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L R Prosnitz

Publications and source records attributed to L R Prosnitz.

At least 19 recordsLinked to original sources
PubMed1992

Prognostic significance of extent of nodal involvement in stage D1 prostate cancer treated with radiotherapy.

The records of 107 patients with newly diagnosed adenocarcinoma of the prostate irradiated with curative intent at Duke University Medical Center from 1970 through 1983 were reviewed. Forty patients (37%) underwent standard bilateral pelvic lymph node dissection (PLND) prior to beginning irradiation. Twenty-four patients (22%) were found to have pelvic nodal metastases (Stage D1). Those found to have a single microscopically positive node at PLND may be curable with irradiation. In contrast, those with more extensive nodal metastases appear to be incurable with radiotherapy. Additional studies are needed to confirm or refute these findings.

Adenocarcinoma↗
PubMed1992

Relationships among tumor temperature, treatment time, and histopathological outcome using preoperative hyperthermia with radiation in soft tissue sarcomas.

The lack of an unambiguous thermal dosimetry continues to impede progress in clinical hyperthermia. In an attempt to define better this dosimetry, a model based on the cumulative minutes during which arbitrary percentages of measured tumor temperature points exceeded an index temperature was tested in patients with soft tissue sarcomas treated with preoperative hyperthermia and conventional radiation therapy. Patients received 5000-5040 cGy at 180-200 cGy per fraction. Hyperthermia was delivered 30-60 minutes after radiation therapy and given for 60 minutes. Patients were randomized between one and two hyperthermia treatments per week for a total of five or 10 treatments, respectively. Lesions were excised 4-6 weeks after completion of hyperthermia/radiation therapy. Successful treatment outcome was considered to be the finding of greater than 80% necrosis of the sarcoma upon histopathologic examination of the resected specimen. Forty-five patients were eligible with thermometry data available in 44 patients. An average of 19 interstitial sites were monitored each treatment per tumor. Sixty percent of tumors had a successful histopathologic outcome. Univariate analysis demonstrated that several descriptors of the temperature distribution were strongly related to treatment outcome; more strongly than nonthermometric factors, such as the number of treatments per week, tumor volume and patient age and more strongly than the commonly used temperature descriptors Tmin and Tmax. Descriptors that incorporated both temperature and time were also superior to the more commonly used descriptors Tmin and Tmax. Multivariate stepwise logistic regression analysis revealed that a descriptor of both the hyperthermia treatment time and the frequency distribution of intratumoral temperatures was the strongest predictor of histopathologic outcome and that the best predictive model combined this time/temperature descriptor and one versus two treatment per week grouping. The more conventional temperature descriptor, minimum measured tumor temperature, did not significantly enhance the predictive power of treatment group. Based on these results, we recommend that descriptors based on both the frequency distribution of intratumoral temperatures and hyperthermia treatment time be tested for relationships with treatment outcome in other clinical data bases. Furthermore, we recommend that temperature descriptors that are less sensitive to catheter placement and tumor boundary identification than Tmin and Tmax (such as T90, T50, and T10) be tested prospectively along with other important thermal variables in Phase II trials in further efforts to define a thermal dosimetry for spatially nonuniform temperature distributions.

Combined Modality Therapy↗
PubMed1992

Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B.

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Adenocarcinoma↗
PubMed1992

Combined chemotherapy and radiotherapy for Hodgkin's disease.

This paper reviews the treatment of advanced and intermediate stage Hodgkin's disease with combination chemotherapy alone and combined chemotherapy and radiation. Relapse following complete remission with chemotherapy occurs principally at initial sites of disease; its occurrence will be reduced by radiotherapy to those sites. There is disagreement regarding the frequency of relapse and hence the impact of consolidation radiotherapy. Our interpretation of the literature is that relapse occurs in approximately 25% to 50% of all patients achieving complete response with chemotherapy, and that consolidation radiation reduces relapse frequency with a resultant increase in survival. The addition of low dose, involved field radiotherapy is generally free of significant adverse effects. In particular, there appears to be no increase in second malignant neoplasms. The risk: benefit ratio for adding radiotherapy to chemotherapy in patients with advanced Hodgkin's disease is, therefore, quite favorable. We believe that combined modality therapy should become the standard treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Multivariate analysis of factors predicting local relapse after radical prostatectomy--possible indications for postoperative radiotherapy.

