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Biomedical subjects

B Samuels

Publications and source records attributed to B Samuels.

At least 19 recordsLinked to original sources
PubMed2002

Trimetrexate in relapsed T-cell lymphoma with skin involvement.

PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX) enters cells by passive diffusion and is not polyglutamylated, its activity in relapsed T-cell lymphoma was investigated. PATIENTS AND METHODS: Eligible patients had histologically confirmed relapsed T-cell lymphoma involving the skin, had received more than one previous regimen, were older than 16 years, had normal organ function, and had no CNS disease or serious infections, including human immunodeficiency virus. TMTX (200 mg/m(2)) was given intravenously every 14 days without topical or systemic corticosteroids. Patients who responded received up to 12 doses. RESULTS: Twenty patients were assessable for response. Median age was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sézary syndrome (14 with large-cell transformation), and two had peripheral T-cell lymphoma. Serum lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0 mg/L in 35% of patients. The median number of previous regimens was three (range, two to 15) and included MTX in five patients. Disease was refractory to the regimen immediately preceding TMTX in 85% of patients. Responses were complete in one and partial in eight patients (overall response rate, 45%). Two of five patients previously treated with MTX responded. Grade 3 or 4 mucositis was observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils less than 100/microL after 4%, and platelets less than 10,000/microL after 3% of TMTX doses. CONCLUSION: TMTX is active with acceptable toxicity in this population and merits further investigation.

Aged↗
PubMed2001

Phase II studies of bryostatin-1 in patients with advanced sarcoma and advanced head and neck cancer.

BACKGROUND: Bryostatin 1 is a marine derived macrolactone with antineoplastic activity modulated through protein kinase C, and with good activity in in vitro and in vivo models. There are few drugs that offer palliation for metastatic soft-tissue sarcoma and head and neck cancer, and drugs with new mechanisms of action warrant detailed disease specific study. PATIENTS AND METHODS: Two phase II studies for patients with incurable soft tissue sarcoma (12), or head and neck cancer (12) were conducted. Patients were treated with bryostatin, 120 mg/m2/72 hours every 2 weeks for 3 cycles prior to re-evaluation. Most patients had received prior chemotherapy. RESULTS: No patients had objective responses to therapy. Six patients had brief periods of disease stabilization. Toxicity was generally mild, with myalgia being prominent (n=8). Hyponatremia, not previously described, occurred in 5 patients. The mechanism of this toxicity was unclear. CONCLUSIONS: Bryosytatin 1 given as a single agent for advanced adult soft tissue sarcoma and head and neck cancer is inactive. Myalgia and hyponatremia were the predominant toxicities.

Adult↗
PubMed2001

Irinotecan in relapsed or refractory non-Hodgkin's lymphoma.

Irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity. Various schedules and doses have been studied, and major complications were delayed diarrhea and myelosuppression. We explored the activity of irinotecan in patients with relapsed or refractory non-Hodgkin's lymphoma, using a 3-week schedule of administration. Eligible patients had histologically proven relapse, had received no more than two previous regimens, were > or = 15 years and < or = 75 years old, had normal renal function, neutrophil count > 1,500/microL, platelet count > 100,000/microL, and no human immunodeficiency virus infection or central nervous system involvement. Patients were treated with irinotecan 300 mg/m2 i.v. every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 25 patients registered so far, 22 are evaluable for response. The median age was 67 years (range: 25 to 74 years) and 11 were male. The median number of previous regimens was 2 (range: 1 to 4 regimens), and 16 patients had disease that was refractory to their last regimen. Serum lactate dehydrogenase level was high in 75%, and beta2-microglobulin was > 3.0 mg/L in 26% of patients. Responses were seen in 8 of 22 (36%) patients with non-Hodgkin's lymphoma. Response rates were 40% for indolent, 0% for mantle cell, 45% for relapsed aggressive, and 33% for refractory aggressive lymphomas. Grade 3/4 toxicities included myelosuppression, neutropenic fever, and delayed diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive non-Hodgkin's lymphoma. Accrual to this study is continuing for better determination of the response rate in all histologic subtypes of non-Hodgkin's lymphoma.

