bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparotomy Versus No Laparotomy in the Management of Early-Stage, Favorable-Prognosis Hodgkin's Disease: A Decision Analysis
Authors: Ng Andrea K. , Weeks Jane C. , Mauch Peter M. , Kuntz Karen M. 
Published: February 2017

PURPOSE: To perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of early-stage, favorable-prognosis Hodgkin's disease (HD) managed with and without staging laparotomy, incorporating data on treatment outcomes of HD in the modern era. METHODS: We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages I and II, favorable-prognosis HD. Markov models were used to simulate the lifetime clinical course of patients, whose prognosis depended on the true pathologic stage and initial treatment. The baseline probability estimates used in the model were derived from results of published studies. Quality-of-life adjustments for procedures and treatments, as well as the various long-term health states, were incorporated. RESULTS: The life expectancy was 36.67 years for the laparotomy strategy and 35.92 years for no laparotomy, yielding a net expected benefit of 0.75 years for laparotomy staging. The corresponding quality-adjusted life expectancies for the two strategies were 35.97 and 35.38 quality-adjusted life years (QALYs), respectively, resulting in a net expected benefit of laparotomy staging of 0.59 QALYs. Sensitivity analysis showed that the decision of laparotomy versus no laparotomy was most heavily influenced by the quality-of-life weight assigned to the postlaparotomy state. CONCLUSION: Our model predicted that on average, for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months. These results suggest that a role remains for surgical staging in the management of early-stage HD.
Multicycle High-Dose Chemotherapy and Filgrastim-Mobilized Peripheral-Blood Progenitor Cells in Women With High-Risk Stage II or III Breast Cancer: Five-Year Follow-Up
Authors: Basser Russell L. , To L. Bik , Collins John P. , Begley C. Glenn , Keefe Dorothy , Cebon Jonathan , Bashford John , Durrant Simon , Szer Jeffrey , Kotasek Dusan , Juttner Christopher A. , Russell Ian , Maher Darryl W. , Olver Ian , Sheridan William P. , Fox Richard M. , Green Michael D. 
Published: February 2017

PURPOSE: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer. PATIENTS AND METHODS: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor–negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter. Twenty-six patients had bone marrow and apheresis collections assessed for the presence of micrometastatic tumor cells. RESULTS: Ninety-nine women (median age, 43 years; range, 24 to 60 years) were treated. Ninety-two completed all three cycles of chemotherapy. The major toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given treatment every 28 days and those treated every 21 days. Febrile neutropenia occurred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles but tended to be short-lived and was reversible. The cardiac ejection fraction fell by a median of 4% during treatment, and three patients developed evidence of cardiac failure after chemotherapy. Two patients (2%) died of acute toxicity. Three of 26 patients had evidence of circulating micrometastatic tumor cells. The actuarial distant disease-free and overall survival rates at 60-month follow-up were 64% (95% confidence interval [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. CONCLUSION: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to those in other studies of myeloablative chemotherapy in poor-prognosis breast cancer. The regimen is being evaluated in a randomized trial of the International Breast Cancer Study Group.
Long-Term Survivors of Advanced Neuroblastoma With MYCN Amplification: A Report of 19 Patients Surviving Disease-Free for More Than 66 Months
Authors: Kawa K. , Ohnuma N. , Kaneko M. , Yamamoto K. , Etoh T. , Mugishima H. , Ohhira M. , Yokoyama J. , Bessho F. , Honna T. , Yoshizawa J. , Nakada K. , Iwafuchi M. , Nozaki T. , Mimaya J. , Sawada T. , Nakamura T. , Miyata H. , Yamato K. , Tsuchida Y. 
Published: February 2017

PURPOSE: According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. PATIENTS AND METHODS: Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A1 (cyclophosphamide 1,200 mg/m2 on day 1, vincristine 1.5 mg/m2 on day 1, pirarubicin 40 mg/m2 on day 3, and cisplatin 90 mg/m2 on day 5) and from March 1991 to September 1993 consisted of regimen A3 (cyclophosphamide 1,200 mg/m2 on days 1 and 2, pirarubicin 40 mg/m2 on day 3, etoposide 100 mg/m2 on days 1 through 5, and continuous infusion cisplatin 25 mg/m2 on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died. CONCLUSION: Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.
Striking Regression of Chronic Radiotherapy Damage in a Clinical Trial of Combined Pentoxifylline and Tocopherol
Authors: Delanian Sylvie , Balla-Mekias Saida , Lefaix Jean-Louis 
Published: February 2017