Between 1970 and 1983, 273 patients underwent radical surgery (radical prostatectomy--261, radical cystoprostatectomy--12) for newly diagnosed adenocarcinoma of the prostate at Duke University Medical Center and received no adjuvant radiotherapy. A total of 46 patients developed local recurrence. Forty developed local relapse only and six developed simultaneous local and distant failure. The crude local relapse rate was 17% (46/273). The actuarial local failure rate at 5, 10, and 15 years was 12%, 32%, and 35%, respectively. Univariate and multivariate analyses were performed to identify factors predictive of local relapse after radical surgery. Possible prognostic factors analyzed were: age, type of biopsy, use of adjuvant hormonal therapy, histologic grade, histologic involvement of seminal vesicles, positive surgical margins, clinical stage, and elevated acid phosphatase. Factors identified as significant predictors of local relapse by univariate analysis were: poorly differentiated histology (p = 0.0001), seminal vesicle involvement (p = 0.0009), and positive surgical margins (p = 0.0001). An elevated preoperative acid phosphatase was of borderline significance (p = 0.06). On multivariate analysis, poorly differentiated histology (p = 0.0007), positive margins (p = 0.0015), and elevated acid phosphatase (p = 0.0273) were significant predictors of local failure. Seminal vesicle involvement was no longer a significant predictor of local failure. However, on subsequent univariate and multivariate analyses, seminal vesicle involvement was the only significant predictor for the development of distant metastases (p = 0.0019, multivariate). Thus, patients with poorly differentiated tumors, positive surgical margins, or elevated preoperative acid phosphatase are at high risk for local relapse after radical prostatectomy. These patients should be included in future clinical trials studying the role of adjuvant radiotherapy after radical prostatectomy, or offered adjuvant radiotherapy if they cannot or will not participate in such trials.

Adenocarcinoma↗
PubMed1991

Transurethral resection of prostate prior to definitive irradiation for prostate cancer. Lack of correlation with treatment outcome.

From 1970 through 1983, 107 patients with newly diagnosed adenocarcinoma of the prostate were treated with radiotherapy with curative intent at Duke University Medical Center. Forty-five patients (42%) underwent transurethral resection of the prostate (TURP) for diagnostic and/or therapeutic purposes prior to beginning radiotherapy. Sixty-one patients (57%) were diagnosed by needle biopsy. TURP and needle biopsy groups were comparable (age, elevated acid phosphatase, early [A2, B] and late [C, D1] disease stages, and follow-up). TURP patients were more likely to have poorly differentiated tumors and were more often given concurrent hormonal therapy. Both univariate and multivariate analyses to study the effect of TURP on patients with prostate cancer treated with radiotherapy were done. We were unable to demonstrate any adverse impact of TURP on the outcome of radiation therapy for prostate cancer. This issue remains controversial and should be addressed in a prospective, randomized trial.

Actuarial Analysis↗
PubMed1990

Impact of radiation therapy and/or chemotherapy on the risk for a second malignancy after breast cancer.

The risk of any second malignancy was determined for all patients treated for a primary cancer of the breast without evidence of distant metastasis at Duke University Medical Center between 1970 and 1981. The incidence, 10-year actuarial risk (AR), and relative risk (RR) of a second malignancy developing were calculated for the 407 patients who were treated with surgery alone, 226 who were treated with surgery followed by adjuvant chemotherapy (CT), 140 who were treated with surgery plus adjuvant radiation therapy (RT), and 308 who received all three modalities (CRT). The AR of a subsequent cancer (8.4% for CRT, 8.7% for CT, 8.7% for RT, and 11.7% for surgery only patients) did not differ significantly between treatment groups. The overall second cancer RR was 1.0% after CRT (95% confidence interval [CI], 0.4 to 2.0), 1.3% after RT (95% CI, 0.6 to 2.5), 1.6% after CT (95% CI, 0.9 to 2.6), and 1.7% after surgery alone (95% CI, 1.2 to 2.4). Contralateral breast cancers (RR of 4.2%; 95% CI, 2.7 to 6.3) account for the statistically significant excess of second malignancies among the surgery alone patients. The AR for contralateral breast cancer in the surgery group was higher than in either group receiving CT (P less than 0.01), but was not significantly different from the RT group. The RR for solid tumors other than breast cancer was not significantly different from unity in any of the treatment groups. The RR for acute leukemia was 16.7% in the CRT group (95% CI, 0.2 to 92.7), 11.1% in the CT group (95% CI, 0.1 to 61.8), 10.0% in the surgery alone group (95% CI, 1.1 to 36.1), and 0.0% in the RT group (95% CI, 0.0 to 61.1). This study indicated that inclusion of RT and/or CT in the initial treatment of breast cancer did not impact negatively on patients' overall risk for a subsequent malignancy during the first decade after therapy, and that adjuvant CT with or without RT may decrease their risk of a contralateral breast cancer.

Actuarial Analysis↗
PubMed1990

Impact on second malignancy risk of the combined use of radiation and chemotherapy for lymphomas.

