bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centralization of Cancer Surgery: Implications for Patient Access to Optimal Care
Authors: Stitzenberg Karyn B. , Sigurdson Elin R. , Egleston Brian L. , Starkey Russell B. , Meropol Neal J. 
Published: September 2009

Purpose The volume-outcomes relationship has led many to advocate centralization of cancer procedures at high volume hospitals (HVH). We hypothesized that in response cancer surgery has become increasingly centralized and that this centralization has resulted in increased travel burden for patients. Patients and Methods Using 1996 to 2006 discharge data from NY, NJ, PA, all patients ≥ 18 years old treated with extirpative surgery for colorectal, esophageal, or pancreatic cancer were examined. Patients and hospitals were geocoded. Annual hospital procedure volume for each tumor site was examined, and multiple quantile and logistic regressions were used to compare changes in centralization and distance traveled. Results Five thousand two hundred seventy-three esophageal, 13,472 pancreatic, 202,879 colon, and 51,262 rectal procedures were included. A shift to HVH occurred to varying degrees for all tumor types. The odds of surgery at a low volume hospital decreased for esophagus, pancreas and colon: per year odds ratios (ORs) were 0.87 (95% CI, 0.85 to 0.90), 0.85 (95% CI, 0.84 to 0.87), and 0.97 (95% CI, 0.97 to 0.98). Median travel distance increased for all sites: esophagus 72%, pancreas 40%, colon 17%, and rectum 28% (P < .0001). Travel distance was proportional to procedure volume (P < .0001). The majority of the increase in distance was attributable to centralization. Conclusion There has been extensive centralization of complex cancer surgery over the past decade. While this process should result in population-level improvements in cancer outcomes, centralization is increasing patient travel. For some subsets of the population, increasing travel requirements may pose a significant barrier to access to quality cancer care.
Concurrent Trastuzumab and HER2/neu-Specific Vaccination in Patients With Metastatic Breast Cancer
Authors: Disis Mary L. , Wallace Danelle R. , Gooley Theodore A. , Dang Yushe , Slota Meredith , Lu Hailing , Coveler Andrew L. , Childs Jennifer S. , Higgins Doreen M. , Fintak Patricia A. , dela Rosa Corazon , Tietje Kathleen , Link John , Waisman James , Salazar Lupe G. 
Published: September 2009

Purpose The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of combination therapy consisting of concurrent trastuzumab and human epidermal growth factor receptor 2 (HER2)/neu-specific vaccination in patients with HER2/neu-overexpressing metastatic breast cancer. Patients and Methods Twenty-two patients with stage IV HER2/neu-positive breast cancer receiving trastuzumab therapy were vaccinated with an HER2/neu T-helper peptide-based vaccine. Toxicity was graded according to National Cancer Institute criteria, and antigen specific T-cell immunity was assessed by interferon gamma enzyme-linked immunosorbent spot assay. Data on progression-free and overall survival were collected. Results Concurrent trastuzumab and HER2/neu vaccinations were well tolerated, with 15% of patients experiencing an asymptomatic decline in left ventricular ejection fraction below the normal range during combination therapy. Although many patients had pre-existing immunity specific for HER2/neu and other breast cancer antigens while treated with trastuzumab alone, that immunity could be significantly boosted and maintained with vaccination. Epitope spreading within HER2/neu and to additional tumor-related proteins was stimulated by immunization, and the magnitude of the T-cell response generated was significantly inversely correlated with serum transforming growth factor beta levels. At a median follow-up of 36 months from the first vaccine, the median overall survival in the study population has not been reached. Conclusion Combination therapy with trastuzumab and a HER2/neu vaccine is associated with minimal toxicity and results in prolonged, robust, antigen-specific immune responses in treated patients.
Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared With Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients With Non-Hodgkin's Lymphoma
Authors: DiPersio John F. , Micallef Ivana N. , Stiff Patrick J. , Bolwell Brian J. , Maziarz Richard T. , Jacobsen Eric , Nademanee Auayporn , McCarty John , Bridger Gary , Calandra Gary 
Published: September 2009

