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Biomedical subjects

R Wesley

Publications and source records attributed to R Wesley.

At least 55 records · Page 3Linked to original sources
PubMed1986

Adverse prognostic influence of hepatitis B virus infection in acute lymphoblastic leukemia.

Liver function test abnormalities were examined in a retrospective survey in a population of 90 children with acute lymphoblastic leukemia (ALL) treated in a similar fashion with therapy, using primarily methotrexate, mercaptopurine, vincristine, and prednisone. A twofold or greater elevation of serum glutamyl pyruvic transaminase (SGPT) was found in 80% of the patients during induction therapy, in 63% of the patients during maintenance therapy, and 31% of the patients who completed therapy. Circulating hepatitis B virus surface antigen (HBsAg) was noted in 26% of patients with liver function test abnormalities during maintenance therapy, and 45% of patients with liver function test abnormalities after the completion of therapy. Hepatitis B virus infection was therefore, the most important single cause of abnormal liver function during remission in our patient population. Though others have asserted that hepatitis B virus infection is relatively benign in immunosuppressed individuals, in our population, this agent often caused severe pathological and clinical sequelae. This may be related to the high frequency (50%) of co-infection with the delta agent in our HBsAg-positive patients. Furthermore, hepatitis B virus surface antigenemia conferred an adverse prognostic influence for these children in terms of their leukemia-free survival.

Acute Disease↗
PubMed1986

5-Fluorouracil chemotherapy and pelvic radiation in the treatment of large bowel cancer. Decreased toxicity in combined treatment with 5-fluorouracil administration through the intraperitoneal route.

Multimodality cancer therapy commonly involves the interactions of surgeon, radiation therapist, and medical oncologist. This prospective study was undertaken to record possible adverse effects of surgery, external beam radiation therapy, and 5-fluorouracil (5-FU) chemotherapy in the treatment of large bowel cancer. The dose of 5-FU by the intraperitoneal (IP) or intravenous (IV) routes was diminished when pelvic radiation therapy was given. The reduction in drug dose that was required was much greater when 5-FU was given IV as compared to IP. The proportion of patients remaining on IV 5-FU chemotherapy was significantly reduced when the patient received pelvic radiation. There was a significant increase in leukopenia and thrombocytopenia when patients received pelvic radiation. Hematologic toxicity was more severe when there was IV compared with IP administration of 5-FU. Pelvic radiation therapy diminished the patient's capacity to receive chemotherapy because of hematologic toxicity. The locoregional administration of 5-FU chemotherapy was better tolerated as part of a multimodality treatment regimen than was systemic administration.

Clinical Trials as Topic↗
PubMed1986

High-grade soft tissue sarcomas of the extremities.

From July 1975 to December 1982, 358 patients were referred to the Surgery Branch of the National Cancer Institute (NCI) with the diagnosis of soft tissue sarcoma of the extremities. Two hundred eleven of these patients presented with resectable, localized high-grade soft-tissue sarcomas and have been included in the present analysis of the management and outcome of patients with high-grade soft tissue sarcomas of the extremity treated at the NCI. One hundred forty-seven of these 211 patients have been included in randomized prospective trials. The remaining 64 patients in this analysis have been followed at the NCI, but were not included in randomized trials because of patient refusal or ineligibility. Tumor size was identified as a highly significant prognostic variable for disease-free and overall survival (P2 = 0.00001 and 0.0081, respectively). Tumor site, histologic type, and microscopic margins of resection were not significant prognostic variables. There was no difference between patients undergoing amputation compared to those undergoing limb-sparing procedures plus postoperative radiotherapy in disease-free or overall survival for all 211 patients in this study (P2 = 0.068 and 0.131, respectively). A significantly greater frequency of local failure among patients treated by local excision was noted compared to patients undergoing amputation (12/128 versus 0/83, P2 = 0.004), but this did not result in decreased overall survival in patients undergoing combined modality limb-sparing procedures. Adjuvant chemotherapy significantly prolonged disease-free survival (P2 = 0.005) for the 124/211 patients treated with adjuvant chemotherapy, although analysis of overall survival did not reveal a significant increase (P2 = 0.10). In a subset of 65 patients included in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy, a significant improvement in both disease-free (P2 = 0.033) and overall (P2 = 0.055) survival was seen in patients receiving chemotherapy. Sixty-five patients developed recurrent disease (65/211, 31%) and 42 of these patients were rendered disease-free surgically. Survival from the time of first recurrence was significantly prolonged among the 42 patients who were rendered disease-free (median survival, 31 months) compared to those who were not (median survival, 9 months, P2 less than 0.001).

