bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II trial of sequential temozolomide (TMZ) and high-dose bolus (HDB) IL-2 in patients with metastatic melanoma
Authors: Agarwala S. S. , Tarhini A. A. , Kirkwood J. M. , Cai C. , Stover L. , Moschos S. , Gooding W.
Published: April 2020

8037

Background: Previous biochemotherapy (BCT) regimens for metastatic melanoma have utilized lower doses of IL-2 and multiple chemotherapeutic agents, adding to toxicity, but not to efficacy. Methods: We designed a 2-stage Simon phase II study testing a unique BCT approach of single agent chemotherapy with TMZ given in an extended schedule (75 mg/m² per day for 3 weeks PO) followed by HDB IL-2 (600,000 U/Kg/dose, maximum 14 doses administered over 5 days). Cycles were repeated every 28 days with a two-week interval between alternate cycles. The first stage accrued 20 patients with promising activity and safety permitting enrollment of additional patients. Results: Thirty-one patients (20 male, 11 female), age 27–74 (median 47) have been enrolled to date. All had AJCC stage IV melanoma (7 M1a, 5 M1b, 19 M1c) and had not previously received therapy for metastatic disease. Twelve had received prior adjuvant interferon. A total of 88 cycles of therapy have been administered (median of 2 cycles per patient; 5 patients continue on therapy). The median number of doses was 9 (range 7–12) during cycle 1, and 6 (range 4–11) during cycle 2. Three patients did not receive any IL-2 due to disease progression, and 6 patients received only one cycle of IL-2. Twenty two patients who received at least 2 cycles are evaluable for response. All 31 patients are evaluable for toxicity. Grade 3 toxicities included hepatic (8), hematologic (4 leukopenia, 2 thrombocytopenia), diarrhea (1). No grade 3–4 cardiovascular or renal toxicities were noted. Overall response rate is 22.7% (2 complete lasting 10.8 and 17+ months, 3 partial lasting 3.7 and 16+ months, 1+ month). Responses were seen in both M1a and M1c disease. Fourteen patients had stable disease after 2 cycles and 10 of these have progressed. As of 12/31/2005, the 4 month PFS rate is 74% [40%, 88%], median TTP is 24 weeks [11, 32] and median OS is 71 weeks (31.4, inf). Conclusions: HDB IL-2 can be safely administered in combination with single agent temozolomide in an extended schedule and appears to have promising efficacy and lower toxicity than previously used BCT regimens. Further follow-up will determine if durability of response exceeds that of single agent HDB IL-2.

[Table: see text]
A phase II study of ABT-510 for the treatment of metastatic melanoma
Authors: Markovic S. , Suman V. , Rao R. , Creagan E. , Maples W. , Kaur J. , McWilliams R. , Allred J. , Pitot H. , Croghan G. , Humerickhouse R.
Published: April 2020

8041

Background: ABT-510 is a synthetic peptide analog of thrombospondin-1 demonstrating inhibition of VEGF/bFGF mediated human endothelial cell migration, proliferation, tube formation, cornea-neovascularization as well as inhibition of tumor growth in vivo (B16F10 melanoma). Having been found to be safe in phase I testing, ABT-510 has entered phase II trials. Presented are the results of a phase II study using ABT-510 for the treatment of stage IV melanoma. Methods: A two stage phase II clinical trial was conducted to assess the anti-tumor activity, safety profile and pharmacodynamics of ABT510 in patients with stage IV melanoma. Patients self-administered 100mg of ABT-510 subcutaneously twice/day. Therapy was continued in the absence of excessive toxicity or tumor progression. Primary endpoint was 18 week progression free survival rate. Enrolled were patients at least 18 years of age with measurable (RECIST) metastatic melanoma, ECOG performance status of 0–2 and normal pre-registration blood tests. Exclusion criteria included: cancer therapy less than 4 weeks prior to registration; failure to recover from prior therapy; brain metastases; significant recent bleeding; uncontrolled hypertension; and ongoing anti-coagulation. Pregnant or nursing women were not eligible. Results: Twenty-one patients (67% male) were enrolled with a median age of 55 years. Most patients had M1c disease (80%) and 62% had prior chemotherapy for stage IV melanoma. None of the patients were ineligible/canceled participation. After the first stage of the trial was complete, only 3 of the first 20 patients enrolled were progression-free at 18 weeks. Having not met the minimal clinical efficacy requirement (at least 7 of the first 20 patients progression-free at 18 weeks) the trial was closed to further accrual. Correlative laboratory studies suggested decreases in some of the measured parameters of angiogenesis (VEGFC, circulating endothelial cells) with no impact on immune homeostasis. Conclusions: Single agent ABT-510 therapy administered at 100mg twice/day to patients with previously treated metastatic melanoma did not demonstrate significant clinical efficacy. However, changes in measured parameters of angiogenesis suggest possible clinical efficacy with higher dosing or in combination with cytotoxic therapy.

