bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities.
Authors: Picci P , Rougraff B T , Bacci G , Neff J R , Sangiorgi L , Cazzola A , Baldini N , Ferrari S , Mercuri M , Ruggieri P 
Published: February 2017

PURPOSE To evaluate more accurately the effectiveness of preoperative chemotherapy in the treatment of patients with Ewing's sarcoma, we studied histopathologically the chemotherapeutic response and correlated it to oncologic outcome. PATIENTS AND METHODS Between June 1983 and December 1989, 68 patients with nonmetastatic Ewing's sarcoma of the extremities were treated at our institute with preoperative chemotherapy (without radiation therapy) and surgery. The specimens were retrospectively evaluated for areas of viable tumor cells and graded from I to III (macroscopic, microscopic, or no residual disease, respectively) in a blinded fashion. Clinical follow-up data were available on all patients for a mean of 60 months (range, 32 to 111). RESULTS This histopathologic analysis was strongly correlated with oncologic outcome (P = .004). Patients who demonstrated grade III response (no identifiable viable tumor nodules present) had improved 5-year disease-free survival rates as compared with patients with grade II (microscopic nodes present; P = .023; 90% v 53%) and grade I responses (macroscopic nodules present; P = .0003; 90% v 32%). Patients with grade II necrosis had statistically improved survival rates over those with grade I necrosis (53% v 32%; P = .074). CONCLUSION This new histopathologic analysis technique for the evaluation of neoadjuvant chemotherapy effectiveness (which does not rely on tumor volume for its assessment) is a valuable prognostic indicator for patients with Ewing's sarcoma treated with surgery. Based on this preliminary report, cases of grade I or II chemotherapeutic tumor response should be considered clinical failures and a different, more aggressive postoperative chemotherapy regimen should be considered.
Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.
Authors: Garaventa A , De Bernardi B , Pianca C , Donfrancesco A , Cordero di Montezemolo L , Di Tullio M T , Bagnulo S , Mancini A , Carli M , Pession A 
Published: February 2017

PURPOSE To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.
Prognostic significance of Ki-67 immunostaining in nonmetastatic renal cell carcinoma.
Authors: de Riese W T , Crabtree W N , Allhoff E P , Werner M , Liedke S , Lenis G , Atzpodien J , Kirchner H 
Published: February 2017

PURPOSE Fresh tissue samples from nonmetastatic renal cell carcinoma (RCC) patients were analyzed by Ki-67 immunostaining to determine the prognostic significance of this tumor-biologic parameter. MATERIALS AND METHODS In a prospective study, Ki-67 immunostaining was performed on frozen sections of histologically proven node-negative RCC from 58 patients operated on between 1986 and 1988 to examine the method's prognostic value and its association with other clinicopathologic parameters such as tumor stage (pT) and grade (G). RESULTS The percentage of Ki-67-positive cells (ie, the proliferation rate [PR]) of all 58 RCC tumors ranged between 1% and 23%, while normal renal tissue exhibited PRs up to 2% only. In almost all cases, the highest PRs were observed in the peripheral zone of malignant tissue close to the normal renal tissue. PR did not correlate with pT, whereas a strongly significant correlation was observed between PR and G, as well as recurrence rate. Twenty-three of 58 patients (39.6%) developed tumor recurrence. Disease-free survival was strongly associated with PR. In a multivariate analysis, G and PR were independent prognostic markers. CONCLUSION The tumor-specific PR obtained by Ki-67 labeling seems to be an independent marker to describe the proliferative activity and aggressiveness of individual tumors. This new tumor-biologic marker detects RCC patients at high risk for recurrent disease, especially in those cases with identical pT and G.
Does interleukin-2 have a role in the management of acute leukemia?
Authors: Foa R 
Published: February 2017

PURPOSE To discuss the possibility that interleukin-2 (IL-2)-based immunotherapeutic protocols may have a role in the management of acute leukemia. DESIGN The preclinical results that have led to the clinical use of IL-2 in acute leukemia will be reviewed. The clinical data obtained with the administration of IL-2 to acute leukemia patients in different phases of their disease will be discussed, together with the clinicohematologic and immunologic modifications induced following the infusion of IL-2. Finally, the possibility that limitations associated with the exogenous administration of high-dose IL-2 may be circumvented by engineering techniques aimed at inserting the IL-2 gene directly into the tumor cells, will be addressed. RESULTS The data indicate that high-dose IL-2 may be administered to acute leukemia patients. Toxicity, recorded in all patients, appears to be controllable using a continuous intravenous (i.v.) infusion protocol based on a daily dose-escalating administration. Complete remissions have been documented in acute myeloid leukemias (AMLs) with a limited, but detectable proportion of residual marrow blasts. Numerous phenotypic and functional changes have been recorded within the immune system of the host. Using retroviral vectors, the IL-2 gene may be productively transduced into human acute leukemia cell lines. CONCLUSION IL-2 appears to represent a therapeutic option for AML patients with limited/minimal residual disease. The results of the ongoing randomized trials in patients in first or second remission are awaited.
Clinical significance of bcl-2-MBR gene rearrangement and protein expression in diffuse large-cell non-Hodgkin's lymphoma: an analysis of 83 cases.
Authors: Tang S C , Visser L , Hepperle B , Hanson J , Poppema S 
Published: February 2017

