10 results on '"Haas RL"'
Search Results
2. Hypofractionated Preoperative Radiation Should Not Yet Be Used as Standard of Care for Extremity and Truncal Soft Tissue Sarcoma.
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Baldini EH, Guadagnolo BA, Salerno KE, Chung P, Bishop AJ, Kalbasi A, Miah A, Bedi M, Harris JP, Petersen I, Gillham C, Wiltink LM, Alektiar KM, Haas RL, and Kirsch DG
- Abstract
Hypofractionated radiation therapy regimens should not be used as standard of care for localized soft tissue sarcoma.
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- 2024
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3. Interleukin-6 in relation to early recurrence in primary, localized soft tissue sarcoma: An addition for existing risk classification systems?
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van der Laan P, van der Graaf WTA, van den Broek D, van Boven H, Heeres BC, Schrage Y, Haas RL, Steeghs N, and van Houdt WJ
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- Humans, Female, Male, Middle Aged, Retrospective Studies, Aged, Adult, Neoplasm Grading, Neutrophils pathology, Prognosis, Necrosis, Risk Assessment, Tumor Burden, Aged, 80 and over, Biomarkers, Tumor blood, Soft Tissue Neoplasms pathology, Soft Tissue Neoplasms blood, Lymphocytes pathology, Interleukin-6 blood, Sarcoma pathology, Sarcoma blood, Neoplasm Recurrence, Local blood, Neoplasm Recurrence, Local pathology, C-Reactive Protein metabolism
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Background: Several inflammatory markers have gained interest as prognostic factors for cancer. The aim of this study is to evaluate the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as predictive markers for aggressive behavior and early recurrences in primary, localized soft tissue sarcoma (STS)., Methods: 115 STS patients were retrospectively reviewed. IL-6 and CRP blood levels, NLR and PLR were obtained prior to treatment. Early recurrence was defined as disease relapse (local or distant) within the first year after surgery. Cox regression analysis was used to identify prognostic factors for early recurrence., Results: IL-6 elevation was associated with a higher tumor grade, increased size, tumor necrosis and a higher mitotic count. NLR elevation was associated with a higher tumor grade, PLR elevation with a larger tumor size. Early recurrences were found in 24 patients (21 %). Univariable analysis revealed that tumor grade (p = 0.029), tumor size (p = 0.030, >10 cm vs < 5 cm), tumor depth (p = 0.036), necrosis on imaging (p = 0.008), mitotic count (p = 0.045, ≥20 mitoses vs 0-9 mitoses), and IL-6 level (p = 0.044) were associated with early recurrence. The factors age at diagnosis, tumor location, necrosis at pathology, (neo)adjuvant radio- or chemotherapy, resection margin, CRP level, NLR and PLR were not related to early disease recurrence., Conclusions: Increased inflammatory markers in STS are associated with an aggressive phenotype. STS patients with elevation of IL-6 may be at risk for early disease recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
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- 2024
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4. Current Management of Desmoid Tumors: A Review.
