bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Year After Head and Neck Cancer: Quality of Life
Authors: Gritz Ellen R. , Carmack Cindy L. , de Moor Carl , Coscarelli Anne , Schacherer Christopher W. , Meyers Eric G. , Abemayor Elliot 
Published: February 2017

PURPOSE: Treatment regimens for head and neck cancer patients profoundly affect several quality-of-life domains. Rehabilitative needs have been identified through cross-sectional analyses; however, few studies have prospectively assessed quality of life, included assessment of psychosocial variables, and identified predictors of long-term follow-up. PARTICIPANTS AND METHODS: The present study addresses these limitations through a prospective assessment of 105 patients with a newly diagnosed first primary squamous cell carcinoma of the oral cavity, pharynx, or larynx. Participants were enrolled onto a larger randomized controlled trial comparing a provider-delivered smoking cessation intervention with a usual-care-advice control condition. Participants completed a battery of self-report measures after diagnosis and before treatment and additional quality-of-life instruments at 1 and 12 months after initial smoking cessation advice. RESULTS: Participants displayed improvements at 12 months in functional status (P = .006) and in the areas of eating, diet, and speech; however, the latter three represent areas of continued dysfunction, and the changes were not statistically significant. Despite these improvements, patients reported a decline in certain quality-of-life domains, including marital (P = .002) and sexual functioning (P = .017), as well as an increase in alcohol use (P < .001). Predictors of quality of life at 12 months included treatment type, the Vigor subscale of the Profile of Mood States instrument, and quality-of-life scores obtained 1 month after initial smoking cessation advice. CONCLUSION: Results reinforce the need for rehabilitation management through the integration of psychologic and behavioral interventions in medical follow-up.
Sequential Dose-Dense Doxorubicin, Paclitaxel, and Cyclophosphamide for Resectable High-Risk Breast Cancer: Feasibility and Efficacy
Authors: Hudis C. , Seidman A. , Baselga J. , Raptis G. , Lebwohl D. , Gilewski T. , Moynahan M. , Sklarin N. , Fennelly D. , Crown J. P.A. , Surbone A. , Uhlenhopp M. , Riedel E. , Yao T. J. , Norton L. 
Published: February 2017

PURPOSE: Dose-dense chemotherapy is predicted to be a superior treatment plan. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophosphamide (A → T → C) as adjuvant therapy. METHODS: Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy, using 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m2 × 3, then paclitaxel 250 mg/m2/24 hours × 3, and then cyclophosphamide 3.0 g/m2 × 3; all doses were given with subcutaneous injections of 5 μg/kg granulocyte colony-stimulating factor on days 3 through 10. Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 mg/day for 5 years. Patients treated with breast conservation, those with 10 or more positive nodes, and those with tumors larger than 5 cm received radiotherapy. RESULTS: Between March 1993 and June 1994, we enrolled 42 patients. The median age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four to 25), and the median tumor size was 3.0 cm (range, 0 to 11.0 cm). The median intertreatment interval was 14 days (range, 13 to 36 days), and the median delivered dose-intensity exceeded 92% of the planned dose-intensity for all three drugs. Hospital admission was required for 29 patients (69%), and 28 patients (67%) required blood product transfusion. No treatment-related deaths or cardiac toxicities occurred. Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was reduced in eight (20%). At a median follow-up from surgery of 48 months (range, 3 to 57 months), nine patients (19%) had relapsed, the actuarial disease-free survival rate was 78% (95% confidence interval, 66% to 92%), and four patients (10%) had died of metastatic disease. CONCLUSION: Dose-dense sequential adjuvant chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide (A → T → C) is feasible and promising. Several ongoing phase III trials are evaluating this approach.
BRCA1/BRCA2 Germline Mutations in Locally Recurrent Breast Cancer Patients After Lumpectomy and Radiation Therapy: Implications for Breast-Conserving Management in Patients With BRCA1/BRCA2 Mutations
Authors: Turner Bruce C. , Harrold Elizabeth , Matloff Ellen , Smith Tanya , Gumbs Andrew A. , Beinfield Malcom , Ward Brian , Skolnick Mark , Glazer Peter M. , Thomas Alun , Haffty Bruce G. 
Published: February 2017

PURPOSE: Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT. PATIENTS AND METHODS: Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences. RESULTS: After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P = .03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P = .03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease. CONCLUSION: In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy.
Declining Rates of Extracapsular Extension After Radical Prostatectomy: Evidence for Continued Stage Migration
Authors: Jhaveri Faiyaaz M. , Klein Eric A. , Kupelian Patrick A. , Zippe Craig , Levin Howard S. 
Published: February 2017

