bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 trial of talabostat and cisplatin in patients with stage IV melanoma
Authors: Cunningham C. , Pavlick A. C. , Khan K. D. , Frenette G. , O’Day S. , Stephenson J. , Gonzalez R. , Yang Z. , Vrhovac V. , Uprichard M. J.
Published: April 2020

8040

Background: Talabostat (TAL) is an oral inhibitor of dipeptidyl peptidases such as fibroblast activation protein found on the stroma of tumors, draining lymph nodes, and in melanomas. TAL up-regulates cytokines and chemokines, leading to specific T-cell immunity and T-cell independent activity. TAL significantly enhances the activity of cisplatin (C) in mice, and reduces tumor size >60% in melanoma xenografts (A375, A2058). This trial evaluated the activity of TAL and C in patients with Stage IV melanoma. Methods: Open-label, single-arm, Phase 2 study of 4 x 3-week cycles of C-75mg/m2 (Day 1) and TAL-300mcg BID orally on Days 2–15 with dose-escalation to TAL-400mcg BID depending on tolerability. Single-agent TAL could be continued beyond 4 cycles until disease progression or unacceptable toxicity. Eligibility criteria included: ≤1 prior bio- or chemotherapy regimen, ECOG 0–2, measureable disease per RECIST, no symptomatic CNS metastases, LDH, ALT, and AST <3X ULN. Primary endpoint was disease response; secondary endpoints included PFS, duration of response, and survival. Results: 74 patients (50 men, 24 women) entered the study; median age was 58 years (range 27 to 79); 94.6% were caucasian. Most patients (71.4%) were M1c, and the majority (64.3%) had received at least 1 prior regimen; 72.9% of these had received prior cytokine treatment. A PR was reported in 5/42 evaluable patients (11.9%), and SD for at least 4 cycles in an additional 21/42 (50%). Median PFS and survival are currently estimated at 2.6 months (95% CI 2.1, 3.4) and 8.5 months (95% CI 5.4, infinity), respectively in the ITT population. Most frequent AEs were nausea (46%), fatigue (35%), and vomiting (34%); the high unevaluability rate patients was due to non-compliance related to C-associated N/V (thus the dose of C was reduced mid-study from 100 to 75mg/m2). Grade 3 toxicities were neutropenia, fatigue, and dehydration, all at 3.4%. Grade 4 toxicities were organ failure, renal failure, and PD (1 patient each). 4 patients died due to PD, and 1 each due to renal and organ failure. Conclusions: The combination of TAL and C is active in patients with Stage IV melanoma. Most AEs were related to C-associated nausea and vomiting, limiting the oral delivery of TAL. Additional studies of TAL in melanoma with other drug combinations are warranted.

[Table: see text]
Molecular dissection of the RAS/RAF/MAPK pathway in primary and metastatic melanoma
Authors: Rother J. , Bailey J. , Alvarado G. , Prieto V. G. , Lazar A. J. , Jones D. , Hwu W. J.
Published: April 2020

8050

Background: Given the reported presence of frequent mutation in NRAS and BRAF in many melanocytic lesions, the association of mutations activating the RAS/RAF/MAPK pathway with tumor progression in melanoma remains unclear. We compared the NRAS and BRAF mutation status with the levels of activated MAPK in paired primary and metastatic melanomas. Methods: 15 patients with material from both primary and metastatic lesions were assessed. Four patients had metastasis at initial diagnosis, the remaining patients developed metastasis from 8.5 to 66 months (mos) following initial diagnosis (median 24.1 mos). Mutations in BRAF (exons 11 and 15) and KRAS and NRAS (exons 1 and 2) were assessed by quantitative pyrosequencing. MAPK levels were assessed by immunohistochemistry on paraffin sections using phosphor-44/42 (Thr202/Tyr204) polyclonal antisera. Results: Activating NRAS point mutations were found in 3 of 15 patients, with 2 detected in the metastatic lesions; both of these had upregulation of activated MAPK compared to the primary lesions. BRAF V599 point mutations were found in 3 of 15 patients and present in both the primary and cognate metastatic lesions. All cases with BRAF or NRAS mutations had moderate to high levels of activated MAPK, as compared to only 2 of 9 patients without such mutations. The correlation of mutational status and clinical course revealed that NRAS/BRAF mutations and/or MAPK activation did not negatively impact overall survival. Conclusions: Molecular alterations in the RAS signaling pathway are associated with activated MAPK in both primary and metastatic melanoma. NRAS mutations and MAPK activation may be preferentially associated with disease progression, as opposed to BRAF mutations. However, neither NRAS/BRAF mutation nor activation of MAPK signaling pathway in primary and/or metastatic melanoma was significantly associated with poor disease outcome. Further molecular dissection using the archived material from two large melanoma neoadjuvant trials conducted in 1988 and 1994 is ongoing to determine the prognostic and predictive power of these biomarkers.

