Brandenburg an der Havel, Germany
Brandenburg an der Havel, Germany

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Joensuu H.,University of Helsinki | Eriksson M.,Skåne University Hospital | Hall K.S.,University of Oslo | Hartmann J.T.,University of Kiel | And 16 more authors.
Cancer | Year: 2014

BACKGROUND Little is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib. METHODS Risk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high-risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months. RESULTS Five factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence-free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5-year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P < .001 for each comparison). CONCLUSIONS The scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.


Joensuu H.,University of Helsinki | Eriksson M.,Lund University | Sundby Hall K.,University of Oslo | Reichardt A.,Sarkomzentrum Berlin Brandenburg | And 15 more authors.
Journal of Clinical Oncology | Year: 2016

Purpose: Three years of adjuvant imatinib therapy are recommended for patients with GI stromal tumor (GIST) with high-risk features, according to survival findings in the Scandinavian Sarcoma Group XVIII/AIO (Arbeitsgemeinschaft Internistische Onkologie) trial. To investigate whether the survival benefits have persisted, we performed the second planned analysis of the trial. Patients and Methods: Eligible patients had macroscopically completely excised, KIT-positive GIST with a high risk of recurrence, as determined by using the modified National Institutes of Health criteria. After surgery, the patients were randomly assigned to receive imatinib for either 1 or 3 years. The primary objective was recurrence-free survival (RFS), and the secondary objectives included survival. Results: A total of 400 patients were entered onto this open-label study between February 4, 2004, and September 29, 2008. During a median follow-up of 90 months, 171 recurrences and 69 deaths were detected. Patients assigned to the 3-year group had longer RFS than those assigned to the 1- year group; 5-year RFS was 71.1% versus 52.3%, respectively (hazard ratio [HR], 0.60; 95% CI 0.44 to 0.81; P < .001), and survival was 91.9% versus 85.3% (HR, 0.60; 95% CI, 0.37 to 0.97; P = .036). Patients in the 3-year group survived longer in the subset with centrally confirmed GIST and without macroscopic metastases at study entry (93.4% v 86.8%; HR, 0.53; 95% CI, 0.30 to 0.93; P = .024). Similar numbers of cardiac events and second cancers were recorded in the groups. Conclusion: Three years of adjuvant imatinib therapy results in longer survival than 1 year of imatinib. High 5-year survival rates are achievable in patient populations with high-risk GIST. © 2015 by American Society of Clinical Oncology.


Joensuu H.,University of Helsinki | Reichardt P.,Sarkomzentrum Berlin Brandenburg | Eriksson M.,Skåne University Hospital | Hall K.S.,University of Oslo | Vehtari A.,Aalto University
Radiology | Year: 2014

Purpose: To develop a mathematical model to adjust the timing of computed tomography (CT) scans with the hazard of cancer recurrence in time to facilitate early detection of cancer recurrence. Materials and Methods: The clinical data were extracted from the randomized Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) trial database. The SSG XVIII/AIO trial was registered (trial no. NCT00116935) and approved by the national or institutional review boards. In the trial, 1- and 3-year durations of adjuvant imatinib mesylate in the treatment of patients with gastrointestinal stromal tumor (GIST) were compared. A nonhomogeneous Poisson model with a piecewise log-constant hazard in time that accounts for the nonlinear pattern of GIST recurrence was applied to tumor site, mitotic count, and recurrence data. The optimal times to obtain follow-up CT scans were computed by modifying the frequency of CT scans with the hazard of tumor recurrence in time. The hazard-adjusted follow-up schedules were compared with the National Comprehensive Cancer Network (NCCN) guidelines of the United States, which suggest imaging with CT at intervals of 3-6 months for 3-5 years and then annually. Results: Optimized timing of CT scans on the basis of hazard of recurrence resulted in follow-up schedule options where CT is performed more sparsely than in the NCCN guidelines during adjuvant imatinib administration and more frequently, at approximately 3-month intervals, during the first 2 years that follow imatinib discontinuation when the risk of recurrence was the greatest. The number of CT scans could be reduced by a median of 31% (from 13 to nine) compared with the standard schedules within the first 6 years of follow-up without increasing the delay in recurrence detection. Conclusion: Detection of GIST recurrence may be enhanced by adjusting the timing of the CT scans with the hazard of recurrence. The method may be applicable to other human tumor types. © RSNA, 2013.


Tunn P.-U.,Sarkomzentrum Berlin Brandenburg | Werner M.,Institute For Gewebediagnostik Berlin
Orthopade | Year: 2015

A secondary peripheral chondrosarcoma (SPC) evolving from an osteochondroma is rare, but it has been described several times. The development of an osteosarcomatous dedifferentiated chondrosarcoma in a locally recurrent SPC is extremely rare. The following case report of a 46-year-old man demonstrates and discusses this phenomenon. © 2015, Springer-Verlag Berlin Heidelberg.