PURPOSE: Prostate-specific antigen (PSA)-based screening is responsible for a profound clinical stage migration in newly detected prostate cancers. Extracapsular extension (ECE) is an important predictor of outcome after radical prostatectomy (RP). We examined trends in the rate of ECE for cancers detected by PSA screening in 731 RP specimens between 1987 and 1997, when screening became routine urologic practice in the United States. METHODS: The rates of ECE were examined in 311 prostates with nonpalpable (stage T1c) disease and 420 with palpable but clinically localized (stage T2) disease. Specimens were step-sectioned and examined by a senior pathologist. Rates of ECE were compared with respect to time, and logistic regression was used to identify predictors of ECE. RESULTS: The rate of ECE decreased from 81% to 36% during the 10-year observation period. Multivariateanalysis involving clinical tumor stage, preoperative serum PSA level, and Gleason score demonstrated that year of treatment was an independent predictor of ECE, with a two-fold reduction of risk occurring during the study period (P < .001; odds ratio, 1.96; 95% confidence interval, 1.37 to 2.78). CONCLUSION: PSA screening has resulted in a downward trend in pathologic stage in clinically localized prostate cancer, independent of preoperative PSA level, tumor stage, and Gleason score. This time-dependent downward stage migration suggests the need for continuous updating of predictive nomograms and caution in interpreting differences in contemporarily treated patients compared with historical controls. Further study is needed to determine whether this trend will translate into improved disease-free survival.
Long-Term Survival in Metastatic Transitional-Cell Carcinoma and Prognostic Factors Predicting Outcome of Therapy
Authors: Bajorin Dean F. , Dodd Paul M. , Mazumdar Madhu , Fazzari Melissa , McCaffrey John A. , Scher Howard I. , Herr Harry , Higgins Geralyn , Boyle Mary G. 
Published: February 2017

PURPOSE: The variation in reported survival of patients with metastatic transitional-cell carcinoma (TCC) treated with systemic chemotherapy may be a consequence of pretreatment patient characteristics. We hypothesized that a prognostic factor–based model of survival among patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy could account for such differences and help guide clinical trial design and interpretation. PATIENTS AND METHODS: A database of 203 patients with unresectable or metastatic TCC was retrospectively subjected to a multivariate regression analysis to determine which patient characteristics had independent prognostic significance for survival. Patients were assigned to three risk categories depending on the number of unfavorable characteristics. Patient selection in phase II studies was addressed by developing a table of expected median survival for patient cohorts that had varying proportions of patients from the three risk categories. RESULTS: Two factors had independent prognosis: Karnofsky performance status (KPS) less than 80% and visceral (lung, liver, or bone) metastasis. Median survival times for patients who had zero, one, or two risk factors were 33, 13.4, and 9.3 months, respectively (P = .0001). The median survival time of patient cohorts could vary from 9 to 26 months simply by altering the proportion of patients from different risk categories. CONCLUSION: The presence of baseline KPS less than 80% or visceral metastasis has an impact on survival. Reporting the proportion of patients with zero, one, and two risk factors will facilitate understanding of the relevance of the median survival in phase II trials. Phase III trials should stratify patients according to the number of risk factors to avoid imbalance in treatment arms.
Prognostic Significance of Occult Metastases Detected by Sentinel Lymphadenectomy and Reverse Transcriptase–Polymerase Chain Reaction in Early-Stage Melanoma Patients
Authors: Bostick Peter J. , Morton Donald L. , Turner Roderick R. , Huynh Kelly T. , Wang He-Jing , Elashoff Robert , Essner Richard , Hoon Dave S.B. 
Published: February 2017