No significant financial relationships to disclose.
Natural history of metastatic melanoma patients with CNS metastases
Authors: Davies M. A. , Bedikian A. Y. , McIntyre S. , Smith T. , Kim K. , Hwu W. , Papadopoulos N. , Hwu P.
Published: April 2020

8054

Background: Melanoma has a high rate of CNS metastasis (mets). The objective of this study was to evaluate the characteristics and outcomes of melanoma patients (pts) who develop CNS mets. Methods: 333 pts with a diagnosis of CNS mets were identified from databases of 743 chemotherapy naïve metastatic melanoma (MM) pts enrolled on clinical trials between 1986 and 2004. Their clinical and pathological characteristics were reviewed. Results: The site of primary melanoma was head or neck (60/333; 18%), trunk/abdomen (144/333; 43%), limbs (66/333; 20%), ocular (2/333; 1%), or unknown (61/333; 18%). Median Breslow thickness (BT) = 2.2 mm; BT < 1 mm = 39/217 (18%); and BT < 2 mm = 95/217 (44%). Median Clark level (CL)= IV; CL I = 0/180 (0%); CL II = 14/180 (8%); CL III = 70/180 (39%); and CL IV = 96/180 (53%) . The median interval from diagnosis of primary melanoma to CNS mets = 29.6 (range 0.3–393) months (mos). Median survival (MS) from CNS diagnosis = 4.6 (range 0–120) mos. MS was highest for pts with brain mets (n=307; 4.8 mos) compared to pts with brain mets plus leptomeningeal disease (LMD) (14; 2.0 mos) or pts with LMD alone (11; 1.2 mos) (p=.0048 for pts with LMD vs. without). MS varied for pts with 1 (6.6 mos), 2 (4.2 mos), 3 (5.9 mos) or >3 (3.5 mos) brain lesions at diagnosis of CNS mets. Among pts diagnosed with CNS mets at or prior to systemic therapy, MS was longer for pts with CNS mets only (n=20; 14.3 mos) compared to pts with CNS mets concurrent with extracranial mets (63; 7 mos) (p=.003). Patients who developed CNS mets after starting chemotherapy for extracranial mets (n=250; 3.7 mos) had a shorter MS than those diagnosed at or before systemic therapy (83; 7.9 mos, p<.001). Among pts diagnosed after starting systemic therapy, CNS mets were detected ≤ 12 months from the start of chemotherapy in 30% of pts (MS = 3 mos), 12–24 mos in 37% of pts (MS = 4.6 mos), and > 36 mos in 32% of pts (MS = 11.1 mos, p=.044 vs. other groups). Conclusions: This study represents one of the largest cohorts of pts with melanoma CNS mets. The presence of LMD, or development of CNS mets after starting systemic therapy, is associated with a worse prognosis. Among pts diagnosed with CNS mets at or before starting systemic therapy, the presence of concurrent non-CNS mets also portends for a worse outcome. Supported in part by Carol Courtney Memorial fund and Chiron Corporation.

No significant financial relationships to disclose.
Methods of detection of recurrence in patients with cutaneous melanoma
Authors: Dalal K. M. , Panageas K. S. , Brady M. S. , Jaques D. P. , Coit D. G.
Published: April 2020

8057

Background: The patterns and methods of identification of initial recurrences of melanoma in patients staged with sentinel lymph node biopsy (SLNB) were studied. Methods: Stage I/II melanoma patients who underwent SLNB from 1991–2004 were identified from a prospective single-institution database. Detection of recurrence by self (awareness of symptoms or abnormal physical findings) or physician (discovered on routine physical exam or scheduled test) and timing of clinic visit were recorded. Postoperative followup included physical exam every 3–4 months for the first year, 3–6 months for the second, and 6–12 months thereafter. Serum LDH and CXR were obtained annually. CT and PET were performed on a selective basis. Results: Of 1062 patients who underwent SLNB, 211 patients (20%) experienced a total of 242 initial sites of recurrence. Recurrence was more common in SLN+ patients (47% vs. 14%; p< 0.001, respectively). There were 198 patients evaluable for follow-up (median 35 months). Symptoms and self-detected physical findings were present in 109 patients (55.1%; table); 85 patients (42.9%) were seen earlier than their scheduled visit. Self-detected physical findings commonly identified in-transit (13%) and nodal (13%) disease. Physician detection occurred in 89 patients (44.9%); nearly half of these were detected by a scheduled radiographic test (CXR, n=14 [7%]; CT, n=26 [13%]; PET, n=1 [0.5%]). Detection of recurrence by an abnormal blood test was uncommon (n=2; 1%). Post-recurrence survival was associated with site of recurrence (table; p<0.0001). In multivariate analysis, independent predictors of post-recurrence survival were site of recurrence and method of detection (p<0.05). Conclusions: The most common site of recurrence following accurate nodal basin staging and management is systemic. Recurrent melanoma is self-detected by half of the patients. Systemic recurrence is detected by patient symptom or routine radiologic test, but it is associated with a less favorable outcome than recurrence detected by physical exam.

[Table: see text]

No significant financial relationships to disclose.
Trajectory of cognitive impairment during breast cancer treatment: A prospective analysis
Authors: Wagner L. I. , Sweet J. J. , Butt Z. , Beaumont J. , Havlin K. A. , Sabatino T. , Cella D.
Published: April 2020

8500

Background: Several studies havedocumented cognitive impairment in cancer patients; however these reports are primarily based on cross-sectional comparisons. Prospective evaluation would better elucidate the onset and course of cognitive dysfunction related to chemotherapy. Methods: Of 72 breast cancer patients enrolled, 51 completed a comprehensive neuropsychological battery before chemotherapy (T1), on Day 1 of Cycle 4 (T2), and at 6-month follow-up (T3). Participants scoring ≥ 1 SD below the normative mean on ≥ 3 neuropsychological tests OR ≥ 2 SD below on 1 test were classified as impaired. Reliable change indices (RCI) conservatively estimated significant change over time. Results: Participants were White (70.6%) females (96.1%) with a mean of 15.9 ± 2.3 years of education. Mean age was 51.6 ± 8.6 years and most had Stage II (78%) or Stage III (16%) disease. Hospital Anxiety and Depression Scale scores were in the normal range at all assessments and were unrelated to T1 cognitive impairment. Consistent with previous research, 9 (17.6%) of patients met criteria for cognitive impairment at T1. By T2, 14 (27.4%) were cognitively impaired; however, at T3 follow up only 5 (9.8%) were impaired. As noted in the table, most impairment occurs during chemotherapy. Among patients not impaired before chemotherapy it was uncommon for impairment at T2 to persist at follow-up. Conclusions: Some breast cancer patients indeed develop cognitive impairment during treatment, much of which appears to resolve at 6 months. Domains most affected include attention, visuospatial skills, and working memory. Attention problems resolved by 6 months, while working memory and visuospatial deficits persisted.

