bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synchronous and Metachronous Squamous Cell Carcinomas of the Head and Neck Mucosal Sites
Authors: Erkal Haldun Ş. , Mendenhall William M. , Amdur Robert J. , Villaret Douglas B. , Stringer Scott P. 
Published: February 2017

PURPOSE: The present study presents the experience at the University of Florida with synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. PATIENTS AND METHODS: This study included 1,112 patients with squamous cell carcinomas of the oropharynx, hypopharynx, and supraglottic larynx treated with radiation therapy with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: The overall survival rate was 45% and the disease-specific survival rate was 67% at 5 years after initial diagnosis of carcinoma of the head and neck mucosal sites. Seventy-seven patients (7%) presented with synchronous carcinomas of the head and neck mucosal sites and 103 patients (9%) developed metachronous carcinomas of the head and neck mucosal sites at 0.6 to 21.7 years (median, 3.6 years). The overall survival rate was 31%, and the disease-specific survival rate was 50% at 5 years after metachronous carcinomas of the head and neck mucosal sites. Seven patients (1%) developed metachronous carcinomas of the thoracic esophagus at 1 to 11.1 years (median, 2.8 years), 15 patients (1%) presented with synchronous carcinomas of the lung, and 83 patients (7%) developed metachronous carcinomas of the lung at 0.6 to 17.6 years (median, 3.5 years). CONCLUSION: Development of synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites are in part responsible for failure to improve overall survival rates for patients with squamous cell carcinomas of the head and neck mucosal sites, justifying rigorous follow-up and studies on chemoprevention.
Reproductive Factors and Risk of Intermediate- or High-Grade B-Cell Non-Hodgkin’s Lymphoma in Women
Authors: Nelson Rebecca A. , Levine Alexandra M. , Bernstein Leslie 
Published: February 2017

PURPOSE: The incidence rates of non-Hodgkin’s lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.
Autologous Stem-Cell Transplantation for Hodgkin’s Disease: Results and Prognostic Factors in 494 Patients From the Grupo Español de Linfomas/Transplante Autólogo de Médula Ósea Spanish Cooperative Group
Authors: Sureda A. , Arranz R. , Iriondo A. , Carreras E. , Lahuerta J.J. , García-Conde J. , Jarque I. , Caballero M.D. , Ferrà C. , López A. , García-Laraña J. , Cabrera R. , Carrera D. , Ruiz-Romero M.D. , León A. , Rifón J. , Díaz-Mediavilla J. , Mataix R. , Morey M. , Moraleda J.M. , Altés A. , López-Guillermo A. , de la Serna J. , Fernández-Rañada J.M. , Sierra J. , Conde E. 
Published: February 2017

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin’s disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Ósea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age ≥ 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.
Mutations With Loss of Heterozygosity of p53 Are Common in Therapy-Related Myelodysplasia and Acute Myeloid Leukemia After Exposure to Alkylating Agents and Significantly Associated With Deletion or Loss of 5q, a Complex Karyotype, and a Poor Prognosis
Authors: Christiansen Debes H. , Andersen Mette K. , Pedersen-Bjergaard Jens 
Published: February 2017

PURPOSE: To study mutations and loss of heterozygosity (LOH) of p53 in therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML). PATIENTS AND METHODS: Fifty-two unselected patients with t-MDS and 25 patients with t-AML were studied by polymerase chain reaction (PCR)–single-strand conformational polymorphism (SSCP) at the DNA level and by reverse transcriptase (RT)-PCR–SSCP at the mRNA level, and cases with aberrant SSCP patterns were sequenced. RESULTS: Somatically acquired mutations of p53 were observed in 21 of 77 cases of t-MDS or t-AML, and 19 of these 21 patients had received alkylating agents. Single-base substitutions at A:T pairs were more common in t-MDS and t-AML, whereas single-base substitutions at G:C pairs are most common in MDS and AML de novo and in solid tumors. Six patients demonstrated a cytogenetic loss of 17p13, and these six and an additional nine patients with p53 mutations demonstrated LOH of p53 at the DNA or mRNA level. This suggests a cytogenetic loss of the normal p53 allele in these nine cases combined with duplication of the homologous chromosome 17 carrying the mutated p53 allele. Mutations of p53 were significantly associated with deletion or loss of 5q (P < .0001) and a complex karyotype (P = .0001), but surprisingly were not associated with deletion or loss of 7q (P = .73), and were infrequent in patients with balanced chromosome translocations (P = .03). Mutations of p53 were more common in older patients (P = .036) and were associated with an extremely poor prognosis (P = .014), apparently restricted to the 15 cases with LOH of p53 ( P = .046). CONCLUSION: Mutations with loss of function of p53 are significantly associated with deletion or loss of 5q in t-MDS and t-AML after previous treatment with alkylating agents and are associated with genetic instability.
Results of the Fludarabine and Cyclophosphamide Combination Regimen in Chronic Lymphocytic Leukemia
Authors: O’Brien Susan M. , Kantarjian Hagop M. , Cortes Jorge , Beran Miloslav , Koller Charles A. , Giles Francis J. , Lerner Susan , Keating Michael 
Published: February 2017

