bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefit of Intensified Therapy for Patients With Local or Regional Embryonal Rhabdomyosarcoma: Results From the Intergroup Rhabdomyosarcoma Study IV
Authors: Baker K. Scott , Anderson James R. , Link Michael P. , Grier Holcombe E. , Qualman Stephen J. , Maurer Harold M. , Breneman John C. , Wiener Eugene S. , Crist William M. 
Published: February 2017

PURPOSE: To compare failure-free survival (FFS) and survival for patients with local or regional embryonal rhabdomyosarcoma treated on the Intergroup Rhabdomyosarcoma Study (IRS)–IV with that of comparable patients treated on IRS-III. PATIENTS AND METHODS: Patients were retrospectively classified as low- or intermediate-risk. Low-risk patients were defined as those with primary tumors at favorable sites, completely resected or microscopic residual, or orbit/eyelid primaries with gross residual disease and tumors less than 5 cm at unfavorable sites but completely resected. Intermediate-risk patients were all other patients with local or regional tumors. RESULTS: Three-year FFS improved from 72% on IRS-III to 78% on IRS-IV for patients with intermediate-risk embryonal rhabdomyosarcoma (P = .02). Subset analysis revealed two groups that benefited most from IRS-IV therapy. FFS at 3 years for patients with resectable node-positive or unresectable (group III) embryonal rhabdomyosarcoma arising at certain favorable sites (head and neck [not orbit/eyelid or parameningeal] and genitourinary [not bladder or prostate]) improved from 72% on IRS-III to 92% on IRS-IV (P = .01). Similarly, 3-year FFS for patients with completely resected tumor or with only microscopic disease remaining (group I or II) at unfavorable sites improved from 71% on IRS-III to 86% on IRS-IV (P = .04). Only patients with unresectable embryonal rhabdomyosarcoma (group III) at unfavorable sites had no improvement in outcome on IRS-IV (3-year FFS for IRS-III and IRS-IV, 72% and 75%, respectively; P = .31). CONCLUSION: IRS-IV therapy benefited certain subgroups of patients with intermediate-risk embryonal rhabdomyosarcoma. A doubling of the intensity of cyclophosphamide (or ifosfamide equivalent) dosing per cycle between IRS-III and IRS-IV is thought to be a key contributing factor for this improvement.
What Would You Do? Specialists’ Perspectives on Cancer Genetic Testing, Prophylactic Surgery, and Insurance Discrimination
Authors: Matloff Ellen T. , Shappell Heather , Brierley Karina , Bernhardt Barbara A. , McKinnon Wendy , Peshkin Beth N. 
Published: February 2017

PURPOSE: To examine what cancer genetics specialists predict they would do personally if they were at 50% risk of carrying a mutation that predisposes to hereditary breast/ovarian cancer (BRCA1/BRCA2) and hereditary nonpolyposis colon cancer (HNPCC). METHODS: Questionnaire survey of the membership of the National Society of Genetic Counselors (NSGC) Special Interest Group (SIG) in Cancer. RESULTS: Of the 296 active members of the NSGC Cancer-SIG surveyed, 163 (55%) responded. Eighty-five percent predicted that if they had a 50% risk of carrying a BRCA1/BRCA2 mutation, they would pursue genetic testing. If they tested positive for a mutation at age 35, 25% predicted they would pursue prophylactic bilateral mastectomies and 68%, prophylactic oophorectomy. Ninety-one percent of respondents believe they would pursue genetic testing for HNPCC, and 17% would elect prophylactic colectomy; 54%, prophylactic hysterectomy; and 52%, prophylactic oophorectomy if they tested positive for a mutation. The majority (68%) would not bill their insurance companies for genetic testing because of fear of discrimination, and 26% would use an alias when undergoing testing. Fifty-seven percent of counselors would seek professional psychologic support to help them cope with the results of testing. CONCLUSION: A large percentage of cancer genetic counseling providers predicted they would opt for prophylactic surgery at a young age if they carried a BRCA or HNPCC mutation, and most would seek professional psychologic assistance when undergoing testing. More than half of respondents would not bill their insurance companies for genetic testing, largely because of fear of genetic discrimination. The vast majority of those providers most familiar with cancer genetic testing and its associated medical, psychologic, and legal implications would still pursue genetic testing.
Randomized, Dose-Escalation Study of SD/01 Compared With Daily Filgrastim in Patients Receiving Chemotherapy
Authors: Johnston Eileen , Crawford Jeffrey , Blackwell Susan , Bjurstrom Toni , Lockbaum Pamela , Roskos Lorin , Yang Bing-Bing , Gardner Sheila , Miller-Messana Mary Ann , Shoemaker Debra , Garst Jennifer , Schwab Gisela 
Published: February 2017

