bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Progression of Breast Cancer Malignant Behavior: What to Expect and When to Expect it
Authors: Heimann Ruth , Hellman Samuel 
Published: February 2017

PURPOSE: Seemingly localized breast cancer is a heterogeneous mix of truly localized cancers and cancers with occult metastases. Our purpose is to determine the parameters of metastatic proclivity for the different clinical presentations of operable breast cancer and to present quantitative prognostic information useful to both doctors and patients.PATIENTS AND METHODS: A series of regionally treated breast cancer patients was analyzed to determine the likelihood and time of the appearance of clinical metastases for different clinical subgroups. Patients operated on at the University of Chicago from 1927 to 1987 for clinically regionally localized breast cancer, who received no systemic therapy as a part of their initial treatment, were included. Overall survival and distant disease-free survival in this mature series are analyzed.RESULTS: Metastagenicity, the metastatic proclivity of a tumor, increases with both tumor size and nodal involvement. This is also true for virulence, which is the rate at which these metastases appear. Each clinical group has a cured population, even those with extensive nodal involvement. A table provides a tool for determining the proportion of risk expended in each clinical group as a function of the distant disease-free survival. Whereas the likelihood of metastasis increases with tumor size and nodal involvement, the time to their appearance decreases.CONCLUSIONS: Breast cancer metastagenicity and virulence are heterogeneous even within clinically similar groups of operable breast cancer patients. Tumor progression is correlated with increasing tumor size and nodal involvement. Markers are needed to identify individual tumor virulence and metastagenicity.
Surveillance for Recurrent Head and Neck Cancer Using Positron Emission Tomography
Authors: Lowe Val J. , Boyd James H. , Dunphy Frank R. , Kim Han , Dunleavy T. , Collins Brian T. , Martin David , Stack Brendan C. , Hollenbeak Chris , Fletcher J.W. 
Published: February 2017

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P = .013) or PE (P = .002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.
Fatigue in Breast Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life
Authors: Bower Julienne E. , Ganz Patricia A. , Desmond Katherine A. , Rowland Julia H. , Meyerowitz Beth E. , Belin Thomas R. 
Published: February 2017

PURPOSE: To describe the occurrence of fatigue in a large sample of breast cancer survivors relative to general population norms and to identify demographic, medical, and psychosocial characteristics of fatigued survivors. PATIENTS AND METHODS: Breast cancer survivors in two large metropolitan areas completed standardized questionnaires as part of a survey study, including the RAND 36-item Health Survey, Center for Epidemiological Studies–Depression Scale, Breast Cancer Prevention Trial Symptom Checklist, Medical Outcomes Study Sleep Scale, and demographic and treatment-related measures. RESULTS: On average, the level of fatigue reported by the breast cancer survivors surveyed (N = 1,957) was comparable to that of age-matched women in the general population, although the breast cancer survivors were somewhat more fatigued than a more demographically similar reference group. Approximately one third of the breast cancer survivors assessed reported more severe fatigue, which was associated with significantly higher levels of depression, pain, and sleep disturbance. In addition, fatigued women were more bothered by menopausal symptoms and were somewhat more likely to have received chemotherapy (with or without radiation therapy) than nonfatigued women. In multivariate analyses, depression and pain emerged as the strongest predictors of fatigue. CONCLUSION: Although the majority of breast cancer survivors in this large and diverse sample did not experience heightened levels of fatigue relative to women in the general population, there was a subgroup of survivors who did report more severe and persistent fatigue. We identified characteristics of these women that may be helpful in elucidating the mechanisms underlying fatigue in this population, as well as directing intervention efforts.
Predictive Role of Interphase Cytogenetics for Survival of Patients With Multiple Myeloma
Authors: Königsberg Robert , Zojer Niklas , Ackermann Jutta , Krömer Elisabeth , Kittler Harald , Fritz Elke , Kaufmann Hannes , Nösslinger Thomas , Riedl Lucia , Gisslinger Heinz , Jäger Ulrich , Simonitsch Ingrid , Heinz Renate , Ludwig Heinz , Huber Heinz , Drach Johannes 
Published: February 2017