PURPOSE: Radiation-induced fibrosis (RIF) remains the most morbid complication of radiotherapy because of the absence of spontaneous regression and the difficulty of patient management. RIF treatment with combined pentoxifylline (PTX) and tocopherol (Vit E) was prompted by recent advances in cellular and molecular biology that have improved researchers' understanding of radiation-induced late-injury mechanisms and by the excellent results from our previous human and animal studies. PATIENTS AND METHODS: Forty-three patients (mean [± SD] age, 59 ± 10 years) presenting with 50 symptomatic RIF areas involving the skin and underlying tissues were treated from April 1995 to September 1997. Patients had had radiotherapy for head and neck or breast cancer a mean period of 8.5 ± 6.5 years previously. RIF developed in the first year after irradiation and gradually worsened, without spontaneous regression. The mean measurable surface area of RIF ([S]) at the time of this study ([S0]) was 42 ± 34 cm2. The initial Subjective Objective Medical management and Analytic (SOMA) injury evaluation score was 13.2 ± 5.9 and included evidence of edema, plexitis, restricted movement, and local inflammatory signs. A combination of PTX (800 mg/d) and Vit E (1,000 IU/d) was administered orally for at least 6 months. RESULTS: Treatment was well tolerated. All assessable injuries exhibited continuous clinical regression and functional improvement. Mean RIF surface area and SOMA scores improved significantly (P < .0001) at 3 months ([S3], −39%; [SOMA3], −22%), 6 months ([S6], −53%; [SOMA6], −35%), and 12 months ([S12], −66%; [SOMA12], −48%), and mean linear dimensions ([D]) diminished from the start of the study ([D0], 6.5 ± 2.5 cm) to the end of treatment 12 months later ([D12], 4 ± 2 cm). At the time of the treatment, we did not attempt to achieve the maximum effect, and the study was continued. CONCLUSION: The PTX-Vit E combination reversed human chronic radiotherapy damage and, because no other treatment is presently available for RIF, should be considered as a therapeutic measure.
Liposomal Doxorubicin and Conventionally Fractionated Radiotherapy in the Treatment of Locally Advanced Non–Small-Cell Lung Cancer and Head and Neck Cancer
Authors: Koukourakis M. I. , Koukouraki S. , Giatromanolaki A. , Archimandritis S. C. , Skarlatos J. , Beroukas K. , Bizakis J. G. , Retalis G. , Karkavitsas N. , Helidonis E. S. 
Published: February 2017

PURPOSE: Stealth (ALZA Corporation, Palo Alto, CA) liposomal drug formulation allows a higher intratumoral accumulation and a prolonged plasma half-life of the encapsulated drugs. In the study presented here, we evaluated the feasibility of Stealth liposomal doxorubicin (Caelyx; ALZA Corporation) administered concurrently with conventionally fractionated radiotherapy in the treatment of non–small-cell lung cancer (NSCLC) and head and neck cancer (HNC). PATIENTS AND METHODS: Fifteen patients with NSCLC and 15 with squamous-cell HNC were recruited in two phase I dose-escalation trials. The starting dose of Caelyx was 10 mg/m2 every 2 weeks (for three cycles during radiotherapy) and was increased by 5 mg/m2 dose increments for every three patients. RESULTS: The maximum tolerated dose of Caelyx was 20 mg/m2 for HNC and 25 mg/m2 in NSCLC patients. Oral/pharyngeal mucositis was the dose-limiting toxicity for HNC patients. “In field” radiation skin toxicity was slightly increased. Hematologic toxicity was minimal. Single photon emission computed tomographic evaluation of Caelyx distribution, using technetium-99m–diethylenetriamine pentaacetic acid labeling, revealed a high intratumoral accumulation of the drug. The tumor to thoracic vessel area count ratio in the NSCLC cases ranged from 0.6 to 1.6 (mean ± SD, 1.01 ± 0.29), whereas this ratio was higher (0.8 to 1.85; mean ± SD, 1.35 ± 0.39) in HNC cases (P = .049). The complete response rate was 21% in the NSCLC cases and 75% in the HNC cases. NSCLC cases with higher Caelyx tumor accumulation responded better to the regimen. The tumor microvessel density assessed with the anti-CD31 monoclonal antibody directly correlated with the degree of the Caelyx accumulation (P = .007; r = .92). CONCLUSION: We conclude that combination of radiotherapy with Stealth liposomal doxorubicin is feasible. The potential role of such a regimen in the treatment of highly angiogenic tumors requires further investigation.
Placebo-Controlled Trial of 13-cis-Retinoic Acid Activity on Retinoic Acid Receptor-Beta Expression in a Population at High Risk: Implications for Chemoprevention of Lung Cancer
Authors: Ayoub J. , Jean-François R. , Cormier Y. , Meyer D. , Ying Y. , Major P. , Desjardins C. , Bradley W.E.C. 
Published: February 2017