PURPOSE: To explore the use of SD/01 (a polyethylene glycol–conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non–small-cell lung cancer were randomized to receive daily filgrastim (5 μg/kg/d) or a single injection of SD/01 (30, 100, or 300 μg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 μg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 μg/kg. Dose-limiting toxicities were not noted. CD34+ cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34+ cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.
Prospective Observational Study of Sentinel Lymphadenectomy Without Further Axillary Dissection in Patients With Sentinel Node–Negative Breast Cancer
Authors: Giuliano Armando E. , Haigh Philip I. , Brennan Meghan B. , Hansen Nora M. , Kelley Mark C. , Ye Wei , Glass Edwin C. , Turner Roderick R. 
Published: February 2017

PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes accurately predict tumor-free axillary nodes in breast cancer. Therefore, we hypothesized that SLND alone in patients with tumor-negative sentinel nodes would achieve axillary control, with minimal complications. PATIENTS AND METHODS: Between October 1995 and July 1997, 133 consecutive women who had primary invasive breast tumors clinically ≤ 4 cm in diameter and no axillary lymphadenopathy were prospectively entered onto a trial of SLND using vital blue dye. Sentinel nodes were examined by standard microscopy or immunohistochemistry. SLND was the only axillary surgery if sentinel nodes were tumor-free. Completion ALND was performed only if sentinel nodes contained metastases or if they were not identified. Excluded from subsequent analysis were patients with unsuspected multifocal carcinoma and those who refused completion ALND. The complication and axillary recurrence rates after SLND without ALND were determined. RESULTS: Sentinel nodes were identified in 132 (99%) of 133 patients. Eight patients were excluded from further analysis. Of the 125 assessable patients, 57 had tumor-positive sentinel nodes and one had an unsuccessful mapping procedure; these patients underwent completion ALND. In the remaining 67 patients (54%), SLND was the only axillary procedure. Complications occurred in 20 patients (35%) undergoing ALND after SLND but in only two patients (3%) undergoing SLND alone (P = .001). There were no local or axillary recurrences at a median follow-up of 39 months. CONCLUSION: Complication rates are negligible after SLND alone. An absence of axillary recurrences supports SLND as an accurate staging alternative for breast cancer and suggests that routine ALND can be eliminated for patients with histopathologically negative sentinel nodes.
Sentinel Lymph Node Biopsy for Breast Cancer: A Suitable Alternative to Routine Axillary Dissection in Multi-Institutional Practice When Optimal Technique Is Used
Authors: McMasters Kelly M. , Tuttle Todd M. , Carlson David J. , Brown C. Matthew , Noyes R. Dirk , Glaser Rebecca L. , Vennekotter Donald J. , Turk Peter S. , Tate Peter S. , Sardi Armando , Cerrito Patricia B. , Edwards Michael J. 
Published: February 2017

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P < .05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2.1 v 1.5; P < .0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P = .03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3.9%; P < .05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.
Fractionated Cyclophosphamide and Etoposide for Children With Advanced or Refractory Solid Tumors: A Phase II Window Study
Authors: Mantadakis Elpis , Herrera Larry , Leavey Patrick J. , Bash Robert O. , Winick Naomi J. , Kamen Barton A. 
Published: February 2017

PURPOSE: Cyclophosphamide (CPA) has a broad spectrum of activity against solid tumors. Hepatic self-induction of the active metabolite 4-hydroxycyclophosphamide occurs after repeated administration. We evaluated the clinical efficacy of a window regimen that administers fractionated CPA in conjunction with etoposide (VP16) in children with advanced or refractory solid tumors. PATIENTS AND METHODS: Seventeen children with advanced (n = 12) or refractory (n = 5) solid tumors were entered onto this phase II window study. The treatment regimen consisted of intravenous (IV) CPA 500 mg/m2/d and IV VP16 100 mg/m2/d. Both drugs were administered daily by short infusions for 5 consecutive days. RESULTS: A total of 34 courses were administered, with a median of two courses per patient. The median interval between chemotherapy courses was 21 days (range, 17 to 35 days). Thirty-three courses were assessable for toxicity, and all patients were assessable for response. No life-threatening toxicities were observed. The incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%. Fever and neutropenia occurred after 12 of 26 courses without recombinant human granulocyte colony-stimulating factor (rhG-CSF) and after one of eight courses with rhG-CSF (P = .09). Grade 3 or 4 thrombocytopenia occurred after 10 courses (29%). There were no positive blood cultures. One heavily pretreated patient developed a localized perirectal abscess that required drainage. There were 10 patients (59%) with partial responses, four (23.5%) with stable disease, and three with progressive disease. CONCLUSION: Fractionated IV CPA and VP16 over 5 days can be safely administered in children with advanced or refractory solid tumors and has notable antineoplastic activity.
Gemcitabine Treatment in Pretreated Cutaneous T-Cell Lymphoma: Experience in 44 Patients
Authors: Zinzani Pier Luigi , Baliva Gianandrea , Magagnoli Massimo , Bendandi Maurizio , Modugno Gino , Gherlinzoni Filippo , Orcioni Giulio Fraternali , Ascani Stefano , Simoni Romeo , Pileri Stefano A. , Tura Sante 
Published: February 2017

