78 results on '"Schrage Y"'
Search Results
2. Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer – an EYSAC international survey
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Smith, H.G., Schlesinger, N.H., Qvortrup, C., Chiranth, D., Lundon, D., Ben-Yaacov, A., Caballero, C., Suppan, I., Kok, J. Herrera, Holmberg, C.J., Mohan, H., Montagna, G., Santrac, N., Sayyed, R., Schrage, Y., Sgarbura, O., Ceelen, W., Lorenzon, L., and Brandl, A.
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- 2023
- Full Text
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3. Sarcomen en andere wekedelentumoren
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van Houdt, W. J., Schrage, Y. M., Heineman, E., editor, Heineman, D.J., editor, Lange jr., J.F.M., editor, Blankensteijn, J.D., editor, Boermeester, M.A., editor, Borel Rinkes, I.H.M., editor, Klaase, J.M., editor, Schipper, I.B., editor, Schreurs, W.H., editor, and Wijnen, R.M.H., editor
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- 2021
- Full Text
- View/download PDF
4. 46P The pre-diagnostic general practitioner care of sarcoma patients: A real-world data study
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Holthuis, E., primary, van der Graaf, W.T.A., additional, Drabbe, C., additional, van Houdt, W., additional, Schrage, Y., additional, Koenen, A.M., additional, van der Kleij, S., additional, Hartman, T. Olde, additional, Uijen, A., additional, Bos, I., additional, Heins, M., additional, and Husson, O., additional
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- 2024
- Full Text
- View/download PDF
5. Extrameningeal solitary fibrous tumors—surgery alone or surgery plus perioperative radiotherapy: A retrospective study from the global solitary fibrous tumor initiative in collaboration with the Sarcoma Patients EuroNet
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Haas, R, Walraven, I, Lecointe-Artzner, E, van Houdt, W, Strauss, D, Schrage, Y, Hayes, A, Raut, C, Fairweather, M, Baldini, E, Gronchi, A, De Rosa, L, Griffin, A, Ferguson, P, Wunder, J, van de Sande, M, Krol, A, Skoczylas, J, Sangalli, C, Stacchiotti, S, Haas R. L., Walraven I., Lecointe-Artzner E., van Houdt W. J., Strauss D., Schrage Y., Hayes A. J., Raut C. P., Fairweather M., Baldini E. H., Gronchi A., De Rosa L., Griffin A. M., Ferguson P. C., Wunder J., van de Sande M. A. J., Krol A. D. G., Skoczylas J., Sangalli C., Stacchiotti S., Haas, R, Walraven, I, Lecointe-Artzner, E, van Houdt, W, Strauss, D, Schrage, Y, Hayes, A, Raut, C, Fairweather, M, Baldini, E, Gronchi, A, De Rosa, L, Griffin, A, Ferguson, P, Wunder, J, van de Sande, M, Krol, A, Skoczylas, J, Sangalli, C, Stacchiotti, S, Haas R. L., Walraven I., Lecointe-Artzner E., van Houdt W. J., Strauss D., Schrage Y., Hayes A. J., Raut C. P., Fairweather M., Baldini E. H., Gronchi A., De Rosa L., Griffin A. M., Ferguson P. C., Wunder J., van de Sande M. A. J., Krol A. D. G., Skoczylas J., Sangalli C., and Stacchiotti S.
- Abstract
Background: Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. Methods: This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. Results: Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow-up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P =.029), an observation further confirmed by propensity score matching (P =.012); however, this association did not translate into an overall survival benefit. Conclusions: The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count.
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- 2020
6. Local control and postponement of systemic therapy after modest dose radiotherapy in oligometastatic myxoid liposarcomas (vol 158, pg 33, 2021)
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Lansu, J., Houdt, W.J. van, Langevelde, K. van, Ende, P.L.A. van den, Graaf, W.T.A. van der, Schrage, Y., H. van boven, Scholten, A.N., and Haas, R.L.
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- 2021
7. Clinicopathological features and treatment outcome of oesophageal gastrointestinal stromal tumour (GIST): A large, retrospective multicenter European study
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Mohammadi, M., IJzerman, Nikki S., Hohenberger, P., Rutkowski, P., Jones, R.L., Martin-Broto, J., Gronchi, A., Schöffski, P, Vassos, N., Farag, S., Baia, M., Oosten, A.W., Steeghs, N., Desar, I.M.E., Reyners, A.K., Sandick, J.W. van, Bastiaannet, E., Gelderblom, H., Schrage, Y., Mohammadi, M., IJzerman, Nikki S., Hohenberger, P., Rutkowski, P., Jones, R.L., Martin-Broto, J., Gronchi, A., Schöffski, P, Vassos, N., Farag, S., Baia, M., Oosten, A.W., Steeghs, N., Desar, I.M.E., Reyners, A.K., Sandick, J.W. van, Bastiaannet, E., Gelderblom, H., and Schrage, Y.
- Abstract
Contains fulltext : 235268.pdf (Publisher’s version ) (Open Access), BACKGROUND: Oesophageal gastrointestinal stromal tumours (GISTs) account for ≤1% of all GISTs. Consequently, evidence to guide clinical decision-making is limited. METHODS: Clinicopathological features and outcomes in patients with primary oesophageal GIST from seven European countries were collected retrospectively. RESULTS: Eighty-three patients were identified, and median follow up was 55.0 months. At diagnosis, 59.0% had localized disease, 25.3% locally advanced and 13.3% synchronous metastasis. A biopsy (Fine Needle aspiration n = 29, histological biopsy n = 31) was performed in 60 (72.3%) patients. The mitotic count was low (<5 mitoses/50 High Power Fields (HPF)) in 24 patients and high (≥5 mitoses/50 HPF) in 27 patients. Fifty-one (61.4%) patients underwent surgical or endoscopic resection. The most common reasons to not perform an immediate resection (n = 31) were; unresectable or metastasized GIST, performance status/comorbidity, patient refusal or ongoing neo-adjuvant therapy. The type of resections were enucleation (n = 11), segmental resection (n = 6) and oesophagectomy with gastric conduit reconstruction (n = 33), with median tumour size of 3.3 cm, 4.5 cm and 7.7 cm, respectively. In patients treated with enucleation 18.2% developed recurrent disease. The recurrence rate in patients treated with segmental resection was 16.7% and in patients undergoing oesophagectomy with gastric conduit reconstruction 36.4%. Larger tumours (≥4.0 cm) and high (>5/5hpf) mitotic count were associated with worse disease free survival. CONCLUSION: Based on the current study, enucleation can be recommended for oesophageal GIST smaller than 4 cm, while oesophagectomy should be preserved for larger tumours. Patients with larger tumours (>4 cm) and/or high mitotic count should be treated with adjuvant therapy.
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- 2021
8. Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial
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Lansu, J., Bovée, J., Braam, P.M., Boven, H. van, Flucke, U.E., Bonenkamp, J.J., Miah, A.B., Zaidi, S.H., Thway, K., Ø, S. Bruland, Baldini, E.H., Jebsen, N.L., Scholten, A.N., Ende, P.L. van den, Krol, A.D., Ubbels, J.F., Hage, J.A. van der, Werkhoven, E. van, Klomp, H.M., Graaf, W.T.A. van der, Coevorden, F. van, Schrage, Y., Houdt, W.J. van, Haas, R.L.M., Lansu, J., Bovée, J., Braam, P.M., Boven, H. van, Flucke, U.E., Bonenkamp, J.J., Miah, A.B., Zaidi, S.H., Thway, K., Ø, S. Bruland, Baldini, E.H., Jebsen, N.L., Scholten, A.N., Ende, P.L. van den, Krol, A.D., Ubbels, J.F., Hage, J.A. van der, Werkhoven, E. van, Klomp, H.M., Graaf, W.T.A. van der, Coevorden, F. van, Schrage, Y., Houdt, W.J. van, and Haas, R.L.M.
- Abstract
Item does not contain fulltext, IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patient
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- 2021
9. A moderate dose of preoperative radiotherapy may improve resectability in myxoid liposarcoma
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Lansu, J., Braam, P.M., Werkhoven, E.v., Scholten, A.N., Schrage, Y., Houdt, W.J. van, Langevelde, K.v., Haas, R.L.M., Lansu, J., Braam, P.M., Werkhoven, E.v., Scholten, A.N., Schrage, Y., Houdt, W.J. van, Langevelde, K.v., and Haas, R.L.M.