PURPOSE: To assess the efficacy of combination therapy with fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia (CLL) based on data suggesting in vitro synergistic activity of the two agents. PATIENTS AND METHODS: A total of 128 patients with CLL were treated with fludarabine 30 mg/m2 intravenously daily for 3 days and cyclophosphamide at either 500 mg/m2 daily for 3 days (n = 11), 350 mg/m2/d for 3 days (n = 26), or 300 mg/m2 daily for 3 days (n = 91). The cyclophosphamide dose was decreased because of myelosuppression in the early part of the study. Patients were divided into four groups based on the expectation for response to single-agent fludarabine, including previously untreated patients, patients previously treated with alkylating agents, patients successfully treated with alkylating agents and fludarabine but relapsing, and patients refractory to fludarabine with or without alkylating agents. RESULTS: Fludarabine and cyclophosphamide produced ≥ 80% response rates in all patients not refractory to fludarabine at the start of therapy as well as a 38% response rate in patients who were refractory to fludarabine. The complete remission (CR) rate was 35% in previously untreated patients, which was not significantly different from the CR rate in historical control patients treated with single-agent fludarabine. However, residual disease assessed by flow cytometry occurred in only 8% of previously untreated patients achieving CR, and median time to progression has not been reached after a median follow-up of 41 months. The main complication of therapy was related to myelosuppression and infection. Neutropenia to less than 500 × 109/L was noted in 48% of patients who received cyclophosphamide 300 mg/m2. Pneumonia or sepsis occurred in 25% of patients, and fever of unknown origin occurred in another 25%. Pneumonia or sepsis were significantly more frequent in patients who were refractory to fludarabine at the start of combination chemotherapy. CONCLUSION: Fludarabine and cyclophosphamide seem to have a significant advantage over single-agent fludarabine in the salvage setting. Although the CR rate was not increased in previously untreated patients, residual disease detected by flow cytometry was rare and remission durations seemed to be prolonged in this subset. Myelosuppression and infection remain the most significant complications of therapy in CLL.
High-Dose Interferon Alfa-2b Does Not Diminish Antibody Response to GM2 Vaccination in Patients With Resected Melanoma: Results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696
Authors: Kirkwood John M. , Ibrahim Joseph , Lawson David H. , Atkins Michael B. , Agarwala Sanjiv S. , Collins Keirsten , Mascari Ruth , Morrissey Donna M. , Chapman Paul B. 
Published: February 2017

PURPOSE: High-dose interferon alfa-2b (IFNα2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNα2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNα2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNα2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies. PATIENTS AND METHODS: This trial enrolled 107 patients with resectable high- or very high–risk melanoma (AJCC stages IIB, III, and IV). RESULTS: The results demonstrate that IFNα2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNα2b and GMK is well tolerated in this patient population. CONCLUSION: Cox analysis of the results of the combination with IFNα2b show improvement in the relapse-free survival of patients with very high–risk melanoma (including those with resectable M1 disease).
Patterns of Use of Chemotherapy for Breast Cancer in Older Women: Findings From Medicare Claims Data
Authors: Du Xianglin , Goodwin James S. 
Published: February 2017

PURPOSE: There is little population-based information available on the use of chemotherapy in women with breast cancer. This study describes the use of chemotherapy through analysis of Medicare claims and determines the correlates of chemotherapy use. PATIENTS AND METHODS: We used the merged Surveillance, Epidemiology, and End Results–Medicare database and identified women ≥ 65 years of age diagnosed with breast cancer in 1991 and 1992. Chemotherapy was ascertained from Medicare claims through procedure codes for chemotherapy made within 24 months of the diagnosis. RESULTS: In women with stages I, II, III, and IV breast cancer, the percentage receiving chemotherapy within 24 months of diagnosis was 5.1%, 19.5%, 33.9%, and 35.2%, respectively. Most women receiving chemotherapy had two to 12 claims; the median number was eight. Use of chemotherapy decreased significantly with age across all tumor stages; eg, in women with stage III cancer, the use of chemotherapy declined from 49% in those aged 65 to 69 years to 10% in those ≥ 80 years old. In a multivariate analysis, there was little variation by ethnicity. Chemotherapy use was highest (70%) in women aged 65 to 69 years with node-positive and estrogen receptor–negative tumors and lowest (5%) in those with node-negative and estrogen receptor–positive tumors. Compared with those without comorbid diseases, patients with a comorbidity score of 2 had significantly lower use of chemotherapy. CONCLUSION: Medicare claims data seem to provide valuable information on the use of chemotherapy for breast cancer in older women. However, external validation of the accuracy and completeness of these data is required before any firm conclusion can be drawn.
Nipple Fluid Carcinoembryonic Antigen and Prostate-Specific Antigen in Cancer-Bearing and Tumor-Free Breasts
Authors: Zhao Yashuang , Verselis Sigitas J. , Klar Neil , Sadowsky Norman L. , Kaelin Carolyn M. , Smith Barbara , Foretova Lenka , Li Frederick P. 
Published: February 2017

