bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and interpretation of clinical trials that evaluate agents that may offer protection from the toxic effects of cancer chemotherapy.
Authors: Phillips K A , Tannock I F 
Published: February 2017

PURPOSE To review the features of randomized clinical trials (RCTs) used in the development of agents that may protect against chemotherapy-induced toxicities, including trials of the cardioprotective agent dexrazoxane, hematologic growth factors, and amifostine; to suggest recommendations based on information gained from such trials and improvements in the design of ongoing and future trials. METHODS Critical review of reports of RCTs obtained from a Medline search, references from these articles, and review of trials listed in the physician data query (PDQ) clinical trials data base. RESULTS Several of the phase III trials did not use a format of comparing widely accepted strategies of chemotherapy with and without a protective agent. Instead, patients in the control arms of some of the trials have been exposed to more prolonged use or increased dosage of toxic chemotherapy that placed them at greater risk of the toxicity the protective agent was designed to prevent (eg, cardiotoxicity in trials of dexrazoxane, myelosuppression or thrombocytopenia in trials of growth factors). CONCLUSION RCTs have shown clear evidence of biologic activity for the protective agents, but this does not imply therapeutic benefit as compared with alternative strategies such as avoidance of prolonged use of cardiotoxic agents or use of standard doses of chemotherapy. Ongoing and future trials of protective agents should be modified to avoid undue risk to patients.
Utility of Magnetic Resonance Imaging in the Management of Breast Cancer: Evidence for Improved Preoperative Staging
Authors: Esserman Laura , Hylton Nola , Yassa Leila , Barclay John , Frankel Steven , Sickles Edward 
Published: February 2017

PURPOSE: The staging and treatment for breast cancer are changing; there is an increase in the incidence of ductal carcinoma-in-situ, the use of fine-needle aspiration and stereotactic biopsy for diagnosis, and the use of neoadjuvant chemotherapy. Thus, there is a need for a tool to assess more precisely the extent of cancer in the breast before surgery. To better plan surgical and chemotherapeutic interventions, we evaluated high-resolution magnetic resonance imaging (MRI) as such a tool. PATIENTS AND METHODS: Fifty-seven patients with 58 cases of breast cancer were evaluated preoperatively with MRI using a technique called the triple-acquisition rapid gradient echo technique to maximize anatomic detail. Imaging results were compared with mammography and subsequent pathology results. RESULTS: Magnetic resonance imaging correctly identified residual or primary cancer in 55 of 58 cases and accurately predicted the extent of the cancer in 54 of 58 cases. The anatomic extent was more accurately defined with MRI compared with mammography (98% v 55%). Magnetic resonance imaging added the greatest value in cases of multifocal disease. CONCLUSION: By applying MRI selectively to patients with a known diagnosis of cancer and focusing on defining the extent of malignant lesions, we were able to obtain clear and accurate anatomic information. Our results suggest that MRI could provide very valuable information for preoperative planning and single-stage resection in breast cancer. Based on preliminary data from our series, MRI would be valuable as a staging tool in the preoperative setting even if the cost is in the range of $1,300 to $2,000. It is already significantly less than the target cost, so it is reasonable to refine this technique for clinical use to help plan the most appropriate surgical intervention and possibly reduce costs as well. A careful prospective study is warranted to validate our findings.
Desmoid Tumor: Prognostic Factors and Outcome After Surgery, Radiation Therapy, or Combined Surgery and Radiation Therapy
Authors: Ballo Matthew T. , Zagars Gunar K. , Pollack Alan , Pisters Peter W.T. , Pollock Raphael A. 
Published: February 2017

PURPOSE: To evaluate the therapeutic value of resection and the potential benefits of and indications for adjuvant and definitive radiation therapy for desmoid tumors. MATERIALS AND METHODS: We performed a retrospective review of 189 consecutive cases of desmoid tumor treated with surgical resection, resection and radiation therapy, or radiation therapy alone. Treatment was surgery alone in 122 cases, surgery and radiation therapy in 46, and radiation therapy alone in 21. Median follow-up was 9.4 years. RESULTS: Overall, 5- and 10-year actuarial relapse rates were 30% and 33%, respectively. Uncorrected survival rates were 96%, 92%, and 87% at 5, 10, and 15 years, respectively. For the patients treated with surgery, the actuarial relapse rates were 34% and 38% at 5 and 10 years, respectively. Among 78 patients with negative margins, the 10-year recurrence rate was 27%, whereas 40 margin-positive patients had a 10-year relapse rate of 54% (P = .003). Tumors located in an extremity also had a poorer prognosis than did those in the trunk. For patients treated with radiation therapy for gross disease, the 10-year actuarial relapse rate was 24%. For patients treated with combined resection and radiation therapy, the 10-year actuarial relapse rate was 25%. The addition of radiation therapy offset the adverse impact of positive margins seen in the surgical group. CONCLUSION: Wide local excision with negative pathologic margins is the treatment of choice for most desmoid tumors. Function-sparing resection is appropriate because adjuvant radiation therapy can offset the adverse impact of positive margins. Unresectable disease should be treated with definitive radiation therapy.
Impaired Testicular Function in Patients With Carcinoma-In-Situ of the Testis
Authors: Petersen Peter Meidahl , Giwercman Aleksander , Hansen Steen W. , Berthelsen Jørgen G. , Daugaard Gedske , Rørth Mikael , Skakkebæk Niels E. 
Published: February 2017