- Abstract
Item does not contain fulltext
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- 2021
10. Primary mesenteric sarcomas: Collaborative experience from the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG)
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Tattersall, HL, Hodson, J, Cardona, K, Lee, RM, Nessim, C, Gladdy, R, Van Der Hage, J, Schrage, Y, Tseng, WW, van Houdt, W, Novak, M, Grignani, G, Tolomeo, F, Goel, N, Ryon, E, Gyorki, D, Bagaria, SP, Gonzalez, JA, Arnau, ABM, Sayyed, R, Tirotta, F, Evenden, C, Desai, A, Almond, M, Glasbey, J, Fiore, M, Gronchi, A, Ford, SJ, Tattersall, HL, Hodson, J, Cardona, K, Lee, RM, Nessim, C, Gladdy, R, Van Der Hage, J, Schrage, Y, Tseng, WW, van Houdt, W, Novak, M, Grignani, G, Tolomeo, F, Goel, N, Ryon, E, Gyorki, D, Bagaria, SP, Gonzalez, JA, Arnau, ABM, Sayyed, R, Tirotta, F, Evenden, C, Desai, A, Almond, M, Glasbey, J, Fiore, M, Gronchi, A, and Ford, SJ
- Abstract
BACKGROUND: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function. OBJECTIVES: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS. METHODS: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019. RESULTS: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery. CONCLUSION: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging.
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- 2021
11. Management of meningeal solitary fibrous tumors/hemangiopericytoma; surgery alone or surgery plus postoperative radiotherapy?
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Haas, R. L., Walraven, I., Lecointe-Artzner, E., van Houdt, W. J., Scholten, A. N., Strauss, D., Schrage, Y., Hayes, A. J., Raut, C. P., Fairweather, M., Baldini, E. H., Gronchi, A., De Rosa, L., Griffin, A. M., Ferguson, P. C., Wunder, J., van de Sande, M. A. J., Krol, A. D. G., Skoczylas, J., Brandsma, D., Doglietto, Francesco, Sangalli, C., Stacchiotti, S., Doglietto F. (ORCID:0000-0002-7438-0734), Haas, R. L., Walraven, I., Lecointe-Artzner, E., van Houdt, W. J., Scholten, A. N., Strauss, D., Schrage, Y., Hayes, A. J., Raut, C. P., Fairweather, M., Baldini, E. H., Gronchi, A., De Rosa, L., Griffin, A. M., Ferguson, P. C., Wunder, J., van de Sande, M. A. J., Krol, A. D. G., Skoczylas, J., Brandsma, D., Doglietto, Francesco, Sangalli, C., Stacchiotti, S., and Doglietto F. (ORCID:0000-0002-7438-0734)
- Abstract
Introduction: A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. Patients and methods: A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan–Meier survival curves. Results: Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011). Conclusion: This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.
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- 2021
12. Cellular Radiosensitivity of Soft Tissue Sarcoma
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Haas, R. L., primary, Floot, B. G. J., additional, Scholten, A. N., additional, van der Graaf, W. T. A., additional, van Houdt, W., additional, Schrage, Y., additional, van de Ven, M., additional, Bovée, J. V. M. G., additional, van Coevorden, F., additional, and Vens, C., additional
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- 2021
- Full Text
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13. Extrameningeal solitary fibrous tumors-surgery alone or surgery plus perioperative radiotherapy: A retrospective study from the global solitary fibrous tumor initiative in collaboration with the Sarcoma Patients EuroNet
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Haas, R.L.M., Walraven, I., Lecointe-Artzner, E., Houdt, W.J. van, Strauss, D., Schrage, Y., Hayes, A.J., Raut, C.P., Fairweather, M., Baldini, E.H., Gronchi, A., Rosa, L. De, Griffin, A.M., Ferguson, P.C., Wunder, J., Sande, Marc van de, Krol, A.D., Skoczylas, J., Sangalli, C., Stacchiotti, S., Haas, R.L.M., Walraven, I., Lecointe-Artzner, E., Houdt, W.J. van, Strauss, D., Schrage, Y., Hayes, A.J., Raut, C.P., Fairweather, M., Baldini, E.H., Gronchi, A., Rosa, L. De, Griffin, A.M., Ferguson, P.C., Wunder, J., Sande, Marc van de, Krol, A.D., Skoczylas, J., Sangalli, C., and Stacchiotti, S.
- Abstract
Contains fulltext : 225859.pdf (Publisher’s version ) (Open Access), BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. METHODS: This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. RESULTS: Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow-up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit. CONCLUSIONS: The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count.
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- 2020
14. Quality of treatment and surgical approach for rectal gastrointestinal stromal tumour (GIST) in a large European cohort
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IJzerman, N.S. (Nikki S.), Mohammadi, M. (Mahmoud), Tzanis, D. (Dimitri), Gelderblom, H. (Hans), Fiore, P.P. di, Fumagalli, E. (Elena), Rutkowski, P. (Piotr), Bylina, E., Zavrakidis, I. (Ioannis), Steeghs, N. (Neeltje), Bonenkamp, J.J. (Han), Etten, B. (Boudewijn) van, Grunhagen, D.J. (Dirk Jan), Rasheed, S. (Shahnawaz), Tekkis, P. (Paris), Honoré, C. (Charles), Houdt, W.J. (Winan) van, Hage, J.A. (Jos) van der, Bonvalot, S. (Sylvie), Schrage, Y. (Yvonne), Smith, M. (Myles), IJzerman, N.S. (Nikki S.), Mohammadi, M. (Mahmoud), Tzanis, D. (Dimitri), Gelderblom, H. (Hans), Fiore, P.P. di, Fumagalli, E. (Elena), Rutkowski, P. (Piotr), Bylina, E., Zavrakidis, I. (Ioannis), Steeghs, N. (Neeltje), Bonenkamp, J.J. (Han), Etten, B. (Boudewijn) van, Grunhagen, D.J. (Dirk Jan), Rasheed, S. (Shahnawaz), Tekkis, P. (Paris), Honoré, C. (Charles), Houdt, W.J. (Winan) van, Hage, J.A. (Jos) van der, Bonvalot, S. (Sylvie), Schrage, Y. (Yvonne), and Smith, M. (Myles)
- Abstract
Background: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach. Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders
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- 2020
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15. Neoadjuvant systemic treatment of primary angiosarcoma
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Heinhuis, K.M. (Kimberley M.), IJzerman, N.S. (Nikki S.), Graaf, W.T.A. (Winette) van der, Kerst, J.M. (Martijn), Schrage, Y. (Yvonne), Beijnen, J.H. (Jos), Steeghs, N. (Neeltje), Houdt, W.J. (Winan) van, Heinhuis, K.M. (Kimberley M.), IJzerman, N.S. (Nikki S.), Graaf, W.T.A. (Winette) van der, Kerst, J.M. (Martijn), Schrage, Y. (Yvonne), Beijnen, J.H. (Jos), Steeghs, N. (Neeltje), and Houdt, W.J. (Winan) van
- Abstract
Angiosarcoma is an extremely rare and aggressive malignancy. Standard of care of localized tumors includes surgery ± radiation. Despite this multimodal treatment, >50% of the angiosarcoma patients develop local or distant recurrent disease. The role of neoadjuvant systemic therapy is still controversial and we therefore performed a systematic review of the literature to define the role of neoadjuvant systemic therapy based on available evidence. We focused on the effects of neoadjuvant systemic therapy on: 1. The success of surgical resection and 2. the long-term survival. All articles published before October 2019 on Ovid Medline, Ovid Embase, Cochrane library and Scopus were evaluated. Eighteen case reports and six retrospective cohort studies were included. There were no randomized controlled trials. This literature showed a beneficial role of neoadjuvant chemotherapy on downsizing of the tumor resulting in an improvement of the resection margins, especially in patients with cardiac or cutaneous angiosarcoma. However, no definitive conclusions on survival can be drawn based on the available literature lacking any prospectiv
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- 2020
- Full Text
- View/download PDF
16. Quality of treatment and surgical approach for rectal gastrointestinal stromal tumour (GIST) in a large European cohort
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IJzerman, Nikki, Mohammadi, M, Tzanis, D, Gelderblom, H, Fiore, M, Fumagalli, E, Rutkowski, P, Bylina, E, Zavrakidis, I, Steeghs, N, Bonenkamp, HJ, Etten, B, Grunhagen, DJ, Rasheed, S, Tekkis, P, Honore, C, van Houdt, W, van der Hage, J, Bonvalot, S, Schrage, Y, Smith, M, IJzerman, Nikki, Mohammadi, M, Tzanis, D, Gelderblom, H, Fiore, M, Fumagalli, E, Rutkowski, P, Bylina, E, Zavrakidis, I, Steeghs, N, Bonenkamp, HJ, Etten, B, Grunhagen, DJ, Rasheed, S, Tekkis, P, Honore, C, van Houdt, W, van der Hage, J, Bonvalot, S, Schrage, Y, and Smith, M
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- 2020
17. Neoadjuvant Systemic Treatment of Primary Angiosarcoma
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Heinhuis, K.M., IJzerman, Nikki S., Graaf, W.T.A. van der, Kerst, J.M., Schrage, Y., Beijnen, J.H., Steeghs, N., Houdt, W.J. van, Heinhuis, K.M., IJzerman, Nikki S., Graaf, W.T.A. van der, Kerst, J.M., Schrage, Y., Beijnen, J.H., Steeghs, N., and Houdt, W.J. van
- Abstract
Contains fulltext : 225983.pdf (publisher's version ) (Open Access), Angiosarcoma is an extremely rare and aggressive malignancy. Standard of care of localized tumors includes surgery ± radiation. Despite this multimodal treatment, >50% of the angiosarcoma patients develop local or distant recurrent disease. The role of neoadjuvant systemic therapy is still controversial and we therefore performed a systematic review of the literature to define the role of neoadjuvant systemic therapy based on available evidence. We focused on the effects of neoadjuvant systemic therapy on: 1. The success of surgical resection and 2. the long-term survival. All articles published before October 2019 on Ovid Medline, Ovid Embase, Cochrane library and Scopus were evaluated. Eighteen case reports and six retrospective cohort studies were included. There were no randomized controlled trials. This literature showed a beneficial role of neoadjuvant chemotherapy on downsizing of the tumor resulting in an improvement of the resection margins, especially in patients with cardiac or cutaneous angiosarcoma. However, no definitive conclusions on survival can be drawn based on the available literature lacking any prospective randomized studies in this setting. We advise that neoadjuvant chemotherapy should be considered, since this could lead to less mutilating resections and a higher rate of free resection margins. An international angiosarcoma registry could help to develop guidelines for this rare disease.
