bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose intense doxorubicin-based regimens in aggressive non-Hodgkin's lymphoma: A systematic overview
Authors: Azim H. A. , Malek R. A. , Santoro L. , Gandini S. , Bociek R. G. , Azim H. A. 
Published: August 2020

e19528 Background: Aggressive non-Hodgkin's lymphoma represents around 60% of lymphomas in the Western world and even more in Egypt. CHOP has been long been recognized as the standard chemotherapy regimen in this disease. The addition of rituximab (R) to CHOP in the treatment of B-cell subtypes has resulted in a significant improvement in all treatment endpoints. Nevertheless, still a significant fraction of patients in the developing world are not offered R due to economical reasons. Thus CHOP is still offered to these patients as well as those with T-cell subtypes. Data from the early 1990s have suggested that the dose intensity (DI) of doxorubicin may have a prognostic value. Hence we conducted a metaanalysis on chemotherapy regimens incorporating higher DI doxorubicin and compare them to CHOP in terms of complete response (CR) rate, event free survival (EFS) and overall survival (OAS). Methods: A MEDLINE and COCHRANE library search was performed using the search terms ‘CHOP‘, ‘lymphoma‘ and ‘randomized trials‘. Eligible trials were randomized trials, having CHOP as a control arm and any chemotherapy regimen administering doxorubicin at a higher DI than that of CHOP (16mg/m2/week) as the investigational arm. Pooling of data was performed using the mixed effect model. The outcome measure for pooling the CR rate was the odds ratio (OR) while the hazard ratio (HR) was the outcome measure for EFS and OAS. Confidence intervals were estimated according to the method developed by Parmar. Results: Eight trials published until February 2008 met the inclusion criteria. They included 3,668 patients randomly assigned to either CHOP (1,660 patients) or DI doxorubicin-based regimen (2008 patients). Patients receiving DI doxorubicin-based regimen had a significantly better overall survival (HR; 0.79; 95% CI: 0.66–0.94). As for the EFS and CR analyses, there was a trend in favor of patients who received the DI regimens; however the difference was not statistically significant (HR: 0.86; 95% CI: 0.71–1.03 & OR: 0.8; 95% CI: 0.63–1.02 respectively). Conclusions: High DI doxorubicin-based regimens are associated with a better OAS compared to CHOP. Such approach should be considered in patients with aggressive B-cell lymphomas not offered R as well as those with T-cell lymphomas. No significant financial relationships to disclose.
Value of International Prognostic Score (IPS) in predicting need for bone marrow biopsy (BMB) in Hodgkin's lymphoma (HL)
Authors: Muslimani A. , Spiro T. , Chaudhry A. , Taylor H. , Jaiyesimi I. , Elson P. , Daw H. 
Published: August 2020

e19531 Background: BMB is frequently performed during the staging of patients (pts) with HL. Previous data suggested routine use of this procedure may be unnecessary. The Ann Arbor classification is currently used to detect pts requiring BMB. Despite sensitivity (sen) of 100%, specificity (spec) is only 40%. We sought to determine whether IPS [as developed by Hasenclever and Diehl (1998)] would yield greater spec while maintaining good sen. Methods: We retrospectively reviewed charts of 1215 histologically proven HL pts from Jan 2000-Dec 2008 at Cleveland Clinic Taussig and Fairview Moll Cancer Centers. Of 1215 pts, 1089 had BMB (90%). 876 pts were included in our study. 213 were excluded due to un-interpretable BMB or missing data. The IPS is calculated as the number of poor risk features present based on male sex, age ≥45, albumin (alb) <4 g/dL, hemoglobin (hem) <10.5 g/dL, stage IV, white blood cell (WBC) ≥15,000/mm3, lymphocyte (lymph) <600/mm3 and/or <8% of total WBC. Multivariable logistic regression was initially used to assess the association between BMI and each factor in the IPS. All 7 factors were significant (p<.001 for sex, age, albu, hem, stage and lymph; .07 for WBC); and therefore recursive partioning algorithm was used to identify a cutoff for determining bone marrow involvement (BMI). Results: 88 pts (10%) had BMI. Using an IPS of >3 to predict BMI, sen was 97% and spec 87%. BMI by histology was 4% lymphocyte-rich, 5% nodular sclerosis, 20% mixed-cellularity and 21% lymphocyte-depleted. Using the IPS>3 cutoff sen and spec were similar across all types of histologies; ranging from 94–100% and 86–89% respectively. Conclusions: using an IPS of >3 for predicting BMI in HL doubled the spec associated with Ann Arbor classification with little loss of sen. The implementation of IPS is a practical and reliable tool that will allow physicians to predict BMI in HL pts. It may, therefore eliminate painful BMB in many Pts. No significant financial relationships to disclose.
Prognostic value of different B symptoms in upper aerodigestive tract NK/T-cell lymphoma
Authors: Xiao J. , Guo C. , Zhai L. , Li H. , Fu X. , Huang Y. , Huang Y. , Huang J. , Pu X. , Lin T. , Ye S. 
Published: August 2020

