Dose-rate effects and tumor control probability in177Lu-based targeted radionuclide therapy: a theoretical analysis.

OBJECTIVE: 177Lu-based targeted radionuclide therapy (TRT) has become an important cancer treatment option in recent years, in particular in the treatment of advanced prostate cancer and metastasized neuroendocrine tumors. Although it is known from conventional radiotherapy that the temporal dynamics of the dose-rate can be of relevance for tumor cell survival, the analysis of TRT efficacy usually considers only the absorbed dose. Thus, the aim of this theoretical analysis is to shed light on the possible effects of the pattern of dose-rate in TRT on tumor control probability (TCP). APPROACH: For this purpose, TCP is studied numerically in a typical four-cycle treatment regime based on the mechanistic lethal-potentially lethal model and the Zaider-Minerbo model for TCP including repopulation of tumor cells. MAIN RESULTS: It is shown that the dose-rate pattern in TRT can have a substantial effect on TCP even though the absorbed dose in the tumor lesion is unchanged. These dose-rate effects are particularly evident when repair of potentially lethal lesions is slow. SIGNIFICANCE: The results indicate that in some situations in the analysis of the efficacy of TRT it is necessary to consider the full dose-rate pattern instead of the absorbed dose alone. This can be highly relevant for optimization and further development of TRTs. In particular, it could be of relevancy in studying the efficacy of newly emerging treatment concepts that combine the use of TRT and drugs that inhibit DNA damage repair.

Sentinel lymph node biopsy in early-stage oral squamous cell carcinoma: A retrospective single-center analysis.

Sentinel lymph node biopsy (SLNB) is increasingly incorporated in European national guidelines for the management of the clinically node-negative neck (cN0) in early-stage oral squamous cell carcinoma (OSCC). In Germany, SLNB in OSCCs is not yet routinely performed. This study aimed to evaluate the clinical outcome of SLNB in a German cohort. Patients with primary early-stage OSCC who underwent tumor resection and SLNB were retrospectively analyzed. Clinical-pathological characteristics were documented. Primary endpoints were sensitivity and the negative predictive value (NPV). A total of 46 patients with a mean age of 62.3 (±14.5) years met the inclusion criteria. Most tumors were located in the tongue (63.0%). Bilateral drainage from a lateral tumor was observed in three cases (6.5%), and sentinel lymph node metastasis was detected in three patients (6.5%). Mean follow-up for all patients was 13.8 months (±9.6). One patient developed regional recurrence following a negative SLNB during the observation period, leading to an NPV of 0.98 and a sensitivity of 75.0%. The 2-year neck-specific relapse-free survival was 92.8%. SLNB in early-stage OSCC is a reliable diagnostic tool of the cN0 neck, ensuring a high NPV and RFS. SLNB can be advantageous in comparison to elective neck dissection due to the detection of contralateral lymph drainage.

ChatGPT: Can You Prepare My Patients for [18F]FDG PET/CT and Explain My Reports?

We evaluated whether the artificial intelligence chatbot ChatGPT can adequately answer patient questions related to [18F]FDG PET/CT in common clinical indications before and after scanning. Methods: Thirteen questions regarding [18F]FDG PET/CT were submitted to ChatGPT. ChatGPT was also asked to explain 6 PET/CT reports (lung cancer, Hodgkin lymphoma) and answer 6 follow-up questions (e.g., on tumor stage or recommended treatment). To be rated "useful" or "appropriate," a response had to be adequate by the standards of the nuclear medicine staff. Inconsistency was assessed by regenerating responses. Results: Responses were rated "appropriate" for 92% of 25 tasks and "useful" for 96%. Considerable inconsistencies were found between regenerated responses for 16% of tasks. Responses to 83% of sensitive questions (e.g., staging/treatment options) were rated "empathetic." Conclusion: ChatGPT might adequately substitute for advice given to patients by nuclear medicine staff in the investigated settings. Improving the consistency of ChatGPT would further increase reliability.

Performance of Deauville Criteria in [18F]FDG-PET/CT Diagnostics of Giant Cell Arteritis.

In this retrospective study, PET/CT data from 59 patients with suspected giant cell arteritis (GCA) were reviewed using the Deauville criteria to determine an optimal cut-off between PET positivity and negativity. Seventeen standardised vascular regions were analysed per patient by three investigators blinded to clinical information. Statistical analysis included ROC curves with areas under the curve (AUC), Cohen's and Fleiss' kappa (κ) to calculate sensitivity, specificity, accuracy, and agreement. According to final clinician's diagnosis and the revised 2017 ACR criteria GCA was confirmed in 29 of 59 (49.2 %) patients. With a diagnostic cut-off ≥ 4 (highest tracer uptake of a vessel wall exceeds liver uptake) for PET positivity, all investigators achieved high accuracy (range, 89.8-93.2%) and AUC (range, 0.94-0.97). Sensitivity and specificity ranged from 89.7-96.6% and 83.3-96.7%, respectively. Agreement between the three investigators suggested 'almost perfect agreement' (Fleiss' κ = 0.84) A Deauville score of ≥4 as threshold for PET positivity yielded excellent results with high accuracy and almost perfect inter-rater agreement, suggesting a standardized, reproducible, and reliable score in diagnosing GCA. However, the small sample size and reference standard could lead to biases. Therefore, verification in a multicentre study with a larger patient cohort and prospective setting is needed.