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- 2020
18. Neoadjuvant systemic treatment of primary angiosarcoma
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Heinhuis, KM, IJzerman, Nikki, van der Graaf, WTA, Kerst, JM, Schrage, Y, Beijnen, JH, Steeghs, N, Van Houdt, WJ, Heinhuis, KM, IJzerman, Nikki, van der Graaf, WTA, Kerst, JM, Schrage, Y, Beijnen, JH, Steeghs, N, and Van Houdt, WJ
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- 2020
19. Management of meningeal solitary fibrous tumors/hemangiopericytoma; surgery alone or surgery plus postoperative radiotherapy?
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Haas, R. L., primary, Walraven, I., additional, Lecointe-Artzner, E., additional, van Houdt, W. J., additional, Scholten, A. N., additional, Strauss, D., additional, Schrage, Y., additional, Hayes, A. J., additional, Raut, C. P., additional, Fairweather, M., additional, Baldini, E. H., additional, Gronchi, A., additional, De Rosa, L., additional, Griffin, A. M., additional, Ferguson, P. C., additional, Wunder, J., additional, van de Sande, M. A. J., additional, Krol, A. D. G., additional, Skoczylas, J., additional, Brandsma, D., additional, Doglietto, F., additional, Sangalli, C., additional, and Stacchiotti, S., additional
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- 2020
- Full Text
- View/download PDF
20. 1112P Intralesional therapy with talimogene laherparepvec for stage IIIB-IVM1a melanoma is able to achieve a high rate of complete and durable responses and is associated with tumour load
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Stahlie, E., primary, Franke, V., additional, Zuur, L., additional, Klop, M., additional, van de Wiel, B.A., additional, van der Hiel, B., additional, Wouters, M., additional, Schrage, Y., additional, van Houdt, W.J., additional, and van Akkooi, A.C.J., additional
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- 2020
- Full Text
- View/download PDF
21. Extrameningeal solitary fibrous tumors-surgery alone or surgery plus perioperative radiotherapy: A retrospective study from the global solitary fibrous tumor initiative in collaboration with the Sarcoma Patients EuroNet
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Michiel A. J. van de Sande, Andrew J. Hayes, Elizabeth H. Baldini, Jay S. Wunder, Augustinus D.G. Krol, Silvia Stacchiotti, Laura De Rosa, Anthony M. Griffin, Peter C. Ferguson, Jacus Skoczylas, Winan J. van Houdt, Chandrajit P. Raut, Dirk C. Strauss, Estelle Lecointe-Artzner, Iris Walraven, Yvonne Schrage, Claudia Sangalli, Mark Fairweather, Rick L. Haas, Alessandro Gronchi, Haas, R, Walraven, I, Lecointe-Artzner, E, van Houdt, W, Strauss, D, Schrage, Y, Hayes, A, Raut, C, Fairweather, M, Baldini, E, Gronchi, A, De Rosa, L, Griffin, A, Ferguson, P, Wunder, J, van de Sande, M, Krol, A, Skoczylas, J, Sangalli, C, and Stacchiotti, S
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Male ,Cancer Research ,Solitary fibrous tumor ,patient advocacy group ,medicine.medical_treatment ,surgery ,0302 clinical medicine ,030212 general & internal medicine ,Hazard ratio ,Torso ,Middle Aged ,Combined Modality Therapy ,Progression-Free Survival ,Solitary Fibrous Tumor, Pleural ,Survival Rate ,Oncology ,Head and Neck Neoplasms ,Solitary Fibrous Tumors ,030220 oncology & carcinogenesis ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Disease Progression ,Female ,Original Article ,Sarcoma ,medicine.medical_specialty ,Soft Tissue and Bone Sarcoma ,Lower risk ,03 medical and health sciences ,Mitotic Index ,medicine ,Humans ,solitary fibrous tumor ,Retroperitoneal Neoplasms ,hemangiopericytoma ,Propensity Score ,radiotherapy ,Retrospective Studies ,Analysis of Variance ,business.industry ,Extremities ,Retrospective cohort study ,Original Articles ,Perioperative ,medicine.disease ,Surgery ,Radiation therapy ,Propensity score matching ,Disease Site ,business ,Follow-Up Studies - Abstract
Background Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. Methods This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. Results Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow‐up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit. Conclusions The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count., This retrospective study of perioperative radiotherapy in patients with primary extrameningeal solitary fibrous tumors suggests that combining radiotherapy with surgery in the management of this population significantly reduces the risk of local failures, especially in patients who have less favorable resection margins or tumors with a high mitotic count.
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- 2020
22. A screening based approach to find new paths for targeted treatment in chondrosarcoma
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Jong, Y. de, Bovée, J.V.M.G., Danen, E., Gelderblom, A.J., Water, B. van de, Schrage, Y., and Leiden University
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Radio resistance ,Chemo resistance ,Survivin ,Chondrosarcoma ,Screening based approach ,Bcl-2 family members - Abstract
Chondrosarcomas are malignant cartilage producing tumours, occurring mostly around the age of fifty. Treatment is mainly by surgery, since tumours are relatively resistant toward chemo-and radiotherapy. This means that patients with inoperable disease have no alternative treatment options. In this thesis we describe the use of compound and siRNA screens to identify new targeted treatment options for patients with chondrosarcoma. Using available chondrosarcoma cell lines as a model we investigated apoptotic proteins, kinases and metabolic regulators in a non-biased way to identify most promising hits. In addition the role of individual Bcl-2 family members Bcl-2, Bcl-xl and Bcl-w was investigated. Results reveal a role for Bcl-2 family member Bcl-xl, anti-apoptotic and cell cycle regulator Survivin, cell cycle regulators AURKA, CHK1 and PLK1 and mTOR as important survival proteins in chondrosarcoma. Moreover treatment with Bcl-xl or CHK1 inhibitors could chemo-sensitize a subset of chondrosarcoma cell lines. Furthermore alterations in the Rb1 pathway have been identified as a marker for radio resistance in chondrosarcoma patient samples. Collectively these studies identify several lead targets that might be useful as targeted treatment options for chondrosarcoma patients. Future research should focus more on the therapeutic value of these targets, and translate these pre-clinical findings to clinical practise.
- Published
- 2020
23. Magnetic seed localization is feasible for non-palpable melanoma, Merkel cell carcinoma, and soft tissue sarcoma lesions.