e19544 Background: Extranodal NK/T-cell lymphoma (ENKL) is a rare disease originated from NK or toxic T cells. ENKL arising from the upper aerodigestive tract (UNKTL) is a newly recognized subtype and commonly presents with B symptoms. This study is to investigate the prognostic value of different B symptoms in UNKTL. Methods: UNKTL cases with detailed clinical, pathological and prognostic data in our center since 2001 to 2007 were retrospectively analyzed with the major study endpoint of overall survival (OS). Central pathological review was performed. Survival curves were estimated by Kaplan-Meier method and tested by Log Rank method. Statistically significant factors in univariate analysis were then included in multivariate analysis. B symptoms were defined as fever, night sweat and weight loss according to the Ann Arbor Cotswolds meeting. The predictive values of survival for each type of B symptoms were studied independently. Results: 172 cases of UNKTL with a median follow-up duration of 27.4 months were included. 45 ladies and 127 gentlemen had a median age of 43 years. 98 cases were Ann Arbor stage I, 54 were stage II and the remaining 20 cases were stage III or IV. About half of the patients present B symptoms: 82 had fever, 5 had night sweat and 6 present weight loss. Totally 18 patients had ECOG PS larger than 1. The 5-year OS rate of the whole group is 41.8%. Patients with persistent fever before treatment indicated a poor outcome in the univariate analysis (p=.033) and its prognostic value was also confirmed by the Cox regression (p=.030) whereas those of night sweat and weight loss were not (p= .960 and .824 respectively). Conclusions: B symptoms were common in UNKTL patients. Our data suggested that only fever among the three types of B symptoms was independent prognostic factor for UNKTL but it still needs further confirmation. No significant financial relationships to disclose.
Reccurent and prolonged panctopenia with rituximab therapy
Authors: Jajeh A. 
Published: August 2020

e19550 Background: Rituximab, a monoclonal antibodies designed against a CD20 glycoprotein expressing lymphocytes. This drug has been implemented in the treatment of B cell lymphoproliferative disorders as well as non-neoplastic disease such as autoimmune thrombocytopenia, immune hemolytic anemia and other disorders related to overexpression of antibodies against the host. Rituximab doccumented side effects such as allergic infusion reaction, tumor lysis syndrome and lymphodepletion are frequently seen. However, transient neutropenia is less common. This abstract reports recurrent and long standing pancytopenia that had adverse deadly sequellae. Methods: This abstract report five cases of recurrent and prolonged pancytopenia not related to concomittant cytotoxic effect of chemotherapy. It is a retrospective analysis of treating three hundred patients in the last six years. Results: Five patient sustained recurrent prolonged pancytopenia post rituximab therapy. Two females (age 33 and 55) and three males (age 40, 50 and sixty). Mean age is 46 years. All developed sever neutropenia as well as pancytopenia. One patient, a female( age 33) had rheumatoid arthritis and the rest had non hodgekin's lymphoma. This female patient died due to sever long standing neutropenia/pancytopenia with pneumonia. All patients had bone marrow biopsy for evaluation. Decreased cellularity below 40% seen. None of the patients with non hodgkin's lymphoma had bone marrow involvement. The four patients are still in remmission. Conclusions: In conclusion the etiology of sustained neutropenia and pancytopenia is not understood. Whether, bone marrow aplasia, dysplasia or other immune mechanism exist need more study. No significant financial relationships to disclose.
Immunological effects and clinical outcomes in patients with high-risk melanoma given adjuvant therapy with granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim)
Authors: Spitler L. E. , Weber R. W. , Cruickshank S. , Whiteside T. L. 
Published: August 2020