[Table: see text]

No significant financial relationships to disclose.
The effect of depression on survival in patients with newly diagnosed advanced non-small cell lung cancer (NSCLC)
Authors: Temel J. S. , Jackson V. A. , Billings A. , Prigerson H. G. , Fidias P. , Lynch T. J. , Pirl W.
Published: April 2020

8511

Background: The impact of emotional distress on cancer-related mortality is unclear. Divergent results in studies are due, in part, from heterogeneous populations in terms of type of cancer, stage of disease, and time of emotional assessment. This study examined the effect of depression and anxiety on a well-defined cohort of patients with newly diagnosed advanced NSCLC. Methods: 46 patients with advanced NSCLC were recruited within eight weeks of diagnosis to participate in a feasibility study of early palliative care. Participants completed the Hospital Anxiety and Depression Scale (HADS) at baseline and were followed for six months. The primary study endpoint was survival at six months. The effects of depression and anxiety were evaluated first by Kaplan-Meier survival analysis and then by Cox regression to control for other variables. Results: Three patients (6%) had stage IIIB with effusions and the remaining 43 (93%) had stage IV disease. The median age of patients was 65.5 years and 28 of the 46 (61%) were women. 34 patients had a PS 1 (74%), 11 (24%) had PS 0 and one (2%) had PS 2. 96% of the patients completed the baseline HADS. 23% met HADS criteria for probable cases of depression (8 or greater) at baseline and 34% met HADS criteria for probable cases of anxiety (8 or greater). Using Kaplan-Meier survival analysis, patients with depression were less likely to have survived at 6 months than non-depressed patients (50% versus 80%, log rank p=0.01). Baseline anxiety did not appear to impact survival. Using Cox proportional hazard regression analyses to control for stage, ECOG performance status, age, and gender, the effect of depression remained significant at p=0.03. Conclusion: Depression in newly diagnosed advanced NSCLC patients was associated with inferior survival in this well-defined patient population. Conversely, anxiety did not appear to be associated with mortality. These findings strengthen the argument that emotional distress influences survival. Larger prospective studies are needed to confirm this conclusion, explore possible mediators, and investigate the effects of treatment for depression.

No significant financial relationships to disclose.
Randomized phase II trial of the neurokinin-1 receptor antagonist (NK-1 RA) casopitant mesylate with ondansetron (ond)/dexamethasone (dex) for chemotherapy-induced nausea/vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC)
Authors: Rolski J. , Ramlau R. , Dediu M. , Russo M. W. , Ross G. A. , Mather R. A. , Bandekar R. R. , Grunberg S. M.
Published: April 2020

8513

Background: A combination of a 5-HT3 receptor antagonist (5-HT3 RA) + dex is standard for prevention of CINV due to HEC. However, NK-1 RAs are now also of interest. The current trial evaluated casopitant mesylate, a potent, oral, selective NK-1 RA, in a triple therapy regimen with a 5-HT3 RA and dex in pts receiving HEC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study, pts receiving HEC were stratified by gender and randomized among six arms. HEC consisted of regimens including cisplatin ≥ 70 mg/m2 IV over 1–4 hours (h) day 1 (D1). All pts received ond 32mg IV D1 and dex PO D1–4 with either placebo control, casopitant 50mg QD D1–3, casopitant 100mg QD D1–3, or casopitant 150mg QD D1–3. Pts on exploratory arms received ond/dex plus either casopitant 150 mg D1 only or aprepitant 125mg D1 and 80mg D2–3. The primary endpoint was complete response (CR) rate (no vomiting, retching, rescue medications or premature withdrawals) during the first 120 h following initiation of HEC. Target intent-to-treat (ITT) group enrollment was 82 pts per arm. Results: 493 enrolled patients comprised the ITT group. CR rate was 60% in the control arm; 76% for casopitant 50mg; 86% for 100mg; and 77% for 150mg (p=.0036, Cochran-Armitage trend test). CR rate was 75% with casopitant 150 mg D1 and 72% for 3-day aprepitant. CR rates at 24 h were similar in all groups (86%-96%). Casopitant prolonged time to emesis (p=.0029) and increased the proportion of pts without vomiting (p=.0122) relative to control. There were no differences in rates of nausea or use of rescue medication among groups. Adverse events were similar across all arms, with neutropenia, nausea, and hiccups (≤ 17%) as most common. All casopitant doses were generally well tolerated. Conclusions: The addition of casopitant to ond/dex at all doses tested and in 1- or 3-day administration regimens was well tolerated and significantly reduced CINV rates over a 5-day period in pts receiving HEC. The results of the exploratory 1-day regimen are of particular interest for future evaluation.

