bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of Central Venous Catheter–Related Infections and Thrombotic Events in Immunocompromised Children by the Use of Vancomycin/Ciprofloxacin/Heparin Flush Solution: A Randomized, Multicenter, Double-Blind Trial
Authors: Henrickson Kelly J. , Axtell Richard A. , Hoover Susan M. , Kuhn Suzanne M. , Pritchett Jodi , Kehl Sue C. , Klein John P.
Published: February 2017

PURPOSE: To determine whether an antibiotic flush solution containing vancomycin, heparin, and ciprofloxacin (VHC) can prevent the majority of line infections.

PATIENTS AND METHODS: A prospective double-blind study was performed comparing VHC to vancomycin and heparin (VH) to heparin alone in 126 pediatric oncology patients.

RESULTS: The 153 assessable lines resulted in 36,944 line days studied. There were 58 blood stream infections (43 Gram-positive, 14 Gram-negative, and one fungal). Forty were defined as line infections (31 heparin, three VH, six VHC). The time to develop a line infection was significantly increased using either antibiotic flush (VH, P = .011; VHC, P = .036). The rate of total line infections (VH, P = .004; VHC, P = .005), Gram-positive line infections (VH, P = .028; VHC, P = .022), and Gram-negative line infections (VH, P = .006; VHC, P = .003) was significantly reduced by either VH or VHC. Sixty-two (41%) of the lines developed 119 occlusion episodes (heparin, 3.99 per 1,000 line days; VHC, 1.75 per 1,000 line days; P = .0005). Neither antibiotic could be detected after flushing, and no adverse events were detected, including increased incidence of vancomycin-resistant Enterococcus colonization or disease.

CONCLUSION: The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care resources.
Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: Mahoney Donald H. , Shuster Jonathan J. , Nitschke Ruprecht , Lauer Stephen , Steuber C. Philip , Camitta Bruce
Published: February 2017

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL).

PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m2 plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1,000 mg/m2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years.

RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen.

CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.
CD56 Expression Is an Indicator of Poor Clinical Outcome in Patients With Acute Promyelocytic Leukemia Treated With Simultaneous All-Trans-Retinoic Acid and Chemotherapy
Authors: Ferrara Felicetto , Morabito Fortunato , Martino Bruno , Specchia Giorgina , Liso Vincenzo , Nobile Francesco , Boccuni Piernicola , Di Noto Rosa , Pane Fabrizio , Annunziata Mario , Schiavone Ettore Mariano , De Simone Mariacarla , Guglielmi Cesare , Del Vecchio Luigi , Lo Coco Francesco
Published: February 2017

PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy.

PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis.

RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56+. No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56+ and CD56− populations. Conversely, compared with patients who were CD56−, patients with CD56+ APL had shorter CR duration (P = .04) and overall survival (P = .002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 × 109 cells/L retained statistical significance in overall survival (P = .04 and P = .02, respectively).

CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.
Long-Term Disease-Free Survivors in Metastatic Undifferentiated Carcinoma of Nasopharyngeal Type
Authors: Fandi Abderrahim , Bachouchi Mounir , Azli Nacer , Taamma Abdelkrim , Boussen Hammouda , Wibault Pierre , Eschwege François , Armand Jean-Pierre , Simon Jonathan , Cvitkovic Esteban
Published: February 2017

PURPOSE: To review incidence and analyze profile of long-term complete responders among patients with undifferentiated carcinoma of nasopharyngeal type (UCNT) treated at a single institution.