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Kasper B, Baldini EH, Bonvalot S, Callegaro D, Cardona K, Colombo C, Corradini N, Crago AM, Dei Tos AP, Dileo P, Elnekave E, Erinjeri JP, Navid F, Farma JM, Ferrari A, Fiore M, Gladdy RA, Gounder M, Haas RL, Husson O, Kurtz JE, Lazar AJ, Orbach D, Penel N, Ratan R, Raut CP, Roland CL, Schut AW, Sparber-Sauer M, Strauss DC, Van der Graaf WTA, Vitellaro M, Weiss AR, and Gronchi A
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- Humans, Fibromatosis, Aggressive therapy, Fibromatosis, Aggressive pathology, Fibromatosis, Aggressive drug therapy
- Abstract
Importance: Desmoid tumor (DT) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Previously, surgery was the standard primary treatment modality; however, within the past decade, a paradigm shift toward less-invasive management has been introduced and an effort to harmonize the strategy among clinicians has been made. To update the 2020 global evidence-based consensus guideline on the management of patients with DT, the Desmoid Tumor Working Group convened a 1-day consensus meeting in Milan, Italy, on June 30, 2023, under the auspices of the European Reference Network on Rare Adult Solid Cancers and Sarcoma Patient Advocacy Global Network, the Desmoid Foundation Italy, and the Desmoid Tumor Research Foundation. The meeting brought together over 90 adult and pediatric sarcoma experts from different disciplines as well as patients and patient advocates from around the world., Observations: The 2023 update of the global evidence-based consensus guideline focused on the positioning of local therapies alongside surgery and radiotherapy in the treatment algorithm as well as the positioning of the newest class of medical agents, such as γ-secretase inhibitors. Literature searches of MEDLINE and Embase databases were performed for English-language randomized clinical trials (RCTs) of systemic therapies to obtain data to support the consensus recommendations. Of the 18 full-text articles retrieved, only 4 articles met the inclusion criteria. The 2023 consensus guideline is informed by a number of new aspects, including data for local ablative therapies such as cryotherapy; other indications for surgery; and the γ-secretase inhibitor nirogacestat, the first representative of the newest class of medical agents and first approved drug for DT. Management of DT is complex and should be carried out exclusively in designated DT referral centers equipped with a multidisciplinary tumor board. Selection of the appropriate strategy should consider DT-related symptoms, associated risks, tumor location, disease morbidities, available treatment options, and preferences of individual patients., Conclusions and Relevance: The therapeutic armamentarium of DT therapy is continually expanding. It is imperative to carefully select the management strategy for each patient with DT to optimize tumor control and enhance quality of life.
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- 2024
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5. Improving Diagnosis and Care for Patients With Sarcoma: Do Real-World General Practitioners Data and Prospective Data Collections Have a Place Next to Clinical Trials?
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Holthuis EI, Heins MJ, van Houdt WJ, Haas RL, Overbeek JA, Olde Hartman TC, Uijen AA, Wee L, van der Graaf WTA, and Husson O
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- Humans, Data Collection methods, Clinical Trials as Topic, Prospective Studies, Sarcoma therapy, Sarcoma diagnosis, Electronic Health Records, General Practitioners
- Abstract
There has been growing interest in the use of real-world data (RWD) to address clinically and policy-relevant (research) questions that cannot be answered with data from randomized controlled trials (RCTs) alone. This is, for example, the case in rare malignancies such as sarcomas as limited patient numbers pose challenges in conducting RCTs within feasible timeliness, a manageable number of collaborators, and statistical power. This narrative review explores the potential of RWD to generate real-world evidence (RWE) in sarcoma research, elucidating its application across different phases of the patient journey, from prediagnosis to the follow-up/survivorship phase. For instance, examining electronic health records (EHRs) from general practitioners (GPs) enables the exploration of consultation frequency and presenting symptoms in primary care before a sarcoma diagnosis. In addition, alternative study designs that integrate RWD with well-designed observational RCTs may offer relevant information on the effectiveness of clinical treatments. As, especially in cases of ultrarare sarcomas, it can be an extreme challenge to perform well-powered randomized prospective studies. Therefore, it is crucial to support the adaptation of novel study designs. Regarding the follow-up/survivorship phase, examining EHR from primary and secondary care can provide valuable insights into identifying the short- and long-term effects of treatment over an extended follow-up period. The utilization of RWD also comes with several challenges, including issues related to data quality and privacy, as described in this study. Notwithstanding these challenges, this study underscores the potential of RWD to bridge, at least partially, gaps between evidence and practice and holds promise in contributing to the improvement of sarcoma care.
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- 2024
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6. Patient-reported outcomes in randomized clinical trials of systemic therapy for advanced soft tissue sarcomas in adults: A systematic review.