Adult↗
PubMed2000

Liposomal vincristine in relapsed non-Hodgkin's lymphomas: early results of an ongoing phase II trial.

OBJECTIVE: Vincristine is an active agent in lymphomas, but is often neurotoxic, and the resulting dose reductions have been associated with lower remission and survival rates in Hodgkin's disease. Liposomal vincristine (Onco-TCS) has prolonged half-life, reaches higher concentration in tumors and lymph nodes than in nerves, and administered at full doses appears to be less neurotoxic, and more active then free vincristine in mice bearing L-1210 and P-388 leukemias. We therefore explored its activity in relapsed non-Hodgkin's lymphomas (NHL) and acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Eligible patients had histologically proven relapse, age > or = 16 years, normal renal function, neutrophils > 500/microliter, platelets > 50,000/microliter, and no HIV infection, central nervous system disease, or serious neuropathy. Patients were treated with 2.0 mg/m2 of liposomal vincristine i.v. over 60 minutes q 14 days. Responders received up to 12 injections. RESULTS: Of the 51 registered patients, 35 are currently evaluable for response. Median age was 62 years (range 19-86), and 21 were male. The median number of prior regimens was 3 (range 1-10) and had included vincristine in all patients, of whom 51% were refractory to their last regimen. Serum LDH was high in 46%, and beta 2-microglobulin > 3.0 mg/l in 63% of patients. Of the 155 administered injections, 138 (89%) were at the 2.0 mg/m2 level. The median injected dose was 3.8 mg (range 2.6-4.8 mg), and median number of injections was 4 (range 1-12). Responses were seen in 14 of 34 (41%) patients with NHL (95% confidence intervals (95% CI) 25%-59%). Response rates were 10% for indolent, 71% for transformed, and 47% for aggressive NHL, but the 95% confidence intervals overlapped. Median progression-free survival was 5.5 months for responders. Grade 3-4 motor or sensory neuropathy was seen in 11, and caused termination of therapy in five patients. All five had prior neuropathy, two had previously received paclitaxel, one platinum, and two paclitaxel and platinum. Fever was detected in three patients, but there were no toxic deaths. CONCLUSIONS: Liposomal vincristine is active and well tolerated in this heavily pretreated population with relapsed NHL, but can be neurotoxic in a fraction of patients heavily exposed to prior neurotoxic agents. These data, if confirmed, would suggest a potential role for liposomal vincristine in the combination therapy of previously untreated patients with NHL.

Adult↗
PubMed2000

Infusional vinorelbine in relapsed or refractory lymphomas.

