bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II study of the tumor-targeting human L19-IL2 monoclonal antibody-cytokine fusion protein in combination with DTIC in metastatic melanoma patients
Authors: Garbe C. , Romanini A. , Spitaleri G. , Giovannoni L. , Zardi L. , Neri D. , Shaw A. , Menssen H. D. , deBraud F. , Eigentler T. K. 
Published: August 2020

9064 Background:L19-IL2 is a tumor targeted immunocytokine constituted by a single chain Fragment variable (scFv) format directed against the ED-B domain of fibronectin and the human cytokine interleukin-2 (IL2). The recommended dose (RD) for monotherapy of advanced solid cancer patients was established to be 22.5 Mio IU IL2 equivalent on day 1, 3, and 5 of a 21-day cycle. Here we report clinical results of the dose escalation part of a phase I/II study assessing L19-IL2 in combination with DTIC chemotherapy in metastatic melanoma patients. Methods: L19-IL2 was administered as an i.v. infusion at doses of 10 (n=3), 15 (n=3) and 22.5 MioIU IL2 equivalent dose (n=4) on days 1, 3 and 5 every 21 days in combination with DTIC 1000 mg/m2 on Day 1 for up to 6 treatment cycles. Serum samples for PK evaluation and induction of human antifusion antibodies to L19 (HAFA) were collected. Flow cytometry (T and NK/B cell panels) was performed. Data on safety and activity were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: All 10 patients had progressive metastatic melanoma and the majority had already received prior systemic therapy. Median age at start of treatment was 62 years (52–74). There were no treatment related deaths and the treatment was well tolerated, details of CTC evaluation will be presented. The dose of 22.5 Mio IU day 1, 3, and 5 in combination with 1000 mg DTIC/m2 on day 1, repeated on day 22 was defined as the RD for up to 6 treatment cycles. 10 patients were evaluable for response. We observed 1 partial remission at the 15 Mio IL2 dose level after 4 treatment cycles. Immunophenotyping analysis showed transient stimulation of NK cells, T4 cells, and CTLs. Pharmacokinetic data will be presented. Conclusions: L19-IL2 at a dose of 22.5 Mio IU IL2 equivalent on days 1, 3, and 5 of a 3-weekly schedule can be safely combined with standard DTIC in metastatic melanoma patients. Toxicity was manageable and reversible. Preliminary evaluation suggests clinical activity of the L19IL2/DTIC regimen in metastatic melanoma patients. [Table: see text]
Prospective analysis of predictors of survival in melanoma patients with brain metastases
Authors: Zakrzewski J. A. , Geraghty L. , Hamilton H. , Christos P. , Krich D. , Mazumdar M. , Polsky D. , Darvishian F. , Pavlick A. , Osman I. 
Published: August 2020

9074 Background: Melanoma patients (pts) with brain metastases (BM) have limited survival, and BM remains an exclusion criterion in most clinical trials. A recent retrospective analysis at Memorial Sloan Kettering Cancer Center (MSKCC) identified 4 clinical variables that were associated with worse post BM survival (Raizer J et al, Neuro Oncol 2008). In this study, we investigated whether primary tumor features could improve the predictability of post BM survival and examined the reproducibility of the variables identified in MSKCC study. Methods: Melanoma pts with BM prospectively enrolled in an interdisciplinary database at NYU Medical Center from 2002 to 2008 were studied. Six primary tumor characteristics, 21 clinical variables, and treatments were examined. Univariate associations were analyzed using Kaplan Meier survival analysis and the independent effect of identified predictors was assessed by multivariate cox proportional hazards regression analysis. Results: Eighty-nine pts (36 F, 53 M, median age 57) were identified. Median post BM survival was 5.75 months. Median follow-up time based on survivors was 4.2 months. Ulceration and mitotic index ≥3/field were univariately associated with worse post BM survival (p=0.004, p=0.009 respectively). Age >65, ≥3 BM lesions, presence of neurological symptoms, and extracranial metastases were also univariately associated with worse post BM survival (the same 4 variables identified in MSKCC retrospective study). An additional 4 clinical parameters were significant by univariate analysis: frontal lobe location (p=0.01), bilateral lesions (p=0.01), ≥2 neurological symptoms (p=0.005), and weakness/fatigue (p<0.0001). After reproducing the significance of the 4 MSKCC variables in a multivariate model, ulceration of the primary tumor was also an independent predictor of post BM survival (hazard ratio [HR] = 2.75; 95% CI = 1.30, 5.83; p=0.008) whereas mitotic index ≥3/field was not (HR=1.24; 95% CI = 0.57, 2.71; p=0.59). Conclusions: Data suggest that ulceration of the primary melanoma might indicate an adverse biologic behavior that impacts post BM survival. Our data also lend independent support for the predictive model of post BM survival. No significant financial relationships to disclose.
Effect of denosumab on bone mineral density (BMD) in women with breast cancer (BC) and men with prostate cancer (PC) undergoing hormone ablation therapy
Authors: Smith M. R. , Ellis G. , Saad F. , Tammela T. , Bone H. , Egerdie B. , Ke C. , Jun S. , Dansey R. , Goessl C. 
Published: August 2020