e20004 Background: Our previous study suggested that administration of GM-CSF to high-risk melanoma patients may prolong survival (JCO 18(8):1614–1621, 2000) and led to a prospective randomized trial (E4697). This study has completed accrual and follow-up is now ongoing. Simultaneously, we conducted a follow-on study to gain further information about the immunological effects and clinical outcomes of adjuvant GM-CSF therapy of melanoma. Methods: GM-CSF, 125 μg/m2, was administered subcutaneously in 28-day cycles of 14 days on/14 days off for 1 year. Blood draws were keyed to GM-CSF administration: Days 0 (before), 15 (after 14 days on GM-CSF), 29 (after 14 days off GM-CSF), 155 and 351 (after 14 days on GM-CSF in the 6th and 13th cycle). Forty- nine patients were evaluable for immunologic responses on Day 15. Immunophenotyping of the white cell population was done on a subset consisting of 6 patients. Results: In 42 patients, there was an increase in the WBC counts to above normal after 14 days of GM-CSF therapy in the first cycle. This increase did not occur in 7 patients and these patients had a significantly shorter survival. There was a similar increase in neopterin levels following 14 days of GM-CSF administration, which returned to baseline after 14 days off therapy and did not correlate with clinical outcome. Immunophenotypic analysis showed an increase in activated and regulatory T cells and a decrease in the percent of CD11c+DC (myeloid) cells in the 6 patients evaluated, all returning to baseline on Day 29. Conclusions: GM-CSF therapy was associated an increase in the WBC counts in the majority of patients after 14 days of treatment and patients who did not experience this increase had a significantly shorter life expectancy. The observed increase in neopterin levels is consistent with macrophage activation as the potential mechanism of action of adjuvant GM-CSF administration. Additional immunologic effects which may play a role during GM-CSF therapy include the increase in activated T-cells and decrease in CD11c+DC, which may be moving from the peripheral circulation into the tissues. [Table: see text]
Metronomic schedule of temozolomide with conventional dose of cisplatin in metastatic melanoma
Authors: Simeone E. , Daponte A. , De Feo G. , Montesarchio V. , Chiarion-Sileni V. , De Michele I. , Caracò C. , Palmieri G. , Mozzillo N. , Ascierto P. A. 
Published: August 2020

e20009 Background: Dacarbazine (DTIC) is the standard treatment for metastatic melanoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Metronomic administration of TMZ might be another way to overcome resistance. Patients and Methods: We reviewed data of metastatic melanoma patients treated at our Institutions with cisplatin (75 mg/m2 every 28 days) plus TMZ (75 mg/m2/die from day 2 for 21 days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); primary melanoma was ulcerated in 19 cases (58%); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases each and grade 2 in 16 and 9 cases, respectively. Other toxicities included thrombocytopenia (2 case grade 3 and 3 cases grade 2), anemia (1 grade 3 and 4 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 6 patients had a partial response (18.2%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI:16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic melanoma are encouraging, in light of the negative prognostic features of treated patients. We are now planning a formal phase II study. [Table: see text]
Possible therapeutic reversal of immune suppression in patients with metastatic melanoma by timed delivery of temozolomide chemotherapy: A pilot study
Authors: Quevedo F. , Ashdown M. L. , Suman V. J. , Robinson A. , Kottschade L. A. , Kaur J. S. , Creagan E. T. , McWilliams R. R. , Markovic S. N. 
Published: August 2020