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Roets E, van der Graaf W, van Riet BHG, Haas RL, Younger E, Sparano F, Wilson R, van der Mierden S, Steeghs N, Efficace F, and Husson O
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- Adult, Humans, Patient Reported Outcome Measures, Randomized Controlled Trials as Topic, Sarcoma drug therapy, Sarcoma therapy
- Abstract
Background: This systematic review evaluates reporting of patient-reported outcomes (PROs) within randomized clinical trials (RCTs) for advanced soft tissue sarcoma (STS) patients., Methods: A systematic literature search from January 2000 - August 2022 was conducted for phase II/III RCTs evaluating systemic treatments in adult patients with advanced STS. Quality of PRO reporting was assessed using the CONSORT PRO extension., Results: Out of 7294 abstracts, 59 articles were included; comprising 43 RCTs. Only 15 RCTs (35%) included PROs, none as primary endpoints. Only 10 of these RCTs reported PROs, either in the primary (6/10) or secondary publication (1/10) or in both (3/10), with a median time interval of 23 months. The median CONSORT PRO adherence score was 5.5/14, with higher scores in publications focusing exclusively on PROs., Conclusion: These results highlight the need for improved and more consistent PRO reporting to inform patient care in the setting of advanced STS., Competing Interests: Declaration of Competing Interest F. Efficace had a consultancy or advisory role for AbbVie, Incyte, Syros, Novartis and JAZZ Pharmaceuticals, outside the submitted work. W. van der Graaf: Advisory boards SpringworkTx, Agenus and PTC Therapeutics (all to the institute) and research grants from Eli Lilly (to the Institute). N. Steeghs: N. Steeghs provided consultation or attended advisory boards for Boehringer Ingelheim, Ellipses Pharma. N Steeghs received research grants for the institute from AB Science, Abbvie, Actuate Therapeutics, ADCtherapeutics, Amgen, Array, Ascendis Pharma, Astex, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio, Bristol-Myers Squibb, Cantargia, Celgene, CellCentric, Cresecendo, Cytovation, Deciphera, Eli Lilly, Exelixis, Genentech, Genmab, Gilead, GlaxoSmithKline, Incyte, InteRNA, Janssen/Johnson&Johnson, Kinate, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Novartis, Numab, Pfizer, Pierre Fabre, Regeneron, Roche, Sanofi, Seattle Genetics, Servier, Taiho, Takeda (outside the submitted work). All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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7. New Sarculator Prognostic Nomograms for Patients With Primary Retroperitoneal Sarcoma: Case Volume Does Matter.
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Callegaro D, Barretta F, Raut CP, Johnston W, Strauss DC, Honoré C, Bonvalot S, Fairweather M, Rutkowski P, van Houdt WJ, Gladdy RA, Tirotta F, Tzanis D, Skoczylas J, Haas RL, Miceli R, Swallow CJ, and Gronchi A
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- Adult, Humans, Prognosis, Nomograms, Disease-Free Survival, Sarcoma diagnosis, Sarcoma surgery, Retroperitoneal Neoplasms diagnosis, Retroperitoneal Neoplasms surgery, Soft Tissue Neoplasms
- Abstract
Objective: To update the current Sarculator retroperitoneal sarcoma (RPS) prognostic nomograms considering the improvement in patient prognosis and the case volume effect., Background: Survival of patients with primary RPS has been increasing over time, and the volume-outcome relationship has been well recognized. Nevertheless, the specific impact on prognostic nomograms is unknown., Methods: All consecutive adult patients with primary localized RPS treated at 8 European and North American sarcoma reference centers between 2010 and 2017 were included. Patients were divided into 2 groups: high-volume centers (HVC, ≥13 cases/year) and low-volume centers (LVC, <13 cases/year). Primary end points were overall survival (OS) and disease-free survival (DFS). Multivariable analyses for OS and DFS were performed. The nomograms were updated by recalibration. Nomograms performance was assessed in terms of discrimination (Harrell C index) and calibration (calibration plot)., Results: The HVC and LVC groups comprised 857 and 244 patients, respectively. The median annual primary RPS case volume (interquartile range) was 24.0 in HVC (15.0-41.3) and 9.0 in LVC (1.8-10.3). Five-year OS was 71.4% (95% CI: 68.3%-74.7%) in the HVC cohort and 63.3% (56.8%-70.5%) in the LVC cohort ( P =0.012). Case volume was associated with both OS (LVC vs. HVC hazard ratio 1.40, 95% CI: 1.08-1.82, P =0.011) and DFS (hazard ratio 1.93, 95% CI: 1.57-2.37, P <0.001) at multivariable analyses. When applied to the study cohorts, the Sarculator nomograms showed good discrimination (Harrell C index between 0.68 and 0.73). The recalibrated nomograms showed good calibration in the HVC group, whereas the original nomograms showed good calibration in the LVC group., Conclusions: New nomograms for patients with primary RPS treated with surgery at high-volume versus low-volume sarcoma reference centers are available in the Sarculator app., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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8. Propranolol monotherapy in angiosarcoma - A window-of-opportunity study (PropAngio).