9520 Background: Hormone ablation therapies, including adjuvant aromatase inhibitor (AI) therapy and androgen deprivation therapy (ADT), improve recurrence-free survival in patients (pts) with BC and PC, respectively. However, these treatments increase bone resorption, leading to bone loss and fractures. RANKL is a key mediator of osteoclast-mediated bone resorption. In this 24 month (mo) comparison, we investigated the effects of denosumab, a fully human monoclonal antibody against RANKL, on preserving BMD across both populations. Methods: Two trials were conducted: a 24-mo BC study and a 36-mo PC study. Postmenopausal women with low BMD receiving AI therapy for nonmetastatic BC and men receiving ADT for nonmetastatic PC (with low BMD or history of osteoporotic fracture if < 70 yrs) were randomized to receive placebo or denosumab 60mg subcutaneously every 6 mos. All pts in both studies were prescribed calcium and vitamin D supplements. The primary endpoint was % change from baseline in lumbar spine (LS) BMD at 12 mos for the BC study and at 24 mos for the PC study. Herein, we present changes in BMD at 24 mos at LS, total hip (TH), and 1/3 radius from both studies. Power calculations were based on enrollment of at least 208 patients in the BC study (for primary endpoint only) and 1226 in the PC study (for primary and key secondary endpoints). The actual numbers randomized were 252 and 1468, respectively. Results: Denosumab increased BMD of the LS, TH, and 1/3 radius compared with placebo at 24 mos in both pt populations ( Table ). In both studies, differences between denosumab and placebo at each skeletal site were consistent, and the effects of denosumab were statistically significantly different from placebo as early as 1 month at the LS in both studies. The overall safety profile was similar to placebo in each study. Conclusions: Denosumab consistently increased BMD at all 3 skeletal sites compared with placebo in both women with BC undergoing AI therapy and in men with PC undergoing ADT. [Table: see text] [Table: see text]
Patient preference as a determinant of breast cancer adjuvant chemotherapy use in older women: CALGB #369901
Authors: Mandelblatt J. , Sheppard V. , Hurria A. , Kimmick G. , Isaacs C. , Taylor K. , Luta G. , Noone A. , Kornblith A. , Barry W. 
Published: August 2020

9544 Background: Decisions about use of breast cancer chemotherapy in women 65 and older (“older”) can be complex due to comorbidity, uncertain efficacy and limited data on patient preference. Methods: Older women diagnosed with invasive, non-metastatic breast cancer between 2004 and 2008 were recruited from 53 CALGB sites for an observational study of preferences and chemotherapy use. Data on preferences and other factors were collected from patient interviews and clinical data were abstracted from charts. Generalized estimating equation regression was used to assess associations between chart-reported chemotherapy and independent variables; associations were also evaluated in 2 subgroups: “chemotherapy indicated” (estrogen receptor [ER] negative and/or node positive) and “consider chemotherapy” (ER positive and node negative). Results: Among 935 eligible women registered, 815 (87.2%) completed interviews. The mean age of the cohort was 73 years (range 65–100); 38% were node positive, 82% were ER positive and all had tumors ≥ 1 cm (44% were AJCC stage 1, 44% stage 2 and 12% stage 3). Based on ER and nodal status, chemotherapy was “indicated” for 47% and could be “considered” for 53%. Crude chemotherapy rates were 70% in the “indicated” group and 17% in the “considered” group, for an overall rate of 42%. Women who would choose chemotherapy for an increase in survival of ≤12 months were 4.1 times (95% CI 2.5–6.7, p<.0001) more likely to receive chemotherapy than women who would only choose chemotherapy if it added more than 12 months, controlling for age, tumor factors, comorbidity and other covariates. Stronger preferences were seen among women with “indications” for chemotherapy (OR 7.9, 95% CI 3.7–17.0, p<.001) than in those where treatment might be “considered” (OR 1.8, 95% CI 0.9–3.4, p=.08). Higher patient rating of communication with providers was independently related to a decision to use chemotherapy among women where chemotherapy could be “considered” but not among those where chemotherapy was “indicated”. Conclusions: Beyond clinical indications, older women's preferences and communication with providers are important correlates of chemotherapy use. [Table: see text]
Risk factors for in-hospital mortality and prolonged length of stay in older patients with solid tumors
Authors: Shayne M. , Culakova E. , Poniewierski M. S. , Wolff D. A. , Lyman G. H. 
Published: August 2020