PATIENTS AND METHODS: We present a cohort of 20 long-term unmaintained complete responders to chemotherapy for metastatic UCNT treated at the Institut Gustave Roussy between April 1978 and November 1996. A patient was considered a long-term survivor if he or she was disease-free for more than 36 months without treatment after obtaining a complete response by chemotherapy. Patient characteristics were as follows: sex, 17 men and three women; median age, 28 years (range, 9 to 62 years); median World Health Organization performance status, 1; and initial tumor-node-metastasis stage (International Union Against Cancer–American Joint Committee on Cancer, 1987) of T3 to T4, 60%, and of N2b to N3, 75%. Epstein-Barr virus serology was characteristic in 19 patients. Of 16 pretreated patients, 11 were pretreated by radiotherapy alone and five by chemotherapy and radiotherapy. Thirteen patients had metastatic relapses of locally controlled UCNT. Tumor sites were bone in 15 patients, lung in four, and liver (biopsy-proven) in two. Chemotherapy included the following: cisplatin, bleomycin, and fluorouracil in five patients; bleomycin, epirubicin, and cisplatin in seven patients; fluorouracil, mitomycin, epirubicin, and cisplatin in four patients; and fluorouracil, bleomycin, epirubicin, and cisplatin in one patient. Three patients were treated with platinum-based regimens before 1985. Patients received a median of six cycles (range, three to 13). Thirteen patients with bone metastases received consolidating radiotherapy.

RESULTS: As of June 1999, 14 of 20 patients were still alive with no evidence of disease after treatment (disease-free survival time, 82+ to 190+ months), three patients died of other causes while in complete response at 61, 109, and 208 months after treatment, and three patients died of disease at 42, 89, and 115 months after treatment. Long-term complete responses were obtained in both bone and visceral disease.

CONCLUSION: Our data support a curative role for chemotherapy in metastatic UCNT and are a major incentive to continue research for better combinations to increase the percentage of patients with metastatic UCNT who attain complete responses and long-term survival.
Randomized Trial Comparing Cisplatin, Gemcitabine, and Vinorelbine With Either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Advanced Non–Small-Cell Lung Cancer: Interim Analysis of a Phase III Trial of the Southern Italy Cooperative Oncology Group
Authors: Comella Pasquale , Frasci Giuseppe , Panza Nicola , Manzione Luigi , De Cataldis Giuseppe , Cioffi Riccardo , Maiorino Luigi , Micillo Enrico , Lorusso Vito , Di Rienzo Gaetano , Filippelli Gianfranco , Lamberti Alfredo , Natale Michele , Bilancia Domenico , Nicolella Gianpaolo , Di Nota Angelo , Comella Giuseppe
Published: February 2017

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non–small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG).

PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of ≤ 70 years, and an Eastern Cooperative Oncology Group performance status ≤ 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m2, gemcitabine 1,000 mg/m2, and vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m2 on days 1 and 29 and vinorelbine 30 mg/m2/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival.

RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P < .01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen.

CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.
Longitudinal Study of Adaptation to the Stress of Bone Marrow Transplantation
Authors: Fife Betsy L. , Huster Gertrude A. , Cornetta Kenneth G. , Kennedy Victoria N. , Akard Luke P. , Broun E. Randolph
Published: February 2017

PURPOSE: This prospective longitudinal study of adaptation to bone marrow transplantation (BMT) addressed three questions: (1) When during BMT do individuals experience the greatest distress? (2) What factors are associated with this distress? (3) Are there variables that could be potential clinical indicators of persons in greatest need of preventive intervention?

PATIENTS AND METHODS: One hundred one participants undergoing either an autologous or allogeneic BMT completed questionnaires before hospitalization, before bone marrow infusion, 7 days and 14 days after transplantation, and then 1 month, 3 months, and 12 months after hospitalization. Adaptation was indicated by the degree of emotional distress. Independent variables were personal control, social support from specific sources, cognitive response, self-perception, and coping strategies, controlling for symptomatology.

RESULTS: The greatest emotional distress occurred after admission to the hospital and before the bone marrow infusion. Anxiety and depression decreased 1 week after the transplant, although symptomatology increased during this time. The periods of least emotional distress were 3 months and 1 year after transplantation. Factors that accounted for the greatest variance in emotional distress/adaptation were the degree of emotional distress at baseline, personal control, cognitive response, and symptomatology.