Actuarial Analysis↗
PubMed1986

Excess prevalence of Pneumocystis carinii pneumonia in patients treated for lymphoma with combination chemotherapy.

A significantly greater prevalence of interstitial pulmonary infiltrates and Pneumocystis carinii pneumonitis occurred on one arm of a randomized study comparing ProMACE-CytaBOM (prednisone, methotrexate with leucovorin, doxorubicin, cyclophosphamide, etoposide; cytarabine, bleomycin, vincristine, methotrexate with leucovorin) to ProMACE-MOPP (ProMACE, mechlorethamine, vincristine, prednisone, procarbazine) chemotherapy in patients with lymphoma. Of the 37 patients receiving ProMACE-CytaBOM, 13 (35.1%) developed an interstitial pulmonary infiltrate compared with 3 of 32 (9.4%) patients receiving ProMACE-MOPP (p2 = 0.02). Of the 13 patients receiving ProMACE-CytaBOM who had infiltrates, open lung biopsy in 7 showed P. carinii; 5 others had clinically suspected P. carinii pneumonia, and 1 had blastomycosis. No patient receiving ProMACE-MOPP had documented or suspected P. carinii pneumonia. Of patients with infiltrates, 3 of 13 on ProMACE-CytaBOM but 0 of 3 on ProMACE-MOPP died. Two other patients on ProMACE-CytaBOM who had P. carinii pneumonia died. Groups did not differ in predisposing risk factors or patient history. The exact cause for the increased prevalence of P. carinii infection in patients receiving ProMACE-CytaBOM was not ascertained. These data emphasize that new drug regimens may lead to unanticipated complications.

Adult↗
PubMed1985

Prospective randomized study of open lung biopsy versus empirical antibiotic therapy for acute pneumonitis in nonneutropenic cancer patients.

Diffuse pulmonary infiltrates and acute respiratory compromise frequently occur in patients with cancer who are undergoing chemotherapy, and treatment remains controversial. We initiated a prospective randomized trial in 22 nonneutropenic patients to compare the efficacy of immediate open lung biopsy with that of empirical trimethoprim-sulfamethoxazole and erythromycin therapy with delayed open lung biopsy if no clinical improvement occurred after 4 days of therapy. Diagnoses included non-Hodgkin's lymphoma (15 patients), T-cell lymphoma (2), acute lymphoblastic leukemia (3), Hodgkin's disease (1), and breast cancer (1). The median age was 40 years, and fever (18) and tachypnea (13) were the most frequent signs. Median room air arterial oxygen tension in 18 hypoxic patients was 53 mm Hg; 19 patients had diffuse pulmonary infiltrates. Eight of the 10 patients randomized to empirical antibiotic therapy showed improvement after 4 days. The 2 patients whose condition did not improve and who underwent delayed open lung biopsy had Pneumocystis carinii pneumonia. One of them did show improvement, and the other died of respiratory failure. Time to clinical resolution in the 9 surviving patients was 14 days; 4 required prolonged ventilation (longer than 24 hours). Findings for the 12 patients randomized to immediate open lung biopsy were P. carinii pneumonia in 7 and nonspecific pneumonitis in 5; there were 3 deaths related to open lung biopsy. Time to resolution in the surviving patients was 13 days for those with P. carinii pneumonia and 5 days for those with nonspecific pneumonitis; 7 required prolonged ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

Patterns of recurrence in patients with high-grade soft-tissue sarcomas.

From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Perioperative blood transfusions are associated with increased rates of recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities.

