bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin/Ifosfamide Window Therapy for Osteosarcoma: Results of the St Jude Children’s Research Hospital OS-91 Trial
Authors: Meyer William H. , Pratt Charles B. , Poquette Catherine A. , Rao Bhaskar N. , Parham David M. , Marina Neyssa M. , Pappo Alberto S. , Mahmoud Hazem H. , Jenkins Jesse J. , Harper James , Neel Michael , Fletcher Barry D. 
Published: February 2017

PURPOSE: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. RESULTS: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. CONCLUSION: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.
Tumor Variants by Hormone Receptor Expression in White Patients With Node-Negative Breast Cancer From the Surveillance, Epidemiology, and End Results Database
Authors: Anderson William F. , Chu Kenneth C. , Chatterjee Nilanjan , Brawley Otis , Brinton Louise A. 
Published: February 2017

PURPOSE: Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. METHODS: Breast cancer records were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER−), independent progesterone receptor (PR+ and PR−), and joint ERPR expression (ER+PR+, ER+PR−, ER−PR+, and ER−PR−). RESULTS: Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER− and PR− breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor size, grade, and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR− to ER−PR+ to ER−PR−. CONCLUSION: Variations of standard tumor cell characteristics and breast cancer–specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical features.
Neuroblastoma With Symptomatic Spinal Cord Compression at Diagnosis: Treatment and Results With 76 Cases
Authors: De Bernardi Bruno , Pianca Clotilde , Pistamiglio Paola , Veneselli Edvige , Viscardi Elisabetta , Pession Andrea , Alvisi Patrizia , Carli Modesto , Donfrancesco Alberto , Casale Fiorina , Giuliano Maria Grazia , di Montezemolo Luca Cordero , Di Cataldo Andrea , Lo Curto Margherita , Bagnulo Serenella , Schumacher Richard Fabian , Tamburini Angela , Garaventa Alberto , Clemente Luigi , Bruzzi Paolo 
Published: February 2017

PURPOSE: To report on the treatment of patients with newly diagnosed neuroblastoma presenting with spinal cord compression (SCC). PATIENTS AND METHODS: Of 1,462 children with neuroblastoma registered between 1979 and 1998, 76 (5.2%) presented with signs/symptoms of SCC, including motor deficit in 75 patients (mild in 43, moderate in 22, severe [ie, paraplegia] in 10), pain in 47, sphincteric deficit in 30, and sensory loss in 11. Treatment of SCC consisted of radiotherapy in 11 patients, laminectomy in 32, and chemotherapy in 33. Laminectomy was more frequently performed in cases with favorable disease stages and in those with severe motor deficit, whereas chemotherapy was preferred in patients with advanced disease. RESULTS: Thirty-three patients achieved full neurologic recovery, 14 improved, 22 remained stable, and eight worsened, including three who become paraplegic. None of the 10 patients with grade 3 motor deficit, eight of whom were treated by laminectomy, recovered or improved. In the other 66 patients, the neurologic response to treatment was comparable for the three therapeutic modalities. All 11 patients treated by radiotherapy and 26 of 32 patients treated by laminectomy, but only two of 33 treated by chemotherapy, received additional therapy for SCC. Fifty-four of 76 patients are alive at time of the analysis, with follow-up of 4 to 209 months (median, 139 months). Twenty-six (44%) of 54 survivors have late sequelae, mainly scoliosis and sphincteric deficit. CONCLUSION: Radiotherapy, laminectomy, and chemotherapy showed comparable ability to relieve or improve SCC. However, patients treated with chemotherapy usually did not require additional therapy, whereas patients treated either with radiotherapy or laminectomy commonly did. No patient presenting with (or developing) severe motor deficit recovered or improved. Sequelae were documented in 44% of surviving patients.
Why Academic Divisions of Hematology/Oncology Are in Trouble and Some Suggestions for Resolution
Authors: Smith Thomas J. , Girtman John , Riggins Jerry 
Published: February 2017

PURPOSE: Academic divisions of hematology/oncology seem to have difficulty recruiting and retaining excellent productive clinicians. A major reason for this is that salaries do not compete with the private sector for similar work. METHODS: We reviewed divisional finances productivity, and experiences from faculty members leaving. RESULTS: The academic salaries are approximately one third of practice because the chemotherapy concession has been given to the academic hospital. In addition, there may be substantial problems in under-billing, lack of attention to detail in billing, and poor collection practices. CONCLUSION: Academic practice still has much to offer, including opportunities for research and multidisciplinary team management, although the differences may narrow over the coming years. Attention to detail in the billing, collection for work performed, and increasing academic salaries to levels nearer to private practice are necessary components of the solution to recruit and retain quality pro-ductive clinicians.
Omission of Histologic Grading From Clinical Decision Making May Result in Overuse of Adjuvant Therapies in Breast Cancer: Results From a Nationwide Study
Authors: Lundin J. , Lundin M. , Holli K. , Kataja V. , Elomaa L. , Pylkkänen L. , Turpeenniemi-Hujanen T. , Joensuu H. 
Published: February 2017

