Prevalence, Impact, and Correlates of Severe Fatigue in Patients With Gastrointestinal Stromal Tumors.

CONTEXT: The introduction of the tyrosine kinase inhibitor (TKI) imatinib in the treatment of gastrointestinal stromal tumor (GIST) in 2000 was the start of a new era of targeted treatment. Since then, the median survival of patients with GIST has substantially increased. Prolonged survival and chronic TKI use are associated with treatment-induced symptoms, such as fatigue, which can compromise quality of life (QoL). OBJECTIVES: This study determined the prevalence of severe fatigue in GIST patients compared to matched healthy controls, the impact of fatigue on daily life, and associations between fatigue and current TKI use. METHODS: One hundred nineteen patients treated with surgery and/or a TKI for GIST were asked to participate. Participants completed questionnaires including the Checklist Individual Strength-Fatigue Severity scale (CIS-fatigue), Short-Form 36-Item Health Survey, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Fatigue Catastrophizing Scale, Self-Efficacy Scale, and the Hospital Anxiety and Depression Scale. RESULTS: Eighty-nine GIST patients (75%) completed questionnaires, 61 patients (69%) were on a TKI. Prevalence of severe fatigue measured with CIS-fatigue was significantly higher in GIST patients (30%) than in 234 matched healthy controls (15%). The prevalence of severe fatigue did not differ significantly between patients receiving treatment with curative (29%) or palliative intent (36%). Severely fatigued patients reported lower QoL and more impairment on all functional domains. TKI use, more psychological distress, and lower physical functioning were associated with fatigue. CONCLUSION: Severe fatigue occurs in 30% of GIST patients and in 33% of GIST patients on a TKI. The fatigue is disabling and is not only associated with current TKI use but also with psychological distress and physical functioning. GIST patients should be informed about these associated factors of fatigue that deserve appropriate management.

Fear of progression in patients with gastrointestinal stromal tumors (GIST): Is extended lifetime related to the Sword of Damocles?

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare and before 2000, patients had a dismal prognosis with a median survival of less than a year after tumor metastasis. However, the median overall survival has increased to more than five years following the introduction of imatinib and other tyrosine kinase inhibitors (TKI). Little is known about the psychosocial consequences of treatment of GIST, but this is important because patients now are treated and live for longer. This cross-sectional study assessed quality of life, distress, and fear of cancer recurrence or progression in patients with GIST. MATERIAL AND METHODS: Eighty-six patients with localized or metastatic GIST were asked to participate. Patients completed self-report questionnaires including the EORTC-Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, Impact of Event Scale, Cancer Worry Scale, and Fear of Cancer Recurrence Inventory. RESULTS: Fifty-four patients (median age 63.3 years) completed the questionnaires, 33 (61%) of whom were receiving TKI treatment at the time of the study. Overall, the GIST patients had a good global quality of life, but 28 patients had high levels of fear of cancer recurrence/progression. This high level of fear was not related to patient- or treatment-related variables. These patients experienced significantly higher levels of psychological distress, functional impairments, and difficulty making plans for the future than did patients with lower levels of fear. CONCLUSIONS: More attention should be paid to specific cancer-related problems, such as fear of cancer recurrence/progression, in addition to general quality of life issues in patients with GIST.

Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors (GIST): the EORTC STBSG experience.

BACKGROUND: Preoperative imatinib therapy of locally advanced GIST may facilitate resection and decrease morbidity of the procedure. METHODS: We have pooled databases from 10 EORTC STBSG sarcoma centers and analyzed disease-free survival (DFS) and disease-specific survival (DSS) in 161 patients with locally advanced, nonmetastatic GISTs who received neoadjuvant imatinib. OS was calculated from start of imatinib therapy for locally advanced disease until death or last follow-up (FU) after resection of the GIST. DFS was calculated from date of resection to date of disease recurrence or last FU. Median FU time was 46 months. RESULTS: The primary tumor was located in the stomach (55%), followed by rectum (20%), duodenum (10%), ileum/jejunum/other (11%), and esophagus (3%). The tumor resection after preoperative imatinib (median time on therapy, 40 weeks) was R0 in 83%. Only two patients have demonstrated disease progression during neoadjuvant therapy. Five-year DSS/DFS rates were 95/65%, respectively, median OS was 104 months, and median DFS was not reached. There were 56% of patients who continued imatinib after resection. Thirty-seven GIST recurrences were diagnosed (only 5 local relapses). The most common mutations affected exon 11 KIT (65%). Poorer DFS was related to primary tumor location in small bowel and lack of postoperative therapy with imatinib. CONCLUSIONS: Our analysis comprising the largest group of GIST patients treated with neoadjuvant imatinib in routine practice indicates excellent long-term results of combined therapy in locally advanced GISTs.

Surgical management of rectal gastrointestinal stromal tumors.

BACKGROUND: Five percent of gastrointestinal stromal tumors (GISTs) are primarily localized in the rectum. We analyzed the outcome of multimodality treatment for rectal GIST in a multicenter retrospective series. METHODS: All surgically treated patients with a rectal GIST were identified from four specialized centers in the Netherlands. Primary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: Thirty-two patients (22 men and 10 women) with rectal GISTs were identified. Twenty-two patients received imatinib before surgery for a median of 9 (range 2-53) months (Group 1). Ten patients received no imatinib because of small tumor size or lack of availability (Group 2). Median tumor size before treatment was 9.3 (range 6-17) cm in Group 1 and median 6 (range 4-14) cm in Group 2. A complete resection was possible in 17/22 (77%) patients in Group 1 versus 7/10 (70%) in Group 2. Median DFS was not reached in Group 1, while it was 36 months in Group 2. Median OS was not reached in both groups. CONCLUSIONS: Preoperative imatinib leads to downsizing of the tumors in Group 1. However, it has not led to less extensive surgery. The DFS is longer in patients treated with pre- and post-operative imatinib, without an effect on OS.

Surgery after treatment with imatinib and/or sunitinib in patients with metastasized gastrointestinal stromal tumors: is it worthwhile?

BACKGROUND: Standard treatment for metastatic gastrointestinal stromal tumors (GISTs) is systemic therapy with imatinib. Surgery is performed to remove metastatic lesions to induce long-term remission or even curation. In other patients, surgery is performed to remove (focal) progressive or symptomatic lesions. The impact and long-term results of surgery after systemic therapy have not been clearly defined. METHODS: Between September 2001 and May 2010, all patients with metastatic GIST who underwent surgery for metastatic GIST after systemic therapy (that is, imatinib and sunitinib) at four Dutch specialized institutions were included. Primary end-points were progression-free survival (PFS) and overall survival (OS). RESULTS: All 55 patients underwent surgery after treatment with systemic therapy. At the last follow-up, tumor recurrence or progression was noted after surgery in 48% of the patients who responded on systemic therapy, and in 85% of the patients who were treated while having progressive disease. Median PFS and OS were not reached in the group of responders. In the non-responders group PFS and OS were median 4 and 25 months, respectively. Response on systemic therapy and a surgical complete resection were significantly correlated to PFS and OS. CONCLUSIONS: Surgery may play a role in responding patients. In patients with progressive disease, the role of surgery is more difficult to distinguish in this retrospective analysis since PFS is short. Which patients benefit and whether this improves long-term outcome should be established in a multicentric randomized trial.