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van der Burg SJC, Kuijpers A, Baetens T, van Akkooi ACJ, Reijers SJM, Wouters MWJM, Schrage YM, and van Houdt WJ
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- Humans, Female, Retrospective Studies, Aged, Male, Middle Aged, Adult, Aged, 80 and over, Margins of Excision, Fiducial Markers, Melanoma diagnostic imaging, Melanoma surgery, Melanoma pathology, Skin Neoplasms pathology, Skin Neoplasms diagnostic imaging, Skin Neoplasms surgery, Sarcoma diagnostic imaging, Sarcoma surgery, Sarcoma pathology, Carcinoma, Merkel Cell diagnostic imaging, Carcinoma, Merkel Cell pathology, Carcinoma, Merkel Cell surgery, Feasibility Studies
- Abstract
Background: Localization of non-palpable melanoma, Merkel cell carcinoma (MCC) and soft tissue sarcoma (STS) lesions can be difficult due to size, location, and obesity of patients or fibrosis due to previous treatments. Magnetic seed localization (MSL) is a common method to localize non-palpable breast lesions, but the feasibility of MSL for non-palpable melanoma, MCC and STS lesions has not yet been described., Methods: In this retrospective single center cohort study, all consecutive patients between January 2021 and October 2023 who had a resection of a non-palpable melanoma, MCC or STS lesion guided by Sirius Pintuition, a MSL technique, were included. The primary endpoint was successful lesion localization during surgery and the secondary endpoints were seed migration, negative resection margins, and complications., Results: Seventy-nine seeds were placed for 76 lesions, which were resected during 68 surgeries in 61 patients. All lesions (100 %) were localized and resected. Median time of surgery was 44 min. No seed migration was observed. A negative resection margin was achieved for 60 (78.9 %) lesions. Clavien Dindo grade ≥2 complications occurred in 7.4 %., Conclusion: Magnetic seed localization with Sirius Pintuition is feasible for both non-palpable melanoma, MCC, and STS lesions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: WJ Van Houdt reports financial support was provided by Sirius Medical Systems B.V. If there are other authors, they 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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24. Reply to: Pioneering combination: Nivolumab and isolated limb perfusion in melanoma in-transit metastases treatment.
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Holmberg CJ, Zijlker LP, Katsarelias D, Huibers AE, Wouters MWJM, Schrage Y, Reijers SJM, van Thienen JV, Grünhagen DJ, Martner A, Nilsson JA, van Akkooi ACJ, Ny L, van Houdt WJ, and Olofsson Bagge R
- Abstract
Competing Interests: Declaration of competing interest Conflicts of interest: ACJvA is a member of the Advisory Board for, and received consultancy honoraria from, Amgen, Bristol-Myers Squibb, Neracare, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC. WvH has received institutional honoraria, speakers honorarium, or institutional research grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Belpharma, Sanofi and Sirius Medical. ROB has received institutional research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme. Remaining authors have no conflicts of interest to declare.
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- 2024
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25. The effect of a single dose of nivolumab prior to isolated limb perfusion for patients with in-transit melanoma metastases: An interim analysis of a phase Ib/II randomized double-blind placebo-controlled trial (NivoILP trial).
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Holmberg CJ, Zijlker LP, Katsarelias D, Huibers AE, Wouters MWJM, Schrage Y, Reijers SJM, van Thienen JV, Grünhagen DJ, Martner A, Nilsson JA, van Akkooi ACJ, Ny L, van Houdt WJ, and Olofsson Bagge R
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- Humans, Double-Blind Method, Male, Female, Middle Aged, Aged, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological administration & dosage, Adult, Extremities, Aged, 80 and over, Melanoma drug therapy, Melanoma secondary, Melanoma pathology, Nivolumab administration & dosage, Nivolumab therapeutic use, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Chemotherapy, Cancer, Regional Perfusion methods
- Abstract
Objective: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM)., Methods: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP. The primary endpoint was complete response (CR) rate at three months, and safety in terms of incidence and severity of adverse events (AEs)., Results: A total of 20 patients were included. AEs of any grade occurred in 90% of patients in the nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 3 AEs were reported in 40% and 30% respectively, most commonly related to wound infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in the placebo arm. The 1-year OS was 100% in both arms., Conclusion: For patients with melanoma ITM, the addition of a single systemic dose of nivolumab the day before ILP is considered safe and feasible with promising efficacy. Accrual will continue in a phase 2 trial., Competing Interests: Declaration of competing interest ACJvA is a member of the Advisory Board for, and received consultancy honoraria from, Amgen, Bristol-Myers Squibb, Neracare, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC. WvH has received institutional honoraria, speakers honorarium, or institutional research grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Belpharma, Sanofi and Sirius Medical. ROB has received institutional research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme. Remaining authors have no conflicts of interest to declare., (© 2024 Published by Elsevier Ltd.)
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- 2024
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26. Current practice in assessment and management of malnutrition in surgical oncology practice - An ESSO-EYSAC snapshot analysis.
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Brandl A, Lundon D, Lorenzon L, Schrage Y, Caballero C, Holmberg CJ, Santrac N, Smith H, Vasileva-Slaveva M, Montagna G, Bonci EA, Sgarbura O, Sayyed R, Ben-Yaacov A, Herrera Kok JH, Suppan I, Kaul P, Sochorova D, Vassos N, Carrico M, Mohan H, Ceelen W, Arends J, and Sandrucci S
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- Humans, Surveys and Questionnaires, Neoplasms complications, Neoplasms surgery, Practice Patterns, Physicians' statistics & numerical data, Malnutrition diagnosis, Nutrition Assessment, Surgical Oncology
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Introduction: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments., Material and Methods: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team., Results: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation., Conclusions: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening., (Copyright © 2023 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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27. Radio-Guided Occult Lesion Localization With 99m Tc for the Localization of Nonpalpable Melanoma and Soft Tissue Sarcoma Lesions: A Feasibility Study.
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Reijers SJM, Mook FJ, Groen HC, Schrage Y, Stokkel MPM, Donswijk ML, and van Houdt WJ
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- Humans, Radiopharmaceuticals, Technetium Tc 99m Aggregated Albumin, Feasibility Studies, Melanoma diagnostic imaging, Sarcoma diagnostic imaging, Sarcoma surgery, Soft Tissue Neoplasms diagnostic imaging, Soft Tissue Neoplasms surgery
- Abstract
Purpose of the Report: Localization techniques are needed to facilitate resection of nonpalpable lesions. In this study, the feasibility of radio-guided occult lesion localization (ROLL) with 99m Tc is investigated for the localization of nonpalpable, small, suspicious, or proven melanoma or soft tissue sarcoma lesions at various locations throughout the body., Patients and Methods: Patients with nonpalpable, suspicious, or proven melanoma or soft tissue sarcoma lesions were selected for this study. Within 24 hours before surgery, a median dose of 33.92 MBq 99m Tc-labeled human albumin particles ( 99m Tc-NA or 99m Tc-MAA) was injected in the lesion under ultrasound guidance. A hand-held gamma probe was used to detect the radioactive signal and guidance during surgery., Results: In this study, 20 patients with a total of 25 lesions were included and analyzed. The median size of the lesions was 1.8 cm (interquartile range [IQR], 1.8-4.0 cm), of which 44% were intramuscular located and 36% were subcutaneous, and 20% consisted of suspicious lymph nodes, mostly in the lower extremity. At median 4 hours (IQR, 3-6 hours) postinjection, 99m Tc ROLL showed a 100% intraoperative identification rate with proper signal identification with the gamma probe in all patients. With a median surgery time of 76 minutes (IQR, 45-157 minutes), all targeted lesions could be resected without 99m Tc-related complications, resulting in 88% microscopically margin-negative resection. No reoperations were needed for the same lesion., Conclusions: The 99m Tc ROLL procedure is feasible for the localization and excision of small, nonpalpable melanoma and soft tissue sarcoma lesions at various locations in the body., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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28. Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study.
