bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychologic effects of chemotherapy on children with cancer: a longitudinal study.
Authors: Copeland D R , Moore B D , Francis D J , Jaffe N , Culbert S J 
Published: February 2017

PURPOSE A prospective study was conducted to assess the effects of chemotherapy for cancer on children's long-term neuropsychologic status. PATIENTS AND METHODS Ninety-nine children who received no cranial radiation therapy (CRT) completed four annual neuropsychologic assessments. Fifty-one patients received intrathecal (IT) chemotherapy (ITC); 48 received no CNS treatment. These two groups were compared using repeated-measures analysis of variance on IQ, memory, language, freedom from distractibility, academic achievement, executive functions, and fine-motor, perceptual-motor, and tactile-spatial skills. In addition, 51 of the sample of 99 patients had been examined 5 to 11 years after diagnosis. Their data were analyzed to evaluate the longer-term effects of chemotherapy. The predictability of demographic and medical variables on neuropsychologic outcome at 3-year and long-term follow-up study were assessed using multiple regression techniques. RESULTS Overall, the effects of chemotherapy in the absence of CRT appear to be slight. Patients who received ITC and intravenous (IV) methotrexate declined slightly on perceptual-motor skills, but were still well within the normal range. Both groups, regardless of treatment, declined on academic achievement tests, although not to a statistically significant degree. Age effects were found on performance IQ (PIQ) and perceptual-motor skills. Socioeconomic status (SES) correlated with a large number of variables. Sex effects were not significant. CONCLUSION The present results are largely consistent with previous findings for nonirradiated groups. Treatment effects from ITC are slightly more apparent 5 to 11 years after diagnosis than at 3-year follow-up evaluation but this does not constitute a clinically meaningful difference. More noticeable are academic declines among all groups, regardless of treatment.
Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group.
Authors: Coppin C M , Gospodarowicz M K , James K , Tannock I F , Zee B , Carson J , Pater J , Sullivan L D 
Published: February 2017

PURPOSE A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival. PATIENTS AND METHODS Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated, 64% with cT3b or cT4. Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation, or to receive radiation without chemotherapy. Patients were stratified by clinical tumor stage and by radiation plan. The median follow-up duration is 6.5 years. RESULTS The occurrence of distant metastases was the same in both study arms. However, 25 of 48 control patients have had a first recurrence in the pelvis, compared with 15 of 51 cisplatin-treated patients (P = .036). The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin (P = .038, log-rank test) and this effect was preserved in a stepwise Cox regression model of prognostic factors (hazards ratio, 0.50; 90% confidence interval [CI], 0.29 to 0.86; P = .036). The hazard reduction was similar for both radiation plans. Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival, but the effect of cisplatin was not significant. CONCLUSION Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation, but has not been shown to improve overall survival. The use of concurrent cisplatin had no detectable effect on distant metastases.
Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study.
Authors: Balmaceda C , Heller G , Rosenblum M , Diez B , Villablanca J G , Kellie S , Maher P , Vlamis V , Walker R W , Leibel S , Finlay J L 
Published: February 2017

PURPOSE Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.
Evaluation of long-term toxicity after chemotherapy for testicular cancer.
Authors: Bokemeyer C , Berger C C , Kuczyk M A , Schmoll H J 
Published: February 2017