[Table: see text]
Effect of nausea vs. vomiting on patients’ quality of life during chemotherapy
Authors: Hickok J. T. , Roscoe J. A. , Morrow G. R. , Giguere J. K. , Colman L. K. , Malcolm A.
Published: April 2020

8514

Background: Antiemetic guidelines are based largely on the presumption that vomiting is of greater concern to cancer patients, and impacts their quality of life (QOL) more strongly, than nausea. We examined the relative influence of chemotherapy-induced nausea and emesis on patients’ overall QOL and on the specific domains of social, emotional, physical and functional well-being. Methods: 667 patients enrolled in a three-arm, randomized, controlled Phase III study that detected no difference in the ability of a serotonin receptor antagonist vs. prochlorperazine (given regularly three times daily or taken only as needed for symptoms) to control the severity of nausea, completed the FACT-G before treatment and on the third day following their first infusion of anti-cancer chemotherapy containing doxorubicin (Day 4 of cycle 1). 93% were female, and 90% had breast cancer. Results: There was a significant reduction in overall QOL and in physical and functional well-being, but no significant change in emotional or social well-being, over the four day period. In a stepwise linear regression analysis predicting change in overall QOL, average nausea severity entered first and accounted for 24% of the variance in reduced QOL (p < 0.001). Occurrence of vomiting (yes, no) accounted for a non-significant less than 1% of additional variance (p = 0.240). No other factors (gender, age, the degree to which patients expected to experience nausea or vomiting, whether or not nausea or vomiting occurred, and maximum nausea severity over the four days) were significant predictors of the reduction in QOL. Similar results were obtained when the relative influence of nausea and vomiting on physical and functional decline were studied. Conclusions: Severity of nausea, not the occurrence of vomiting, was the key factor in patients’ perceived decline in quality of life in the days immediately following chemotherapy infusion. Nausea severity should be a primary outcome measure in studies evaluating antiemetic efficacy. Supported in part by NCI Public Health Service grant U10 CA37420 and ACS grant RSG-01–071-PBP

No significant financial relationships to disclose.
Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events
Authors: Basch E. M. , McDonough T. , Iasonos A. , Siegel E. , Culkin A. , Kris M. , Scher H. I. , Schrag D.
Published: April 2020

8515

Background: During NCI-sponsored clinical trials, clinicians elicit and report patient toxicity symptoms using the Common Terminology Criteria for Adverse Events (CTCAE). Alternatively, patients may be able to report this information directly, but it remains unclear how these patient reported outcomes (PROs) compare to clinician reports. Methods: Language from the CTCAE version 3 was adapted for patient self-reporting and pilot tested to assure comprehension. Then, a paper questionnaire containing 12 common CTCAE symptoms was administered to consecutive outpatients and their clinicians (physicians and nurses) in clinics specializing in lung or genitourinary malignancies at a specialty cancer center. Results: Between March and May 2005, 435 patients and their clinicians were approached in order to obtain 400 completed paired surveys. For most symptoms agreement was high and this was especially true for more observable symptoms (vomiting, diarrhea) compared to more subjective areas (fatigue, dyspnea) (Table). Most discrepancies were within one point. Only rarely would differences have altered treatment decisions (grade <2 vs. ≥3). Patients more commonly assigned greater severity than clinicians. There was no significant difference when patients reported before versus after caregivers. Kappa values did not accurately measure agreement due to asymmetry in the marginal distribution of scores. Conclusion: Patients and clinicians generally agree on CTCAE symptom severity. Future research should examine the impact of symptom PROs on clinical outcomes and the use of real-time reporting for early detection of SAEs.

[Table: see text]

No significant financial relationships to disclose.
Improving palliative care: A 2x2x2 factorial cluster randomized controlled trial of case conferencing and educational outreach visiting
Authors: Abernethy A. P. , Currow D. C. , Shelby-James T. , Williams H. , Roder-Allen G. , Hunt R. , Rowett D. , Esterman A. , May F. , Phillips P. A.
Published: April 2020

8517

Background: Evidence-based palliative care service delivery models are needed. General practitioner (GP) and patient-centered case conferences may increase multidisciplinary interaction and enhance patient care. Educational outreach visiting in pain management may empower learners and improve care. Methods: Three interventions were tested against a routine care control in a 2×2×2 cluster factorial randomized controlled trial. Interventions were case conferencing, educational visiting for GPs, and educational visiting for patients. Subjects were adult patients referred to palliative care services in southern Adelaide, Australia, with any pain in the preceding 3 months. Participants were followed longitudinally until death. Main outcomes included performance status (Australian-modified Karnofsky Performance Status (AKPS)) and hospitalization rates. Longitudinal intention-to-treat analyses using cluster-specific methods were conducted. The sample goal was 460. Results: 461 participants were enrolled from 4/02–6/04. Mean age was 71 yrs, 50% were male, 91% had cancer. Mean and median survival was 146 and 87 days; median baseline AKPS was 60%. When participants had AKPS <70 (i.e. required a caregiver) at referral, those randomized to case conferencing or patient education had higher mean performance status than routine care (case conferencing: average daily AKPS, 54.9% vs 46.3%, p=0.0106; patient education: 54.7% vs 46.4%, p=0.0120). GP education did not improve performance status. Both case conferencing and patient education significantly decreased hospitalization rates compared to routine care (case conferencing: least-squares mean number of hospitalizations, 1.4 (standard error (SE) 0.1) vs 1.9 (SE 0.1), p=0.0002; patient education: 1.4 (SE 0.1) vs 1.8 (SE 0.1), p=0.0078). The addition of both interventions decreased hospitalizations to 1.2 (SE 0.1). Conclusion: At a time when declining function and higher healthcare utilization is the norm, palliative care that includes a case conference or patient educational visiting for pain leads to improved performance status and decreased hospitalizations. Patients with deteriorating performance status derive the greatest benefit.

