bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a multimarker blood assay for postoperative assessment of stage IV melanoma patients in a prospective international phase III trial
Authors: Hoshimoto S. , Shingai T. , Wang H. , Elashhoff R. M. , Morton D. L. , Hoon D. S. 
Published: August 2020

9045 Background: Currently there are no validated prognostic molecular biomarkers for assessment of outcome after complete resection of stage IV melanoma patients. To validate blood molecular biomarkers for prognostic value and monitoring of these patients, we evaluated the clinical utility of a multimarker quantitative reverse-transcription PCR (qRT-PCR) for detecting circulating tumor cells (CTC) of patients blood enrolled in a multicenter international (29 sites) phase III trial of postoperative adjuvant therapy. After complete metastasectomy, AJCC stage IV patients underwent immunotherapy with bacille Calmette-Guerin (BCG) plus placebo or BCG plus melanoma vaccine. Methods: Bleeds were taken before and during treatment in both randomized treatment arms. Pre- and during treatment bleeds from patients were assessed by an optimized qRT-PCR assay for MART1, MAGEA3, and PAX3 genes mRNA. Median clinical follow-up time was 21.8 and 24.2 mos. for disease-free survival (DFS) and overall survival (OS), respectively. Results: MART1, MAGEA3, and PAX3 were detected in 64 (26%), 56 (23%), 73 (29%) of 244 post-operative pretreatment patients, respectively. Multivariate Cox analysis showed that biomarker-negative patients had significantly higher DFS than biomarker- positive patients (risk ratio 1.56, 95% CI, 1.14 - 2.15; P=0.0062). In serial-bleeds (pretreatment, mos 1 and 3) analysis of 214 patients, biomarker-negative patients had significantly higher OS than patients with 1–2 positive- or 3 positive-biomarkers (risk ratio 2.37, 95% CI 1.14 - 4.94, P=0.021; and risk ratio 2.90, 95% CI 1.28 - 6.53, P=0.01, respectively). Multivariate analysis confirmed that 1–2 positive- and 3 positive-biomarkers were significant independent prognostic factors for poor OS (risk ratio 2.44, 95% CI 1.16 - 5.12, P=0.019; and risk ratio 3.08, 95% CI 1.36 to 6.98, P=0.007, respectively). Conclusions: This prospective multicenter blood biomarker validation study demonstrates that multimarker qRT-PCR analysis of CTC has significant clinical utility as a prognostic factor of disease outcome at pretreatment, and as a treatment monitoring prognostic factor in stage IV melanoma patients. No significant financial relationships to disclose.
Phase II study of vincristine sulfate liposomes injection in patients with metastatic uveal melanoma
Authors: Bedikian A. Y. , Sato T. , Kim K. B. , Papadopoulos N. E. , Hwu W. , Homsi J. , Davies M. , Cheung C. , Imperiale S. M. , Prasad P. , Hwu P. 
Published: August 2020

9067 Background: Preclinical and clinical studies showed that liposomal encapsulation of vincristine sulfate (VCR) results in increased drug circulation time and accumulation of VCR at the tumor site. Marqibo has been administered safely at 2.25 mg/m2, a dose exceeding that typically employed for VCR ( dose capped at 2 mg), with tolerable clinical toxicities consistent with VCR. Of the 27 previously treated patients with metastatic melanoma in the Marqibo pharmacokinetic studies, 3 patients had a tumor response, including one patient with uveal melanoma metastatic to the lung that experienced a complete response. Methods: Patients with metastatic uveal melanoma with no more than one prior systemic therapy were enrolled. Patients with controlled brain metastases were allowed. Marqibo (2.25 mg/m2 by 1-hour intravenous infusion, no dose capping) was administered every 14 days until tumor progression. Responses were assessed every 6 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was assessed at least as frequently as before each dose. Results: Preliminary data is available for 22 enrolled patients (73% female). Median age was 65 years (range 38–79), 23% were previously treated with systemic chemotherapy, 86% had liver metastasis and 96% had M1c disease. Baseline serum LDH levels were elevated in 73% and were more than 2 × ULN in 37% of the patients. Twenty-one patients were evaluable for response; one patient discontinued the treatment after a single dose of therapy for toxicity without tumor progression. No patients died of drug toxicity while on the study. Twelve patients (57%) had stable disease. Estimated median survival is 6.4 months. Fourteen patients are alive, 2 for more than 12 months. Treatment related side effects were mostly grade 1 or 2; peripheral neuropathy was the only grade 3 toxicity, seen in 18% of the patients. The hematologic toxicities were minor; no neutropenia or thrombocytopenia was seen. Conclusions: Marqibo is well tolerated as single agent therapy in patients with advanced stage IV uveal melanoma. Its impact on the progression-free and overall survival of these critically ill patients will be presented. No significant financial relationships to disclose.
Impact of concomitant immunosuppression on the presentation and prognosis of patients with melanoma
Authors: Frankenthaler A. , Lee M. , Seery V. , Renzi S. , Kinnaman M. , Liu V. , Friedman E. , Atkins M. B. 
Published: August 2020

