bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of BAY 43–9006 in metastatic melanoma with molecularly characterized B-Raf status
Authors: Hardin E. , Pavlick A. C. , Liebes L. , Osman I. , Hamilton A. , Soon J. , Polsky D. , Friedman K. , Wright J. , Muggia F. 
Published: April 2020

8046 Background: BAY 43–9006 is a multikinase inhibitor. The RAS/BRAF/MEK/MAPK pathway (pw) is a major pw for transmitting extracellular growth factor signals to the nucleus. Activating mutations in any of the pw kinases would be expected to result in uncontrolled cell proliferation. Approximately 60% of melanomas carry B-Raf mutations. The primary trial goals are: 1) determine if treatment (tx) with BAY 43–9006 can disrupt the RAS/BRAF/MEK/MAPK pw by depleting intra-tumor stores of B-Raf and/or CDK4; and 2) determine if tx with BAY 43–9006 results in differential anti-tumor responses in pts whose tumors have been molecularly characterized. Methods: Eligibility criteria: Biopsy (bx)-accessible, untreated metastatic melanoma. Measurable disease (RECIST). Adequate hematologic and serologic parameters. Signed ICF. All pts had tumor bx for B-Raf status determined by PCR sequencing prior to tx. Exon 3 of N-Ras and exon 15 of B-Raf were sequenced. Pts stratified by B-Raf. Tx: BAY 43–9006 was administered at 400 mg po BID. D1–28 q4w. Repeat bx was done on Day 28. Re-imaging was done every 2 cycles and pts treated until POD. Stats: Stratification by B-Raf mutation status. 2 stage study design with accrual of 13 pts/arm in first stage and total of 29 pts/arm if ≥ 1 objective response (OR) in initial cohort. Results: 8 pts (2-M1a, 1-M1b, 5-M1c) enrolled. 7 wild type (WT) and 1 mutant (M) B-Raf. Median age: 54 (range 22–91). No pts with LDH ≥ 1.5 × nl. 2 withdrew prior to tx. Responses: M B-Raf (1 evaluable)-PR (lymph nodes and large SQ arm masses); WT B-Raf-1 POD during cycle 1 (NE), 1PD, 3 too early. Toxicity: Grade I diarrhea, Grade II hypertension, fatigue and oral mucositis. Correlative immunoassays of tumor B-Raf, CDK4, phospho-MAPK and cyclin-D1 and correlation of DNA extracted from peripheral blood cells assayed by fluorescent, mutant-specific PCR and tumor B-RAF are being evaluated. Conclusions: This Phase II trial will molecularly characterize tumors for B-Raf status prior to tx with BAY 43–9006 and assess the effects on Ras-Raf signaling and correlate clinical responses. This trial will address potential differences in sensitivity to BAY 43–9006 based on B-Raf. While premature, 1 pt with M B-Raf has had an OR with a significant decrease in tumor volume. Supported by NCI N01-CM17103 and TRI. No significant financial relationships to disclose.
CXCR4 in melanoma: A prognostic biomarker and a target of therapy
Authors: Scala S. , Napolitano M. , Fulciniti F. , Giuliano P. , Mauro F. , Ieranò C. , Simeone E. , Ottaiano A. , Botti G. , Ascierto P. , Castello G. 
Published: April 2020

8051 Background: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. In melanoma metastases CXCR4 is also expressed and functional suggesting that CXCR4 has a role in the melanoma biology. Differential chemokine receptors expression by activated tumor specific CD8+ T cells can be associated with divergent clinical outcomes. Expression of CXCR3 by CD8+ T cells was reported to be associated with survival in melanoma patients with stage III disease. To further characterize the role of CXCR4 in the melanoma metastatization we analyzed Fine Needle Ago Biopsy (FNAB) from disease involved lymph nodes. Moreover, we are currently evaluating CD8+ subpopulation for the expression of CXCR4 during the follow up Methods: FNAB of suspicious disease involved lymphnodes. was performed and the cell suspension was analyzed by flow cytometry and .immunocytochemistry. Peripheral blood lymphocytes (PBL) was analyzed by flow cytometry Results: FNAB were performed on 25. suspicious lymphnodes. Out of 25 FNAB 19 were positive per melanoma cells (HMB45 positive). Concomitant expression of HMB45 and CXCR4 was detected in 15 out of 19 samples.with the percentage of cells CXCR4 positive being the large majority ( 40–100%) of the detected melanoma cells. Ongoing studies are further characterizing the biology of the CXCR4/HMB45 cells. The inhibition of this cells migrating through the lymphnode may interfere with the metastatization. In relation to the CD8+ subpopulation for the expression of CXCR4 during the follow up preliminary data at the time of diagnosis showed a correlation between the activated CD8 + lymphocytes (HLA-DR+) /CXCR4 + and the level of invasion of the lesion. Conclusion: Altoghether these evidences confirm a role of CXCR4 in melanoma biology and as therapeuthic target . No significant financial relationships to disclose.
Lessons learned from two decades of sentinel node biopsies for melanoma
Authors: Scheri R. P. , Kavanagh M. , Wanek L. , Essner R. , Morton D. 
Published: April 2020

