Publications by authors named "Ivar Hompland"

14 Publications

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Outcome in dedifferentiated chondrosarcoma for patients treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study.

Eur J Cancer 2021 Jul 11;151:150-158. Epub 2021 May 11.

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy.

Introduction: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study.

Materials And Methods: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models.

Results: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles.

Conclusions: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
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http://dx.doi.org/10.1016/j.ejca.2021.04.017DOI Listing
July 2021

Integrating Anatomical, Molecular and Clinical Risk Factors in Gastrointestinal Stromal Tumor of the Stomach.

Ann Surg Oncol 2021 Mar 2. Epub 2021 Mar 2.

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.

Background: Adjuvant imatinib for 3 years is recommended to patients with high-risk gastrointestinal stromal tumor (GIST). Risk stratification is inaccurate, and risk assessments are further complicated by the increased use of neoadjuvant treatment. Anatomical criteria for prognostication have not been investigated.

Methods: Clinical, molecular, and anatomical variables were retrospectively studied in a population-based cohort of 295 patients with gastric GIST resected between 2000 and 2018. Gastric subsite was divided into the upper, middle, and lower thirds. Growth pattern was classified as luminal, exophytic, or transmural based on imaging and surgical reports.

Results: Of 113 tumors in the upper third of the stomach, 103 (91.2%) were KIT mutated, 7 (6.2%) were PDGFRA mutated, and 104 (92.0%) harbored genotypes sensitive to imatinib. Transmural tumors were strongly associated with a high mitotic index. Five-year recurrence-free survival (RFS) was 71% for patients with transmural tumors versus 96% with luminal or exophytic tumors (hazard ratio [HR] 8.45, 95% confidence interval [CI] 3.69-19.36; p < 0.001), and, in high-risk patients, 5-year RFS was 46% for patients with transmural tumors versus 83% with luminal or exophytic tumors (HR 4.47, 95% CI 1.71-11.66; p = 0.001). Among 134 patients with tumors > 5 cm, there were 29 recurrences. Only five patients with exophytic or luminal tumors had recurrent disease, of whom four had tumor rupture. Five-year RFS for patients with exophytic/luminal tumors >5 cm without rupture was 98%.

Conclusions: In the upper third, over 90% of tumors were sensitive to imatinib. Patients with exophytic or luminal tumors without rupture, irrespective of size, had an excellent prognosis and may not benefit from adjuvant therapy.
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http://dx.doi.org/10.1245/s10434-021-09605-8DOI Listing
March 2021

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial.

Cancer Immunol Immunother 2021 Feb 12. Epub 2021 Feb 12.

IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

Aim: To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

Material And Methods: The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways.

Results: Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2-2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8-9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response.

Conclusion: In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.
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http://dx.doi.org/10.1007/s00262-021-02876-wDOI Listing
February 2021

Striving towards Normality in Daily Life: A Qualitative Study of Patients Living with Metastatic Gastrointestinal Stromal Tumour in Long-Term Clinical Remission.

Sarcoma 2020 6;2020:1814394. Epub 2020 Oct 6.

Department of Interdisciplinary Health Sciences, Institute of Health and Society, University of Oslo, P.O. Box 1089, Blindern-0317, Oslo, Norway.

Background: This study explored how patients with metastatic gastrointestinal stromal tumour (GIST) experience the psychosocial challenges associated with their disease and its treatment, as well as how that experience influenced their practical, relational, vocational, and existential life.

Methods: This qualitative study has an explorative design and applied a phenomenological and hermeneutical approach. We conducted in-depth, semistructured interviews with 20 patients with metastatic GIST in long-term clinical remission. The gathered data were interpreted using a thematic analysis.

Results: Living with metastatic GIST, as well as the side effects of the required medication, led to changes that limited the participants' daily life. They expressed how tiredness, impaired memory, and physical challenges were among the detrimental impacts of the disease on their family life, vocational life, social life, and leisure time. Adjustments were necessary to ensure they had sufficient energy to cope with the practical and relational aspects of everyday life. Feelings of uncertainty stemming from drug resistance, disease progression, and the possibility of early death were also experienced as challenging. Half the participants stated that it was difficult to keep negative mental health issues at bay, and all of them considered the time spent waiting for their scheduled follow-up scan to be burdensome.

