bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of age on the treatment of limited-stage small-cell lung cancer.
Authors: Siu L L , Shepherd F A , Murray N , Feld R , Pater J , Zee B 
Published: February 2017

PURPOSE To evaluate the prognostic importance of age on response rate and survival in patients with limited-stage small-cell lung cancer (SCLC), and to determine the effect of age on chemotherapy dose delivery and toxicity. PATIENTS AND METHODS We undertook a retrospective analysis of data from two multicenter, randomized trials conducted by the National Cancer Institute of Canada (NCIC) in which 608 SCLC patients who presented with limited disease (LD) all received the same chemotherapy. Treatment consisted of cyclophosphamide, doxorubicin, and vincristine (CAV), and etoposide plus cisplatin (EP) administered in an immediate or delayed alternating fashion, plus cranial and thoracic irradiation. RESULTS There were 520 patients aged less than 70 years, and 88 > or = 70. No significant differences existed between the two age groups in baseline characteristics, including treatment protocol, performance status, and serum lactate dehydrogenase (LDH) level. There were more men in the older group (P = .05). Overall response rates were comparable (78% v 82%, P = .50), and 5-year survival rates were also similar (P = .14), with 11% alive in the younger group and 8% in the older group. Age was a significant predictor of overall survival when analyzed as a continuous variable in a univariate model (P = .01), but it was no longer an independent prognostic factor in our multivariate regression analysis. An analysis of chemotherapy delivery between the two age groups showed that patients aged > or = 70 years received lower total doses of each drug compared with the intended full protocol dose, primarily as a result of dose omissions, rather than dose reductions. The frequency of dose delays was not different between groups. No significant differences were seen in the incidence of either hematologic or most nonhematologic toxicities. CONCLUSION Age is not a significant adverse prognostic variable in SCLC patients with LD. Moderately aggressive chemotherapy may be delivered safely to elderly patients with a good performance status, although modest attenuation of therapy through either dose reduction or omission may occur more frequently in this population.
Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy.
Authors: Wexler L H , Weaver-McClure L , Steinberg S M , Jacobson J , Jarosinski P , Avila N , Pizzo P A , Horowitz M E 
Published: February 2017

PURPOSE To evaluate whether recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients. PATIENTS AND METHODS Thirty-seven newly diagnosed patients age 1 to 25 years were randomized to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3. GM-CSF (5 to 15 micrograms/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was > or = 500/microliter on 2 consecutive days. RESULTS GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P < .0001), but did not significantly affect the grade of granulocyte nadir. No differences were seen in the incidence or types of infectious complications, incidence or duration of hospitalization and antimicrobial therapy, response to chemotherapy, or event-free or overall survival. GM-CSF was associated with more severe and protracted thrombocytopenia (median platelet nadir, 29,500/microliter [range, 3,000 to 288,000] v 59,000/microliter [range, 3,000 to 309,000], P < .0001; median time to recovery > 75,000/microliter, 16.0 days [range, 0 to 61] v 14.0 days [range, 0 to 38], P < .0001). CONCLUSION GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia. GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications. We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity.
Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine.
Authors: Weintraub M , Adde M A , Venzon D J , Shad A T , Horak I D , Neely J E , Seibel N L , Gootenberg J , Arndt C , Nieder M L , Magrath I T 
Published: February 2017

PURPOSE We have observed a severe atypical neuropathy (SAN) in patients with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) treated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. PATIENTS AND METHODS Fifty-four adult and pediatric patients consecutively treated according to the same chemotherapy protocol were included in the analysis. Low-risk patients received three cycles of cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of four cycles. Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF. A statistical analysis, which included a logistic regression model, was undertaken to examine the importance of potential contributing factors to the development of SAN. RESULTS SAN, which consisted of excruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients. There was a highly significant association between the occurrence of this syndrome and the administration of CSFs, and an independent association with the cumulative dose of vincristine given in the first cycle of chemotherapy. Furthermore, the analysis suggested a synergistic effect between administration of the CSFs and vincristine in the genesis of this neuropathy. CONCLUSION Our results indicate that CSFs can precipitate SAN when given in conjunction with vincristine. The development of SAN was associated most strongly with the cumulative dose of vincristine -- the size of individual doses and the number of doses given in cycle 1 were important to the extent that they influenced the cumulative dose.
Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study.
Authors: Simons J P , Aaronson N K , Vansteenkiste J F , ten Velde G P , Muller M J , Drenth B M , Erdkamp F L , Cobben E G , Schoon E J , Smeets J B , Schouten H C , Demedts M , Hillen H F , Blijham G H , Wouters E F 
Published: February 2017