e20013 Background: Recent evidence suggests that patients with advanced cancer exhibit an underlying anti-tumor immune response that is continuously attenuated by regulatory T cells (Treg). Depletion of Treg using conventional chemotherapy may be feasible and clinically beneficial. C-reactive protein (CRP) is reported to rise/fall with initiation/termination of the immune response, and may be a surrogate for the periodicity of Treg proliferation that could be utilized for timing of anti-proliferative therapy. Timed delivery of chemotherapy therapy based on CRP cycling may deplete Treg and yield clinical benefit. Methods: We conducted a pilot clinical for 12 patients with metastatic melanoma who underwent serial CRP measurements (every 2–3 days) for 2 weeks. The CRP oscillation cycle was identified and chemotherapy with temozolomide (200mg/m2 for 5 days, every 28 days) was initiated at the estimated peak of plasma CRP. Patients were evaluated for clinical and immune response endpoints every 8 weeks until progression. Results: All 12 patients (median age 61; 4 female; 7 with M1c disease) exhibited oscillating CRP levels with an average periodicity of 7.8 days. Only 11 patients were treated (1 patient had rapid tumor progression). The two patients who remain progression-free for >2 years (1 PR, 1 CR), were treated in the pre-peak section of the CRP cycle, distinctly separate from the other patients treated post CRP-peak (all progressed <5 months). Presented are peripheral blood immunological laboratory correlates (cellular and cytokine) to CRP oscillation. Conclusions: These data suggest that patient clinical outcome may be dependent on the timing of therapy relative to an individual patient's immune response cycle and outline the dynamic equilibrium of systemic immune homeostasis in patients with advanced melanoma. Further investigations of these observations are under way. [Table: see text]
Intra-arterial hepatic bio-chemotherapy for the treatment of melanoma patients with liver metastasis: A phase II clinical study
Authors: Chi Z. , Cui C. , Yuan X. , Si L. , Sheng X. , Shen L. , Guo J. 
Published: August 2020

e20014 Background: To investigate the efficacy and safety of hepatic intra-arterial infusion of cisplatin, fotemustine combined with systemic dacarbazine for the treatment of melanoma patients with liver metastasis. Methods: From 2005.7 to 2008.7, thirty-six melanoma patients with liver metastatic were enrolled. Systemic dacarbazine (250mg/m2 d1–5) and intra-arterial hepatic (i.a.h.) of cisplatin (75mg/m2 d6) and fotemustine (100mg/m2 d7) were given repeated for 4-weeks. Response, progress free survival(PFS), and toxicity were analyzed. Results: 27 of the 36 patients were evaluable, with mean cycle 2.16±1.19, one achieved CR, one PR and seven SD. The disease control rate was 33.3% (9/27) with a median PFS of 3.5 months (95% CI 3.45–7.02months), overall survival of 7.5 months (95 CI 6.87–11.06 months, following to 2008.8). The Grade 3/4 toxicity was mainly myelosuppression, with occurrence rates of 40.7% (10/27). Conclusions: Intra-arterial hepatic chemotherapy show its efficacy and may prolong PFS in melanoma patients with liver metastasis. No significant financial relationships to disclose.
Safety and tolerability of 1-hour intravenous infusion of tremelimumab (CP-675,206) in patients with surgically incurable stage III or IV melanoma
Authors: Chesney J. , Ribas A. , Gonzalez R. , Gordon M. , Gomez-Navarro J. , Marshall M. A. , Huang B. , Hsyu P. , Gernhardt D. 
Published: August 2020

e20016 Background: In previous tremelimumab clinical trials, monoclonal antibody was infused over 3–5 hours. Shorter infusion times would be more convenient. Therefore, this study assessed safety and tolerability of tremelimumab 1-hr infusion. Methods: This ongoing study is an open-label, multicenter, phase I clinical trial evaluating safety and tolerability of tremelimumab (15 mg/kg 1-hr infusion every 90 days for up to 4 doses) in patients with surgically incurable stage III or IV melanoma. Primary endpoint was any tremelimumab-related adverse events (AEs) that occur from start of infusion to 1 hr post-end of infusion of Dose 1 and either prevented full dose from being administered or were ≥ grade 3. Results: Forty-five patients (71% male; median age, 59 years) were enrolled and received ≥ 1 dose of tremelimumab. Patients experienced no AEs during first infusion that met criteria for the primary endpoint. With a 1-sided exact binomial test at 10% significance level (α=0.10), p value was 0.099 (<0.10). Therefore, the null hypothesis (H0: infusion-related reaction rate ≥ 5%) was rejected. Four (9%) patients reported a mild to moderate AE during or within 1 hr after first infusion. These included 1 patient each who experienced grade 2 hypertension (considered unrelated to tremelimumab by the investigator), grade 1 hypotension, grade 2 hypersensitivity, and grade 1 transient flushing. Mean (SD) Cmax (n=32) was 325 (66) μg/mL, mean (SD) AUC (N=16) was 102,000 (35,000) μg×h/mL, and mean half-life was 20 days. These single-dose PK results were similar to those from previous studies using 3- to 5-hr infusion times, suggesting that 1-hr infusion of tremelimumab did not significantly alter PK. No human-anti-human antibodies were detected in any patients. Conclusions: In patients with advanced melanoma, 1-hr infusion of tremelimumab resulted in a safety profile during infusion that was consistent with tremelimumab studies using longer infusion times, and single-dose PK analysis did not reveal any perturbations in tremelimumab distribution or clearance. Therefore, a more convenient 1-hr infusion is a reasonable option for administration of tremelimumab. [Table: see text]
A pilot study comparing objective physical activity to the physical component of the Eastern Cooperative Oncology Group (ECOG) performance status scale
Authors: Walsh J. , Hussey J. , O'Donnell D. 
Published: August 2020