No significant financial relationships to disclose.
Treatment decision-making preferences in older patients with metastatic colorectal cancer
Authors: Elkin E. B. , Lee S. , Casper E. S. , Kissane D. , Kemeny N. E. , Schrag D.
Published: April 2020

8519

Background: Shared decision-making is a tenet of contemporary oncology practice. However, it is uncertain how involved elderly patients want to be in making treatment decisions and how physicians perceive patient preferences for involvement in decision-making. Methods: In structured interviews about multiple facets of chemotherapy treatment decision-making, we asked patients age 70 and older seen at our specialty cancer center with a recent diagnosis of metastatic colorectal cancer (CRC) about their preferences for making treatment decisions. We used Degner’s control preference scale to measure patient preference for decision control. Treating oncologists described their perception of each patient’s preference for decision control using the same scale. Control preference was assessed in relation to socio-demographic characteristics and functional status. Results: Of 52 patients interviewed, the mean age was 76 years (range 70–89), 52% were male, 60% were educated beyond high school and 25% required some help with activities of daily living (ADL). Preferences for involvement in treatment decision-making demonstrated marked variation (Table). Compared with female patients, males expressed a stronger preference for decision control (p<0.05). Preference for decision control was somewhat greater in patients under age 80, those with more education, and those with no ADL impairment, but these associations were not statistically significant. In 26% of cases, the treating physician’s perception and the patient’s expressed preference for decision control were concordant. Conclusions: In older patients with advanced CRC, preference for control in treatment decision-making shows marked heterogeneity and some correlation with socio-demographic characteristics and functional status. Physicians’ perceptions of patient preference for decision control are often inconsistent with patients’ actual preferences.

[Table: see text]

No significant financial relationships to disclose.
Do pain, depression and fatigue cluster in advanced cancer?
Authors: Hauser K. , Rybicki L. , Walsh D.
Published: April 2020

8522

Background: A cancer symptom cluster of pain, depression and fatigue has been proposed. We evaluated the frequency and strength of association between these symptoms in advanced cancer, and the risk factors for experiencing all three. Methods: Symptoms from 1,000 patients presenting to a palliative medicine program were recorded prospectively. Possible clustering of pain, depression and fatigue was tested (Spearman correlations). Univariate and multivariate logistic regression analyses were performed of demographics, disease site, laboratory and clinical risk factors for the presence all three symptoms. Results: No association was found between pain and depression (r=0.051, p=0.13), or pain and fatigue (r=0.001, p=0.97) and little between depression and fatigue (r=0.173, p<0.001). 27% (n=261) had all three symptoms and in 9% (n=71) all were moderate or severe. Univariate predictors for the presence of all three were: anorexia-cachexia, anxiety, dyspnea, nausea, sleep problems (all p<0.001), vomiting (p=0.007), and younger age (p=0.007). Univariate predictors of moderate-severe pain, depression and fatigue were: anorexia and early satiety (p<0.001), anxiety (p<0.001), dyspnea (p=0.004), low creatinine (p=0.07), poor performance status (p=0.002), sleep problems (p=0.002), >10% weight loss (p=0.046) and vomiting (p=0.047). Those with pain, depression and fatigue had a median 12 (range 2–24) other symptoms vs. 5 (range 1–14) if none were present (p<0.001). Multivariate predictors of pain, depression and fatigue were: anxiety OR 3.81 (95% CI 2.74–5.30, p<0.001); early satiety OR 1.86 (1.35–2.56, p<0.001); nausea OR 1.44 (1.05–1.97, p=0.023); sleep problems OR 1.52 (1.11–2.08, p=0.009); weight loss OR 1.47 (1.08–2.01, p=0.016). Multivariate predictors of moderate-severe pain, depression and fatigue were anorexia OR 3.11 (1.74–5.55, p<0.001); anxiety OR 6.53 (3.64–11.73, p<0.001); poor performance status OR 1.49 (1.09–2.04, p=0.012). Conclusions: The 3 symptoms co-occur in 1 in 4 advanced cancer patients. Risk factors include younger age, symptom burden and the anorexia-cachexia syndrome. Pain, depression and fatigue do not cluster in advanced cancer.

No significant financial relationships to disclose.
Nutritional status in elderly cancer patients: Why is it so important?
Authors: Terret C. , Pérol D. , Albrand G. , Fingal C. , Roux P. , Courpron P. , Droz J.
Published: April 2020

