bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical correlates of circulating immune complexes and antibody reactivity in squamous cell carcinoma of the head and neck. The Department of Veterans Affairs Laryngeal Cancer Study Group.
Authors: Vlock D R , Schantz S P , Fisher S G , Savage H E , Carey T E , Wolf G T 
Published: February 2017

PURPOSE To evaluate the correlation between the presence and titer of host-derived antibody reactivity, circulating immune complexes, and clinical course and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS Serum samples, obtained from untreated patients with squamous cell carcinoma of the larynx entered onto a multiinstitutional trial, were evaluated for the presence of elevated circulating immune complexes (221 patients) and host-derived antibody directed against two SCCHN cell lines (107 patients). RESULTS Patients had significantly elevated levels of circulating immune complexes as measured by C1q binding compared with normal controls. Patients with higher levels of circulating immune complexes were less likely to respond to chemotherapy. No correlations were noted between immune complex levels and stage of disease, nodal status, site of disease, recurrence, or survival. Evaluation of native antibody titers for their relationship to clinical correlates showed no statistically significant associations. In sera subjected to immune complex dissociation, patients with moderately or poorly differentiated tumors had significantly higher antibody titers when compared with patients with well-differentiated tumors. Because marked variation in the increase of antibody titers following immune complex dissociation was noted, the ratio of immune complex-dissociated to native antibody titer was examined. Patients with a high ratio had a lower proportion of complete and partial responses to chemotherapy. CONCLUSION Our results support the conclusion that the formation of tumor-associated immune complexes in patients with SCCHN is associated with a decreased response to chemotherapy.
Late relapse in early-stage Hodgkin's disease patients enrolled on European Organization for Research and Treatment of Cancer protocols.
Authors: Bodis S , Henry-Amar M , Bosq J , Burgers J M , Mellink W A , Dietrich P Y , Dupouy N , Noordijk E M , Raemaekers J M , Thomas J 
Published: February 2017

PURPOSE The great majority of relapses after the treatment for early-stage Hodgkin's disease are observed within 4 to 5 years after treatment completion. This study describes the characteristics and outcome of patients who had late relapses, which was defined as relapses that occurred 5 or more years after initial treatment start. PATIENTS AND METHODS A total of 1,082 adult patients with early clinical stage Hodgkin's disease were enrolled on three consecutive European Organization for Research and Treatment of Cancer (EORTC) protocols (H1, H2, and H5 trials) from 1964 to 1981. Of these, 1,044 patients satisfied the eligibility criteria with a supradiaphragmatic localization, age greater than 15 years, and initial complete remission. Overall, 341 patients (32.6%) relapsed, 304 (29.1%) early and 37 (3.5%) late. For each of these 37 late relapsers, questionnaires were sent to the participating centers and detailed information for 34 relapses was obtained. Cumulative probabilities for developing a late relapse were estimated using the Kaplan and Meier method. Quantification of the relationship between late relapse and several confounding variables was performed using the Cox's proportional hazards model. RESULTS The 10- and 15-year cumulative probabilities of late relapse in patients who were disease-free at 5 years were 4.8% and 8.3%, respectively. Patients treated on more recent protocols had a higher incidence of late relapse, possibly due to an attempt to tailor therapy to the specific prognostic factors (10-year cumulative probabilities, 4.6%, 2.6%, and 7.5% in trials H1, H2, and H5, respectively). Incidence of late relapses significantly correlated with male sex, B symptoms, mediastinal involvement, and treatment modality. Salvage treatment induced a complete response in 27 patients (79%) and a prolonged complete remission in 24 patients (71%). Twenty years after initial treatment start, similar overall survival rates were observed for late relapsing (72%) and nonrelapsing patients (75%). CONCLUSION Late relapses of Hodgkin's disease are uncommon, but may be more frequent with recent protocols tailored to specific prognostic factors. If treated, their outcome is favorable. Late relapse is therefore another factor indicating that careful, long-term follow-up is needed for patients with Hodgkin's disease.
Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias.
Authors: Schwartz M A , Lovett D R , Redner A , Finn R D , Graham M C , Divgi C R , Dantis L , Gee T S , Andreeff M , Old L J 
Published: February 2017