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Reijers SJM, Davies E, Grünhagen DJ, Fiore M, Honore C, Rastrelli M, Vassos N, Podleska LE, Niethard M, Jakob J, Perhavec A, Duarte C, González F, Deroose JP, Stas M, Boecxstaens V, Schrage Y, Snow H, Algarra SM, Said HM, Garcia-Ortega DY, Martin K, Mattsson J, Djafarrian R, Di Lorenzo G, Colombo C, Gronchi A, Matter M, Verhoef C, Olofsson Bagge R, Hohenberger P, Hayes AJ, and van Houdt WJ
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- Adult, Humans, Retrospective Studies, Chemotherapy, Cancer, Regional Perfusion methods, Melphalan therapeutic use, Extremities pathology, Perfusion, Tumor Necrosis Factor-alpha, Antineoplastic Agents, Alkylating therapeutic use, Sarcoma pathology, Soft Tissue Neoplasms pathology, Sarcoma, Kaposi
- Abstract
Objective: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study., Materials and Methods: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded., Results: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001)., Conclusion: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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29. Elevated preoperative serum interleukin-6 level is predictive for worse postoperative outcome after soft tissue sarcoma surgery.
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van der Laan P, van der Graaf WTA, Reijers SJM, Schrage YM, Hendriks JJH, Haas RL, van den Broek D, Steeghs N, and van Houdt WJ
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- Humans, Interleukin-6, Prognosis, Cytokines, Sarcoma pathology, Soft Tissue Neoplasms pathology
- Abstract
Background: The pro-inflammatory cytokine interleukin-6 (IL-6) plays a role in cancer development and progression, but research into the predictive value of IL-6 on postoperative outcome in soft tissue sarcoma (STS) is scarce. The purpose of this study is to investigate the predictive value of serum IL-6 level for the achievement of assumed (post)operative outcome after STS surgery, the so-called textbook outcome., Methods: Preoperative IL-6 serum levels were collected in all patients with a STS at first presentation between February 2020 and November 2021. Textbook outcome was defined as a R0 resection, no complications, no blood transfusions, no reoperation within the postoperative period, no prolonged hospital stay, no hospital readmission within 90-days, and no mortality within 90-days. Factors associated with textbook outcome were determined by multivariable analysis., Results: Among 118 patients with primary, non-metastatic STS, 35.6% achieved a textbook outcome. Univariate analysis showed that smaller tumor size (p = 0.026), lower tumor grade (p = 0.006), normal hemoglobin (Hb, p = 0.044), normal white blood cell (WBC) count (p = 0.018), normal C-reactive protein (CRP) serum level (p = 0.002) and normal IL-6 serum level (p = 1.5 × 10
-5 ) were associated with achieving textbook outcome after surgery. Multivariable analysis showed that elevated IL-6 serum level (p = 0.012) was significantly associated with not achieving a textbook outcome., Conclusions: Increased IL-6 serum level is predictive for not achieving a textbook outcome after surgery for primary, non-metastatic STS., 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 © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)- Published
- 2023
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30. Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.
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Reijers SJM, Gennaro N, Bruining A, van Boven H, Snaebjornsson P, Bekers EM, van Coevorden F, Scholten AN, Schrage Y, van der Graaf WTA, Haas RLM, and van Houdt WJ
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- Adult, Humans, Retrospective Studies, Necrosis, Fibrosis, Neoadjuvant Therapy, Sarcoma diagnostic imaging, Sarcoma radiotherapy, Sarcoma pathology
- Abstract
Background: The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome., Methods: A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS)., Results: For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS ( p = .038)., Conclusion: RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.
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- 2023
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31. Prognosis of Patients with Cutaneous Angiosarcoma After Surgical Resection with Curative Intent: Is There a Difference Between the Subtypes?
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Reijers SJM, Huis In 't Veld EA, Grünhagen DJ, Smith MJF, van Ginhoven TM, van Coevorden F, van der Graaf WTA, Schrage Y, Strauss DC, Haas RLM, Verhoef CJ, Hayes AJ, and van Houdt WJ
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- Aged, Female, Humans, Retrospective Studies, Male, Middle Aged, Hemangiosarcoma
- Abstract
Background: The etiology of cutaneous angiosarcoma (cAS) may be idiopathic (I-cAS), or arise secondary to radiotherapy (RT-cAS), in chronic lymphedema (ST-cAS), or related to UV exposure (UV-cAS). The aim of this study was to evaluate oncological outcomes of different cAS subtypes., Patients and Methods: Non-metastatic cAS patients, treated with surgery for primary disease with curative intent, were retrospectively analyzed for oncological outcome, including local recurrence (LR), distant metastases (DM), and overall survival (OS)., Results: A total of 234 patients were identified; 60 I-cAS, 122 RT-cAS, 9 ST-cAS, and 43 UV-cAS. The majority was female (78%), the median age was 66 years (IQR 57-76 years), the median tumor size was 4.4 cm (IQR 2.5-7.0 cm), and most common site of disease was the breast (59%). Recurrence was identified in 66% (44% LR and/or 41% DM), with a median follow up of 26.5 months (IQR 12-60 months). The 5-year OS was estimated at 50%, LRFS at 47%, and DMFS at 50%. There was no significant difference in LR, DM, or OS between the subtypes. Age < 65 years and administration of radiotherapy (RT) were significantly associated with lower LR rates (HR 0.560, 95% CI 0.3373-0.840, p = 0.005 and HR 0.421, 95% CI 0.225-0.790, p = 0.007, respectively), however no prognostic factors were identified for development of DM. Development of DM, but not LR (p = 0.052), was significantly associated with decreased OS (HR 6.486, 95% CI 2.939-14.318 p < 0.001)., Conclusion: We found no significant difference in oncological outcome between the different cAS subtypes. OS remains relatively poor, and RT is associated with lower LR rates., (© 2022. Society of Surgical Oncology.)
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- 2023
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32. Standards in surgical training in advanced pelvic malignancy across Europe and beyond - A Snapshot analysis.
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Brandl A, Lundon D, Lorenzon L, Schrage Y, Caballero C, Holmberg CJ, Santrac N, Vasileva-Slaveva M, Montagna G, Sgarbura O, Sayyed R, Ben-Yaacov A, Herrera Kok JH, Suppan I, Mohan H, Kovacs T, D'Ugo D, Sandrucci S, and Ceelen W
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- Humans, Europe, Surveys and Questionnaires, Pelvic Neoplasms surgery, Urology education, Surgical Oncology education, Surgeons
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Introduction: Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM., Material and Methods: An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R., Results: The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing >25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful., Conclusion: This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training., Competing Interests: Declaration of competing interest Andreas Brandl, Dara Lundon, Laura Lorenzon, Yvonne Schrage, Carmela Caballero, Carl Jacob Holmberg, Nada Santrac, Mariela Vasileva-Slaveva, Giacomo Montagna, Olivia Sgarbura, Raza Sayyed, Almog Ben-Yaacov, Johnn Henry Herrera Kok, Ina Suppan, Helen Mohan, Wim Ceelen, Tibor Kovacs, Domenico D'Ugo, Sergio Sandrucci declared that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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33. Correction to: Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).
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Nessim C, Raut CP, Callegaro D, Barretta F, Miceli R, Fairweather M, Rutkowski P, Blay JY, Strauss D, Gonzalez R, Ahuja N, Grignani G, Quagliuolo V, Stoeckle E, De Paoli A, Pillarisetty VG, Swallow CJ, Bagaria SP, Canter RJ, Mullen JT, Schrage Y, Pennacchioli E, van Houdt W, Cardona K, Fiore M, Gronchi A, and Lahat G
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- 2022
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34. Correction to: Analysis of Differentiation Changes and Outcomes at Time of First Recurrence of Retroperitoneal Liposarcoma by Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).
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Nessim C, Raut CP, Callegaro D, Barretta F, Miceli R, Fairweather M, Blay JY, Strauss D, Rutkowski P, Ahuja N, Gonzalez R, Grignani G, Quagliuolo V, Stoeckle E, Lahat G, De Paoli A, Pillarisetty VG, Canter RJ, Mullen JT, Pennacchioli E, van Houdt W, Swallow CJ, Schrage Y, Cardona K, Fiore M, Gronchi A, and Bagaria SP
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- 2022
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35. Correction: Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.
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Bagaria SP, Swallow C, Suraweera H, Raut CP, Fairweather M, Cananzi F, Quagliuolo V, Grignani G, Hompes D, Ford SJ, Nessim C, Apte S, Skoczylas J, Rutkowski P, Bonvalot S, Tzanis D, Gabriel E, Pennacchioli E, Albertsmeier M, Canter RJ, Pollock R, Grignol V, Cardona K, Gamboa AC, Novak M, Stoeckle E, Almquist M, Ahuja N, Klemen N, Van Houdt W, Gyorki D, Gangi A, Rastrelli M, van der Hage J, Schrage Y, Valeri S, Conti L, Spiegel MR, Li Z, Fiore M, and Gronchi A
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- 2022
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36. A phase II study on the neo-adjuvant combination of pazopanib and radiotherapy in patients with high-risk, localized soft tissue sarcoma.