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Embaby A, Heinhuis KM, IJzerman NS, Koenen AM, van der Kleij S, Hofland I, van Boven H, Sanders J, van der Graaf WTA, Haas RL, Huitema ADR, van Houdt WJ, and Steeghs N
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- Humans, Positron Emission Tomography Computed Tomography, Endothelial Cells, Adrenergic beta-Antagonists therapeutic use, Propranolol therapeutic use, Hemangiosarcoma drug therapy
- Abstract
Background: Angiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment., Methods: Propranolol was dosed 80 mg to 240 mg/day for 3 to 6 weeks according to a dose titration schedule. The primary endpoint was clinical response (response according to RECIST 1.1 or stable disease with improvement of cutaneous lesions) in at least three patients. Exploratory objectives included histologic response (>30% decrease in Ki-67), FDG PET response, and β-receptor expression levels., Results: Fourteen patients were enrolled. The median duration of treatment was 26 days (range 21-42 days). The median highest propranolol dose was 160 mg/day (range 80 - 240 mg). Two patients showed clinical response (14%, 95% CI 3-100%). One of these patients showed a partial metabolic response on PET-CT. None of the tumors showed histologic response. The most common adverse event was grade 1/2 bradycardia (86%). There were no grade ≥ 3 adverse events. ADRB2 was overexpressed in 16 out of 18 tumors, in both responders and non-responders. None of the tumors showed ADRB1 overexpression., Conclusions: This window-of-opportunity trial did not show clinical efficacy of propranolol monotherapy. However, two out of 14 patients did show clinical benefit. ADRB1/2 expression did not correlate with clinical response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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9. Update on Dosing and Fractionation for Neoadjuvant Radiotherapy for Localized Soft Tissue Sarcoma.
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Roohani S, Wiltink LM, Kaul D, Spałek MJ, and Haas RL
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- Humans, Neoadjuvant Therapy, Prospective Studies, Radiotherapy, Adjuvant, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Sarcoma diagnosis, Sarcoma radiotherapy, Sarcoma pathology, Liposarcoma, Myxoid
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Opinion Statement: Neoadjuvant radiotherapy (RT) over 5-6 weeks with daily doses of 1.8-2.0 Gy to a total dose of 50-50.4 Gy is standard of care for localized high-grade soft tissue sarcomas (STS) of the extremities and trunk wall. One exception is myxoid liposarcomas where the phase II DOREMY trial applying a preoperative dose of 36 Gy in 2 Gy fractions (3-4 weeks treatment) has achieved excellent local control rates of 100% after a median follow-up of 25 months.Hypofractionated preoperative RT has been investigated in a number of phase II single-arm studies suggesting that daily doses of 2.75-8 Gy over 1-3 weeks can achieve similar oncological outcomes to conventional neoadjuvant RT. Prospective data with direct head-to-head comparison to conventional neoadjuvant RT investigating oncological outcomes and toxicity profiles is eagerly awaited.For the entire group of retroperitoneal sarcomas, RT is not the standard of care. The randomized multi-center STRASS trial did not find a benefit in abdominal recurrence-free survival by the addition of preoperative RT. However, for the largest histological subgroup of well-differentiated and grades I and II dedifferentiated liposarcomas, the STRASS trial and the post-hoc propensity-matched STREXIT analysis have identified a possible benefit in survival by preoperative RT. These patients deserve to be informed about the pros and cons of preoperative RT while the longer follow-up data from the STRASS trial is awaited., (© 2024. The Author(s).)
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- 2024
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10. Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study.
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Kruiswijk AA, van de Sande MAJ, Verhoef C, Schrage YM, Haas RL, Bemelmans MHA, van Ginkel RJ, Bonenkamp JJ, Witkamp AJ, van den Akker-van Marle ME, Marang-van de Mheen PJ, and van Bodegom-Vos L
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Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18-65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS., Methods: HRQoL of participants from the VALUE-PERSARC trial ( n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L., Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed., Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.
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- 2024
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