8055 Background: The long term prognosis for patients with melanoma staged by sentinel node biopsy (SNB) remains unclear, largely due to limited follow-up from a variety of small single institution studies. We evaluated our extensive 20-year experience to evaluate the long term prognostic significance of SNB. Methods: We retrospectively reviewed the records of 2001 successive patients who underwent LM/SNB at our center from 1985 until 2004. After preoperative lymphoscintigraphy, blue dye and a hand-held gamma probe were used for intraoperative identification of sentinel nodes (SN). SN were evaluated for metastases by hemotoxylin and eosin and immunohistochemical staining with HMB45, S-100, and more recently with antibodies to melanA. Patients with tumor-positive SN underwent completion dissection (SCLND). Clinicopathological features of the patients, primaries and SN status were evaluated for their influence on survival using multivariate Cox regression analysis. Results: After median follow-up of 49 months (range 1–237). Median age for our patients was 51 years (range 10–91). Of the 2,001 patients, 1584 (79%) had tumor-negative and 417 (21%) had tumor-positive SN. Survival rates were higher in patients with tumor-negative vs. tumor-positive SN (91 + 2% vs. 72 + 5% at 5 years, log-rank p<0.0001; and 84 + 3% vs. 64 + 7% at 10 years, log-rank p<0.0001). Of the 417 patients with SN metastases, 293 (70%) had a single tumor-positive node, 101 (24%) had 2–3 positive nodes, and 25 (6%) had at least 4 positive nodes (sentinel plus nonsentinel). Overall survival was significantly better when metastases were confined to single vs. multiple nodes (77 + 3% vs. 63 + 5%; p=0.0017). Multivariate analysis with Cox regression identified SN status (p<0.0001) as the most important prognostic factor, Hazard Ratio 3.44 (2.47–4.79). Breslow thickness (p<0.0001) and ulceration (p=0.0001) are also independently significant for survival. Gender and primary site were not significant. Conclusions: Our results demonstrate the long term prognostic significance of SN status. LM/SNB should become standard of care for primary melanoma because it is the most accurate factor for the quantification of the risk for recurrence and death available. No significant financial relationships to disclose.
Ultrasound (US) and US-guided fine needle aspiration cytology (FNAC) prior to sentinel lymph node biopsy (SLNB) in melanoma patients: Accuracy of US-FNAC and lack of further improvement by RT-PCR of the aspirate
Authors: Voit C. A. , Schaefer G. , Schoengen A. , Akkooi A. C. , Eggermont A. M. , Rademaker J. , Lukowsky A. , Schwuerzer M. , Sterry W. , Kron M. 
Published: April 2020