One hundred fifty-six patients with high-grade soft-tissue sarcomas of the extremities treated on prospective randomized trials were analyzed to determine the impact of perioperative blood transfusions on tumor recurrence and patient survival. A significant increase in the incidence of tumor recurrence and decrease in survival were associated with the receipt of blood transfusions at the time of definitive surgical therapy of the sarcoma. Actuarial 5-year continuous disease-free survival was 70% in patients who had not been transfused compared to 48% in patients who received one or more transfusions (P = .007). Overall 5-year survival was also substantially decreased in patients receiving transfusions (85% compared to 63%; P = .0035). A direct relationship existed between the number of transfusions administered and the decrease in disease-free and overall survival; the larger the number of transfusions the worse the prognosis (P less than .0001 and P = .0001, respectively). A large number of other prognostic factors were included in the analysis including the age, sex, race of the patient, histology of the primary lesion, anatomic site of the primary lesion, final surgical margins, size of the tumor, type of surgery required, the use of chemotherapy, actual time in the operating room under anesthesia, the exact anesthetic agent used, and the individual surgeon who performed the operation. Accounting for all of these factors a strong association continued to exist between the receipt of blood transfusion and poor patient prognosis. We have previously shown that adjuvant chemotherapy is of benefit to patients with high-grade extremity sarcomas, and 132 (84.6%) of 156 patients in this series received chemotherapy. In patients receiving chemotherapy, blood transfusions were associated with increased recurrence (P less than .0001) and decreased survival (P = .0001). The only other significant independent prognostic variable in these patients was the size of the primary tumor. An analysis of all patients, stratified for tumor size, revealed an impact of transfusions on increasing recurrence (P = .007) and decreasing survival (P = .016). An analysis of the subpopulation of patients with large tumors (greater than 150 mL) gave the same results (P = .03 and .015, respectively). It thus appears that the receipt of blood transfusions is associated with increased tumor recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1985

Prospective, randomized trial of intravenous versus intraperitoneal 5-fluorouracil in patients with advanced primary colon or rectal cancer.

No new chemotherapy agents have been developed recently that present hope for improving survival in patients with colon or rectal cancer. We undertook this study to investigate a new route of administering an old drug, 5-fluorouracil (5-FU). Sixty-six patients with advanced primary colon or rectal cancer were randomized to receive 12 cycles with increasing dosages of intravenous (IV) or intraperitoneal (IP) 5-FU; the mean follow-up time was three years. The maximal tolerable dose and objective adverse side effects were prospectively recorded. The mean daily dose of 5-FU given by the IV route was 904 mg; for the IP route it was 1361 mg (p2 less than 0.0001). Two of ten patients had recurrent peritoneal carcinomatosis when treated with IP 5-FU; ten of eleven patients treated with IV 5-FU developed peritoneal implants (p2 less than 0.003). The incidence of serious complications was the same, but hematologic toxicity and hepatic toxicity were significantly reduced in patients who received IP 5-FU. When 5-FU is delivered by the IP route, the tolerable dose of drug was markedly increased without an increase in adverse side effects. The natural history of surgically treated disease was changed by reducing the incidence of peritoneal carcinomatosis but time to relapse and survival was not improved. IP 5-FU may be recommended for investigation in patients with perforated colon cancer, peritoneal implants, or as one part of a multimodality treatment protocol for colorectal cancer. If 5-FU is given to patients with gastrointestinal malignancy, the IP route should be strongly considered.

Adult↗
PubMed1985

Prospective randomized trial of intravenous v intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer.

No new chemotherapy agents have been developed in the recent past that present hope for improving survival in patients with colon or rectal cancer. This study was undertaken to investigate a new route of administering an old drug, 5-fluorouracil (5-FU). When 5-FU is delivered by the intraperitoneal (IP) route the tolerable dose of drug was markedly increased without an increase in adverse side effects. The natural history of surgically treated disease was changed by reducing the incidence of peritoneal carcinomatosis, but time to relapse and survival was not improved. Intraperitoneal 5-FU may be recommended for investigation in patients with perforated colon cancer, peritoneal implants, or as one part of a multimodality treatment protocol for colorectal cancer. If 5-FU is given to patients with gastrointestinal malignancy, the IP route should be strongly considered.