PURPOSE: To establish the incidence of abnormalities in the expression of retinoic acid receptor-beta (RARβ) in bronchial cells and determine the capacity of 13-cis-retinoic acid (13-CRA) to correct such abnormalities. PATIENTS AND METHODS: One hundred eighty-eight smokers had a medical indication for bronchoscopy and were studied with bronchial brushings. Bronchial brushing samples were obtained for cytology analysis and for molecular analysis. After RNA was extracted, RARβ sequences were amplified by reverse transcriptase polymerase chain reaction and Southern blots were performed to assess RARβ expression. Forty-four eligible individuals with diminished RARβ expression consented to double-blind randomization to receive a placebo or 13-CRA 30 mg orally daily for 6 months. A second bronchoscopy was performed at the end of the treatment period. An analysis of variance was used to analyze changes in RARβ expression before and after treatment. RESULTS: The 6-month treatment course was completed by 27 patients, and results were obtained for a total of 18 patients (eight patients treated with 13-CRA and ten treated with the placebo). In the placebo group, there was no difference between the results of RARβ expression before and after treatment (P = .43). In the 13-CRA group, there was an upregulation of RARβ expression at the end of 13-CRA treatment (P = .001). Cytologic changes were uncommon. Toxicities were primarily of grade 1. Palatal brushings were compared with bronchial brushings in 40 smokers. A perfect correlation of the results of RARβ expression was obtained from 27 patients. CONCLUSION: RARβ expression is frequently decreased in the bronchial epithelium of smokers and is upregulated at the end of 13-CRA treatment. These results support undertaking a phase III chemoprevention trial of 13-CRA treatment for lung cancer.
Patients With t(8;21)(q22;q22) and Acute Myeloid Leukemia Have Superior Failure-Free and Overall Survival When Repetitive Cycles of High-Dose Cytarabine Are Administered
Authors: Byrd John C. , Dodge Richard K. , Carroll Andrew , Baer Maria R. , Edwards Colin , Stamberg Judith , Qumsiyeh Mazin , Moore Joseph O. , Mayer Robert J. , Davey Frederick , Schiffer Charles A. , Bloomfield Clara D. 
Published: February 2017

PURPOSE: To examine the effect of single compared with repetitive (at least three) cycles of high-dose cytarabine after induction therapy for patients with acute myeloid leukemia (AML) who have the t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS: Patients entered onto the study had AML and t(8;21) and attained a complete remission on four successive Cancer and Leukemia Group B studies. In these studies, either ≥ three cycles of high-dose cytarabine or one cycle of high-dose cytarabine was administered, followed by sequential cyclophosphamide/etoposide and mitoxantrone/diaziquone with or without filgrastim support. Outcomes of these two groups of t(8;21) patients were compared. RESULTS: A total of 50 patients with centrally reviewed AML and t(8;21) were assigned to receive one (n = 29) or ≥ three cycles (n = 21) of high-dose cytarabine as postinduction therapy. The clinical features of these two groups of patients were similar. Initial remission duration for t(8;21) patients assigned to one cycle of high-dose cytarabine was significantly inferior (P = .03), with 62% of patients experiencing relapse with a median failure-free survival of 10.5 months, compared with the group of patients who received ≥ three cycles, in which only 19% experienced relapse and failure-free survival is estimated to be greater than 35 months. Furthermore, overall survival was also significantly compromised (P = .04) in patients assigned to one cycle of high-dose cytarabine, with 59% having died as a consequence of AML, compared with 24% of those who received ≥ three cycles of high-dose cytarabine. CONCLUSION: These data demonstrate that failure-free survival and overall survival of patients with t(8;21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy.
Phase II Trial of Paclitaxel and Cisplatin in Metastatic and Recurrent Carcinoma of the Uterine Cervix
Authors: Papadimitriou Christos A. , Sarris Kyrillos , Moulopoulos Lia A. , Fountzilas George , Anagnostopoulos Athanassios , Voulgaris Zannis , Gika Dimitra , Giannakoulis Nikolaos , Diakomanolis Emmanuel , Dimopoulos Meletios A. 
Published: February 2017