CONCLUSION: According to this longitudinal study, which includes pretransplant data, data from in-hospital transplantation, and posttransplant data, (1) psychosocial vulnerability of these BMT recipients was greatest during hospitalization before the transplant, (2) perceived personal control may be a potential indicator of vulnerability to secondary psychosocial morbidity, and (3) the demonstrated significance of psychosocial well-being before BMT indicates the importance of obtaining prospective data for both research and clinical purposes.
Osteoporosis Due to Cancer Treatment: Pathogenesis and Management
Authors: Pfeilschifter Johannes , Diel Ingo J.
Published: February 2017

ABSTRACT: Many therapeutic regimens in cancer treatment carry the risk of causing or favoring the development of osteoporosis. Therapies in which hypogonadism may occur are most relevant in this respect. Prompt hormone replacement therapy is indicated in these patients. In patients in whom this is undesirable because of a hormone-dependent tumor, the risk of osteoporosis should be assessed by means of osteodensitometry, and prophylactic or therapeutic measures should be instituted if necessary. Early intervention improves outcome because osteoporosis therapy is most effective in preventing deterioration of bone mass. There remains much uncertainty in assessing the risk of combination chemotherapy with regard to the development of osteoporosis. Negative effects on the skeleton have, however, been demonstrated for individual drugs, such as methotrexate and ifosfamide. Negative effects of the tumor itself on bone metabolism may aggravate the degree of osteoporosis. Detailed data and long-term experience to assess the risk are urgently needed in this area and constitute an important research topic for the coming years and decades. This review discusses the most prevalent mechanisms of osteoporosis caused by cancer treatment and outlines therapeutic strategies for the prevention and treatment of therapy-induced bone loss.
Concurrent Chemotherapy and Pelvic Radiation Therapy Compared With Pelvic Radiation Therapy Alone as Adjuvant Therapy After Radical Surgery in High-Risk Early-Stage Cancer of the Cervix
Authors: Peters William A. , Liu P.Y. , Barrett Rolland J. , Stock Richard J. , Monk Bradley J. , Berek Jonathan S. , Souhami Luis , Grigsby Perry , Gordon William , Alberts David S.
Published: February 2017

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma.

PATIENTS AND METHODS: Patients with clinical stage IA2, IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m2 and a 96-hour infusion of fluorouracil 1,000 mg/m2/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT.

RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P = .003) and 1.96 (P = .007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group.

CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.
Influence of Biologic Factors and Anatomic Site in Completely Resected Liposarcoma
Authors: Linehan David C. , Lewis Jonathan J. , Leung Denis , Brennan Murray F.
Published: February 2017

PURPOSE: Soft tissue sarcoma (STS) encompasses a group of neoplasms that are anatomically and biologically diverse. Retroperitoneal/visceral (RP/V) tumors have a poorer prognosis than extremity/trunk (E/T) lesions, and this has been attributed to frequent presentation with tumors of large size and multiorgan involvement that precludes complete resection. The worse prognosis that is associated with RP/V tumors has also been thought to be histopathologically dependent and not necessarily related to anatomic site. The aim of this study was to determine the role of anatomic site and biologic features in prognosis and outcome in patients after complete resection by examining a large cohort of STS patients with a single histopathology, ie, liposarcoma.

METHODS: All patients who were treated for liposarcoma from July 1, 1982, through July 1, 1998, were included. Univariate analyses were performed using log-rank test and Kaplan-Meier estimates, and multivariate analyses were performed using Cox regression. The three end points examined were local recurrence (LR), distant recurrence, and disease-specific survival (DSS).

RESULTS: Seven hundred twenty patients with liposarcoma were evaluated, and of these, 460 had completely resected primary or completely resected locally recurrent disease. Breakdown of anatomic site was 65% E/T (n = 301) and 35% RP/V (n = 159). The median follow-up period for patients who underwent complete resection was 42 months (range, 1 to 194 months). We found that RP/V site is a poor prognosticator that is independent of patient sex and age; tumor size, grade, and margin; and recurrent presentation. Sixty-nine percent of patients with RP/V tumors who died had local disease only and no distant metastasis at the time of death.

