Toward a more individualised treatment of patients with gastrointestinal stromal tumour

Gastrointestinal stromal tumour (GIST) is a relatively rare soft tissue tumour most often occurring in the stomach or small intestine. The clinical behaviour can be highly variable between patients, indicating that individualised therapeutic approaches are needed. The aim of this thesis was to improve the classification, treatment and follow-up of patients with GIST by investigating real-life data from different cohorts of patients treated at Oslo University Hospital (OUH). Metastatic GIST patients are treated with the tyrosine kinase inhibitor imatinib. We performed measurements of imatinib concentrations in plasma, and revealed clinical scenarios where individualised drug dosage could be beneficial, such as in elderly patients, in patients with prior gastrectomy and at the time of disease progression. A more precise prediction of long-term outcome in metastatic GIST could result in better therapeutic decisions. We identified oligometastatic disease, defined as ≤3 metastases at the start of imatinib treatment, as a new predictor of long-term survival in metastatic GIST, and suggest that this should be regarded as a separate disease category. Rupture of the primary tumour before or during surgery could lead to dissemination of tumour cells in the abdominal cavity. Using a strict definition of tumour rupture, we showed that patients with localised gastric GIST had significantly worse recurrence-free survival compared to those without rupture. We also found that tumours with deletions involving codon 557 and 558 in exon 11 of the KIT gene had an increased risk of rupture. Preoperative treatment with imatinib could be considered to reduce rupture risk, and we propose that mutation analysis should be included in the risk assessment. In summary, the work in this thesis provides new knowledge on classification, follow-up and treatment, which may lead to a more individualised treatment for patients with GIST

Exploring Mentorship as a Novel Approach to Improving Quality of Life in Sarcoma Survivors: A Qualitative Pilot Study

Backgrounds. To investigate whether a formal mentoring program involving mentors from the business community could improve the quality of life (QoL) of sarcoma survivors struggling with the late effects of treatment. Methods. Seven former sarcoma patients participated in an eight-month formal mentoring program. The program was assessed through a qualitative study involving a phenomenological approach that utilized a hermeneutical design. In-depth, semistructured interviews were conducted with the mentees after the intervention and six months later. The mentors were interviewed after the program was over. The gathered data were interpreted using a thematic analysis. Results. The program facilitated dialogue between the mentors and mentees as well as between the mentees. Afterwards, the mentees were more willing to accept the challenges they faced following cancer treatment. During the program, the mentees were pushed out of their comfort zone, which led to mastery and personal growth in them all. However, the program also revealed some additional challenges, including unfulfilled expectations in two mentor-mentee relationships. Conclusions. The mentoring program facilitated the mentees’ reorientation and enhanced their QoL. Its eight-month duration appeared important in terms of allowing the mentees to go through a long-lasting process with continued support. The program could serve as the basis for larger studies involving other cancer survivors.</jats:p

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

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 (P < 0.005) than those with STS. Patients who had undergone multimodal treatment with chemotherapy raised fatigue more frequently (P < 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

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

Abstract 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 (P &lt; 0.005) than those with STS. Patients who had undergone multimodal treatment with chemotherapy raised fatigue more frequently (P &lt; 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. </jats:sec

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

Background: Imatinib mesylate (IM) is the preferred treatment for the majority of patients with metastatic gastrointestinal stromal tumour (GIST). Low trough IM concentration (C-min) 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 (Cmin) 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 Cmin plasma concentrations for patients taking &lt; 400, 400 and &gt; 400 mg daily were 782, 1132 and 1665 ng/mL, respectively (p = 0.010). High IM C-min 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

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

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.</jats:p