68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT.

PURPOSE: We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). METHODS: In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). RESULTS: SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUVmax between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). CONCLUSION: (68)Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients.

AIM: Over the last decade, somatostatin (SST) receptor (R)-positive tumors have been treated using either (90)Y-DOTA-TOC, (177)Lu-DOTA-TATE or (90)Y-DOTA-LAN/(177)Lu-DOTA-LAN, at the Innsbruck Medical University. This report presents data from the evaluation of the initial 100 patients receiving receptor mediated radionuclide therapy (PRRT) according to our protocol. METHODS: One-hundred patients with SSTR-positive tumors were treated (36 female, 64 male; mean age, 58 years; range, 13 to 84 years), including 68 patients with neuroendocrine tumors (NET), and patients with other non-neuroendocrine tumors, e.g. patients with radioiodine-negative thyroid carcinoma, refractory to conventional treatment modalities. Patients were selected based on high SSTR expression as assessed by (68)Ga-DOTA-TOC as first choice tracer for patients with NET, or (68)Ga-DOTA-LAN for patients with other tumor entities, or if the (68)Ga-DOTA-TOC PET was negative. Following positron emission tomography (PET), individual dosimetry was regularly performed using (111)In-labeled compounds. Therapy cycles were repeated every 10 weeks using either (90)Y-DOTA-TOC (3.7 GBq, 3-5 cycles) or (177)Lu-DOTA-TATE (7.4 GBq, 3-4 cycles). Thirteen patients received both and 5 patients even 3 different therapeutic compounds. Each patient received an amino acid solution (arginin, lysine) to reduce the kidney dose. Between the radioactive cycles a long-acting SST analog was applied. Dosages were individually adapted depending on several disease related factors. RESULTS: Overall, following PRRT partial remission (PR) was observed in 23 patients (23 %), minor remission (MR) in 10 (10 %), stable disease (SD) in 42 patients (42 %). Although 25 patients (25 %) showed progressive disease (PD), palliative care was provided in most of these patients. In the group treated with 90Y-DOTA-TOC, 12 patients showed PR, 3 MR, 32 SD and 13 had PD. In the group of patients treated with (177)Lu-DOTA-TATE, PR was observed in 15 patients, MR in 8, SD in 19 and PD in 13 patients. Severe side effects (WHO Grad 3 and 4) were seen in only 6 % of patients. Severe long-term nephrotoxicity was observed in none of the patients. These adverse reactions were especially seen in patients who were treated with high doses per cycle, in patients pre-treated with chemotherapy and in patients with low clinical performance. CONCLUSIONS: PRRT with differently labelled tracers (Y-90 or Lu-177) and different SST-analogs is generally well tolerated without serious side effects. These results favour the combined use of radiolabeled SST analogs providing a customized tumour targeting for size reduction and improvement of quality-of-life. Extended time intervals and reduced individual doses make sense in patients with advanced tumor stages, in case of moderate SSTR-expression, and in patients with higher age.

Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control?

PURPOSE: To determine if a delay of irradiation to the intact breast for administration of adjuvant chemotherapy results in increased local recurrence in breast cancer. PATIENTS AND METHODS: The records of 262 women with 264 cases of breast cancer were reviewed. Group I contained 105 patients treated with conservative surgery, chemotherapy, and radiotherapy. Group II contained 157 patients (used as a concurrent control) treated with conservative surgery and radiotherapy only. Eighty-nine percent of subjects in group I received all chemotherapy before radiotherapy. Fifty-eight percent of patients received hormone therapy. Seventy-one percent of patients had negative surgical margins, and 74% had negative lymph nodes. For group I, conservative surgery-radiotherapy intervals in months were less than 1 (five, 5%), > or = 1 to less than 3 (10, 9%), > or = 1 to less 6 (48, 46%), and > or = 6 (42, 40%), mean of 5. For group II, the intervals were less than 1 (20, 13%), > or = 1 to less than 3 (123, 79%), > or = 3 to less than 6 (11, 7%), and > or = 6 (two, 1%), mean of 1.5. RESULTS: Thirty patients (11.5%) have disease recurrence (19 distant [6%] and 12 local [5%]). There were no significant differences in local recurrence (group I, four [4%]; group II, eight [5%]; difference not significant). There were no significant differences in local recurrence in any surgery-radiotherapy interval within each group. Although we found marginal increases in the percentage of local recurrences in group I patients (with prolonged surgery-radiotherapy intervals) who had positive margins, positive lymph nodes, and tumor size more than 2 cm versus group II (without prolonged surgery-radiotherapy intervals), these results were not significant. CONCLUSION: We could not identify any surgery-radiotherapy interval that resulted in increased local recurrence if radiotherapy was delayed for administration of adjuvant chemotherapy in breast cancer patients. Because of the heterogenous population of breast cancer patients, our results also support the need for further study to determine the optimum integration of radiotherapy and chemotherapy in the management of the conservatively treated breast.

Are axillary recurrence and overall survival affected by axillary extranodal tumor extension in breast cancer? Implications for radiation therapy.

PURPOSE: To determine the overall survival and local recurrence significance of axillary lymph node extranodal tumor extension (ETE) and whether axillary/chest-wall irradiation influenced any of these outcomes. MATERIALS AND METHODS: The records of 81 breast cancer patients treated with radical or modified radical mastectomy at a single surgical practice were eligible for study. Thirty-four patients had ETE: 17 with focal ETE (< 10 x high-power field) and 17 with extensive ETE (> 10 x high-power field). RESULTS: With a median follow-up duration of 92 months, only two patients had an axillary recurrence (2%): one had focal ETE and one had no ETE. Neither of these patients received axillary radiation therapy. Overall survival and recurrence-free survival were significantly decreased with ETE in patients whether axillary radiation therapy had been administered or not. Analysis showed that the age of the patient correlated significantly with extensive ETE (P = .04) and that the number of positive lymph nodes (< or = three v > three) correlated significantly with ETE (whether focal or extensive) (P = .0001). A multivariate analysis of extranodal tumor extension and number of positive lymph nodes showed that ETE was associated with decreased survival (P = .05), although to a lesser degree than number of positive lymph nodes (P = .003). CONCLUSION: These results show that ETE is associated with decreased survival and increased recurrence rates regardless of the extent of the radiation therapy field. Also, ETE does not necessarily indicate a significantly increased incidence of axillary recurrence. Therefore, axillary irradiation based on this pathologic finding may not be indicated.