CONCLUSION: In liposarcoma, tumor location exerts as strong an influence on prognosis as biology. In contrast to extremity liposarcoma, LR without distant metastasis often results in death for patients with RP/V tumors. For these patients, local control accomplished by complete surgical resection ± adjuvant radiation therapy should impact strongly on DSS.
Economic Impact of Harmonizing Medical Practices: Compliance With Clinical Practice Guidelines in the Follow-Up of Breast Cancer in a French Comprehensive Cancer Center
Authors: Mille Dominique , Roy Thomas , Carrère Marie-Odile , Ray Isabelle , Ferdjaoui Nora , Späth Hans-Martin , Chauvin Franck , Philip Thierry
Published: February 2017

PURPOSE: The introduction of clinical practice guidelines (CPGs) and the increasing desire to harmonize clinical practices draw attention to the economic impact of these trends. In 1994, CPGs were introduced in a French Comprehensive Cancer Center (Centre Régional Léon Bérard, Lyon). We evaluated the application of these CPGs in addition to the consequences of harmonizing clinical practices with respect to the distribution of resources by specifically analyzing the posttherapeutic follow-up of patients with localized breast cancer.

METHODS: A before-and-after analysis of the records of patients who received posttherapeutic follow-up for localized breast cancer as of either 1993 or 1995 was performed. Two hundred records were chosen at random, 100 from 1993 and 100 from 1995. Follow-up was continued for as long as possible and CPG compliance was studied for each year of the follow-up periods.

RESULTS: Follow-up that was not CPG-compliant required a significantly greater amount of resources. This difference was due to neither consultations nor mammographies, but was due to other examinations that were systematically performed without any warning signs to justify them. Depending on the follow-up year, noncompliant follow-up cost the Social Security from 2.2 to 3.6 times more than compliant follow-up. A noticeable change in medical practices was observed after the introduction of CPGs in 1994. This was confirmed by a sharp decrease in mean Social Security expenditure per patient of more than one third between 1993 and 1995, regardless of the follow-up year considered.

CONCLUSION: In the follow-up of patients with localized breast cancer, a large decrease in costs has been observed along with the evolution of medical practices toward CPG compliance. This finding is probably generalizable to other settings, but there is nothing that proves that it is applicable to other treatment strategies.
Selection of Active Drugs for Ovarian Cancer Based on CA-125 and Standard Response Rates in Phase II Trials
Authors: Rustin Gordon J. S. , Nelstrop Ann E. , Bentzen Søren M. , Bond Simon J. , McClean Patrick
Published: February 2017

PURPOSE: To determine whether precise definitions of response based on serial CA-125 levels can predict the activity of drugs in phase II trials for ovarian cancer as accurately as standard criteria.

PATIENTS AND METHODS: Fourteen different drugs for relapsed ovarian cancer were analyzed in 25 treatment groups in 19 clinical trials. Response rates were estimated in 1,457 assessable patients according to standard criteria and in 1,092 assessable patients according to CA-125. For each drug trial, the observed response rates acted as the input data for an evaluation of how the two criteria would perform in a hypothetical Gehan two-stage phase II trial, accepting a target drug efficacy rate of 20% and a rejection error of 5%.

RESULTS: CA-125 and clinical response criteria were concordant in 20 of the 25 groups, with less than 5% chance of rejecting the drug in nine groups and greater than 5% in 11 groups. In four groups, the drug had less than 5% chance of being rejected by CA-125 but greater than 5% chance of being rejected by standard criteria. The difference in the classification of drugs by the standard and CA-125 response criteria was not statistically significant (P = .38, McNemar’s test). CA-125 response rates were slightly higher than standard response rates by a factor of 1.11.

