bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.
Authors: Silber J H , Radcliffe J , Peckham V , Perilongo G , Kishnani P , Fridman M , Goldwein J W , Meadows A T 
Published: February 2017

PURPOSE Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.
Microgranular variant of acute promyelocytic leukemia in children.
Authors: Rovelli A , Biondi A , Cantù Rajnoldi A , Conter V , Giudici G , Jankovic M , Locasciulli A , Rizzari C , Romitti L , Rossi M R 
Published: February 2017

PURPOSE The microgranular variant (M3v) of acute promyelocytic leukemia (APL) rarely has been reported in a pediatric series of acute nonlymphoblastic leukemia (AnLL). We reviewed the clinical and biologic features of childhood M3v cases in our AnLL series. PATIENTS AND METHODS From January 1970 to January 1991, 11 children with M3v were admitted and treated at our center. A diagnosis was made according to French-American-British (FAB) criteria. Morphologic examination, cytochemical analysis, and immunophenotyping were performed by a single pathologist. From January 1984, the diagnosis was confirmed by cytogenetic and, subsequently, by molecular analysis on frozen material. RESULTS In our series, the overall incidence of children with APL was unusually high, 31.2% of the AnLL and M3v constituted one case in every four cases of APL. Even restriction of the analysis to the time when either cytogenetic and DNA studies confirmed the diagnosis, the incidence did not change. The immunophenotype of M3v cases was identical to that described for the hypergranular type, but an unexpected association of CD2 with M3v was shown. The onset was characterized by marked hyperleukocytosis (median WBC count, 87 x 10(9)/L) unlike classic APL. Disseminated intravascular coagulation (DIC) was always present and severe. Hyperleukocytosis and DIC were responsible for the high incidence of deaths for hemorrhagic events in the first days after onset (eight of 11 patients). CONCLUSIONS In our experience, for unknown reasons, M3v may occur in childhood more than generally was considered. The clinical course and prognosis seem worse in M3v than in typical APL cases.
Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
Authors: Steward W P , Verweij J , Somers R , Spooner D , Kerbrat P , Clavel M , Crowther D , Rouesse J , Tursz T , Tueni E 
Published: February 2017

PURPOSE This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.
Survival of breast cancer patients receiving adjunctive psychosocial support therapy: a 10-year follow-up study.
Authors: Gellert G A , Maxwell R M , Siegel B S 
Published: February 2017

PURPOSE The impact of an adjunctive psychosocial support program on length of survival with breast cancer was evaluated in a retrospective cohort study. The duration of observation of survival was extended 10 years beyond a previous study of the same cohort of patients. PATIENTS AND METHODS One hundred two nonparticipants were individually matched to 34 participants on major prognostic factors. Both groups were monitored from the date of cancer diagnosis (1971 through 1980) until March 1991. The support program consisted of weekly cancer peer support and family therapy, individual counseling, and use of positive mental imagery. Survival analysis controlled for the effects of other major prognostic factors in the outcome of breast cancer. RESULTS The mean +/- SD survival time from date of cancer diagnosis to last date of follow-up was 96.0 +/- 53.2 months in the participant group compared with 85.1 +/- 63.4 months in the nonparticipant group, a nonsignificant difference (P = .1). Median survival was 84.0 months for participants (95% confidence interval [CI], 59 to 133) and 66.0 months for nonparticipants (95% CI, 48 to 105). A second analysis restricted nonparticipants to those who had a survival time > or = that of the matched case at time of entry into the support program. Survival increased to a mean of 101.1 months (median, 105.0; 95% CI, 71 to 132) for nonparticipants and remained unchanged for participants, also a statistically nonsignificant difference (P = .9). CONCLUSION While the program may have beneficial effects on quality of life, this study does not indicate a significant favorable impact on survival with breast cancer or that the program is serving as a social locus for the gathering of exceptional survivors.
A randomized, double-blind trial of fluorouracil plus placebo versus fluorouracil plus oral leucovorin in patients with metastatic colorectal cancer.
Authors: Laufman L R , Bukowski R M , Collier M A , Sullivan B A , McKinnis R A , Clendennin N J , Guaspari A , Brenckman W D 
Published: February 2017

PURPOSE A prospectively randomized trial was performed to determine whether the combination of fluorouracil (FU) plus leucovorin (FU-LV) administered orally is more effective than equitoxic FU for patients with metastatic colorectal cancer. PATIENTS AND METHODS A double-blind, placebo-controlled trial design was used to eliminate observer bias. An escalating FU dosing schedule was used to achieve equal toxicity. End points were response, time to treatment failure (TTF), and eight quality-of-life (QL) parameters. A crossover arm allowed FU-treated patients to receive FU-LV combination treatment after treatment failure. RESULTS Response rate was 32% for FU-LV versus 23% for FU (P = .15). Median TTF was 22 versus 16 weeks (P = .27). Median survival time was 44 versus 54 weeks (P = .26). QL was the same for both treatments, except for days of hospitalization, which was greater for FU-LV (P < .001). Toxicities were similar to those previously reported for FU-LV and FU alone. CONCLUSION Oral LV-FU produces the same efficacy and toxicity pattern as has been reported for intravenous LV-FU. When FU-LV is compared with equitoxic doses of FU, there is no difference in patient outcome. These results suggest that patients with advanced disease should receive FU at doses adequate to produce toxicity.
Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.
Authors: Gilchrist K W , Gray R , Fowble B , Tormey D C , Taylor S G 
Published: February 2017

