bluuebunny/crossref_metadata_2025 huggingface dataset:
Positron Emission Tomography Using [18F]-Fluorodeoxy-d-Glucose to Predict the Pathologic Response of Breast Cancer to Primary Chemotherapy
Authors: Smith Ian C. , Welch Andrew E. , Hutcheon Andrew W. , Miller Iain D. , Payne Simon , Chilcott Felice , Waikar Smruti , Whitaker Teena , Ah-See Antoinne K. , Eremin Oleg , Heys Steven D. , Gilbert Fiona J. , Sharp Peter F.
Published: February 2017

PURPOSE: To determine whether [18F]-fluorodeoxy-d-glucose ([18F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy.

PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [18F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens.

RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P = .037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P = .013), complete macroscopic (P = .003), or complete microscopic (P = .001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P = .076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P = .037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P = .038; K, P = .012).

CONCLUSION: [18F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.
Positron Emission Tomography Using [18F]Fluorodeoxyglucose for Monitoring Primary Chemotherapy in Breast Cancer
Authors: Schelling M. , Avril N. , Nährig J. , Kuhn W. , Römer W. , Sattler D. , Werner M. , Dose J. , Jänicke F. , Graeff H. , Schwaiger M.
Published: February 2017

PURPOSE: To address the role of positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) to monitor primary (neoadjuvant) chemotherapy in patients with locally advanced breast cancer.

PATIENTS AND METHODS: Quantification of regional FDG uptake of the breast acquired after the first and second courses of chemotherapy was compared with the baseline scan in 22 patients with a total of 24 breast carcinomas. To evaluate the predictive value of PET imaging, histopathologic response after completion of chemotherapy classified as gross residual disease (GRD) or minimal residual disease (MRD) served as the gold standard.

RESULTS: Significant differences in tracer uptake between nonresponding tumors (GRD) and responding lesions (MRD) were observed (P < .05) as early as after the first course of chemotherapy. Tracer uptake showed little change in tumors with GRD found later in pathologic analysis but decreased sharply to the background level in most tumors with MRD. After the first course, all responders were correctly identified (sensitivity 100%, specificity 85%) by a standardized uptake value decrease below 55% of the baseline scan. At this threshold, histopathologic response could be predicted with an accuracy of 88% and 91% after the first and second courses of therapy, respectively.

CONCLUSION: This study demonstrates that in patients with advanced breast cancer undergoing primary chemotherapy, FDG-PET differentiates responders from nonresponders early in the course of therapy. This may help improve patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose-intensive preoperative chemotherapy in responding patients.
Phase I Clinical and Pharmacokinetic Study of Bcl-2 Antisense Oligonucleotide Therapy in Patients With Non-Hodgkin’s Lymphoma
Authors: Waters Justin S. , Webb Andrew , Cunningham David , Clarke Paul A. , Raynaud Florence , di Stefano Francesca , Cotter Finbarr E.
Published: February 2017

PURPOSE: To evaluate the pharmacokinetics and toxicity of an antisense oligonucleotide targeting bcl-2 in patients with non-Hodgkin’s lymphoma (NHL) and to determine efficacy using clinical and biologic end points.

PATIENTS AND METHODS: Twenty-one patients with Bcl-2–positive relapsed NHL received a 14-day subcutaneous infusion of G3139, an 18-mer phosphorothioate oligonucleotide complementary to the first six codons of the bcl-2 open reading frame. Plasma pharmacokinetics were measured by anion exchange high-performance liquid chromatography. Response was assessed by computed tomography. Changes in Bcl-2 expression were measured by fluorescence-activated cell sorting of patients’ tumor samples.

RESULTS: Eight cohorts of patients received doses between 4.6 and 195.8 mg/m2/d. No significant systemic toxicity was seen at doses up to 110.4 mg/m2/d. All patients displayed skin inflammation at the subcutaneous infusion site. Dose-limiting toxicities were thrombocytopenia, hypotension, fever, and asthenia. The maximum-tolerated dose was 147.2 mg/m2/d. Plasma levels of G3139 equivalent to the efficacious plasma concentration in in vivo models were produced with doses above 36.8 mg/m2/d. Plasma levels associated with dose-limiting toxicity were greater than 4 μg/mL. By standard criteria, there was one complete response, 2 minor responses, nine cases of stable disease, and nine cases of progressive disease. Bcl-2 protein was reduced in seven of 16 assessable patients. This reduction occurred in tumor cells derived from lymph nodes in two patients and from peripheral blood or bone marrow mononuclear cell populations in the remaining five patients.