PURPOSE: To elucidate the biologic association between germ cell neoplasia and testicular dysfunction, through investigation of Leydig cell function and semen quality in men with carcinoma-in-situ (CIS) of the testis. PATIENTS AND METHODS: We examined two groups of men, unilaterally orchidectomized for testicular cancer. Biopsy of the contralateral testis had showed CIS in a group of 24 patients and no evidence of CIS in the other group of 30 patients. Semen quality and serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were compared in these two groups of men after orchidectomy but before further treatment for testicular cancer. RESULTS: Significantly higher LH levels (median, 8.1 IU/L v 4.8 IU/L; P < .001) and generally lower testosterone levels (median, 12.5 nmol/L v 15.5 nmol/L; P = .13) were found in the CIS group. The proportion of patients with Leydig cell dysfunction was higher in the group of patients with CIS (11 of 24) than in the group of patients without (two of 30) (P = .01). Sperm concentration and total sperm count were significantly lower (P < .001) in patients with CIS (median, 0.03 × 106/mL and 0.10 × 106, respectively) than in patients without (median, 9.1 × 106/mL and 32 × 106, respectively), whereas the levels of FSH were significantly higher (P < .001) in the former group of men (median, 19.6 IU/L v 9.0 IU/L). CONCLUSION: Not only spermatogenesis but also Leydig cell function is impaired in testes with CIS. This impairment could be due to common factors in the pathogenesis of germ cell neoplasm and testicular dysfunction. Alternatively, CIS cells may have a negative impact on Leydig cell function.
Childhood Acute Lymphoblastic Leukemia With the MLL-ENL Fusion and t(11;19)(q23;p13.3) Translocation
Authors: Rubnitz Jeffrey E. , Camitta Bruce M. , Mahmoud Hazem , Raimondi Susana C. , Carroll Andrew J. , Borowitz Michael J. , Shuster Jonathan J. , Link Michael P. , Pullen D. Jeanette , Downing James R. , Behm Frederick G. , Pui Ching-Hon 
Published: February 2017

PURPOSE: To determine the molecular characteristics, clinical features, and treatment outcomes of children with acute lymphoblastic leukemia (ALL) and the t(11;19)(q23;p13.3) translocation. PATIENTS AND METHODS: A retrospective analysis of leukemic cell karyotypes obtained from patients with new diagnoses of ALL who were treated at St. Jude Children's Research Hospital or by the Pediatric Oncology Group was performed to identify cases with the t(11;19)(q23;p13.3) translocation. Molecular analyses were performed on these cases to determine the status of the MLL gene and the presence of the MLL-ENL fusion transcript. RESULTS: Among 3,578 patients with ALL and successful cytogenetic analysis, we identified 35 patients with the t(11;19)(q23;p13.3) translocation: 13 infants and 11 older children had B-precursor leukemia, whereas 11 patients had a T-cell phenotype. Although all of the cases examined had MLL rearrangements and MLL-ENL fusion transcripts, outcome varied according to age and immunophenotype. Among B-precursor cases, only two of the 13 infants remain in complete remission, compared with six of the 11 older children. Most strikingly, no relapses have occurred among B-precursor patients 1 to 9 years of age or among T-cell patients. CONCLUSION: Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis. Our results suggest that patients with this genetic abnormality who have T-cell ALL or are 1 to 9 years of age should not be considered candidates for hematopoietic stem-cell transplantation during their first remission.
Allogeneic Bone Marrow Transplantation Versus Chemotherapy for the Treatment of Childhood Acute Lymphoblastic Leukemia in Second Remission: A Single-Institution Study
Authors: Boulad Farid , Steinherz Peter , Reyes Bernadette , Heller Glenn , Gillio Alfred P. , Small Trudy N. , Brochstein Joel A. , Kernan Nancy A. , O'Reilly Richard J. 
Published: February 2017