PURPOSE: Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase–polymerase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC), and that MM expression is predictive of disease relapse. PATIENTS AND METHODS: Seventy-two consecutive patients with clinical early-stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were serially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expression by RT-PCR, in parallel with H&E staining and IHC, for melanoma metastases. MM expression in the SNs was correlated with H&E and IHC assay results, standard prognostic factors, and disease-free survival. RESULTS: In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) expressed two or more mRNAmarkers. Twenty (36%) of 55 patients with histopathologically negative SNs expressed two or more mRNA markers. By multivariate analysis, patients at increased risk of metastases to the SN had thicker lesions (P = .03), were 60 years of age or younger (P < .05), and/or were MM-positive (P < .001). Patients with histopathologically melanoma-free SNs who were MM-positive, compared with those who were positive for one or fewer mRNA markers, were at increased risk of recurrence (P = .02). Patients who were MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P = .01). CONCLUSION: H&E staining and IHC underestimate the true incidence of melanoma metastases. MM expression in the SN more accurately reflects melanoma micrometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone.
Sequential Biochemical Modulation of Fluorouracil With Folinic Acid, N-Phosphonacetyl-L-Aspartic Acid, and Interferon Alfa-2a in Advanced Colorectal Cancer
Authors: Royce Melanie E , McGarry William , Bready Beth , Dakhil Shaker R. , Belt Robert J. , Goodwin J. Wendall , Gray Richard , Hoff Paulo M. , Winn Rodger , Pazdur Richard 
Published: February 2017

PURPOSE: Several agents have been evaluated for their effect as biochemical modulators of fluorouracil (5-FU) in the treatment of metastatic colorectal carcinoma. In this study, we used folinic acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNα-2a) in a sequential order to assess the efficacy of this approach in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Forty-four patients with metastatic colorectal carcinoma were enrolled onto the study. The treatment course consisted of three cycles: (cycle 1) FA 20 mg/m2 followed by 5-FU 425 mg/m2 on days 1 to 5; (cycle 2) PALA 250 mg/m2 on days 29, 36, 43, and 50 and 5-FU 2,600 mg/m2 as a 24-hour infusion on days 30, 37, 44, and 51; and (cycle 3) IFNα-2a 9 million units (MU) three times a week for 5 weeks beginning on day 57, with a continuous infusion of 5-FU 750 mg/m2 on days 57 to 61, and then weekly bolus of 5-FU 750mg/m2/wk on days 71, 78, and 85. Response was determined after cycle 3. RESULTS: All patients had a Zubrod performance status ≥ 2, measurable disease, and had received no prior chemotherapy for their metastatic disease. A total of 212 cycles were given. Thirty-six patients were assessable for response. No complete responses were seen. Seven patients had a partial response, eight had stable disease, and 15 had progressive disease. The median duration of response was 25 weeks, and the median survival was 53 weeks. Grade 3 and 4 toxic effects included granulocytopenia, stomatitis, diarrhea, rash, nausea, and fatigue. CONCLUSION: This trial provided no evidence that sequential biochemical modulation of 5-FU in patients with metastatic colorectal carcinoma had any therapeutic advantage over conventional treatment regimens of 5-FU plus FA.
Rapid Switching From Morphine to Methadone in Cancer Patients With Poor Response to Morphine
Authors: Mercadante Sebastiano , Casuccio Alessandra , Calderone Luciano 
Published: February 2017

PURPOSE: The aim of this study was to evidence the clinical effects of an abrupt substitution of morphine with methadone using a fixed ratio of 1:5 in patients for whom limiting adverse effects occurred before adequate analgesia was achieved with oral morphine. PATIENTS AND METHODS: A cross-sectional prospective study was carried out on 24 consecutive patients who were switched from oral morphine to oral methadone because they experienced substantial adverse effects that limited further increase in morphine dose. A fixed conversion morphine-to-methadone ratio of 5:1 was chosen. Subsequently, doses were changed according to clinical need, with frequent visits or phone contacts. Pain and symptom intensity, preswitching doses of morphine, initial and subsequent doses of methadone, and survival were recorded. RESULTS: A significant decrease in pain and symptom intensity was found within 24 hours after the substitution took place. The switching was effective in most patients (19 of 24), although five patients required alternative treatments. No significant changes in methadone dose were reported in the 3 days after switching. Methadone dose was significantly higher in patients who had lower preswitching doses of morphine and vice versa. No relevant complications were reported. CONCLUSION: A rapid substitution of morphine with methadone using an initial fixed ratio of 5:1 is a safe and effective method for improving the balance between analgesia and adverse effects in cancer patients with poor morphine response. An appropriate system of patient monitoring is necessary, because further changes in dose may be required according to clinical needs.
Procarbazine, Lomustine, and Vincristine (PCV) Chemotherapy for Anaplastic Astrocytoma: A Retrospective Review of Radiation Therapy Oncology Group Protocols Comparing Survival With Carmustine or PCV Adjuvant Chemotherapy
Authors: Prados Michael D. , Scott Charles , Curran Walter J. , Nelson Diana F. , Leibel Steve , Kramer Simon 
Published: February 2017

