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Brandenburg an der Havel, Germany

Joensuu H.,University of Helsinki | Reichardt P.,Sarkomzentrum Berlin Brandenburg | Eriksson M.,Skane 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. Source

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. Source

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. Source

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. Source

Joensuu H.,University of Helsinki | Eriksson M.,Skane 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. Source

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