PURPOSE: Mammograms and breast examinations are established methods for early breast cancer detection. Routine mammography screening reduces breast cancer mortality among women ages ≥ 50 years, but additional screening methods are needed. We and others have found high levels of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) in nipple aspirate fluids (NAFs), but the usefulness for these bio-markers for early breast cancer detection is unknown. PATIENTS AND METHODS: NAFs from one or both breasts of 388 women were analyzed for CEA, PSA, and albumin levels. The study included 44 women with newly diagnosed invasive breast cancers, 67 women with proliferative breast lesions (ductal and lobular carcinoma in situ and atypical ductal hyperplasia), and 277 controls without these breast lesions. Analyses were conducted using the log10-transformed CEA and PSA levels to normalize the distributions of these tumor markers. RESULTS: Nipple fluid CEAs are significantly higher for cancerous breasts than tumor-free breasts (median 1,830 and 1,400 ng/mL, respectively; P < .01). However, at 90% specificity of the assay (CEA = 11,750 ng/mL), the corresponding sensitivity for cancer detection is 32%. CEA levels are not significantly different for breasts with proliferative lesions compared with tumor-free breasts. Nipple fluid PSAs do not differ by tumor status. Analyses of NAF albumin-standardized CEAs and PSAs yield similar results. Nipple fluid CEA and PSA titers are correlated in the affected and unaffected breast of women with unilateral lesions. CONCLUSION: Nipple fluid CEAs are higher for breasts with untreated invasive cancers, but the test sensitivity is low. Nipple fluid PSA titers do not seem to be useful for breast cancer detection.
Phase I and Pharmacokinetic Study of Exatecan Mesylate (DX-8951f): A Novel Camptothecin Analog
Authors: Royce Melanie E. , Hoff Paulo M. , Dumas Pamela , Lassere Yvonne , Lee J. Jack , Coyle John , Ducharme Murray P. , De Jager Robert , Pazdur Richard 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3 weeks to patients with solid tumors. PATIENTS AND METHODS: Twenty-two patients with advanced solid tumors, all previously treated, and with performance status ≤ 2, were entered. The starting dose of DX-8951f was 0.15 mg/m2; the dose was escalated according to the modified continual reassessment method. The drug was administered until disease progression or until unacceptable toxic effects occurred. RESULTS: Seven dose escalations were completed, and a total of 53 courses were delivered (median, two courses; range, one to eight courses) during the study. At doses 1.2 mg/m2 and lower, toxicities were mostly grade 1, primarily hematologic. In the initial cohort of three patients treated at 2.4 mg/m2, grade 2 hematologic toxicity was observed. Of the six additional patients entered at 2.4 mg/m2, three had grade 3 or 4 granulocytopenia. At doses higher than 2.4 mg/m2, DLT granulocytopenia was observed. Nonhematologic toxicities, including nausea, vomiting, diarrhea, fatigue, and alopecia, were mild to moderate. Neither complete nor partial responses were observed, but four patients had stable disease. The PK profile of DX-8951f seemed linear at the doses administered. The plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours, respectively. CONCLUSION: The DLT of this DX-8951f schedule was granulocytopenia for minimally pretreated patients, and both granulocytopenia and thrombocytopenia for heavily pretreated patients. The MTD for both minimally and heavily pretreated patients was 2.4 mg/m2. DX-8951f seems to have a linear PK profile on the basis of single-dose administration. The recommended phase II dose with this schedule is 2.4 mg/m2 for minimally pretreated patients. A lower dose should be used for heavily pretreated patients.
Phase I/II Study of the P-Glycoprotein Modulator PSC 833 in Patients With Acute Myeloid Leukemia
Authors: Dorr R. , Karanes C. , Spier C. , Grogan T. , Greer J. , Moore J. , Weinberger B. , Schiller G. , Pearce T. , Litchman M. , Dalton W. , Roe D. , List A. F. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m2/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/kg/d. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m2 of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P = .04). Daunorubicinol clearance decreased 3.3-fold (P = .016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.
Second-Line Chemotherapy in Patients With Relapsed Extragonadal Nonseminomatous Germ Cell Tumors: Results of an International Multicenter Analysis
Authors: Hartmann Jörg T. , Einhorn Lawrence , Nichols Craig R. , Droz Jean-P. , Horwich Alan , Gerl Arthur , Fossa Sophie D. , Beyer Jörg , Pont Jörg , Schmoll Hans-J. , Kanz Lothar , Bokemeyer Carsten 
Published: February 2017

PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival. PATIENTS AND METHODS: We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment. RESULTS: Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P = .003), sensitivity to cisplatin (P = .003), elevated β-HCG at relapse (P = .04), and normal LDH at diagnosis (P = .01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis. CONCLUSION: Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.