PURPOSE: To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. PATIENTS AND METHODS: The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. RESULTS: Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. CONCLUSION: Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.
Microsomal Epoxide Hydrolase Expression as a Predictor of Tamoxifen Response in Primary Breast Cancer: A Retrospective Exploratory Study With Long-Term Follow-Up
Authors: Fritz Peter , Mürdter Thomas E. , Eichelbaum Michel , Siegle Isabel , Weissert Matthias , Zanger Ulrich M. 
Published: February 2017

PURPOSE: It has been suggested that estrogen receptor–independent high-affinity binding sites for antiestrogens could limit their local bioavailability and response. Microsomal epoxide hydrolase (mEH) was recently shown to be a component of the antiestrogen binding site complex. We investigated whether mEH expression in primary breast tumors is related to disease outcome and to the efficacy of tamoxifen treatment. PATIENTS AND METHODS: Expression of mEH was semiquantitatively assessed by immunohistochemistry in sections prepared from archival paraffin blocks of primary breast cancers from 179 patients with a mean follow-up time of 81 months. RESULTS: Expression of mEH was correlated with poor disease outcome in all patients (P < .01; n = 179) and in patients receiving tamoxifen (P < .01; n = 78), but not in patients not treated with tamoxifen. Moreover, mEH was an independent prognostic factor by Cox regression analysis. CONCLUSION: The results of this first exploratory study suggest that mEH expression in primary breast cancer could be of predictive value for response to tamoxifen treatment and/or may be a novel independent prognostic factor for survival. The results are in agreement with the model that mEH participates in an estrogen receptor–independent tamoxifen- binding complex.
Equivalent Racial Outcome After Conformal Radiotherapy for Prostate Cancer: A Single Departmental Experience
Authors: Connell Philip P. , Ignacio Lani , Haraf Daniel , Awan Azhar M. , Halpern Howard , Abdalla Ibrahim , Nautiyal Jaishanker , Jani Ashesh B. , Weichselbaum Ralph R. , Vijayakumar Srinivasan 
Published: February 2017

PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P = .91), intermediate (52% v 62%, P = .44), and unfavorable categories (36% v 45%, P = .09). Race was not an independent prognostic factor (P = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.
Transurethral Resection of Muscle-Invasive Bladder Cancer: 10-Year Outcome
Authors: Herr Harry W. 
Published: February 2017

PURPOSE: To determine the 10-year outcome of patients with muscle-invasive bladder cancer treated by transurethral resection (TUR) alone. PATIENTS AND METHODS: Of 432 newly evaluated patients with muscle-invasive bladder cancer, 151 were treated by standard radical cystectomy or by definitive TUR, if restaging TUR of the primary tumor site showed no (T0) or only non–muscle-invasive (T1) residual tumor. Patients were followed-up every 3 to 6 months thereafter for a minimum of 10 years and up to 20 years. Primary end points of the study were disease-specific survival, survival with a bladder, frequency of recurrent invasive tumors in the bladder, and survival after salvage cystectomy. RESULTS: The 10-year disease-specific survival was 76% of 99 patients who received TUR as definitive therapy (57% with bladder preserved) compared with 71% of 52 patients who had immediate cystectomy (P = .3). Of the 99 patients treated with TUR, 82% of 73 who had T0 on restaging TUR survived versus 57% of the 26 patients who had residual T1 tumor on restaging TUR (P = .003). Thirty-four patients (34%) relapsed in the bladder with a new muscle-invasive tumor, 18 (53%) were successfully treated with salvage therapy via cystectomy, and 16 patients (16%) died of disease. CONCLUSION: Radical TUR for muscle-invasive bladder cancer is a successful bladder-sparing therapeutic strategy in selected patients who have no residual tumor on a repeat vigorous resection of the primary tumor site.
Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Micrometastases of Primary Cutaneous Malignant Melanoma
Authors: Acland K.M. , Healy C. , Calonje E. , O’Doherty M. , Nunan T. , Page C. , Higgins E. , Russell-Jones R. 
Published: February 2017