PURPOSE Mouse monoclonal antibody (mAb) M195 (anti-CD33) is reactive with most myeloid leukemia cells, monocytes, and hematopoietic progenitors, but not with other hematopoietic cells or stem cells nor with nonhematopoietic human tissues. A therapeutic dose-escalation study of M195 labeled with iodine 131 was conducted in patients with relapsed or refractory myeloid leukemias. METHODS Twenty-four patients (16 relapsed or refractory acute myeloid leukemias, five blastic myelodysplastic syndromes [MDS], two chemotherapy-related secondary leukemias, and one blastic chronic myelogenous leukemia [CML]), including seven who had failed to respond to prior bone marrow transplantation (BMT), received from 50 mCi/m2 to 210 mCi/m2 of 131I-M195 in divided doses. RESULTS In 22 patients, whole-body gamma-imaging demonstrated marked uptake of antibody into all areas of bone marrow. Twenty-three patients (96%) demonstrated decreases in peripheral-blood cell counts, with decreased percentage of bone marrow blasts seen in 83% of cases. Eighty-nine percent of bone marrow biopsies examined quantitatively demonstrated substantial decreases in the number of blasts, with greater than 99% of blasts killed in some patients. The two cases that failed to demonstrate leukemic cytoreduction occurred in the first two dose levels. For 131I doses of 135 mCi/m2 or greater, pancytopenia was profound and lasted for at least 12 days. Eight patients had sufficient marrow cytoreduction to proceed to BMT. Three of these achieved marrow remission, one of 6+, and one of 9 months' duration. Two patients in blastic phase temporarily reverted to their original myelodysplastic states. Thirty-seven percent of assessable patients developed human anti-mouse antibody (HAMA). In two patients with HAMA who were re-treated, plasma 131I-M195 levels could not be maintained and no therapeutic effect resulted. Significant nonhematologic toxicity (hepatic) was seen in one patient and the maximum-tolerated dose (MTD) was not reached. CONCLUSION These data suggest that safe leukemic cytoreduction can be achieved with 131I-M195 even in multiply relapsed or chemotherapy-refractory leukemias. This agent may be useful as part of a preparative regimen for BMT.
Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group.
Authors: Murray N , Coy P , Pater J L , Hodson I , Arnold A , Zee B C , Payne D , Kostashuk E C , Evans W K , Dixon P 
Published: February 2017

PURPOSE The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial. METHODS All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks). RESULTS Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006). CONCLUSION The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI.
Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.
Authors: Kaufmann M , Jonat W , Abel U , Hilfrich J , Caffier H , Kreienberg R , Trams G , Brunnert K , Schermann J , Kleine W 
Published: February 2017

PURPOSE We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.
Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group.
Authors: Grossman S A , Finkelstein D M , Ruckdeschel J C , Trump D L , Moynihan T , Ettinger D S 
Published: February 2017

PURPOSE This prospective randomized cooperative group study was conducted in patients with neoplastic meningitis treated with intrathecal methotrexate or thiotepa to assess response rates and survival, prognostic factors, and the toxicity of these regimens. PATIENTS AND METHODS Fifty-nine adults with nonleukemic malignancies, performance status of 0 to 3, and positive CSF cytologies were assigned to receive intrathecal methotrexate (10 mg) or thiotepa (10 mg) twice weekly. Radiation, was administered to mass lesions and/or symptomatic sites and appropriate systemic therapy was given concomitantly. RESULTS Fifty-two patients were assessable. Most were female (79%), nonambulatory (77%), had been pretreated with radiation (52%) and chemotherapy (77%), and had evidence of systemic disease (65%). Most primary cancers were of the breast (48%), lung (23%), or lymphatics (19%). Treatment arms were well balanced, except that more patients randomized to methotrexate had breast cancer (61% v 33%) and were without evidence of systemic cancer (21% v 4%). No patient had important neurologic improvement with therapy, and 75% deteriorated neurologically within 8 weeks of initiating therapy. Survival ranged from 4 days to 110.5+ weeks. Median survival for patients receiving methotrexate was 15.9 weeks and 14.1 weeks for patients treated with thiotepa. Factors predictive of shorter survival included progressive systemic disease (P = .0005), poor performance status (P = .03), and significant cranial nerve palsies (P = .02). Although serious toxicities were similar, mucositis (P = .04) and neurologic complications (P = .008) were more common in patients who received methotrexate. CONCLUSION The efficacy and overall toxicities of intraventricular methotrexate and thiotepa seem similar and neither reverses fixed neurologic deficits. Early diagnosis and treatment and new therapeutic approaches are needed to improve the outcome for patients with neoplastic meningitis.
Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy.
Authors: Dana B W , Dahlberg S , Nathwani B N , Chase E , Coltman C , Miller T P , Fisher R I 
Published: February 2017

