bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Study of the Clinical Course, Prognostic Factors, Causes of Death, and Survival in Patients With Long-Standing Zollinger-Ellison Syndrome
Authors: Yu Fang , Venzon David J. , Serrano Jose , Goebel Stephan U. , Doppman John L. , Gibril Fathia , Jensen Robert T. 
Published: February 2017

PURPOSE: The long-term clinical course of unselected patients with gastrinomas as well as other functional pancreatic endocrine tumors (PETs) in whom the excess-hormone state is controlled is largely unknown. To address this issue, patients with gastrinomas were assessed. PATIENTS AND METHODS: Two hundred twelve patients with Zollinger-Ellison syndrome (ZES) were prospectively studied. All had controlled acid hypersecretion and were assessed yearly, with a mean follow-up period of 13.8 ± 0.6 years (range, 0.1 to 31 years). Annual assessments of possible factors that might affect prognosis or treatment approaches were performed, such as those for tumor size and location; the presence, location, and extent of metastases; and the occurrence of ectopic Cushing's syndrome or another PET syndrome. Deaths were categorized as ZES-related or non–ZES-related and classified into different causes. RESULTS: Thirty-one percent of patients died, all of non–acid-related causes. One half died of a ZES-related cause; they differed from those who died of non–ZES deaths by having a large primary tumor, more frequently a pancreatic tumor; lymph node, liver, or bone metastases; ectopic Cushing's syndrome; or higher gastrin levels. The extent of liver metastases correlated with survival rate. The presence of liver metastases alone only moderately decreased survival time; however, the additional development of bone metastases or ectopic Cushing's syndrome markedly decreased survival rate. CONCLUSIONS: In ZES, gastrinoma growth is now the main single determinant of long-term survival, with one half of patients dying a gastrinoma-related death and none an acid-related death. Large primary tumors that are pancreatic in location, the development of liver metastases, (especially if associated with bone metastases or Cushing's syndrome), and the extent of liver metastases are all important prognostic factors. The identification of these factors allows the recognition of subgroups that can be used to tailor antitumor treatment approaches.
Preradiotherapy Computed Tomography as a Predictor of Local Control in Supraglottic Carcinoma
Authors: Mancuso Anthony A. , Mukherji Suresh K. , Schmalfuss Ilona , Mendenhall William , Parsons James , Pameijer Frank , Hermans Robert , Kubilis Paul 
Published: February 2017

PURPOSE: To determine the utility of pretreatment computed tomography (CT) for predicting primary site control in patients with supraglottic squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT). MATERIALS AND METHODS: Pretreatment CT studies in 63 patients were reviewed. Minimum length of follow-up was 2 years. Local recurrence and treatment complications resulting in permanent loss of laryngeal function were documented. Tumor volume was calculated using a computer digitizer, and pre-epiglottic space (PES) spread was estimated. The data were analyzed using a combination of Fisher's exact test, logistic regression modeling, and multivariate analyses. Five-year local control rates were calculated using the product-limit method. RESULTS: Local control rates were inversely and roughly linearly related to tumor volume, although there seemed to be a threshold volume at which primary site prognosis diminished. Local control was 89% in tumors less than 6 cm3 and 52% when volumes were ≥ 6 cm3 (P = .0012). The likelihood of maintaining laryngeal function also varied with tumor volume: 89% for tumors less than 6 cm3 and 40% for tumors ≥ 6 cm3 (P = .00004). Pre-epiglottic space involvement by tumor of ≥ 25% was associated with a reduced chance of saving the larynx (P = .0076). Multivariate analyses revealed that only tumor volume independently altered these end points. CONCLUSION: Pretreatment CT measurements of tumor volume permits stratification of patients with supraglottic SCC treated with RT alone (which allows preservation of laryngeal function) into groups in which local control is more likely and less likely. Pre-epiglottic space spread is not a contraindication to using RT as the primary treatment for supraglottic SCC.
Procarbazine and High-Dose Tamoxifen as a Second-Line Regimen in Recurrent High-Grade Gliomas: A Phase II Study
Authors: Brandes Alba A. , Ermani Mario , Turazzi Sergio , Scelzi Elvira , Berti Franco , Amistà Pietro , Rotilio Antonino , Licata Claudio , Fiorentino Mario V. 
Published: February 2017