PURPOSE The goal of this study was to assess the prognostic significance of a rearrangement of the major breakpoint region of the bcl-2 gene and/or expression of bcl-2 protein in diffuse large-cell lymphomas of B-cell origin. PATIENTS AND METHODS All 83 patients diagnosed at the Cross Cancer Institute between 1987 and 1992 with malignant lymphoma (ML), diffuse large-cell ML non-cleaved-cell ML or cleaved-cell ML, or with diffuse large-cell immunoblastic ML were studied. bcl-2 rearrangement was identified by a polymerase chain reaction technique. This technique detects the approximately 60% of rearrangements involving the major breakpoint region bcl-2 gene (bcl-2-MBR). bcl-2 protein expression was studied by immunohistochemistry. RESULTS More than 66% of the cases expressed bcl-2 protein, whereas 18% had a detectable bcl-2-MBR gene rearrangement. Overall, cases with bcl-2-MBR rearrangement had shorter disease-free periods. Cases with nodal and extranodal presentation had a similar frequencies of bcl-2-MBR rearrangement; however, the disease-free period of patients with extranodal presentation and bcl-2-MBR rearrangement was significantly shorter than that of those without rearrangement. CONCLUSION bcl-2 protein is frequently expressed in diffuse large-cell lymphomas, but does not influence prognosis. The bcl-2-MBR gene rearrangement may possibly be associated with a shorter disease-free period, particularly in the specific setting of a lymphoma with extranodal presentation.
Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy.
Authors: Rabinovitch R A , Zelefsky M J , Gaynor J J , Fuks Z 
Published: February 2017

PURPOSE This report is a patterns-of-failure analysis of resected renal cell carcinoma (RCC) performed to determine the relative incidences of local failure (LF) and distant failure, to identify the pathologic features predicting for each using a multivariate analysis, and to assess the relative impact of each form of failure on overall survival (OS). In this way, the potential value of and selection of patients for adjuvant local and/or systemic therapy can be better evaluated. MATERIALS AND METHODS The records of 172 patients with unilateral, nonmetastatic RCC who were treated with definitive surgery between 1978 and 1988, and who had a minimum follow-up duration of 1 year, were identified through the Memorial Sloan-Kettering tumor registry. Distribution by stage included T1, 10 patients; T2, 102; T3a, 32; T3b, 27; and T4, one. The incidences of positive lymph nodes (LNs) and positive margins were 5.8% and 6.4%, respectively. RESULTS LF developed in only six patients, yielding a 7-year actuarial incidence of 5%. In this subset, four patients developed distant metastases (DM), three occurring concurrently with or before LF. DM developed in 30 patients, yielding a 7-year actuarial incidence of 26%. Among the variables that had an impact on the development of DM according to univariate log-rank tests, only positive LNs (P = .026) and renal vein extension (P = .001) remained as significant independent prognosticators. The overall 7-year actuarial survival rate was 80%. Eleven patients died of RCC during follow-up, nine of whom (82%) died of metastatic disease. CONCLUSION LF is rare following surgical management of RCC, and shows no clear causal relationship with the development of DM. Patients die of DM, and not LF. These data do not support the role of adjuvant radiation therapy in this disease. Patients with LN involvement or renal vein extension have a significantly increased risk for developing DM, and are therefore appropriate candidates for trials investigating systemic therapy.
Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study.
Authors: Ayash L J , Elias A , Wheeler C , Reich E , Schwartz G , Mazanet R , Tepler I , Warren D , Lynch C , Gonin R 
Published: February 2017

PURPOSE Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. PATIENTS AND METHODS Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. CONCLUSION With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.
Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial.
Authors: Maksymiuk A W , Jett J R , Earle J D , Su J Q , Diegert F A , Mailliard J A , Kardinal C G , Krook J E , Veeder M H , Wiesenfeld M 
Published: February 2017

PURPOSE The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.
Phase I study of highly selective supradose cisplatin infusions for advanced head and neck cancer.
Authors: Robbins K T , Storniolo A M , Kerber C , Vicario D , Seagren S , Shea M , Hanchett C , Los G , Howell S B 
Published: February 2017