PURPOSE We reviewed survival data of patients with low-grade lymphoma entered on Southwest Oncology Group (SWOG) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) in such patients. PATIENTS AND METHODS We identified all patients with low-grade lymphoma, no prior therapy, and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204, 7426, or 7713. Survival data for this group of patients were correlated with pretreatment prognostic factors, including histology, patient age, sex, symptom status, performance status, bone marrow or extranodal involvement, and the number of disease sites. The effect of maintenance treatment was also assessed. RESULTS Four hundred fifteen patients met criteria for inclusion in the study group. With median follow-up periods of 12.8 years (maximum, 19.8 years), the median survival duration was 6.9 years. Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology, age greater than 40 years, male sex, B-symptom status, and SWOG performance status greater than 1. Multivariate regression analysis showed histology, age, and sex to be independent predictors of survival. There was no definite survival plateau of cured patients in any subgroup, although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25%. Maintenance therapy did not prolong survival. CONCLUSION Doxorubicin-containing treatment did not prolong the overall median survival of low-grade lymphoma patients compared with results with less-aggressive programs.
High complete remission rate from 2-chloro-2'-deoxyadenosine in previously treated patients with B-cell chronic lymphocytic leukemia: response predicted by rapid decrease of blood lymphocyte count.
Authors: Juliusson G , Liliemark J 
Published: February 2017

PURPOSE This study attempted to characterize the response of previously treated patients with B-cell chronic lymphocytic leukemia (CLL) to the purine analog 2-chloro-2'-deoxyadenosine (CdA) and to assess factors that predict response. PATIENTS AND METHODS We treated 18 CLL patients with about-monthly courses of five daily 2-hour intravenous infusions of 0.12 mg CdA/kg. RESULTS Complete remissions (CRs) were achieved in seven patients (39%), with a total response rate of 67%. CR patients received a median of 4.5 courses. One patient with CR relapsed and died 14 months from start of CdA treatment, whereas the other six patients with CR remain in remission following a mean observation period of 14 months. The median duration of partial remissions (PRs) was 9 months, with a median treatment-free interval of 15 months. Thrombocytopenia was the most common dose-limiting toxicity. Non-responding patients had a median survival of 3.5 months, and systemic fungal infections were the most common cause of death. Immunoglobulin (Ig) levels improved significantly in hypogammaglobulinemic patients during CdA treatment. Responses were predicted by a rapid decrease of blood lymphocyte counts following the first treatment course. CONCLUSION A high CR rate was achieved with limited toxicity. A treatment strategy to enable high-quality response and limitation of treatment-related toxicity is provided.
Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms.
Authors: Grossbard M L , Lambert J M , Goldmacher V S , Spector N L , Kinsella J , Eliseo L , Coral F , Taylor J A , Blättler W A , Epstein C L 
Published: February 2017

PURPOSE This phase I trial was undertaken to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the B-cell-restricted immunotoxin anti-B4-blocked ricin (anti-B4-bR) when it is administered by 7-day continuous infusion. PATIENTS AND METHODS Thirty-four patients with relapsed and refractory B-cell neoplasms (26 non-Hodgkin's lymphoma [NHL], four chronic lymphocytic leukemia [CLL], four acute lymphoblastic leukemia [ALL]) received 7-day continuous infusion anti-B4-bR. Successive cohorts of at least three patients were treated at doses of 10 to 70 micrograms/kg/d for 7 days with the dose increased by 10 micrograms/kg/d for each cohort. The initial three cohorts of patients (10, 20, and 30 micrograms/kg/d x 7 days) also received a bolus infusion of 20 micrograms/kg before beginning the continuous infusion. RESULTS The MTD was reached at 50 micrograms/kg/d x 7 days. The DLTs were National Cancer Institute Common Toxicity Criteria (NCI CTC) grade IV reversible increases in AST and ALT, and grade IV decreases in platelet counts. Adverse reactions included fevers, nausea, headaches, myalgias, hypoalbuminemia, dyspnea, edema, and capillary leak syndrome. Potentially therapeutic serum levels of anti-B4-bR could be sustained for 4 days in patients treated at the MTD. Two complete responses (CRs), three partial responses (PRs), and 11 transient responses (TRs) were observed. CONCLUSION Anti-B4-bR can be administered safely by 7-day continuous infusion with tolerable, reversible toxicities to patients with relapsed B-cell neoplasms. Although occasional responses were seen, future trials will use anti-B4-bR in patients with lower tumor burdens to circumvent the obstacle of immunotoxin delivery to bulk disease.
Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.
Authors: Loprinzi C L , Michalak J C , Schaid D J , Mailliard J A , Athmann L M , Goldberg R M , Tschetter L K , Hatfield A K , Morton R F 
Published: February 2017