8059 Background: We have previously shown that US guided FNAC identifies positive SNs prior to SLND in 19% of cases (Voit et al., Ann Surg Oncol: 2006, in press). Originally, in this prospective study, we had tested the feasibility of in vivo US as screening tool and FNAC for verification of sentinel nodes (SN) prior to SLNB. Here we report the results of tyrosinase RT-PCR examinations of SNs aspirated pre-SLNB and of post-SLNB FNAC of the excised SN. Additionally, pts were followed up by blood sample tyrosinase RT-PCR at regular intervals. Methods: Between 7/2001 and 7/2003, 127 AJCC staged melanoma pts with a median tumor thickness of 2.1mm [0.4–18] underwent a FNAC to verify SN detected by US. Follow-up data are updated until 1/1/2006 (mean/median FU 29/31 (0 - 51) months). In 127 pts 141 SNs have been excised. SN involvement was predicted with a combined sensitivity for US with FNAC of 82% [65–93%] and a specificity of 72% [62–81%]. 19 patients already identified as SN+ by US guided FNAC reduced the need for the SLNB procedure in 16% (19/121). SN Size pre- and post-SLNB was measured by US. Results: US identified the SN in 121/141 (86%). None of the 20 SNs not identified by US were malignant. Median pre-SLNB SN size was 842 mm3 [35–107,272], median post-SLNB SN size was 714 mm³ [32–13,409]. Pre- and post-SLNB SN sizes were virtually identical. 34/121 SNs were histologically malignant. In 7/34 no measurements were made for various reasons. In 27 SNs histological patterns of involvement were examined. 10/27 showed solitary nests in subcapsular/parenchymal or combined localization. 17/27 SN were involved by multiple nests. RT-PCR of the aspirate of SNs was confirmative pos. in 11/27 and false neg. in 16/27. Size analyses of the lesions showed an av. 2.8 mm2 (median 0.5 [0.005–32.0]) in the false neg. pop. and 28.5 mm2 (median 20 [0.003–80.0]) in the confirmative pos. pop. Blood RT-PCR as well as DFS and OS will be updated and provided at the meeting. Conclusions: US guided FNAC is highly accurate. Additional RT-PCR of the aspirate does not further enhance SN pos. identification rate. US-FNAC can reduce the need of SLNB in 16% of patients. No significant financial relationships to disclose.
Identification of prognostic factors predictive of CNS metastasis in patients (pts) with advanced unresectable metastatic melanoma (MM)
Authors: Bedikian A. Y. , Wei C. , Detry M. , Kim K. , Papadopoulos N. , Hwu W. , McIntyre S. , Smith T. , Gumpel X. , Hwu P. 
Published: April 2020

8060 Background: Diagnosis (Dx) ofCNS metastasis (met) in MM is associated with poor prognosis. The objective of this study was to find prognostic factors that may predict CNS met. Methods: 743 chemotherapy (CRx) naïve MM pts were treated on 12 clinical trials during the past 15 years at MDACC. Demographics, tumor stage, and Rx outcomes were collected. Seven prognostic factors likely to predispose pts to CNS met were assessed: presence of liver met, elevated serum LDH, low serum albumin, site of primary, Clark level ≥ IV / Breslow thickness (BT) > 3.5 mm, M1 stage, and number of visceral met sites. Time to event analyses considered the time from unresectable stage III/ IV disease to Dx of CNS met, or last follow-up if noCNS met. Prognostic factors were examined separately using a Cox proportional hazards model, with time from Dx of primary melanoma to Dx of unresectable stage III/ IV disease also included as a covariate. Estimates of CNS met-free curves were calculated using the Kaplan-Meier product-limit method. The incidence of CNS met between CRx-sensitive and CRx-resistant groups was assessed by Chi-square test. Results: CNS met (n=333) and CNS met-free (n=410) pt groups were similar in median age, gender distribution and primary M sites. Compared to CNS met-free pts, CNS met pts were more likely to have M1b + M1c advanced disease stage (M1b+c 291/333 (87%) vs. 286/410 (70%); p<0.0001) and ≥ 2 visceral met sites (138/333 (41%) vs. 126/410 (30%), p=0.003), as well as greater BT (median 2.3 vs. 1.5 mm). Pts with elevated serum LDH had significantly shorter CNS met-free interval those with normal serum LDH (p=0.0009). CNS met-free interval was also significantly shorter for M1b (p=0.028) and M1c pts (p=0.05), but not M1a (p=0.8) pts, compared to unresectable stage III pts. Compared to pts with soft tissue/l. node disease, CNS met-free interval was significantly shorter for pts with 1–3 met sites (p<0.0001), but not for pts with ≥ 4 sites (p=0.03). The incidence of CNS met was not significantly different between CRx-sensitive and CRx-resistant pts (p=0.2821). Conclusion: Prognostic factors predictive of high risk CNS met were identified that could be used to individualize Rx for MM pts. Supported in part by Chiron Corporation and Carol Courtney Memorial Fund. No significant financial relationships to disclose.
Phase III double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea during pelvic radiation therapy: Results of North Central Cancer Treatment Group protocol N00CA
Authors: Martenson J. A. , Sloan J. A. , Deming R. L. , Wender D. B. , Stien K. J. , Tai T. H. , Proulx G. M. , Zhu A. W. , Miller R. C. , Atherton P. J. 
Published: April 2020