PURPOSE To determine the maximum dose-intensity of cisplatin (DDP) that could be administered by selective intraarterial (IA) infusion in combination with systemic sodium thiosulfate neutralization to patients with head and neck carcinoma. PATIENTS AND METHODS Forty-two patients (23 untreated stage III/IV, 19 recurrent) received highly selective IA DDP, rapidly delivered through microcatheters placed angiographically, to a maximum dose-intensity of 200 mg/m2/wk. Concurrently, the systemic effects of DDP were neutralized by intravenous (IV) bolus sodium thiosulfate. RESULTS Problems related to the infusion technique occurred in eight of 140 courses, all of which were inconsequential. The rates of reversible grade I/II and grade III/IV toxicity were 14.8% and 1.1%, respectively. Dose-limiting toxicity, which consisted of severe electrolyte loss, occurred at a dose of 200 mg/m2/wk. The maximum-tolerated dose of DDP was 150 mg/m2 administered weekly for four doses. The overall and complete response rates in 38 assessable patients were 19 of 22 (86%) and nine of 22 (41%) for stage III/IV untreated tumors and 10 of 16 (62%) and four of 16 (25%) for patients with recurrent disease, respectively. CONCLUSION This pharmacologic strategy permits the selective and rapid delivery of extremely high doses of DDP to head and neck carcinomas with minimal procedural complications, low systemic toxicity, and high tumor response rates.
Treatment of children with stages II to IV anaplastic Wilms' tumor: a report from the National Wilms' Tumor Study Group.
Authors: Green D M , Beckwith J B , Breslow N E , Faria P , Moksness J , Finklestein J Z , Grundy P , Thomas P R , Kim T , Shochat S 
Published: February 2017

PURPOSE To evaluate the effect of the combination of vincristine, dactinomycin, and doxorubicin with (regimen J) or without (regimen DD-RT) cyclophosphamide on the relapse-free survival of children with stages II to IV Wilms' tumor and focal or diffuse anaplasia. PATIENTS AND METHODS We reviewed the clinical courses of all randomized patients from National Wilms' Tumor Study (NWTS)-3 and NWTS-4 with stages II to IV anaplastic Wilms' tumor, and determined the 4-year relapse-free survival rate separately for those with focal or diffuse anaplasia. Anaplasia was evaluated using newly developed topographic definitions for focal and diffuse anaplasia. RESULTS The 4-year relapse-free survival rate for five children with focal anaplasia who received regimen DD-RT was 80.0%, compared with 100.0% for eight children who received regimen J (P = .68). The 4-year relapse-free survival rate for 29 children with diffuse anaplasia treated with regimen DD-RT was 27.2%, compared with 54.8% for 30 children treated with regimen J (P = .02). CONCLUSION We conclude that children with focal anaplasia have an excellent prognosis when treated with vincristine, doxorubicin, and dactinomycin. The addition of cyclophosphamide to the three-drug treatment regimen improved the 4-year relapse-free survival rate of children with stage II to IV diffuse anaplasia. This result suggests that further intensification of the treatment regimen for children with diffuse anaplasia may result in an additional improvement in prognosis.
Neurotoxicity of purine analogs: a review.
Authors: Cheson B D , Vena D A , Foss F M , Sorensen J M 
Published: February 2017

PURPOSE The purine analogs, fludarabine, cladribine, and pentostatin, are active against a broad spectrum of indolent lymphoid malignancies. They also have similar toxicities, including myelosuppression, immunosuppression, and sporadic neurotoxicity. This review compares the spectrum of neurotoxicity of each of these agents. Now that these drugs are commercially available and are being widely used, physicians should be aware of potentially serious side effects that may be encountered. METHODS The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the fall of 1993. In addition, case records from National Cancer Institute (NCI) Group C protocols were reviewed for fludarabine in chronic lymphocytic leukemia (CLL), and cladribine and pentostatin in hairy cell leukemia (HCL), as well as adverse drug reactions reported to the NCI from January 1980 through September 1993. RESULTS At higher than recommended doses, life-threatening and fatal neurotoxicity were encountered with all three drugs. At the recommended doses, each agent induced neurotoxicity in approximately 15% of patients, mostly mild and reversible. However, severe neurologic complications were reported; these were occasionally delayed, sometimes fatal, but often at least partially reversible. CONCLUSION The doses of these three agents should not be increased above the recommended levels. Development of moderate or worse neurotoxicity should result in discontinuation of that drug.
Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer.
Authors: Francis P , Schneider J , Hann L , Balmaceda C , Barakat R , Phillips M , Hakes T 
Published: February 2017

PURPOSE This phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in the treatment of patients with platinum-refractory ovarian cancer. PATIENTS AND METHODS Twenty-five patients with platinum-refractory advanced ovarian cancer were treated. Twenty of the patients had failed to respond to platinum-based front-line chemotherapy and five had failed to respond to platinum-based therapy repeated at relapse. One patient had received prior pelvic radiation therapy. Patients were required to have bidimensionally measurable disease. Docetaxel was administered at a dose of 100 mg/m2 intravenously (i.v.) over 1 hour every 21 days. Twenty patients received no corticosteroid premedication and five received premedication with corticosteroids and antihistamines. RESULTS Eight of 23 assessable patients (35%) had a partial response (PR; 95% confidence interval, 16% to 57%). The median response duration was 5 months. Hospitalization for toxicity, predominantly neutropenic fever, occurred in 12 patients (48%) and 16% of courses. Anemia was common in the study population. Nonhematologic toxicities included alopecia, rash, fluid retention, diarrhea, peripheral neuropathy, and hypersensitivity reactions. CONCLUSION Docetaxel demonstrates significant activity in patients with platinum-refractory advanced ovarian cancer. Routine premedication is recommended. Further investigations of this agent in ovarian cancer, including combinations with other active agents, appear indicated.