bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stanford V and Radiotherapy for Locally Extensive and Advanced Hodgkin’s Disease: Mature Results of a Prospective Clinical Trial
Authors: Horning Sandra J. , Hoppe Richard T. , Breslin Sheila , Bartlett Nancy L. , Brown B. William , Rosenberg Saul A. 
Published: February 2017

PURPOSE: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin’s disease. PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin’s disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (≥ 5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. RESULTS: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P < .0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. CONCLUSION: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin’s disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.
Does Menopausal Hormone Replacement Therapy Interact With Known Factors to Increase Risk of Breast Cancer?
Authors: Ursin Giske , Tseng Chiu-Chen , Paganini-Hill Annlia , Enger Shelley , Wan Peggy C. , Formenti Silvia , Pike Malcolm C. , Ross Ronald K. 
Published: February 2017

PURPOSE: We and other investigators have previously shown that postmenopausal combined estrogen and progestin replacement therapy (EPRT) increases the risk of breast cancer and that the risk associated with EPRT is substantially higher than for estrogen replacement therapy (ERT) alone. The present study was conducted to determine whether any particular subgroup of women are at particularly high risk of breast cancer if they use EPRT and whether tumor characteristics in women who develop cancer while on ERT or EPRT are different from those in women not using ERT or EPRT. PATIENTS AND METHODS: We conducted a population-based case-control study in Los Angeles, CA, with patients diagnosed with breast cancer in the late 1980s and early 1990s. Control subjects were matched to patients on age, ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal patients and 1,637 controls aged 55 to 72 years who had not undergone a simple hysterectomy. RESULTS: Relative risk of breast cancer associated with EPRT use did not vary with body mass index (body mass index at or below v above median [24.6 kg/m2]; P = .98), alcohol intake (≥ one v < one drink per week; P = .16), parity (nulliparous v parous; P = .45), history of benign breast disease (yes v no; P = .99), or family history of breast cancer (first degree v none; P = .57). All of these results were compatible with our previously reported estimate of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone users, principally EPRT users, were more likely to have hormone receptor–positive, especially progesterone-positive, tumors. CONCLUSION: We found no evidence that the risk of breast cancer associated with EPRT is limited to subgroups of women with specific cofactors. Tumors in EPRT users are more often hormone receptor–positive, indicating that they may have a better prognosis than breast cancer overall.
Association of Angiogenesis and Disease Outcome in Node-Positive Breast Cancer Patients Treated With Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil: A Cancer and Leukemia Group B Correlative Science Study From Protocols 8541/8869
Authors: Guidi Anthony J. , Berry Donald A. , Broadwater Gloria , Helmchen Birgit , Bleiweiss Ira J. , Budman Daniel R. , Henderson I. Craig , Norton Larry , Hayes Daniel F. 
Published: February 2017

PURPOSE: Increased microvessel density (MVD), a reflection of tumor angiogenesis, is associated with diminished relapse-free and overall survival (OS) in several subsets of breast cancer patients. However, the utility of this assay in node-positive patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) has not been well studied. PATIENTS AND METHODS: Immunostaining for factor VIII–related antigen was performed on tissue sections from a subset of node-positive patients who received one of three dose/schedule regimens of CAF during participation in Cancer and Leukemia Group B protocol 8541. Sections from 577 cancers exhibited acceptable tumor and immunostaining quality and were included in the study. Each section was examined quantitatively for MVD as well as nonquantitatively by scoring the presence or absence of a prominent vascular pattern. RESULTS: MVD counts were not associated with relapse-free or OS in univariate analysis. The presence of a prominent plexiform vascular pattern was correlated with decreased OS (P = .0085) in univariate analysis, but this pattern was not an independent prognostic indicator of survival in multivariate analysis. No apparent clinically important interactions between measures of angiogenesis, other prognostic factors, administration of tamoxifen, and chemotherapy dose were observed. CONCLUSION: Assessment of angiogenesis does not provide useful information regarding prognosis in node-positive breast cancer patients treated with adjuvant CAF, nor do these measures predict which patients will benefit from dose intensification or addition of tamoxifen.
Practices and Attitudes of Japanese Oncologists and Palliative Care Physicians Concerning Terminal Sedation: A Nationwide Survey
Authors: Morita Tatsuya , Akechi Tatsuo , Sugawara Yuriko , Chihara Satoshi , Uchitomi Yosuke 
Published: February 2017

