bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries.
Authors: Bunt A M , Hermans J , Smit V T , van de Velde C J , Fleuren G J , Bruijn J A 
Published: February 2017

PURPOSE Possible causes underlying the substantial differences in gastric cancer survival rates observed between Japan and the West were examined in a randomized trial comparing the Western R1 resection with limited lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy. PATIENTS AND METHODS The effect of four factors associated with lymphadenectomy on microscopic tumor-node-metastasis (TNM) staging, and on stage-specific survival rates was assessed in 473 curatively resected patients. RESULTS After application of extended lymphadenectomy, additional information on N status was available, only in R2 resections with up-staging to N2 status in 30% of patients. The calculated effect of this stage migration on known 5-year survival rates was as follows: an increase of 1% in TNM stage Ia, 2% in Ib, 7% in II, 15% in IIIa, and 15% in IIIb. A further increase in survival was observed by stage migration to N3 or N4 status, due to selective extension of lymphadenectomy to clinically overt metastases located outside the allocated level of clearance (contamination). Incomplete lymphadenectomy of N1- or N2-level stations indicated for dissection (noncompliance) demonstrates that more migration can occur when strictly adhering to the protocol. Examining more nodes per N level (diligence) induces even more migration, since the number of nodes that were histologically examined per N level correlated significantly with nodal status (lymph node-negative [N-] or lymph node-positive [N+]). CONCLUSION These factors explain, at least partially, superior stage-specific survival rates after R2 compared with R1 resections, without a real survival benefit in individual patients.
Complications of indwelling venous access devices in cancer patients.
Authors: Eastridge B J , Lefor A T 
Published: February 2017

PURPOSE We undertook this study to review our experience with indwelling vascular access devices in cancer patients to identify factors associated with complications. PATIENTS AND METHODS A total of 322 indwelling devices were placed in 274 cancer patients by a single surgeon. Devices were placed via percutaneous insertion in 72% (231 of 322) and via venous cutdown in 28% (91 of 322). We placed external catheters in 209 of 322 patients (65%) and subcutaneous infusion ports in 113 of 322 (35%). RESULTS Pneumothorax occurred in four of 231 (1.7%) of the percutaneously placed devices. Postoperative complications included sepsis and thrombosis, which necessitated premature removal of the devices. Device related sepsis occurred in 28 of 209 patients (13%) with catheters and six of 113 patients (5%) with subcutaneous ports. Thrombosis occurred in 21 of 209 patients (10%) with catheters and seven of 113 (6%) with subcutaneous ports. In 15 of 19 devices removed for thrombosis, the tip was above the T3 level. Seventeen devices were placed in the saphenous vein, with a complication rate similar to that observed in upper-body devices. CONCLUSION We found a significantly (P < .05, chi 2 analysis) increased incidence of thrombotic complications in patients with triple-lumen catheters (10 of 48) compared with double-lumen catheters (11 of 160), as well as a significantly (P < .05) decreased mean time until catheter failure (40 v 146 days). We also observed a significant increase in the rate of thrombosis in patients with a catheter tip above the T3 level. We therefore recommend the use of fluoroscopy at the time of placement to assure adequate catheter length and tip position and the use of triple-lumen catheters only when necessary for concurrent drug administration.
High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial.
Authors: Bezwoda W R , Seymour L , Dansey R D 
Published: February 2017

PURPOSE The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival. PATIENTS AND METHODS Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable. RESULTS The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy. CONCLUSION HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.
Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.
Authors: Waber D P , Tarbell N J , Fairclough D , Atmore K , Castro R , Isquith P , Lussier F , Romero I , Carpenter P J , Schiller M 
Published: February 2017

PURPOSE We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy. PATIENTS AND METHODS Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue. RESULTS There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001). CONCLUSION We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.
Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.
Authors: Hammel P , Haioun C , Chaumette M T , Gaulard P , Divine M , Reyes F , Delchier J C 
Published: February 2017

PURPOSE The treatment of low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma with prominent gastric expression is controversial. Total gastrectomy has been proposed, but is associated with significant morbidity. The aim of this monocentric study was to assess the efficacy of continuous oral chemotherapy with a single alkylating agent. PATIENTS AND METHODS Twenty-four consecutive patients, 13 men and 11 women, were studied. Their mean age was 51 years (range, 22 to 79). Low-grade B-cell MALT lymphoma was diagnosed by histologic and immunohistologic examination of endoscopic biopsies. Seventeen patients had stage I disease and seven stage IV disease, with lung and gastric involvement. Two of these seven patients also had bone marrow involvement. The alkylating agent (cyclophosphamide or chlorambucil) was administered orally and daily for periods of 12 to 24 months. RESULTS The median follow-up time was 45 months (range, 14 months to 14 years). Complete remission was obtained in 18 patients (75%) after a median treatment duration of 12 months. Five patients relapsed; two of them were successfully re-treated, and one died of MALT lymphoma that had transformed into large-cell lymphoma. Chemotherapy was stopped after 24 months for six patients who only achieved a partial remission; two of them required further treatment for progressive disease (surgery for a small-bowel localization in one case and cyclophosphamide rechallenge in the other). Nine patients had neutropenia that required a reduced chemotherapy dosage. CONCLUSION In low-grade MALT lymphoma with prominent gastric expression, continuous monochemotherapy may constitute an efficient alternative to gastrectomy, regardless of disease stage.
Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.
Authors: Bui B N , Chevallier B , Chevreau C , Krakowski I , Peny A M , Thyss A , Maugard-Louboutin C , Cupissol D , Fargeot P , Bonichon F 
Published: February 2017

