bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Autologous Stem-Cell Transplantation Versus Conventional Chemotherapy as Front-Line Therapy in High-Risk, Aggressive Non-Hodgkin’s Lymphoma: An Italian Multicenter Randomized Trial
Authors: Martelli Maurizio , Gherlinzoni Filippo , De Renzo Amalia , Zinzani Pier Luigi , De Vivo Antonio , Cantonetti Maria , Falini Brunangelo , Storti Sergio , Meloni Giovanna , Rizzo Manuela , Molinari Anna Lia , Lauria Francesco , Moretti Luciano , Lauta Vito Michele , Mazza Patrizio , Guardigni Luciano , Pescarmona E. , Pileri S.A. , Mandelli Franco , Tura Sante 
Published: March 2003

Purpose: To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin’s lymphoma (NHL). Patients and Methods: We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease. Results: The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P = .95), 5-year progression-free survival was 49% and 61% (P = .21), and 5-year relapse-free survival was 65% and 77% (P = .22), respectively. Conclusion: Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.
Phase III Study of Interferon Alfa-NL as Adjuvant Treatment for Resectable Renal Cell Carcinoma: An Eastern Cooperative Oncology Group/Intergroup Trial
Authors: Messing Edward M. , Manola Judith , Wilding George , Propert Kathleen , Fleischmann Jonathan , Crawford E. David , Pontes J. Edson , Hahn Richard , Trump Donald 
Published: March 2003

Purpose: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. Patients and Methods: A total of 283 eligible patients with pT3–4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. Results: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P = .09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P = .33). Performance status (P = .003), nodal status (N2 v N0, P < .0001), and tumor stage (P = .0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P = .009) and shorter time to recurrence (P < .0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. Conclusion: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.
Prostate Cancer DNA Ploidy and Response to Salvage Hormone Therapy After Radiotherapy With or Without Short-Term Total Androgen Blockade: An Analysis of RTOG 8610
Authors: Pollack A. , Grignon D.J. , Heydon K.H. , Hammond E.H. , Lawton C.A. , Mesic J.B. , Fu K.K. , Porter A.T. , Abrams R.A. , Shipley W.U. 
Published: March 2003

Purpose: DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (∼4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB). Patients and Methods: The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival. Results: DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation. Conclusions: Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.
Acute Myeloid Leukemia and Myelodysplastic Syndrome After Doxorubicin-Cyclophosphamide Adjuvant Therapy for Operable Breast Cancer: The National Surgical Adjuvant Breast and Bowel Project Experience
Authors: Smith Roy E. , Bryant John , DeCillis Arthur , Anderson Stewart 
Published: March 2003

Purpose: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Materials and Methods: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m2 q 21 days × 4. C was given as follows: 600 mg/m2 q 21 days × 4 (“standard AC”); 1,200 mg2 q 21 days × 2; 1,200 mg/m2 q 21 days × 4; 2,400 mg/m2 q 21 days × 2; and 2,400 mg/m2 q 21 days × 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with or without breast radiotherapy. Results: The incidence of AML/MDS was sharply elevated in the more intense regimens. In patients receiving two or four cycles of C at 2,400 mg/m2 with granulocyte colony-stimulating factor (G-CSF) support, cumulative incidence of AML/MDS at 5 years was 1.01% (95% confidence interval [CI], 0.63% to 1.62%), compared with 0.21% (95% CI, 0.11% to 0.41%) for patients treated with standard AC. Patients who received breast radiotherapy experienced more secondary AML/MDS than those who did not (RR = 2.38, P= .006), and the data indicated that G-CSF does may possibly also be independently correlated with increased risk. Conclusion: AC regimens employing intensified doses of cyclophosphamide requiring G-CSF support were characterized by increased rates of subsequent AML/MDS, although the incidence of AML/MDS was small relative to that of breast cancer relapse. Breast radiotherapy appeared to be associated with an increased risk of AML/MDS.
Intensification of Mercaptopurine/Methotrexate Maintenance Chemotherapy May Increase the Risk of Relapse for Some Children With Acute Lymphoblastic Leukemia
Authors: Schmiegelow Kjeld , Björk Olle , Glomstein Anders , Gustafsson Göran , Keiding Niels , Kristinsson Jon , Mäkipernaa Anne , Rosthøj Susanne , Szumlanski Carol , Sørensen Tine M , Weinshilboum Richard 
Published: March 2003