The risk of a second malignancy was determined for 999 patients given primary treatment using chemotherapy only, radiation therapy only, or both for Hodgkin's Disease or a non-Hodgkin's lymphoma at Duke University Medical Center between 1970 and 1981. The incidence, 10-year actuarial risk, and relative risk of developing an acute leukemia, solid tumor, or second lymphoma were determined by treatment modality and initial lymphoma type. Among the 313 Hodgkin's disease patients, the acute leukemia actuarial risk was 2.0% after chemotherapy, 1.4% after radiation therapy, and 0.9% after combined treatment with chemotherapy and radiation therapy. Their relative risk for acute leukemia was 51.3 overall (95% confidence interval [CI] 13.8 to 131.8) and was elevated in each treatment group. Among the 686 non-Hodgkin's lymphoma patients, the acute leukemia actuarial risk was zero after radiation therapy, 4.6% after chemotherapy, and 4.5% after the combined treatment, again not significantly different between treatment groups. The leukemia relative risk was 10.6 (95% CI 3.4 to 24.8) in the chemotherapy and 11.9 (95% CI 3.2 to 30.6) in the combined treatment group. Among both the Hodgkin's disease and non-Hodgkin's lymphoma populations, the combined treatment group had a lower actuarial risk for solid tumors than either the chemotherapy or radiation therapy group (P less than 0.02). Solid tumor actuarial risk did not differ significantly between the chemotherapy and radiation therapy groups. Hodgkin's disease patients had a solid tumor relative risk that was elevated significantly after radiation therapy (6.5; 95% CI 2.4 to 14.0) and to a lesser extent after chemotherapy (2.6; 95% CI 0.8 to 6.1) or combined treatment (1.7; 95% CI 0.2 to 6.0). Solid tumor relative risk among non-Hodgkin's lymphoma patients was 0.3 for the combined treatment, 0.8 for the chemotherapy, and 1.0 for the radiation therapy group. None of the Hodgkin's disease patients developed a non-Hodgkin's lymphoma. This study found no significant difference in leukemia risk among lymphoma patients treated with chemotherapy and the combined treatment. It also found that the overall risk of a second malignancy is no higher after treatment with the combined therapy than with chemotherapy or radiation therapy alone.

Adolescent↗
PubMed1990

Improved survival in advanced Hodgkin's disease with the use of combined modality therapy.

To compare the effectiveness of combined modality therapy and chemotherapy alone for the treatment of advanced Hodgkin's disease (Stages IIB-IV), records of 154 patients who achieved a complete or partial response to induction combination chemotherapy were analyzed. Sixty-seven patients received consolidation radiotherapy and 87 patients received no further treatment. Thirty of 154 patients participated in a prospective randomized trial of the Southeastern Cancer Study Group (SEG). Ten-year actuarial survival (Hodgkin's disease deaths only) was 93% for the combined modality therapy patients compared with 59% for the chemotherapy alone patients (p less than 0.0005). Combined modality therapy patients had an 87% 10-year actuarial freedom from relapse as opposed to 56% for the chemotherapy alone patients (p less than 0.0005). Relapse occurred in 33 of the chemotherapy alone patients, 28 (85%) being in sites involved at initial diagnosis. Seven combined modality therapy patients recurred with only two true in-field failures. Multi-variate analysis demonstrated treatment (combined modality) as the only variable affecting outcome. Patients prospectively treated with combined modality therapy in the Southeastern Cancer Study Group trial also showed a statistically significant improvement in both survival and freedom from relapse compared with patients receiving chemotherapy only. There was no apparent increase in toxicity from using combined modality therapy compared with chemotherapy. Three chemotherapy patients and one combined modality therapy patients developed acute leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Radiotherapy vs. hormonal therapy for the management of locally recurrent prostate cancer following radical prostatectomy.

Forty patients out of 273 who had undergone radical surgery for adenocarcinoma of the prostate at Duke University Medical Center between 1970 and 1983 developed palpable, biopsy-proven local recurrence without evidence of distant metastases. Of these 40 patients, 16 were treated with irradiation alone (Group I) and 16 patients were treated with hormonal therapy only (Group II). The remaining eight patients received either no therapy (4 patients) or both radiotherapy and hormonal therapy (4 patients) and are not further analyzed. Local control, as determined by palpation, was achieved in 14/16 patients in Group I versus only 7/16 patients in Group II (p less than 0.05). Subsequently, six patients in each group have relapsed, all with distant metastases. Thus, 8/16 patients in Group I remain alive without disease versus only 1/16 patients in Group II (p less than 0.05). There was no difference in survival between Groups I and II. No patient in either group has died free of disease. In Group I, 4/16 patients have died with cancer. Six of 16 in Group II have died with cancer. Severe complications occurred more frequently following irradiation compared to hormonal therapy. Irradiation appears to be superior to hormonal therapy in achieving local control and prolonging disease-free survival. Neither therapy conveys an advantage over the other in terms of survival. Thus, even if local control is achieved, distant failure may be an inevitable consequence of locally recurrent prostate cancer. Therefore, prevention of local recurrence after radical prostatectomy is of paramount importance. These findings support the use of adjuvant post-operative irradiation in patients at high risk for local recurrence.

Adenocarcinoma↗
PubMed1988

Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.

Adult↗
PubMed1987

Inflammatory breast carcinoma. Effective multimodal approach.

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.

Adult↗