bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic values of lung resistance protein (LRP) and P53 in patients with multiple myeloma (MM)
Authors: Elsawy W. H. , Abdel Kader M. , Gharib A. F. , Elnemr M. M. , Eltarhony S. A. , Gendia A. Y. , Abdullah M. , Dorgham Y. T. 
Published: March 2020

8113 Background: This study was undertaken to assess the significance of lung-resistance related protein (LRP) expression and p53 mutations in plasma cells from untreated multiple myeloma (MM) patients and to determine whether LRP expression and p53 deletions was associated with a poor response and survival in patients treated with a conventional dose of melphalan. Methods: We have studied LRP expression by immunocytochemistry and p53 deletions by interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 in bone marrow plasma cells from 38 untreated patients with MM received conventional oral dose melphalan (0.25 mg/kg, day 1 to 4) combined with prednisone (MP). We also studied their association with both response to chemotherapy and survival of the patients. Results: By FISH, deletions of p53, were detected in 31.5% of patients and LRP was found positive in 36.8%. Patients with a p53 deletion were predominantly at stage III (p53 deletion in 83.4% of stage III patients vs. 8.3% of patients at stages I and II respectively; P = 0.04). Both p53 deletion and LRP expression were correlated with other laboratory and clinical parameters. The overall response rate of all of the evaluable patients was 63.2%. The response rate was 79.2% for patients without LRP expression but only 35.7% for patients with LRP expression (P = 0.01). Among the 12 patients with a p53 deletion by FISH, 25% responded compared with 75% of patients without p53 deletion (P = 0.001). With the exception of LRP expression and p53 deletions, there was no other prognostic variable sharing any correlation with response. The median survival of LRP-positive patients was 11 months (95%-Cl: 9 to 24), whereas the median survival duration of LRP negative patients was not reached (Cl: 26 to 82; P < .002; hazard ratio [HR] = 2.9 (1.4–5.7). Patients with and without p53 deletions had significantly different overall survival times (median 13.9 months, 95%-CI: 8 to 26 and median not reached, CI: 24 to84, respectively; P < .0001; hazard ratio [HR] = 2.6). Conclusions: For patients with MM who were treated with conventional-dose chemotherapy, LRP expression and p53 deletions provides prognostically relevant information in addition to that provided by standard prognostic factors. No significant financial relationships to disclose.
Quantitative bone ultrasonography at phalanges in patients with high-risk monoclonal gammopathy of unknown significance (MGUS) and myeloma treated with zoledronic acid
Authors: Iuliano F. , Guzzo I. , Deterlizi F. , Di Maio M. , Infusino S. , Perricelli A. , Pomillo A. , Molica S. , Baserga M. 
Published: March 2020

8115 Background: Bisphosphonates are commonly used for metastatic bone disease in order to prevent skeletal-related events, to reduce bone pain and to improve quality of life. Zoledronic acid is commonly used in myeloma patients (pts), but additional studies are needed to determine the optimal timing, schedule and duration of treatment. Aim of the present study is to assess bone mineral density (BMD) in patients with high-risk MGUS and myeloma receiving zoledronic acid, using quantitative ultrasound analysis in transmission through phalanges. Methods: DBM Sonic Bone Profiler is the only ultrasound device that applies the method of signal analysis in transmission through phalanges. This technique has proven to be particularly effective in the diagnosis and treatment monitoring of post-menopausal osteoporosis. Measurements of BMD were performed by ultrasonography at distal metaphysis of the first phalanx of the II, III, IV and V hand finger, at baseline and at 1, 3, 6, 9, 12, 15 and 18 months. Results: 12 pts with high-risk MGUS (8 IgG k, 4 IgG lambda) and 4 pts with myeloma IIIA (3 IgG k, 1 IgA lambda), 6 males/ 10 females, median age 69 years, received zoledronic acid 4 mg intravenously every 4 weeks for at least 12 courses. All subjects took daily oral supplements containing elemental calcium (1 g) and vitamin D (400 IU). Myeloma patients also received chemotherapy. 4/6 males (66%) and 5/10 females (50%) improved amplitude-dependent speed of sound (AD-SoS) over the least significant change after 6 months. Mean difference from baseline value of AD-SoS shows a trend after 4 months of treatment, and became significant after 16 months (p<0.005). Conclusions: Densitometric-structural evaluation of bone tissue at phalanges is safe and useful to evaluate bone quality changes during treatment with zoledronic acid, that determines a significant and sustained increase in ultrasonographic parameters of bone density and structure. No significant financial relationships to disclose.
A randomized phase III trial of 1 month versus 1 year adjuvant high-dose interferon alfa-2b in patients with resected high risk melanoma
Authors: Gogas H. , Dafni U. , Bafaloukos D. , Polyzos A. , Kokkalis G. , Kalofonos H. P. , Fountzilas G. , Skarlos D. , Tsoutsos D. , Pectasides D. 
Published: March 2020