CONCLUSION: Bcl-2 antisense therapy is feasible and shows potential for antitumor activity in NHL. Downregulation of Bcl-2 protein suggests a specific antisense mechanism.
P-Glycoprotein Inhibitor Valspodar (PSC 833) Increases the Intracellular Concentrations of Daunorubicin In Vivo in Patients With P-Glycoprotein–Positive Acute Myeloid Leukemia
Authors: Tidefelt U. , Liliemark J. , Gruber A. , Liliemark E. , Sundman-Engberg B. , Juliusson G. , Stenke L. , Elmhorn-Rosenborg A. , Möllgård L. , Lehman S. , Xu D. , Covelli A. , Gustavsson B. , Paul C.
Published: February 2017

PURPOSE: The aim of the present study was to evaluate the effect of the cyclosporine derivative valspodar (PSC 833; Amdray, Novartis Pharma, Basel, Switzerland) on the concentration of daunorubicin (dnr) in leukemic blast cells in vivo during treatment.

PATIENTS AND METHODS: Ten patients with acute myeloid leukemia (AML) were included. Leukemic cells from seven of the patients were P-glycoprotein (Pgp)–positive. dnr 100 mg/m2 was given as a continuous infusion over 72 hours. After 24 hours, a loading dose of valspodar was given, followed by a 36-hour infusion of 10 mg/kg per 24 hours. Blood samples were drawn at regular intervals, and concentrations of dnr and its main metabolite, daunorubicinol, in plasma and isolated leukemic cells were determined by high-pressure liquid chromatography.

RESULTS: The mean dnr concentrations in leukemic cells 24 hours after the start of infusion (before valspodar) were 18.8 μmol/L in Pgp-negative samples and 13.5 μmol/L in Pgp-positive samples. After 8 hours of valspodar infusion, these values were 25.8 and 24.0 μmol/L, respectively. The effect of valspodar was evaluated from the ratio of the area under the curve (AUC) for dnr concentration versus time in leukemic cells to the AUC for dnr concentration against time in the plasma. For the seven patients with Pgp-positive leukemia, the mean ratio increased by 52%, from 545 on day 1 to 830 on day 2 (P < .05) when valspodar was given. In the three patients with Pgp-negative leukemia, no significant difference was observed.

CONCLUSION: These results strongly suggest that valspodar, by interacting with Pgp, can increase the cellular uptake of dnr in leukemic blasts in vivo.
Phase II Trial of Gemcitabine Plus Cisplatin in Patients With Metastatic Urothelial Cancer
Authors: Kaufman Donald , Raghavan Derek , Carducci Michael , Levine Ellis Glenn , Murphy Barbara , Aisner Joseph , Kuzel Timothy , Nicol Steven , Oh William , Stadler Walter
Published: February 2017

PURPOSE: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer.

PATIENTS AND METHODS: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m2 was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle. Cisplatin was administered after gemcitabine on day 1 of each cycle. The first 11 patients received an initial cisplatin dose of 100 mg/m2. Due to the hematologic toxicity observed in several of these patients, the dose was reduced to 75 mg/m2 in the remaining 35 patients. Patients were treated with six cycles, unless disease progression or severe toxicity necessitated earlier discontinuation.

RESULTS: Ten of the 46 patients achieved a complete response and nine showed a partial response. The overall response rate was 41%. The median time to treatment failure was 5.5 months. The median survival was 14.3 months, and the 1-year survival probability was 54%. Most of the toxicities were hematologic and, in general, easily manageable.

CONCLUSION: Gemcitabine plus cisplatin is active in the treatment of metastatic urothelial cancer in chemotherapy-naive patients and has an acceptable clinical safety profile. Studies are under way to further define the place of gemcitabine in combination with other chemotherapeutic agents in the treatment of metastatic urothelial cancer.
Dexamethasone for the Prophylaxis of Radiation-Induced Emesis: A National Cancer Institute of Canada Clinical Trials Group Phase III Study
Authors: Kirkbride P. , Bezjak A. , Pater J. , Zee B. , Palmer M.J. , Wong R. , Cross P. , Gulavita S. , Blood P. , Sun A. , Dundas G. , Ganguly P.K. , Lim J. , Chowdhury A.D. , Kumar S.E. , Dar A.R.
Published: February 2017

PURPOSE: To investigate the efficacy of dexamethasone as a prophylactic antiemetic for patients receiving fractionated radiotherapy to the upper abdomen in a randomized controlled trial.