9070 Background: Melanoma has been reported to be susceptible to immune control. Therefore, we hypothesized that concomitant immune suppression might impact the course of the disease. Methods: We examined the Beth Israel Deaconess Medical Center Cutaneous Oncology Program database for pts with immune suppression at the time of melanoma diagnosis. The demographics and stage of these pts were compared to those in the database as a whole. In addition, 3 controls matched for age, gender, stage and tumor location were identified for each case and disease outcome was compared between cases and controls. Results: 19 pts were identified with melanoma and concomitant immune suppression in a database of 1820 melanoma pts. Other diagnoses included renal transplant (4) inflammatory arthritis (8), Multiple Sclerosis (2), and ulcerative colitis (3). Immunosuppressive meds included methotrexate, azothioprine, cyclosporine, prednisone, infliximab, and natalizumab. Melanoma stages at diagnosis were in situ 1, IB 7, IIA 1, IIB 1, IIIB 3, IIIC 5, and IV 1. Compared to the database as a whole, cases were more likely to be female (84% vs 45%) and have a higher disease stage (42% stage IIIB/C vs 26%). In addition, more cases appeared to have an amelanotic primary (21% vs. 5.4%) or an atypical mole syndrome (21% vs 10.2%). For pts who relapsed, the cases had a shorter disease free interval (DFI) (2.1 vs 9.7 yrs) than the controls. At a median f/up of 52 mos, 37% of the cases had relapsed and all of these pts had died. At a median f/up of 76 mos, 30% of the controls had relapsed yet only 47% of these pts had died. As a consequence, cases appeared more likely to have died of their disease than controls (42% vs 23%) (p=0.10). Conclusions: Compared to the general melanoma population, pts with concomitant immune suppression appear more likely to be female, have an amelanotic primary or atypical mole syndrome and more advanced disease at presentation. Although pts with concomitant immune suppression are equally likely to relapse compared to matched controls, those that relapse appear to have a shorter DFI and to be less likely to be salvaged, suggesting more aggressive tumor behavior in this setting. Thus, diagnosis and treatment of a primary melanoma at an early stage appears especially important in an immunosuppressed population. No significant financial relationships to disclose.
Multicenter study on prognostic factors in 692 patients with brain metastases of malignant melanoma
Authors: Eigentler T. K. , Figl A. , Krex D. , Mohr P. , Kurschat P. , Tilgen W. , Bostroem A. , Heese O. , Garbe C. , Schadendorf D. 
Published: August 2020

9081 Background: This multicenter study aimed to identify prognostic factors in patients with brain metastases from malignant melanoma (BM-MM). Methods: In a retrospective survey in nine cancer centres of the German Cancer Society 692 patients were identified with BM-MM during the period 1986–2007. Overall survival was analysed using Kaplan-Meier estimator and compared by log-rank analysis. Cox proportional hazards models were used to identify prognostic factors significant for survival. Results: The median overall survival of the entire cohort was 5.0 months (95%CI: 4–5). Prognostic factors in the univariate Kaplan- Meier analysis were: Karnofsky Performance Status (≥ 70 vs. <70; p<0.001), number of BM-MM (single vs. multiple; p<0.001), pre-treatment levels of serum LDH (normal vs. elevated; p<0.001), pre-treatment levels of S100 (normal vs. elevated; p<0.001), Prognostic groups according to Radiation Therapy Oncology Group (Class I vs. Class II vs. Class III; p=0.0485), kind of applied treatment (for the cohort with single BM-MM, only) (stereotactic radiotherapy or neurosurgical metastasectomy vs. others; p=0.036). Cox proportional hazards models revealed pre-treatment elevated level of serum LDH (HR: 1.6, 95%CI: 1.3–2.0; p=0.00013) and number of BM-MM (HR: 1.6, 95%CI: 1.3–2.0; p=0.00011) in the whole cohort of patients as independent prognostic variables, whereas in patients with single BM-MM the kind of applied treatment (stereotactic radiotherapy or neurosurgical metastasectomy vs. others; HR: 1.5, 95%CI: 1.1–1.9; p=0.0061) was identified as unique prognostic factor. Conclusions: Overall survival of patients with BM-MM mainly depends on the number of metastases and pre-treatment levels of LDH. In case of a single brain metastasis the application of stereotactic radiotherapy or neurosurgical metastasectomy is by far the most important factor for improving survival. No significant financial relationships to disclose.
Ginger for chemotherapy-related nausea in cancer patients: A URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients
Authors: Ryan J. L. , Heckler C. , Dakhil S. R. , Kirshner J. , Flynn P. J. , Hickok J. T. , Morrow G. R. 
Published: August 2020