PURPOSE: Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations. PATIENTS AND METHODS: Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed. RESULTS: By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P = .006 and 40.0% v 73.2%, P = .008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P = .008 and 16.2 v 51.3 months, P = .008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P = .02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P < .001, respectively). CONCLUSION: For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.
Silent Lacunar Lesions Detected by Magnetic Resonance Imaging of Children With Brain Tumors: A Late Sequela of Therapy
Authors: Fouladi Maryam , Langston James , Mulhern Raymond , Jones Dana , Xiong Xiaoping , Yang Jianping , Thompson Stephen , Walter Andrew , Heideman Richard , Kun Larry , Gajjar Amar 
Published: February 2017

BACKGROUND: Cerebral lacunes, which generally appear on magnetic resonance imaging as foci of white matter loss, usually occur in adults after ischemic infarcts. We report the development of lacunes in children after therapy for brain tumors. PATIENTS AND METHODS: We reviewed the clinical characteristics and radiologic studies of 524 consecutive children with brain tumors treated over a 10-year period. We documented the neuropsychologic findings associated with lacunes and the factors predictive of lacunar development. RESULTS: Lacunes developed in none of the 103 patients observed or treated with surgery alone. Twenty-five of the 421 patients treated with chemotherapy or radiation therapy or both had lacunes. Patients were a median of 4.5 years old at the time of both diagnosis (range, 0.3 to 19.8 years) and radiotherapy (range, 1.5 to 20 years). Fourteen patients were treated with craniospinal irradiation, and 11 were treated with local radiotherapy. The median time from radiotherapy to the appearance of lacunes was 2.01 years (range, 0.26 to 5.7 years). For all patients, lacunes were an incidental finding with no corresponding clinical deficits. The factor most predictive of lacunar development was age less than 5 years at the time of radiotherapy (P = .010). There was no significant difference in estimated decline in intelligence quotient scores between patients with lacunes and age and diagnosis-matched controls. CONCLUSION: Lacunes may be caused by therapy-induced vasculopathy in children with brain tumors, with the most significant predictor being age less than 5 years at the time of radiotherapy.
Primary Mediastinal Germ Cell Tumors in Children and Adolescents: Results of the German Cooperative Protocols MAKEI 83/86, 89, and 96
Authors: Schneider Dominik T. , Calaminus Gabriele , Reinhard Harald , Gutjahr Peter , Kremens Bernhard , Harms Dieter , Göbel Ulrich 
Published: February 2017

PURPOSE: To evaluate children and adolescents with primary mediastinal teratoma and malignant germ cell tumors (GCTs). PATIENTS AND METHODS: Forty-seven patients from the German nontesticular GCT studies were analyzed (median age, 2.5 years; range, neonate to 17 years). Teratoma (n = 21) were resected, and no adjuvant treatment was given. Malignant GCTs (n = 26) were treated with cisplatin-based chemotherapy and resection. Three of 26 patients underwent radiotherapy. RESULTS: In all patients with teratoma, tumor markers were normal. Surgery of teratoma was complete in 17 of 21 patients and microscopically incomplete in four of 21 patients, and we observed no relapse after a median follow-up of 29 months. In 23 of 26 patients with malignant GCTs, alpha-fetoprotein and/or beta-human chorionic gonadotropin were elevated. Twelve of 26 patients received adjuvant chemotherapy after initial resection, which was complete in six of 12 patients, whereas delayed resection after preoperative chemotherapy was complete in 10 of 11 patients (P = .03). Four of six patients underwent second-look thoracotomy after incomplete primary surgery. Three of 26 patients did not undergo tumor resection. The final completeness of resection was the strongest prognostic indicator (event-free survival [EFS], 0.94 ± 0.06 v 0.42 ± 0.33; P < .002). Local stage and distant metastases were not prognostically significant at the .05 level. For all malignant GCTs, the 5-year survival rate was 0.87 ± 0.05 (median follow-up, 51 months), with an EFS of 0.83 ± 0.05. CONCLUSION: The prognosis of mediastinal teratoma is excellent after complete or microscopically incomplete resection. In children with malignant GCT, the prognosis is favorable with a therapeutic strategy of delayed resection after preoperative chemotherapy. In most children, the diagnosis can be based on elevated tumor markers and imaging. Biopsy is indicated in nonsecreting GCT.
Phase I Evaluation of Sequential Doxorubicin Gemcitabine Then Ifosfamide Paclitaxel Cisplatin for Patients With Unresectable or Metastatic Transitional-Cell Carcinoma of the Urothelial Tract
Authors: Dodd Paul M. , McCaffrey John A. , Hilton Susan , Mazumdar Madhu , Herr Harry , Kelly W. Kevin , Icasiano Evelyn , Boyle Mary G. , Bajorin Dean F. 
Published: February 2017