Purpose This study evaluates the safety and efficacy of plerixafor (AMD3100), a CXCR4 antagonist, in mobilizing hematopoietic stem cells for autologous stem-cell transplantation in non-Hodgkin's lymphoma (NHL) patients. Patients and Methods This is a phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with non-Hodgkin's lymphoma requiring an autologous hematopoietic stem-cell transplantation in first or second complete or partial remission were eligible. Patients received granulocyte colony-stimulating factor (G-CSF; 10 μg/kg) subcutaneously daily for up to 8 days. Beginning on evening of day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 μg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until ≥ 5 × 106 CD34+ cells/kg were collected. The primary end point was the percentage of patients who collected ≥ 5 × 106 CD34+ cells/kg in 4 or fewer apheresis days. Results This report presents all data for all patients (n = 298) through 12 months follow-up. Eighty-nine (59%) of 150 patients in the plerixafor group and 29 (20%) of 148 patients in the placebo group met the primary end point (P < .001). One hundred thirty-five patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation after initial mobilization. Median time to engraftment was similar in both groups. The most common plerixafor-associated adverse events were GI disorders and injection site reactions. Conclusion Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34+ cell target for transplantation in fewer apheresis days, compared with G-CSF alone.
Occult Nipple Involvement in Breast Cancer: Clinicopathologic Findings in 316 Consecutive Mastectomy Specimens
Authors: Brachtel Elena F. , Rusby Jennifer E. , Michaelson James S. , Chen L. Leon , Muzikansky Alona , Smith Barbara L. , Koerner Frederick C. 
Published: September 2009

Purpose Although breast-conserving surgery is a standard approach for patients with breast cancer, mastectomy often becomes necessary. Surgical options now include nipple-sparing mastectomy but its oncological safety is still controversial. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients with the retroareolar margin as possible indicator of nipple involvement. Patients and Methods Three hundred sixteen consecutive mastectomy specimens (232 therapeutic, 84 prophylactic) with grossly unremarkable nipples were evaluated by coronal sections through the entire nipple and subareolar tissue. Extent and location of nipple involvement by carcinoma was assessed with the tissue deep to the skin as potential retroareolar en-face resection margin. Results Seventy-one percent of nipples from therapeutic mastectomies showed no pathologic abnormality, 21% had ductal carcinoma in situ (DCIS), invasive carcinoma (IC), or lymphovascular invasion (LVI), and 8% lobular neoplasia (lobular carcinoma in situ). Human epidermal growth factor receptor 2 amplification, tumor size, and tumor-nipple distance were associated with nipple involvement by multivariate analysis (P = .0047, .0126, and .0176); histologic grade of both DCIS (P = .002) and IC (P = .03), LVI (P = .03), and lymph node involvement (P = .02) by univariate analysis. Nipple involvement by IC or DCIS was identified in the retroareolar margin with a sensitivity of 0.8 and a negative predictive value of 0.96. None of the 84 prophylactic mastectomies showed nipple involvement by IC or DCIS. Conclusion Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy.
Health-Related Quality of Life Among Long-Term Rectal Cancer Survivors With an Ostomy: Manifestations by Sex
Authors: Krouse Robert S. , Herrinton Lisa J. , Grant Marcia , Wendel Christopher S. , Green Sylvan B. , Mohler M. Jane , Baldwin Carol M. , McMullen Carmit K. , Rawl Susan M. , Matayoshi Eric , Coons Stephen Joel , Hornbrook Mark C. 
Published: September 2009

