bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II/III Trial of Etoposide and High-Dose Ifosfamide in Newly Diagnosed Metastatic Osteosarcoma: A Pediatric Oncology Group Trial
Authors: Goorin Allen M. , Harris Michael B. , Bernstein Mark , Ferguson William , Devidas Meenakshi , Siegal Gene P. , Gebhardt Mark C. , Schwartz Cindy L. , Link Michael , Grier Holcombe E. 
Published: February 2017

PURPOSE: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. PATIENTS AND METHODS: Eligible patients received infusions of 100 mg/m2 per day of etoposide and 3.5 g/m2 per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. RESULTS: Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% ± 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% ± 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% ± 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi’s syndrome was observed in five patients. CONCLUSION: The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity.
Neuropsychologic Impact of Standard-Dose Systemic Chemotherapy in Long-Term Survivors of Breast Cancer and Lymphoma
Authors: Ahles Tim A. , Saykin Andrew J. , Furstenberg Charlotte T. , Cole Bernard , Mott Leila A. , Skalla Karen , Whedon Marie B. , Bivens Sarah , Mitchell Tara , Greenberg E. Robert , Silberfarb Peter M. 
Published: February 2017

PURPOSE: The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 ± 10.7 years; lymphoma: n = 36, age, 55.9 ± 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 ± 10.5 years; lymphoma: n = 22, age, 48.7 ± 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study–Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). RESULTS: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P < .04), particularly in the domains of verbal memory (P < .01) and psychomotor functioning (P < .03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P < .01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P < .02). CONCLUSION: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy.
When the Treatment Goal Is Not Cure: Are Cancer Patients Equipped to Make Informed Decisions?
Authors: Gattellari Melina , Voigt Katie J. , Butow Phyllis N. , Tattersall Martin H.N. 
Published: February 2017

PURPOSE: Informed decision making now is considered the underpinning of ethical medical practice. We aimed to determine the extent to which patients with incurable cancer are adequately informed of their prognosis and treatment options and encouraged to participate in treatment decisions. PATIENTS AND METHODS: One hundred eighteen cancer patients with incurable disease presenting for an initial consultation with one of nine oncologists at two Sydney tertiary referral hospitals participated in the study. Consultations were recorded on audiotape to permit a content analysis of doctor-patient interactions. We devised a coding system to assess disclosure of information and to evaluate doctor encouragement of patient participation in treatment decision making. Patient recall, satisfaction, anxiety, and perceptions of the decision-making process were assessed to determine the effects of informed decision making on patient outcomes. RESULTS: Most patients were informed about the aim of anticancer treatment (84.7%), that their disease was incurable (74.6%), and about life expectancy (57.6%). An alternative to anticancer treatments was presented to 44.1%, 36.4% were informed about how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Oncologists checked patient understanding in only 10.2% of consultations. Although greater information disclosure did not seem to elevate anxiety levels, greater patient participation in the decision-making process was associated with increased anxiety levels (P = .0005), which persisted over a 2-week time span. CONCLUSION: Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to anticancer treatment. These gaps invite the question concerning whether patients are led toward anticancer treatment.
Identification and Referral of Families at High Risk for Cancer Susceptibility
Authors: Sweet Kevin M. , Bradley Terry L. , Westman Judith A. 
Published: February 2017

PURPOSE: Obtainment of family history and accurate assessment is essential for the identification of families at risk for hereditary cancer. Our study compared the extent to which the family cancer history in the physician medical record reflected that entered by patients directly into a touch-screen family history computer program. PATIENTS AND METHODS: The study cohort consisted of 362 patients seen at a comprehensive cancer center ambulatory clinic over a 1-year period who voluntarily used the computer program and were a mixture of new and return patients. The computer entry was assessed by genetics staff and then compared with the medical record for corroboration of family history information and appropriate physician risk assessment. RESULTS: Family history information from the medical record was available for comparison to the computer entry in 69%. It was most often completed on new patients only and not routinely updated. Of the 362 computer entries, 101 were assigned to a high-risk category. Evidence in the records confirmed 69 high-risk individuals. Documentation of physician risk assessment (ie, notation of significant family cancer history or hereditary risk) was found in only 14 of the high-risk charts. Only seven high-risk individuals (6.9%) had evidence of referral for genetic consultation. CONCLUSION: This study demonstrates the need to collect family history information on all new and established patients in order to perform adequate cancer risk assessment. The lack of identification of patients at highest risk seems to be directly correlated with insufficient data collection, risk assessment, and documentation by medical staff.
Tumor Hypoxia Has Independent Predictor Impact Only in Patients With Node-Negative Cervix Cancer
Authors: Fyles A. , Milosevic M. , Hedley D. , Pintilie M. , Levin W. , Manchul L. , Hill R. P. 
Published: February 2017