e20501 Background: The ECOG performance status (PS) scale is widely used in oncology for clinical decision-making, being a good predictor of survival, prognosis, and treatment response. It has never been formally compared to objective measures of physical activity (PA). Accelerometers are now established as detailed valid measures of PA. The aim of this study was to compare the ECOG PS scale to objectively measured PA. Methods: Accelerometer data (RT3) as well as self-report (International Physical Activity Questionnaire (IPAQ)) was collected for at least 3 days immediately before cancer outpatient assessment on 15 patients (6 males, 9 females) with a mean age of 65 years (range 47–51), all with solid tumours. RT3 and self-report data were compared to the ECOG PS score assigned by the treating physician. Time ‘up and about’ is all activity, however minimal, detected by the RT3, except lying flat. Institutional ethics committee approval was gained. Results: Most subjects were assigned an ECOG score of 1. In all subjects, the score assigned over-estimated PA levels ( Table ). Spearman's rank correlation coefficient showed poor correlation between percentage waking time ‘up and about’ and the ECOG PS score assigned (p = -0.1), and between the IPAQ and ECOG scores (p = 0.1). Conclusions: Although ECOG PS is recognized as a good predictor of clinical outcome, a poor correlation was found between ECOG PS assigned, objective PA, and self-report. Subjects were far more sedentary than estimated using physician-assigned ECOG PS. A large study to investigate these relationships further is ongoing. [Table: see text] No significant financial relationships to disclose.
Pain and analgesic use in men with metastatic prostate cancer
Authors: Basch E. M. , Sit L. , Fruscione M. , Burke L. , Kane R. , George D. , Carducci M. A. , Matthew P. , Beer T. M. , Scher H. I. 
Published: August 2020

e20515 Background: Pain is an important endpoint in metastatic prostate cancer and was the basis for the 1996 FDA approval of mitoxantrone. Standards for pain assessment have evolved, and a 2006 draft FDA guidance provides new recommendations for patient- reported outcomes. Contemporary palliation models generally require pain reduction starting from baseline worst pain scores of ≥4/10, and progression models require a sufficient proportion of patients’ pain scores to worsen in order to assure an adequate effect size. The prevalence and distribution of pain severity at specific points in the prostate cancer disease continuum are not well defined. Consequently, it is unclear if sufficient numbers of patients are available to conduct prospective studies using pain palliation or prevention as primary endpoints. Methods: A questionnaire that includes the Brief Pain Inventory and additional pain/analgesia items was developed as a collaboration between the DOD/PCF-supported Prostate Cancer Clinical Trials Consortium (PCCTC) and FDA Study Endpoints and Labeling Design (SEALD) team. IRB waivers were obtained for anonymous administration at 5 PCCTC institutions (Sloan-Kettering, Duke, Johns Hopkins, Anderson, OHSU). Administration is ongoing. Results: Between August-December 2008, 325 men with prostate cancers representing different disease states being seen in outpatient clinics of participating centers were each queried once. Median age was 70 (range 49–87). More than half (n=175) self-reported metastatic disease, including 129 with bone metastases. Among those with bone metastases, 76 (59%) reported experiencing any level of pain in the last week; 49 (38%) reported a worst pain score ≥4/10 of which 38 (78%) used analgesics over the past week and 31 (63%) used daily analgesia. In addition, 70 of the 76 (92%) noted that their pain interfered with work, sleep, or enjoyment of life, with 25 (33%) noting severe interference. Among the 49 patients with pain scores ≥4/10, current or past docetaxel use was reported by 32 (65%), androgen deprivation therapy by 47 (96%), and 28 (57%) had been or were currently enrolled in a clinical trial. Conclusions: Pain is sufficiently prevalent in men with metastatic prostate cancer to enable prospective assessment of palliation endpoints in clinical trials. No significant financial relationships to disclose.