8505 Background: High dose IFNa regimen as reported in E1684 was unique for the incorporation of an induction phase of maximally-tolerated dosages of IV therapy for the initial 4 weeks. This is the only trial that has shown prolongation of overall survival and disease-free survival in comparison to observation. Analysis of the hazard curves for DFS and OS in E1684 reveal early and durable separation of the high-dose and observation arms suggesting that the induction phase may represent a critical component of the high-dose regimen, although this has not been tested prospectively. Methods: We conducted a prospective randomized study of IV induction therapy vs a full year of high-dose IFN with primary endpoints of DFS and OS for stage IIB, IIC and III melanoma patients within 56 days of curative surgery. Patients were randomized to receive IFN alfa-2b 15×106 U/m2 IV × 5/7 days weekly × 4 weeks (arm A) versus the same regimen followed by 10×106 U(flat dose) SC 3 times a week for 48 weeks (arm B). The proposed treatment would be considered at least as good as the conventional treatment, if the relapse rate at 3 years from study entry is at most 15% higher in the former arm (power 85%, one-sided test a=0.05, required sample size: 340). Results: Between 1998 and 2004, 364 patients were enrolled (355 eligible: 178 arm A and 177 arm B). Patients′ and tumor characteristics were well balanced between the two arms. At a median follow up of 51 months (95% CI 46–55), the median DFS is 32 months vs 31 months (p=0.836) and the median OS is 61 months vs 63 months (p=0.444). Eleven patients discontinued treatment in arm A and 54 in arm B. The discontinuation rate is significantly higher in group B (p<0.001), possibly due to the longer duration. Reasons for discontinuation were disease progression (69%) and toxicity (19%). Patients in arm B had more grade 3–4 hematologic, constitutional and neurologic toxicity. Conclusions: There are no significant differences in OS and DFS between the regimen of 1 month and 1 year treatment tested. [Table: see text]
Role of ultrasound (US) and US-guided fine needle aspiration cytology (US-FNAC) prior to sentinel lymph node biopsy (SLNB) in 500 melanoma patients: Reduction of need for SNLB by high US-FNAC SN positive identification rate
Authors: Voit C. A. , van Akkooi A. C. , Schäfer-Hesterberg G. , Schoengen A. , Sterry W. , Eggermont A. M. 
Published: March 2020

8512 Background: SN status as the important prognostic factor reflects the likelihood of metastatic melanoma and the MSLT-1 trial showed similar 5ys-survival rates of ∼85% both in the SN-staged group and in the watch&wait group. SN-staging far outperforms PET-scanning, since PET is only reliable for detection of metastatic lesions > 125 mm3. SN-staging is an invasive procedure and better screening methods are required to identify early disease in SNs. This ongoing study examines the role of US to demonstrate SN metastasis thus avoiding surgical SN- staging in a proportion of melanoma pts. Methods: In this prospective study 503 consecutive melanoma pts. underwent scintigraphy and then US-exam prior to scheduled SLNB. When US was suspicious for malignant deposits in the SN, pts underwent a FNAC. So far we determined outcome in 400 AJCC staged pts (median Br 2.7 mm). Interim FU-data are updated until 10/06 (mean/median FU 26/24 (1 - 64) mo. For pts with a positive SN we considered the pre-SN US/US-FNAC pos. if either US and/or FNAC were positive. If both were only suspicious, it was considered negative. Results: US identified the SN in 52/80 (86%). Specificity was 99% (317/320) with a PPV of 95% and NPV of 92%. SN identification rate by FNAC increased from 40% in stage pT1a/b to 79% in stage pT4a/b according to the higher probability for nodal disease in higher pT stages (4% in pT1ab vs 57% in pT4ab). FNAC became more sensitive with increasing tu load: SN with deposits of 0.50–1.99 mm were verified in 13/25 (52%), whereas with deposits > 2 mm in 13/16 (83%). 80/400 SNs were histologically malignant with 15/80 (22%) submicroscopic involvement (<0.1 mm), an identical percentage as in the Rotterdam series (van Akkooi, Ann Oncol 2006). Of the node pos. pts, 50% (40/80) already found positive on US guided FNAC could have avoided undergoing a SLNB and proceeded straight to TLND. Histolog. patterns of involvement in 68 SNs were examined: 26/68 showed subcapsular, 6/68 parenchymal and 20/68 combined. Updated DFS and OS will be reported. Conclusions: US of the SN and US-guided FNAC is highly accurate. In this prospective study 50% of the SN positive pts could have been spared the need to undergo a SLNB. No significant financial relationships to disclose.
Prospective center-randomized trial of melanoma surveillance in 3,833 patients: An analysis of the early detection of recurrences
Authors: Garbe C. , Leiter U. M. , Weichenthal M. , Figl A. , Schadendorf D. , Hauschild A. 
Published: March 2020