Adult↗
PubMed1984

Glucose intolerance in sarcoma patients.

Twenty-seven otherwise healthy patients with localized sarcoma were examined to determine if glucose intolerance can be detected before the appearance of clinical signs of cachexia. No patient had lost weight or demonstrated severe malnutrition. Fasting plasma samples for glucose, insulin, glucagon, and free fatty acids (FFA) were obtained, and a standard intravenous glucose tolerance test performed. Glucose disappearance rate (K) was calculated between 5 and 60 minutes. K levels were compared to those of normal controls and to those of patients with more extensive cancer (statistics obtained from the literature). Levels for K were compared to tumor volume measurements following surgery. Fasting glucose, insulin, and glucagon levels were normal. Fasting FFA levels were slightly elevated. K levels for sarcoma patients were significantly lower than in control patients (P = 0.04), and higher than in patients with advanced cancer (P less than 0.0001). The subset of patients who weighed less than the ideal had a significantly lower K level than did the rest of the sarcoma population. K levels correlated inversely with tumor volume (r = -0.34; P = 0.04). These data indicate that mild glucose intolerance (reduction in clearance of a glucose load) occurs early in untreated sarcoma patients, is most prevalent in patients who maintain less than the ideal weight, correlates with tumor burden, and occurs before other signs of cachexia appear.

Adolescent↗
PubMed1983

Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities.

Sixty-five patients with high-grade soft tissue sarcomas of the extremities were treated in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy with doxorubicin, cyclophosphamide, and high-dose methotrexate. Local therapy was administered using either amputation or wide local resection plus radiation therapy and the chemotherapy was begun in the immediate postoperative period. Actuarial analysis with median follow-up of 653 days revealed an advantage in continuous disease-free and overall survival in the patient group receiving chemotherapy (P = 0.0008 and P = 0.04, respectively, one-sided Mantel-Haenszel test). The continuous disease-free survival at three years is 92% in the chemotherapy group compared to 60% in the no chemotherapy group. Overall survival is 95% and 74% in these two patient groups. Fifty-eight percent of patients had limb-sparing surgery plus radiation therapy and 42% underwent amputation. In both treatment subgroups analyzed separately, chemotherapy resulted in an improvement in disease-free survival compared to randomized controls not receiving chemotherapy (P = 0.006 and P = 0.04 for groups receiving amputation and limb sparing, respectively). There were no local failures in the patients receiving chemotherapy and two local failures in the no chemotherapy group. The results of this trial confirm the historically controlled pilot trial performed in 26 patients between 1975 and 1977. A current update of the patients in the pilot trial, with a minimum four-year follow-up, reveals an improvement in disease-free and overall survival due to chemotherapy (P less than 0.002). Analysis of the previous pilot trial indicates that only few recurrences are seen beyond three years. Thus, it appears that adjuvant chemotherapy should be a part of the treatment adult patients with soft tissue sarcomas of the extremities.

Adult↗
PubMed1983

Prospective evaluation of doxorubicin-induced cardiomyopathy resulting from postsurgical adjuvant treatment of patients with soft tissue sarcomas.

One hundred and one soft tissue sarcoma patients from an adjuvant chemotherapy study of the Surgery Branch, National Cancer Institute who had received greater than or equal to 430 mg/m2 (range, 430-600 mg/m2) of doxorubicin were followed for evidence of cardiomyopathy. Fourteen patients developed clinical congestive heart failure attributable to doxorubicin. Nine of these fourteen were evaluated by radionuclide angiography (RNA), and all were abnormal with mean ejection fraction both at rest and exercise less than 30%. Sixty-one asymptomatic patients were studied at least once with RNA. In this asymptomatic group, 13 of 61 patients (21%) had abnormal resting left ventricular function. Exercise studies identified an additional 19 abnormal individuals (31%). Overall incidence of cardiomyopathy, as evidenced by RNA, in the asymptomatic group was 52%. By including the fourteen symptomatic patients, the incidence of cardiomyopathy detected either clinically or by RNA in the 75 evaluated patients was 46%. Comparison of patients by age (less than 40 versus greater than 40) revealed a highly significant difference in the incidence of cardiomyopathy (P less than .001). Fourteen of 36 patients (38%) less than or equal to 40 had either clinical or RNA evidence of cardiotoxicity while 32 of 39 (82%) individuals greater than 40 demonstrated cardiomyopathy. No significant difference was seen in those asymptomatic patients in whom RNA was performed less than or equal to 12 months as compared with greater than 12 months after the end of doxorubicin treatment. In the entire group there was no apparent improvement in cardiomyopathy with time, but results suggest that left ventricular function in the group older than 40 years does deteriorate. The cardiac function of patients younger than age 40 appeared to remain stable or possibly improve with time after the completion of treatment. Sex, tumor location, and radiation treatment were not associated with an increased risk of cardiomyopathy. These results emphasize the dangers of full-dose doxorubicin therapy. This high incidence of cardiomyopathy became apparent because of our ability to prospectively evaluate a large group of patients with prolonged life expectancy that received adjuvant doxorubicin chemotherapy after surgery.