Vinorelbine (Navelbine is a semisynthetic vinca alkaloid devoid of serious neurotoxicity. When given weekly vinorelbine has documented activity against many tumors, including lymphomas. Since weekly schedules cannot be easily incorporated in combination regimens, we tested an infusional schedule of vinorelbine given every 21 days in adults with relapsed or refractory lymphoma. Patients with inadequate organ or bone marrow reserve, HIV or other serious infection, central nervous system disease, or prior stem cell or bone marrow transplantation were ineligible. In the phase I part, patients received a constant intravenous bolus of 8 mg/m(2), followed by intravenous continuous infusion over 24 hours daily for four days increasing from 10, 12, to 14 mg/m(2) /d in successive three-patient cohorts. Cycles were repeated every 21 days, and the daily continuous infusion dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were reached at the continuous dose of 14 mg/m(2) /d. Consequently, for the Phase II trial the starting continuous infusion dose was 12 mg/m(2) /d. After the first 19 patients were entered in the phase II study, the starting infusion dose was reduced to 10 mg/m(2) /d because of frequent grade (3/4) myelosuppression and mucositis. Forty-four patients were entered in the phase II study, of whom 41 are evaluable. Median age was 61 years, 23 were males, with clinically aggressive non-Hodgkin's lymphoma (NHL) in 22, indolent NHL in 18, and Hodgkin's Disease in one patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was refractory to the initial regimen in nine patients, and to the regimen immediately before vinorelbine in 20 patients. Serum LDH was high in 2(1/4)1, and serum beta(2) -microglobulin > 3.0 mg / L in 16/31 patients. Responses were observed in four of 22 patients with aggressive NHL (18%, 95% confidence interval 5%-40%), and in six of 18 with indolent NHL (33%, 95% confidence interval 13%-59%). Median progression-free survival was 6 months for responders. During the Phase II trial 114 vinorelbine courses were administered. Neutrophil nadir was < 1000/microl in 65% and < 100/microl in 35% of courses, respectively. Platelet nadir was < 100,000/microl in 30% and < 20,000/microl in 8% of courses, respectively. Grade (3/4) mucositis was seen in 18% of courses, and neutropenic fever in 13%, and was complicated by death in one patient. We conclude that this dosage and schedule of vinorelbine has modest activity in patients with relapsed or refractory NHL. Myelosuppression is frequent but reversible, but there is no significant neurotoxicity. The role of vinorelbine in combination regimens for patients with relapsed lymphomas, particularly those of indolent histology, should be further investigated.

Adult↗
PubMed1999

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced biliary carcinoma.

PRECIS: UFT 300 mg/m2/day and leucovorin 90 mg/day could be administered safely to patients with advanced biliary cancer with good performance status; however, this combination and schedule of 28-day administration has no activity in this disease. PURPOSE: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) plus oral calcium leucovorin in the treatment of patients with advanced biliary (gallbladder and bile duct) carcinoma. PATIENTS AND METHODS: Thirteen patients with advanced measurable biliary carcinoma were enrolled onto the trial. All patients had a Karnofsky performance status > or = 60%, platelet count > or = 75,000/microL, total bilirubin < or = 2.0x institutional upper limit of normal but otherwise normal liver and kidney function profile and bidimensionally measurable disease by CT scan or ultrasound examination. None of these patients previously received cytotoxic chemotherapy or radiation therapy for advanced disease. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days repeated every 35 days. Objective tumor response, the primary endpoint of this trial, was evaluated after two courses of therapy. Other endpoints included toxicity, time to progression, and overall survival. RESULTS: All patients were evaluable for response and toxicity. No complete or partial responses were observed in this trial. Four patients had stable disease lasting 17, 30, 33, and 35 weeks, respectively. The median (range) time to progression and survival were 9 (1-35) and 28 (1-61) weeks, respectively. Treatment-related toxicity was mild with severe (grade 3 or 4) diarrhea seen in 2 (15%). Grade 3-4 hyperbilirubinemia (31%) and nausea/vomiting (31%) were observed and likely related to the underlying disease. Grade 1 and 2 toxic effects included mainly anorexia and fatigue. CONCLUSION: UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days repeated every 35 days is ineffective in the treatment of advanced biliary carcinoma.

Aged↗
PubMed1999

Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.

BACKGROUND: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus-lymphoma effect in such patients post allogeneic hematopoietic transplantation. PATIENTS AND METHODS: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. RESULTS: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%-100%) compared with 44% (95% CI: 1%-88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). CONCLUSIONS: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

Adult↗
PubMed1999

Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma.