Purpose: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). Patients and Methods: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group). Results: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P = .00003), high WBC at diagnosis (P = .03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P = .002), and high average neutrophil counts during maintenance therapy (P = .0009), with a significant interaction between sex and randomization group (P = .0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P = .001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P < .0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P = .03; boys 19.3 v 18.0 U/mL, P = .04). Conclusion: Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.
New Malignancies After Blood or Marrow Stem-Cell Transplantation in Children and Adults: Incidence and Risk Factors
Authors: Baker K. Scott , DeFor Todd E. , Burns Linda J. , Ramsay Norma K.C. , Neglia Joseph P. , Robison Leslie L. 
Published: March 2003

Purpose: To determine the incidence and risk factors for the development of new malignancies occurring after stem-cell transplantation (SCT). Patients: Between January 1, 1974, and March 31, 2001, 3,372 patients underwent SCT at the University of Minnesota. From these transplants, 147 posttransplant malignancies (PTMs) were identified in 137 patients. Results: Excluding nonmelanoma skin cancers (n = 19) and carcinoma-in-situ (n = 5), the remaining 123 cases represented an 8.1-fold (95% confidence interval [CI], 6.7 to 9.6) increased risk of a PTM, an excess risk of 102.7 cases/10,000 persons/yr (age and sex adjusted). This includes a significantly elevated risk for developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML; standardized incidence ratio [SIR] = 300; 95% CI, 210 to 406), non-Hodgkin’s lymphoma including posttransplant lymphoproliferative disorder (PTLD; SIR = 54.3; 95% CI, 39.5 to 41.1), Hodgkin’s disease (SIR = 14.8; 95% CI, 3.9 to 32.9), or solid tumors overall (SIR = 2.8; CI, 2.0 to 3.7) and in specific for melanoma, brain, and oral cavity tumors. The cumulative incidence for the development of any PTM was 6.9% (95% CI, 5.2 to 8.6) at 20 years post-SCT. For PTLD (n = 43), the cumulative incidence plateaued at 1.4% (95% CI, 1.0 to 1.8) by 10 years post-SCT. For MDS or AML, the cumulative incidence plateaued at 1.4% (95% CI, 0.9 to 1.9) by 10 years post-SCT. The cumulative incidence of developing a solid tumor did not plateau and was 3.8% (95% CI, 2.2 to 5.4) at 20 years post-SCT. Conclusion: These data reveal that the risk of PTMs, especially solid tumors, continues to increase even 20 years after transplant, necessitating long-term close follow-up for these patients.
Quality of Surgery and Outcome in Extra-Abdominal Aggressive Fibromatosis: A Series of Patients Surgically Treated at a Single Institution
Authors: Gronchi A. , Casali P.G. , Mariani L. , Lo Vullo S. , Colecchia M. , Lozza L. , Bertulli R. , Fiore M. , Olmi P. , Santinami M. , Rosai J. 
Published: March 2003

Purpose: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). Patients and Methods: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. Results: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). Conclusion: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.
T-Cell/Histiocyte-Rich Large B-Cell Lymphomas and Classical Diffuse Large B-Cell Lymphomas Have Similar Outcome After Chemotherapy: A Matched-Control Analysis
Authors: Bouabdallah R. , Mounier N. , Guettier C. , Molina T. , Ribrag V. , Thieblemont C. , Sonet A. , Delmer A. , Belhadj K. , Gaulard P. , Gisselbrecht C. , Xerri L. 
Published: March 2003

Purpose: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). Patients and Methods: More than 4,500 patients were enrolled onto non-Hodgkin’s lymphoma trials conducted by the Groupe d’Etude des Lymphomes de l’Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). Results: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was ≥ 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean ± SD) were 58% ± 18% and 53% ± 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P = .06), whereas no difference was observed in OS (P = .9) and EFS (P = .8). Conclusion: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.
Prognostic Model for Predicting Survival in Men With Hormone-Refractory Metastatic Prostate Cancer
Authors: Halabi Susan , Small Eric J. , Kantoff Philip W. , Kattan Michael W. , Kaplan Ellen B. , Dawson Nancy A. , Levine Ellis G. , Blumenstein Brent A. , Vogelzang Nicholas J. 
Published: March 2003