PURPOSE The Eastern Cooperative Oncology Group (ECOG) entered 766 patients onto two prospectively randomized surgical adjuvant clinical trials for lymph node-positive breast cancer (T1-3N1M0). Ninety-five percent (n = 728) of eligible patients have complete information on the prognostic covariables under study (tumor necrosis [TN], tumor size, number of positive lymph nodes, age) and a median follow-up duration of 10.3 years. METHODS TN was defined as confluent cell death in invasive areas of primary cancers, visible at 4 x objective lens magnification. Cox proportional hazards models were used to estimate presence versus absence of TN effects on clinical outcomes over full cross-stratification of variables, including delivery of chemotherapy versus observation only. Time-varying effects were modeled using spline functions of time, and by fixing proportional hazards models separately in the time periods 0 to 2 and 2+ years. RESULTS Presence of TN was an independent predictor for time to recurrence (TTR) (P = .007) and for survival (P = .0003) in the overall 10-year follow-up period. Presence of TN was also an independent predictor for TTR and for survival (each P < .0001) in the period 0 to 2 years after diagnosis. Spline function time-modeling calculations showed different hazard ratios in the TN-present (TN+) versus TN-absent (TN-) groups for both TTR and survival (each P < .0001). This difference is changing over time (P = .0001 for TTR, P = .0005 for survival). Once a patient has been disease-free beyond 2 years after diagnosis, presence or absence of TN is irrelevant to future prognosis. CONCLUSION Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.
Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study.
Authors: Lorusso V , Catino A , Leone B , Rabinovich M , Gargano G , Paradiso A , De Lena M 
Published: February 2017

PURPOSE This study aimed to evaluate the activity and toxicity of carboplatin (PPL) and ifosfamide (IFO) in patients with epithelial ovarian cancer previously treated with cisplatin (CDDP)-containing regimens. PATIENTS AND METHODS From July 1989 to December 1991, 35 patients with epithelial ovarian cancer relapsed or refractory to CDDP as first-line chemotherapy were treated. PPL was administered at a dose of 300 mg/m2 intravenously (IV) on day 1 and IFO at a dose of 1,500 mg/m2 IV on days 1 to 3 every 3 to 4 weeks. Criteria for evaluating previous response to CDDP were strictly defined. RESULTS The overall response rate was 43% (complete response [CR], 6%; partial response [PR], 37%) and the median duration of response was 7 months (range, 3 to 16). In potentially platinum-sensitive (PPS; relapsed) patients, the overall response rate was 56%. None of the primary platinum-resistant (PPR) patients obtained a clinical response to PPL plus IFO, whereas one of five secondary platinum-resistant (SPR) patients obtained a PR. The regimen was easily manageable. CONCLUSION PPL plus IFO is useful and well-tolerated combination in salvage treatment of patients with advanced ovarian cancer. However, clear synergism between PPL and IFO that could overcome intrinsic or acquired CDDP resistance was not observed. The advantage of PPL plus IFO as compared with CDDP-containing regimens is represented by the increased tolerability and the reduced neurotoxicity, nephrotoxicity, and ototoxicity as compared with CDDP-containing regimens. It is essential that the patient population be defined according to their previous response to platinum therapy in trials involving second-line therapy of ovarian cancer.
Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.
Authors: Rosen P P , Groshen S , Kinne D W , Norton L 
Published: February 2017

PURPOSE This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma < or = 1.0 cm in diameter or special tumor types < or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.
With modern imaging techniques, is staging laparotomy necessary in pediatric Hodgkin's disease? A Pediatric Oncology Group study.
Authors: Mendenhall N P , Cantor A B , Williams J L , Ternberg J L , Weiner M A , Kung F H , Marcus R B , Ferree C R , Leventhal B G 
Published: February 2017

