| 1. |
- Bergström, Mats, et al.
(författare)
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PET with [11C]-Metomidate for the Visualization of Adrenocortical Tumors and Discrimination from Other Lesions
- 1999
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Ingår i: Clinical Positron Imaging. - 1095-0397 .- 1878-5751. ; 2:6, s. 339-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:The purpose of the study was to evaluate the potential role of PET with the adrenocortical-specific tracer 11C-metomidate in the characterization of incidentally found adrenal cortical lesions and in adrenocortical carcinomas.Methods:PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT (incidentalomas) and in 9 additional patients with adrenocortical cancer. All incidentalomas subsequently underwent surgery, except 2 subjected to biopsy only. These lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2) and nodular hyperplasia (n = 1). The remaining were non-cortical lesions including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.Results:All lesions, except 1, with an adrenocortical origin were easily identified due to exceedingly high uptake of 11C-metomidate, whereas the non-cortical lesions showed very low uptake. The 1 false negative was a cancer that at surgery was found to be extensively necrotic. High uptake was also seen in normal adrenal glands. The tracer uptake kinetics indicated trapping of the tracer in the cortical lesions. For quantitative evaluation of tracer binding in individual lesions, the simple SUV concept was found to be equally accurate as more elaborate kinetic analyses.Conclusion:The patients presented and altogether over 40 PET investigations have demonstrated 11C-metomidate to be an attractive tracer for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from non-cortical lesions. Additionally the method allows the assessment of metastases from adrenocortical cancers, and the very high contrast has allowed partial whole-body examinations.
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| 2. |
- Fröss-Baron, Katarzyna, et al.
(författare)
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177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated With Chemotherapy : Analysis of Outcome, Safety and Their Determinants
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:4, s. 330-343
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS) and their determinants in patients with advanced pancreatic neuroendocrine tumors (panNETs), previously pretreated with chemotherapy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE.Methods: In total, 102 patients with advanced panNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy were included, of whom 90 % had progressive disease and the majority (74.5%) with grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6 to 8 weeks interval, in 88 % of patients utilizing a dosimetry-guided protocol, until an absorbed dose of 23 Gy to the kidneys was reached.Results: Mean 32±10.9 GBq per patient was administered in 1-10 cycles starting median 36 months after panNET diagnosis. Median follow-up was 34 months. Median PFS was 24 months and median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy and elevated alkaline phosphatase (ALP). Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3-4 occurred in 10.8%. One patient (1.0 %) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity and absorbed dose to the bone marrow.Conclusion: 177Lu-DOTATATE therapy was feasible, highly effective and safe in patients with advanced panNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy related independent risk factor for shorter PFS and OS.
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| 3. |
- Garske, Ulrike, 1963-, et al.
(författare)
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Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs) : feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity
- 2018
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 45:6, s. 970-988
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.
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| 6. |
- Khan, Tanweera Shaheena
(författare)
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New Diagnostic and Therapeutic Approaches in Adrenocortical Cancer
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adrenocortical cancer (ACC) is a rare disease that is often difficult to diagnose, and therefore often presents at an advanced stage. Various cytotoxic treatments have been tried with little success. Evaluation of new diagnostic methods and improvement of medical therapies are therefore crucial.The diagnostic potential of 11C-metomidate positron emission tomography (PET) was evaluated in eleven ACC patients. PET visualized all viable tumors with high tracer uptake, including two lesions that CT failed to detect. Necrotic or fibrotic tumors were PET negative. Medication with adrenal steroid inhibitors and chemotherapy may decrease the tracer uptake.We performed a phase-II study with streptozocin and o,p’-DDD (SO) combination therapy in 40 ACC patients. The SO therapy was found to have impact on the disease-free interval (P = 0.02) as well as on survival (P = 0.01) in patients who received adjuvant therapy after curative resection. Complete or partial response was obtained in 36.4% of patients with measurable disease.The efficacy and tolerability of combination therapy with vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) were evaluated in eleven patients with advanced ACC after failure of SO therapy. The median survival was 21 months from the start of treatment. A partial response was achieved in two patients. Adverse events were mainly restricted to grade 1-2 toxicities, and grade 3 toxicities were observed in only two cycles.We tested 21 ACC tumors to analyze the expression of receptor tyrosine kinases and 15 ACC for mutation analysis of c-Kit exon 11, which can be targeted by antagonists such as imatinib. All ACCs expressed one or more kinases: c-Kit in 19 ACC and phospho-c-Kit in three while 14 ACCs expressed PDGFR-beta, suggesting the potential usefulness of tyrosine kinase inhibitors. No c-Kit mutations were detected in exon 11. Further evaluation of other mutations targeted by this drug may be needed.
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| 7. |
- Khan, Tanweera Shaheena, et al.
(författare)
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Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients : long-term survival in its adjuvant use
- 2000
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 11:10, s. 1281-1287
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:To evaluate the efficacy of streptozocin and o.p'DDD (SO) in adrenocortical cancer (ACC) patients since other chemotherapeutic regimens have limited effects.PATIENTS AND METHODS:We performed a phase II study with SO therapy in 40 ACC patients (median age 44 years). Oral o,p'DDD administration (1-4 g/d, every day) was given together with intravenous streptozocin (1 g/d for five days, thereafter 2 g once every three weeks). 5HT3-receptor blocker was used as standard premedication for streptozocin.RESULTS:The SO therapy was found to have significant effects on disease-free interval (P = 0.02) as well as on survival (P = 0.01) in adjuvantly treated cases (n = 17) in comparison to the patients who did not get any therapy after complete resection (n = 11). Complete or partial response was obtained in 36.4% of patients with measurable disease (n = 22). The overall two-year and five-year survival rates were 70% and 32.5%, respectively. The presence of metastases at diagnosis was identified as a poor prognostic factor (P = 0.02).CONCLUSIONS:The present study necessitates further randomized clinical study of SO therapy in the treatment of ACC, mainly as adjuvant treatment immediately after curative intended surgery, and could be developed into a regular treatment regimen.
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| 8. |
- Khan, Tanweera Shaheena, et al.
(författare)
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Vincristine, Cisplatin, Teniposide and Cyclophosphamide Combination in the Treatment of Recurrent or Metastatic Adrenocortical Cancer
- 2004
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Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 21:2, s. 167-177
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.
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