PURPOSE To investigate the effects of medroxyprogesterone acetate (MPA) on appetite, weight, and quality of life (QL) in patients with advanced-stage, incurable, non-hormone-sensitive cancer. PATIENTS AND METHODS Two hundred six eligible patients were randomized between double-blind MPA 500 mg twice daily or placebo. Appetite (0 to 10 numerical rating scale), weight, and QL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed before the start of treatment (t = 0), and 6 weeks (t = 6) and 12 weeks (t = 12) thereafter. RESULTS One hundred thirty-four patients (68 MPA and 66 placebo) were assessable at t = 6 and 99 patients (53 MPA and 46 placebo) at t = 12. A beneficial effect of MPA on appetite was observed after both 6 weeks (P = .008) and 12 weeks (P = .01) of treatment. After 12 weeks, a mean weight gain of 0.6 +/- 4.4 kg was seen in the MPA, versus an ongoing mean weight loss of 1.4 +/- 4.6 kg in the placebo group. This difference of 2.0 kg was statistically significant (P = .04). During the study, several areas of QL deteriorated in the total group of patients. With the exception of an improvement in appetite and possible also a reduction in nausea and vomiting, no measurable beneficial effects of MPA on QL could be demonstrated. The side effects profile of MPA was favorable: only a trend toward an increase in (usually mild) peripheral edema was observed. CONCLUSION In weight-losing, advanced-stage non-hormone-sensitive cancer patients, MPA exhibits a mild side effects profile, has a beneficial effect on appetite, and may prevent further weight loss. However, general QL in the present study was not measurably influenced by MPA treatment.
Synovial sarcoma: prognostic significance of tumor size, margin of resection, and mitotic activity for survival.
Authors: Singer S , Baldini E H , Demetri G D , Fletcher J A , Corson J M 
Published: February 2017

PURPOSE The present study serves to describe outcomes-based prognostic variables characteristic of synovial cell sarcoma. PATIENTS AND METHODS An analysis was performed of a prospectively compiled data base of 48 consecutive patients with extremity and truncal synovial sarcomas seen between 1966 and 1994. RESULTS No local recurrences were observed among 27 patients who presented with localized primary disease. Patients with synovial sarcoma less than 5 cm in size has a cancer-specific survival rate at 10 years of 100%, compared with a 10-year survival rate of 32% and 0% for those with sarcoma 5 to 10 cm and greater than 10 cm, respectively (P = .002). Patients with synovial sarcoma with less than 10 mitoses per 10 high-power fields (hpf) had a 10-year cancer-specific survival rate of 46%, compared with a 10-year survival rate of 14% for those with sarcomas with greater than 10 mitoses per hpf (P = .04). Patients with a clean margin of excision were found to have a 10-year cancer-specific survival rate of 43%, compared with 0% for those with microscopic positive margins (P = .03). Among 14 patients treated with neoadjuvant chemotherapy, seven (50%) had objective responses. CONCLUSION Local control for patients with nonmetastatic disease was excellent. The overall cancer-specific survival rate for patients with localized synovial sarcoma was 34% at 10 years. Primary tumor size, margin of resection, and mean mitotic activity were prognostic factors for survival in synovial sarcoma. There was a high objective response rate to treatment with neoadjuvant chemotherapy; however, there was no detectable beneficial effects on survival in the subset of patients treated with chemotherapy versus nonrandomized patients who received no chemotherapy. Patients with synovial sarcoma > or = 5 cm in size, microscopic positive margins, and/or mean mitotic activity greater than 10 mitoses per 10 hpf should be targeted for new therapeutic studies.
Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients?
Authors: Zoubek A , Dockhorn-Dworniczak B , Delattre O , Christiansen H , Niggli F , Gatterer-Menz I , Smith T L , Jürgens H , Gadner H , Kovar H 
Published: February 2017