PURPOSE: To clarify the frequency of practice of sedation therapy for terminally ill cancer patients and to identify physicians’ attitudes toward sedation. METHODS: Questionnaires were mailed to 1,436 Japanese oncologists and palliative care physicians with a request to report their practice of and attitudes toward palliative sedation therapy. RESULTS: A total of 697 physicians returned questionnaires (response rate, 49.6%). Use of mild, intermittent-deep, or continuous-deep sedation for physical and psychologic distress was reported by 89% and 64%, 70% and 46%, and 66% and 38%, respectively. In vignettes in which physicians were asked whether they would use sedation for a patient with refractory dyspnea or with existential distress, 14% and 15%, respectively, chose continuous-deep sedation as a strong possibility. Those physicians less confident with psychologic care and with higher levels of professional burnout were more likely to choose continuous-deep sedation. In vignettes in which they were asked whether they use sedation for a patient with depression or delirium, 39% and 31%, respectively, considered psychiatric treatment to be a strong possibility, and 42% and 50% regarded continuous-deep sedation as a potential treatment option. Physicians less involved in caring for the terminally ill and less specialized in palliative medicine were significantly less likely to choose psychiatric treatment. CONCLUSION: Sedation is frequently used for severe physical and psychologic distress of cancer patients. Physicians’ clinical experiences with the terminally ill and their levels of professional burnout influence the decisions. Training and education for physicians in regard to end-of-life care and valid clinical guidelines for palliative sedation therapy are necessary.
Up-to-Date Long-Term Survival Curves of Patients With Cancer by Period Analysis
Authors: Brenner Hermann , Hakulinen Timo 
Published: February 2017

PURPOSE: Provision of up-to-date long-term survival curves is an important task of cancer registries. Traditionally, survival curves have been derived for cohorts of patients diagnosed many years ago. Using data of the Finnish Cancer Registry, we provide an empirical assessment of the use of a new method of survival anlysis, denoted period analysis, for deriving more up-to-date survival curves. PATIENTS AND METHODS: We calculated 10-year relative survival curves actually observed for patients diagnosed with one of the 15 most common forms of cancer in 1983 to 1987, and we compared them with the most up-to-date 10-year relative survival curves that might have been obtained in 1983 to 1987 using either traditional (cohort-wise) or period analysis. We also give the most recent 10-year survival curves obtained by period analysis for the 1993 to 1997 period. RESULTS: For all forms of cancer, period analysis of the 1983 to 1987 data yielded survival curves that were very close to the survival curves later observed for patients who were newly diagnosed in that period (median and maximum difference of 10-year relative survival estimates: 0.9 and 5.7 percent units, respectively). By contrast, the survival curves obtained by traditional (cohort-wise) survival analysis in 1983 to 1987 would have been much lower for most forms of cancer (median and maximum difference: 5.8 and 18.4 percent units, respectively). The 10-year survival curves for the 1993 to 1997 period are substantially more favorable than previously available, traditionally derived survival curves for most forms of cancer. CONCLUSION: Period analysis is a useful tool for deriving up-to-date long-term survival curves of patients with cancer.
Association of Preoperative Plasma Levels of Insulin-Like Growth Factor I and Insulin-Like Growth Factor Binding Proteins-2 and -3 With Prostate Cancer Invasion, Progression, and Metastasis
Authors: Shariat Shahrokh F. , Lamb Dolores J. , Kattan Michael W. , Nguyen Cuong , Kim JaHong , Beck Josie , Wheeler Thomas M. , Slawin Kevin M. 
Published: February 2017