Conclusions: It is important to focus increased attention on how the daily practical and psychosocial life of patients with chronic cancer, including metastatic GIST, is affected by their disease. Doing so might provide health-care workers with clues regarding how best to guide and support such patients throughout their emotional journey and, therefore, to improve their quality of life. As new medical treatments can also prolong survival and induce long-term clinical remission in relation to several other forms of metastatic cancer, the findings concerning GIST reported in this study might have widespread implications.
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http://dx.doi.org/10.1155/2020/1814394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559492PMC
October 2020

Cardiac sarcoma.

Tidsskr Nor Laegeforen 2020 04 20;140(6). Epub 2020 Apr 20.

Background: Although very rare, cardiac sarcoma is the most common malignant cardiac tumour. Cardiac tumours may present with constitutional symptoms and this can lead to delayed diagnosis.

Case Presentation: A woman in her late twenties was admitted to the acute psychiatric ward with suspected depressive psychosis. Although she presented with insomnia, auditory hallucinosis and paranoid delusions, her main symptoms were dyspnoea, tachycardia and exhaustion. She was discharged after 17 days and admitted directly to the medical ward for further examination. A thorough somatic examination, including diagnostic imaging, revealed a tumour in the left atrium obstructing the mitral ostium in the diastole, resulting in orthopnoea. She had urgent cardiac surgery and the histology was consistent with an intimal sarcoma.

Interpretation: This case illustrates a rare disease presenting with atypical symptoms. Her psychiatric symptoms resolved after surgery and oncologic treatment of her cardiac tumour.
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http://dx.doi.org/10.4045/tidsskr.19.0455DOI Listing
April 2020

Use of a simple form to facilitate communication on long-term consequences of treatment in sarcoma survivors.

Clin Sarcoma Res 2020 16;10. Epub 2020 Jan 16.

1Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Nydalen, P.O. Box 4953, Oslo, 0424 Norway.

Background: To report on our experience using a simple optional form to facilitate communication on late effects between the patients and the oncologists during outpatient follow-up and to detail on the spectrum of challenges reported by sarcoma survivors.

Methods: The form was presented for the patients to complete before their consultation and covered topics related to late effects and unmet needs that the patient wished to discuss with the medical personnel. Logistic regression analysis examined how the distribution of the topics varied with age, gender, diagnosis and type of treatment received.

Results: The form was manageable in a busy outpatient clinic. Of the 265 patients that received the form, 236 (89%) returned it. Patients in a palliative setting and those with other diagnosis than bone sarcoma (BS) and soft-tissue sarcoma (STS) were excluded for subsequent analyses. The final study-cohort comprised 160 patients, 54 (34%) with BS and 106 (66%) with STS. Among these, 140 (88%) had late-effect topics they wanted to discuss with their oncologist. Fatigue was raised by 39% of the patients, pain by 29% and impaired mobility by 23%. BS patients raised fatigue more often (< 0.005) than those with STS. Patients who had undergone multimodal treatment with chemotherapy raised fatigue more frequently ( < 0.001) than those who had only undergone surgery, radiotherapy or both.

Conclusions: A simple form on the long-term consequences of sarcoma treatment achieved a high response rate, was feasible to use in an outpatient clinic and facilitated communication on these issues. Fatigue was the most frequent topic raised and it was raised significantly more often in patients who had undergone chemotherapy.
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http://dx.doi.org/10.1186/s13569-019-0124-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964017PMC
January 2020

Perspectives on treatment side effects in patients with metastatic gastrointestinal stromal tumour: a qualitative study.

Clin Sarcoma Res 2019 30;9. Epub 2019 Apr 30.

1Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, P.O. Box 5960, Nydalen, 0424 Oslo, Norway.

Background: This study aims to explore how patients with metastatic gastrointestinal stromal tumour (GIST) experience the adverse effects of treatment, as expressed by the individuals themselves.

Methods: A qualitative, phenomenological and hermeneutic design was applied. Twenty patients with metastatic GIST participated in the study. In-depth and semi-structured interviews were conducted and then analysed by means of an inductive thematic analysis.

Results: The majority of participants reported experiencing a changed life after being diagnosed with metastatic GIST and commencing systemic medical treatment. More than half of them described partially debilitating self-reported side effects and complaints that had a detrimental impact on their lives. The life-prolonging tyrosine kinase inhibitor treatment prompted the participants to adapt to 'a new normal'. Several participants also emphasised having an ambivalent relationship with the pill, although most looked upon it as 'a friend' because it kept them alive. Paradoxically, while the participants struggled with the side effects of treatment as well as the consequences of living with a chronic cancer, half of them considered themselves to be healthy and, thus, to not actually be cancer patients.