PURPOSE: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m2/d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33 weeks for patients with AA (P = .006). The median survival time (MST) was 27 weeks for patients with GBM and 57 weeks for those with AA (P = .006). CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it was not followed by an increased TTP or MST.
Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer
Authors: Graziano Stephen L. , Gamble Gary P. , Newman Nancy B. , Abbott Lynn Z. , Rooney Michelle , Mookherjee Sulagna , Lamb Melissa L. , Kohman Leslie J. , Poiesz Bernard J. 
Published: February 2017

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.
Phase I and Pharmacokinetic Trial of Oral Irinotecan Administered Daily for 5 Days Every 3 Weeks in Patients With Solid Tumors
Authors: Drengler Ronald L. , Kuhn John G. , Schaaf Larry J. , Rodriguez Gladys I. , Villalona-Calero Miguel A. , Hammond Lisa A. , Stephenson, Jr. Joseph A. , Hodges Stephanie , Kraynak Maura A. , Staton Brian A. , Elfring Gary L. , Locker Paula K. , Miller Langdon L. , Von Hoff Daniel D. , Rothenberg Mace L. 
Published: February 2017

PURPOSE: We conducted a phase I dose-escalation trial of orally administered irinotecan (CPT-11) to characterize the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetic profile, and antitumor effects in patients with refractory malignancies. PATIENTS AND METHODS: CPT-11 solution for intravenous (IV) use was mixed with CranGrape juice (Ocean Spray, Lakeville-Middleboro, MA) and administered orally once per day for 5 days every 3 weeks to 28 patients. Starting dosages ranged from 20 to 100 mg/m2/d. RESULTS: Grade 4 delayed diarrhea was the DLT at the 80 mg/m2/d dosage in patients younger than 65 years of age and at the 66 mg/m2/d dosage in patients 65 or older. The other most clinically significant toxicity of oral CPT-11 was neutropenia. A linear relationship was found between dose, peak plasma concentration, and area under the concentration-time curve (AUC) for both CPT-11 and SN-38 lactone, implying no saturation in the conversion of irinotecan to SN-38. The mean metabolic ratio ([AUCSN-38 total + AUCSN-38G total]/AUCCPT-11 total) was 0.7 to 0.8, which suggests that oral dosing results in presystemic conversion of CPT-11 to SN-38. An average of 72% of SN-38 was maintained in the lactone form during the first 24 hours after drug administration. One patient with previously treated colorectal cancer and liver metastases who received oral CPT-11 at the 80 mg/m2/d dosage achieved a confirmed partial response. CONCLUSION: The MTD and recommended phase II dosage for oral CPT-11 is 66 mg/m2/d in patients younger than 65 years of age and 50 mg/m2/d in patients 65 or older, administered daily for 5 days every 3 weeks. The DLT of diarrhea is similar to that observed with IV administration of CPT-11. The biologic activity and favorable pharmacokinetic characteristics make oral administration of CPT-11 an attractive option for further clinical development.
Phase I Study of Liposomal Vincristine
Authors: Gelmon K. A. , Tolcher A. , Diab A. R. , Bally M. B. , Embree L. , Hudon N. , Dedhar C. , Ayers D. , Eisen A. , Melosky B. , Burge C. , Logan P. , Mayer L. D. 
Published: February 2017