8506 Background: A randomized study (Int J Rad Oncol Biol Phys 54:195–202, 2002) demonstrated a beneficial effect for octreotide in the treatment of diarrhea in patients receiving pelvic radiation therapy. This North Central Cancer Treatment Group study was undertaken to determine the effectiveness of depot octreotide in the prevention of diarrhea during pelvic radiation therapy. Methods: Patients receiving pelvic radiation therapy, with a planned minimum dose of 45 Gy at 1.70–2.1 Gy per day, were eligible for this study. The study was designed for a Wilcoxon test, with 112 evaluable patients, to have 85% power to detect a further one grade decrease in diarrhea over and above that experienced by patients treated with placebo. Between June 13, 2002 and October 28, 2005, 120 evaluable patients were randomly allocated, in double blind fashion, to receive octreotide (62 patients) or placebo (58 patients), prior to the fourth radiation therapy fraction. Octreotide dosing: Octreotide, 100 micrograms subcutaneously on day 1 followed by depot octreotide, 20 milligrams intramuscularly on days 2 and 29. Results: Grade 0, 1, 2 and 3 diarrhea was observed in 17%, 32%, 26% and 26% of patients treated with octreotide and 18%, 34%, 22%, and 26% of patients treated with placebo (P=0.86). Grade 0, 1, 2 and 3 tenesmus was observed in 55%, 30%, 11% and 4% of patients treated with octreotide and 76%, 16%, 4%, and 4% of patients treated with placebo (P=0.04). No other statistically significant differences in toxicity were observed. Conclusions: Octreotide, as administered in this study, did not decrease diarrhea during pelvic radiation therapy. [Table: see text]
Examining the dilemmas of prognostic information disclosure and understanding in those with terminal cancer: In-depth interviews with advanced cancer patients in phase I trials
Authors: Hlubocky F. J. , Daugherty C. K. 
Published: April 2020

8516 Background: Timely and accurate prognostic information is essential if patients are to make ethically appropriate medical decisions. Yet, prior research indicates advanced cancer patients (acp) with limited prognoses either misunderstand or fail to receive physician (md)-disclosed information regarding prognoses. Methods: Using semi-structured quantitative and qualitative interviews, acp were queried about prior discussions of prognosis (dop) with md and perceptions about treatment benefit. Results: To date, 87 (93%) acp receiving experimental (phase I) chemotherapy have been interviewed: median age 61 (33–82); 52% male; 80% Ca; 90% married; 58% >high school education. Quantitative interview data include: Likert scores (1–10) of likelihood of chemotherapy in: “stabilizing” cancer (mean 7.6); “halting” cancer (mean 7.1); producing “remission” (mean 6.9); and “curing” (mean 2.9). In response to a specific query, only 52% reported having dop with their md regarding life expectancy and 42% actually stated they initiated this dop. Although 45% denied any dop with md, a significant number of this group provided subsequent qualitative descriptions of dop within our interviews. As well, 61% described receiving specific quantitative estimates indicating a priori dop. When asked about their own thoughts on prognosis, only 4% described quantitative estimates or timeframes. Overwhelmingly so, patients were hopeful for a positive outcome or prolonged survival due to phase I trial participation. Several were currently deferring further dop. Conclusions: Despite prior data indicating that acp have a poor understanding of their prognoses, our findings indicate that at least 75% of interviewed acp recalled having had at least one specific dop and two-thirds describe having received a quantitative estimate of their prognosis. The majority of acp in phase I trials continue to have significant beliefs in the benefits of further therapy. No significant financial relationships to disclose.
What role do cancer patients want to play in treatment decision making: A pooled-analysis
Authors: Sloan J. A. , Huschka M. , Atherton P. , Degner L. F. , Hack T. , Smith T. , Rummans T. , Clark M. 
Published: April 2020

8521 Background: The extent of patient involvement in the decision making process for cancer treatment can impact satisfaction with care. A pooled-analysis of clinical studies from the US and Canada incorporating the Control Preferences Scale (CPS) was conducted to produce normalized data regarding patient preferences and examine differences in role preference related to country, tumor type, gender and other demographics. Methods: Patient data culled from six trials indicated the treatment decision making role preferred and the role actually experienced clinically. Fisher’s Exact Tests were performed to compare role distribution concordance and association with clinical and demographic variables. Results: Data available for 3,491 patients indicated that 25% preferred an active role, 46% a collaborative role, and 29% a passive role in their medical treatment decision making. In terms of actual experience, 30% of patients reported taking on an active role, 34% collaborative, and 36% passive. Overall, 61% of patients reported playing the role they prefer. Differences between genders in the preferred role were slight, but males achieved their preferred role more often than females (66% vs. 60%, p=0.011). More women actually took a passive role than men (40% vs. 24%, p<0.0001) as did more patients in the US than Canada (84% vs. 54%, p<0.001). Canadian patients preferred more passive than active roles (33% vs 22.4%) and US patients preferred more active to passive roles (31.9% vs 14.2%) (p<0.001). Older patients preferred a more passive role and took on that role. Differences in role preference across tumor types were negligible. Conclusions: Roughly one half of the cancer patients studied indicated that they preferred to have a collaborative relationship with physicians, the remaining patients split equally between an active and passive role. The US cohort seemed to want to be more assertive than their Canadian counterparts and women ended up playing a more passive role than they preferred. Given these gender and cross-county differences these findings highlight the need for individualized patient communication styles to be incorporated into treatment plans No significant financial relationships to disclose.
Physiological correlates of cancer-related fatigue in advanced non-small cell lung cancer (NSCLC) patients
Authors: Swanson T. , Dalzell M. A. , Small D. , MacDonald N. , Kreisman H. , St-Pierre D. 
Published: April 2020