PURPOSE Because of the high heterogeneity of EWS gene fusions with FLI1 and ERG genes due to variable chromosomal breakpoint locations in Ewing tumors (ET) (14 different chimeric transcripts identified so far), we evaluated the clinical impact of the expression of diverse fusion transcripts in ET patients. PATIENTS AND METHODS In a European multicenter study, 147 ET were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and the molecular data statistically compared with all clinical data available. RESULTS Most tumors expressed chimeric transcripts with fusion of EWS exon 7 to FLI1 exon 6 (75 of 147) (type I) or five (39 of 147) and EWS exon 10 to FLI1 exon 5 (eight of 147) or 6 (five of 147). In five cases, chimerism between EWS exon 9 and FLI1 exons 4 and EWS exon 7 and FLI1 exon 7 or 8 was observed. Fifteen cases of EWS-ERG rearrangement were identified. In 85 of these patients treated in the European Cooperative Ewing Sarcoma Studies, molecular results were analyzed in comparison to age, sex, tumor localization, tumor volume, and disease extension. No significant correlation between the various fusion types and these features were observed. Relapse-free survival (RFS) for the 31 patients with localized disease and fusion type I tended to be longer compared with the 24 patients with localized tumors bearing other chimeric transcripts (P = .04). CONCLUSION Results suggest a possible advantage in PFS for patients with localized disease and fusion type I transcripts, although this will require prospective validation with a larger number of patients and longer follow-up periods.
Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma.
Authors: McLaughlin P , Hagemeister F B , Romaguera J E , Sarris A H , Pate O , Younes A , Swan F , Keating M , Cabanillas F 
Published: February 2017

PURPOSE Although most patients with indolent lymphomas respond to initial therapy, virtually all experience relapse. Secondary therapy is often beneficial, but responses are rarely, if ever, durable. We conducted this phase II trail to evaluate the therapeutic efficacy and toxicity of fludarabine, mitoxantrone, and dexamethasone (FND) in patients with relapsed indolent lymphoma. PATIENTS AND METHODS Fifty-one patients with recurrent or refractory indolent lymphoma were treated with a regimen of fludarabine 25 mg/m2/d intravenously (IV) on days 1 to 3, mitoxantrone 10 mg/m2 IV on day 1, and dexamethasone 20 mg/d IV or orally on days 1 to 5. Treatment was repeated at 4-week intervals for a maximum of eight courses. Late in the course of this trial, trimethoprim-sulfamethoxazole (TMP-SMX) was incorporated for Pneumocystis carinii (PCP) prophylaxis. RESULTS Responses were complete (CR) in 24 patients (47%) and partial (PR) in 24 (47%). The median failure-free survival time was 21 months for CR patients and 9 months for PR patients. Notable activity of FND was seen even in the elderly, in those with high serum lactate dehydrogenase (LDH) or beta2-microglobulin levels, and in those with multiple prior treatment regimens. The predominant toxic effects were myelosuppression and infections; other toxic effects were modest. Infections occurred in 12% of courses. Almost half of the infections were proven or suspected opportunistic infections, including six cases of dermatomal herpes zoster and two cases of proven PCP pneumonia. CONCLUSION The FND combination is highly active in patients with recurrent or relapsed indolent lymphoma and results in a high percentage of CRs. Because of the risk of opportunistic infections, we currently recommend prophylaxis with TMP-SMX and advise deletion of corticosteroids for patients who develop opportunistic infections.
Mantle-cell lymphoma: a population-based clinical study.
Authors: Velders G A , Kluin-Nelemans J C , De Boer C J , Hermans J , Noordijk E M , Schuuring E , Kramer M H , Van Deijk W A , Rahder J B , Kluin P M , Van Krieken J H 
Published: February 2017

PURPOSE From a population-based non-Hodgkin's lymphoma (NHL) registry, 41 patients with mantle cell lymphoma (MCL) -- a recently defined distinct B-cell NHL -- were selected and compared with patients with low- or intermediate-grade NHL from the same registry. PATIENTS AND METHODS The incidence and behavior of MCL in the area of the Comprehensive Cancer Center West (CCCW) from 1981 to 1989 were analyzed. Age, performance, tumor bulk, extranodal localization, stage, response to therapy, and survival were registered. Expression of cyclin D1 protein and Ki-67 were measured in 29 patients. RESULTS MCL made up 3.7% of NHLs. The median age was 68 years, and the male-to-female ratio was 1.6:1. Seventy-eight percent presented with stage IV, with the majority having bone marrow involvement. The complete response (CR) rate was 32% (13 of 41), with a median duration of 25 months. The median overall survival time was 31.5 months. The International Prognostic Index identified five patients with a low-risk score and a median survival time of 93+ months. In 23 of 29 patients, cyclin D1 overexpression was present, without any relation to overall or disease-free survival. In contrast, a proliferative index less than 10% was significantly related to a better overall survival time (50 v 24 months). CONCLUSION MCL is a disease of the elderly, who present with widespread disease and with a poor response to therapy. Although it harbors features of an indolent NHL, it behaves clinically as an aggressive NHL with a short overall survival time.
Use of cytokines in the treatment of acute myelocytic leukemia: a critical review.
Authors: Geller R B 
Published: February 2017