PURPOSE: A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively RESULTS: The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 × 109/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 × 109/L (DFS, 73% v 35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%). CONCLUSION: In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.
Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study
Authors: Byrne M. J. , Davidson J. A. , Musk A. W. , Dewar J. , van Hazel G. , Buck M. , de Klerk N. H. , Robinson B. W.S. 
Published: February 2017

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.
Prognostic Significance of Magnetic Resonance Imaging of Femoral Marrow in Patients With Myelodysplastic Syndromes
Authors: Takagi Shojiro , Tanaka Osamu , Origasa Hideki , Miura Yasusada 
Published: February 2017

PURPOSE: To investigate whether the abnormalities observed on femoral marrow magnetic resonance images are related to the development of leukemia and survival of patients with myelodysplastic syndromes (MDS).PATIENTS AND METHODS: The findings on magnetic resonance images of the femoral marrow were evaluated over periods of 1 to 92 months (median, 18 months) in 42 consecutive adult patients with newly diagnosed MDS. Magnetic resonance images were obtained by the T1-weighted spin echo method and the short TI inversion recovery technique.RESULTS: Magnetic resonance images showed that the femoral marrow patterns changed from fatty, faint, or nodular to scattered or uniform as the disease progressed. Development of acute myeloid leukemia was observed in only 13 patients whose marrow exhibited a scattered or uniform pattern. The overall survival of the 29 patients with a scattered or uniform marrow pattern was significantly shorter than that of the 13 patients with a fatty, faint, or nodular marrow pattern (10.7% v 73.3% at 7 years; P < .01). The period of leukemia-free survival was also significantly shorter in the patients with a scattered or uniform marrow pattern versus a fatty, faint, or nodular pattern (37.7% v 100% at 7 years; P < .01).CONCLUSION: Magnetic resonance images of the femoral marrow can provide valuable information for assessing the prognosis and determining the most appropriate management of patients with MDS.
CD56 Expression in Acute Promyelocytic Leukemia: A Possible Indicator of Poor Treatment Outcome?
Authors: Murray Clinton K. , Estey Elihu , Paietta Elisabeth , Howard Robin S. , Edenfield William J. , Pierce Sherry , Mann Karen P. , Bolan Charles , Byrd John C. 
Published: February 2017

PURPOSE: Blast expression of CD56 is frequent in patients with t(8;21)(q22;q22) acute myeloid leukemia and is associated with an inferior outcome. The expression of CD56 has rarely been reported in acute promyelocytic leukemia (APL) and has not been clinically characterized. Therefore, we examined the prognostic significance of CD56 expression in APL. PATIENTS AND METHODS: We identified all reported cases of CD56+ APL in the medical literature and collected clinical, biologic, and therapeutic details. RESULTS: Data were obtained for 12 patients with CD56+ APL (> 20% blast expression of CD56), including four cases from a single institution with a total of 42 APL patients. All of the CD56+ APL patients had documented cytogenetic presence of t(15;17), and of the nine reported isotypes, eight (89%) were S-isoform. Only six CD56+ patients (50%) attained complete remission (CR); the other six individuals died within 35 days of presentation. Of the six patients who attained a CR, three (50%) relapsed at 111, 121, and 155 weeks, whereas three remained in continuous CR at 19, 90, and 109 weeks. Comparison of the control CD56− to CD56+ APL patients demonstrated that the latter group had a significantly lower fibrinogen level (P = .007), and among patients for whom data were available, there was a higher frequency of the S-isoform (P = .006). Additionally, the CR rate (50% v 84%, P = .025) and overall median survival (5 v 232 weeks; P = .019) were significantly inferior for CD56+ APL patients. CONCLUSION: CD56+ acute promyelocytic leukemia is infrequent, seems to occur more frequently with the S-isoform subtype, and may be associated with a lower CR rate and inferior overall survival.
Bone Marrow Transplant Patients With Life-Threatening Organ Failure: When Should Treatment Stop?
Authors: Perry Amanda R. , Rivlin Michael M. , Goldstone Anthony H. 
Published: February 2017