8532

Background: To assess the prevalence of malnutrition in elderly patients (pts) with cancer and to determine the effect of malnutrition on Overall Survival (OS). Methods: Cancer pts aged 65 and older underwent a multidimensional geriatric assessment at our institution. Data were collected for calorie and protein intakes, Mini Nutritional assessment (MNA Nestlé), functional status (ADL score), and comorbidity (CIRS-G). Survival time was defined as the time from geriatric assessment to date of death or last follow-up. A Cox regression model was used to estimate the hazards ratio (HR) and 95 percent confidence intervals (95%CI) of risk factors for death. Results: 133 consecutive pts (68% male, 50% hospitalized) were evaluated from 05/1999 to 08/2002. Median age was 78 years (range: 66–92). Main tumour sites were prostate (36%), breast (15%), bladder (12%) and Head and Neck (10%). Forty eight pts (36%) had metastatic disease. Only 55 pts (43%) were fully independent in ADLs (score = 6), and 15 pts were completely independent in IADLs (score = 14). Fifty one pts (43%) had mild to severe disability/morbidity status (CIRS-G severity index ≥2). Regarding nutritional status, only 34% were estimated well nourished with MNA >23.5, 54% had calorie intake ≤1500 kcal/day and 38% had body weight loss > 5% in the last 3 months. Survival analysis was performed with a 16-month median follow up. Median survival time was 7 months (95%CI 6–9 months). In the univariate analysis, male gender, metastatic stage, MNA, ADL score and CIRS-G severity index were significantly correlated with OS. In the multivariate analysis, male gender (HR=2.3, 95% CI: 1.3–4.1), metastasis (HR=1.6, 95% CI: 1.0–2.6), MNA<23.5 (HR=3.3, 95% CI: 1.8–6.0), CIRS-G severity index ≥2 (HR=2.8, 95%CI: 1.7–4.7) and ADL score <6 (HR=1.9, 95%CI: 1.1–3.3), were found to be independent prognostic factors for shorter OS. Conclusions: These data show that malnutrition has a major impact on survival independently of cancer severity. Thus, nutritional status must be systematically assessed before treatment decision-making. Benefits of nutritional interventions need to be studied in future trials.

No significant financial relationships to disclose.
Gene expression patterns identify patients with non-small cell lung cancer (NSCLC) who are at increased risk for venous thromboembolism (VTE)
Authors: Ramiah V. S. , Potti A. , Dressman H. , Bild A. , Peterson R. , Moore M. , Conlon D. , Harpole D. , Nevins J. R. , Ortel T. L.
Published: April 2020

8535

Background: VTE is the leading cause of death in patients with cancer. The 1 year survival rate in patients diagnosed with cancer at time of VTE is 12% compared to 36% in cancer patients who are free of VTE .Also, a thrombotic event in a hospitalized cancer patient leads to higher in-hospital mortality.Thus,VTE in cancer patients may indicate a more aggressive phenotype. Methods: With the overarching goal of testing the ability of genomic profiling to detect biologically and clinically significant differences in patients with cancer and VTE, using NSCLC as a proof of principle, we expanded on previous work wherein we have shown the ability of multiple gene expression patterns (‘metagenes’) to predict a thrombotic event .96 patients with NSCLC were enrolled in this study. RNA was extracted and gene array data obtained using an Affymetrix U133 2.0 plus GeneChip. The clinical history of all 96 patients was reviewed to identify patients with a definitive VTE episode after the initial diagnosis of cancer and not within six weeks of surgery.14/96 (14.5%) patients met these criteria. We then identified 14 additional patients with NSCLC matched by age, gender and clinical stage patients who did not have VTE for at least 2 years following the diagnosis of cancer. Gene expression data was analyzed using a binary regression analysis. Results: Using the metagene approach, a discriminator gene set (n = 45) that differentiated patients with NSCLC and VTE from patients with NSCLC without VTE was identified. A leave-one-out cross validation performed to further assess the reliability of the discriminator metagene set was more than 85% accurate in identifying patients with NSCLC and VTE. Also, significant biologically relevant differences were seen between the comparison groups, to include genes such as P53, VEGFC, E2F4, TFPI and EPHB2 Conclusions: Our data suggests that a genomic approach can be used to identify with NSCLC that develop VTE, while also providing information important to an understanding of the underlying biology of the association between cancer and thrombosis. We are in the process of validating these results in a prospective trial.

No significant financial relationships to disclose.
Communicating adjuvant treatment goals and side effects to older breast cancer patients
Authors: Naeim A. , Pezeshki B. , Levin J. , Bartfeld N. , Coscarelli A.
Published: April 2020

8541

Background: The use of adjuvant therapy, particularly adjuvant chemotherapy, in older breast cancer patients is controversial. For patients to participate and provide their treatment preferences, information regarding adjuvant treatment and its side effects need to be communicated in lay language. This study explored what older breast cancer women understand about adjuvant therapy, and to elicit feedback on a pre-developed informational handout. Methods: This qualitative study of 35 women with breast cancer over the age of 65 with recent experience with adjuvant therapy participated in six focus groups in Los Angeles County. Focus groups were audio taped and transcribed. In addition, patients filled 2 questionnaires: (a) a demographic questionnaire regarding age, income, education, insurance, and beliefs about cancer and treatment benefits and (b) another to define adjuvant therapy and document patient specific experiences with side effects and physician-patient discussion related to adjuvant therapy. Transcript based analysis was used to identify themes and patterns that arise during the groups. Results: One (3%) of the 35 participants was able to define the term correctly and 63% of participants were unable to answer or provided an incorrect guess to the definition of adjuvant therapy. In addition, patients perceptions were spit between: (a) curing current disease versus (b) preventing future re-occurence. In terms of symptoms, many participants were shocked at their underestimation of fatigue and reoccurring discussions occurred within and throughout each group as to whether side effects were related to treatment or advanced age. Participants unanimously agreed that a handout describing adjuvant therapy would be beneficial. Conclusion: Discussions regarding adjuvant therapy are conceptually challenging, thus providing information regarding the goals and side effects of treatment using lay language is the 1st step in helping older breast cancer patients participate in the decision making process.