PURPOSE: To determine any differences in outcome for patients with anaplastic astrocytoma (AA) treated with adjuvant carmustine (BCNU) versus procarbazine, lomustine, and vincristine (PCV) chemotherapy. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) database was reviewed for patients with newly diagnosed AA treated according to protocols that included either BCNU or PCV adjuvant chemotherapy. All patients were treated with radiation therapy. The outcome analysis included overall survival, taking into account patient age, extent of resection, Karnofsky performance status (KPS), and treatment group (BCNU v PCV). Stratified and nonstratified Cox proportional hazards models were used, as well as an analysis using matched cases between the groups. RESULTS: A total of 257 patients were treated with BCNU according to RTOG protocols 70-18, 83-02, and 90-06; 175 patients were treated with PCV according to RTOG protocol 94-04. All pretreatment characteristics except KPS were well balanced by treatment group; 61% of the BCNU group had a KPS of 90 to 100 compared with 73% of the PCV group (P = .0075). No statistically significant difference in survival was observed in any age group or by KPS or extent of surgery. The stratified analysis also showed no trends for improved survival by treatment group (P = .40). The Cox model identified only age, KPS, and extent of surgery as important variables influencing survival, not treatment group. Matching cases between groups using age, KPS, and surgery resulted in 133 matched pairs. No difference in survival was observed (P = .41). In a Cox model in which each matched pair is a strata, there was no difference between groups (P = .20). CONCLUSION: Using this retrospective analysis, there does not seem to be any survival benefit to PCV chemotherapy. Future phase III studies for patients with AA may need to consider whether BCNU or PCV is used in the control arm.
Granulocyte-Macrophage Colony-Stimulating Factor Treatment Before Doxorubicin and Cyclophosphamide Chemotherapy Priming in Women With Early-Stage Breast Cancer
Authors: Kobrinsky Nathan L. , Sjolander Diane E. , Cheang Mary S. , Levitt Ralph , Steen Preston D. 
Published: February 2017

PURPOSE: To determine if inhibition of stem-cell activity induced by granulocyte-macrophage colony-stimulating factor ([GM-CSF]; Sargramostim; Immunex Corporation, Seattle, WA) withdrawal or priming protects hematopoietic stem cells from the cytotoxic effects of adjuvant chemotherapy for early-stage breast cancer. PATIENTS AND METHODS: Serial blood counts were performed in 20 women with early-stage breast cancer receiving four courses of cyclophosphamide and doxorubicin chemotherapy. By a double-blind, placebo-controlled, balanced randomization, subjects received GM-CSF priming on days 5 to 1 for courses 1 and 3 or courses 2 and 4. RESULTS: Compared with before priming, after priming the times to neutrophil nadir (12.8 ± 2.5 days v 14.8 ± 1.5 days, respectively; P = .0001) and platelet nadir (mean ± SD, 10.1 ± 1.9 days v 11.1 ± 2.2 days, P < .05) were shorter, indicating a shift of cytotoxicity to later progenitors. The neutrophil nadir was similar with and without priming (mean ± SD, 490 ± 310/μL v 550 ± 350/μL, respectively; P = .2); however, on day 16 the mean neutrophil count was higher (mean ± SD, 1030 ± 580/μL v 690 ± 370/μL, P = .004), and the proportion of patients with a neutrophil count less than 500/μL was lower after priming than before (six of 35 or 17.1% v 12 of 34 or 35.3%, respectively; P = .04). The platelet nadir was higher (mean ± SD, 166,000 ± 51,000/μL after priming v 151,000 ± 45,000/μL before priming, P = .007), and the duration of thrombocytopenia, ie, a platelet count less than 150,000/μL, was shorter (1.5 ± 2.1 days v 2.8 ± 2.9 days, P = .0025) after priming. Episodes of fever and neutropenia were not observed. CONCLUSIONS: GM-CSF priming from days 5 to 1 before doxorubicin and cyclophosphamide chemotherapy was associated with an earlier neutrophil and platelet nadir. On day 16, a higher mean neutrophil count and a lower proportion of patients with severe (< 500/μL) neutropenia were observed. Beneficial effects on the severity and duration of thrombocytopenia were also noted. These observations support the hypothesis that GM-CSF priming protects hematopoietic progenitors from the cytotoxic effects of chemotherapy.