PURPOSE: This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy. PATIENTS AND METHODS: Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO2) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO2 readings less than 5 mm/Hg (abbreviated as HP5) and the median PO2. RESULTS: The median HP5 in individual patients was 48%, and the median PO2 was HP5. Progression-free survival (PFS) for patients with hypoxic tumors (HP5 > 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P = .004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P = .0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P = .0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P = .006), and further analysis indicated that HP5 was an independent predictor of outcome in patients with negative nodes on imaging (P = .007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP5 < 50%; P = .0023), but not in pelvic relapse (37% v 27%; P = .12). CONCLUSION: Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.
Intraperitoneal Chemotherapy for Ovarian Carcinoma: Results of Long-Term Follow-Up
Authors: Barakat Richard R. , Sabbatini Paul , Bhaskaran Dharmendra , Revzin Margarita , Smith Alex , Venkatraman Ennapadam , Aghajanian Carol , Hensley Martee , Soignet Steven , Brown Carol , Soslow Robert , Markman Maurie , Hoskins William J. , Spriggs David 
Published: February 2017

PURPOSE: To determine long-term survival and predictors of recurrence in a retrospective cohort of patients with epithelial ovarian cancer treated with intraperitoneal (IP) chemotherapy. PATIENTS AND METHODS: Records were reviewed of 433 patients who received IP therapy for ovarian cancer between 1984 and 1998; follow-up data were available for 411 patients. IP therapy was provided as consolidation therapy (n = 89), or for treatment of persistent (n = 310) or recurrent (n = 12) disease after surgery and initial systemic therapy; therapy usually consisted of platinum-based combination therapy. Statistical analysis included tests for associations between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox proportional hazard model. RESULTS: The mean age of patients was 52 years (range, 25 to 76 years). Distribution by stage and grade was as follows: stage I, 7; II, 24; III, 342; IV, 52; not available (NA), 8; and grade 1, 30; 2, 99; and 3, 289; NA, 15. The median survival from initiation of IP therapy by residual disease was none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more than 1 cm, 1.2 years. In a multivariate analysis, the only significant predictors of long-term survival were grade and size of residual disease at initiation of IP therapy. CONCLUSION: Prolonged survival was observed in selected patients receiving IP platinum-based therapy. It is not possible to determine the contribution of IP therapy to survival in this study. A relationship between size of disease at the initiation of IP therapy and long-term survival was demonstrated.
Blinded, Randomized, Multicenter Study to Evaluate Single Administration Pegfilgrastim Once per Cycle Versus Daily Filgrastim as an Adjunct to Chemotherapy in Patients With High-Risk Stage II or Stage III/IV Breast Cancer
Authors: Holmes F.A. , O’Shaughnessy J.A. , Vukelja S. , Jones S.E. , Shogan J. , Savin M. , Glaspy J. , Moore M. , Meza L. , Wiznitzer I. , Neumann T.A. , Hill L.R. , Liang B.C. 
Published: February 2017

PURPOSE: This multicenter, randomized, double-blind, active-control study was designed to determine whether a single subcutaneous injection of pegfilgrastim (SD/01, sustained-duration filgrastim; 100 μg/kg) is as safe and effective as daily filgrastim (5 μg/kg/d) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy. PATIENTS AND METHODS: Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m2 and doxorubicin 60 mg/m2 on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 μg/kg per chemotherapy cycle (154 patients) or daily subcutaneous injections of filgrastim 5 μg/kg/d (156 patients). Absolute neutrophil count (ANC), duration of grade 4 neutropenia, and safety parameters were monitored. RESULTS: One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points, including the duration of severe neutropenia and the depth of ANC nadir in all cycles. Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim. The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day. Pegfilgrastim was safe and well tolerated, and it was similar to filgrastim. Adverse event profiles in the pegfilgrastim and filgrastim groups were similar. CONCLUSION: A single injection of pegfilgrastim 100 μg/kg per cycle was as safe and effective as daily injections of filgrastim 5 μg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m2 and docetaxel 75 mg/m2.
Role of Radiotherapy in the Treatment of Supratentorial Primitive Neuroectodermal Tumors in Childhood: Results of the Prospective German Brain Tumor Trials HIT 88/89 and 91
Authors: Timmermann Beate , Kortmann Rolf-Dieter , Kühl Joachim , Meisner Christoph , Dieckmann Karin , Pietsch Torsten , Bamberg Michael 
Published: February 2017

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.
Prospective Evaluation of the Peptide-Bound Collagen Type I Cross-Links N-Telopeptide and C-Telopeptide in Predicting Bone Metastases Status
Authors: Costa Luis , Demers Laurence M. , Gouveia-Oliveira A. , Schaller J. , Costa Eduardo B. , de Moura Miguel C. , Lipton Allan 
Published: February 2017