8516 Prospective center-randomized trial of melanoma surveillance in 3,833 patients: An analysis of the early detection of recurrences Garbe C, Leiter U, Weichenthal M, Figl A, Schadendorf D and Hauschild A Background: A follow up strategy with reduced imaging techniques in melanoma = 1.0mm, performed at the department of dermatology in Tuebingen (arm A) was compared to the previous more extended follow up schedule at the departments of dermatology in Kiel and Mannheim (arm B), table 1 . Methods: Follow up examinations were evaluated in stage I-III melanoma patients for a time period of two years. The early detection of recurrences (size of metastasis = 2 cm in diameter, <10 metastases, R0 resection) was the primary endpoint of the study. Results: 2,577 (arm A) and 1,256 (arm B) patients were documented with 12,965 physical examinations, 7,610 blood tests and 10,599 examinations with imaging techniques. 211 patients (112 arm A, 99 arm B) presented with 452 recurrences (240 arm A, 212 arm B). Of these 55.4 % were classified as early detected (arm A 64.3%, arm B 45.5%). A reduction of clinical and technical examinations in stage I melanoma (= 1.0 mm) did not have an effect on the early detection of recurrences. Loco-regional recurrences were mainly detected by physical examinations and lymph node ultrasound and were discovered earlier in arm A (P=0.01). This may be attributed to lymph node ultrasound which is more frequently applied in melanoma >1.0mm and stage III patients. No difference was observed in the detection of distant metastases, where CT scans and S100 blood tests had the highest diagnostic impact. Conclusions: A reduction of physical and technical examinations in primary melanoma =1.0mm, application of lymph node ultrasound in melanoma > 1.0 mm and an intensified follow up program in stage III may be considered as appropriate follow-up strategy. No significant financial relationships to disclose. [Table: see text]
The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma
Authors: Weber J. S. , Hersh E. M. , Yellin M. , Nichol G. M. , Urba W. , Powderly J. D. , O’Day S. J. 
Published: March 2020

8523 Background: Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), enhances antitumor immune responses resulting in durable objective responses. In this study we examined the efficacy and safety of different ipilimumab preparations and regimens in patients with unresectable metastatic melanoma. Methods: In this study (MDX010–15), 34 patients received either 2.8 or 5 mg/kg transfectoma- or 3 mg/kg hybridoma-derived ipilimumab on days 1, 57 and 85. Additionally, 30 patients received single doses of 7.5 (6 pts), 10 (7 pts), 15 (6 pts) or 20 mg/kg (11 pts) transfectoma-derived ipilimumab. Once single doses up to 20 mg/kg were found to be well tolerated, 24 additional patients were given up to 4 doses of 10 mg/kg ipilimumab on days 1, 22, 43 and 64. Complete or partial responses (CR, PR), stable disease (SD) and adverse events (AEs) were monitored. Results: 1 CR, 3 PRs and 10 durable SDs were confirmed in 88 treated patients at the time of analysis. ORs were durable (∼29+, 34, 38+ and 39+ weeks [w]) and ongoing in 3 patients at study completion. PR in 1 patient was observed after ∼18.5w and developed to an ongoing CR at ∼51w. In another, SD for ∼16w preceded a ∼30w+ PR. Durable SD ranged from ∼21 to 79+w and is ongoing in 4 patients. Patients with OR or SD had immune-related AEs including rash, pruritis (G1/2), diarrhea (G1/2/3) or colitis (G2). AEs were severe in 27 patients, and considered ipilimumab-related (mostly G3/G4 colitis and diarrhea) in 9 (10% of all treated patients). Conclusions: Preliminary results suggest ipilimumab is generally safe and well tolerated. Late-onset ORs can occur, sometimes preceded by months of SD. ORs and SDs tend to be durable. Drug-related AEs of an immune nature are probably related to the biologic effects of ipilimumab, and are similar to those reported previously. No obvious dose relationship to AEs has been seen to date. [Table: see text]
A phase II study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion in patients with unresectable stage III or stage IV melanoma
Authors: Gonzalez R. , Lewis K. , Samlowski W. , Cranmer L. , Catlett J. , Kirkwood J. , Whitman E. , Lawson D. , Bartels P. , Drake T. 
Published: March 2020