BACKGROUND: The combination of carmustine, etoposide, cytarabine and melphalan (BEAM) is an effective autologous transplantation preparative regimen for lymphoma and has little toxicity, but the feasibility and tolerance of BEAM as a preparative regimen for allogeneic transplantation has not been established. PATIENTS AND METHODS: Thirty adults with primary refractory or recurrent intermediate- or low-grade lymphoma were treated on a prospective phase II study with carmustine 300 mg/m2 i.v. day -6, etoposide 200 mg/m2 i.v. followed by cytarabine 200 mg/m2 i.v. twice daily days -5 to -2, melphalan 140 mg/m2 i.v. day -1, and marrow or blood stem cells from an HLA-identical donor on day 0. Tacrolimus and methotrexate were used to prevent graft-vs.-host disease (GVHD). RESULTS: Median time from transplantation was 20 mos (range 6-32 months). Median maximal regimen-related toxicity grade was 2, and four patients (13%) had a grade 3-4 regimen-related toxicity. Two patients had idiopathic interstitial pneumonitis. One patient had primary graft failure, and a second had autologous reconstitution documented at three months posttransplant. Grades 2-4 acute GVHD occurred in 31%, grades 3-4 in 16%, and chronic GVHD in 54%. Day-100 survival was 70%. Twenty-three patients achieved a complete response. The two-year relapse rate was 23%, survival was 48%, and disease-free survival (DFS) was 42%. CONCLUSIONS: BEAM supports engraftment of allogeneic transplants and is a tolerable preparative regimen for allogeneic transplantation for lymphoma.

Adult↗
PubMed1998

Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.

PURPOSE: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS: Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS: Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION: The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.

Adult↗
PubMed1997

Documentation by intravascular ultrasound of thrombus overlying a small atheromatous plaque in a coronary artery in unstable angina pectoris and in acute myocardial infarction.

Rupture of atheromatous plaques leading to acute coronary syndromes usually occur in lipid-reach and well-developed coronary lesions. We describe 2 unusual patients with acute coronary syndromes in whom there was angiographic and intravascular ultrasound evidence of an intraluminal thrombus overlying a small, nonocclusive plaque in an enlarged coronary artery.

Adult↗
PubMed1997

In search of specimen adequacy in fine-needle aspirates of nonpalpable breast lesions.

Pathology-related medical malpractice claims frequently concern fine-needle aspirations (FNAs) of breast lesions, and diagnostic errors have been attributed in part to the inadequacy of the specimens. Cytologic criteria for adequate FNA specimens, specifically in cases without malignancy, have not been clearly defined. From January 1988, to August 1995, 669 ultrasonographic-guided FNAs of nonpalpable, solid breast lesions with subsequent histologic examination were performed at our institution. From these, 54 cases with cytologic diagnoses of insufficient or nonspecific benign findings were identified. All aspirates were reviewed, and the number and size of the epithelial cell groups were quantitated in each case. By using criteria for adequate aspirates of palpable breast lesions (six or more epithelial cell groups per case with a minimum of 5-10 cells per group), 23 of the 54 aspirates were deemed inadequate and 31 adequate. Eleven (48%) of the inadequate aspirates and 17 (55%) of the adequate aspirates were from histologically confirmed carcinomas (ductal carcinoma in situ, 6; invasive carcinoma, 22, of which 12 were ductal, 7, lobular, and 3, mixed ductal and lobular). For the mammographic diagnoses "probably benign," "indeterminate," and "suggestive of malignancy or malignant," the probability of malignancy in aspirates of adequate cellularity (eg, > 6 epithelial groups) was 9%, 40%, and 93%, respectively. These findings indicate that a significant proportion of breast aspirates still may yield false-negative results despite adequate to high cellularity. Although a definition of adequacy based on cellularity is useful in reducing false-negative results, cellularity alone cannot be relied on in the management of nonpalpable lesions. For mammographic findings that are indeterminate or suggestive of malignancy or malignant, nonspecific FNA findings should be followed by core or excisional biopsy to exclude carcinoma.

Adult↗
PubMed1996

Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.

The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.

Adult↗
PubMed1996

Her2/neu overexpression is associated with treatment failure in women with high-risk stage II and stage IIIA breast cancer (>10 involved lymph nodes) treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support following standard-dose adjuvant chemotherapy.