[Table: see text]
Phase II trial of extended-dosing temozolomide in patients with melanoma
Authors: Rietschel P. , Ejadi S. , Wolchok J. , Krown S. , Gerst S. , Jungbluth A. A. , Busam K. , Smith K. , Panageas K. , Chapman P.
Published: April 2020

8042

Background: We previously reported a 30% response rate in metastatic melanoma (mel) patients (pts) treated with temozolomide (TMZ) using an extended dosing schedule of 6 weeks on/ 2 weeks off with either thalidomide or interferon. We hypothesized that these responses were largely due to TMZ alone and conducted a phase II trial using extended dosing TMZ alone. We also tested the hypothesis that a) mel expression of methylguanine methyltransferase (MGMT) would correlate with drug resistance, and b) TMZ would cause decreased CD4+ T cell function during the first cycle of therapy. Methods: A phase II trial stratified metastatic mel patients into two cohorts based on whether or not they had stage IV M1c. 25 patients/cohort are planned. No brain metastases or prior chemotherapy were allowed. Each cycle consisted of TMZ 75mg/m2/day for 6 weeks followed by 2 weeks with no treatment. Primary endpoint was the proportion of objective responses by RECIST criteria. The trial was powered to exclude the null hypothesis that the response rate in each cohort was ≤10%. MGMT promoter methylation status was assessed by methylation-specific PCR. MGMT tumor expression was measured by immunohistochemistry (IHC). CD4+ T cell function was assessed by measuring interferon-γ responses to CMV by intracellular cytokine FACS analysis (FastImmune, BD Biosciences) at pretreatment, week 4 and week 8 of cycle 1. Results: To date 19 evaluable pts, 8 in the M1c cohort, have progressed with no objective responses; 6 other patients are currently on study. 4/19 pts who have gone off study because of progression were stable for 6 months and received ≥3 cycles. To date, 14/15 tumors analyzed for MGMT promoter methylation were unmethylated (≤15%). Promoter methylation of 21% was seen in one tumor. Conclusions: The MGMT promoter of metastatic mel tumors are hypomethylated predicting expression of the enzyme. This is being assessed directly by IHC and will be correlated with promoter methylation and clinical response. The effect of TMZ on anti-CMV CD4+ T cell function is being assessed. Accrual is ongoing and will be completed in Spring 2006. The study was supported by Schering-Plough.

