In this retrospective cohort study, all 212 patients with metastatic Si-NET G2 diagnosed between 2000 and 2019 and receiving any treatment at the Department of Endocrine Oncology, Uppsala University Hospital, a tertiary referral centre, and at the Department of Oncology, Ryhov County Hospital, a regional hospital, were eligible for inclusion. One-third of the patients were referred from other hospitals in Sweden and Norway. Patients with radical surgical resection not relapsing during the study period were not included. Following approval from the Uppsala ethical review board, data on patients’ clinical status including Eastern Cooperative Oncology Group performance status (ECOG PS), treatments given, Ki-67, laboratory tests, radiology and cause of death were extracted from the hospitals’ medical records. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) were reported as times the upper limit of normal. In case of multiple biopsies, the highest Ki-67 value before or within 6 months of the start of a new line of treatment was reported. SSTR status was evaluated on Octreoscan in the majority of patients; during the final years of the study, 68Gallium DOTATATE positron emission tomography could alternatively be used. An uptake below or equal to liver uptake was considered negative/low. Cases with small tumours not visible on the initial Octreoscan, which upon progression showed clear uptake in subsequent imaging, were considered positive. Survival status was censored on October 31, 2021, or at last known contact. Causes of death due to tumour progression, adverse events, surgical morbidity and cases where cause of death was indeterminate but cancer-related death likely were classified as cancer-specific mortality. Patients dying from causes unrelated to their NET tumour were censored at the time of death.
Treatments studied included SSA, PRRT, everolimus, IFNα and chemotherapy. Patients were treated with various doses of SSA. In the first study years, treatment was often initiated at lower (hereby referred to as below-label) doses, mostly 20 mg of octreotide long-acting release (LAR) every 4 weeks. After the publication of PROMID and CLARINET trials, a standard (label) dose of 30 mg octreotide LAR/120 mg lanreotide autogel every 4 weeks was used. Dose could be escalated to above-label doses, often in consecutive steps, for progression or symptom control.
Cancer-specific survival (CSS) and OS for first-line treatment were calculated from start of treatment for metastatic disease to cancer-related death or death from any cause, respectively. PFS was calculated from start of each treatment to radiological progression, unequivocal clinical progression or death. Radiological progression was based on conventional multidisciplinary team assessment at 3- to 6-month intervals and defined as any unequivocal increase in the size of known tumours or detection of new lesions. Biochemical partial response was defined as a reduction of baseline CgA or 5-HIAA by at least 50% and biochemically progressive disease (PD) as an increase by at least 25%, whereas values in between were deemed as biochemically stable disease (SD).
Treatments studied included SSA, PRRT, everolimus, IFNα and chemotherapy. Patients were treated with various doses of SSA. In the first study years, treatment was often initiated at lower (hereby referred to as below-label) doses, mostly 20 mg of octreotide long-acting release (LAR) every 4 weeks. After the publication of PROMID and CLARINET trials, a standard (label) dose of 30 mg octreotide LAR/120 mg lanreotide autogel every 4 weeks was used. Dose could be escalated to above-label doses, often in consecutive steps, for progression or symptom control.
Cancer-specific survival (CSS) and OS for first-line treatment were calculated from start of treatment for metastatic disease to cancer-related death or death from any cause, respectively. PFS was calculated from start of each treatment to radiological progression, unequivocal clinical progression or death. Radiological progression was based on conventional multidisciplinary team assessment at 3- to 6-month intervals and defined as any unequivocal increase in the size of known tumours or detection of new lesions. Biochemical partial response was defined as a reduction of baseline CgA or 5-HIAA by at least 50% and biochemically progressive disease (PD) as an increase by at least 25%, whereas values in between were deemed as biochemically stable disease (SD).
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