PURPOSE: Sentinel node biopsy (SNB) is a surgical technique for detecting micrometastatic disease in the regional draining nodes. 2-fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scanning is an imaging technique that can detect clinically undetectable metastases. This prospective study was undertaken to compare the sensitivity of FDG-PET scanning with SNB in the detection of micromatastatic malignant melanoma.PATIENTS AND METHODS: Fifty consecutive patients (23 women, 27 men; mean age, 53 years) with primary melanoma >1 mm thick or lymphatic invasion were recruited (mean, 2.41 mm). Primary lesions had been narrowly excised (<1 cm). Patients underwent PET scanning followed by SNB, using a dual technique. Preoperative lymphoscintigraphy was used to identify the draining basin. Lymph nodes were examined histologically and immunostained for S100 and HMB 45.RESULTS: The sentinel node (SN) was identified in all patients. Fourteen patients (28%) had positive SNBs, including eight patients with melanoma <1.5 mm thick. In none of these 14 patients did PET scans identify metastatic disease in the SN or draining basin. In seven patients, the PET scans were positive in other locations, and in four cases, this was suspicious of metastatic disease. However, no patient has developed recurrent melanoma (mean follow-up, 15 months). All patients with positive SNBs underwent therapeutic lymph node dissection. Further lymph node involvement was found in two patients (primary lesions, 1.3 mm and 3.5 mm thick).CONCLUSION: This study demonstrates the limitations of FDG-PET scanning in staging patients with primary melanoma. SNB is the only reliable method for identifying micrometastatic disease in the regional draining node.
Definitive Results of a Phase II Trial of Cisplatin, Epirubicin, Continuous-Infusion Fluorouracil, and Gemcitabine in Stage IV Pancreatic Adenocarcinoma
Authors: Reni M. , Passoni P. , Panucci M. G. , Nicoletti R. , Galli L. , Balzano G. , Zerbi A. , Di Carlo V. , Villa E. 
Published: February 2017

PURPOSE: To evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients ≤ 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m2/d as a protracted venous infusion. RESULTS: Between April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients. CONCLUSION: PEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.
Discrepancies in Clinical Laboratory Testing of Eligibility for Trastuzumab Therapy: Apparent Immunohistochemical False-Positives Do Not Get the Message
Authors: Tubbs R.R. , Pettay J.D. , Roche P.C. , Stoler M.H. , Jenkins R.B. , Grogan T.M. 
Published: February 2017

BACKGROUND: Several studies have reported what seem to be false-positive results using the Food and Drug Administration (FDA)–approved HercepTest (Dako Corp, Carpinteria, CA) to profile Her-2/neu amplification and overproduction in breast carcinoma. False-positive status has been based on comparisons with gene copy enumeration by fluorescence in situ hybridization (FISH) and with comparisons to immunohistochemistry (IMH) results using a monoclonal antibody. However, simple overexpression by tumor cells that have normal gene copy has not been evaluated by profiling mRNA expression, ie, such cases could simply represent true-positive, transcriptionally upregulated overexpression. MATERIALS AND METHODS: Four hundred infiltrating ductal carcinomas of breast were evaluated by IMH using monoclonal (CB11; Ventana Medical Systems, Inc, Tucson, AZ) and polyclonal (HercepTest; Dako) antibodies after antigen retrieval (AR). A polyclonal antibody sans AR (PCA/SAR) was also used. All IMH stains were evaluated and scored according to the guidelines for the FDA-approved HercepTest. A total of 145 of 400 carcinomas were subsequently evaluated by direct and digoxigenin-labeled (Dig) FISH, and 144 of 400 were evaluated by detection of mRNA overexpression via autoradiographic RNA:RNA in situ hybridization. RESULTS: Overall HercepTest/CB11 IMH discordance was 12%. Expression of mRNA was highly concordant with FISH and DigFISH amplification and with CB11 and PCA/SAR immunohistology. IMH false-positive cases (no Her-2/neu gene amplification) occurred with both HercepTest (23%) and CB11 (17%), and the majority of false-positive results (34 of 44) were scored as 2+. All 2+ false-positive cases were mRNA-negative. Combined results of HercepTest and CB11 showed that 79% (38 of 48) of 3+ cases were Her-2/neu gene amplified, but only 17% (seven of 41) of 2+ cases had increased gene copy. CONCLUSION: Discordant HercepTest/FISH results, and to a lesser extent discordance with CB11 IMH, are most commonly false-positive results with a score of 2+. The 2+ score as defined in the guidelines for the FDA-approved HercepTest should not be used as a criterion for trastuzumab therapy unless confirmed by FISH. Determination of Her-2 gene copy number by FISH may be a more accurate and reliable method for selecting patients eligible for trastuzumab therapy.
Effects of Epoetin Alfa on Hematologic Parameters and Quality of Life in Cancer Patients Receiving Nonplatinum Chemotherapy: Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Littlewood T. J. , Bajetta E. , Nortier J. W.R. , Vercammen E. , Rapoport B. ,   for the Epoetin Alfa Study Group
Published: February 2017

PURPOSE: This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival. PATIENTS AND METHODS: Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels ≤ 10.5 g/dL, or greater than 10.5 g/dL but ≤ 12.0 g/dL after a hemoglobin decrease of ≥ 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study. RESULTS: Epoetin alfa, compared with placebo, significantly decreased transfusion requirements (P = .0057) and increased hemoglobin (P < .001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, and fatigue, was significantly (P < .01) greater for epoetin alfa versus placebo patients. Although the study was not powered for survival as an end point, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa (P = .13, log-rank test), and Cox regression analysis showed an estimated hazards ratio of 1.309 (P = .052) favoring epoetin alfa. Adverse events were comparable between groups. CONCLUSION: Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy. Encouraging results regarding increased survival warrant another trial designed to confirm these findings.