bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.
Authors: Sandor V , Stark-Vancs V , Pearson D , Nussenblat R , Whitcup S M , Brouwers P , Patronas N , Heiss J , Jaffe E , deSmet M , Kohler D , Simon R , Wittes R 
Published: February 2017

PURPOSE Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.
High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors.
Authors: Kushner B H , Heller G , Cheung N K , Wollner N , Kramer K , Bajorin D , Polyak T , Meyers P A 
Published: February 2017

PURPOSE To help fill the gap in knowledge about the risk of leukemia from repetitive high-dose use of alkylating agents and topoisomerase-II inhibitors in young patients with solid tumors. METHODS Poor-risk solid tumors were treated with four courses of cyclophosphamide (4,200 mg/m2)/ doxorubicin (75 mg/m2), and three courses of ifosfamide (9,000 mg/m2)/etoposide (500 mg/m2). The cumulative incidence of treatment-related myelodysplasia/ leukemia (t-AML) was calculated using the method of competing risks. The expected number of leukemic events was calculated by applying national incidence rates to person-years classified by age and sex. RESULTS Among 86 patients (median age, 17 years) monitored for 6 to 88 months (median, 24), five cases of t-AML were detected at 10 to 37 months (median, 17). The expected number of leukemic events in this cohort was .001. Clinical and cytogenetic findings implicated prior alkylator therapy in three cases and prior treatment with topoisomerase-II inhibitors in two. At 40 months, the cumulative incidence of t-AML was 8% (SE 7%). CONCLUSION Repetitive high-dose use of alkylating agents given with topoisomerase-II inhibitors is strongly leukemogenic, even with modest cumulative doses of each drug. This finding is notable for the following reasons: (1) it undermines predictions that limited use of high-dose chemotherapy might be minimally leukemogenic, and (2) it contrasts strikingly with the previously reported low risk of t-AML following treatment of pediatric solid tumors with chemotherapy lacking the alkylator dose-intensity and prominence of etoposide that are hallmarks of current regimens.
Relation between literacy, race, and stage of presentation among low-income patients with prostate cancer.
Authors: Bennett C L , Ferreira M R , Davis T C , Kaplan J , Weinberger M , Kuzel T , Seday M A , Sartor O 
Published: February 2017

PURPOSE Diagnosis of advanced prostate cancer is a major health problem, especially among low-income men. Opportunities vary for early detection of prostate cancer for low-income black and white men because of financial, cultural, and social factors. In this study, we evaluated the association of poor literacy skills with higher rates of presentation of advanced stages of prostate cancer among low-income black and white men who received care in equal-access medical systems. PATIENTS AND METHODS Literacy and stage at diagnosis of prostate cancer were evaluated in 212 low-income men who received medical care in Shreveport, LA, and Chicago, IL. The patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM), an individually administered reading screening test designed specifically for use in the medical setting. Logistic regression models were used to evaluate predictors of metastatic disease at presentation as a function of patient age, race, literacy, and city. RESULTS Whereas black men were almost twice as likely to present with stage D prostate cancer (49.5% v 35.9%; P < .05), they were significantly more likely to have literacy levels less than sixth grade (52.3% v 8.7%; P < .001). However, after adjustment for differences in literacy, age, and city, race was not a significant predictor of advanced-stage prostate cancer. CONCLUSION Low literacy may be an overlooked but significant barrier to the diagnosis of early-stage prostate cancer among low-income white and black men. The development of culturally sensitive, low-literacy educational materials may improve patient awareness of prostate cancer and improve the frequency of diagnosis of early-stage cancer.
Risk-based recommendations for mammographic screening for women in their forties.
Authors: Gail M , Rimer B 
Published: February 2017

PURPOSE To develop risk-based recommendations for mammographic screening for women in their 40s that take into account the woman's age, race, and specific risk factors. METHODS We assumed that regular mammographic screening is justified for a 50-year-old woman, even one with no risk factors, and that a younger woman with an expected 1-year breast cancer incidence rate as great or greater than that of a 50-year-old woman with no risk factors would benefit sufficiently to justify regular screening. Recommendations under this criterion were based on age- and race-specific breast cancer incidence rates from the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results (SEER) Program; assessments of risk factors from the Breast Cancer Detection and Demonstration Project (BCDDP); and reports in the literature. RESULTS Two methods, the exact-age procedure (EAP) and the grouped-age procedure (GAP), were developed. The less precise GAP only requires following a flow diagram. The proportion of white women recommended for screening by the EAP ranges from 10% for 40-year-old women to 95% for 49-year-old women, and the corresponding percentages for black women are 16% and 95%. The assumptions that underlie the guidelines are discussed critically. CONCLUSION For women or physicians who prefer an individualized approach in deciding whether to initiate regular mammographic screening in the age range of 40 to 49 years, the present report offers recommendations based on individualized risk-factor data and clearly stated assumptions that have an empiric basis. These recommendations can be used to facilitate the counseling process.
Low biologic aggressiveness in breast cancer in women using hormone replacement therapy.
Authors: Holli K , Isola J , Cuzick J 
Published: February 2017