9511 Background: Despite the widespread use of antiemetics, post-chemotherapy nausea and vomiting continue to be reported by up to 70% of patients receiving chemotherapy. Ginger (Zingiber Officinale), an ancient spice, is used by practitioners worldwide to treat nausea and vomiting. We conducted a multi-site, phase II/III randomized, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for chemotherapy-related nausea in cancer patients at the University of Rochester-affiliated Community Clinical Oncology Program (CCOP) member sites. Methods: Cancer patients who experienced nausea following any chemotherapy cycle and were scheduled to receive at least three additional cycles were eligible. Patients were randomized into four arms: 1) placebo, 2) 0.5g ginger, 3) 1.0g ginger, or 4) 1.5g ginger. All patients received 5-HT3 receptor antagonist antiemetics on Day 1 of all cycles and took three 250mg capsules of ginger or placebo twice daily for six days starting three days before the first day of the next two cycles. Patients reported the severity of nausea during the morning, afternoon, evening, and night on a 7-point semantic rating scale (‘1' = ‘Not at all Nauseated' and ‘7' = “Extremely Nauseated”) for Days 1–4 of each cycle. The goal was to determine if ginger was more effective than placebo in controlling chemotherapy-related nausea in participants given a 5-HT3 receptor antagonist antiemetic. Results: A total of 644 patients were accrued (90% female, mean age = 53). Breast (66%), alimentary (6.5%), and lung (6.1%) cancers were the most common cancer types. Analysis of covariance (ANCOVA) examined change in nausea in the four study arms on Day 1 of cycles 2 and 3. All doses of ginger significantly reduced nausea (p=0.003). The largest reduction in nausea occurred with 0.5g and 1.0g of ginger. Also, time of day had a significant effect on nausea (p<0.001) with a linear decrease over 24 hours for patients using ginger. Conclusions: Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of nausea during the first day of chemotherapy. Supported by NCI PHS grants 1R25CA10618 and U10CA37420. No significant financial relationships to disclose.
Spiritual support of patients with advanced illness and associations with end-of-life care and quality of death
Authors: Balboni T. A. , Paulk M. E. , Balboni M. J. , Trice E. D. , Wright A. A. , Phelps A. C. , Block S. D. , Prigerson H. G. 
Published: August 2020

9514 Background: Little is known about whether spiritual support is associated with advanced cancer patients' medical care and quality of death (QoD) at the end of life (EoL). Methods: Coping with Cancer is an NCI/NIMH-funded, prospective, longitudinal, multi-institutional study of advanced, incurable cancer patients conducted from September 2002-August 2008. Analyses were based on 343 deceased patients who were interviewed at baseline and then followed until death a median of 117 days later. At baseline, spiritual support was assessed by (1) patient-rated support of spiritual needs by the medical system (eg, physicians, nurses, chaplains) scored from 0 (not at all) to 5 (completely supported) and (2) patient-reported receipt of hospital/clinic pastoral care services. Outcomes measured included medical care received in the last week of life (hospice; receipt of aggressive EoL care defined as ICU admission, resuscitation, ventilation or chemotherapy in the last week of life; and death in an acute care facility) and QoD. QoD assessments (possible 0–30, with increasing scores reflecting better QoD) were obtained by post-mortem interviews of a caregiver present in the patient's last week of life. Multivariable analyses examined (1) associations between spiritual support variables and EoL care outcomes, controlling for baseline confounds (eg, race, religiousness, patient EoL care preferences) and (2) associations between spiritual support variables and QoD with adjustment for confounds (eg, baseline quality of life, aggressive EoL care). Results: In adjusted analyses, greater medical system spiritual support was associated with increased receipt of hospice care [OR = 2.97 (1.24–7.11), p = .01], but not with receipt of aggressive EoL care or death in an acute care facility. Receipt of pastoral care services was not associated with any EoL care outcome. In adjusted analyses, spiritual support from the medical system and receipt of pastoral care services were significantly associated with better patient QoD (standardized β = 0.16, p = .009 and β = 0.20, p = .0005, respectively). Conclusions: Support of advanced cancer patients' spiritual needs by the medical care team is associated with increased receipt of hospice care and improved patient QoD. No significant financial relationships to disclose.
Acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) and overall mortality with chemotherapy (CT) and granulocyte colony-stimulating factor (G-CSF): A meta-analysis of randomized controlled trials (RCTs)
Authors: Lyman G. H. , Dale D. C. , Culakova E. , Poniewierski M. S. , Wolff D. , Kuderer N. M. , Lambert K. , Crawford J. 
Published: August 2020