CONCLUSION: Definitions based on a 50% or 75% decrease of CA-125 levels accurately predicted which drugs in phase II trials for relapsed ovarian cancer were active and justified further investigation.
Randomized Trial of Neoadjuvant Cisplatin, Vincristine, Bleomycin, and Radical Hysterectomy Versus Radiation Therapy for Bulky Stage IB and IIA Cervical Cancer
Authors: Chang Ting-Chang , Lai Chyong-Huey , Hong Ji-Hong , Hsueh Suei , Huang Kuan-Gen , Chou Hung-Hsueh , Tseng Chih-Jen , Tsai Chien-Sheng , Chang Joseph T. , Lin Cheng-Tao , Chang Huei-Hsin , Chao Pei-Jung , Ng Koon-Kwan , Tang Simon Guo-Jeng , Soong Yung-Kwei
Published: February 2017

PURPOSE: To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer.

PATIENTS AND METHODS: Women with previously untreated bulky (primary tumor ≥ 4 cm) stage IB or IIA non–small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m2 and vincristine 1 mg/m2 for 1 day and bleomycin 25 mg/m2 for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative.

RESULTS: Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival.

CONCLUSION: NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.
Allopurinol: Intravenous Use for Prevention and Treatment of Hyperuricemia
Authors: Smalley Richard V. , Guaspari Al , Haase-Statz Sandra , Anderson Susan A. , Cederberg Donna , Hohneker John A.
Published: February 2017

PURPOSE: To tabulate data obtained over a 21-year period to determine the efficacy and safety of an intravenous (IV) allopurinol preparation.

PATIENTS AND METHODS: IV allopurinol was provided on a compassionate plea basis to patients of any age in whom xanthine oxidase inhibitor therapy was indicated as an adjunct to chemotherapy and for whom oral intake was restricted. Three hundred twenty-seven investigators at multiple hospitals in the United States treated 1,172 patients with IV allopurinol. The vast majority of these patients had a malignancy and were in danger of developing tumor lysis syndrome (TLS) and subsequent acute uric acid nephropathy (AUAN) and were unable to take oral allopurinol. Data referable to the time period of IV allopurinol administration were collected, collated, and analyzed retrospectively. There was no randomization.

RESULTS: In patients initiating treatment for an elevated serum uric acid (SUA), the SUA normalized or improved in 87% of adult patients and normalized or improved in 95% of pediatric patients. IV allopurinol, administered prophylactically to patients at high risk of developing hyperuricemia and TLS, prevented an increase in SUA levels in 93% of adults and 92% of children. Toxicities caused by IV allopurinol were minimal and consisted of 10 instances of mild to moderate skin or allergic reactions.

CONCLUSION: IV allopurinol is as efficacious and safe as oral allopurinol and will be of significant benefit to patients at risk of TLS and AUAN and unable to take oral medication.
Detection of Circulating Tumor Cells by Reverse Transcriptase Polymerase Chain Reaction of Maspin in Patients With Breast Cancer Undergoing Conventional-Dose Chemotherapy
Authors: Sabbatini Roberto , Federico Massimo , Morselli Monica , Depenni Roberta , Cagossi Katia , Luppi Mario , Torelli Giuseppe , Silingardi Vittorio
Published: February 2017

PURPOSE: To establish, in patients with breast cancer subjected to primary conventional chemotherapy and enrolled in a prospective study, the mobilizing effect of therapy on potentially neoplastic cells by means of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for mRNA of maspin, a protein related to the serpin family of protease inhibitors.

PATIENTS AND METHODS: Peripheral-blood samples were collected from 30 patients with histologically proven breast cancer before and 4 and 8 days after conventional chemotherapy for three consecutive courses. A total of 216 samples were screened for the presence of maspin mRNA by RT-PCR.

RESULTS: Before therapy, all samples but one were negative. After chemotherapy, 11 patients (38%) had positive samples. No difference in the rate of positivity was observed between groups defined according to initial stage, type of chemotherapy, Ki-67–related proliferative activity, or CA 15.3 expression.