9550 Background: Little is known about risk factors that contribute to prolonged hospitalization and mortality in older patients with cancer. Methods: Cancer patients ≥65 years of age hospitalized between 1995 and 2003 at 133 academic medical centers were evaluated using the University Health System Consortium discharge database. This study identified 386,377 older hospitalized patients with various solid tumors. Multivariate analyses were performed to determine variables independently associated with the primary endpoints: length of stay (LOS) ≥10 days and in-hospital mortality (IHM). Results: Average LOS was 7.5 days with 23% hospitalized ≥10 days. A significant improvement in LOS was observed over the study timeframe (p<.0001). Patients with gastric cancer had the greatest risk of prolonged LOS while those with breast cancer had the lowest risk. Additional risk factors for prolonged LOS included infection, venous thromboembolism and red blood cell transfusion (RBCT). The overall rate of IHM was 7.3% with a significant improvement in risk over the study timeframe (p<.0001). IHM was strongly associated with prolonged LOS (p<.0001). Older patients with primary central nervous system malignancies had the highest rates of IHM (OR=1.81; 95% CI: 1.59–2.07), followed by esophageal and lung cancer. Male gender was a risk factor for both IHM and prolonged LOS (p<.0001). Older African American cancer patients were more likely to experience prolonged LOS and IHM compared with Caucasian patients (p<.0001) after adjustment for cancer type and comorbidities. Additional risk factors associated with IHM included metastatic disease, active infection, neutropenia, renal disease, lung disease, arterial and venous thromboembolism, congestive heart failure, hepatic disease, and RBCT. Conclusions: Improving trends in LOS and IHM for older patients with solid tumors were observed over time in this study. Risk factors associated with IHM such as infection, neutropenia and RBCT, when modified, could potentially further reduce rates of prolonged LOS and IHM in older cancer patients. [Table: see text]
Cognitive function and fatigue in colorectal cancer (CRC) patients: Baseline assessments prior to chemotherapy
Authors: Vardy J. L. , Dhillon H. , Xu W. , Dodd A. , Park A. , Rourke S. B. , Clarke S. J. , Ringash J. , Burkes R. , Tannock I. F. 
Published: August 2020

9557 Background: A subset of women with breast cancer have cognitive impairment &/or fatigue before and after chemotherapy (CTh). We evaluated these symptoms and potential mechanisms prior to CTh in patients with CRC. Methods: Chemo-naïve patients with stage I-III CRC (Group 1) and pts with limited stage IV CRC prior to 1st line metastatic CTh (Group 2) were evaluated. Neuropsychological (NP) performance was assessed by classical and computerized (CANTAB) test batteries, with cognitive impairment defined using a global deficit score approach, and concurrent questionnaires for fatigue & quality of life (FACT-F), anxiety/depression (GHQ), and perceived cognitive function (FACT-COG). Group 1 had blood tests to evaluate 10 cytokines, clotting factors, sex hormones, CEA and apoE genotype. Primary endpoints were cognitive function (classical tests) and fatigue in group 1. Associations between test results, demographic and disease-related factors were sought. Results: We assessed 326 patients: Group 1, 253 (post-surgery [median 56 days] 174; pre-surgery 79); Group 2, 73. Median age was 59 (23–75); 61% were male. In group 1, 36% had cognitive impairment on classical tests & 29% on CANTAB; 32% and 30% in group 2. No differences were seen by disease stage or surgery status. Men had more cognitive impairment than women on classical tests (p=.001). Self-reported cognitive symptoms was 10%; higher in women (p=.08). Fatigue, QOL, anxiety/depression & self-reported cognitive symptoms were strongly associated with each other (r=.45-.76, p<.0001), but not with NP test performance. Fatigue was 52% in Group 1 vs 66% in Group 2 (p=.03); and greater in women (p=.002). All cytokines were elevated compared to healthy volunteers (p<.001). Cognitive function and fatigue prior to CTh were not associated with cytokines, sex hormones, clotting factors, CEA or apoE genotype. Symptoms of anxiety/depression were reported by 13% of group 1 pts vs 25% in group 2 (p=.02). Conclusions: Cognitive impairment was present in 36% of CRC patients prior to adjuvant CTh, with 10% self-reporting impairment and 52% reporting fatigue. Cytokine levels were elevated but were not associated with cognitive function or fatigue. The etiology of cognitive impairment prior to cancer treatment remains unknown. No significant financial relationships to disclose.
Paradoxical cutaneous squamous cell proliferations in patients treated with sorafenib
Authors: Arnault J. P. , Mateus C. , Wechsler J. , Spatz A. , Tomasic G. , Sibaud V. , Aractingi S. , Grange J. D. , Escudier B. , Robert C. 
Published: August 2020

