Results
GIST, SDH-deficient GIST, Tumor, fatigue, diarrhea, cutaneous rash, toxicities, toxicity, lymphocytopenia, neutropenia, thrombocytopenia, anemia, hypertension, anorexia
PALMAR-PLANTAR ERYTHRODYSESTHESIA, RECURRENCE, TUMOR, POSITIVE, LYMPHOCYTOPENIA, ADVERSE EVENTS, NEUTROPENIA, DISEASE, THROMBOCYTOPENIA, SDH, ANEMIA, MAY, SECONDARY, GIST, HYPERTENSION, ANOREXIA
From May 2016 to October 2020, 30 advanced GIST patients, with no mutations found by Sanger sequencing in The median age was 57 years (16–72), without any predominant gender (8 female and 7 male patients). Tumor locations were distributed as follows: gastric 10 (67%), intestinal 2 (13%) and mesenteric 3 (20%). In 9 patients, an SDH-deficient GIST was detected by immunohistochemistry, 5 of them harbored mutations in the 
Patients demographics (n = 15) - Male - Female7 (47%)8 (53%) - 0 - 110 (67%)5 (33%) - Localized - Locally advanced - Metastatic6 (40%)2 (13%)7 (47%) - Locally advanced - Metastatic2 (13%)13 (87%) - Positive - Negative - Not available5 (33%)8 (53%)2 (13%) - Yes - No - Not available10 (67%)4 (27%)1 (6%) - SDH - Other gene - No mutation - Not available6 (40%)4 (27%)4 (27%)1 (6%) - Yes - No12 (80%)3 (20%) - Yes - No9 (60%)6 (40%)A total of 220 1-month cycles of treatment were given to the 15 enrolled patients with a median of 9 (0.3–55) cycles per patient. Dose reductions and dose interruptions were registered in 8 (53%) and 14 (93%) patients, respectively. The median dose intensity for regorafenib was 74% (4-100%). At baseline, 5 (33%) patients had previously received imatinib, 4 of which were in the adjuvant setting. The patient that had received imatinib in the advanced disease was accrued as RECIST progression, as were the 6 cases that had a metastatic recurrence. The remaining 8 cases that presented as advanced disease were enrolled at the time of diagnosis without a watch-and-wait period.The most frequent secondary adverse events of any grade in the 15 accrued patients were hypertension (66.7%), fatigue (60%), diarrhea (46.7%), anorexia (40%) and cutaneous rash (40%). The most common grade 3 and 4 toxicities were increased alanine aminotransferase concentration (20%), increased aspartate aminotransferase (13.3%), hypertension (13.3%), palmar-plantar erythrodysesthesia (13.3%) and anorexia (13.3%). While the most frequent hematological toxicity was anemia (20%), followed by lymphocytopenia (13.3%). No grade 3 or 4 neutropenia or thrombocytopenia were observed (Additional File Based on RECIST criteria and central radiology assessment, 2 (13%) patients had partial response (Additional File 
Swimmers plot for progression-free survival according to RECIST central radiological review. Each bar represents one patient. Red arrows identify patients with absence of progression at the last radiological follow up. The vertical line represents the median progression-free survival for the whole seriesWith a median follow up of 42 months (95% CI 28–56), the median of PFS in accordance with central review was 11 months (95% CI, 0.79–21.21) by RECIST and 14.9 months (95% CI, 0–47) by Choi criteria (Additional File No significant correlation was found between SDH-deficient GIST and clinical outcome with the exception of a longer PFS, according to Choi criteria (Additional File 