PATIENTS AND METHODS: One hundred fifty-four patients planned to receive fractionated radiotherapy to fields involving the upper abdomen (minimum total dose, 20 Gy; minimum number of fractions, five) were randomized to receive prophylactic dexamethasone (2 mg orally three times a day [tid], starting in the morning of first treatment and continuing until after their fifth treatment) or placebo. The primary end point of the study was the proportion of patients free from emesis during the study period. Secondary end points included a quality-of-life assessment using the core questionnaire of the European Organization for Research and Treatment of Cancer and side effects of dexamethasone therapy in this population of patients.

RESULTS: Fifty-four (70%) out of 75 patients receiving dexamethasone had complete protection versus 37 (49%) out of 75 patients on placebo (P = .025). Most emetic episodes occurred during the initial phase of treatment. Although there was no difference in global quality of life between the two sets of patients, patients receiving dexamethasone had less nausea and vomiting and less loss of appetite but more insomnia.

CONCLUSION: Dexamethasone 2 mg tid seems to be an effective prophylactic antiemetic in this situation. Side effects were acceptable, but there seemed to be no overall effect on global quality of life.
Measuring the Incremental Cost of Clinical Cancer Research
Authors: Goldman Dana P. , Schoenbaum Michael L. , Potosky Arnold L. , Weeks Jane C. , Berry Sandra H. , Escarce Jose J. , Weidmer Beverly A. , Kilgore Meredith L. , Wagle Nikhil , Adams John L. , Figlin Robert A. , Lewis Joy H. , Cohen Joel , Kaplan Richard , McCabe Mary
Published: February 2017

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials.

METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute–sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost.

RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs.

CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.
Phase II Study of Paclitaxel, Ifosfamide, and Cisplatin as Second-Line Treatment in Relapsed Small-Cell Lung Cancer
Authors: Kosmas Christos , Tsavaris Nicolas B. , Malamos Nikolaos A. , Vadiaka Maria , Koufos Christos
Published: February 2017

PURPOSE: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC).

PATIENTS AND METHODS: Eligible patients were those with SCLC who had progressed or relapsed after therapy with carboplatin and etoposide (with or without chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m2 on day 1, ifosfamide 5 g/m2 divided over days 1 and 2, and cisplatin 100 mg/m2 divided over days 1 and 2; PIC was given every 21 days with granulocyte colony-stimulating factor support.

RESULTS: Thirty-three patients (30 men and three women) were entered onto the study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 2]). Metastatic sites at study entry included the lymph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lung nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses included eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two had progressive disease. Median time to progression and overall survival were 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC initiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 [73%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia in six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patients (27%) . No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-related deaths.

CONCLUSION: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned.
Dose Escalation in Non–Small-Cell Lung Cancer Using Three-Dimensional Conformal Radiation Therapy: Update of a Phase I Trial
Authors: Hayman James A. , Martel Mary K. , Ten Haken Randall K. , Normolle Daniel P. , Todd Robert F. , Littles J. Fred , Sullivan Molly A. , Possert Peter W. , Turrisi Andrew T. , Lichter Allen S.
Published: February 2017

PURPOSE: High-dose radiation may improve outcomes in non–small-cell lung cancer (NSCLC). By using three-dimensional conformal radiation therapy and limiting the target volume, we hypothesized that the dose could be safely escalated.

MATERIALS AND METHODS: A standard phase I design was used. Five bins were created based on the volume of normal lung irradiated, and dose levels within bins were chosen based on the estimated risk of radiation pneumonitis. Starting doses ranged from 63 to 84 Gy given in 2.1-Gy fractions. Target volumes included the primary tumor and any nodes ≥ 1 cm on computed tomography. Clinically uninvolved nodal regions were not included purposely. More recently, selected patients received neoadjuvant cisplatin and vinorelbine.