8538 Background: In cell line studies, YM155 showed markedly potent antiproliferative activity against melanoma with 50% growth inhibition (GI50) values ranging from 0.35 nM to 910 nM. In melanoma tumor-bearing mouse xenograft models, YM155 showed significant antitumor activity including regression of tumors, at doses ranging from 1 to 10 mg/kg/day. Methods: Chemotherapy naive patients with unresectable Stage III or IV melanoma were eligible. The primary endpoint was tumor response defined by RECIST criteria. Secondary endpoints included progression-free survival and toxicity. A Simon's two stage minimax design was utilized with the first stage requiring 1 response (N=27) and a total of 2 responses required at the conclusion of stage II (N=29). Patients were considered evaluable if they completed 2 cycles. YM155 was given as a 168-hour (7-day) continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m2/day. Results: Enrollment is complete at 34 pts in order to reach 29 evaluable with treatment ongoing. Results are available for the first 26 pts. Median age was 59 y/o, (range 29 - 88) with ECOG PS of 0–1. There is one objective response of intrabdominal lymph nodes based on Investigator assessment at Cycle 2 confirmed at Cycle 4; another patient had a minor response (24% reduction) at Cycle 6 (currently at Cycle 8). Two subjects have shown stable disease after 6 cycles and remain on study. The median number of cycles is 3 (range 1 - 9). Two of 26 pts reported a grade 3 AE considered possibly related to YM155 (chest pain - nos and catheter related thrombosis). Nineteen of 26 pts have discontinued the study (18 PD, 1 withdrew consent). Conclusions: YM155 induced responses in 2 pts and was generally well tolerated. Given this encouraging response as a single agent, studies of YM155 combined with other agents are under consideration. [Table: see text]
Quality of life in patients with advanced melanoma receiving vaccine therapy alone (V) or vaccine with high-dose interleukin-2 (V-HIL2)
Authors: Marden S. F. , Muehlbauer P. , Soeken K. , Kline Leidy N. , Parchen D. , Schwartzentruber D. J. 
Published: March 2020

8549 Background: Melanoma is a public health concern with 1 in 75 Americans diagnosed during their lifetime and 5-year survival rate of about 10% for those with advanced melanoma. With curative options limited, new regimens must be evaluated and attention given to outcomes of how patients feel and function as a result of therapy. Methods: We examined the effect of biotherapy and fatigue on health-related quality of life (HRQL) in patients with stage IV melanoma enrolled in phase II clinical trials at the NCI receiving peptide vaccines with or without high dose IL-2. Generic HRQL was measured by physical (PCS) and mental (MCS) summary scores of the Short Form-36 health survey (SF-36). The Functional Assessment of Cancer Therapy-General (FACT-G) with a fatigue scale (FS) measured disease-specific HRQL and fatigue. Higher scores on measures indicate better physical, emotional, social function and well-being and less fatigue. Between 2000–2003, patients (F=22, M=47; mean age 46 ± 11) completed measures by computer at baseline (BL) and first follow-up after 2 cycles of treatment, before discussion of response to therapy. Data were analyzed using two-way ANCOVA with biotherapy (V or V-HIL2) and fatigue (worse (W) or improved/stable (I/S)) as factors and BL HRQL as covariate. A clinically important difference on FS is reported as 3 points. Fatigue levels with decrease of 3 from BL to follow-up were classified as W and <3 as I/S. Results: Patients were Caucasian (99%), married (77%), BL ECOG 0 or 1 (99%), mean BL Hgb 13 ± 2 and received 2 prior therapies (38%) or more (42%). Adjusting for BL HRQL, there was no biotherapy (p >.30) or interaction effect (p >.60; table ). There was a fatigue effect (p <.001) with lower HRQL adjusted mean scores in W versus I/S. Conclusions: HRQL does not differ in patients with advanced melanoma ECOG 0 or 1 who receive investigational V versus V-HIL2 at follow-up evaluation. Patients’ reporting of worsened fatigue is associated with poorer HRQL, regardless of the biotherapy received. [Table: see text] [Table: see text]
Pegylated liposomal doxorubicin plus paclitaxel as an individualized chemosensitivity-directed treatment in advanced metastatic melanoma
Authors: Ugurel S. , Neuber K. , Pfoehler C. , Mauch C. , Ulrich J. , Schadendorf D. 
Published: March 2020