PURPOSE: This phase I trial sought to evaluate the toxicity of and determine the maximum-tolerated dose (MTD) for the two-drug regimen doxorubicin and gemcitabine (AG) followed by the three-drug regimen of ifosfamide, paclitaxel, and cisplatin (ITP) in patients with unresectable or metastatic transitional-cell carcinoma. PATIENTS AND METHODS: Patients received AG every other week for six cycles followed by ITP every 3 weeks for four cycles. Five AG dose levels were investigated, up to doxorubicin 50 mg/m2 and gemcitabine 2,000 mg/m2, to determine the MTD of the regimen. The dose and schedule of ITP were constant: ifosfamide 1,500 mg/m2 (days 1 to 3); paclitaxel 200 mg/m2 (day 1); and cisplatin 70 mg/m2 (day 1). Granulocyte colony-stimulating factor was given between all cycles of therapy. RESULTS: Fifteen patients enrolled onto this phase I trial. AG was well tolerated at all dose levels, with no grade 3 or 4 myelosuppression. Toxicity experienced with ITP included grade 3 and 4 granulocytopenia in four patients and grade 3 nausea/vomiting in three patients. No grade 3 and 4 neurotoxicity was observed. Eight of 14 assessable patients experienced a major response to AG, including five of six patients treated at the two highest AG dose levels. After completion of AG-ITP, nine of 14 assessable patients had a major response (three complete responses and six partial responses). CONCLUSION: AG is a well-tolerated and active regimen. Sequential chemotherapy with AG-ITP is also well tolerated, and phase II investigation at the highest dose level is ongoing.
Etoposide and Cisplatin/Etoposide, Methotrexate, and Actinomycin D (EMA) Chemotherapy for Patients With High-Risk Gestational Trophoblastic Tumors Refractory to EMA/Cyclophosphamide and Vincristine Chemotherapy and Patients Presenting With Metastatic Placental Site Trophoblastic Tumors
Authors: Newlands E.S. , Mulholland P.J. , Holden L. , Seckl M.J. , Rustin G.J. S. 
Published: February 2017

PURPOSE: To evaluate the results of etoposide, cisplatin/etoposide, methotrexate, and actinomycin D (EP/EMA) chemotherapy in patients with gestational trophoblastic tumors (GTTs), who have relapsed after or who have become refractory to EMA/cyclophosphamide and vincristine (CO) chemotherapy, and in patients presenting with metastatic placental site trophoblastic tumors (PSTTs). PATIENTS AND METHODS: We have treated a total of 34 patients with GTT and eight patients with metastatic PSTT with the EP/EMA chemotherapy schedule. RESULTS: Twenty-two patients received EP/EMA because of apparent drug resistance to EMA/CO, and because the human chorionic gonadotropin (hCG) was near normal, they were not assessable for response. Twenty-one of these patients (95%) are alive and in remission. In the group where the hCG was high enough to confirm a response (greater than one log fall in hCG) to EP/EMA, all 12 patients responded and nine of these patients (75%) are alive and in remission. We have treated three patients with PSTT where the interval from antecedent pregnancy was less than 2 years, and all patients (100%) are alive and in remission. We have treated five patients where the interval from antecedent pregnancy was greater than 2 years and one fifth (20%) remain in remission. The survival for patients with GTT is 30 (88%) out of 34 patients and four (50%) out of eight patients for PSTT, giving an overall survival for these two cohorts of 34 (81%) out of 42 patients. The toxicity of this schedule is significant, with grade 3 or 4 toxicity (National Cancer Institute common toxicity criteria) recorded in hemoglobin (21%), WBC (68%), and platelets (40%). The role of surgery in this group of patients is important and contributed to sustained remission in five patients (23%) and possibly helped an additional seven patients (32%). CONCLUSION: EP/EMA is an effective but moderately toxic regimen for patients with high-risk GTT who become refractory to or relapse from EMA/CO chemotherapy. Also, EP/EMA clearly has activity in patients with metastatic PSTT.
Depression in Patients With Lung Cancer: Prevalence and Risk Factors Derived From Quality-of-Life Data
Authors: Hopwood Penelope , Stephens Richard J. ,   for the British Medical Research Council Lung Cancer Working Party
Published: February 2017