Purpose: To develop and validate a model that can be used to predict the overall survival probability among metastatic hormone-refractory prostate cancer patients (HRPC). Patients and Methods: Data from six Cancer and Leukemia Group B protocols that enrolled 1,101 patients with metastatic hormone-refractory adenocarcinoma of the prostate during the study period from 1991 to 2001 were pooled. The proportional hazards model was used to develop a multivariable model on the basis of pretreatment factors and to construct a prognostic model. The area under the receiver operating characteristic curve (ROC) was calculated as a measure of predictive discrimination. Calibration of the model predictions was assessed by comparing the predicted probability with the actual survival probability. An independent data set was used to validate the fitted model. Results: The final model included the following factors: lactate dehydrogenase, prostate-specific antigen, alkaline phosphatase, Gleason sum, Eastern Cooperative Oncology Group performance status, hemoglobin, and the presence of visceral disease. The area under the ROC curve was 0.68. Patients were classified into one of four risk groups. We observed a good agreement between the observed and predicted survival probabilities for the four risk groups. The observed median survival durations were 7.5 (95% confidence interval [CI], 6.2 to 10.9), 13.4 (95% CI, 9.7 to 26.3), 18.9 (95% CI, 16.2 to 26.3), and 27.2 (95% CI, 21.9 to 42.8) months for the first, second, third, and fourth risk groups, respectively. The corresponding median predicted survival times were 8.8, 13.4, 17.4, and 22.80 for the four risk groups. Conclusion: This model could be used to predict individual survival probabilities and to stratify metastatic HRPC patients in randomized phase III trials.
Role of Sentinel Lymphadenectomy in Thin Invasive Cutaneous Melanomas
Authors: Bleicher Richard J. , Essner Richard , Foshag Leland J. , Wanek Leslie A. , Morton Donald L. 
Published: March 2003

Purpose: Regional lymph node status is the strongest prognostic determinant in early-stage melanoma. Lymphatic mapping and sentinel lymphadenectomy (LM/SL) is standard to stage regional nodes because it is accurate and minimally morbid, yet its role for thin (≤ 1.5 mm) primary melanomas is unknown. Patients and Methods: Our melanoma database of more than 10,000 patients was reviewed for patients with melanomas ≤ 1.50 mm thick who underwent LM/SL. All had lymphoscintigrams and LM/SL via dye alone or with radiopharmaceutical. Patients with tumor-positive sentinel nodes (SNs) underwent completion dissections. Results: Five hundred twelve patients underwent LM/SL. Most were men (57%), and median age was 49 years. Most primary melanomas were on the torso (44%). Twenty-five patients (4.9%) had tumor-positive SNs. The thinnest lesion with a nodal metastasis was 0.35 mm. The SN-negative and SN-positive cohorts were equivalent by sex, but SN+ patients tended to be younger (P = .053), with significantly more SN metastases in those younger than 44 years (P = .005). No consistent pathology among SN-positive primary melanomas was found. Among those with 1.01- to 1.05-mm primaries, 7.1% were SN-positive. Among 272 patients with lesions ≤ 1.00 mm, 2.9% had positive SNs and 1.7% with lesions ≤ 0.75 mm had SN metastases. All 13 deaths were in SN-negative patients. Median follow-up durations in SN-positive and SN-negative patients were 25 and 45 months, respectively. Conclusion: The high nodal positivity rate associated with primary melanomas 1.01 to 1.50 mm thick suggests that LM/SL is indicated in this group. Younger age may be correlated with nodal metastases in patients with lesions ≤ 1.00 mm. Lesions ≤ 0.75 mm have minimal metastatic potential, and therefore LM/SL is rarely indicated.
Obesity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study
Authors: Oeffinger Kevin C. , Mertens Ann C. , Sklar Charles A. , Yasui Yutaka , Fears Thomas , Stovall Marilyn , Vik Terry A. , Inskip Peter D. , Robison Leslie L. 
Published: March 2003

Purpose: To determine whether adult survivors (≥ 18 years of age) of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity and to assess patient and treatment variables that influence risk. Patients and Methods: A retrospective cohort of participants of the Childhood Cancer Survivor Study was used to compare 1,765 adult survivors of childhood ALL to 2,565 adult siblings of childhood cancer survivors. Body-mass index (BMI; kilograms per square meter), calculated from self-reported heights and weights, was used to determine the prevalence of being overweight (BMI, 25–29.9) or obese (BMI ≥ 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors relative to the sibling control group. Results: The age- and race-adjusted OR for being obese in survivors treated with cranial radiation doses ≥ 20 Gy in comparison with siblings was 2.59 for females (95% CI, 1.88 to 3.55; P < .001) and 1.86 for males (95% CI, 1.33 to 2.57; P < .001). The OR for obesity was greatest among females diagnosed at 0 to 4 years of age and treated with radiation doses ≥ 20 Gy (OR, 3.81; 95% CI, 2.34 to 5.99; P < .001). Obesity was not associated with treatment consisting of chemotherapy only or with cranial radiation doses of 10 to 19 Gy. Conclusion: Cranial radiotherapy ≥ 20 Gy is associated with an increased prevalence of obesity, especially in females treated at a young age. It is imperative that healthcare professionals recognize this risk and develop strategies to enhance weight control and encourage longitudinal follow-up.