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van Meekeren M, Bovee JVMG, van Coevorden F, van Houdt W, Schrage Y, Koenen AM, Miah AB, Zaidi S, Hayes AJ, Thway K, Krol S, Fiocco M, Gelderblom H, Steeghs N, and Haas RL
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- Humans, Indazoles, Prospective Studies, Pyrimidines, Sulfonamides adverse effects, Neoadjuvant Therapy, Sarcoma drug therapy
- Abstract
Purpose: A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination., Patients and Methods: Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4-8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells., Results: 25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension., Conclusion: Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation.
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- 2021
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37. Surgical navigation for challenging recurrent or pretreated intra-abdominal and pelvic soft tissue sarcomas.
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Reijers SJM, Heerink WJ, Van Veen R, Nijkamp J, Hoetjes NJ, Schrage Y, Van Akkooi A, Beets GL, Van Coevorden F, Ruers TJM, Groen HC, and Van Houdt WJ
- Subjects
- Abdominal Neoplasms diagnostic imaging, Aged, Blood Loss, Surgical, Contrast Media, Female, Humans, Imaging, Three-Dimensional, Male, Middle Aged, Neoplasm Recurrence, Local diagnostic imaging, Operative Time, Pelvic Neoplasms diagnostic imaging, Prospective Studies, Sarcoma diagnostic imaging, Soft Tissue Neoplasms diagnostic imaging, Tomography, X-Ray Computed, Abdominal Neoplasms surgery, Neoplasm Recurrence, Local surgery, Pelvic Neoplasms surgery, Sarcoma surgery, Soft Tissue Neoplasms surgery, Surgery, Computer-Assisted
- Abstract
Background: This study assessed whether electromagnetic navigation can be of added value during resection of recurrent or post-therapy intra-abdominal/pelvic soft tissue sarcomas (STS) in challenging locations., Materials and Methods: Patients were included in a prospective navigation study. A pre-operatively 3D roadmap was made and tracked using electromagnetic reference markers. During the operation, an electromagnetic pointer was used for the localization of the tumor/critical anatomical structures. The primary endpoint was feasibility, secondary outcomes were safety and usability., Results: Nine patients with a total of 12 tumors were included, 7 patients with locally recurrent sarcoma. Three patients received neoadjuvant radiotherapy and three other patients received neoadjuvant systemic treatment. The median tumor size was 4.6 cm (2.4-10.4). The majority of distances from tumor to critical anatomical structures was <0.5 cm. The tumors were localized using the navigation system without technical or safety issues. Despite the challenging nature of these resections, 89% were R0 resections, with a median blood loss of 100 ml (20-1050) and one incident of vascular damage. Based on the survey, surgeons stated navigation resulted in shorter surgery time and made the resections easier., Conclusion: Electromagnetic navigation facilitates resections of challenging lower intra-abdominal/pelvic STS and might be of added value., (© 2021 Wiley Periodicals LLC.)
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- 2021
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38. Longitudinal prognostication in retroperitoneal sarcoma survivors: Development and external validation of two dynamic nomograms.
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Callegaro D, Barretta F, Swallow CJ, Strauss DC, Bonvalot S, Honorè C, Stoeckle E, van Coevorden F, Haas R, Rutkowski P, Schrage Y, Fairweather M, Conti L, Vassos N, Gladdy RA, Ng D, van Houdt WJ, Miceli R, Raut CP, and Gronchi A
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- Adolescent, Adult, Aged, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local prevention & control, Prospective Studies, Retroperitoneal Neoplasms surgery, Sarcoma surgery, Young Adult, Cancer Survivors statistics & numerical data, Neoplasm Recurrence, Local epidemiology, Nomograms, Retroperitoneal Neoplasms mortality, Sarcoma mortality
- Abstract
Purpose: The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS)., Methods: Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts., Results: Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (T
LM ), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM , histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes., Conclusion: Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors., Competing Interests: Conflict of 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 article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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39. Analysis of Differentiation Changes and Outcomes at Time of First Recurrence of Retroperitoneal Liposarcoma by Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).
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Nessim C, Raut CP, Callegaro D, Barretta F, Miceli R, Fairweather M, Blay JY, Strauss D, Rutkowski P, Ahuja N, Gonzalez R, Grignani G, Quagliuolo V, Stoeckle E, Lahat G, De Paoli A, Pillarisetty VG, Canter RJ, Mullen JT, Pennacchioli E, van Houdt W, Swallow CJ, Schrage Y, Cardona K, Fiore M, Gronchi A, and Bagaria SP
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- Humans, Neoplasm Recurrence, Local surgery, Retrospective Studies, Liposarcoma surgery, Retroperitoneal Neoplasms surgery, Sarcoma
- Abstract
Background: Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differentiated (WD) and dedifferentiated (DD) RLPS are distinct entities with differing outcomes. A few reports suggest that WDLPS can recur as DDLPS and that DDLPS can recur as WDLPS. This study evaluates whether this change in differentiation from the primary tumor to the first local recurrence impacts long-term outcomes., Methods: Retrospective review from 22 sarcoma centers identified consecutive patients who underwent resection for a first locally recurrent RLPS from January 2002 to December 2011. Outcomes measured included overall survival, local recurrence, and distant metastasis., Results: A total of 421 RPLS patients were identified. Of the 230 patients with primary DDLPS, 34 (15%) presented WDLPS upon recurrence (DD → WD); and of the 191 patients with primary WDLPS, 54 (28%) presented DDLPS upon recurrence (WD → DD). The 6-year overall survival probabilities (95% CI) for DD → DD, DD → WD, WD → WD, and WD → DD were 40% (32-48%), 73% (58-92%), 76% (68-85%), and 56% (43-73%) (p < 0.001), respectively. The 6-year second local recurrence incidence was 66% (59-73%), 63% (48-82%), 66% (57-76%), and 77% (66-90%), respectively. The 6-year distant metastasis incidence was 13% (9-19%), 3% (0.4-22%), 5% (2-11%), and 4% (1-16%), respectively. On multivariable analysis, DD → WD was associated with improved overall survival when compared with DD → DD (p < 0.001). Moreover, WD → DD was associated with a higher risk of LR (p = 0.025) CONCLUSION: A change in RLPS differentiation from primary tumor to first local recurrence appears to impact survival. These findings may be useful in counseling patients on their prognosis and subsequent management., (© 2021. Society of Surgical Oncology.)
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- 2021
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40. Corrigendum to "Local control and postponement of systemic therapy after modest dose radiotherapy in oligometastatic myxoid liposarcomas" [Radiother. Oncol. 158 (2021) 33-39].
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Lansu J, van Houdt WJ, van Langevelde K, van den Ende PLA, van der Graaf WTA, Schrage Y, van Boven H, Scholten AN, and Haas RL
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- 2021
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41. Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.
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Bagaria SP, Swallow C, Suraweera H, Raut CP, Fairweather M, Cananzi F, Quagliuolo V, Grignani G, Hompes D, Ford SJ, Nessim C, Apte S, Skoczylas J, Rutkowski P, Bonvalot S, Tzanis D, Gabriel E, Pennacchioli E, Albertsmeier M, Canter RJ, Pollock R, Grignol V, Cardona K, Gamboa AC, Novak M, Stoeckle E, Almquist M, Ahuja N, Klemen N, Van Houdt W, Gyorki D, Gangi A, Rastrelli M, van der Hage J, Schrage Y, Valeri S, Conti L, Spiegel MR, Li Z, Fiore M, and Gronchi A
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- Humans, Morbidity, Neoplasm Recurrence, Local surgery, Pancreatic Fistula etiology, Postoperative Complications etiology, Retrospective Studies, Pancreatectomy adverse effects, Sarcoma surgery
- Abstract
Background: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS., Methods: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes., Results: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042)., Conclusion: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection., (© 2021. Society of Surgical Oncology.)
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- 2021
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42. A moderate dose of preoperative radiotherapy may improve resectability in myxoid liposarcoma.