PURPOSE: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent cancer of the cervix, and the combination of these two agents has shown activity and possible synergism in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent cervical cancer to evaluate its activity. PATIENTS AND METHODS: Thirty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m2 administered intravenously over a 3-hour period followed by cisplatin 75 mg/m2 administered intravenously with granulocyte colony-stimulating factor support. The chemotherapy was administered every 3 weeks for a maximum of six courses. RESULTS: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an objective response, including five complete responses and 11 partial responses. Responses occurred in 28% of patients with disease within the radiation field only and in 57% of patients with disease involving other sites. The median duration of response was 5.5 months, and the median times to progression and survival for all patients were 5 and 9 months, respectively. Grade 3 or 4 toxicities included anemia in 18% of patients and granulocytopenia in 15% of patients. Fifty-three percent of patients developed some degree of neurotoxicity; 21% of cases were grade 2 or worse. CONCLUSION: The combination of paclitaxel with cisplatin seems relatively well tolerated and moderately active in patients with metastatic or recurrent cervical cancer. The significant incidence of neurotoxicity is of concern, and alternative methods of administration of the two agents could be evaluated. Then, further study of this combination, alone or with the addition of other active agents, is warranted.
Additional Value of Whole-Body Positron Emission Tomography With Fluorine-18-2-Fluoro-2-deoxy-d-glucose in Recurrent Colorectal Cancer
Authors: Flamen Patrick , Stroobants Sigrid , Van Cutsem Eric , Dupont Patrick , Bormans Guy , De Vadder Nancy , Penninckx Freddy , Van Hoe Lieven , Mortelmans Luc 
Published: February 2017

PURPOSE: To assess the additional value of the whole-body [18F]-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scan as a staging modality complementing conventional diagnostic methods (CDM) in patients suspected of having recurrent colorectal adenocarcinoma.PATIENTS AND METHODS: In 103 patients, the discordances between FDG-PET and CDM results were identified and related to the final diagnosis obtained by histopathology or clinical follow-up (> 1 year). All FDG-PET studies were reviewed with full knowledge of the CDM findings.RESULTS: In a region-based analysis, discordances between CDM and FDG-PET findings were found in 40 of 412 regions (10%). In these, FDG-PET had additional diagnostic value in 14 of 16 locoregional, six of seven hepatic, seven of eight abdominal, and eight of nine extra-abdominal regions. In a patient-based analysis, CDM categorized a subgroup of 60 patients as having resectable recurrent disease limited to the liver (n = 37) or locoregional region (n = 23). In 13 of these patients, there were discordant FDG-PET findings, detecting additional tumor sites in nine patients and excluding disease in three patients and yielding an additional diagnostic value in 20% of the patients. A second subgroup consisted of 13 patients with inconclusive CDM findings (n = 5) or with elevated plasma carcinoembryonic antigen levels and an otherwise negative conventional work-up (n = 8). In these patients, FDG-PET results were correct in eight of nine discordances, yielding a positive additional diagnostic value in 62% of the patients.CONCLUSION: Whole-body FDG-PET can have a clear impact on the therapeutic management in the follow-up of patients with colorectal cancer.
Prognostic Factors in Children With Localized Malignant Nonseminomatous Germ Cell Tumors
Authors: Baranzelli M. C. , Kramar A. , Bouffet E. , Quintana E. , Rubie H. , Edan C. , Patte C. 
Published: February 2017

PURPOSE: Prognostic factors were studied in children older than 1 year who were treated with chemotherapy for extracranial localized malignant non seminomatous germ cell tumors. PATIENTS AND METHODS: Data from two consecutive protocols were pooled. The TGM 85 (1985-1989) protocol consisted of alternating courses of cyclophosphamide, dactinomycin and vinblastine, bleomycin, and cisplatin at a dose of 100 mg/m2 per course. The TGM 90 (1990-1994) protocol was initiated with carboplatin 400 mg/m2 substituted for cisplatin as the only modification to the previous protocol. RESULTS: We examined alpha-fetoprotein (AFP) levels, disease stage, and primary site and identified three prognostic groups. Patients with a poor prognosis had either an AFP level ≥ 10,000 ng/mL or stage III disease and a sacrococcygeal or mediastinal primary site; such patients represented 46% of the patient population and experienced a 43% 3-year failure-free survival rate and a 77% overall survival rate. Patients with a good prognosis had an AFP level less than 10,000 ng/mL, stage I or II disease, and a testicular, ovarian, perineal, or retroperitoneal primary site; such patients represented 22% of the patient population and experienced no treatment failures. The other patients were classified in the intermediate prognosis group and represented 37% of the patient population, with an 81% 3-year failure-free survival rate and a 92% overall survival rate. CONCLUSION: Initial AFP level, disease stage, and primary site are the most important prognostic factors in this analysis. Prognostic models for pediatric germ cell tumors should allow the stratification of patients for a risk-adapted approach to treatment.
Safety and Efficacy of Using a Single Agent or a Phase II Agent Before Instituting Standard Combination Chemotherapy in Previously Untreated Metastatic Breast Cancer Patients: Report of a Randomized Study—Cancer and Leukemia Group B 8642
Authors: Costanza Mary E. , Weiss Raymond B. , Henderson I. Craig , Norton Larry , Berry Donald A. , Cirrincione Constance , Winer Eric , Wood William C. , Frei III Emil , McIntyre O. Ross , Schilsky Richard L. 
Published: February 2017

PURPOSE: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF. RESULTS: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm. CONCLUSION: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.