PURPOSE Several placebo-controlled randomized clinical trials have demonstrated that megestrol acetate can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/d. METHODS This trial randomized 342 assessable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800, or 1,280 mg/d. Patients were evaluated monthly by history, examination, patient-completed questionnaires, and serum albumin levels. RESULTS The data demonstrate that there is a positive dose-response effect for megestrol acetate on appetite stimulation (P < or = .02). In concert, there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. CONCLUSION The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature. Nonetheless, based primarily on the cost and inconvenience associated with the use of higher doses of this drug, it is reasonable to use 160 mg/d for the initial treatment of cancer anorexia/cachexia in routine clinical practice.
The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women.
Authors: Smith T J , Hillner B E 
Published: February 2017

PURPOSE AND METHODS We used decision analysis to model the natural history of breast cancer in hypothetical cohorts of 45-year-old women receiving tamoxifen, chemotherapy, or combined therapy. We used recurrence and efficacy data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), utility values from focus groups, and costs from clinic charges and Medicare data. RESULTS Tamoxifen alone provides minimal benefit in estrogen receptor-negative (ER-; 0.2 to 0.4 months) and modest benefit in receptor-positive (ER+; 3.5 to 5.2 months) cancer. Chemotherapy adds substantial benefit independent of receptor status (4.9 to 10.7 quality-adjusted months). In ER+ cancer, combined therapy adds an additional benefit (1.2 to 2.1 months) compared with chemotherapy alone. The incremental costs (United States dollars) necessary to add an additional year of life to the average woman ranged from $4,300 to $11,400 for tamoxifen alone for ER+ cancer, $4,900 to $11,400 for chemotherapy alone, and $14,800 to $33,100 for combined therapy. CONCLUSION In premenopausal early-stage breast cancer, chemotherapy adds substantial clinical benefit at a modest cost. Tamoxifen alone adds meaningful benefit only in ER+ cancer. Combined therapy is effective for all women, but is most beneficial and only cost-effective in ER+ women. If secondary effects of tamoxifen in reduction of cardiovascular and osteoporosis mortality are confirmed, then combined treatment may be optimal for all premenopausal women.
Intermediate lymphocytic lymphoma: clinical and pathologic features of a recently characterized subtype of non-Hodgkin's lymphoma.
Authors: Shivdasani R A , Hess J L , Skarin A T , Pinkus G S 
Published: February 2017

PURPOSE We present a comprehensive review of clinical, pathologic, molecular, and prognostic features and therapy of intermediate lymphocytic (mantle cell) lymphoma (ILL/MCL), a recently characterized subtype that represents 2% to 8% of non-Hodgkin's lymphomas (NHLs), but which has not been included in most classification schemes, including the International Working Formulation. DESIGN The English-language literature encompassing the above aspects, published between 1977 and 1992, is critically reviewed. RESULTS AND CONCLUSION ILL/MCL is a disease of proliferating B lymphocytes that is characterized by generalized lymphadenopathy and frequent, often extensive, involvement of the spleen, bone marrow, and gastrointestinal tract. The malignant cells usually express the markers CD5 and IgM with or without IgD, but not CD10, on the cell surface, and grow in one of two dominant histologic patterns: mantle zone and diffuse. The characteristic cytogenetic abnormality is a t(11;14)(q13;q32) translocation, which juxtaposes the bcl-1 locus on chromosome 11 with the immunoglobulin (Ig) heavy-chain locus on chromosome 14, and appears to result in dysregulated expression of the gene encoding cyclin D1. Median survival is in the range of 2 to 5 years. While responses to chemotherapy may be seen in up to half the patients, relapses are the rule, and longterm survival is uncommon. The optimal treatment remains undefined, although therapy may be deferred until there are symptoms or complications, at which time judicious administration of alkylating agents and glucocorticoids may result in effective palliation.