PURPOSE: To discuss issues surrounding life support in bone marrow transplant (BMT) patients, issues that may determine how far we go to keep a deteriorating BMT patient alive—and when we stop trying. How can we define survival chance in BMT patients, and when should prolongation of life be deemed inappropriate? Who should make the decision to terminate support? And how should life support be terminated? DESIGN: Prognostic factors that predict for almost certain nonsurvival have been identified in BMT patients with life-threatening organ failure. The concept of futility raises the question of how low the chance of survival must be before termination of life support is justified—but the concept is flawed, and the value judgments involved in decision making must also be considered. Then, once a decision is made, the manner of withholding or withdrawing life support is also open to discussion. CONCLUSION: Despite controversies, there are areas in which improvements to current practice might be considered. More data are required to determine survival chances of BMT patients with life-threatening organ failure. Greater attention might be devoted, in pretransplant counseling, to issues of intensive life support, with the patient's own views being ascertained before transplantation. And, because technologic possibilities are now imposing fewer boundaries, the problem of finite resources may need to be readdressed, with treatment limits being set down before transplantation.
Randomized Phase II Study of the Neurokinin 1 Receptor Antagonist CJ-11,974 in the Control of Cisplatin-Induced Emesis
Authors: Hesketh P. J. , Gralla R. J. , Webb R. T. , Ueno W. , DelPrete S. , Bachinsky M. E. , Dirlam N. L. , Stack C. B. , Silberman S. L. 
Published: February 2017

PURPOSE: To determine the efficacy and safety of the neurokinin type 1 receptor antagonist CJ-11,974 for the control of high-dose cisplatin-induced emesis. PATIENTS AND METHODS: A double-blind, randomized, phase II design with a group sequential stopping rule was used in this study. Sixty-one patients with cancer who were receiving cisplatin at a dose of at least 100 mg/m2 for the first time were enrolled. All patients received granisetron 10 μg/kg and dexamethasone 20 mg intravenously 30 minutes before they were given cisplatin. Patients were randomly assigned to two groups: group 1 received CJ-11,974 100 mg, and group 2 received placebo orally 30 minutes before and 12 hours after cisplatin and then twice daily on days 2 through 5 after cisplatin. The primary end point was the percentage of patients who developed delayed emesis (emesis on the second to fifth days after cisplatin). RESULTS: Thirty patients were enrolled in group 1, and 31 patients were enrolled in group 2. Fifty-eight patients were assessable for efficacy. Complete control of emesis (expressed as the percentage of patients who had no emesis) was as follows: day 1, 85.7% (group 1) and 66.7% (group 2) (P = .090); days 2 through 5, 67.8% (group 1) and 36.6% (group 2) (P = .0425, adjusted); days 1 through 5, 64.3% (group 1) and 30% (group 2) (P = .009). Patients in group 1 experienced significantly less nausea than patients in group 2 on day 1 (P = .024). Treatment was well tolerated in both groups. CONCLUSION: We conclude from this exploratory phase II trial that CJ-11,974 is superior to placebo in controlling cisplatin-induced delayed emesis and may provide additive benefit in acute emesis and nausea control when combined with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Additional larger trials are indicated to confirm the clinical value of CJ-11,974.
Radiosensitization With Carboplatin for Patients With Unresectable Stage III Non–Small-Cell Lung Cancer: A Phase III Trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group
Authors: Clamon Gerald , Herndon James , Cooper Robert , Chang Alex Y. , Rosenman Julian , Green Mark R. 
Published: February 2017

PURPOSE: To determine whether the administration of carboplatin concurrently with radiation treatment improves survival in patients with inoperable stage III non–small-cell lung cancer. PATIENTS AND METHODS: Two hundred eighty-three patients with inoperable stage III non–small-cell lung cancer were entered onto a randomized trial by the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. Randomization was performed before initiation of any therapy. All patients received an induction chemotherapy program with vinblastine and cisplatin for 5 weeks, followed by 6,000 cGy of radiation therapy over 6 weeks. One hundred thirty-seven patients were randomized to this therapy regimen alone; 146 patients were randomized to receive carboplatin at 100 mg/m2/wk concurrent with the radiation therapy. RESULTS: The complete response was 18% with concurrent carboplatin versus 10% with radiotherapy alone (P = .101). There was no difference with respect to failure-free survival (10% with carboplatin and 9% with radiotherapy alone) or overall survival (13% with carboplatin and 10% with radiotherapy alone) at 4 years. In patients not receiving carboplatin, the relapse rate was 69% within the field of radiation and 53% in the boost volume. In patients receiving carboplatin, the relapse rate was 59% within the field of radiation and 43% in the boost volume. Patients with cancers more than 70 cm2 in size had significantly poorer survival (P = .01) CONCLUSION: Carboplatin at the dose and schedule used did not significantly impact on disease control or survival. The relapse rate within the chest remained more than 50%. More effective regimens will be required to impact on local disease control and survival.