8551 Background: Melanoma is a cutaneous neoplasm known for its high agressiveness and its poor prognosis once metastasized. Dacarbacine chemotherapy is actually considered standard first-line treatment of metastatic melanoma, with reported response rates of 6–7%. Due to this unsatisfactory situation, a number of non-standard anti-cancer drugs have been tested for improved efficacy. The present study was aimed to test doxorubicin plus paclitaxel in metastatic melanoma patients based on in-vitro chemosensitivity of this drug combination in fresh tumor samples. Methods: The primary study endpoint was objective response, secondary endpoints were safety and overall survival. Patients with histologically confirmed metastatic melanoma (AJCC stage IV), measurable tumor parameters, and an in-vitro chemosensitivity to doxorubicin plus paclitaxel which is superior to other test drugs determined by an ATP-based luminescence viability assay, were eligible. Patients received paclitaxel 175 mg/m2 i.v. followed by pegylated liposomal doxorubicin 30 mg/m2 i.v. at d1 every 28 days. Tumor assessment was performed every 8 weeks and evaluated according to RECIST. Treatment was continued at a tumor response of stable disease (SD) or better, and stopped in case of disease progression (PD) or intolerable side effects. Results: Out of 14 patients enrolled into this study, 12 received study treatment as first-line, and two as second-line therapy. Objective response was 14.3% (1 CR, 1 PR); progression arrest was 28.6% (1 CR, 1 PR, 2 SD). Median overall survival was 9.7 months. Common slight to moderate side effects were myelosuppression and neurotoxicity. Severe toxicities (CTC grade 3/4) were experienced by three patients (21.4%), with two of them presenting severe myelosuppression, and one experiencing myocardial infarction. Conclusions: Pegylated liposomal doxorubicin combined with paclitaxel shows significant efficacy in advanced metastatic melanoma if applied in an individualized, sensitivity- directed regimen. The observed side effects were comparable to other combination chemotherapies. This treatment regimen needs further evaluation in larger clinical trials containing standard therapy control groups. No significant financial relationships to disclose.
LDH is a prognostic factor in stage IV melanoma patients (pts) but is a predictive factor only for bcl2 antisense treatment efficacy: Re-analysis of GM301 and EORTC18951 randomized trials
Authors: Keilholz U. , Suciu S. , Bedikian A. Y. , Punt C. J. , Gore M. , Kruit W. , Pavlick A. C. , Spatz A. , Gilles E. , Eggermont A. M. 
Published: March 2020

8552 Background: Two large studies with identical eligibility criteria and using serum LDH as stratification for randomization were re-analyzed in order to 1) confirm the prognostic importance of LDH in advanced melanoma; 2) to assess whether an interaction between LDH and treatment efficacy exists. Methodology: Oblimersen (OBL) trial GM301 randomized 771 pts between DTIC vs. DTIC+OBL, whereas EORTC trial 18951 randomized 365 pts between biochemotherapy vs biochemotherapy+IL2 (JCO, 2004). LDH was divided into 5 groups: 5 UNL. Cox model was used to asses the prognostic importance of LDH, treatment difference and LDH-treatment interaction regarding the main endpoint, overall survival (OS). Results: In each study LDH appeared to be of strong and incremental prognostic importance (p<0.0001): the higher the LDH the shorter the OS. Median OS in pts with LDH<0.8 UNL was ±1 yr vs. 5 UNL. In both trials, pts with LDH 0.8–1.1 UNL had already a shorter median OS (± 9 months) as compared to the <0.8 group. In each study, overall, treatment differences were not significant. However, an interaction between LDH and treatment difference was observed in GM301 (p=0.01), but not in 18951 (p=0.51). In GM301, the largest benefit in favor of OBL was confined to the LDH <0.8 UNL subgroup (see table ), whereas in EORTC18951 the trend for an IL2 advantage was spread over several LDH groups. The observation was consistent also for response and PFS, and was not related to known confounding variables including metastatic disease site and PS. Conclusion: LDH is a biomarker with remarkable prognostic value for OS in advanced melanoma, and our analysis provides evidence for its prognostic value already below the UNL. Furthermore, OBL only had an effect in pts with low pretreatment LDH levels representing more favorable biology. No significant financial relationships to disclose. [Table: see text]