PURPOSE: We tested the hypothesis that preoperative plasma levels of insulin-like growth factor (IGF) binding protein (BP)-2 or IGFBP-3 would predict cancer stage and prognosis in patients undergoing radical prostatectomy. MATERIAL AND METHODS: Plasma levels of IGF-I, IGFBP-2, and IGFBP-3 were measured preoperatively in 120 consecutive patients who underwent radical prostatectomy for clinically localized disease, postoperatively in 51 of these patients, in 44 healthy men, in 19 patients with metastases to regional lymph nodes, and in 10 patients with bone metastases. RESULTS: Plasma IGFBP-3 levels were lowest in patients with bone metastases (P ≤ .043). IGFBP-2 levels were elevated in prostate cancer patients compared with healthy subjects (P ≤ .006). However, within the group of prostatectomy patients, preoperative plasma IGFBP-2 levels were lower in patients with advanced disease (P ≤ .033), were inversely correlated with prostatic tumor volume (P = .037), and declined after prostate removal (P = .044). Lower preoperative IGFBP-2 and IGFBP-3 levels and biopsy Gleason score were independent predictors of biochemical progression (P = .043, P = .040, and P = .020, respectively). In patients with disease progression, preoperative plasma IGFBP-3 levels were lower in those with aggressive than in those with nonaggressive failure (P = .042). CONCLUSION: Elevation of plasma IGFBP-2 levels in prostate cancer patients apparently is due to increased release directly from the prostate. For patients with clinically localized prostate cancer, preoperative plasma IGFBP-2 levels are inversely associated with biologically aggressive disease and disease progression. Preoperative plasma IGFBP-3 levels were decreased in patients with prostate cancer metastases and were an independent predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
Induction Chemotherapy Followed by Low-Dose Involved-Field Radiotherapy for Intracranial Germ Cell Tumors
Authors: Aoyama Hidefumi , Shirato Hiroki , Ikeda Jun , Fujieda Kenji , Miyasaka Kazuo , Sawamura Yutaka 
Published: February 2017

PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-β)–secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomas, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). RESULTS: Disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG-β-secreting germinomas, respectively. All six patients with nongerminomatous GCTs were alive at the last follow-up. All eight relapses (one pure germinoma, five HCG-β-secreting germinomas, and two IMT/G), except one in a course of salvage treatment, were salvaged and free of disease at the last follow-up. No decline was observed in the full-scale, verbal, or performance intelligence quotient at 12 to 51 months after the treatment in 11 patients. CONCLUSION: Our results support an excellent prognosis after EP and ICE regimens followed by radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve a field set-up after EP chemotherapy for the treatment of pure germinomas.
Prognostic Significance of Cytokeratin-20 Reverse Transcriptase Polymerase Chain Reaction in Lymph Nodes of Node-Negative Colorectal Cancer Patients
Authors: Rosenberg Robert , Hoos Axel , Mueller James , Baier Patricia , Stricker Dominik , Werner Martin , Nekarda Hjalmar , Siewert Jörg-Rüdiger 
Published: February 2017