Purpose Intestinal stomas can pose significant challenges for long-term (≥ 5 years) rectal cancer (RC) survivors. Specifying common challenges and sociodemographic or clinical differences will further the development of tailored interventions to improve health-related quality of life (HRQOL). Patients and Methods This was a matched cross-sectional study of long-term RC survivors conducted in three Kaiser Permanente regions. The mailed questionnaire included the modified City of Hope Quality of Life-Ostomy (mCOH-QOL-Ostomy) and Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2). Groups surveyed were permanent ostomates (cases) and those who did not require an ostomy (controls). RC survivors were matched on sex, age, and time since diagnosis. Comparisons between groups used regression analysis with adjustment for age, comorbidity score, history of radiation therapy, income, and work status. Results Response rate was 54% (491 of 909). Cases and controls had similar demographic characteristics. On the basis of the mCOH-QOL-Ostomy, both male and female cases had significantly worse social well-being compared with controls, while only female cases reported significantly worse overall HRQOL and psychological well-being. For younger females (< age 75 years), ostomy had a greater impact on physical well-being compared with older females. Based on the SF-36v2, statistically significant and meaningful differences between female cases and controls were observed for seven of the eight scales and on the physical and mental component summary scores. Conclusion Men and women report a different profile of challenges, suggesting the need for targeted or sex-specific interventions to improve HRQOL in this population. This may include focus on physical HRQOL for female ostomy survivors younger than age 75.
Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study
Authors: Sikov William M. , Dizon Don S. , Strenger Rochelle , Legare Robert D. , Theall Kathy P. , Graves Theresa A. , Gass Jennifer S. , Kennedy Teresa A. , Fenton Mary Anne 
Published: September 2009

Purpose To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel ± weekly trastuzumab in resectable and locally advanced breast cancer. Patients and Methods Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m2 weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) –positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians. Results Fifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER) –negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%). Conclusion Neoadjuvant carboplatin and weekly paclitaxel ± trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted.
Impact of Pathological Characteristics on Local Relapse After Breast-Conserving Therapy: A Subgroup Analysis of the EORTC Boost Versus No Boost Trial
Authors: Jones Heather A. , Antonini Ninja , Hart Augustinus A.M. , Peterse Johannes L. , Horiot Jean-Claude , Collin Françoise , Poortmans Philip M. , Oei S. Bing , Collette Laurence , Struikmans Henk , Van den Bogaert Walter F. , Fourquet Alain , Jager Jos J. , Schinagl Dominic A.X. , Wárlám-Rodenhuis Carla C. , Bartelink Harry 
Published: September 2009

Purpose To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT). Patients and Methods In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed. Results The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio [HR], 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively. Conclusion Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer.
Influence on the Health of the Partner Affected by Tumor Disease in the Wife or Husband Based on a Population-Based Register Study of Cancer in Sweden
Authors: Sjövall Katarina , Attner Bo , Lithman Thor , Noreen Dennis , Gunnars Barbro , Thomé Bibbi , Olsson Håkan 
Published: September 2009

Purpose To examine health care use and health care costs among partners of persons with cancer. Patients and Methods Partners of patients with colon, rectal, lung, breast, and prostate cancer (N = 11,076) were identified via linked data from the Tumor Registry of Southern Sweden and Census Registry of Sweden. Health care use, total costs of health care, and diagnosis of the partner were studied before and after diagnosis of the cancer patient. Results Health care use for partners increased in terms of in-patient care after the cancer diagnosis. A significant increase was seen the second year for partners of patients with colon cancer (risk ratio [RR], 1.55; 95% CI, 1.28 to 1.87) and lung cancer (RR, 1.50; 95% CI, 1.26 to 1.79). Psychiatric diagnoses increased after the cancer diagnosis in the total sample, with a significant increase for partners of colon (RR, 2.66; 95% CI, 1.71 to 4.22), lung (RR, 3.16; 95% CI, 2.23 to 4.57), and prostate cancer patients (RR, 1.68; 95% CI, 1.32 to 2.15). Costs of care increased more than the consumer price index the two years after the cancer diagnosis. Costs of care increased most for male partners and especially for younger male partners (age 25 to 64 years) of patients with colon, rectal, and lung cancers. Conclusion The results showed increased health care costs and an increase in psychiatric diagnoses after the cancer diagnosis among partners of cancer patients. Further research is needed to learn more about the situation of the partner and to identify persons at risk of psychiatric morbidity. Knowledge is also needed on how to support the partner in the most efficient way.
Prediction of Local Recurrence, Distant Metastases, and Death After Breast-Conserving Therapy in Early-Stage Invasive Breast Cancer Using a Five-Biomarker Panel
Authors: Millar Ewan K.A. , Graham Peter H. , O'Toole Sandra A. , McNeil Catriona M. , Browne Lois , Morey Adrienne L. , Eggleton Sarah , Beretov Julia , Theocharous Constantine , Capp Anne , Nasser Elias , Kearsley John H. , Delaney Geoff , Papadatos George , Fox Christopher , Sutherland Robert L. 
Published: September 2009