RESULTS: At the time of this writing, 104 patients had been enrolled. Twenty-four had stage I, four had stage II, 43 had stage IIIA, 26 had stage IIIB, and seven had locally recurrent disease. Twenty-five received chemotherapy, and 63 were assessable for escalation. All bins were escalated at least twice. Although grade 2 radiation pneumonitis occurred in five patients, grade 3 radiation pneumonitis occurred in only two. The maximum-tolerated dose was only established for the largest bin, at 65.1 Gy. Dose levels for the four remaining bins were 102.9, 102.9, 84 and 75.6 Gy. The majority of patients failed distantly, though a significant proportion also failed in the target volume. There were no isolated failures in clinically uninvolved nodal regions.

CONCLUSION: Dose escalation in NSCLC has been accomplished safely in most patients using three-dimensional conformal radiation therapy, limiting target volumes, and segregating patients by the volume of normal lung irradiated.
Factors Affecting the Use of Palliative Radiotherapy in Ontario
Authors: Huang J. , Zhou S. , Groome P. , Tyldesley S. , Zhang-Solomans J. , Mackillop W. J.
Published: February 2017

PURPOSE: To describe the use of palliative radiotherapy (PRT) and to identify factors associated with the use of PRT.

MATERIALS AND METHODS: The Ontario Cancer Registry was used to identify 193,253 adult patients who died of cancer between 1986 and 1995. Radiotherapy records from all Ontario cancer centers and the data on socioeconomic status (SES) from the Canadian Census were linked to the Ontario Cancer Registry data. The proportion of cases who received at least one course of PRT at any time within 2 years of death (PRT2Y) was used as a primary measure of the use rate of PRT.

RESULTS: Overall, 26.4% of cases underwent at least one course of PRT. PRT2Y remained relatively constant over the study period. PRT2Y was disease-specific and ranged from 4% for pancreatic cancer to 41% for prostate cancer. Age was negatively associated with PRT2Y (adjusted odds ratio [OR], 4.5 for the youngest group), and SES was positively associated with PRT2Y (adjusted OR, 1.2 for patients from wealthy communities). Patients who were initially diagnosed in a hospital affiliated with a cancer center (adjusted OR, 1.4) or who lived in a county in which a cancer center is located (adjusted OR, 1.2), or who resided in certain regions (adjusted OR, 1.20 for Hamilton and 1.17 for Kingston), were more likely to be treated with PRT.

CONCLUSION: The use of PRT varied across the dispersed population in Ontario and was influenced by factors unrelated to the patient’s needs. An effort should be made to reduce barriers to access for disadvantaged groups.
Attitudes and Practices Among Pediatric Oncologists Regarding End-of-Life Care: Results of the 1998 American Society of Clinical Oncology Survey
Authors: Hilden Joanne M. , Emanuel Ezekiel J. , Fairclough Diane L. , Link Michael P. , Foley Kathleen M. , Clarridge Brian C. , Schnipper Lowell E. , Mayer Robert J.
Published: February 2017

PURPOSE: In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications for care of children dying from cancer.

METHODS: The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which was completed by 228 pediatric oncologists. Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year.

RESULTS: Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as a barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control.

CONCLUSION: Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge.
Relation Between Smoking and Skin Cancer
Authors: De Hertog Sofie A.E. , Wensveen Christianne A.H. , Bastiaens Maarten T. , Kielich Christine J. , Berkhout Marjo J.P. , Westendorp Rudi G.J. , Vermeer Bert J. , Bouwes Bavinck Jan N. ,   for the members of the Leiden Skin Cancer Study
Published: February 2017

PURPOSE: Tobacco smoking is a risk factor for several cancers. The risk of cutaneous malignancies related to smoking, however, is relatively unknown. We investigated the possible association between smoking and skin cancer.

PATIENTS AND METHODS: A hospital-based case-control study was performed that included 161 patients with squamous cell carcinoma, 301 with nodular basal cell carcinoma, 153 with superficial multifocal basal cell carcinoma, 125 with malignant melanoma, and 386 controls. Information on smoking history was collected in personal interviews. Relative risks were estimated using exposure odds ratios from cross-tabulation and logistic regression.

RESULTS: An association between smoking and squamous cell carcinoma of the skin was found (relative risk, 2.3; 95% confidence interval, 1.5 to 3.6; P = .0001), with a higher risk for current smokers (relative risk, 3.3; 95% confidence interval, 1.9 to 5.5) than for former smokers (relative risk, 1.9; 95% confidence interval, 1.2 to 3.0). After adjustment for age, sex, and sun exposure, the relative risk of squamous cell carcinoma was 2.0 (95% confidence interval, 1.2 to 3.2; P = .008). There was a dose-response relationship with number of cigarettes and pipes smoked. No significant association was found between smoking and nodular basal cell carcinoma, superficial multifocal basal cell carcinoma, or malignant melanoma.