PURPOSE: Approximately 20% to 30% of patients with curatively resected, node-negative (pN0) colorectal cancer die of tumor recurrence, which can be caused by minimal residual disease. To identify patients with an increased risk of tumor recurrence and evaluate the prognostic value of cytokeratin-20 (CK-20), we detected CK-20–positive cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer. PATIENTS AND METHODS: Two peritumoral lymph nodes each from 85 patients with completely resected (R0) colorectal cancer without lymph node metastases (pN0) by routine examination were analyzed using a CK-20–specific reverse transcriptase polymerase chain reaction (RT-PCR) and compared with CK-20–specific immunohistochemistry (IHC). The results were correlated with histopathologic findings and with survival. RESULTS: CK-20 RT-PCR was positive in 44 patients (52%) and detected 83% of cancer-related death. Positive RT-PCR was significantly correlated with poorer overall survival (P < .009). Comparing RT-PCR with IHC, 13 patients with positive RT-PCR were identified, where the CK-20 expression was caused by tumor cell contamination located exclusively outside the lymph node capsule and had no prognostic impact. Defining these 13 patients as RT-PCR negative improved specificity of the RT-PCR assay from 57% to 75%. The 5-year overall survival of the 31 RT-PCR–positive patients was 71%, compared with 96% in the 54 negative patients (P < .001). Multivariate analysis showed expression of CK-20 mRNA to be an independent prognostic factor with a relative risk of cancer-related death of 6.1. CONCLUSION: CK-20 RT-PCR in peritumoral histopathologic tumor-free (pN0) lymph nodes of colorectal cancer is an independent prognostic factor for overall survival. Additional CK-20 IHC improves the specificity and prognostic value of RT-PCR for cancer-related death.
Determination of the Molecular Relationship Between Multiple Tumors Within One Patient Is of Clinical Importance
Authors: van der Sijp Joost R.M. , van Meerbeeck Jan P.A.M. , Maat Alex P.W.M. , Zondervan Pieter E. , Sleddens Hein F.B.M. , van Geel Albert N. , Eggermont Alex M.M. , Dinjens Winand N.M. 
Published: February 2017

PURPOSE: To determine the molecular relationship between multiple tumors within one patient and to evaluate the impact of this knowledge on clinical management. PATIENTS AND METHODS: In 25 consecutive patients with multiple tumors, proven by histology and immunohistochemistry to be identical, molecular aberrations were determined. Each patient had at least one lesion in the lung or head and neck region. Loss of heterozygosity (LOH) and p53 aberration analyses were carried out, and similar aberration profiles suggest clonality and metastasis whereas different profiles suggest independent primary tumors. RESULTS: The molecular determinations indicated that 12 patients had a probable second primary tumor and 10 patients had a metastasis of the first lesion. In three patients, both an independent primary tumor and a metastasis were present. The molecular findings determined the course of additional treatment in all 10 patients with metastases, in all three patients with both a second primary tumor and a metastasis, and in seven of 12 patients with a second primary tumor. CONCLUSION: By comparing DNA alterations of multiple tumors within one patient, the relationship between the tumors can be assessed. This study shows that in 20 of 25 patients, knowledge of the nature of both lesions was essential in clinical decision making. Furthermore, after thorough analysis of the five cases where clinical decision making was not influenced, there was in retrospect no clear indication for LOH or p53 analysis. Because these molecular analyses can be performed on routine specimens, they can be applied in almost all patients.
Postchemotherapy Ejaculatory Azoospermia: Fatherhood With Sperm From Testis Tissue With Intracytoplasmic Sperm Injection
Authors: Damani M. N. , Masters V. , Meng M. V. , Burgess C. , Turek P. , Oates R. D. 
Published: February 2017

PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patients fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis was performed in all patients. The presence or absence of sperm, fertilization rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS: Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the predominant pattern observed was Sertoli cell only (47.8%), followed by hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%). The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in 30.8% of cycles. Six healthy boys and four healthy girls have been born to date. CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up a small subgroup of males with nonobstructive azoospermia. It is important to define and characterize this subgroup and better define their true fertility potential. Approximately two thirds of these men have retrievable testis sperm, which may be used with ICSI to have healthy offspring. This exciting avenue for paternity has heretofore not been available to such patients.
Adrenocortical Carcinoma: Clinical, Morphologic, and Molecular Characterization
Authors: Stojadinovic Alexander , Ghossein Ronald A. , Hoos Axel , Nissan Aviram , Marshall David , Dudas Maria , Cordon-Cardo Carlos , Jaques David P. , Brennan Murray F. 
Published: February 2017

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters.PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression.RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P = .005).The phenotype Ki-67(−)p53(−)mdm-2(+)cyclinD1(−)Bcl-2(−)p21(−)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P = .01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue.CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.