PURPOSE The current study evaluates the extent and reversibility of late sequelae after chemotherapy in longterm survivors of testicular cancer. The influence of therapy and patient characteristics and the relationship between different toxicities are assessed. PATIENTS AND METHODS Ninety patients with a median age of 28 years (range, 19 to 53) and a median followup time of 58 months (range, 15 to 159) participated in the clinical examinations, a personal interview, and technical investigations. Overall health and the impact of late toxicity were assessed by the patients. All patients were in complete remission (CR) for at least 1 year. Chemotherapy had consisted of cisplatin (P), bleomycin (B), and vinblastine (V) in 30 patients (33%); P, B, and etoposide (E) in 26 patients (29%); P, B, E, and a vinca alkaloid in 22 patients (24%); and other P-based combination regimens in 12 patients (13%). RESULTS Alterations of gonadotropin levels (follicle-stimulating hormone [FSH] luteinizing hormone [LH]) in up to 68% of patients and Leydig cell insufficiency in one third of patients were the most frequently detected abnormalities. Approximately 20% of patients had low serum magnesium [Mg] or phosphate levels, or elevated creatinine levels. Cardiovascular risk factors were identified in one third of patients with elevated serum cholesterol levels with or without obesity; 15% had developed arterial hypertension after chemotherapy. The most frequent symptomatic toxicities were Raynaud's phenomenon (RP) in 30% of patients, ototoxicity in 21%, and peripheral neuropathy in 17%. Major risk factors for the development of toxicity were cumulative dose of P (P < .0001 for ototoxicity and neurotoxicity; P < .01 for overall toxicity, gonadal toxicity, and dehydroepiandrosteron elevation; P < .05 for hypertension and Mg depletion) and type of chemotherapy (57% of PVB-treated patients v25% of PEB +/- vincristine-treated patients with RP; P < .01). CONCLUSION The cumulative dose of P was a major predictor for toxicity. Patients and treatment characteristics such as noise exposure, age, history of smoking, and mode of B application were less important. Further clinical trials should evaluate the sequelae of chemotherapy treatment for testicular cancer prospectively.
High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumors in children: a pilot pediatric oncology group study.
Authors: Mahoney D H , Strother D , Camitta B , Bowen T , Ghim T , Pick T , Wall D , Yu L , Shuster J J , Friedman H 
Published: February 2017

PURPOSE To determine the maximum-tolerated dose of cyclophosphamide (CTX) when administered sequentially with melphalan 60 mg/m2/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children with recurrent or progressive malignant brain tumors, and to make preliminary observations on efficacy. PATIENTS AND METHODS Nineteen patients between the ages of 2 and 21 years were enrolled and 18 were assessable for effects of therapy. CTX was administered to seven patients at 750 mg/m2/d for 4 days, to five patients at 975 mg/m2/d, to three patients at 1,200 mg/m2/d, and to three patients at 1,500 mg/m2/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therapy, time to progression, and survival and monitored. RESULTS The median time to a granulocyte count more than 500/dL was 19 days (range, 11 to 39), and for a platelet count more than 50,000/dL was 33 days (range, 16 to 60). Four heavily pretreated patients (22%) died of transplant-related complications. No dose-limiting, non-hematologic toxicities were defined for the study. Seven of 18 patients (39%) had a complete response (CR) or a partial response (PR). These included four patients with medulloblastoma (CR and three PRs), two with germinomas (two CRs), and one with ependymoma (one CR). The estimated 1-year survival rate was 39% (SE 12%). CONCLUSION CTX, at a maximum total dose of 6,000 mg/m2, administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not been heavily pretreated. Responses were seen in patients with medulloblastoma and germinomas. Further trials in children with chemosensitive tumors, with minimal residual disease, are planned.
Prognostic significance of the microvascular count in colorectal cancer.
Authors: Lindmark G , Gerdin B , Sundberg C , Påhlman L , Bergström R , Glimelius B 
Published: February 2017

PURPOSE To investigate the potential correlations between a high microvascular count and the survival rate in colorectal cancer. MATERIALS AND METHODS Three markers for endothelial cells--Ulex Europaeus Lectin (UEA), a polyclonal anti-von Willebrand factor (vWF) antibody, and a monoclonal anti-CD31 antibody (all from Dakopatts, Glostrup, Denmark)--were used for immunohistochemical detection of microvessels in whole-mount sections from 15 colorectal cancers. Areas with higher microvascular density were homogeneously distributed in the sections, regardless of the marker used. The anti-vWF antibody was subsequently used for quantification of microvessels in full-cross tumor biopsies collected from 212 consecutive surgical specimens. The correlations between the mean number of microvessels in areas with the highest microvascular density and tumor differentiation, tumor stage according to Dukes', and survival time were investigated. RESULTS A significantly longer survival time was shown for patients who had tumors with a mean of more than 10 anti-vWF-positive microvessels, as compared with those who had < or = five. Tumors with a microvascular count between six and 10 microvessels behaved in-between. There was no correlation between the number of microvessels and tumor differentiation or Dukes' stage. CONCLUSION The number of microvessels measurable in tumor biopsies seems to be a prognostic predictor independent of Dukes' stage in colorectal cancer. However, our results are opposite to the findings in other tumor types investigated so far; we found that a high microvascular count predicted a longer survival time, rather than a shorter one. Determination of the microvascular count can be of importance in therapy selection even before, or immediately after, surgery, ie, before Dukes' stage is known.
Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.
Authors: Feugeas O , Guriec N , Babin-Boilletot A , Marcellin L , Simon P , Babin S , Thyss A , Hofman P , Terrier P , Kalifa C , Brunat-Mentigny M , Patricot L M , Oberling F 
Published: February 2017