CONCLUSION: Tobacco smoking is an independent risk factor for cutaneous squamous cell carcinoma.
The Fifty-Year Decline of Cancer in America
Authors: Rodu Brad , Cole Philip
Published: February 2017

PURPOSE: From 1950 to 1990, the overall cancer mortality rate increased steadily in the United States, a trend which ran counter to declining mortality from other major diseases. The purpose of this study was to assess the impact of lung cancer on all-cancer mortality over the past 50 years.

METHODS: Data from the National Centers for Health Statistics were used to develop mortality rates for all forms of cancer combined, lung cancer, and other-cancer (all-cancer minus lung cancer) from 1950 to 1998.

RESULTS: When lung cancer is excluded, mortality from all other forms of cancer combined declined continuously from 1950 to 1998, dropping 25% during this period. The decline in other-cancer mortality was approximately 0.4% annually from 1950 to 1990 but accelerated to 0.9% per year from 1990 to 1996 and to 2.2% per year from 1996 to 1998.

CONCLUSION: The long-term decline is likely due primarily to improvements in medical care, including screening, diagnosis, and treatment.
Increasing Volume and Changing Characteristics of Invasive Pulmonary Aspergillosis on Sequential Thoracic Computed Tomography Scans in Patients With Neutropenia
Authors: Caillot Denis , Couaillier Jean-Francois , Bernard Alain , Casasnovas Olivier , Denning David W. , Mannone Lionel , Lopez Jose , Couillault Gerard , Piard Francoise , Vagner Odile , Guy Henri
Published: February 2017

PURPOSE: In patients with neutropenia, thoracic computed tomography (CT) halo and air-crescent signs are recognized as major indicators of invasive pulmonary aspergillosis (IPA). Nevertheless, the exact timing of CT images is not well known.

PATIENTS AND METHODS: Seventy-one thoracic CT scans were analyzed in 25 patients with neutropenia with surgically proven IPA.

RESULTS: On the first day of IPA diagnosis with early CT scan (d0), a typical CT halo sign was observed in 24 of 25 patients. At that time, the median number of thoracic lesions was two (range, one to six), and pulmonary involvement was bilateral in 12 cases. The halo sign was present in 68%, 22%, and 19% of cases on d3, d7, and d14, respectively. Similarly, the air-crescent sign was seen in 8%, 28%, and 63% of cases on the same days. Otherwise, a nonspecific air-space consolidation aspect was seen in 31%, 50%, and 18% of cases on the same days. The analysis of calculated aspergillary volumes on CT showed that, despite antifungal treatment, the median volume of lesions increased four-fold from d0 to d7, whereas it remained stable from d7 to d14. Overall, 21 patients (84%) were cured by the medical-surgical approach.

CONCLUSION: In patients with neutropenia, CT halo sign is a highly effective modality for IPA diagnosis. The duration of the halo sign is short, and it demonstrates the value of early CT. The increase of the aspergillosis size on CT in the first days after IPA diagnosis is not correlated with a pejorative immediate outcome when using a combined medical-surgical approach.
Upper-Tract Tumors After an Initial Diagnosis of Bladder Cancer: Argument for Long-Term Surveillance
Authors: Rabbani Farhang , Perrotti Michael , Russo Paul , Herr Harry W.
Published: February 2017

PURPOSE: To determine the relative risk (RR) of upper-tract tumors (UTT) after bladder cancer, stratified by bladder tumor characteristics, demographic factors, and follow-up duration, in order to develop an improved risk-based surveillance strategy.

PATIENTS AND METHODS: The 1973 to 1996 Surveillance, Epidemiology, and End Results (SEER) database was used to determine the observed and expected number of UTT after bladder cancer. The RR with 95% confidence intervals (CI) were calculated, stratifying by race, sex, stage, grade, histology, and follow-up duration. The tumor characteristics and clinical outcome were compared in patients with UTT after bladder cancer and those with de novo UTT.

