bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomized controlled trial of lenograstim in small-cell lung cancer.
Authors: Woll P J , Hodgetts J , Lomax L , Bildet F , Cour-Chabernaud V , Thatcher N 
Published: February 2017

PURPOSE The use of granulocyte colony-stimulating factor (G-CSF) to increase cytotoxic dose-intensity was assessed in a randomized trial in better-prognosis small-cell lung cancer (SCLC). Both control and G-CSF arms were subject to the same dose-intensification strategy. PATIENTS AND METHODS Patients with newly diagnosed SCLC and either no or one adverse prognostic factor were randomized to receive vincristine, ifosfamide, carboplatin, and etoposide (VICE) alone or with recombinant human (rHu)G-CSF (lenograstim) 5 micrograms/kg/d between cycles. Six chemotherapy cycles were given, with prophylactic cranial irradiation after cycle 1 and thoracic irradiation after cycle 3. There was no fixed dose interval. In both arms, patients were eligible for re-treatment when the WBC count was > or = 3 x 10(9)/L and platelet count was > or = 100 x 10(9)/L. No dose reductions were permitted. Dose-intensity was expressed relative to standard every-4-weeks VICE. RESULTS Sixty-five consecutive patients in one institution were randomized to control (n = 31) or G-CSF (n = 34). WBC and neutrophil counts were consistently higher in G-CSF patients than in the control group, but there were no significant differences in the incidence of febrile neutropenia, antibiotic or transfusion requirements, or days in hospital. In both treatment arms, the median dose-intensity was greater than one for each cycle (control group, P = .0009; G-CSF group, P = .0001). The G-CSF group received a significantly higher dose-intensity than the control group, with the greatest difference in the first three cycles (1.34 v 1.17, P = .001). There were more chemotherapy-related deaths in the G-CSF group than in the control group (six v one), but this group had a better 2-year survival rate (32% with G-CSF, 95% confidence interval [CI], 16 to 48; 15% with controls, 95% CI, 2 to 27). CONCLUSION The dose-intensity of VICE chemotherapy was increased in both groups. Patients randomized to receive G-CSF achieved a significantly higher dose-intensity than controls. Despite early toxicity, they had a better 2-year survival rate.
Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation.
Authors: Pfister D G , Harrison L B , Strong E W , Shah J P , Spiro R W , Kraus D H , Armstrong J G , Zelefsky M J , Fass D E , Weiss M H 
Published: February 2017

PURPOSE To evaluate the feasibility and efficacy of a strategy using induction chemotherapy followed by radiation therapy (RT) as a means of organ-function preservation in patients with advanced oropharynx cancer. PATIENTS AND METHODS From January 1983 to December 1990, 33 patients with advanced squamous cell oropharynx cancer whose appropriate surgical management would have required a tongue procedure and potential total laryngectomy were treated with one to three cycles of cisplatin (CDDP)-based induction chemotherapy. Patients with a complete response (CR) or partial response (PR) at the primary site then received definitive external-beam RT with or without interstitial implant with or without neck dissection with surgery to the primary tumor site reserved for disease persistence or relapse; patients with less than a PR after chemotherapy had appropriate surgery and postoperative RT recommended. RESULTS With a median follow-up period of 6.2 years, actuarial overall and failure-free survival rates at 5 years are 41% and 42%, respectively. Chemotherapy toxicity contributed to the death of two patients and was possibly a factor in two others. Local control was achieved in 14 patients (42%) without any surgery to the larynx or tongue. Among 13 patients currently alive, all had a preserved larynx and only one required tongue surgery; 12 of 13 have speech subjectively described as always understandable; and nine of 13 have no significant restrictions in their diet. CONCLUSION This treatment program is feasible and effective in patients with advanced oropharynx cancer and produces an excellent functional outcome in most long-term survivors. Modifications to optimize patient selection, minimize toxicity, and improve local control are indicated. The relative toxicity, efficacy, and functional outcome provided by this and other chemotherapy and RT programs versus either standard surgery and/or RT options can only be addressed in a randomized comparison of these therapies.
Improved control of invasive cervical cancer in Sweden over six decades by earlier clinical detection and better treatment.
Authors: Sparén P , Gustafsson L , Friberg L G , Pontén J , Bergström R , Adami H O 
Published: February 2017

PURPOSE Cancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed. PATIENTS AND METHODS We compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality. RESULTS For each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter. CONCLUSION Improvements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources.
Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma.
Authors: De Bernardi B , Conte M , Mancini A , Donfrancesco A , Alvisi P , Tomà P , Casale F , Cordero di Montezemolo L , Cornelli P E , Carli M 
Published: February 2017

PURPOSE To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience. PATIENTS AND METHODS Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months. RESULTS Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates. CONCLUSION Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.
Phase I trial of 13-cis-retinoic acid in children with neuroblastoma following bone marrow transplantation.
Authors: Villablanca J G , Khan A A , Avramis V I , Seeger R C , Matthay K K , Ramsay N K , Reynolds C P 
Published: February 2017