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Lansu J, Braam PM, van Werkhoven E, Scholten AN, Schrage Y, van Houdt WJ, van Langevelde K, and Haas RL
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- Adipose Tissue diagnostic imaging, Adiposity, Adult, Blood Vessels diagnostic imaging, Dose Fractionation, Radiation, Female, Humans, Liposarcoma, Myxoid pathology, Liposarcoma, Myxoid surgery, Magnetic Resonance Imaging, Male, Margins of Excision, Middle Aged, Neoadjuvant Therapy, Neoplasm, Residual, Peripheral Nerves diagnostic imaging, Preoperative Period, Prospective Studies, Radiotherapy, Adjuvant, Soft Tissue Neoplasms pathology, Soft Tissue Neoplasms surgery, Tumor Burden, Liposarcoma, Myxoid diagnostic imaging, Liposarcoma, Myxoid radiotherapy, Soft Tissue Neoplasms diagnostic imaging, Soft Tissue Neoplasms radiotherapy
- Abstract
Background: Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on resectability and to correlate MRI parameters to pathological treatment response in Myxoid Liposarcoma (MLS)., Methods: This prospective, multicenter, single-arm, phase 2 trial assessed the radiological effects of 36 Gy of preoperative radiotherapy in primary non-metastatic MLS (n=34). Distance of the tumor to the neurovascular bundle, tumor dimensions, fat fraction, enhancing fraction were determined on MRI scans at baseline, after 8 and 16 fractions, and preoperatively. Pathological response was established by central pathology review., Results: Preoperative radiotherapy resulted in a median increase of 2 mm (IQR 0 to 6) of the distance of the tumor to the neurovascular bundle. As compared to baseline, the median change of the tumor volume, craniocaudal diameter and axial diameter at preoperative MRI were -60% (IQR -74 to -41), -19% (IQR -23 to -7) and -20% (IQR -29 to -12), respectively. The median fat fraction of 0.1 (IQR 0.0-0.1) and enhancing fraction of 0.8 (IQR 0.6 to 0.9) at baseline, changed to 0.2 (IQR 0.1 to 0.5) and to 0.5(IQR 0.4 to 0.9) preoperatively, respectively. Radiological signs of response in terms of volume, enhancing fraction and fat fraction were correlated with specific pathological signs of response like hyalinization, necrosis and fatty maturation., Conclusions: A moderate dose of preoperative radiotherapy may improve resectability in MLS and could facilitate achievement of clear margins and function preservation. MRI features which were predictive for expressions of pathological response, can play a role in further personalization of neoadjuvant treatment strategies in order to improve outcome in MLS., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
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- 2021
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43. Clinicopathological features and treatment outcome of oesophageal gastrointestinal stromal tumour (GIST): A large, retrospective multicenter European study.
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Mohammadi M, IJzerman NS, Hohenberger P, Rutkowski P, Jones RL, Martin-Broto J, Gronchi A, Schöffski P, Vassos N, Farag S, Baia M, Oosten AW, Steeghs N, Desar IME, Reyners AKL, van Sandick JW, Bastiaannet E, Gelderblom H, and Schrage Y
- Subjects
- Aged, Anastomotic Leak epidemiology, Biopsy, Fine-Needle, Chemotherapy, Adjuvant, Disease-Free Survival, Esophageal Neoplasms pathology, Europe, Female, Gastrointestinal Stromal Tumors pathology, Gastrointestinal Stromal Tumors secondary, Humans, Male, Margins of Excision, Middle Aged, Mitotic Index, Neoadjuvant Therapy, Neoplasm Metastasis, Postoperative Complications, Progression-Free Survival, Plastic Surgery Procedures, Retrospective Studies, Treatment Outcome, Tumor Burden, Antineoplastic Agents therapeutic use, Esophageal Neoplasms surgery, Esophagectomy, Esophagoscopy, Gastrointestinal Stromal Tumors surgery, Imatinib Mesylate therapeutic use
- Abstract
Background: Oesophageal gastrointestinal stromal tumours (GISTs) account for ≤1% of all GISTs. Consequently, evidence to guide clinical decision-making is limited., Methods: Clinicopathological features and outcomes in patients with primary oesophageal GIST from seven European countries were collected retrospectively., Results: Eighty-three patients were identified, and median follow up was 55.0 months. At diagnosis, 59.0% had localized disease, 25.3% locally advanced and 13.3% synchronous metastasis. A biopsy (Fine Needle aspiration n = 29, histological biopsy n = 31) was performed in 60 (72.3%) patients. The mitotic count was low (<5 mitoses/50 High Power Fields (HPF)) in 24 patients and high (≥5 mitoses/50 HPF) in 27 patients. Fifty-one (61.4%) patients underwent surgical or endoscopic resection. The most common reasons to not perform an immediate resection (n = 31) were; unresectable or metastasized GIST, performance status/comorbidity, patient refusal or ongoing neo-adjuvant therapy. The type of resections were enucleation (n = 11), segmental resection (n = 6) and oesophagectomy with gastric conduit reconstruction (n = 33), with median tumour size of 3.3 cm, 4.5 cm and 7.7 cm, respectively. In patients treated with enucleation 18.2% developed recurrent disease. The recurrence rate in patients treated with segmental resection was 16.7% and in patients undergoing oesophagectomy with gastric conduit reconstruction 36.4%. Larger tumours (≥4.0 cm) and high (>5/5hpf) mitotic count were associated with worse disease free survival., Conclusion: Based on the current study, enucleation can be recommended for oesophageal GIST smaller than 4 cm, while oesophagectomy should be preserved for larger tumours. Patients with larger tumours (>4 cm) and/or high mitotic count should be treated with adjuvant therapy., 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 © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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44. The value of lymph node ultrasound and whole body 18 F-FDG PET/CT in stage IIB/C melanoma patients prior to SLNB.
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Stahlie EHA, van der Hiel B, Bruining A, van de Wiel B, Schrage YM, Wouters MWJM, van Houdt WJ, and van Akkooi ACJ
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- Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Female, Fluorodeoxyglucose F18, Humans, Lymphatic Metastasis pathology, Male, Melanoma pathology, Middle Aged, Neoplasm Staging, Pilot Projects, Prospective Studies, Radiopharmaceuticals, Skin Neoplasms pathology, Melanoma, Cutaneous Malignant, Lymphatic Metastasis diagnostic imaging, Melanoma diagnostic imaging, Positron Emission Tomography Computed Tomography, Skin Neoplasms diagnostic imaging, Ultrasonography, Whole Body Imaging
- Abstract
Background: Stage IIB/IIC (8th AJCC) melanoma patients are known to have high-risk primary tumors, however they follow the same routine to sentinel lymph node biopsy (SLNB) as more low risk tumors. Guidelines are not conclusive regarding the use of preoperative imaging for these patients. The aim of this pilot study was to assess the value of ultrasound (US) and
18 F-FDG PET/CT prior to lymphoscintigraphy (LSG) and SLNB for stage IIB/C melanoma patients., Methods: From 2019-04 till 2020-01, all stage IIB/C melanoma patients underwent US of the regional lymph nodes and whole body18 F-FDG PET/CT before their planned LSG and SLNB. Suspected metastases were confirmed with fine needle aspiration (FNA), prior to surgery., Results: In total 23 patients were screened: six had metastases detected by imaging, two by US, one by18 F-FDG PET/CT and three were detected by both imaging modalities. All metastases were nodal and therefore treatment was altered to lymph node dissection and all but one also received adjuvant therapy. Eight (47%) of the 17 patients without macroscopic disease, still had a positive SN. Sensitivity, specificity and false negative rate for US and18 F-FDG PET/CT were 36%, 89%, 64% and 29%, 100% and 71%, respectively., Conclusion: Preoperative negative imaging does not exclude the presence of SN metastases, therefore SLNB cannot be foregone. However, US detected metastases in 22% of patients, altering their treatment, which suggests it is effective in the work-up of stage IIB/C melanoma. Staging with18 F-FDG PET/CT is not of added value prior to LSG and SLNB and should therefore not be used., Competing Interests: Declaration of competing interest WvH declares advisory board/consultancy agreement and research grant received from Amgen. MW declares a research grant received from Novartis. AvA declares advisory board/consultancy agreements for Amgen, Bristol-Myers Squibb, Novartis, MSD – Merck, Merck – Pfizer, Sanofi, Sirius Medical en 4SC and received a research grant from Amgen and Merck – Pfizer., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)- Published
- 2021
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45. Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).
