Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, ... more Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, but their local aggressive tumour growth and unpredictable behaviour can have a significant impact on health-related quality of life (HRQoL). Little is known about which DTF patients are particularly affected by an impaired HRQoL. The objectives of this study were to assess HRQoL among different groups of DTF patients and to investigate which socio-demographic and clinical characteristics were associated with DTF-specific HRQoL. A cross-sectional study was conducted among DTF patients from the United Kingdom and the Netherlands. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), accompanied by the DTF-QoL to assess DTF-specific HRQoL. The scores were compared amongst subgroups, based on the socio-demographic and clinical characteristics of DTF patients. Multiple linear regression analyses with a b...
Curative treatment of most solid tumors includes surgical interference. However, the incidence of... more Curative treatment of most solid tumors includes surgical interference. However, the incidence of local recurrence or distant micrometastases is significantly lower when patients are treated with systemic or locally administered chemo- or targeted therapy. In the last decade, many novel targeting strategies have been developed for several tumor types. This thesis aims to identify promising targeting strategies for glioma and colorectal carcinoma and reveals resistance mechanisms for these new promising strategies. In the first part, the therapeutic effects of oncolytic viral vectors on glioma and colorectal cancer are explored. Infectivity and cell killing properties of transductional and transcriptional targeted adenoviral vectors is evaluated on glioma cell lines and freshly derived glioma tissue from patients. In this part, a very selective, conditionally replicating adenovirus based on the survivin promoter is presented for the treatment of glioma. In colon cancer samples, this ...
This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (L... more 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. 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. 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. 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.
International journal of radiation oncology, biology, physics, Jan 17, 2018
Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of lar... more Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of large prospective studies on radiation therapy (RT) with definitive and/or palliative intent in SFT patients, this retrospective study aimed to better define the benefit of RT in this disease. A retrospective observational study was performed across 7 sarcoma centers. Clinical information was retrieved from all patients receiving RT without surgery over the course of their locally advanced and/or metastatic disease. Differences in treatment characteristics between subgroups were tested using analysis-of-variance tests. Local control (LC) and overall survival (OS) rates were calculated as time from the start of RT until local progression and death from any cause, respectively. Since 1990, a total of 40 patients were identified. RT was applied with definitive intent in 16 patients and with palliative intent in 24. The median follow-up period was 62 months. In patients treated with definitive ...
Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give a... more Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give an overview of current standards in treatment of this disease and discuss new developments. Surgery with complete resection of the primary tumor is still the only curative modality. The role of preoperative radiotherapy is not clear and is currently being investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard of care but can be considered occasionally when complete resection is uncertain. Local and distant recurrent disease carries a dismal prognosis, although long-term survival can be achieved. Liposarcomas tend to recur locally, whereas distant recurrences are more often seen in leiomyosarcoma and other subtypes. Outcome improves when patients are treated in high volume sarcoma centers. In the metastatic setting, newer systemic agents have recently been approved. Treatment of retroperitoneal sarcomas is complex and all patients should be treated in a multidiscip...
Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability. The go... more Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability. The goal of this study was to analyze oncologic outcome and quality of life after resection in order to better select patients who are more likely to benefit from this operation. Patients treated with a hindquarter amputation between 1989 and 2015 for a bone or soft tissue sarcoma were selected from our database. Clinical and histopathological features were analyzed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. In addition, performance status, ambulatory status, and pain were assessed from the hospital charts for patients surviving longer than 1 year after surgery. Overall, 78 patients underwent a hindquarter amputation for sarcoma. The median hospital stay was 24 days and 49% of patients had wound complications. In-hospital mortality was 6%. Overall survival for patients with metastases at presentation was significantly worse than patients with localized ...
Data from seminal randomized trials over the last several decades has resulted in local control r... more Data from seminal randomized trials over the last several decades has resulted in local control rates of 80–95% of patients with localized extremity and trunk sarcoma (ETSTS) undergoing limb-sparing surgery with preor postoperative radiation therapy (RT) and anthracyclinebased chemotherapy; however, up to 50% of patients with localized disease will develop distant metastases. Although doxorubicin (± ifosfamide) has remained the backbone of systemic chemotherapy for ETSTS over the last 40 years, it benefits only a subset of patients with sometimes significant toxicity, highlighting the need for novel therapies in this rare disease.