PURPOSE The colony-stimulating factors (CSFs) have been evaluated in patients with acute myelocytic leukemia (AML), both as potential priming agents and during and/or following induction chemotherapy to shorten the period of myelosuppression. The purpose of this review is to evaluate critically the safety and efficacy of the CSFs, primarily granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF), in the treatment of patients with AML. METHODS All phase III trials that have either been presented or published that used CSFs during and/or following induction chemotherapy in patients with de novo AML are discussed. Relevant background information and future directions are also addressed. RESULTS AND CONCLUSION There have been six phase III trials that used either GM-CSF or G-CSF in induction therapy in patients with AML. It is difficult to compare these trials due to differences in patient age, induction therapy administered, disease characteristics, whether leukemia response or documentation of marrow hypoplasia was required before cytokine use, and the different cytokines administered during the study. In particular, the timing of CSF administration in relation to the chemotherapy may be important due to the different biologic effects these agents may have on leukemia cells, such as leukemia cell recruitment. Most of these studies administered either GM-CSF or G-CSF before or during induction therapy, as well as following completion of chemotherapy until neutrophil recovery. Only one of six trials required documentation of marrow hypoplasia before CSF use. Despite these differences, administration of either GM-CSF or G-CSF was found to be safe without an increase in acute toxicity or an increase in relapse rates. In addition, most trials demonstrated a significant improvement in neutrophil recovery, with several trials demonstrating an improvement in complete remission and overall survival rates. Therefore, the use of selected CSFs may be of benefit following induction chemotherapy in those patients with AML who are at increased risk for early morbidity and mortality.
Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.
Authors: Sankila R , Garwicz S , Olsen J H , Döllner H , Hertz H , Kreuger A , Langmark F , Lanning M , Möller T , Tulinius H 
Published: February 2017

PURPOSE To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). PATIENTS AND METHODS There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. RESULTS A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. CONCLUSION Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.
High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma.
Authors: Bensinger W I , Rowley S D , Demirer T , Lilleby K , Schiffman K , Clift R A , Appelbaum F R , Fefer A , Barnett T , Storb R , Chauncey T , Maziarz R T , Klarnet J , McSweeney P , Holmberg L , Maloney D G , Weaver C H , Buckner C D 
Published: February 2017

PURPOSE To evaluate the outcome of patients with multiple myeloma (MM) who received high-dose therapy followed by autologous bone marrow (BM) or peripheral-blood stem-cell (PBSC) infusion. PATIENTS AND METHODS Sixty-three consecutive patients with MM received autologous BM (n = 13) or PBSC with or without BM (n = 50) following regimens that contained busulfan (Bu) and cyclophosphamide (Cy) (n = 18), modified total-body irradiation (TBI) followed by Bu and Cy (n = 36), or Bu, melphalan, and thiotepa (n = 9). Two thirds of the patients had resistant disease and 69% had received more than 6 months of previous chemotherapy. RESULTS AND CONCLUSION Recovery of peripheral-blood cell counts was more rapid in patients who received PBSC with or without BM than in patients who received BM alone. Sixteen of 63 patients (25%) died of complications of treatment within 100 days. Nineteen (40%) of 48 assessable patients achieved a complete response (CR), 23 (48%) had a partial response (PR), and six (12%) had no response. The probabilities of survival and survival without relapse or progression for all 63 patients at 3.0 years were .43 and .21, respectively. The probability of relapse or progression at 3 years was .69, and 17 patients (27%) have died of progressive MM. The probabilities of survival and relapse-free survival at 3 years for the 19 patients who achieved a CR were .42 and .17, respectively. In the multivariate analysis, beta2-microglobulin levels more than 2.5 micrograms/mL, more than two regimens of prior therapy and eight cycles of treatment, time to transplant longer than 3 years from diagnosis, and prior radiation were associated with adverse outcomes. Additional strategies, such as intervention earlier in the disease course, improved treatment regimens, sequential high-dose treatments, and posttransplant therapies may improve outcome of selected patients with MM.