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine, a novel pyrimidine antimetabolite with a low-toxicity profile and activity in several solid tumors, in patients with relapsed or refractory cutaneous T-cell lymphomas. PATIENTS AND METHODS: Between May 1997 and February 1999, 44 previously treated patients with mycosis fungoides (MF; n = 30) and peripheral T-cell lymphoma unspecified (PTCLU) with exclusive skin involvement (n = 14) were enrolled onto a two-institution, phase II trial and treated with gemcitabine. This drug was given on days 1, 8, and 15 of a 28-day schedule at a dose of 1,200 mg/m2 intravenously over 30 minutes for a total of three courses. RESULTS: Of the 44 patients, five (11.5%) achieved complete responses (CRs), 26 (59%) partial responses (PRs), and the remaining 13 showed no benefit from the treatment. Two of the CRs were histologically confirmed. The CR and PR rates were the same for patients with MF and those with PTCLU, respectively. No difference in terms of overall response rate was observed between relapsed and refractory patients. The median durations of CR and PR were 15 months (range, 6 to 22 months) and 10 months (range, 2 to 15 months), respectively. Treatment was well tolerated; hematologic toxicity was mild, and no nausea/vomiting or organ toxicity was recorded. CONCLUSION: The results of the present phase II study show activity of gemcitabine as a single agent in patients with pretreated cutaneous T-cell lymphoma. Further studies that use gemcitabine alone or in combination with other drugs in earlier stages of the disease are needed.
Acquired Chromosome 11q Deletion Involving the Ataxia Teleangiectasia Locus in B-Cell Non-Hodgkin’s Lymphoma: Correlation With Clinicobiologic Features
Authors: Cuneo Antonio , Bigoni Renato , Rigolin Gian Matteo , Roberti Maria Grazia , Milani Raffaella , Bardi Antonella , Minotto Claudia , Agostini Paola , De Angeli Cristiano , Narducci Maria Grazia , Sabbioni Silvia , Russo Giandomenico , Negrini Massimo , Castoldi Gianluigi 
Published: February 2017

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/−) in B-cell non-Hodgkin’s lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22–23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/− patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/− more frequently had a complex karyotype (P = .01) and the AA karyotype (P = .04) compared with patients without ATM+/−. With the exception of a poor performance status (P = .001), no correlation was found between ATM+/−, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P < .0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P = .0004), along with performance status (P = .0006), serum lactate dehydrogenase level (P = .03), splenomegaly (P = .01), and histologic grade (P = .03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/− maintained its prognostic importance as an independent variable in both histologic groups (P = .0001 and P = .016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/− status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.
Final Results of a Randomized Phase III Trial of Sequential High-Dose Methotrexate, Fluorouracil, and Doxorubicin Versus Etoposide, Leucovorin, and Fluorouracil Versus Infusional Fluorouracil and Cisplatin in Advanced Gastric Cancer: A Trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group
Authors: Vanhoefer Udo , Rougier Philippe , Wilke Hansjochen , Ducreux Michel P. , Lacave Angel J. , Van Cutsem Eric , Planker Manfred , Santos José Guimaraes Dos , Piedbois Pascal , Paillot Bernard , Bodenstein Heinrich , Schmoll Hans-Jochen , Bleiberg Harry , Nordlinger Bernard , Couvreur Marie-Laure , Baron Benoit , Wils Jacques A. 
Published: February 2017

PURPOSE: To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer. PATIENTS AND METHODS: A total of 399 patients with advanced adenocarcinoma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points. RESULTS: The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX). CONCLUSION: All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.
Randomized Phase III Study Comparing Conventional-Dose Doxorubicin Plus Ifosfamide Versus High-Dose Doxorubicin Plus Ifosfamide Plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Soft Tissue Sarcomas: A Trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group
Authors: Le Cesne A. , Judson I. , Crowther D. , Rodenhuis S. , Keizer H.J. , Van Hoesel Q. , Blay J.Y. , Frisch J. , Van Glabbeke M. , Hermans C. , Van Oosterom A. , Tursz T. , Verweij J. 
Published: February 2017

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m2 on day 1) and ifosfamide (5 g/m2 on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m2 on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 μg/m2 on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P = .65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P = .03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified arm. There was no difference in overall survival (P = .98) between the two therapeutic arms. Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6% in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B. CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses. Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen failed to demonstrate any impact on survival in patients with ASTS. The low complete response rate, the high incidence of leiomyosarcomas, and liver metastases may in part explain these results. However, the lengthening of the PFS in the intensive arm, because of the quality of stable disease and inappropriate tumor evaluation policies that potentially lead to an underestimation of antitumor activity, does not definitively refute the use of a high-dose chemotherapy regimen in selected patients with ASTS.