Twenty-five patients with high-risk stage II and IIIA breast cancer (>10 or more involved lymph nodes) were treated with six cycles of standard-dose chemotherapy (5-fluorouracil, doxorubicin, and cyclophosphamide) followed by high-dose chemotherapy (2.5 g/m2 cyclophosphamide for 3 days and 225 mg/m2 thiotepa for 3 days) with autologous hematopoietic progenitor cell support. The actuarial relapse free survival at 3 years is 80%; the actuarial survival at 3 years is 96%. Four patients relapsed systemically between 6 and 18 months; all four patients who relapsed had breast cancers that overexpressed Her2/neu. In contrast, none of the 21 patients who had no or borderline overexpression of Her2/neu relapsed (P = 0.00004, Fisher's exact test). Patients with high-risk stage II and IIIA breast cancer who have overexpression of Her2/neu appear to be at a high risk for relapse, even when treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support.

Adult↗
PubMed1995

Conservative surgery and adjuvant radiation therapy in the management of adult soft tissue sarcoma of the extremities: clinical and radiobiological results.

PURPOSE: The outcome of adult patients with soft tissue sarcoma of the extremities treated with conservative surgery and adjuvant irradiation was evaluated to (a) determine the appropriate treatment volume and radiation dosage in the postoperative setting, and (b) correlate in vitro radiobiological parameters obtained prior to therapy with clinical outcome. METHODS AND MATERIALS: Sixty-four consecutive adult patients with soft tissue sarcoma of the extremities (40 lower, 24 upper) who underwent conservative surgery and adjuvant irradiation 7 preoperative, 50 postoperative, 7 perioperative) between 1978 and 1991 were reviewed. The initial radiation field margin surrounding the tumor bed/scar was retrospectively analyzed in all postoperative patients. Initial field margins were < 5 cm in 12 patients, 5-9.9 cm in 32 and > or = 10 cm in 6. Patients with negative pathological margins were initially treated with traditional postoperative doses (64-66 Gy); however, in later years the postoperative dose was reduced to 60 Gy. Thirteen cell lines were established prior to definite therapy, and radiobiological parameters (multitarget and linear-quadratic) were obtained and correlated with outcome. RESULTS: Postoperative patients treated with an initial field margin of < 5 cm had a 5-year local control of 30.4% vs. 93.2% in patients treated with an initial margin of > or = 5 cm (p = 0.0003). Five-year local control rates were similar in patients treated with initial field margins of 5-9.9 cm (91.6%) compared with those treated with > or = 10 cm margins (100%) (p = 0.49). While postoperative patients receiving < 60 Gy had a worse local control than those receiving > or = 60 Gy (p = 0.08), no difference was seen in local control between patients receiving less than traditional postoperative doses (60-63.9 Gy) (74.4% vs. those receiving 64-66 Gy (87.0%) (p = 0.5). The local control of patients treated in the later years of the study, with strict attention to surgical and radiotherapeutic technique, was 87.6%. Severe late sequelae were more frequent in patients treated with doses > or = 63 Gy compared to patients treated with lower doses (23.1% vs. 0%) (p < 0.05). Mean values for Do, alpha, beta, D, n and SF2 obtained from the 13 cell lines were 115.7, 0.66, 0.029, 2.15, 0.262, respectively. Four of the 13 cell lines established prior to therapy ultimately failed locally. The radiobiological parameters of these cell lines were similar to the other nine cell lines in terms of radiosensitivity. CONCLUSIONS: Our data confirm the importance of maintaining an initial field margin of at least 5 cm around the tumor bed/scar in the postoperative setting. No benefit was seen with the use of margins > or = 10 cm. In addition, patients undergoing wide local excision with negative margins can be treated with lower than traditional postoperative doses (60 Gy) without compromising local control and with fewer chronic sequelae. Finally, it does not appear that inherent tumor cell sensitivity is a major determinant of local failure following radiation therapy and conservative surgery in soft tissue sarcoma.