PURPOSE Hormone replacement therapy (HRT) has been associated with an increased risk for breast cancer. Cancers in women who use HRT are often less advanced, and lower mortality has been reported in those who use HRT than in nonusers. We sought to explain this by a comparison of indicators of tumor aggressiveness in patients who received HRT with those in patients who did not. PATIENTS AND METHODS A population-based cohort of 477 postmenopausal women with breast cancer were interviewed for the use, type, and duration of HRT. Clinical variables and indicators of tumor aggressiveness (histologic grade, hormone receptors, DNA ploidy, S-phase fraction, and c-erbB-2 oncoprotein overexpression) were analyzed. RESULTS Breast tumors from HRT users were smaller (odds ratio, 0.47; P=.005), had better histologic differentiation (P=.04), and had a lower proliferation rate (S-phase fraction, P=.009) than tumors from nonusers. These differences persisted after adjustments for age and method of diagnosis (mammography screening v self-referral) by multiple logistic regression. No significant differences were observed in the estrogen (ER) or progesterone receptor content, c-erbB-2 oncogene overexpression, or axillary node involvement. A subgroup analysis showed that the tumor proliferation rates among HRT users were significantly lower only if HRT had been used at the time of diagnosis (P=.001). The type of HRT (estrogen v combination of estrogen and progesterone) was not associated with any clinical parameter or tumor phenotype. The association of HRT with lower proliferation rate and smaller tumor size was exclusively caused by ER-positive tumors (P=.0001 and P=.0035 v P > .1, respectively). CONCLUSION The results indicate that breast cancer in women who receive HRT is biologically less aggressive than those without previous HRT. The lower cell-proliferation rate and smaller tumor size found in ER-positive tumors from current HRT users suggest a direct ER-mediated growth inhibitory effect of HRT on established breast tumors. This may at least partly explain why breast cancer in HRT users has a more favorable clinical course.
Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer
Authors: Cardenal Felipe , López-Cabrerizo M. Paz , Antón Antonio , Alberola Vicente , Massuti Bartomeu , Carrato Alfredo , Barneto Isidoro , Lomas María , García Margarita , Lianes Pilar , Montalar Joaquín , Vadell Catalina , González-Larriba José Luis , Nguyen Binh , Artal Angel , Rosell Rafael 
Published: February 2017

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.
Adjuvant Treatment and Onset of Menopause Predict Weight Gain After Breast Cancer Diagnosis
Authors: Goodwin Pamela J. , Ennis Marguerite , Pritchard Kathleen I. , McCready David , Koo Jarley , Sidlofsky Saul , Trudeau Maureen , Hood Nicky , Redwood Sheila 
Published: February 2017

PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P ≤ .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.
Elements of Informed Consent for Hormone Replacement Therapy in Patients With Diagnosed Breast Cancer
Authors: Chlebowski Rowan T. , McTiernan Anne 
Published: February 2017

PURPOSE: An approach to providing informed consent to breast cancer survivors considering hormone replacement therapy (HRT) is offered. METHODS: Current information on HRT, breast cancer, and chronic disease prevention is reviewed in the context of risks faced by women with resected breast cancer. RESULTS: Breast cancer patients, unwilling to trade symptom reduction for even a small increase in recurrence risk, are at substantially increased risk of death from breast cancer relative to other causes. Observational studies suggest that long-term HRT increases breast cancer development. The influence of HRT on the growth of established breast cancer has not been determined; however, estrogen reduction (oophorectomy) significantly reduces recurrence in premenopausal women, and current evidence cannot exclude a risk that HRT increases recurrence to the same degree. The following issues are of particular relevance to breast cancer survivors: HRT reduces mammographic sensitivity, increases thromboembolic events, and increases endometrial cancer risk. Although benefit for HRT is commonly inferred from observational studies, randomized trials of HRT on all-cause mortality have not been completed. For coronary heart disease prevention, an array of strategies independent of HRT are available, with some (tamoxifen, selective estrogen receptor modifiers [SERMs], diet, and exercise) likely to favorably influence breast cancer risk; for osteoporosis prevention, an array of strategies also are available, with some (bisphosphonates, tamoxifen, SERMs, and exercise) likely to favorably influence breast cancer risk. CONCLUSION: Current data preclude the generation of evidence-based guidelines for HRT use in breast cancer survivors, and clinical trials in this setting should be supported. However, given available therapeutic alternatives for menopausal symptom management and chronic disease prevention, breast cancer survivors should be offered HRT only with caution and with their full participation in the decision-making process.
Physical and Psychological Morbidity After Axillary Lymph Node Dissection for Breast Cancer
Authors: Hack Thomas F. , Cohen Lorenzo , Katz Joel , Robson Lynda S. , Goss Paul 
Published: February 2017