No significant financial relationships to disclose.
Phase II study of pegylated arginine deiminase (ADI-PEG20), a novel targeted therapy for melanoma
Authors: Feun L. G. , Savaraj N. , Marini A. , Wu C. , Robles C. , Herrera C. , Spector S. , Luedemann K. , Moffat F. , Bomalaski J.
Published: April 2020

8045

Background: Melanoma cells may be sensitive to arginine (Arg) deprivation due to lack of expression of argininosuccinate synthetase (ASS) which is needed to synthesize Arg, a nonessential amino acid in humans, from citrulline (Ctr). ADI-PEG20 lowers plasma Arg levels by catalyzing the conversion of Arg into Ctr. A phase I-II trial of ADI-PEG20 in metastatic melanoma (MM) showed intramuscular (i.m.) weekly doses of 160 IU/m² was well tolerated and resulted in responses in European patients (pts) (JCO 23:7660, 2005). Based on these encouraging results, we performed a phase 2 clinical and pharmacological study of ADI-PEG20 in USA pts with MM. Methods: Pts had weekly i.m. injection of ADI-PEG20 at a starting dose of 160 IU/m². Serum Arg levels were determined q 2 weeks. The dose of ADI-PEG20 was escalated up to 320 IU/m² weekly if Arg levels were still detectable. Tumor evaluation was done q 8 weeks. Tumor samples were assayed for ASS expression using immunohistochemical staining and/or PCR prior to start of therapy and at time of relapse. Results: 17 pts were treated and evaluable. Median age was 69 (range 29- 80). Median performance status was 90 (range 70- 100). Median number of metastatic sites was 2 (range 1- 8). 11 pts had stage M1c and 11 had prior chemotherapy and/or immunotherapy for advanced disease. Responses include partial response (PR) 4 pts (24 %), minor response 2(12 %), mixed response 2 (12%). Duration of PR from start of therapy was 4(+), 6(+), 12, and 16 months. Sites of response include soft tissue/nodal (3 pts) and lung (1 pt). Tumor tissue was available for ASS determination in 12 pts. ASS expression was associated with treatment failure and relapse. Conclusions: This work confirms that ADI-PEG20 appears to be active in MM. Side effects include minor discomfort at the injection site, slight fatigue, and mild elevation of serum uric acid consistent with tumor destruction. ASS expression may correlate with response. This study is continuing to accrue pts. ADI-PEG20 may be beneficial in MM.

No significant financial relationships to disclose.
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.
Persistance of residual vein thrombosis after an episode of deep vein thrombosis of the lower limbs and the risk of new cancer and cardiovascular disease
Authors: Fulfaro F. , Siragusa S. , Anastasio R. , Malato A. , Casuccio A. , Arcara C. , Badalamenti G. , Valerio M. , Abbene I. , Gebbia N.
Published: April 2020

8531

Background: In patients with a first episode of idiopathic or provoked Deep Vein Thrombosis (DVT), the presence of Residual Vein Thrombosis (RVT), detected by UltraSonography (US) at the 3rd month from the index DVT, is an independent risk factor for developing recurrent Venous Thromboembolism (VTE) in the subsequent 2 years. Its absence can safely permit to stop Oral Anticoagulants (OA). At the present, it is unknown whether RVT may also identify patients at increased risk for developing cancer and/or cardiovascular disease (CD). In patients with previous DVT of the lower limbs, we conducted a prospective study for evaluating the correlation between RVT findings and the risk of new cancer and/or CD. Methods: Three hundred-forty-five patients, with a previous episode of idiopathic or provoked DVT, were evaluated; presence/absence of RVT was detected at the 3rd month of OA and patients managed consequently. In the present study, the incidence of VTE recurrence, cancer and new CD was evaluated in the subsequent 3 years after the index DVT. The Kaplan-Meyer curve and the Breslow test has been used for the statistical comparison among groups. Results: The results among the 3 groups are listed in the Table. Patients without RVT had a significant reduction in recurrent VTE and new cancer in comparison to patients with RVT; they also showed a not significant trend in the reduction of CD; these data are applicable in patients with idiopathic or provoked index DVT. In patients with RVT, the advantage of prolonging anticoagulation over 12 months (Group A1) is lost at the end of the treatment. Conclusions: US-detected RVT, at 3rd month from the index DVT, is an independent risk factor for recurrent VTE and cancer; this risk remains over a period of 3 years, independently whether index DVT was idiopathic or provoked. In these patients, the advantage of indefinite anticoagulation should be assessed in properly designed study.