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Short-term acenocumarine (A) or dalteparine (D) for the prevention of central venous catheter-related thrombosis (CVCrT) in cancer patients. A randomized controlled study based on serial venographies
Authors: De Cicco M. , Matovic M. , Pacenzia R. , Fantin D. , Caserta M. , Bortolussi R. , Fabiani F. , Santantonio C. , Nigri P. , Veronesi A.
Published: April 2020

8549

Background: Timing and frequency of non occlusive (nO) or occlusive (O) CVCrT in cancer patients (pts) remain unclear. In this randomized controlled trial we studied these points and evaluated the efficacy and safety of short-term prophylaxis with A or D in the prevention of CVCrT. Methods: Consecutive cancer pts without contraindications to short-term anticoagulation, scheduled for chemotherapy via CVC, were randomly assigned to receive: A 1 mg/day for 3 days before and 8 days after CVC insertion; D 5,000 IU 2 hours before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All pts underwent venography (V) at day 8 and 30 after CVC insertion and then every two months until CVC removal . The primary endpoint was V detected CVCrT, evaluated as nO or O when it was partially or completely occlusive of the vein lumen, respectively. Bleeding episodes were recorded. Proportions were compared using chi-square test together with odds ratio (OR). Results: 450 pts were randomized, 348 of whom (120/150 A, 114/150 D, and 114/150 NT) underwent V (median number of procedures 4, range 2–8). Both A and D reduced the frequency of V detected CVCrT (21.9% A vs 55.3% NT, OR= 4.35 (95% CI 2.43–7.69), p<0.001; 40% D vs 55.3% NT, OR= 1.85 (95% CI 1.10–3.13), p=0.02). A was more effective than D (OR= 2.37 (CI 1.34–4.22), p= 0.003). The frequency of O CVCrT was not different in the 3 groups (0.9% A, 5.0% D, 4.4% NT; p= 0.18). Overall, 5.1% of pts with CVCrT were symptomatic, all presenting O CVCrT (42% of pts with O CVCrT were not symptomatic). Most CVCrTs (95.6%) were observed at day 8 after CVC insertion. No major bleeding or pulmonary embolism occurred. Conclusions: In this study, acenocumarine was more effective than dalteparine in reducing V detected CVCrT. The doses of prophylactic agents used in this study proved to be safe. Symptomatic CVCrT evaluation alone underestimates the actual CVCrT frequency. The first days following CVC insertion are at highest risk for CVCrT. Short term thrombosis prophylaxis appears to be superior to no treatment without the expenses and inconveniences inherent in long-term prophylaxis.

No significant financial relationships to disclose.
Characterization of cancer pain syndromes (PS) seen at a Comprehensive Cancer Center (CCC) and pain response (PR) to palliative care consultation (PCC)
Authors: Zhukovsky D. S. , Palmer J. , Bruera E. , Pei B. , Zhang T. , Nekolaichuk C. , Fainsinger R.
Published: April 2020

8551

Background: Comparison of cancer PS across settings is challenging due to differences in prognostic features. Data from 1 CCC participating in a multi-site international study of a pain classification system is presented to characterize cancer PS & response to PCC. Methods: The Edmonton Classification System for Cancer Pain was completed by prospective chart review to characterize PS of 100 consecutive hospitalized patients (pts) seen in PCC. Pts were followed until major PR, hospital discharge or death. Major PR was defined as <2 p.r.n. opioid doses/d & pain intensity (PI) <3/10 for 3 consecutive days (d). Results: 85% of pts had pain (n=85), with age 62.9+13.3, 47.1% male & KPS 44.5+23.1. The most common tumor diagnoses were lung (24.7%) & GU (21.2%). Pts were followed for a median of 4 d (0–27). 39% achieved a major PR. Except for steroids (49.4%) & anticonvulsants (29.4%), other adjuvant analgesic use was all <10%. Pain-associated features: *Numeric Rating Scale 0–10, 10=worst suggestivie of alcoholism + Mean morphine equivalent dailydose On univariate analysis, older age (p=.006), lower initial PI (p=.003), lower final PI (p=.001) & lower final MEDD (p=.002) were significantly associated with achieving major PR. On multivariate analysis, lower initial PI (p=.03) & lower final MEDD (p=.02) retained significance for achieving major PR. Conclusions: Only 39%of pts with cancer pain seen in PCC achieve a major PR by discharge or death. Despite aggressive opioid titration, 61% do not achieve a major PR & require better pain management. Potential strategies for achieving improved PR include earlier PCC, identification of more sensitive prognostic variables &critical evaluation of targeted therapies.

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No significant financial relationships to disclose.
International multi-centre study of incidence and risk factors of symptomatic deep venous thrombosis (DVT) and or pulmonary embolism (PE) in prostate cancer patients undergoing laparoscopic radical prostatectomy (LRP)
Authors: Secin F. P. , Fournier G. , Gill I. S. , Abbou C. C. , Schulmann C. , Tuerk I. , Piéchaud T. , Janetschek G. , Vickers A. , Guillonneau B.
Published: April 2020

