than or equal to 10% was significantly longer than for those with S phase greater than 10% (P = 0.0008). S-phase greater than 10% was strongly correlated with high tumor grade (P less than 0.00001) and abnormal DNA index (P less than 0.00001) but only weakly correlated with nodal, hormone receptor, and menopausal status. Multivariate analysis using a Cox proportional hazard model suggested that the prognostic significance of the percentage of S phase was related to the association with tumor grade. Because it gives rapid, objectively determined information about biological aggressiveness DNA flow cytometry may well establish a role in routine clinical practice, but further technical refinements are required before it can be used for treatment decision making in nodes positive early breast cancer patients.

Breast Neoplasms↗
PubMed1987

Outcome of pregnancy in survivors of Wilms' tumor.

Outcome of pregnancy was reported by 99 patients who were cured of childhood Wilms' tumor at seven pediatric cancer centers during 1931 to 1979. These patients carried or sired 191 singleton pregnancies of at least 20 weeks in duration. Among the 114 pregnancies in women who had received abdominal radiotherapy for Wilms' tumor, an adverse outcome occurred in 34 (30%). There were 17 perinatal deaths (five in premature low-birth-weight infants) and 17 other low-birth-weight infants. Compared with white women in the United States, the irradiated women had an increased perinatal mortality rate (relative risk, 7.9) and an excess of low-birth-weight infants (relative risk, 4.0). In contrast, an adverse outcome was found in two (3%) of the 77 pregnancies in nonirradiated female patients with Wilms' tumor and wives of male patients. The high risk of adverse pregnancy outcome should be considered in the counseling and prenatal care of women who have received abdominal radiotherapy for Wilms' tumor.

Abdomen↗