PURPOSE: A phase I study of vincristine encapsulated inside 120-nm-diameter distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary objectives were to determine the maximum-tolerated dose (MTD), recommended phase II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS). PATIENTS AND METHODS: Twenty-five patients with histologically confirmed malignancies were enrolled and assessable. Vincristine doses were increased from 0.5 mg/m2 to 1.0, 1.5, 2.0, 2.4, and 2.8 mg/m2 with cohorts of three or more patients per dose level. A total of 64 courses of ONCO-TCS were administered intravenously once every 3 weeks. The pharmacokinetics of total vincristine content in plasma were determined using a high-performance liquid chromatography method. RESULTS: Patients were treated with vincristine doses up to 2.8 mg/m2; however, 2.4 mg/m2 was defined as the MTD and 2.0 mg/m2 as the phase II recommended dose. Pain and obstipation were the dose-limiting toxicites. Other toxicities were fever, rigors, fatigue, myalgias, and peripheral neuropathy. Hematologic toxicity was mild. All patients who were treated with doses above 1.5 mg/m2 received in excess of 2.0 mg of vincristine, with doses as high as 6.2 mg. One partial response was seen in a patient with pancreatic cancer. Tumor response not meeting partial response criteria was seen in two other patients. Pharmacokinetic studies revealed significantly elevated concentrations of total vincristine, but parameters varied and were not directly correlated with toxicity or response. CONCLUSION: The ability to administer elevated doses of vincristine, as well as indications of efficacy, suggests that ONCO-TCS warrants further clinical investigation in a phase II setting.
Recruiting Minority Cancer Patients Into Cancer Clinical Trials: A Pilot Project Involving the Eastern Cooperative Oncology Group and the National Medical Association
Authors: McCaskill-Stevens Worta , Pinto Harlan , Marcus Alfred C. , Comis Robert , Morgan Randall , Plomer Kathy , Schoentgen Sarah 
Published: February 2017

PURPOSE: Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted a study to identify barriers and solutions to African American accrual onto clinical trials. METHODS: We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992. Fifteen workshops were conducted using discussions and open-ended, self-administered questionnaires. RESULTS: Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%). ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v 4%). CONCLUSION: NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators.
Mechanisms of Action of and Resistance to Antitubulin Agents: Microtubule Dynamics, Drug Transport, and Cell Death
Authors: Dumontet Charles , Sikic Branimir I. 
Published: February 2017

PURPOSE: To analyze the available data concerning mechanisms of action of and mechanisms of resistance to the antitubulin agents, vinca alkaloids and taxanes, and more recently described compounds. DESIGN: We conducted a review of the literature on classic and recent antitubulin agents, focusing particularly on the relationships between antitubulin agents and their intracellular target, the soluble tubulin/microtubule complex. RESULTS AND CONCLUSION: Although it is widely accepted that antitubulin agents block cell division by inhibition of the mitotic spindle, the mechanism of action of antitubulin agents on microtubules remains to be determined. The classic approach is that vinca alkaloids depolymerize microtubules, thereby increasing the soluble tubulin pool, whereas taxanes stabilize microtubules and increase the microtubular mass. More recent data suggest that both classes of agents have a similar mechanism of action, involving the inhibition of microtubule dynamics. These data suggest that vinca alkaloids and taxanes may act synergistically as antitumor agents and may be administered as combination chemotherapy in the clinic. However, enhanced myeloid and neurologic toxicity, as well as a strong dependence on the sequence of administration, presently exclude these combinations outside the context of clinical trials. Although the multidrug resistance phenotype mediated by Pgp appears to be an important mechanism of resistance to these agents, alterations of microtubule structure resulting in altered microtubule dynamics and/or altered binding of antitubulin agents may constitute a significant mechanism of drug resistance.
Rituximab Therapy in Hematologic Malignancy Patients With Circulating Blood Tumor Cells: Association With Increased Infusion-Related Side Effects and Rapid Blood Tumor Clearance
Authors: Byrd John C. , Waselenko Jamie K. , Maneatis Thomas J. , Murphy Timothy , Ward Frank T. , Monahan Brian P. , Sipe Melissa A. , Donegan Sarah , White Christine A. 
Published: February 2017