CONCLUSION: Our results confirm that RT-PCR for maspin mRNA is a sensitive assay for the study of circulating potentially neoplastic mammary cells in patients with breast cancer. Moreover, our findings indicate a marked effect of conventional-dose chemotherapy on the mobilization of these cells in breast tumors. In our series of patients, this phenomenon does not seem to be associated with other known risk factors. Finally, the data suggest, without proving, an association between the presence of circulating maspin positive cells and a higher risk of disease progression. If this association could be confirmed, then the assay could have prognostic significance. However, larger confirmatory studies are necessary.
Impact of the Number of Treatment Courses on the Clinical Response of Patients Who Receive High-Dose Bolus Interleukin-2
Authors: Lindsey Kimberly R. , Rosenberg Steven A. , Sherry Richard M.
Published: February 2017

PURPOSE: To determine the impact of treatment with successive courses of high-dose bolus interleukin-2 (IL-2) on the incidence of clinical responses in patients with metastatic melanoma or renal cell cancer.

PATIENTS AND METHODS: A consecutive series of 350 patients with either metastatic melanoma or renal cell cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer Institute, between September 1985 and November 1996 was analyzed, with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg of IL-2 administered by a 15-minute intravenous infusion every 8 hours for up to 5 days, as clinically tolerated per cycle. Patients were retreated according to clinical response and tolerance to the IL-2 therapy.

RESULTS: Of the 149 patients with melanoma, 10 achieved complete responses (CRs) and 13 partial responses (PRs), for an overall response rate of 15.4%. Of the 201 patients with renal cell cancer, 18 achieved CRs and 20 PRs, for an overall response rate of 19.0%. Among responding patients, 21 of 23 with melanoma and 34 of 38 with renal cell cancer developed at least PRs after the first course of IL-2.

CONCLUSION: Most patients with metastatic melanoma and renal cell cancer who achieved PRs or CRs to intravenous high-dose bolus IL-2 were identified after the first course of therapy. Those who demonstrated no response after two treatment courses failed to respond to additional IL-2 therapy. Based on this retrospective analysis, we recommend that patients who exhibit objective responses to treatment with high-dose bolus IL-2 receive additional treatment courses until either CR or IL-2 intolerance develops. Patients who do not achieve objective responses after two courses of IL-2 should receive no further treatment with this regimen.
Prophylactic Surgery in Women With a Hereditary Predisposition to Breast and Ovarian Cancer
Authors: Eisen Andrea , Rebbeck Timothy R. , Wood William C. , Weber Barbara L.
Published: February 2017

PURPOSE: To review the published literature on the efficacy and adverse effects of prophylactic mastectomy (PM) and prophylactic oophorectomy (PO) in women with a hereditary predisposition to breast and ovarian cancer and to provide management recommendations for these women.

METHODS: Using the terms “prophylactic,” “preventive,” “bilateral,” “mastectomy,” “oophorectomy,” and “ovariectomy,” a MEDLINE search of the English-language literature for articles related to PM and PO was performed. The bibliographies of these articles were reviewed to identify additional relevant references.

RESULTS: There have been no prospective trials of PM or PO for the reduction of breast cancer or ovarian cancer incidence or mortality. Most of the available retrospective studies are composed of women who had surgery for a variety of indications and in whom genetic risk was not well characterized. However, some reports in women at increased risk of breast or ovarian cancer have shown that PM and PO can reduce cancer incidence.

CONCLUSION: Interest in and use of PM and PO are high among physicians and high-risk women. PM and PO seem to be associated with considerable reduction in the risk of breast and ovarian cancer, albeit incomplete. The surgical morbidity of PM and PO is low, but the complications of premature menopause may be significant, and few studies address quality-of-life issues in women who have opted for PM and PO. Management recommendations for high-risk individuals are presented on the basis of the available evidence.
Adjuvant Clodronate Treatment Does Not Reduce the Frequency of Skeletal Metastases in Node-Positive Breast Cancer Patients: 5-Year Results of a Randomized Controlled Trial
Authors: Saarto Tiina , Blomqvist Carl , Virkkunen Pekka , Elomaa Inkeri
Published: February 2017

PURPOSE: Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer.