PURPOSE Treatment of neuroblastoma cell lines with 13-cis-retinoic acid (cis-RA) can cause sustained inhibition of proliferation. Since cis-RA has demonstrated clinical responses in neuroblastoma patients, it may be effective in preventing relapse after cytotoxic therapy. This phase I trial was designed to determine the maximal-tolerated dosage (MTD), toxicities, and pharmacokinetics of cis-RA administered on an intermittent schedule in children with neuroblastoma following bone marrow transplantation (BMT). PATIENTS AND METHODS Fifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg/m2/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted. RESULTS The MTD of cis-RA was 160 mg/m2/d. Dose-limiting toxicities in six of nine patients at 200 mg/m2/d included hypercalcemia (n = 3), rash (n = 2), and anemia/thrombocytopenia/emesis/rash (n = 1). All toxicities resolved after cis-RA was discontinued. Three complete responses were observed in marrow metastases. Serum levels of 7.4 +/- 3.0 mumol/L (peak) and 4.0 +/- 2.8 mumol/L (trough) at the MTD were maintained during 14 days of therapy. The DLT correlated with serum levels > or = 10 mumol/L. CONCLUSION The MTD of cis-RA given on this intermittent schedule was 160 mg/m2/d. Serum levels known to be effective against neuroblastoma in vitro were achieved at this dose. The DLT included hypercalcemia, and may be predicted by serum cis-RA levels. Monitoring of serum calcium and cis-RA levels is indicated in future trials.
Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study.
Authors: Grever M , Kopecky K , Foucar M K , Head D , Bennett J M , Hutchison R E , Corbett W E , Cassileth P A , Habermann T , Golomb H 
Published: February 2017

PURPOSE Therapy of hairy cell leukemia has markedly improved. Interferon alfa-2a and pentostatin are active agents. The National Cancer Institute organized an intergroup trial to compare these agents prospectively in untreated patients. METHODS Patients were randomized to receive either interferon alfa-2a (3 x 10(6) U subcutaneously three times per week) or pentostatin (4 mg/m2 intravenously every 2 weeks). Patients who did not respond to initial treatment were crossed over. RESULTS Of 356 patients on study, 313 were eligible. Among interferon patients, 17 of 159 (11%) achieved a confirmed complete remission and 60 of 159 (38%) had a confirmed complete or partial remission. Among pentostatin patients, 117 of 154 (76%) achieved a confirmed complete remission and 121 of 154 (79%) had a confirmed complete or partial remission. Additional patients achieved criteria for complete remission, but lacked confirmatory follow-up evaluation. Response rates were significantly higher (P < .0001) and relapse-free survival was significantly longer with pentostatin than interferon (P < .0001). The median follow-up duration is 57 months (range, 19 to 82). Myelosuppression was more frequent with pentostatin (P = .013). A multivariate logistic regression analysis of the confirmed complete remissions on pentostatin showed the following factors to be important for achieving a complete remission: high hemoglobin level (two-tailed P = .024), young age (P = .0085), and no or little splenomegaly (P = .0029). CONCLUSION Both agents were well tolerated. Pentostatin produced higher response rates, and the responses were durable. Patient age and clinical status had an impact on outcome with pentostatin. Pentostatin is effective therapy for hairy cell leukemia.
Test/retest study of the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire.
Authors: Hjermstad M J , Fossa S D , Bjordal K , Kaasa S 
Published: February 2017

PURPOSE The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated instrument that assesses health-related quality of life (HRQOL) in cancer patients. It is used in cancer clinical trials in Europe, Canada, and the United States, and has demonstrated high reliability and validity in different groups of cancer patients. Despite thorough testing of reliability and validity, we have not identified any reports on its test/retest reliability; thus, a test/retest study was performed at the Norwegian Radium Hospital (NRH). MATERIALS AND METHODS Cancer patients from the outpatient clinic who were off treatment for > or = 3 months were eligible for the study. The EORTC QLQ-C30 was given to the patients when they presented for their visit. The second questionnaire was received by the patients 4 days later. Of 291 eligible patients, 270 (93%) agreed to participate and 190 (73%) completed both questionnaires. RESULTS The test/retest reliability measured by Pearson's correlation coefficient was high for all functional scales, with a range from .82 for cognitive and role function to .91 for physical function. The r value for global HRQOL was .85. For the symptom scales--nausea/vomiting, fatigue, and pain--the coefficients were .63, .83, and .86, respectively. The single-item coefficients ranged from .72 for diarrhea to .84 for financial impact. The Spearman rank correlation was in the same range for all dimensions. CONCLUSION The EORTC QLQ-C30 seems to yield high test/retest reliability in patients with various cancer diagnoses whose condition is not expected to change during the time of measurement.
Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group.
Authors: Jakacki R I , Zeltzer P M , Boyett J M , Albright A L , Allen J C , Geyer J R , Rorke L B , Stanley P , Stevens K R , Wisoff J 
Published: February 2017

PURPOSE To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of radiation therapy (RT) and/or chemotherapy. PATIENTS AND METHODS Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen. RESULTS Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease. CONCLUSION (1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure.
Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.
Authors: Sarkis A S , Bajorin D F , Reuter V E , Herr H W , Netto G , Zhang Z F , Schultz P K , Cordon-Cardo C , Scher H I 
Published: February 2017