PURPOSE To determine whether the information gained from staging laparotomy can be predicted by imaging and/or clinical factors in children with Hodgkin's disease. PATIENTS AND METHODS Between 1986 and 1991, 216 consecutive pediatric patients with Hodgkin's disease underwent laparotomy and were treated on two concurrent protocols in a multiinstitutional cooperative group. All patients had computed tomography (CT) of the chest, abdomen, and pelvis. Clinical factors studied included sedimentation rate, B symptoms, histology, number and location of involved sites, sex, mediastinal involvement, and age. Pretreatment CTs were centrally reviewed in 88 cases for the presence and size of both supradiaphragmatic and infradiaphragmatic lymph nodes, intrinsic spleen lesions, and splenic size. Models were generated that were predictive of any abdominal disease, splenic involvement, extensive splenic involvement, and upstaging at the laparotomy. False-positive and false-negative rates were calculated. RESULTS For the end point of any abdominal disease, a model based on B symptoms, histology, sedimentation rate, and number and location of involved sites was highly significant (P < .0001). However, the success in predicting abdominal disease in an individual patient was limited: false-negative rate, 26%; false-positive rate, 32%. Highly significant models based on clinical factors and/or radiographic findings were also generated to predict splenic involvement, extensive splenic involvement, and upstaging with laparotomy, but they also had high false-positive and false-negative rates. CONCLUSION Laparotomy findings cannot be predicted accurately in the majority of patients based on knowledge of CT findings and clinical factors.
Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.
Authors: Carde P , Hagenbeek A , Hayat M , Monconduit M , Thomas J , Burgers M J , Noordijk E M , Tanguy A , Meerwaldt J H , Le Fur R 
Published: February 2017

PURPOSE To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.
Ondansetron versus ondansetron, dexamethasone, and chlorpromazine in the prevention of nausea and vomiting associated with multiple-day cisplatin chemotherapy.
Authors: Fox S M , Einhorn L H , Cox E , Powell N , Abdy A 
Published: February 2017

PURPOSE This study is designed to evaluate the effectiveness of ondansetron alone (OND) or in combination with 2 days of dexamethasone and 5 days of chlorpromazine (ODC) in the prevention of emetic episodes in patients receiving multiple-day cisplatin. PATIENTS AND METHODS Forty-four patients receiving 20 or 40 mg/m2 of cisplatin daily for 4 to 5 days plus etoposide (VP-16) alone or in combination with bleomycin or ifosfamide were randomized to receive three doses of OND (0.15 mg/kg 30 minutes before and 4 and 8 hours after cisplatin) versus the identical OND regimen plus dexamethasone 8 mg before cisplatin and 4 mg 4 and 8 hours later on days 1 and 2, plus chlorpromazine 50 mg every 4 hours for four doses per day. Patients were chemotherapy-naive, had a Karnofsky performance status > or = 60, and were not receiving nonstudy antiemetics. RESULTS Nineteen of 22 patients (86%) on ODC had fewer than three emetic episodes throughout the study period, compared with 10 of 22 (46%) on OND (P = .009), and 55% of patients on ODC had no emetic episodes, compared with 32% on OND (P = .22). The ODC arm had fewer treatment failures (5%) than the OND arm (32%). The mean nausea ratings per visual analog scale were 15.0 for OND and 5.5 for ODC (P = .046). Headache was less frequent with ODC versus OND (14% and 41%, respectively, P = .09). CONCLUSION ODC was superior to OND with respect to therapeutic efficacy and decreased headaches. Both OND and ODC were more effective on days 1 and 2, rather than days 4 and 5, suggesting tachyphylaxis, anticipatory nausea, or delayed nausea from the first few days of cisplatin combination chemotherapy.
Phase I/pharmacokinetic study of high-dose progesterone and doxorubicin.
Authors: Christen R D , McClay E F , Plaxe S C , Yen S S , Kim S , Kirmani S , Wilgus L L , Heath D D , Shalinsky D R , Freddo J L 
Published: February 2017

PURPOSE We developed a new formulation of progesterone that permits administration of up to 10 g of progesterone as a continuous intravenous infusion over 24 hours and conducted a phase I clinical trial to determine whether progesterone could modulate the in vivo cytotoxicity of the P-glycoprotein substrate doxorubicin. PATIENTS AND METHODS Thirty-four patients with advanced malignancies were treated with increasing doses of progesterone and a fixed dose of 60 mg/m2 of doxorubicin given as an intravenous bolus 2 hours after starting a 24-hour intravenous infusion of progesterone. RESULTS Progesterone enhanced doxorubicin-induced myelotoxicity in a dose-dependent fashion without altering the pharmacokinetics of doxorubicin. The steady-state plasma concentration of progesterone at a dose level of 4 g was 4.1 +/- 0.9 mumol/L, which was higher than the minimal concentration required to reverse multidrug resistance (MDR) in vitro. CONCLUSION Progesterone enhanced the hematologic toxicity of doxorubicin without altering its pharmacokinetics, suggesting that progesterone could modulate P-glycoprotein at the level of pluripotent hematopoietic stem cells. Adequate tissue concentrations of progesterone could be achieved in vivo to modulate doxorubicin toxicity in the bone marrow and thus potentially in tumor tissue as well. Selectivity may potentially be gained by using hematopoietic growth factors to offset the enhanced hematologic toxicity of doxorubicin while leaving the enhancement of toxicity to tumor cells unchanged.