RESULTS: A total of 94,591 patients had a first diagnosis of bladder cancer, of whom 91,245 had follow-up (median, 4.1 years), with no antecedent or synchronous UTT. UTT developed subsequently in 657 of 91,245 (0.7%), with 12.80 expected cases (RR = 51.3; 95% CI, 47.5 to 55.4). The respective RRs for UTT for white men and women were 64.2 (95% CI, 55.1 to 74.3) and 75.4 (95% CI, 57.7 to 96.9) at less than 2 years, 44.3 (95% CI, 36.7 to 53.0) and 40.5 (95% CI, 27.9 to 56.8) at 2 to 5 years, 50.8 (95% CI, 42.2 to 60.7) and 42.1 (95% CI, 28.8 to 59.4) at 5 to 10 years, and 43.2 (95% CI, 32.6 to 56.1) and 22.2 (95% CI, 10.1 to 42.2) at ≥ 10 years. Similar RRs were seen among different strata of race, stage, grade, and histology. Patients with UTT after bladder cancer had lower stage and improved disease-specific survival compared with those with de novo UTT.

CONCLUSION: The incidence of UTT is stable on long-term follow-up, with no significant risk factors identified. These findings suggest that upper-tract surveillance remain rigorous on extended follow-up of bladder cancer patients.
Weekly Trastuzumab and Paclitaxel Therapy for Metastatic Breast Cancer With Analysis of Efficacy by HER2 Immunophenotype and Gene Amplification
Authors: Seidman Andrew D. , Fornier Monica N. , Esteva Francisco J. , Tan Lee , Kaptain Stamatina , Bach Ariadne , Panageas Katherine S. , Arroyo Crispinita , Valero Vicente , Currie Violante , Gilewski Teresa , Theodoulou Maria , Moynahan Mary Ellen , Moasser Mark , Sklarin Nancy , Dickler Maura , D’Andrea Gabriella , Cristofanilli Massimo , Rivera Edgardo , Hortobagyi Gabriel N. , Norton Larry , Hudis Clifford A.
Published: February 2017

PURPOSE: This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results.

PATIENTS AND METHODS: Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH.

RESULTS: Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m2/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications.

CONCLUSION: Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.
Superior Efficacy of Letrozole Versus Tamoxifen as First-Line Therapy for Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Study of the International Letrozole Breast Cancer Group
Authors: Mouridsen Henning , Gershanovich Mikhail , Sun Yan , Pérez-Carrión Ramón , Boni Corrado , Monnier Alain , Apffelstaedt Justus , Smith Robert , Sleeboom Harm P. , Jänicke Fritz , Pluzanska Anna , Dank Magdolna , Becquart Dominique , Bapsy Poonamalle P. , Salminen Eeva , Snyder Ray , Lassus Mercedes , Verbeek J. Arnold , Staffler Beatrix , Chaudri-Ross Hilary A. , Dugan Margaret
Published: February 2017

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer.

PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor– and/or progesterone receptor–positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability.

RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P = .0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P = .0006), as was the rate of clinical benefit (49% v 38%; P = .001). Survival data are currently immature and not reported here. Both treatments were well tolerated.

CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.
Randomized Trial of Black Cohosh for the Treatment of Hot Flashes Among Women With a History of Breast Cancer
Authors: Jacobson Judith S. , Troxel Andrea B. , Evans Joel , Klaus Lorissa , Vahdat Linda , Kinne David , Lo K. M. Steve , Moore Anne , Rosenman Pamela J. , Kaufman Elizabeth L. , Neugut Alfred I. , Grann Victor R.
Published: February 2017

PURPOSE: Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients.

PATIENTS AND METHODS: Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits.

RESULTS: Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups.

CONCLUSION: Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.
Experience With 2-Chlorodeoxyadenosine in Previously Untreated Children With Newly Diagnosed Acute Myeloid Leukemia and Myelodysplastic Diseases
Authors: Krance R. A. , Hurwitz C. A. , Head D. R. , Raimondi S. C. , Behm F. G. , Crews K. R. , Srivastava D. K. , Mahmoud H. , Roberts W. M. , Tong X. , Blakley R. L. , Ribeiro R. C.
Published: February 2017

PURPOSE: To develop more effective chemotherapy regimens for childhood acute myelogenous leukemia (AML).