[Table: see text]

No significant financial relationships to disclose.
Continuous low-dose intravenous lidocaine is effective for visceral pain secondary to peritoneal carcinomatosis in terminal cancer patients
Authors: Tanaka T. , Okano S. , Tsukui R. , Tomaru M. , Ueno M. , Tsuchiya M. , Obokata K. , Saigo S. , Ogawa T. , Abe T. , Ikeya T.
Published: April 2020

8533

Background: Lidocaine, a local anesthetic, is often used as an anti-arrhythmic and as an analgesic of best support care (BSC) for patients with neuropathic pain. However, little is known about the effect of low-dose lidocaine on the abdominal pain of terminally-ill patients with peritoneal carcinomatosis. Aim: To evaluate whether visceral pain is controlled and activities of daily life (ADL) are improved during continuous lidocaine infusion. Methods: 28 terminally ill patients with peritoneal carcinomatosis due to the gastrointestinal (26) and gynecologic (2) cancers were studied. Despite aggressive pain management with opiates, non-steroidal anti-inflammatory drugs and other adjuvants, debilitating pain persisted. After a test dose of 2mg/kg intravenously, lidocaine was administered at low-doses (0.4 and/or 0.8mg/kg-h) through a vein and continued for more than 24 hours. Pain was quantitated on a faces rating scale from the level 0 (no pain) to 5 (severe pain); doses of opiates, amounts of oral intake, side effects, and ADL were measured before and after lidocaine. Results: Age (mean±SE) was 62±2, and percentage of males was 54%. Patients were not hypercalcemia but were slightly malnutrished (albumin 2.9±0.1g/dl) and anemic (hemoglobin 10.3±0.4g/dl). The duration of lidocaine administration in hospital was 18±3days. Abdominal symptoms improved within 1.2±0.1days after beginning lidocaine, and pain scale decreased from 2.7±0.2 to 0.6±0.2; p<0.001. In 68% of patients, the pain level became zero. Blood concentration of lidocaine at 0.8mg/kg-h was 3.0±0.4μg/ml 1 week later. 68% of patients needed no increase in opiate dosage during lidocaine administration. Waist size did not decrease, however, oral intake increased (p=0.002) during lidocaine administration. No obvious side effects, such as perioral numbness, were seen except for emotional lability noted in 4 patients. 43% patients were able to be discharged for continued end-of-life comfort care with home parenteral nutrition and continuation of lidocaine administration. Conclusions: We suggest that continuous, low-dose intravenous lidocaine is BSC and is a very effective approach for analgesia and improvement of ADL in patients with peritoneal carcinomatosis.

No significant financial relationships to disclose.
SNPs associated with the genetic predisposition to develop therapy-related acute myelogenous leukemia after chemotherapy for breast cancer
Authors: Guillem V. , Mata M. , Lluch A. , Gonzalez M. , Esteve J. , Nomdedeu J. , Calasanz M. , Cervantes A. , Chirivella I. , Tormo M.
Published: April 2020