Adolescent↗
PubMed1983

Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy.

A new treatment program was developed in an attempt to increase the complete remission rate and survival of previously untreated patients with advanced stages of diffuse aggressive lymphomas. A flexible number of cycles of ProMACE chemotherapy (prednisone, methotrexate, doxorubicin, cyclophosphamide, and epipodophyllotoxin VP-16) was alternated with a flexible number of cycles of MOPP chemotherapy (mechlorethamine, vincristine sulfate, procarbazine, and prednisone), and finally late intensification with ProMACE therapy was given. The duration of each phase of treatment was determined by the patient's rate of tumor response. Complete remissions were achieved in 55 of 74 patients (74%) with a median duration of follow-up exceeding 2 1/2 years. Only ten of the complete responders (18%) have had relapse. The dose-limiting toxicity is myelosuppression, and eight patients (10%) died from sepsis. Median survival for all patients has not been reached but is predicted to exceed 4 years with 65% of patients alive at 4 years. Previously we achieved a 46% complete remission rate with 38% of all patients alive at 4 years; relapse-free survival beyond 2 years was tantamount to cure. Therefore, ProMACE-MOPP chemotherapy represents a substantial improvement in treating patients with diffuse aggressive lymphomas.

Adolescent↗
PubMed1982

A randomized trial of cytoreductive surgery followed by chemotherapy versus chemotherapy alone in bulky stage testicular cancer with poor prognostic features.

Thirty-nine patients with Stage III nonseminomatous testicular cancer were treated in a prospective randomized trial comparing cytoreductive surgery followed by a cis-platinum containing combination chemotherapy regimen versus chemotherapy alone. All patients had one or more of the following poor prognostic signs: palpable retroperitoneal disease, liver involvement, invasion or obstruction of the inferior vena cava, or lung metastases larger than 2 cm in diameter. Cytoreductive surgery was technically feasible in this group of patients as assessed radiographically (70-90% reduction in tumor mass) and by the decline in serum levels of alpha-fetoprotein and human chorionic gonadotropin in 75% of the patients following surgery. However, there was no statistically significant improvement in overall response rate (75% versus 84%), complete response rate (50 versus 37%) or in survival between the patients treated with surgery prior to chemotherapy or with chemotherapy as the initial treatment. It is unlikely (P less than 0.028) that any true beneficial effect of surgery was missed due to the relatively small number of patients in each treatment arm. The authors of this study conclude that cytoreductive surgery prior to chemotherapy in patients with poor prognosis Stage III testicular carcinoma is not routinely indicated. Since the overall complete response rate to chemotherapy in these 39 patients with bulky Stage III disease was only 43%, alternate approaches, other than cytoreductive surgery, are necessary to improve the prognosis for this group of patients.

Antineoplastic Agents↗
PubMed1982

The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.

Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m2), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p1 = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (71% and 78% at five years; p2 = 0.75) or overall survival rates (83% and 88% at five years; p2 = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p1 less than 0.0001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p1 = 0.0008) and overall survival (95% vs. 74%; p1 = 0.04). Thus limb-sparing surgery, radiation therapy, and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity.

Adolescent↗