PATIENTS AND METHODS: Between June 1991 and December 1996, we administered the nucleoside analog 2-chlorodeoxyadenosine (2-CDA) to 73 children with primary AML and 20 children with secondary AML or myelodysplastic syndrome (MDS). Patients received one or two 5-day courses of 2-CDA (8.9 mg/m2/d) given by continuous infusion. All patients then received one to three courses of daunomycin, cytarabine, and etoposide (DAV) remission induction therapy.

RESULTS: Seventy-two patients with primary AML were assessable for response. Their rate of complete remission (CR) was 24% after one course of 2-CDA, 40% after two courses of 2-CDA, and 78% after DAV therapy. Of the 57 patients who entered CR, 11 subsequently underwent allogeneic bone marrow transplantation (BMT), and 40 underwent autologous BMT. Twenty-nine patients remain in continuous CR after BMT. Two patients remain in CR after chemotherapy only. The 5-year event-free survival (EFS) estimate was 40% (SE = 0.080%). Patients with French-American-British (FAB) M5 AML had a higher rate of CR after treatment with 2-CDA (45% after one course and 70.6% after two courses) than did others (P = .002). In contrast, no patient with FAB M7 AML (n = 10) entered CR after treatment with 2-CDA. Similarly, no patient with primary MDS (n = 6) responded to 2-CDA. Seven patients with secondary AML or MDS (n = 14) had a partial response to one course of 2-CDA.

CONCLUSION: This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.
Preoperative Plasma Levels of Transforming Growth Factor Beta1 (TGF-β1) Strongly Predict Progression in Patients Undergoing Radical Prostatectomy
Authors: Shariat Shahrokh F. , Shalev Moshe , Menesses-Diaz Andres , Kim Isaac Yi , Kattan Michael W. , Wheeler Thomas M. , Slawin Kevin M.
Published: February 2017

PURPOSE: Elevated local and circulating levels of transforming growth factor beta1 (TGF-β1) have been associated with prostate cancer invasion and metastasis. We tested the hypothesis that preoperative plasma TGF-β1 levels would independently predict cancer stage and prognosis in patients who undergo radical prostatectomy.

PATIENTS AND METHODS: The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer (median follow-up, 53.8 months). Preoperative plasma levels of TGF-β1 were measured and correlated with pathologic parameters and clinical outcomes. TGF-β1 levels also were measured in 44 healthy men without cancer, in 19 men with prostate cancer metastatic to regional lymph nodes, and in 10 men with prostate cancer metastatic to bone.

RESULTS: Plasma TGF-β1 levels in patients with lymph node metastases (14.2 ± 2.6 ng/mL) and bone metastases (15.5 ± 2.4 ng/mL) were higher than those in radical prostatectomy patients (5.2 ± 1.3 ng/mL) and healthy subjects (4.5 ± 1.2 ng/mL) (P < .001). In a preoperative analysis, preoperative plasma TGF-β1 level and biopsy Gleason sum both were predictors of organ-confined disease (P = .006 and P = .006, respectively) and PSA progression (P < .001 and P = .021, respectively). In a postoperative multivariate analysis, preoperative plasma TGF-β1 level, pathologic Gleason sum, and surgical margin status were predictors of PSA progression (P = .020,P = .020, and P = .022, respectively). In patients who progressed, preoperative plasma TGF-β1 levels were higher in those with presumed distant compared with local-only failure (P = .019).

CONCLUSION: Plasma TGF-β1 levels are markedly elevated in men with prostate cancer metastatic to regional lymph nodes and bone. In men without clinical or pathologic evidence of metastases, the preoperative plasma TGF-β1 level is a strong predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
Ensuring Quality Cancer Care by the Use of Clinical Practice Guidelines and Critical Pathways
Authors: Smith Thomas J. , Hillner Bruce E.
Published: February 2017

PURPOSE: We describe the impact of clinical practice guidelines (CPGs) on improvement in oncology treatment processes or outcomes.

METHODS: We performed a comprehensive search of the literature from 1966 to the present and a directed review of the literature.

RESULTS: Improvements have been demonstrated in compliance with evidence-based guidelines or evidence-based medicine, and in short-term length of stay, complication rates, and financial outcomes. The data suggest that patient satisfaction can be maintained despite a shorter length of stay. There has been one example of province-wide improvement in disease-free and overall survival of breast cancer patients coincident with the adoption of CPGs. The components of successful guidelines can be summarized as follows: (1) development is based on evidence, with the guideline formulated by key physicians in the group; (2) the guidelines are disseminated to all affected health care professionals for critique; (3) implementation includes direct feedback on performance to physicians or general feedback on system performance; and (4) there is accountability for performance according to the guidelines. This accountability can consist of voluntary peer pressure to conform to evidence-based medicine, and it does not require a financial reward or penalty.

