Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors.

Importance: Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. Objective: To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). Design, Setting, and Participants: This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. Exposures: Upfront PRRT or upfront chemotherapy or targeted therapy. Main Outcomes and Measures: The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. Results: Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95% CI, 0.4-1.0 years]; HR, 0.37 [95% CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95% CI, 10.7-14.1 years] vs 11.6 years [95% CI, 9.1-13.4 years]; HR, 0.81 [95% CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95% CI, 9.2-17.9 years]; HR, 0.83 [95% CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95% CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95% CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95% CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95% CI, 0.12-0.34]; grade 2: aHR, 0.52 [95% CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95% CI, 0.24-0.61]; intestinal: aHR, 0.19 [95% CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95% CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95% CI, 0.29-1.43; P = .31). Conclusions and Relevance: In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.

Usefulness of PET-CT scan in recurrent thyroid cancer.

The aim of this paper is to discuss the risk of recurrence in patients with differentiated thyroid cancer and emphasize the importance of risk-group stratification, early recurrence identification and application of new imaging modalities, what is the PET-CT. Moreover, follow-up of patients with thyroid carcinoma should be carried out by specialized teams throughout life. Therefore, interdisciplinary case discussions in tumor conferences may improve the use of multimodal therapy especially in patients with poorly differentiated thyroid carcinomas. After baseline follow-up, if there is a suspicion of thyroid carcinoma, early PET-CT should be used for early detection and appropriate planning. Fortunately, due to the good localization possibility, the PET-CT enables a focused surgical procedure with avoidance of an unnecessary tumor search and thereby a reduction of the risk of injury of neighboring structures which is a concern with reoperative neck surgery.

Recombinant human thyrotropin (rhTSH) versus Levo-thyroxine withdrawal in radioiodine therapy of differentiated thyroid cancer patients: differences in abdominal absorbed dose.

PURPOSE: In DTC patients, 131-radioiodine therapy has routinely been used for many years for thyroid remnant ablation after thyroid surgery. To date, two different strategies can be used to achieve sufficient TSH stimulation on thyroid remnant: (I) Levo-thyroxine withdrawal or (II) rhTSH stimulation. The aim of our study was to compare the abdominal absorbed dose ratio between differentiated thyroid cancer patients who underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. METHODS: We reviewed the records of 63 patients affected by differentiated thyroid cancer. All patients underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. A post-therapy whole-body scan was obtained 5 days after 131-radioiodine therapy. Qualitative and quantitative image analysis was performed. Quantitative analysis was performed by drawing seven regions of interest on the abdomen (anterior and posterior views) to estimate both the activity ratio (AR) and absorbed dose ratio (DR) obtained in patients treated in hypothyroidism or after rhTSH stimulation. RESULTS: The values of the activity and absorbed dose ratios obtained on each abdomen region (liver, stomach, ascending colon, transverse colon, descending colon, rectum, and small intestine) were always higher in patients treated after L-T4 withdrawal than after rhTSH stimulation with p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, and 0.002, respectively. CONCLUSIONS: DTC patients treated with 131-radioiodine after rhTSH stimulation have lower abdominal radioiodine activity than hypothyroid patients. Our data could be of practical relevance in terms of patient management. The potential impact on rare radioiodine-related gastrointestinal side effects is to be established in specifically designed prospective studies.

Undetectable or low (<1 ng/ml) postsurgical thyroglobulin values do not rule out metastases in early stage differentiated thyroid cancer patients.

BACKGROUND: Differentiated thyroid cancer (DTC) work-up is based on (near)total-thyroidectomy plus thyroid remnant ablation (TRA) with 131-radioiodine in many patients, and long-life follow-up. 131I-post therapy whole body scan (pT-WBS) and serum thyroglobulin (Tg) are used in identifying metastatic patients. Some authors have evaluated the possibility of using post-surgical Tg (ps-Tg) values in deciding for or against TRA. The aim of our study was to verify the diagnostic accuracy of 131I-pT-WBS and SPECT/CT imaging (post-therapeutic imaging) compared to serum Tg levels in detecting metastases in early stage of DTC patients. RESULTS: Post-therapeutic imaging revealed metastases in 82 out of 570 (14.4%) patients. Metastases were successively confirmed by other diagnostic tools or by histology (sensitivity and PPV = 100%). Seventy-three out of 82 patients (90.2%) showed ps-Tg levels ≤1 ng/ml. In fifty-four per cent of patients, serum Tg levels at TRA remained ≤1 ng/ml. CONCLUSION: In conclusion, ps-Tg levels cannot be used in deciding for or against TRA. In early stage of DTC, post-therapeutic imaging (131I-pT-WBS and SPECT/CT) is an accurate method of detecting metastases, also in patients with stimulated serum Tg values ≤1 ng/ml. METHODS: We retrospectively reviewed the records of 570 consecutive patients affected by pT1-pT3 DTC (F = 450, M = 120), referred to our Nuclear Medicine Units in the last five years to perform TRA after (near)-total-thyroidectomy.All patients underwent TRA 3-4 months after thyroid surgery either in euthyroid or in hypothyroid state. Serum Tg values evaluated in post-surgical period and at TRA were matched with post-therapeutic imaging results.

Association of parathyroid carcinoma and thyroid disorders: A clinical review.

Parathyroid carcinoma is a rare malignancy, which usually occurs as a sporadic disease, and less frequently in the setting of genetic syndromes. Despite the association of parathyroid and thyroid disorders being quite common, the coexistence of parathyroid carcinoma and thyroid disease is rare. We reviewed the pertinent literature. The terms "parathyroid carcinoma" and "thyroid disease, hyperthyroidism, thyrotoxicosis, hypothyroidism, thyroid nodule(s), Graves' disease, autonomously functioning thyroid nodules" were used both separately and in reciprocal conjunction to search MEDLINE for articles published from January 2007 to March 2016. The search was prompted by the observation of a never reported association of autonomously functioning thyroid nodules and parathyroid carcinoma. Two hundred and twenty-one parathyroid carcinoma patients have been described during the last 10 years. Neck ultrasonography and parathyroid scintigraphy are the most common instrumental studies used in detecting parathyroid lesions. Serum parathyroid hormone and calcium levels are high in the majority of parathyroid carcinoma patients. Only 21 patients with parathyroid carcinoma and thyroid disorders were found. Our patient is the first casual association between parathyroid carcinoma and autonomously functioning thyroid nodules reported in literature and diagnosed using parathyroid and thyroid scintigraphies. Parathyroid carcinoma is a very rare endocrine tumor and association with thyroid disease is not frequent. Parathyroid carcinoma pre-operative diagnosis is often difficult also because available literature data are not homogenous and there is not a common operative guideline. Our case confirms the role of parathyroid scintigraphy, encouraging the association with thyroid scintigraphy, especially in the presence of (multi)-nodular goiter in order to address the most appropriate surgical management.