PURPOSE This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy. PATIENTS AND METHODS Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner. RESULTS Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles. CONCLUSION Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.
Coherent view of non-Hodgkin's lymphoma.
Authors: Aisenberg A C 
Published: February 2017

PURPOSE Even though non-Hodgkin's lymphoma is already sixth in incidence and mortality among malignant neoplasms (and the incidence was increasing at a rate of 3% to 4% per year before the advent of AIDS epidemic-associated lymphomas), most physicians and many oncologists find the disorder arcane. The problem lies in the complexity of human lymphoma, which encompasses more than a dozen neoplasms of the lymphoid system. The goal of this review is to provide user-friendly access to the condition. METHODS The variety of inputs required for a subdivision of non-Hodgkin's lymphoma that is useful to clinicians includes lymphocyte lineage and sublineage based on microscopic appearance and immunophenotype, clinical behavior manifest in survival and early dissemination, and analysis of molecular genetic and cytogenetic abnormalities, which reflect pathogenic oncogene derangements. Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-1) are important in certain uncommon lymphomas. RESULTS AND CONCLUSION The subtypes of primary B-lineage nodal lymphoma include low-grade (small lymphocytic, lymphoplasmacytic-lymphoplasmacytoid, follicular small cleaved cell, and follicular mixed small cleaved and large cell), intermediate-grade (follicular large cell, diffuse small cleaved or mixed, and intermediate lymphocytic), and high-grade (diffuse large cell, immunoblastic, and small noncleaved cell) neoplasms. The less common lymphomas of T lineage and lymphomas that arise in extranodal sites are placed in separate subdivisions. This subdivision serves as a guide to prognosis and treatment.
Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.
Authors: Weber B L , Vogel C , Jones S , Harvey H , Hutchins L , Bigley J , Hohneker J 
Published: February 2017

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.
Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults.
Authors: Kushner B H , Meyers P A , Gerald W L , Healey J H , La Quaglia M P , Boland P , Wollner N , Casper E S , Aledo A , Heller G 
Published: February 2017

PURPOSE To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). PATIENTS AND METHODS This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. RESULTS Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. CONCLUSION Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.
Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer.
Authors: Moertel C G , Fleming T R , Macdonald J S , Haller D G , Laurie J A , Tangen C M , Ungerleider J S , Emerson W A , Tormey D C , Glick J H 
Published: February 2017

PURPOSE To determine the effectiveness of fluorouracil plus levamisole administered postoperatively to patients with resected stage II (Dukes' B2) colon cancer. PATIENTS AND METHODS This randomized controlled clinical trial (INT-0035) was performed by National Cancer Institute-sponsored cancer clinical trials cooperative groups. Patients were assigned to observation only or to fluorouracil (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side effects were assessed. RESULTS Three hundred eighteen eligible patients were analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole reduced the recurrence rate by 31%, although this trend was not statistically significant (P = .10). A total of 87 patients died: 43 on observation and 44 on fluorouracil plus levamisole. Disparity between effects on recurrence rate and overall survival is partially explained by a higher rate of non-colon cancer-related deaths on fluorouracil plus levamisole (15 v seven) and by the effects of salvage surgery with curative intent. Of seven patients with recurrence who were rendered disease-free by salvage surgery, six were on the observation arm. As was observed in patients treated with fluorouracil plus levamisole for stage III disease, toxicity was acceptable and compliance was excellent. CONCLUSION Fluorouracil plus levamisole is tolerable and accepted as standard surgical adjuvant therapy for patients with stage III colon cancer, but the data from this study in stage II patients suggest a decreased relapse rate without a significant improvement in survival.
Evaluation of the efficacy of the VEEP regimen in adult Hodgkin's disease with assessment of gonadal and cardiac toxicity.
Authors: Hill M , Milan S , Cunningham D , Mansi J , Smith I , Catovsky D , Gore M , Zulian G , Selby P , Horwich A 
Published: February 2017

PURPOSE The aim of this phase II study was to investigate the potential of the vincristine, epirubicin, etoposide, and prednisolone (VEEP) regimen to reduce the risks of long-term sequelae of chemotherapy such as sterility, cardiopulmonary damage, and second malignancies, while maintaining efficacy in terms of response and survival. PATIENTS AND METHODS Eighty-five adult patients with newly diagnosed and previously untreated stage II to IV Hodgkin's disease (HD) were entered and monitored for a minimum of 1 year. Patients were treated to maximum response plus two further courses, and if they had not attained a complete response (CR) or CR-unconfirmed/uncertain [CR(u)] were changed to second-line chemotherapy. Adjuvant radiotherapy was administered to patients with bulky disease and those with postchemotherapy residual masses. Measurements of left ventricular ejection fraction (LVEF), gonadotropins in females, and sperm count in males were taken both before and after treatment with VEEP. RESULTS The maximum rates of response were as follows: CR, 32%; CR(u), 47%; and PR, 21% [CR + CR(u), 79%]. The median follow-up duration is 45 months, with a 5-year overall survival (OS) rate of 89% and failure-free survival (FFS) rate of 62%. Patients in CR at the end of chemotherapy had a higher FFS at 5 years compared with patients in CR(u) (88% v 56%). Acute toxicity was mild, with no pulmonary toxicity or treatment-related deaths. The median LVEF was 62% before VEEP and 57% after VEEP. Gonadal function tests following treatment were normal in 92% of males and 100% of females. No second malignancies have been observed. CONCLUSION VEEP is an active combination with tolerable acute toxicity that preserves fertility and cardiopulmonary function. The efficacy of VEEP is comparable to that of established regimens, but a definitive evaluation of its potential to reduce second malignancies will require a longer follow-up duration.