CONCLUSION: Some attempts to improve practice have been moderately successful in achievement of reduced health care costs, reduced hospital length of stay, and possibly improved outcomes. Other methods that are still in use have been demonstrated to have little effect. Programs that have not succeeded have relied on voluntary change in practice behavior without incentives to change or have had no accountability component. Further research is needed to assess how guidelines are enacted in organizations other than those demonstrably committed to improvement, ways to improve compliance of health care providers who are not committed to change, and methods to improve accountability.
Paclitaxel and Gemcitabine Chemotherapy for Advanced Transitional-Cell Carcinoma of the Urothelial Tract: A Phase II Trial of the Minnie Pearl Cancer Research Network
Authors: Meluch Anthony A. , Greco F. Anthony , Burris Howard A. , O’Rourke Timothy , Ortega Gregory , Steis Ronald G. , Morrissey Lisa H. , Johnson Valerie , Hainsworth John D.
Published: February 2017

PURPOSE: To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract.

PATIENTS AND METHODS: Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered, community-based, phase II trial between May 1997 and December 1999. All patients were treated with paclitaxel 200 mg/m2 by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m2 IV on days 1, 8, and 15; courses were repeated every 21 days. Patients who had objective response or stable disease continued treatment for six courses.

RESULTS: Twenty-nine of 54 patients (54%; 95% confidence interval, 40% to 67%) had major responses to treatment, including 7% complete responses. With a median follow-up of 24 months, 16 patients (30%) remain alive and nine (17%) are progression-free. The median survival for the entire group was 14.4 months; 1- and 2-year actuarial survival rates were 57% and 25%, respectively. Seven (47%) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine. Grade 3/4 toxicity was primarily hematologic, including leukopenia (46%), thrombocytopenia (13%), and anemia (28%). Ten patients (19%) required hospitalization for neutropenia and fever, and one patient had treatment-related septic death.

CONCLUSION: The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract. Response rate and duration compare favorably with those produced by other active, first-line regimens. This regimen should be further evaluated in phase II and III studies, as well as in patients with compromised renal function.
Prognostic Value of Initial Fasting Serum Gastrin Levels in Patients With Zollinger-Ellison Syndrome
Authors: Berger Adam C. , Gibril Fathia , Venzon David J. , Doppman John L. , Norton Jeffrey A. , Bartlett David L. , Libutti Steven K. , Jensen Robert T. , Alexander H. Richard
Published: February 2017

PURPOSE: To assess the value of the initial fasting serum gastrin (FSG) at presentation in patients with Zollinger-Ellison Syndrome (ZES) in predicting primary tumor characteristics and survival.

PATIENTS AND METHODS: A total of 239 patients were treated for ZES between December 1981 and September 1998, with a mean follow-up of 9.1 ± 0.6 years. At initial evaluation, 86 patients (36%) had mild (0 to 499 pg/mL), 61 (25.5%) had moderate (500 to 1,000 pg/mL), and 92 (38.5%) had severe (> 1,000 pg/mL) elevations in FSG. Primary tumor location and size, presence of lymph node or hepatic metastases, and survival were analyzed based on the level of initial FSG.

RESULTS: In patients with sporadic ZES, but not in those with multiple endocrine neoplasia type 1 (MEN-1) and ZES, there was a significant relationship between the level of initial FSG and tumor size and location of primary tumor, frequency of lymph node and liver metastases, and survival. The median 5- and 10-year survival decreased with increasing initial FSG (P < .001) in patients with sporadic ZES; MEN-1 patients lived longer than sporadic ZES patients (P = .012), and survival in this group was not associated with the level of initial FSG. Multivariate analysis showed that factors independently associated with death from disease in patients with sporadic ZES were liver metastases (P = .0001), a pancreatic site (P = .0027), and primary tumor size (P = .011) but not initial FSG (P > .30).

CONCLUSION: The severity of FSG at presentation is associated with size and site of tumor and the presence of hepatic metastases, factors that are significant independent predictors of outcome. The level of FSG at presentation may be useful in planning the nature and extent of the initial evaluation and management in patients with sporadic ZES.