8555

Background: There is no data regarding the incidence and variables associated with symptomatic DVT and or PE in patients undergoing LRP. Our aim was to evaluate the multi-centric incidence and risk factors for perioperative symptomatic DVT and PE after LRP. Methods: Patients with symptomatic DVT and or PE occurring within 2 months of surgery since start of the respective institutional LRP experience were included. Eight academic centers from both the United States and Europe participated. Diagnoses were made by Doppler ultrasound for DVT; and lung ventilation/perfusion scan and or chest computed tomography for PE. Associations between variables and DVT and/or PE were evaluated using Fisher’s exact test for categorical predictors and logistic regression for continuous predictors. Results: Patient reoperation (p value) (<0.001), tobacco exposure (0.02), prior DVT (0.007), larger prostate size (0.02) and length of hospital stay (0.009) were significantly associated with higher risk of symptomatic DVT/PE. The nonuse of perioperative heparin was not a risk factor (1), as well as neoadjuvant therapy (1), perioperative transfusion (0.1), body mass index (0.9), surgical technique (0.3), operating time (0.2) and pathologic stage (0.5). There were no related deaths. Patients receiving preoperative heparin had significantly higher mean operative blood loss, 480cc vs 332cc (<0.001) However, this did not translate into longer hospital stay (0.07); higher transfusion rates (0.09) or reoperation rates (0.3). The estimated cost of heparin prophylaxis in these patients exceeded $2.5 million. Conclusion: The incidence of symptomatic DVT or PE was similar despite different prophylactic regimens. Our data does not support the administration of prophylactic heparin in LRP to low risk patients (no prior DVT, no tobacco exposure, no prostate enlargement and or no anticipation of prolonged hospital stay).

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No significant financial relationships to disclose.
Final results of a large, community-based, prospective study evaluating the impact of first and subsequent cycle pegfilgrastim on neutropenic events in patients receiving myelosuppressive chemotherapy
Authors: Ozer H. , Mirtsching B. , Rader M. , Ding B. , Truscinski D. , Dreiling L.
Published: April 2020

8569

Background: Neutropenia is the major dose-limiting complication of myelosuppressive chemotherapy (CT). The Awareness of Neutropenia in CT (ANC) Study Group has prospectively documented cycle 1 febrile neutropenia (FN) in 8% of patients (pts) receiving CT with or without growth factor support in community practice. Our study was conducted to assess the impact of first and subsequent cycle pegfilgrastim use on neutropenic events in pts receiving CT in community practice. Interim data were previously reported (Ozer ASCO 2005). Methods: Pts ≥18 years with cancers other than leukemia or MDS were eligible, including pts with major comorbidities. Key exclusion criteria of this open-label study were weekly CT or concurrent radiotherapy (RT). Pts were to receive pegfilgrastim 6 mg ∼24 hours after CT (min 4 cycles planned). Primary endpoints were neutropenic hospitalization and CT dose delays and reductions; additionally, FN (absolute neutrophil count <1×109/L with temperature ≥38.2oC) was measured. Results: 319 centers enrolled 2,249 pts (2,500 planned); 2,112 patients who received CT and pegfilgrastim after proper consent were included in final analyses. Most pts were women (75%). Major tumor types included: breast (46%), lung (16%), and ovarian (8%) cancers, and lymphoma (18%). 36% of pts were ≥65 years (mean age [SD]: 59 [12.8]), 55% had stage 3/4 or extensive disease, 23% received prior CT, 17% received prior RT, and 27% had a significant comorbidity. Neutropenic complications occurred infrequently (table). FN was experienced by 3.6% (95% CL: 2.8, 4.5) of pts in cycle 1 and in 6.3% (5.3, 7.5) in all cycles. Serious adverse events were consistent with toxicities observed in pts receiving CT. Conclusions: Pts treated in community practice receiving pegfilgrastim in every cycle of myelosuppressive CT experienced a low incidence of neutropenic complications and alterations in CT dose and schedule due to neutropenia.

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Survival prediction in terminally ill cancer patients by clinical estimates, laboratory and psychometric tests
Authors: Gripp S. , Moeller S. , Willers R.
Published: April 2020

8578

Background: To improve general survival estimates in advanced cancer pat. we studied physicians’ clinical estimates, the impact of emotional disorders (anxiety and depression), and laboratory tests in palliative patients. Methods: From 12/03 to 7/04 patients with advanced cancer referred to radiation oncology for palliative treatment were invited to participate in this prospective cohort study. Pat. with adjuvant or curative treatment intent were not considered. The life span was independently estimated by two physicians and the institutional tumor board according to 3 categories (<1, 1–6, and >6 months). Agreement of survival predictions was analyzed with contingency tables and kappa statistics. Primary tumor, metastatic spread, performance status, pain, dyspnoea, weight loss, nausea, fatigue, serum enzymes (AP, LDH), function parameters (creatinine, bilirubin, CRP), and blood count (WBC, RBC) were also studied. Emotional disorders were measured using a validated psychometric self-assessment scale (Hospital Anxiety and Depression Scale, HADS). Life table analysis with log-rank test and stepwise Cox regression analysis with univariate significant variables were performed. Results: 216 pat. were enrolled and followed for at least 6 months. 580 prognoses were obtained. 94% (204) had complete blood tests. HADS questionnaires were completed by 71% (154). Survival was <1 mo in 15% (33), 1–6 mo in 36% (78), and >6 mo in 49% (105).Survival prediction was poor (kappa= 0.33) and consistently too optimistic (test of symmetry, p<0.0001). In life table analysis primary tumor (hazard ratio 2.0), brain metastases, performance status (HR 1.9), dyspnoea (HR 2.0), nausea (HR 2.0), LDH (HR 1.9), WBC (HR 2.1), fatigue, anxiety and depression (HADS) were highly significant (p< 0.0002). Conclusions: Physicians generally overestimated survival of advanced cancer patients emphasizing the need of objective prognostic models. Even short-term survival estimates (< 1 mo.) were unreliable. Combined objective variables may improve survival prediction. Psychometric tests are promising candidates to be incorporated in more accurate prognostic models.

No significant financial relationships to disclose.