9524 Background: To evaluate the risk of AML/MDS and overall mortality in patients receiving CT ± G-CSF, a meta-analysis of RCTs were conducted. Methods: Electronic databases searched through August 2008 identified 3,794 articles for initial screening. Eligibility included RCTs of solid tumor or lymphoma patients randomized to CT ± primary G-CSF support, ≥2 years follow-up and reporting AML/MDS or all second malignancies. Pre-specified study categories included: a)same dose/schedule, b)dose-dense or c)dose-escalated CT. Primary outcomes were AML/MDS and mortality. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk difference (ARD) were estimated by Mantel-Haenszel. Results: Median follow-up was 54 months. 12,642 patients were randomized to CT ± primary G-CSF support. Second malignancies were reported in 3.3% and 3.2% with and without G-CSF, respectively (P=.942). RR for AML/MDS with CT+G-CSF compared to control was 1.92 [P=.006] with ARD increase of 0.4% [P=.008]. RR for AML/MDS in study categories to receive the same, dose-dense or dose-escalated CT+G-CSF were 1.95 [P=.346], 1.20 [P=.666] and 2.47 [P=.006], respectively. RR for mortality with CT+G-CSF was 0.898 [P<.0001] with ARD decrease of 3.3% [P<.0001]. RR for mortality in study categories to receive the same, dose-dense or dose-escalated CT+G-CSF were 0.95 [P=.140], 0.84 [P<.001] and 0.91 [P=.019], respectively. Delivered relative dose intensities (RDI) were 1.18, 1.46 and 1.23 in studies planned to receive the same, dose-dense or dose-escalated CT, respectively. A significant association was observed between delivered RDI and reduced mortality [P=.013]. No differences in estimates of AML/MDS or mortality were observed between industry and non-industry-funded studies. Conclusions: Risk of AML/MDS is increased with dose escalated CT+G-CSF. Nevertheless, CT+G-CSF is associated with greater reductions in overall mortality. Dose-dense regimens are associated with the greatest RR reduction in mortality and lowest risk of AML/MDS. Further research is needed to differentiate any impact of G-CSF on the risk of AML/MDS from that due to increased CT intensity. [Table: see text]
The use of vitamin E for prevention of chemotherapy-induced peripheral neuropathy: A phase III double-blind, placebo controlled study—N05C31
Authors: Kottschade L. A. , Sloan J. A. , Mazurczak M. A. , Johnson D. B. , Murphy B. , Rowland K. M. , Smith D. A. , Berg A. , Stella P. J. , Loprinzi C. L. 
Published: August 2020

9532 Background: Chemotherapy induced peripheral neuropathy (CIPN) continues to be a substantial problem for many cancer patients (pts). Pursuant to promising appearing pilot data, the current study evaluated the use of vitamin E for the prevention of CIPN. Methods: A phase III, randomized, double-blind, placebo controlled study was conducted in pts undergoing therapy with neurotoxic chemotherapy, utilizing twice daily dosing of vitamin E (400mg)/placebo. The primary endpoint was the incidence of grade 2+ sensory neuropathy (SN) toxicity (CTCAE v 3.0) in each treatment arm, analyzed by Chi-square testing. Major eligibility criteria included: planned curative intent adjuvant chemotherapy with neurotoxic chemotherapy, ≥ 18 years of age, ECOG PS of ≤2, no existing peripheral neuropathy or coronary artery disease, no prior treatment with neurotoxic chemotherapy, and no concurrent treatment with neuropathic or opioid pain medication. Planned sample size was 100 patients per arm, to provide 80% power to detect a difference in incidence of grade 2+ SN toxicity from 25% in the placebo group to 10% in the vitamin E group. Results: Two-hundred seven pts were enrolled between 12/01/2006 and 12/14/2007. Cytotoxic agents included taxanes (109), cisplatin (8), carboplatin (2), oxaliplatin (50) or combination (20). Eleven pts canceled prior to starting treatment and there were 7 ineligible pts on study. Thus there were 189 evaluable pts included in the current analysis. In this analysis, there was no difference in the incidence of grade 2+ SN between the 2 arms (vitamin E- 34% [95% CI- 25.0–44.8%] placebo- 29% [20.1–39.4%]; P=0.43). There, likewise, were no significant differences between treatment arms for time to onset of neuropathy (P= 0.72), for chemotherapy dose reductions due to neuropathy (P= 0.21) or patient questionnaire reported neuropathy symptoms. The treatment was well tolerated overall. Conclusions: Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy but it appeared to be well tolerated. No significant financial relationships to disclose.
Low-molecular-weight heparin for venous thromboprophylaxis in ambulatory cancer patients: A meta-analysis
Authors: Kuderer N. M. , Khorana A. A. , Francis C. W. , Lyman G. H. , Falanga A. , Ortel T. L. 
Published: August 2020