PURPOSE The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.
Prognostic significance of a positive microscopic margin in high-risk extremity soft tissue sarcoma: implications for management.
Authors: Heslin M J , Woodruff J , Brennan M F 
Published: February 2017

PURPOSE A positive microscopic margin (PMM) is a significant prognostic variable and leads to local recurrence (LR) in high-grade soft tissue sarcoma (STS) patients. Its effect on the rate of distant metastasis (DM) and tumor mortality (TM) remains controversial. PATIENTS AND METHODS One hundred sixty-eight primary, high-risk (high-grade, deep, > or = 5 cm) extremity STS patients were identified from our data base, of which 42 had a PMM. Limb-sparing surgery (LSS) was the primary surgical therapy in 144 patients; 24 received amputation (AMP). Statistical analysis was by log-rank test and Cox model. Significance was defined as a P value less than .05. RESULTS A PMM was a significant negative prognostic factor for both DM and TM (P = .002 and .002, respectively). However, those patients who received LSS with 28% PMMs showed no significant difference in the rate of DM or TM compared with patients who received AMP with only 8% PMMs (log-rank, P = .057 and .28, respectively). A PMM was significantly associated with > or = 1,000 mL blood loss and more than 3 hours of operating time (P < .006 and .001, respectively). CONCLUSION The strong statistical significance that relates a PMM to DM and TM in high-risk STS of the extremity is likely related to biologically aggressive tumors and LSS. Residual microscopic disease is not a guarantee of LR. The main problem in this group of patients is not LR, but DM and subsequent death. Therefore, to increase a disability with further surgery or amputate a patient's limb without clear evidence of LR in this group at high risk for distant recurrence is not recommended.
Phase II trial of fludarabine monophosphate as first-line treatment in patients with advanced follicular lymphoma: a multicenter study by the Groupe d'Etude des Lymphomes de l'Adulte.
Authors: Solal-Céligny P , Brice P , Brousse N , Caspard H , Bastion Y , Haïoun C , Bosly A , Tilly H , Bordessoule D , Sebban C , Harousseau J L , Morel P , Dupas B , Plassart F , Vasile N , Fort N , Leporrier M 
Published: February 2017

PURPOSE Fludarabine monophosphate (FAMP) is a major drug in the treatment of chronic lymphocytic leukemia and showed efficacy in selected groups of patients with low-grade lymphomas, most of them pretreated. The aim of this trial was to assess the efficacy and the toxicity of FAMP in untreated patients with follicular lymphoma. PATIENTS AND METHODS Fifty-four untreated patients with advanced follicular lymphoma were treated with intravenous (i.v.) fludarabine at a dose of 25 mg/m2/d during 5 days every 4 weeks, to a maximum of nine cycles. RESULTS The toxicity of the drug was mild, mainly granulocytic. Granulocytopenia > or = 3 (World Health Organization [WHO]) was observed during 48 of 328 cycles (14.6%) and in 22 of 53 (41%) patients assessable for toxicity. Fludarabine had to be stopped prematurely because of toxicity in nine patients: marrow toxicity in five, peripheral neuropathy in two, and interstitial pneumonitis and hepatitis in one patient each. Among 49 patients assessable for response, the overall response rate was 65% and the complete response (CR) rate 37%. The median progression-free survival interval for all patients was 13.6 months. CONCLUSION These results confirm that fludarabine is active when used as first-line treatment in patients with follicular lymphoma and has a low toxicity rate. It may be used as single treatment in elderly patients. Associations of fludarabine with other drugs active against follicular lymphoma need to be determined.
Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas.
Authors: Glantz M J , Choy H , Kearns C M , Cole B F , Mills P , Zuhowski E G , Saris S , Rhodes C H , Stopa E , Egorin M J 
Published: February 2017

PURPOSE Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. PATIENTS AND METHODS Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) > or = 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3-hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients. RESULTS Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose-limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors. CONCLUSION The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.
Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer.
Authors: Fisherman J S , Cowan K H , Noone M , Denicoff A , Berg S , Poplack D , Balis F , Venzon D , McCabe M , Goldspiel B , Chow C , Ognibene F P , O'Shaughnessy J 
Published: February 2017

PURPOSE We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.