8525 Background: Fatigue is a debilitating consequence of lung cancer and its treatments. The etiology of fatigue is unclear, and our current knowledge does not point to logical interventions. In this study, global fatigue score was assessed using the Brief Fatigue Inventory (BFI). A symptom questionnaire, as well as muscular and cardiorespiratory function, were assessed as potential contributors to the global fatigue score. Methods: Participants were evaluated by a physical therapist within the McGill Cancer Nutrition and Rehabilitation Program. Performance-based measures of physical function [upper limb strength and endurance (Jamar dynamometry), lower limb strength (30sec chair rise), cardiorespiratory function (2 minute walk -2MW)] and a symptom questionnaire [Edmonton Symptom Assessment Scale (ESAS)] were conducted at one point in time. Results: Eighty patients (43M:37F, mean age 68 ± 12 ) participated in the study. Forty-seven percent were actively receiving treatment at the time of assessment. On the BFI, 56% had moderate or severe fatigue and 88% indicated fatigue had interfered with their functioning during the past 24 hours. Global fatigue scores were unrelated to hand grip strength or endurance measurements but were significantly correlated with chair rise performance (R= -0.31, p<0.05), 2MW (R= -0.31, p<0.05), ESAS rating of pain (R=0.47, p<0.01), overall ESAS rating of breathlessness (R= 0.59, p<0.01), and ESAS rating of strength (R=0.58, p<0.01). Multivariate regression analysis suggested the best model for global fatigue scores incorporates chair rise performance, 2MW performance, ESAS rating of strength and ESAS rating of shortness of breath (adjusted R sq = 0.68, p<0.01). Conclusions: Fatigue is prevalent and impacts on the function of advanced NSCLC patients. Several key factors contribute to this fatigue, with muscular and cardiorespiratory restrictions playing an important role. Such findings may have clinical implications in the recommendations of rest and exercise to best manage fatigue. No significant financial relationships to disclose.
Comparison of baseline quality of life between minority and non-minority patients participating in oncology clinical trials
Authors: Tan A. D. , Novotny P. J. , Kaur J. S. , Buckner J. C. , Schaefer P. L. , Stella P. J. , Sloan J. A. 
Published: April 2020

8527 Background: Minority patients (MP) suffer deficits in access to care and socioeconomic status. This study uses a patient-level pooled analysis to explore whether these deficits translate into quality of life (QOL) differences between MP and non-MP on clinical trials. Method: Baseline QOL scores were combined from 47 clinical trials (6,513 patients) conducted either at the Mayo Clinic Cancer Center or in the North Central Cancer Treatment Group. QOL scales used were the Uniscale, Linear Analogue Self Assessment (LASA), Symptom Distress Scale (SDS), Profile of Mood States (POMS) and Functional Assessment of Cancer Therapy - General (Fact-G). Fisher’s Exact tests and linear regression adjusted for age, site, and performance score. Survival data was compared using the method of Kaplan-Meier. Results: Eight percent (531) of patients self-reported as MP (0.45% American Indian/Alaskan Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native Hawaiian and 0.3% Other). MP had no meaningful deficits in overall QOL or the SDS and were slightly worse on FACT-G total score, physical, social/family, functional, and SDS nausea severity. MP among lung cancer patients reported greater nausea (58 vs 69) and sleep problems (34 vs 54), with neurological cancers reported worse emotional well-being (53 vs 74), and with GI tumors had lower social/family well-being (60 vs 67). Regression models confirmed these results. Median survival time was shorter for MP (198 vs 310 days, p=0.001) but was not significant after adjusting for disease severity. Conclusions: MP on these clinical trials did not report large QOL deficits at baseline relative to non-MP. MP did indicate small deficits in physical, social, and emotional subscales. MP experienced large tumor-specific deficits for a few QOL domains that might bear further attention. [Table: see text] No significant financial relationships to disclose.