PURPOSE: The objective assessment of bone metastases is currently based on serial changes in skeletal survey. We performed a prospective study to determine whether a correlation exists between the biochemical markers of bone turnover and x-ray evaluation of bone metastases in patients with or without bisphosphonate therapy, and whether bone markers are influenced by extraskeletal disease. PATIENTS AND METHODS: Patients with either bone or extraskeletal metastases were consecutively enrolled and World Health Organization response criteria were applied for both bone and extraosseous disease every 3 to 4 months. Serum levels of bone-specific alkaline phosphatase (B-AP) and C-telopeptide (ICTP) and urine levels of N-telopeptide (NTX) were measured monthly. The data were analyzed by generalized estimation equation regression. RESULTS: We studied 97 patients with bone metastases (52 also with extraskeletal metastases) and 26 with extraosseous disease only. Median time on study was 153 days, and 281 objective evaluations (171 in bone) were performed. With bisphosphonates (49 patients receiving pamidronate and three receiving clodronate), percent change from levels without therapy was 47% for NTX (P < .001) and 69% for B-AP (P = .008). With disease progression in bone, percent change from mean levels during stable disease was 152% for NTX (P < .001) and 144% for ICTP (P < .001) regardless of bisphosphonate therapy. NTX had the highest positive predictive value (71%) for the diagnosis of bone metastases progression. Extraskeletal disease had no significant effect on bone markers. CONCLUSION: Urinary NTX may be a valuable bone marker to assess the antiresorptive effect of bisphosphonate therapy and to evaluate the progression of bone metastases.
Clinical Relevance of Invasion Factors Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 for Individualized Therapy Decisions in Primary Breast Cancer Is Greatest When Used in Combination
Authors: Harbeck Nadia , Kates Ronald E. , Schmitt Manfred 
Published: February 2017

PURPOSE: A strong prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor and plasminogen activator inhibitor type 1 (PAI-1) as individual factors is well established in breast cancer. The improvement in clinical risk assessment gained by combining these factors is evaluated here. PATIENTS AND METHODS: uPA and PAI-1 levels were prospectively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer. RESULTS: In the clinically important subgroup of node-negative patients without adjuvant systemic therapy (n = 269; median follow-up, 60 months), the clinical value of testing both uPA and PAI-1 is demonstrated. The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group. uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival; patients with high uPA/PAI-1 have an increased relapse risk (P < .001; relative risk, 4.8; 95% confidence interval [CI], 2.5 to 9.1), in particular for early relapse. Even within risk groups stratified by established criteria (nodal or menopausal status, tumor size, grade, or steroid hormone receptors), uPA/PAI-1 provides significant risk group discrimination. In the whole collective, the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1. CONCLUSION: The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination. The particular combination of uPA and PAI-1 (both low v either or both high) is superior to either factor alone and supports risk-adapted individualized therapy decisions.
Hodgkin’s Disease in the Elderly: Improved Treatment Outcome With a Doxorubicin-Containing Regimen
Authors: Weekes Colin D. , Vose Julie M. , Lynch Jim C. , Weisenburger Dennis D. , Bierman Philip J. , Greiner Timothy , Bociek Gregory , Enke Charles , Bast Martin , Chan Wing C. , Armitage James O. 
Published: February 2017

PURPOSE: Hodgkin’s disease (HD) is a malignancy that displays a bimodal age distribution. Previous reports of treatment in patients ≥ 60 years have found a poor outcome, particularly in patients with advanced disease. Because of an improved side-effect profile, the regimen of chlorambucil, vinblastine, procarbazine, and prednisone (ChlVPP) has been proposed for use in elderly patients.
PATIENTS AND METHODS: From September 1982 to May 1998, 262 patients with previously untreated HD received either ChlVPP (n = 176) or ChlVPP plus doxorubicin/bleomycin/vincristine (ChlVPP/ABV hybrid; n = 86). Fifty-six patients were ≥ 60 years old, and 206 were younger than 60 years.

RESULTS: The 5-year overall survival (OS; 87%
v
39%) and the 5-year event-free survival (EFS; 75%
v
31%) favored patients younger than 60 years of age. Prognostic factors analyzed in patients ≥ 60 years of age, other than type of therapy, included sex, stage, Karnofsky performance score, lactic dehydrogenase, number of extranodal sites, B symptoms, size of largest mass, and histologic subtype. In patients older than 60 years, none of the clinical features was a statistically significant predictor of EFS; however, ChlVPP/ABV hybrid was associated with a decreased risk of an event (relative risk, 0.40; 95% confidence interval, 0.19 to 0.83;
P
= .014) compared with ChlVPP. The 5-year OS for patients ≥ 60 years who received ChlVPP was 30%, compared with 67% for those patients receiving the ChlVPP/ABV regimen (
P
= .0086)

CONCLUSION: Patients ≥ 60 years with HD who require chemotherapy are better treated with ChlVPP/ABV hybrid than with ChlVPP alone.