Joensuu H.,University of Helsinki | Eriksson M.,Skåne University Hospital | Hall K.S.,University of Oslo | Hartmann J.T.,University of Tübingen | And 18 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo. Objective: To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery. Design, Setting, and Patients: Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria. Intervention: Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery. Main Outcome Measures: The primary end point was RFS; the secondary end points included overall survival and treatment safety. Results: Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P<.001; 5-year RFS, 65.6% vs 47.9%, respectively) and longer overall survival (HR, 0.45; 95% CI, 0.22-0.89; P=.02; 5-year survival, 92.0% vs 81.7%). Imatinib was generally well tolerated, but 12.6% and 25.8% of patients assigned to the 12- and 36-month groups, respectively, discontinued imatinib for a reason other than GIST recurrence. Conclusion: Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence. ©2012 American Medical Association. All rights reserved.


Friesenbichler J.,Medical University of Graz | Leithner A.,Medical University of Graz | Maurer-Ertl W.,Medical University of Graz | Szkandera J.,Medical University of Graz | And 6 more authors.
International Orthopaedics | Year: 2014

Purpose: Primary malignant bone tumours and soft tissue sarcomas of the chest wall are exceedingly rare entities. The aim of this study was a retrospective two-institutional analysis of surgical therapy with respect to the kind and amount of the resection performed, the type of reconstruction and the oncological outcome. Methods: Between September 1999 and August 2010 31 patients (seven women and 24 men) were treated due to a primary malignant bone tumour or soft tissue sarcoma of the chest wall in two centres. Eight low-grade sarcomas were noted as well as 23 highly malignant sarcomas. The tumours originated from the sternum in six cases, from the ribs in 12 cases, from the soft tissues of the thoracic wall in 11 cases and from a vertebral body and the clavicle in one case each. Results: In 26 cases wide resection margins were achieved, while four were intralesional and one was marginal. In all 31 cases the defect of the chest wall was reconstructed using mesh grafts. At a mean follow-up of 51 months 20 patients were without evidence of disease, three were alive with disease, seven patients had died and one patient was lost to follow-up. One recurrence was detected after wide resection of a malignant triton tumour. Conclusions: Primary malignant bone tumour or soft tissue sarcoma of the chest wall should be treated according to the same surgical oncological principles as established for the extremities. Reconstruction with mesh grafts and musculocutaneous flaps is associated with a low morbidity. © Springer-Verlag 2014.


Reichardt A.,Sarkomzentrum Berlin Brandenburg | Reichardt P.,Sarkomzentrum Berlin Brandenburg
Internistische Praxis | Year: 2012

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. For localized GIST complete surgical resection is standard of care. Tumor rupture should be avoided since it has a high risk of peritoneal metastases. For small tumors laparoscopic approach is acceptable maintaining the standards of oncologic surgery. Depending on tumor size, mitotic count, and localization of primary, the risk of recurrence might be very high after potentially curative surgery. Patients with intermediate and high risk according MIETTINEN classification should be treated with imatinib adjuvant for 3 years. Recent data show that this does significantly increase not only the progression-free but also the overall survival compared with 1 year adjuvant treatment, with the exemption of patients with a D842V mutation in exon 18 of PDGRFA receptor. They should not be treated adjuvant. For resectable locally advanced tumors where complete surgery might be mutilating neoadjuvant treatment is recommended. For not resectable locally advanced and metastatic GIST, standard of care is 400 mg imatinib daily. Patients with a Kit exon 9 mutation should be treated with 800 mg daily, since they have a significantly longer progression free survival with the higher dose. Imatinib therapy should by all means be continued until progression or intolerance. In case of disease progression ESMO guidelines recommend an increased dose of 800 mg daily. For further tumor progression second line therapy with sunitinib is recommended. Upon failure with approved treatments, patients should be referred for treatment within clinical trials.


Soft tissue sarcomas are rare tumors that represent a major challenge due to varying clinical presentations and often interdisciplinary treatment concepts. Gold standard for the treatment of localized resectable soft tissue sarcomas is complete surgical removal. In metastatic soft tissue sarcoma, systemic therapy is the treatment of choice. The most active drugs are anthracyclines and ifosfamide. Combination chemotherapy has improved both response rate and progression-free survival at the cost of increased toxicity. Imatinib at a dose of 400 mg/day is the gold standard for patients with advanced or metastatic gastrointestinal stromal tumors (GIST). In patients with a mutation in KIT exon 9, 800 mg/day is the recommended dose. In imatinib refractory or intolerant patients, sunitinib is recommended. Regorafenib has been approved for third-line therapy. © 2016, Springer-Verlag Berlin Heidelberg.

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