9564 Background: The new multikinase inhibitor sorafenib is associated with multiple and usually manageable skin side effects. We report 12 patients presenting with solitary or multiple cutaneous squamous cell proliferations occurring in the months following initiation of sorafenib and we discuss the significance of this unexpected association. Results: Twelve patients treated by sorafenib for renal cell cancer or hepatocellular carcinoma presented one or several skin tumours with a typical keratoacanthoma (KA) appearance 3 to 9 months after the onset of sorafenib therapy. Some KAs had a spontaneous regression. No recurrence after surgical excision or metastatic dissemination was reported. Histologic examination of 22 lesions found classical non aggressive KAs in 16 cases and more aggressive squamous cell carcinoma-like lesions with deep dermis invasion and cellular atypias in 5 patients. Conclusions: Sorafenib treatment can be associated with cutaneous squamous cell proliferation resembling KAs. Although our observations suggest that these skin neoplasms have a low aggressive potential, these reports address the questions of the paradoxical proliferating effect of a drug that usually has an anti-proliferating effect. They also reactivate the unresolved controversy about the relationship between KA and authentic squamous cell carcinoma. More practically, although the exact frequency of this side effect is unknown, physicians should be aware of this side effect and regularly perform skin examination of their patients. Surgical excision is the treatment of choice in order to rule out authentic squamous cell carcinoma. Impact and management of these skin proliferations will have to be further evaluated, especially if sorafenib is to be tested in an adjuvant setting. No significant financial relationships to disclose.
Neoplastic meningitis—Is MRI as sensitive as CSF cytology?
Authors: Strik H. M. , Proemmel P. , Pilgram-Pastor S. , Buhk J. H. 
Published: August 2020

9566 Background: Although CSF cytology and MRI are standard methods for the diagnosis of neoplastic meningitis (NM), this complication of neoplastic disease still remains to be difficult to detect in some cases. We therefore re-evaluated the sensitivity of gadolinium(GD)-enhanced MRI and cerebrospinal-fluid (CSF)-cytology for the diagnosis of LM differentially for solid and haematological malignancies and for normal or elevated cell counts. Methods: We identified retrospectively 101 cases of NM diagnosed in our CSF laboratory since 1990 with complete data of both MRI and CSF-cytology. 34 had haematological, 67 solid neoplasms. CSF-cell counts were increased in 63 and normal in 35 patients. Results: For haematological neoplasms, MRI was positive in 53%. CSF cytology was positive in 97%. In solid tumours, we found MRI-sensitivity of 0.81 and cytological sensitivity of 0.76. With normal CSF-cell-counts, MRI was positive in 63%, (0.57 haematological, 0.75 solid malignancies), CSF-cytology in 78%, (0.9 in haematological, 0,64 in solid neoplasms). In cases of increased cell-counts, MRI-sensitivity was 0.75 (0.52 for haematological, 0.87 for solid malignancies), and sensitivity of CSF-cytology was 0.89 (1.0 for haematological and 0.82 for solid neoplasms). 23 patients were treated with intrathecal MTX or Ara-C, 16 patients with liposomal Ara-C. 62 patients were not treated intrathecally. Conclusions: We confirmed here the high overall sensitivity of MRI for the diagnosis of neoplastic meningitis. The best sensitivity, however, was seen in solid tumours and elevated cell counts. In haematological malignancies, a markedly lower sensitivity of MRI was seen. Of note, we consider the very high sensitivity of cytology in haematological malignancies to be artificial due to methodological reasons of this retrospective study. We conclude that MRI is a very sensitive method to detect NM especially in solid tumours and elevated cell counts. With normal cell counts and haematological neoplasms, CSF-cytology remains to be superior to radiological methods. [Table: see text]
Acquired and inherited risk factors for the developing of venous thromboembolism in cancer patients receiving adjuvant chemotherapy: A prospective trial
Authors: Labianca R. , Mandalà M. , Barni S. , Falanga A. 
Published: August 2020