PATIENTS AND METHODS: Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients.

RESULTS: Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P = .009; DFS, 56% v 71%, P = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P = .009).

CONCLUSION: Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.
Clinical Impact of 18F Fluorodeoxyglucose Positron Emission Tomography in Patients With Non–Small-Cell Lung Cancer: A Prospective Study
Authors: Kalff Victor , Hicks Rodney J. , P. MacManus Michael , Binns David S. , McKenzie Allan F. , Ware Robert E. , Hogg Annette , Ball David L.
Published: February 2017

PURPOSE: To prospectively study the impact of 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: One hundred five consecutive patients with NSCLC undergoing 18F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patient’s death.

RESULTS: Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions < 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET.

CONCLUSION: FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.
Impact of Number of Nodes Retrieved on Outcome in Patients With Rectal Cancer
Authors: Tepper Joel E. , O’Connell Michael J. , Niedzwiecki Donna , Hollis Donna , Compton Carolyn , Benson Al B. , Cummings Bernard , Gunderson Leonard , Macdonald John S. , Mayer Robert J.
Published: February 2017

PURPOSE: We postulated that the pathologic evaluation of the lymph nodes of surgical specimens from patients with rectal cancer can have a substantial impact on time to relapse and survival.

PATIENTS AND METHODS: We analyzed data from 1,664 patients with T3, T4, or node-positive rectal cancer treated in a national intergroup trial of adjuvant therapy with chemotherapy and radiation therapy. Associations between the number of lymph nodes found by the pathologist in the surgical specimen and the time to relapse and survival outcomes were investigated.

RESULTS: Patients were divided into groups by nodal status and the corresponding quartiles of numbers of nodes examined. The number of nodes examined was significantly associated with time to relapse and survival among patients who were node-negative. For the first through fourth quartiles, the 5-year relapse rates were 0.37, 0.34, 0.26, and 0.19 (P = .003), and the 5-year survival rates were 0.68, 0.73, 0.72, and 0.82 (P = .02). No significant differences were found by quartiles among patients determined to be node-positive. We propose that observed differences are primarily related to the incorrect determination of nodal status in node-negative patients. Approximately 14 nodes need to be studied to define nodal status accurately.

CONCLUSION: These results suggest that the pathologic assessment of lymph nodes in surgical specimens is often inaccurate and that examining greater number of nodes increases the likelihood of proper staging. Some patients who might benefit from adjuvant therapy are misclassified as node-negative due to incomplete sampling of lymph nodes.
Anthracycline-Induced Clinical Heart Failure in a Cohort of 607 Children: Long-Term Follow-Up Study
Authors: Kremer L. C.M. , van Dalen E. C. , Offringa M. , Ottenkamp J. , Voûte P. A.
Published: February 2017

PURPOSE: To determine the early and late cumulative incidence of anthracycline-induced clinical heart failure (A-CHF) after anthracycline therapy in childhood and to identify associated risk factors.

PATIENTS AND METHODS: The cumulative incidence of A-CHF and the risk factors of A-CHF were assessed in a cohort of 607 children who had been treated with anthracyclines between 1976 and 1996. For 96% of the cohort, we obtained the clinical status up to at least January 1997. The mean follow-up time was 6.3 years.

RESULTS: The cumulative incidence of A-CHF was 2.8%, after a mean follow-up time of 6.3 years and a mean cumulative dose of anthracyclines of 301 mg/m2. A cumulative dose of anthracycline higher than 300 mg/m2 was associated with an increased risk of A-CHF (relative risk, 11.8; 95% confidence interval, 1.6 to 59.5) compared with a cumulative dose lower than 300 mg/m2. The estimated risk of A-CHF increased with time after the start of anthracycline chemotherapy to 2% after 2 years and 5% after 15 years.