Purpose To determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost. Patients and Methods Four hundred ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer. Results Median follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer–specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer–specific death (P = .0482), but not for IBTR (P = .346). Conclusion The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.
Phase I and Biomarker Study of ABT-869, a Multiple Receptor Tyrosine Kinase Inhibitor, in Patients With Refractory Solid Malignancies
Authors: Wong Chiung-Ing , Koh Tong-San , Soo Ross , Hartono Septian , Thng Choon-Hua , McKeegan Evelyn , Yong Wei-Peng , Chen Chien-Shing , Lee Soo-Chin , Wong John , Lim Robert , Sukri Norita , Lim Siew-Eng , Ong Ai-Bee , Steinberg Joyce , Gupta Neeraj , Pradhan Rajendra , Humerickhouse Rod , Goh Boon-Cher 
Published: September 2009

Purpose To determine the safety and tolerability of ABT-869 at escalating doses and its effects on biomarkers relevant for antiangiogenic activity in patients with solid malignancies. Patients and Methods Patients with solid malignancies refractory to or for which no standard effective therapy exists were enrolled onto escalating-dose cohorts and treated with oral ABT-869 once daily continuously. Results Thirty-three patients were studied at doses of 10 mg/d, 0.1 mg/kg/d, 0.25 mg/kg/d, and 0.3 mg/kg/d. Dose-limiting toxicities in the first cycle (21 days) included grade 3 fatigue in a patient at 10 mg/d, grade 3 proteinuria and grade 3 hypertension in two separate patients at 0.25 mg/kg/d, and grade 3 hypertension and grade 3 proteinuria in two separate patients at 0.3 mg/kg/d, which was the maximum-tolerated dose. Other significant treatment-related adverse events included asthenia, hand and foot blisters, and myalgia. Oral clearance of ABT-869 was linear, with a mean of 2.7 ± 1.2 L/h and half-life of 18.4 ± 5.7 hours, with no evidence of drug accumulation at day 15. Two patients with lung cancer and one patient with colon cancer achieved partial response. Stable disease for more than four cycles was observed in 16 patients (48%). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) showed dose-dependent reduced tumor vascular permeability that correlated with drug exposure. By day 15 of treatment, circulating endothelial cells were significantly reduced (P = .007), whereas plasma vascular endothelial growth factor was increased (P = .004). Conclusion ABT-869 by continuous once-daily dosing was tolerable at doses ≤ 0.25 mg/kg/d. Biomarker evidence of antiangiogenic activity and DCE-MRI evidence of tumor antiangiogenesis were observed together with promising clinical activity.
Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study
Authors: Monk Bradley J. , Sill Michael W. , McMeekin D. Scott , Cohn David E. , Ramondetta Lois M. , Boardman Cecelia H. , Benda Jo , Cella David 
Published: September 2009

PurposeAssess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma.Patients and MethodsPatients were randomly assigned to paclitaxel 135 mg/m2over 24 hours plus Cis 50 mg/m2day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m2days 1 and 8 plus Cis 50 mg/m2day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m2day 1 and 8 plus Cis 50 mg/m2day 1 every 3 weeks (GC); or topotecan 0.75 mg/m2days 1, 2, and 3 plus Cis 50 mg/m2day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected.ResultsA total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia.ConclusionVC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.