PURPOSE This study sought to examine the prognostic role of p53 nuclear overexpression in muscle-invasive bladder cancer because of its correlation with progression of superficial bladder cancer. PATIENTS AND METHODS Ninety of 111 patients treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with a median follow-up duration of 5.8 years were evaluated. p53 nuclear overexpression was determined by immunohistochemistry on deparaffinized tissue sections. Patients were stratified into two groups according to the percent of tumor cells with positive nuclear reactivity. Overexpression was defined as tumors with > or = 20% cells with positive nuclear reactivity and nonoverexpression as tumors with less than 20% reactivity. RESULTS Nuclear overexpression was observed in 47 patients and nonoverexpression in 43 patients. Patients whose tumors had p53 overexpression had a significantly higher proportion of cancer deaths. A multivariate analysis that evaluated the pretreatment variables p53 nuclear overexpression, age, sex, palpable mass, prechemotherapy tumor stage, performance status, ureteral obstruction, tumor size, multifocality, and grade showed that p53 overexpression had independent significance for survival (P = .001; relative risk ratio, 3.1). The impact of p53 overexpression on survival was predominantly in T2 and T3a tumors. Long-term survival was evident in seven of 17 patients (41%) with p53 overexpression versus 20 of 26 (77%) in whom p53 was not overexpressed (P = .007). CONCLUSION p53 nuclear overexpression has independent prognostic value for survival in patients with invasive bladder cancer treated with neoadjuvant chemotherapy.
Appropriateness of adjuvant systemic therapy for axillary node-negative breast cancer: a physician opinion survey.
Authors: Sawka C A , O'Connor A M , Llewellyn-Thomas H A , To T , Pinfold S P , Harrison-Woermke D 
Published: February 2017

PURPOSE To examine variations in physicians' recommendations for systemic adjuvant therapy in the treatment of women with node-negative breast cancer (NNBC) and to determine factors used in making specific recommendations. MATERIALS AND METHODS A questionnaire was sent by mail to all 149 Ontario physicians who actively treated breast cancer in 1993. The questionnaire described 48 clinical scenarios of women with NNBC, which included all possible combinations of the following factors: menopausal status, tumor size, hormone receptor status, histologic and nuclear grade, and lymphatic and/or vascular invasion. Respondents rated the appropriateness of administering tamoxifen, combination chemotherapy, or both tamoxifen and combination chemotherapy on a nine-point scale from extremely inappropriate to extremely appropriate. Respondent agreement and disagreement were tabulated for each scenario, and factors associated with specific treatment ratings were analyzed by logistic regression. RESULTS The response rate was 87%. Agreement for the appropriateness of specific therapies was most evident where clinical trials have demonstrated efficacy, whereas disagreement was observed in scenarios in which support for a specific treatment is not available in the current literature. Relevant tumor- and patient-specific factors were used in decision-making; personal characteristics of the respondents had no statistically significant impact on appropriateness ratings. CONCLUSION The physicians surveyed had good knowledge of NNBC prognostic factors, but had a range of opinion on optimal therapy for many clinical scenarios, which reflects current knowledge of the benefits of adjuvant therapy for NNBC.
High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.
Authors: Le Cesne A , Antoine E , Spielmann M , Le Chevalier T , Brain E , Toussaint C , Janin N , Kayitalire L , Fontaine F , Genin J 
Published: February 2017

PURPOSE The study was designed to assess the toxicity and activity of high-dose ifosfamide (HDI) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas (ASTS) pretreated with doxorubicin and/or a standard-dose ifosfamide (SDI)-containing regimen. PATIENTS AND METHODS Between January 1991 and November 1993, 40 patients with progressive ASTS were entered onto the study. Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows: SDI-refractory (n = 21), SDI-resistant (n = 2), and indeterminate SDI-sensitive (n = 5). Patients were treated until progression or major toxicity. RESULTS One hundred forty-seven cycles of HDI were administered. Neutropenia was dose-limiting, with 100% of patients experiencing grade 3 to 4 toxicity and 12 admissions for febrile neutropenia (30% of patients). Neurotoxicity (17% of patients) was significantly associated with acute renal failure (n = 4) (P < .001), grade 4 thrombocytopenia (P < .01) and febrile neutropenia (P = .048). Chronic renal toxicity (n = 4) was significantly associated with retroperitoneal masses and/or prior nephrectomy (P = .008). Partial responses (PRs) were observed in 12 of 36 assessable patients (33%) and eight patients (22%) experienced disease stabilization. All but one response occurred in patients pretreated with SDI, with five PRs among SDI-refractory patients. Leiomyosarcomas appear resistant to HDI. The median response duration was 8 months (range, 6 to 13+) and the median overall survival time was 12 months. CONCLUSION The activity of HDI in these pretreated ASTS patients and the apparent circumvention of SDI resistance suggest a real dose-response relationship for ifosfamide and deserve further evaluation. Although toxic, this treatment appears feasible and manageable using routine clinical support. Since prophylaxis of ifosfamide-induced renal damage remains unknown, frequent monitoring of renal and tubular functions during therapy is highly recommended.