8536

Background: t-AML is a syndrome occurring after exposure to chemo or radiotherapy. Since for similar treatments only some patients ends developing a secondary leukemia, it has been proposed a genetic predisposition associated to this syndrome. Methods: To analyse single nucleotide polymorphisms (SNPs) on genes that could be involved on risk of developing t-AML by means of RFLP and SNP genome screening using high density microarrays .Two groups of individuals were genotyped: Group A, composed by patients that develop t-AML after chemotherapy for breast cancer (BC) and Group B (control), formed by chemotherapy treated BC patients that after a period of more than 10 years have not developed t-AML. We have studied 12 polymorphisms on genes from drug detoxification pathways (NOQ1, GSTP1), DNA repair (XPC[3 ], XRCC1[2 ], NBS1, ERCC5 and XRCC3) and DNA synthesis (MTHFR[2 ]), in which the nucleotide change implies a change in the protein sequence (nA=16, nB=18) . Alternatively, for each patient, more than 10.000 SNPs were genotyped by means of of high density microarrays (Affymetrix) (nA=12, nB=18). The alele frequencies for each SNP between two groups were compared. Results: In RFLP study, we observe two SNPs on MTHFR gene displaying remarkably different allele frequencies between BC patients (Table). In microarray study, we found 12 SNPs with differences of allele frequency higher that 45% between A and B groups, located 6 on chromosome 8. Conclusions: The results suggest that the MHFTR gene is a candidate for being studied by its possible relation with the genetic predisposition to develop t-AML after BC treatment although its functional implication with the disease must still be elucidated. Moreover, data from SNP arrays suggest that the genome regions marked by those 12 SNPs, specially those on chromosome 8, are candidate for being studied by its possible relation with the genetic predisposition to develop t-AML after BC treatment. Financed by FIS G03/008.

[Table: see text]

No significant financial relationships to disclose.
A pilot study of the Vulnerable Elders Survey-13 (VES-13) as compared to Comprehensive Geriatric Assessment (CGA) to examine geriatric domains in older prostate cancer patients at risk for decline
Authors: Mohile S. G. , Bylow K. , Stadler W. M. , Rodin M.
Published: April 2020

8539

Background: Impairments in geriatric domains (e.g. function and cognition) adversely affect health outcomes of the elderly. CGA is a key component of the treatment approach for older cancer pts, but is time-consuming. We evaluated the reliability and validity of a brief functionally-based screening tool, the VES-13, in identifying those older prostate cancer (PCa) pts at risk for impairment in the oncology clinic setting. Methods: PCa pts aged ≥ 70 yrs treated with androgen ablation followed within the oncology clinics at the University of Chicago were eligible. Pts self-completed VES-13 and CGA at baseline with VES-13 repeated 1 mth later. Physical performance and cognitive assessments were administered by a research assistant. Pts with impairment were offered follow-up in a “standard of care” frail geriatric elders program. Results: Of 36 participating pts, 50% were impaired by VES-13 (score ≥ 3). 62% of pts scored as impaired on ≥ 2 tests within the CGA exhibiting deficits in multiple geriatric domains. The reliability of the VES-13 (comparing baseline to 1 mth scores) was 0.92 (pearsons correlation coefficient). The cut-off point of 3 on the VES-13 had 72.7% sensitivity and 85.7% specificity and was highly predictive in identifying impairment (ROC AUC 0.8977) when compared to the CGA. Pts with a mean score of VES-13 ≥ 3 performed significantly worse on evaluations of Instrumental Activities of Daily Living (measures ability to live independently) (p=.006), physical performance (p=.024), comorbidity (p<.001), numbers of medications (p=.022), and cognition (p=.018). In multivariate analysis, low education remained significant for VES-13 impairment after adjustment for age (p=.039). 50% of pts accepted referral to an off-site multidisciplinary geriatrics clinic. Reasons for refusal included perceived lack of need by the pt and transportation difficulties. Conclusions: Older PCa pts receiving androgen ablation have significant geriatric impairment. The VES-13 screening measure was predictive in identifying impairment when compared to the CGA and demonstrates feasibility for use in the oncology clinic setting.