Conclusions: We observed a gap between the biomedical perspective on disease that health professionals typically adopt and the individual experiences of patients living with metastatic GIST. For those patients who are living in limbo between having metastatic cancer and offered an effective treatment, a holistic view of health on the part of their healthcare providers seems crucial. A vital goal should hence be to improve communication between healthcare professionals and GIST patients so as to secure an individualised follow-up with guidance on coping with, and adapting to, their new normal. The study was approved by the data protection officer of the Oslo University Hospital (Approval Number 2016/15358).
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http://dx.doi.org/10.1186/s13569-019-0116-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492319PMC
April 2019

Multimodal kreftbehandling av gastrointestinal stromal tumor.

Tidsskr Nor Laegeforen 2018 10 1;138(15). Epub 2018 Oct 1.

Gastrointestinal stromal tumour (GIST) is a subtype of sarcoma that may occur in any part of the gastrointestinal system, most frequently in the stomach and small intestine. The most common symptoms are bleeding and abdominal pain. In this clinical review, we summarise the progress made with this condition and discuss the recommended diagnostics and treatment of GIST.
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http://dx.doi.org/10.4045/tidsskr.18.0200DOI Listing
October 2018

Pazopanib in relapsed osteosarcoma patients: report on 15 cases.

Acta Oncol 2019 Jan 12;58(1):124-128. Epub 2018 Sep 12.

d Department of Oncology , Oslo University Hospital, The Norwegian Radium Hospital , Oslo , Norway.

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http://dx.doi.org/10.1080/0284186X.2018.1503714DOI Listing
January 2019

Recurrence-Free Survival After Resection of Gastric Gastrointestinal Stromal Tumors Classified According to a Strict Definition of Tumor Rupture: A Population-Based Study.

Ann Surg Oncol 2018 May 12;25(5):1133-1139. Epub 2018 Feb 12.

Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.

Background: In gastrointestinal stromal tumors (GISTs), rupture is a high-risk feature and an indication for adjuvant treatment; however, the independent impact of rupture on prognosis is uncertain and the term is inconsistently defined. In the present study, a previously proposed definition of 'tumor rupture' was applied on a population-based cohort of gastric GISTs.

Methods: Patients undergoing surgery for non-metastatic gastric GISTs from 2000 to 2015 were identified in the regional sarcoma database of Oslo University Hospital. Tumor rupture included spillage or fracture, piecemeal resection, incisional biopsy, blood-tinged ascites, gastric perforation, and microscopic adjacent infiltration. Minor defects of tumor integrity were not considered rupture, i.e. core needle biopsy, peritoneal tumor penetration, superficial peritoneal rupture, and R1 resection. Risk was assessed according to the modified National Institutes of Health consensus criteria.

Results: Among 242 patients, tumor rupture occurred in 22 patients and minor defects of tumor integrity occurred in 81 patients. Five-year recurrence-free survival (RFS) for patients with tumor rupture, minor defects of tumor integrity, and no defect was 37, 91, and 96%, respectively (p < 0.001). In the high-risk group, 5 year RFS for patients with rupture was 37%, versus 77% without rupture (hazard ratio 3.56, 95% confidence interval 1.57-8.08, p = 0.001). On multivariable analysis, tumor rupture and mitotic index were independently associated with recurrence. Of 13 patients who received adjuvant imatinib after tumor rupture, 11 relapsed.

Conclusions: Tumor rupture according to the present definition was independently associated with recurrence. With tumor rupture, patients relapsed despite adjuvant treatment. Without rupture, prognosis was good, even in the high-risk group.
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http://dx.doi.org/10.1245/s10434-018-6353-5DOI Listing
May 2018

Prediction of long-term survival in patients with metastatic gastrointestinal stromal tumor: analysis of a large, single-institution cohort.

Acta Oncol 2017 Oct 30;56(10):1317-1323. Epub 2017 May 30.

a Department of Oncology , Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway.

Background: A subset of patients with metastatic GIST become long-term survivors, and a more precise prediction of outcome could improve clinical decision-making.

Material And Methods: One-hundred and thirty-three patients diagnosed with metastatic GIST from 1995 to 2013 were identified from the sarcoma database at Oslo University Hospital. Clinical data prospectively registered in the database were supplemented with retrospective review of medical records. Factors associated with survival were analyzed using Kaplan-Meier curves, log-rank test, univariate and multivariate Cox regression analyses.