9537 Background: Patients with cancer have an increased risk of venous thromboembolism (VTE). However, routine VTE prophylaxis is generally not recommended in ambulatory cancer patients. Several randomized controlled trials (RCTs) of low-molecular-weight heparin (LMWH) in ambulatory cancer patients have been reported with inconclusive results. Methods: A systematic review of RCTs of LMWH in ambulatory cancer patients without a VTE diagnosis was conducted. Included trials had to report VTE as primary or secondary outcome. An extensive electronic database search was conducted, including Medline, EMBASE, Cochrane Library along with abstracts from major meetings. Dual-blinded data extraction was performed. Meta-analysis was conducted using Mantel and Haenszel method to estimate relative risk (RR) and absolute risk difference (ARD) ± 95% CI. Primary outcomes in this analysis were all reported VTE and major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results: Six RCTs were identified with a total of 2,648 patients including 1,525 receiving LMWH and 1,123 controls. No significant heterogeneity was observed across trials. Among patients receiving LMWH, the crude incidence of VTE was 2.95% compared to 5.25% among control patients. LMWH reduced the RR of VTE by 36% compared to controls (RR=0.64 [0.44 - 0.94], P=0.021), and reduced the ARD by 1.8% [0.2% - 3.4%]. Major bleeding events were reported in 1.57% LMWH patients compared to 0.98% in controls. The non-significant RR increase by LMWH for major bleeding was 1.85 [0.923 - 3.68], P=0.081, with an ARD of 0.9% [0.0% - 1.8%]. Results were comparable in the analysis limited to studies with VTE as primary outcome. Conclusions: While patients experienced a 36% relative risk reduction in VTE with LMWH, the absolute risk reduction was small, and concerns remain about the potential increase in major bleeding. Therefore, routine VTE prophylaxis in ambulatory cancer patients cannot be recommended at this time. Additional research is needed to identify cancer outpatients at high risk for VTE, in whom prophylaxis may have a more favorable risk-benefit ratio. [Table: see text]
Willingness of cancer patients to discuss advance directives with admitting doctor or oncologists
Authors: Dow L. A. , Smith T. J. , Matsuyama R. , Lamont E. B. , Ramakrishnan V. , Kuhn L. , Lyckholm L. 
Published: August 2020

9539 Background: Many seriously ill cancer patients do not discuss prognosis or advance directives (ADs), which may lead to aggressive care at end of life (Harrison & Smith, JAMA 2008). Ten years ago, cancer patients did not want to discuss ADs with their oncologist (ONC), but would discuss them with an admitting doctor (Lamont JPM 2000).We assessed if this still held. Methods: We administered semi-structured interviews to cancer inpatients on the VCUHS Hematology-Oncology service. 55/63 consecutive patients accrued. Information was collected regarding ADs and knowledge of hospice/palliative care. Results: Of those enrolled, 22/55 (40%) reported having ADs. Only 2/55 had discussed ADs with their oncologist. Only 12/55 (22%) would want to discuss ADs with their ONC. But when specifically asked, 22/55 (40%) of patients would prefer to discuss ADs with their oncologist, and 40% with their primary care doctor. 86% would discuss ADs with the admitting doctor. There was no difference in doctor preference based upon prior AD completion. The preference not to discuss ADs with the oncologist was often because they felt their family could make the decisions, or that it was only necessary “If it got serious.” There was a common misconception that ADs mean death is imminent and lead to termination of care. Conclusions: Most patients (86%) are willing to discuss ADs with an admitting doctor, but only a small number (22%) want to discuss with their ONC. However, most patients will discuss ADs and 40% actually prefer their ONC if ADs are discussed. We therefore need to train primary care doctors, house staff, hospitalists, and oncologists to have these difficult discussions. [Table: see text] No significant financial relationships to disclose.