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| 3. |
- Bielack, Stefan S, et al.
(author)
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Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial
- 2015
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In: Journal of Clinical Oncology. - 1527-7755. ; 33:20, s. 2279-2287
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Journal article (peer-reviewed)abstract
- Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.
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- Boye, Kjetil, et al.
(author)
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High-Dose Chemotherapy with Stem Cell Rescue in the Primary Treatment of Metastatic and Pelvic Osteosarcoma: Final Results of the ISG/SSG II Study
- 2014
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 61:5, s. 840-845
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Journal article (peer-reviewed)abstract
- BackgroundPatients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. MethodsFrom May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. ResultsTwenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P=0.72) or OS (P=0.49) between patients who did or did not receive HDCT. ConclusionsThe administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma. Pediatr Blood Cancer 2014;61:840-845. (c) 2013 Wiley Periodicals, Inc.
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- Danielsen, Stine A, et al.
(author)
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Methylated RASSF1A in malignant peripheral nerve sheath tumors identifies neurofibromatosis type 1 patients with inferior prognosis.
- 2015
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In: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 17:1, s. 63-69
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Journal article (peer-reviewed)abstract
- Malignant peripheral nerve sheath tumor (MPNST) is a rare and highly aggressive disease with no evidence of effect from adjuvant therapy. It is further associated with the hereditary syndrome neurofibromatosis type 1 (NF1). Silencing of the tumor suppressor gene RASSF1A through DNA promoter hypermethylation is known to be involved in cancer development, but its impact in MPNSTs remains unsettled.
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- Engellau, Jacob, et al.
(author)
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Time dependence of prognostic factors for patients with soft tissue sarcoma : a Scandinavian Sarcoma Group Study of 338 malignant fibrous histiocytomas
- 2004
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In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 100:10, s. 2233-2239
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prognostic factors for metastasis in soft tissue sarcoma govern decisions regarding adjuvant treatment. However, the significance of initial tumor-related prognostic factors over time is largely unknown.METHODS: The current study included 338 patients with malignant fibrous histiocytoma (MFH) of the extremities or the trunk wall whose tumors were reviewed by the Scandinavian Sarcoma Pathology Review Group. Of these 338 patients, 329 (97%) had high-grade tumors. The median follow-up period was 7 years. Metastases occurred in 110 of 338 of patients after a median follow-up period of 14 months, with roughly one-third (32 of 110) occurring after 2 years. The authors investigated the prognostic significance of tumor size, tumor depth, histologic grade, microscopic tumor necrosis, vascular invasion, mitotic rate, and local tumor recurrence at various time intervals using metastases as an endpoint.RESULTS: On univariate analysis, all investigated factors were found to be correlated with metastases for the entire follow-up period and also for the first 2 years of follow-up; beyond this time point, only size, tumor depth, and local recurrence were significant. On multivariate analysis, necrosis and local tumor recurrence were significant for the entire follow-up duration and also for the first 2 years of follow-up, whereas only tumor depth and local recurrence were significant beyond 2 years of follow-up. For all initial factors, the annual metastasis risks in the high-risk and low-risk groups converged to < 0.1 after 2 years and to near 0 after 5 years.CONCLUSIONS: Prognostic factors for metastasis in MFH were time dependent. The predictive value of the initial prognostic factors was limited to the first 2 years of follow-up. The lack of observed prognostic value beyond 2 years of follow-up probably was attributable to heterogeneity within risk categories as a result of measurement errors and unknown biologic variations.
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| 8. |
- Eriksson, Mikael, et al.
(author)
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Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST)
- 2021
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.
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| 9. |
- Eriksson, Mikael, et al.
(author)
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Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence?
- 2016
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 59, s. 128-133
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Journal article (peer-reviewed)abstract
- PURPOSE: Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes.METHODS: We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS).RESULTS: A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour ≥10 cm in diameter.CONCLUSION: A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy.
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| 10. |
- Ferrari, Stefano, et al.
(author)
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EURO-B.O.S.S. : A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma
- 2018
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In: Tumori. - : SAGE Publications. - 0300-8916 .- 2038-2529. ; 104:1, s. 30-36
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma.METHODS: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study.RESULTS: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity.CONCLUSIONS: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.
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