PURPOSE: Alternatives to axillary lymph node dissection (ALND) are being developed amid controversy surrounding the therapeutic benefit and overall utility of this routine surgical procedure. Although potential negative side effects associated with ALND are known, we set out to examine whether these side effects contribute significantly to patient reports of quality of life and mental health. PATIENTS AND METHODS: We surveyed 222 women who had received an ALND as part of breast cancer surgery. All women underwent a physical therapy assessment of range of arm/shoulder motion and completed the Modified Post-operative Pain Questionnaire, the Pain Disability Index, the McGill Pain Questionnaire (short form), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and the Mental Health Inventory. RESULTS: Seventy-two percent of the women experienced arm/shoulder pain, weakness, or numbness in the week before the interview, and range of motion of the affected arm/shoulder was impaired in 73% of the women. Severity of pain was reported to be low to moderate, and younger patients experienced greater pain than older patients. Pain severity correlated positively with the number of lymph nodes removed and receipt of chemotherapy and was not significantly related to length of time since surgery or receipt of radiation therapy. Generally high levels of cancer-specific quality of life and mental health were reported. Quality of life was significantly predicted by the McGill Pain Questionnaire, and mental health was significantly predicted by the Pain Disability Index and the physical therapy assessment. CONCLUSION: Surgery-related symptoms after ALND persist for a majority of women with breast cancer and are not significantly related to time since surgery or receipt of radiation therapy. These symptoms and associated disability are significantly predictive of cancer-specific quality of life and mental health.
Prognostic Factors for the Outcome of Chemotherapy in Advanced Soft Tissue Sarcoma: An Analysis of 2,185 Patients Treated With Anthracycline-Containing First-Line Regimens—A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study
Authors: Van Glabbeke M. , van Oosterom A.T. , Oosterhuis J.W. , Mouridsen H. , Crowther D. , Somers R. , Verweij J. , Santoro A. , Buesa J. , Tursz T. 
Published: February 2017

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and χ2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.
Pretreatment Nomogram for Prostate-Specific Antigen Recurrence After Radical Prostatectomy or External-Beam Radiation Therapy for Clinically Localized Prostate Cancer
Authors: D'Amico Anthony V. , Whittington Richard , Malkowicz S. Bruce , Fondurulia Julie , Chen Ming-Hui , Kaplan Irving , Beard Clair J. , Tomaszewski John E. , Renshaw Andrew A. , Wein Alan , Coleman C. Norman 
Published: February 2017

PURPOSE: To present nomograms providing estimates of prostate-specific antigen (PSA) failure–free survival after radical prostatectomy (RP) or external-beam radiation therapy (RT) for men diagnosed during the PSA era with clinically localized disease. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine the prognostic significance of the pretreatment PSA level, 1992 American Joint Committee on Cancer (AJCC) clinical stage, and biopsy Gleason score in predicting the time to posttherapy PSA failure in 1,654 men with T1c,2 prostate cancer managed with either RP or RT. RESULTS: Pretherapy PSA, AJCC clinical stage, and biopsy Gleason score were independent predictors (P < .0001) of time to posttherapy PSA failure in patients managed with either RP or RT. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in the format of a nomogram stratified by the pretreatment PSA, AJCC clinical stage, biopsy Gleason score, and local treatment modality. CONCLUSION: Men at high risk (> 50%) for early (≤ 2 years) PSA failure could be identified on the basis of the type of local therapy received and the clinical information obtained as part of the routine work-up for localized prostate cancer. Selection of these men for trials evaluating adjuvant systemic and improved local therapies may be justified.