Results: One-hundred and fifteen patients with metastatic GIST were included in the final study cohort. Median overall survival (OS) was 6.9 years (95% CI 5.6-8.3). Factors associated with long-term survival in univariate analysis were good baseline performance status (ECOG ≤1; p < .001), young age (p = .022), oligometastatic disease (OMD) (≤3 metastases; p < .001), maximum tumor diameter <5 cm (p < .001), surgery for metastatic disease (p = .005), surgery of the primary tumor (p < .001), normal baseline hemoglobin level (p = .05), normal baseline albumin level (p = .001) and normal baseline neutrophil count (p = .03). On multivariate analysis, good performance status, small tumor diameter and, OMD were the factors associated with long-term survival. Five and 10-year OS for patients with OMD were 89% and 71%, respectively, compared to 38% and 20% for patients with polymetastatic disease (p < .001).

Conclusions: In this single-institution cohort of patients, OMD was as a strong prognostic factor in patients with metastatic GIST. Patients with OMD had an outcome similar to patients with high-risk localized disease, and should be regarded as a separate category among patients with metastatic GIST.
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http://dx.doi.org/10.1080/0284186X.2017.1330555DOI Listing
October 2017

Clinical implications of repeated drug monitoring of imatinib in patients with metastatic gastrointestinal stromal tumour.

Clin Sarcoma Res 2016 15;6:21. Epub 2016 Dec 15.

Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, 0424 Oslo, Norway ; Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Background: Imatinib mesylate (IM) is the preferred treatment for the majority of patients with metastatic gastrointestinal stromal tumour (GIST). Low trough IM concentration (C) values have been associated with poor clinical outcomes in GIST patients. However, there are few studies of repeated measurements of IM levels, and therapeutic drug monitoring is not yet a part of routine clinical practice. This study was conducted to reveal clinical scenarios where plasma concentration measurement of IM trough level (C) is advantageous.

Methods: Patients with advanced GIST receiving IM were included from January 2011 to April 2015. Heparin plasma was collected at each follow-up visit. Ninety-six samples from 24 patients were selected for IM concentration measurement. Associations between IM plasma concentration and clinical variables were analyzed by Students' t test, univariate and multivariate linear regression analyses.

Results: The mean IM C plasma concentrations for patients taking <400, 400 and >400 mg daily were 782, 1132 and 1665 ng/mL, respectively (p = 0.010). High IM C levels were correlated with age, low body surface area, low haemoglobin concentration, low creatinine clearance, absence of liver metastasis and no prior gastric resection in univariate analysis. In multivariate analysis age, gastric resection and liver metastasis were included in the final model. Eight patients had disease progression during the study, and mean IM levels were significantly lower at time of progression compared to the previous measurement for the same patients (770 and 1223 ng/mL, respectively; p = 0.020).

Conclusions: Our results do not support repeated monitoring of IM levels on a routine basis in all patients. However, we have revealed clinical scenarios where drug measurement could be beneficial, such as for patients who have undergone gastric resection, suspicion of non-compliance, subjectively reported side effects, in elderly patients and at the time of disease progression.
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http://dx.doi.org/10.1186/s13569-016-0062-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157085PMC
December 2016

Can Imatinib Be Safely Withdrawn in Patients with Surgically Resected Metastatic GIST?

Anticancer Res 2015 Nov;35(11):5759-65

Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Patients with advanced gastrointestinal stromal tumors (GIST) are currently recommended for treatment with tyrosine kinase inhibitors (TKI) in a life-long sequence. The standard first-line treatment is imatinib mesylate (IM), which is switched to other drugs at progression or if the patient does not tolerate IM. This strategy has served many patients well as patients with advanced GIST now live for a median of approximately 5 years, compared to 18 months prior the TKI era. The prevailing hypothesis is that IM and other TKIs fail to completely eradicate metastatic GIST and that progression is inevitable if IM treatment is discontinued. Following a response to IM and surgery of metastatic lesions harbouring foci responsible for drug resistance and subsequent clinical relapse, we hypothesize that this may lead to a cure and the justification to stop IM in selected patients. We suggest that this novel strategy, a priori, warrants further investigation. We reviewed the available literature, present three clinical cases and put forward for discussion a treatment algorithm that needs confirmation within the context of a prospective clinical study.
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November 2015

[A boy with a wound on his finger that would not heal].

Tidsskr Nor Laegeforen 2015 Mar 10;135(5):445-8. Epub 2015 Mar 10.

Avdeling for kreftbehandling Oslo universitetssykehus, Radiumhospitalet.

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http://dx.doi.org/10.4045/tidsskr.14.0759DOI Listing
March 2015
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