Carolyn Nessim, MD, MSc, FRCSC, FACS, Chandrajit P. Raut, MD, MSc, Dario Callegaro, MD, Francesco... more Carolyn Nessim, MD, MSc, FRCSC, FACS, Chandrajit P. Raut, MD, MSc, Dario Callegaro, MD, Francesco Barretta, PhD, Rosalba Miceli, PhD, Mark Fairweather, MD, Jean-Yves Blay, MD, PhD, Dirk Strauss, MD, Piotr Rutkowski, MD, PhD, Nita Ahuja, MD, MBA, Ricardo Gonzalez, MD, Giovanni Grignani, MD, Vittorio Quagliuolo, MD, Eberhard Stoeckle, MD, Guy Lahat, MD, Antonino De Paoli, MD, Venu G. Pillarisetty, MD, Robert J. Canter, MD, John T. Mullen, MD, Elisabetta Pennacchioli, MD, Winan van Houdt, Carol J. Swallow, MD, PhD, Yvonne Schrage, MD, PhD, Kenneth Cardona, MD, Marco Fiore, MD, Alessandro Gronchi, MD, and Sanjay P. Bagaria, MD Department of Surgery, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada; Department of Surgery, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, MA; Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Applied Research and Technological Development, Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Center Léon Bérard Cancer Center, Lyon, France; Department of Surgery, Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom; Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Surgery, Yale School of Medicine, New Haven, CT; John Hopkins University School of Medicine, Baltimore, MD; Department of Surgery, Moffitt Cancer Center, Tampa, FL; Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, TO, Italy; Department of Surgery, Istituto Clinico Humanitas IRCCS, Milan, Italy; Department of Surgery, Institut Bergonié, Bordeaux, France; Department of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano, Italy; Department of Surgery, University of Washington School of Medicine, Seattle, WA; Department of Surgery, UC Davis Health, Sacramento, CA; Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Istituto Europeo di Oncologia, Milan, Italy; Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Surgery, Mount Sinai Hospital and Princess Margaret Cancer Center, Toronto, Canada; Department of Surgery, Leiden University Medical Center, Leiden, Netherlands; Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Department of Surgery, Mayo Clinic, Jacksonville, FL
Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differ... more 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. 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. 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) 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.
Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related ... more Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). Methods: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. Results: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with wors...
Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, ... more Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, but their local aggressive tumour growth and unpredictable behaviour can have a significant impact on health-related quality of life (HRQoL). Little is known about which DTF patients are particularly affected by an impaired HRQoL. The objectives of this study were to assess HRQoL among different groups of DTF patients and to investigate which socio-demographic and clinical characteristics were associated with DTF-specific HRQoL. A cross-sectional study was conducted among DTF patients from the United Kingdom and the Netherlands. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), accompanied by the DTF-QoL to assess DTF-specific HRQoL. The scores were compared amongst subgroups, based on the socio-demographic and clinical characteristics of DTF patients. Multiple linear regression analyses with a b...
Curative treatment of most solid tumors includes surgical interference. However, the incidence of... more Curative treatment of most solid tumors includes surgical interference. However, the incidence of local recurrence or distant micrometastases is significantly lower when patients are treated with systemic or locally administered chemo- or targeted therapy. In the last decade, many novel targeting strategies have been developed for several tumor types. This thesis aims to identify promising targeting strategies for glioma and colorectal carcinoma and reveals resistance mechanisms for these new promising strategies. In the first part, the therapeutic effects of oncolytic viral vectors on glioma and colorectal cancer are explored. Infectivity and cell killing properties of transductional and transcriptional targeted adenoviral vectors is evaluated on glioma cell lines and freshly derived glioma tissue from patients. In this part, a very selective, conditionally replicating adenovirus based on the survivin promoter is presented for the treatment of glioma. In colon cancer samples, this ...
This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (L... more 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. 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. 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. 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.
International journal of radiation oncology, biology, physics, Jan 17, 2018
Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of lar... more Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of large prospective studies on radiation therapy (RT) with definitive and/or palliative intent in SFT patients, this retrospective study aimed to better define the benefit of RT in this disease. A retrospective observational study was performed across 7 sarcoma centers. Clinical information was retrieved from all patients receiving RT without surgery over the course of their locally advanced and/or metastatic disease. Differences in treatment characteristics between subgroups were tested using analysis-of-variance tests. Local control (LC) and overall survival (OS) rates were calculated as time from the start of RT until local progression and death from any cause, respectively. Since 1990, a total of 40 patients were identified. RT was applied with definitive intent in 16 patients and with palliative intent in 24. The median follow-up period was 62 months. In patients treated with definitive ...
Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give a... more Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give an overview of current standards in treatment of this disease and discuss new developments. Surgery with complete resection of the primary tumor is still the only curative modality. The role of preoperative radiotherapy is not clear and is currently being investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard of care but can be considered occasionally when complete resection is uncertain. Local and distant recurrent disease carries a dismal prognosis, although long-term survival can be achieved. Liposarcomas tend to recur locally, whereas distant recurrences are more often seen in leiomyosarcoma and other subtypes. Outcome improves when patients are treated in high volume sarcoma centers. In the metastatic setting, newer systemic agents have recently been approved. Treatment of retroperitoneal sarcomas is complex and all patients should be treated in a multidiscip...
Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability. The go... more Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability. The goal of this study was to analyze oncologic outcome and quality of life after resection in order to better select patients who are more likely to benefit from this operation. Patients treated with a hindquarter amputation between 1989 and 2015 for a bone or soft tissue sarcoma were selected from our database. Clinical and histopathological features were analyzed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. In addition, performance status, ambulatory status, and pain were assessed from the hospital charts for patients surviving longer than 1 year after surgery. Overall, 78 patients underwent a hindquarter amputation for sarcoma. The median hospital stay was 24 days and 49% of patients had wound complications. In-hospital mortality was 6%. Overall survival for patients with metastases at presentation was significantly worse than patients with localized ...
Data from seminal randomized trials over the last several decades has resulted in local control r... more Data from seminal randomized trials over the last several decades has resulted in local control rates of 80–95% of patients with localized extremity and trunk sarcoma (ETSTS) undergoing limb-sparing surgery with preor postoperative radiation therapy (RT) and anthracyclinebased chemotherapy; however, up to 50% of patients with localized disease will develop distant metastases. Although doxorubicin (± ifosfamide) has remained the backbone of systemic chemotherapy for ETSTS over the last 40 years, it benefits only a subset of patients with sometimes significant toxicity, highlighting the need for novel therapies in this rare disease.
Carolyn Nessim, MD, MSc, FRCSC, FACS, Chandrajit P. Raut, MD, MSc, Dario Callegaro, MD, Francesco... more Carolyn Nessim, MD, MSc, FRCSC, FACS, Chandrajit P. Raut, MD, MSc, Dario Callegaro, MD, Francesco Barretta, PhD, Rosalba Miceli, PhD, Mark Fairweather, MD, Jean-Yves Blay, MD, PhD, Dirk Strauss, MD, Piotr Rutkowski, MD, PhD, Nita Ahuja, MD, MBA, Ricardo Gonzalez, MD, Giovanni Grignani, MD, Vittorio Quagliuolo, MD, Eberhard Stoeckle, MD, Guy Lahat, MD, Antonino De Paoli, MD, Venu G. Pillarisetty, MD, Robert J. Canter, MD, John T. Mullen, MD, Elisabetta Pennacchioli, MD, Winan van Houdt, Carol J. Swallow, MD, PhD, Yvonne Schrage, MD, PhD, Kenneth Cardona, MD, Marco Fiore, MD, Alessandro Gronchi, MD, and Sanjay P. Bagaria, MD Department of Surgery, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada; Department of Surgery, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, MA; Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Applied Research and Technological Development, Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Center Léon Bérard Cancer Center, Lyon, France; Department of Surgery, Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom; Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Surgery, Yale School of Medicine, New Haven, CT; John Hopkins University School of Medicine, Baltimore, MD; Department of Surgery, Moffitt Cancer Center, Tampa, FL; Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, TO, Italy; Department of Surgery, Istituto Clinico Humanitas IRCCS, Milan, Italy; Department of Surgery, Institut Bergonié, Bordeaux, France; Department of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano, Italy; Department of Surgery, University of Washington School of Medicine, Seattle, WA; Department of Surgery, UC Davis Health, Sacramento, CA; Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Istituto Europeo di Oncologia, Milan, Italy; Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Surgery, Mount Sinai Hospital and Princess Margaret Cancer Center, Toronto, Canada; Department of Surgery, Leiden University Medical Center, Leiden, Netherlands; Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Department of Surgery, Mayo Clinic, Jacksonville, FL
Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differ... more 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. 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. 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) 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.
Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related ... more Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). Methods: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. Results: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with wors...
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Papers by Winan Van Houdt