PURPOSE: Rituximab was recently approved for use in relapsed, low-grade non-Hodgkin's lymphoma; however, few data exist regarding the safety of this agent in patients with a high number of tumor cells in the blood. METHODS AND RESULTS: After the observation at our institution of a rapid reduction of peripheral-blood tumor cells with associated severe pulmonary infusion-related toxicity in two patients with refractory hematologic malignancies, data on three additional cases were collected from physician-submitted reports of adverse events related to rituximab treatment. Five patients with hematologic malignancies possessing a high number of blood tumor cells were treated with rituximab and developed rapid tumor clearance. The median age was 68 years (range, 26 to 78 years). Patients were diagnosed with B-cell prolymphocytic leukemia (n = 2), chronic lymphocytic leukemia (n = 2), or transformed non-Hodgkin's lymphoma (n = 1). All of these patients had bulky adenopathy or organomegaly. All five patients developed a unique syndrome of severe infusion-related reactions, thrombocytopenia, rapid decrement in circulating tumor cell load, and mild electrolyte evidence of tumor lysis, and all required hospitalization. In addition, one patient developed ascites. These events resolved, and four patients were subsequently treated with rituximab without significant complications. CONCLUSION: Rituximab administration in patients who have a high number of tumor cells in the blood may have an increased likelihood of severe initial infusion-related reactions. These data also suggest that rituximab may have activity in a variety of other lymphoid neoplasms, such as chronic lymphocytic leukemia and B-cell prolymphocytic leukemia.
Long-Term Follow-Up of High-Risk Allogeneic Peripheral-Blood Stem-Cell Transplant Recipients: Graft-Versus-Host Disease and Transplant-Related Mortality
Authors: Brown R. A. , Adkins D. , Khoury H. , Vij R. , Goodnough L. T. , Shenoy S. , DiPersio J. F. 
Published: February 2017

PURPOSE: To determine the risks of graft-versus-host disease (GVHD) and transplant-related mortality after allogeneic peripheral-blood stem-cell (PBSC) transplantation. PATIENTS AND METHODS: Between December 1994 and July 1996, 50 consecutive patients with high-risk hematologic malignancies in first remission or relapse received high-dose therapy followed by transplantation of granulocyte colony-stimulating factor–mobilized, allogeneic PBSCs collected from HLA-identical siblings. GVHD prophylaxis included cyclosporine and corticosteroids. RESULTS: As of April 1, 1998, 18 patients (36% ± 13%) survived with a median follow-up period of 767 days (range, 602 to 1,127 days). The actuarial probability of grades 2-4 acute GVHD was 0.37 ± 0.14 (95% confidence interval). Of 36 assessable patients, 26 (72% ± 15%) developed chronic GVHD. The actuarial probability of chronic GVHD 2 years after transplantation was 0.87 ± 0.15. Of 14 progression-free survivors, 11 (79% ± 22%) have active, chronic GVHD. All 11 patients require ongoing immunosuppression, and nearly two thirds have extensive disease. Thirteen patients died as a result of transplant-related mortality (26% ± 12%), six (12%) before and seven (14%) after day +100. CONCLUSION: We observed a high risk of chronic GVHD after allogeneic PBSC transplantation, which compromised the performance status of most long-term survivors and resulted in a relatively high risk of late transplant-related mortality. Approximately 75% of transplant-related deaths were associated with GVHD; thus, reduction in transplant-related mortality after allogeneic PBSC transplantation will require more effective strategies for the prophylaxis and/or treatment of GVHD.
Management of Breast Cancer During Pregnancy Using a Standardized Protocol
Authors: Berry David L. , Theriault Richard L. , Holmes Frankie A. , Parisi Valerie M. , Booser Daniel J. , Singletary S. Eva , Buzdar Aman U. , Hortobagyi Gabriel N. 
Published: February 2017

PURPOSE: No standardized therapeutic interventions have been reported for patients diagnosed with breast cancer during pregnancy. Of the potential interventions, none have been prospectively evaluated for treatment efficacy in the mother or safety for the fetus. We present our experience with the use of combination chemotherapy for breast cancer during pregnancy. PATIENTS AND METHODS: During the past 8 years, 24 pregnant patients with primary or recurrent cancer of the breast were managed by outpatient chemotherapy, surgery, or surgery plus radiation therapy, as clinically indicated. The chemotherapy included fluorouracil (1,000 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2), administered every 3 to 4 weeks after the first trimester of pregnancy. Care was provided by medical oncologists, breast surgeons, and perinatal obstetricians. RESULTS: Modified radical mastectomy was performed in 18 of the 22 patients, and two patients were treated with segmental mastectomy with postpartum radiation therapy. This group included patients in all trimesters of pregnancy. The patients received a median of four cycles of combination chemotherapy during pregnancy. No antepartum complications temporally attributable to systemic therapy were noted. The mean gestational age at delivery was 38 weeks. Apgar scores, birthweights, and immediate postpartum health were reported to be normal for all of the children. CONCLUSION: Breast cancer can be treated with chemotherapy during the second and third trimesters of pregnancy with minimal complications of labor and delivery.