Adolescent↗
PubMed1995

Adenosine pharmacologic stress myocardial perfusion tomographic imaging in patients with significant aortic stenosis. Diagnostic efficacy and comparison of clinical, hemodynamic and electrocardiographic variables with 100 age-matched control subjects.

OBJECTIVES: This study assessed the safety and diagnostic accuracy of adenosine stress myocardial perfusion scintigraphy for the detection of coronary artery disease using single-photon emission computed tomography (SPECT) in patients with significant aortic stenosis. BACKGROUND: Exercise cardiac stress testing in patients with significant aortic stenosis is generally avoided because of concerns for safety. In addition, those studies that have analyzed the utility of exercise testing both with and without myocardial thallium-201 scintigraphy for the diagnosis of coronary artery disease have yielded low specificity. Currently, no safe and accurate means exists to noninvasively assess the presence, extent and severity of coronary artery disease in patients with significant aortic stenosis. METHODS: The study included 35 patients with moderate to severe aortic stenosis (mean [+/- SD] aortic valve area 0.84 +/- 0.16 cm2, range 0.5 to 1.2; mean maximal instantaneous aortic valve gradient 44.4 +/- 15.9 mm Hg, range 20 to 84). All patients underwent a 6-min adenosine infusion (140 micrograms/kg body weight per min) protocol and either separate acquisition rest thallium-201/stress technetium-99m sestamibi or stress and 4-h redistribution thallium-201 SPECT: Visual 20-segment SPECT analysis used a standard five-point scoring system from 0 (normal tracer uptake) to 4 (absent uptake). The SPECT results were considered abnormal if more than two segments had a stress score > or = 2. Hemodynamic, electrocardiographic and clinical responses were compared with those in a reference group of 100 consecutive age-matched patients undergoing adenosine SPECT who did not have aortic stenosis. RESULTS: Hemodynamic responses during adenosine stress testing between the study and control patients demonstrated no significant difference in the net change in systolic blood pressure (18% of baseline vs. 14%, patients with aortic stenosis vs. control subjects), heart rate (21% vs. 19%), rate-pressure product (0% vs. 2%) or incidence of chest pain (23% vs. 35%) or transient second-(9% vs. 9%) or third-degree atrioventricular block (3% vs. 1%). In the 20 patients who had coronary angiography, sensitivity for detection of coronary artery disease was 92% (12 of 13) and specificity was 71% (5 of 7). CONCLUSIONS: In this preliminary study, adenosine was found to be well tolerated and diagnostically accurate in patients with moderate to severe aortic stenosis.

Adenosine↗
PubMed1995

A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for autologous transplantation for malignant lymphoma.

Thirty-four adults with malignant lymphoma at high-risk for relapse were treated on a Phase I-II study of high-dose thiotepa (THIO), busulfan (BU) and cyclophosphamide (CYC) with autologous marrow or peripheral blood stem cell support. Four patients were in untreated relapse, 7 had stable or progressive disease, 12 were in partial remission, and 11 were in complete remission after reinduction chemotherapy before proceeding to the preparative regimen. Median follow-up time is 22 months. Grades 3-4 regimen-related toxicity occurred in 3 (14%) of 22 patients treated with THIO 250 mg/m2 x 3, BU 1 mg/kg x 10 and CYC 50 mg/kg x 3, and this was considered the maximal tolerated dose-schedule. Of the 23 patients with active disease at the time of transplantation, 52% (95% CI 31-73%) achieved a complete response, and 26% (95% CI 10-48%) achieved a partial response. For all patients, median time to progression was 13 months, median survival was 16 months, and disease-free survival at 18 months was 34% (95% CI 18-51%). The combination of THIO, BU and CYC is tolerable as a preparative regimen for lymphoma and has a high response rate, but further measures are needed to reduce the relapse rate for patients with advanced disease.

Adult↗