CONCLUSION: Up to 5% of patients will develop A-CHF 15 years after treatment, and patients treated with a cumulative dose of anthracyclines higher than 300 mg/m2 are at highest risk for A-CHF. This is thus a considerable and serious problem among these young patients. The findings reinforce the need for strategies for early detection of patients at risk for A-CHF and for the evaluation of other chemotherapeutic possibilities or cardioprotective agents in relation to the survival.
Up-Front Window Trial of Topotecan in Previously Untreated Children and Adolescents With Metastatic Rhabdomyosarcoma: An Intergroup Rhabdomyosarcoma Study
Authors: Pappo Alberto S. , Lyden Elizabeth , Breneman John , Wiener Eugene , Teot Lisa , Meza Jane , Crist William , Vietti Teresa
Published: February 2017

PURPOSE: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS).

PATIENTS AND METHODS: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m2 of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m2, dactinomycin 1.5 mg/m2, and cyclophosphamide 2.2 g/m2 (VAC) and vincristine 1.5 mg/m2, topotecan 0.75 mg/m2 daily × 5, and cyclophosphamide 250 mg/m2 daily × 5. Patients who did not respond to topotecan received continuation therapy with VAC alone.

RESULTS: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival.

CONCLUSION: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.
Patient Preference for Cancer Therapy: An Overview of Measurement Approaches
Authors: Stiggelbout A. M. , de Haes J. C.J.M.
Published: February 2017

PURPOSE: In the era of evidence-based medicine and shared decision making, the formal assessment of patient preference for treatments or treatment outcomes has attracted much attention. In this article, the two most common approaches to the evaluation of preference, ie, utility assessment and probability trade-off assessment, are described. The purpose is to provide clinicians with the background knowledge needed to interpret preference studies published in the literature and to judge whether the reported findings are relevant to their own patients.

METHODS: An overview is given of the methods used to assess utilities and probability trade-off scores. Evidence on determinants of such scores is presented. Examples from oncology are provided. Because experience with the treatment plays an important role as a determinant of preferences for both treatments and treatment outcomes, special attention is paid to the interpretation of studies in the light of subject selection. Directions for future research are suggested.

CONCLUSION: The choice of approach and the measuring instrument depend on the goal of the preference assessment. Normal psychologic processes, such as coping, adaptation, and cognitive dissonance reduction, cause patients who are about to undergo a therapy or have experienced a therapy to rate it more favorably than other patients do. This should be remembered when using evidence from the literature to inform patients or for patient decision making.
Clinical Trial Designs for Cytostatic Agents: Are New Approaches Needed?
Authors: Korn Edward L. , Arbuck Susan G. , Pluda James M. , Simon Richard , Kaplan Richard S. , Christian Michaele C.
Published: February 2017

ABSTRACT: Preclinical data suggest that some new anticancer agents directed at novel targets demonstrate tumor growth inhibition but not tumor shrinkage. Such cytostatic agents may offer clinical benefits for patients in the absence of tumor shrinkage. In addition, lower doses of some of these agents may be just as effective as higher doses, implying that toxicity may not be an ideal end point for dose finding. Because of these factors, the sequence and design of traditional phase I, II, and III trials used for cytotoxic agents (which typically shrink tumors and in a dose-dependent manner) may not be appropriate for cytostatic agents. This article discusses options for modifying trial designs to accommodate cytostatic agents. Examples are given where these options have been tried or are currently being tried. Recommendations given for choosing among the trial designs depend on what is known preclinically about the agents (eg, does one have a validated and reproducible biologic end point that can be used to guide a dose escalation?), what is known about the patient population being studied (eg, does one have a well-documented historical progression-free survival rate at 1 year for comparison with the experience of the new agent?), and the numbers of agents and patients available for participation in trials. Planned and ongoing trials will test the utility of some of these new approaches.