9572 Background: To assess the thrombogenic role of adjuvant chemotherapy, following radical surgical resection, in ambulatory cancer patients, is of particular interest, because of the little or no tumor burden. The relation between adjuvant chemotherapy and thrombosis has been investigated in breast cancer. Limited information is available in GI cancers. Aim of this study was to investigate the acquired and inherited risk factors for VTE and the incidence of symptomatic VTE in patients on adjuvant chemotherapy for breast or GI cancer. Methods: In a prospective observational study (January 2003 and February 2006), 199 GI (82F/117M; age range, 26–84 years) and 182 breast (180F/2M; age range, 29–85 years) cancer patients were enrolled and followed-up for symptomatic VTE during adjuvant chemotherapy. We prospectively evaluated the effect of acquired (i.e. age, chemotherapy, tumor hystotype, history of thrombosis, body mass index and smoke) and inherited risk factors (i.e. antithrombin, protein C, protein S, homocysteine, activated protein C [APC] resistance, factor V Leiden [FVL] and Prothrombin [PT] mutations). Results: Overall 30 VTE events (7.87%) were recorded: 28 (7.35%) during treatment and 2 (0.52%) during the subsequent follow-up. Among all the 381 cancer patients, FVL was detected in 14 cases (3.67%) and PT mutation in 10 cases (2.62%). At multivariate analysis thrombocytosis (HR 2.8; 95% CI, 1.13–7.30, P< 0.026) and a previous episode of thrombosis (HR 12.4; 95% CI, 2.48–62.6, P< 0.0026) were significantly associated to the development of VTE . There was no association between the FVL or PT mutations and the risk of VTE. Conclusions: Our data demonstrate that, in the adjuvant setting, most VTE occur during therapy. Thrombocytosis prechemotherapy and an history of VTE strongly predict the developing of VTE in the adjuvant setting. No significant financial relationships to disclose.
Randomized clinical trial of medical qigong on quality of life, fatigue, side effects, mood, status, and inflammation of cancer patients
Authors: Oh B. , Butow P. , Mullan B. , Clarke S. , Beale P. , Pavlakis N. , Rosenthal D. 
Published: August 2020

9617 Background: The quality of life (QOL) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself. This study examines the impact of Medical Qigong (MQ), including gentle exercise and relaxation through meditation and breathing exercise based on the Chinese Medicine theory of energy channels, on quality of life (QOL), fatigue, side effects, mood status and inflammation. Methods: One hundred sixty two patients diagnosed with a range of cancers recruited from three university teaching hospitals were randomly assigned to two groups: a control group (n=83) that received usual health care and an intervention group (n=79) who participated in a MQ program for 10 weeks in addition to receiving usual health care at the hospital. Quality of life and symptoms were measured by the FACT-G, cancer related fatigue by FACT-F and mood status by POMS. The inflammatory marker serum C-reactive protein (CRP) was also monitored serially. Results: Regression analysis indicated that the MQ intervention group significantly improved on measures of overall QOL (t144= -5.761, p<0.001), fatigue (t153= -5.621, p<0.001), mood disturbance (t122=2.346, p=0.021) and inflammation (CRP) (t99=2.042, p<0.044) compared to the usual care control group after controlling for baseline variables. Analysis of the FACT-G subscales revealed that the MQ intervention group also significantly improved in satisfaction with sex life (t92=-3.783, p<0.001) and reduced side effects of nausea (t152=-2.071, p=0.040) and sleep disturbance (t150=-2.603, p=0.010) compared to the usual care control group. Pain was improved in both intervention and control groups. Conclusions: This study suggests that MQ with usual health care can improve overall QOL, fatigue, positive mood status and reduce the side effects of nausea, sleep disturbance and inflammation of cancer patients. This study supports the use of MQ as an intervention for cancer care. No significant financial relationships to disclose.