PURPOSE: To evaluate self-reported depression rates in patients with inoperable lung cancer and to explore demographic, clinical, and quality-of-life (QOL) factors associated with depression and thus identify patients at risk. PATIENTS AND METHODS: Nine hundred eighty-seven patients from three palliative treatment trials conducted by the Medical Research Council Lung Cancer Working Party formed the study sample. 526 patients (53%) had poor prognosis small-cell lung cancer (SCLC) and 461 patients (47%) had good prognosis non–small-cell lung cancer (NSCLC). Hospital Anxiety and Depression Scale data and QOL items from the Rotterdam Symptom Checklist were analyzed, together with relevant demographic and clinical factors. RESULTS: Depression was self-rated in 322 patients (33%) before treatment and persisted in more than 50% of patients. SCLC patients had a three-fold greater prevalence of case depression than those with NSCLC (25% v 9%; P < .0001). An increased rate for women was found for good performance status (PS) patients (PS of 0 or 1) but the sex difference reduced for poor PS patients (PS of 3 or 4) because of increased depression rates for men (χ2 for trend, P < .0001). Multivariate analysis showed that functional impairment was the most important risk factor; depression increased by 41% for each increment on the impairment scale. Pretreatment physical symptom burden, fatigue, and clinician-rated PS were also independent predictors, but cell type was not. CONCLUSION: Depression is common and persistent in lung cancer patients, especially those with more severe symptoms or functional limitations. Psychologic screening and appropriate intervention is an essential part of palliative care.
Phase I and Pharmacokinetic Study of Farnesyl Protein Transferase Inhibitor R115777 in Advanced Cancer
Authors: Zujewski J. , Horak I.D. , Bol C.J. , Woestenborghs R. , Bowden C. , End D.W. , Piotrovsky V.K. , Chiao J. , Belly R.T. , Todd A. , Kopp W.C. , Kohler D.R. , Chow C. , Noone M. , Hakim F.T. , Larkin G. , Gress R.E. , Nussenblatt R.B. , Kremer A.B. , Cowan K.H. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks.PATIENTS AND METHODS: Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1.RESULTS: Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months.CONCLUSION: R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1,000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing.
“Low-Risk” Prediction Rule for Pediatric Oncology Patients Presenting With Fever and Neutropenia
Authors: Klaassen Robert J. , Goodman T. Robin , Pham Ba , Doyle John J. 
Published: February 2017

PURPOSE: To prospectively derive and validate a clinical prediction rule to allow a more tailored approach to the management of pediatric oncology outpatients presenting with fever and neutropenia. PATIENTS AND METHODS: The clinical prediction rule was derived over a 1-year period and then validated over the following 8 months in a new set of fever and neutropenia episodes. Patients were excluded if they presented with comorbidity or an abnormal chest x-ray (CXR). RESULTS: Significant bacterial infection (SBI; defined as any blood or urine culture positive for bacteria, interstitial or lobar consolidation on CXR, or unexpected death from infection) was documented in 43 of the 227 episodes. Multivariate analysis found four significant factors: bone marrow disease, general appearance unwell on initial examination, monocyte count less than 0.1 × 109/L, and peak oral or oral equivalent temperature greater than 39°C. Only the monocyte count contributed to determining a low-risk group, excluding SBI with 84% sensitivity (95% confidence interval [CI], 61% to 100%), 42% specificity (95% CI, 38% to 46%), and a negative predictive value of 92% (95% CI, 76% to 100%). If the monocyte count was ≥ 0.1 × 109/L at the time of presentation (low risk), the incidences of SBI and bacteremia were 8% and 5%, respectively, versus 25% and 17% in the high-risk group. When validated in a new population of 136 episodes of fever and neutropenia, the incidences of SBI and bacteremia in the low-risk group were 12% and 5%, respectively, and 25% and 19% in the high-risk group. CONCLUSION: Pediatric oncology outpatients with fever and neutropenia who present with an initial monocyte count of ≥ 0.1 × 109/L and do not have comorbidity or an abnormal CXR at the time of presentation are at lower risk for SBI and can be considered for less aggressive initial therapy.