No significant financial relationships to disclose.
Management and survival of frail elderly cancer patients within a Geriatric Oncology Program
Authors: Basso U. , Vamvakas L. , Falci C. , Lamberti E. , Pasetto L. M. , Brunello A. , Tonti S. , Lonardi S. , Vigorelli S. , Monfardini S.
Published: April 2020

8547

Background: Abstention from administration of either chemo- or endocrine therapy to elderly cancer patients deemed frail at the Multidimensional Geriatric Assessment is still controversial, and few data are available concerning the actual survival of such patients. Methods: To evaluate the management and survival of all consecutive frail cancer patients older than 70 years, seen from October 2004 to December 2005 within our Geriatric Oncology Program. Frailty was defined by one or more of the following: age ≥ 85 years, dependence in one or more Activity of Daily Living (ADL), presence of at least three comorbidity of grade 3 or one of grade 4 according to CIRS-G, one or more geriatric syndromes [Balducci L, Cancer Control 2001]. Results: A total of 364 elderly patients were divided into three categories: fit (26.4%), vulnerable (49.5%) and frail patients (24.2%). These 88 frail patients had a median age of 79 years (range, 70–93), 43.2% males. Motives for being considered frail were age alone (13.6% of patients), ADL dependence (25%), comorbidity (14.8%), geriatric syndromes (6.8%) or, more frequently, the co-existence of two or more of these factors (39.8%). Thirty patients (34.1%) underwent chemotherapy: 8 for gastro-intestinal tumors, 7 lung, 7 hematological and 8 other sites. Patients received standard regimens at standard doses (27.6%) or with ≥ 25% dose reduction (24.1%), age-adapted regimens at standard doses (44.8%) or with reduced doses (6.9%). Six patients (20%) derived some clinical benefit but only two (6.7%) showed radiological response. Twenty-two patients interrupted chemotherapy prematurely due to toxicity/death (23.3%) or refusal/drop out (26.7%). All twenty-eight women with estrogen receptor positive breast cancer (31.9% of all frail patients) were prescribed endocrine therapy either adjuvantly, neo-adjuvantly or for metastatic disease, with a predominance of aromatase inhibitors (82.1%) compared to tamoxifen. Thirty out of 88 patients have died, with a 2-year overall survival of 35%. Conclusions: Frailty was observed in one fourth of all our elderly patients, but it did not prevent treatment of tumor with either chemo- or endocrine therapy in 66% of cases. Overall survival of frail elderly patients with cancer appears worse than in geriatric series.

No significant financial relationships to disclose.
Impact on the cosmetic outcome of concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery: Differences between patient’s and doctor’s views
Authors: Toledano A. , Garaud P. , Serin D. , Fourquet A. , Bosset J. , Breteau N. , Body G. , Azria D. , Suzanne I. , Calais G.
Published: April 2020

8554

Purpose: A multicenter randomized study comparing after breast-conservative surgery, sequential versus concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEI). After a median follow-up of 6.7 (4.3–9) years, we assessed prospectively late effects and cosmesis satisfaction of these two strategies. Methods and material: After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with the same normofractinnated breast RT (arm B).With structured questions, 214 patients (107 in each arm) rated their satisfaction considering cosmesis, the difference in overall appearance, and specific changes of the breast. Late toxicity (LENT/SOMA scale) and cosmesis were blinded to treatment and assessed by a radiation oncologist by a qualitative scale and another semi-qualitative and semi-quantitative evaluation. Results: Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Patient’s cosmesis satisfaction was not statistically different between the two arms with 92.6% of good results in arm A and 86% in arm B (p=0.72); although patients have found more important differences in the treated breast in arm B than in arm A, with 28.8% vs 14.3% of bad results, respectively. Physician’s prospective assessment found less favorable cosmesis results with concomitant treatment than with sequential one, with 40% and 15% of unsatisfaction, respectively (p=0.0014) using a semi-quantitative and qualitative scale; The use of a subjective 5-point scale found also a worse physician’s cosmesis satisfaction in arm B than in arm A (p=0.0013) Conclusion: The concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects. Rating of cosmesis is also subjective. Patients’ satisfaction with cosmesis is greater than the doctors’ for concomitant radiochemotherapy in breast cancer, and is not only determined by radiation late effects. With two methods, physician found a worse cosmesis outcome for concomitant radiochemotherapeutic arm.

No significant financial relationships to disclose.