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Nessim C, Raut CP, Callegaro D, Barretta F, Miceli R, Fairweather M, Rutkowski P, Blay JY, Strauss D, Gonzalez R, Ahuja N, Grignani G, Quagliuolo V, Stoeckle E, De Paoli A, Pillarisetty VG, Swallow CJ, Bagaria SP, Canter RJ, Mullen JT, Schrage Y, Pennacchioli E, van Houdt W, Cardona K, Fiore M, Gronchi A, and Lahat G
- Subjects
- Female, Humans, Male, Middle Aged, Morbidity, Neoplasm Recurrence, Local surgery, Retrospective Studies, Survival Rate, Liposarcoma surgery, Retroperitoneal Neoplasms surgery, Sarcoma surgery
- Abstract
Background: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking., Methods: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011. Uni- and multivariable logistic models were fitted to study the association between major (Clavien-Dindo grade ≥ 3) complications and patient/surgery characteristics as well as outcome. The resected organ score, a method of standardizing the number of organs resected, as previously described by the TARPSWG, was used., Results: The 681 patients in this study had a median age of 59 years, and 51.8% were female. The most common histologic subtype was de-differentiated liposarcoma (43%), the median resected organ score was 1, and 83.3% of the patients achieved an R0 or R1 resection. Major complications occurred for 16% of the patients, and the 90-day mortality rate was 0.4%. In the multivariable analysis, a transfusion requirement was found to be a significant predictor of major complications (p < 0.001) and worse overall survival (OS) (p = 0.010). However, having a major complication was not associated with a worse OS or a higher incidence of local recurrence or distant metastasis., Conclusions: A surgical approach to recurrent RPS is relatively safe and comparable with primary RPS in terms of complications and postoperative mortality when performed at specialized sarcoma centers. Because alternative effective therapies still are lacking, when indicated, resection of a recurrent RPS is a reasonable option. Every effort should be made to minimize the need for blood transfusions.
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- 2021
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46. Local control and postponement of systemic therapy after modest dose radiotherapy in oligometastatic myxoid liposarcomas.
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Lansu J, van Houdt WJ, van Langevelde K, van den Ende PLA, van der Graaf WTA, Schrage Y, van Boven H, Scholten AN, and Haas RL
- Subjects
- Adult, Combined Modality Therapy, Humans, Neoplasm Recurrence, Local, Retrospective Studies, Liposarcoma, Myxoid radiotherapy, Radiation Oncology
- Abstract
Introduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS., Methods: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy. The primary endpoint was local progression free survival(LPFS). Secondary endpoints included postponement of systemic therapy, symptom reduction, radiological objective response, and toxicity., Results: Nine patients with a total of 25 lesions were included, with a median follow-up of 23 months. The median number of lesions per patient was three and the trunk wall and bone were the most frequently affected sites. In lesions treated with definitive RT(n = 21), LPFS rates at 1, 2, and 3 years were respectively 73%, 61%, and 40%. Radiological objective response and clinical symptom reduction were achieved in 8/15(53%) and 9/10(90%) of the evaluable lesions, respectively. No local recurrences occurred in lesions treated with RT and metastasectomy(n = 4). For the entire study population, the median postponement of systemic therapy was 10 months. Grade ≥ 2 toxicity was observed in 2/9(22%) of patients., Conclusions: This trial suggests that 36 Gy could possibly be effective to achieve local control, postpone systemic therapy and reduce symptoms in oMLS. Given the minimal toxicity this treatment could be reasonably considered in oMLS., Competing Interests: Declaration of Competing Interest W.vd.G: advisory Bayer and GSK, consultant Spingworks, research grant Novartis. The other authors have nothing to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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47. Primary mesenteric sarcomas: Collaborative experience from the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).
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Tattersall HL, Hodson J, Cardona K, Lee RM, Nessim C, Gladdy R, Van Der Hage J, Schrage Y, Tseng WW, van Houdt W, Novak M, Grignani G, Tolomeo F, Goel N, Ryon E, Gyorki D, Bagaria SP, Gonzalez JA, Arnau ABM, Sayyed R, Tirotta F, Evenden C, Desai A, Almond M, Glasbey J, Fiore M, Gronchi A, and Ford SJ
- Subjects
- Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Prognosis, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms surgery, Retrospective Studies, Sarcoma pathology, Sarcoma surgery, Survival Rate, Mesentery pathology, Neoplasm Recurrence, Local mortality, Retroperitoneal Neoplasms mortality, Sarcoma mortality
- Abstract
Background: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function., Objectives: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS., Methods: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019., Results: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery., Conclusion: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging., (© 2020 Wiley Periodicals LLC.)
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- 2021
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48. Has the Outcome for Patients Who Undergo Resection of Primary Retroperitoneal Sarcoma Changed Over Time? A Study of Time Trends During the Past 15 years.
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Callegaro D, Raut CP, Ng D, Strauss DC, Honoré C, Stoeckle E, Bonvalot S, Haas RL, Vassos N, Conti L, Gladdy RA, Fairweather M, van Houdt W, Schrage Y, van Coevorden F, Rutkowski P, Miceli R, Gronchi A, and Swallow CJ
- Subjects
- Adult, Follow-Up Studies, Humans, Neoplasm Recurrence, Local surgery, Retrospective Studies, Survival Rate, Bone Neoplasms, Retroperitoneal Neoplasms surgery, Sarcoma surgery
- Abstract
Background: This study aimed to investigate changes in treatment strategy and outcome for patients with primary retroperitoneal sarcoma (RPS) undergoing resection at referral centers during a recent period., Methods: The study enrolled consecutive adult patients with primary non-metastatic RPS who underwent resection with curative intent between 2002 and 2017 at 10 referral centers. The patients were grouped into three periods according to date of surgery: t1 (2002-2006), t2 (2007-2011), and t3 (2012-2017). Five-year overall survival (OS), disease-specific survival (DSS), and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariable analyses for OS and DSS were performed., Results: The study included 1942 patients. The median follow-up period after resection varied from 130 months (interquartile range [IQR], 124-141 months) in t1 to 37 months (IQR, 35-39 months) in t3. The 5-year OS was 61.2% (95% confidence interval [CI], 56.4-66.3%) in t1, 67.0% (95 CI, 63.2-71.0%) in t2, and 71.9% (95% CI, 67.7-76.1%) in t3. The rate of macroscopically incomplete resection (R2) was 7.1% in t1 versus 4.7% in t3 (p = 0.066). The median number of resected organs increased over time (p < 0.001). In the multivariable analysis resection during t3 was associated with better OS and DSS. The 90-day postoperative mortality improved over time (4.3% in t1 to 2.3% in t3; p = 0.031). The 5-year CCI of LR and DM did not change significantly over time., Conclusions: The long-term survival of patients who underwent resection for primary RPS has increased during the past 15 years. This increased survival is attributable to better patient selection for resection, quality of surgery, and perioperative patient management.
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- 2021
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49. Management of meningeal solitary fibrous tumors/hemangiopericytoma; surgery alone or surgery plus postoperative radiotherapy?
- Author
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Haas RL, Walraven I, Lecointe-Artzner E, van Houdt WJ, Scholten AN, Strauss D, Schrage Y, Hayes AJ, Raut CP, Fairweather M, Baldini EH, Gronchi A, De Rosa L, Griffin AM, Ferguson PC, Wunder J, van de Sande MAJ, Krol ADG, Skoczylas J, Brandsma D, Doglietto F, Sangalli C, and Stacchiotti S
- Subjects
- Adult, Humans, Neoplasm Recurrence, Local, Retrospective Studies, Hemangiopericytoma radiotherapy, Hemangiopericytoma surgery, Meningeal Neoplasms radiotherapy, Meningeal Neoplasms surgery, Solitary Fibrous Tumors radiotherapy, Solitary Fibrous Tumors surgery
- Abstract
Introduction: A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs., Patients and Methods: A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t -test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves., Results: Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT ( p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011)., Conclusion: This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.
- Published
- 2021
- Full Text
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50. Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.
- Author
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Lansu J, Bovée JVMG, Braam P, van Boven H, Flucke U, Bonenkamp JJ, Miah AB, Zaidi SH, Thway K, Bruland ØS, Baldini EH, Jebsen NL, Scholten AN, van den Ende PLA, Krol ADG, Ubbels JF, van der Hage JA, van Werkhoven E, Klomp HM, van der Graaf WTA, van Coevorden F, Schrage Y, van Houdt WJ, and Haas RL
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Prospective Studies, Liposarcoma, Myxoid radiotherapy, Preoperative Care, Radiation Dosage
- Abstract
Importance: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity., Objective: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity., Design, Setting, and Participants: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020., Interventions: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks., Main Outcomes and Measures: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects., Results: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%., Conclusions and Relevance: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers., Trial Registration: ClinicalTrials.gov Identifier: NCT02106312.
- Published
- 2021
- Full Text
- View/download PDF
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