Same same but different: dopamine transporter SPECT on scanners with CZT vs. NaI detectors.

BACKGROUND: The aims of this study were to establish a normal database (NDB) for semiquantification of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with [123I]FP-CIT on a cadmium zinc telluride (CZT) camera, test the preexisting NaI-derived NDB for use in CZT scans, and compare the diagnostic findings in subjects imaged with a CZT scanner with either the preexisting NaI-based NDB or our newly defined CZT NDB. METHODS: The sample comprised 73 subjects with clinically uncertain parkinsonian syndrome (PS) who prospectively underwent [123I]FP-CIT SPECT on a CZT camera according to standard guidelines with identical acquisition and reconstruction protocols (DaTQUANT). Two experienced readers visually assessed the images and binarized the subjects into "non-neurodegenerative PS" and "neurodegenerative PS". Twenty-five subjects from the "non-neurodegenerative PS" subgroup were randomly selected to establish a CZT NDB. The remaining 48 subjects were defined as "test group". DaTQUANT was used to determine the specific binding ratio (SBR). For the test group, SBR values were transformed to z-scores for the putamen utilizing both the CZT NDB and the manufacturer-provided NaI-based NDB (GE NDB). A predefined fixed cut-off of -2 was used for dichotomization of z-scores to classify neurodegenerative and non-neurodegenerative PS. Performance of semiquantification using the two NDB to identify subjects with neurodegenerative PS was assessed in comparison with the visual rating. Furthermore, a randomized head-to-head comparison of both detector systems was performed semiquantitatively in a subset of 32 out of all 73 subjects. RESULTS: Compared to the visual rating as reference, semiquantification based on the dedicated CZT NDB led to fewer discordant ratings than the GE NDB in CZT scans (3 vs. 8 out of 48 subjects). This can be attributed to the putaminal z-scores being consistently higher with the GE NDB on a CZT camera (median absolute difference of 1.68), suggesting an optimal cut-off of -0.5 for the GE NDB instead of -2.0. Average binding ratios and z-scores were significantly lower in CZT compared to NaI data. CONCLUSIONS: Use of a dedicated, CZT-derived NDB is recommended in [123I]FP-CIT SPECT with a CZT camera since it improves agreement between semiquantification and visual assessment.

Sentinel lymph node biopsy in recurrent or secondary oral squamous cell carcinoma after previous neck dissection.

OBJECTIVES: The aim of this retrospective study was to evaluate the potential of sentinel lymph node biopsy (SLNB) in patients with recurrent or a secondary oral squamous cell carcinoma (OSCC) without clinical signs of lymph node metastases (cN0), who were previously treated with a surgical approach. PATIENTS AND METHODS: Retrospective analysis of all patients with cN0 recurrent or secondary OSCC, who were treated using SLNB after previous neck dissection. Endpoints were sentinel lymph node (SLN) detection rate, negative predictive value (NPV) and sensitivity. RESULTS: A total of 17 patients with a mean age of 68.6 years were included. SLN were detected in 15 of 17 cases (detection rate: 88.2%). In seven patients (41.2%), a bilateral or contralateral lymph drainage of a unilateral carcinoma was found. Two patients (11.8%) demonstrated a positive SLN upon pathohistological analysis, which led to an upstaging. In one case, a non-SLN was positive, which is considered a false-negative result. The mean follow-up for all patients with histologically negative SLN including the patients without a detected SLN was 11.8 months (range: 0-31 months). Of these, one patient developed (isolated) neck recurrence after 12 months resulting in an overall NPV of 86.7% and a sensitivity of 50.0% for the SLNB as a neck staging procedure. CONCLUSION: SLNB can improve the staging of patients with recurrent or secondary OSCC, who present with a history of a previous neck dissection. Further studies are required to demonstrate the oncological benefit of SLNB in this patient cohort.

Bio-policy and the place of institutionalised ethics in political decision making.

Questions concerning moral problems caused by the life-sciences and concerning the adequate methods and instruments to solve these are timely and urgent; especially in the face of intense debates on the acceptability of research on human embryonic stem cells and preimplantation diagnostics, to name only two applications developed from research on the life-sciences. Unfortunately, the constant and accusing demand that life-scientists must behave morally does not give us a clue on how ethics may help in establishing guidelines for moral behaviour. In this heated situation the foundation of ethics-committees seems to be the motto of the day. But instead of functioning as necessary and fruitful scientific advisory boards, these committees run the risk of being misused as a fashionable (and soon forgotten) weapon in the battle for political opinion-leadership. In the following article, the view is defended that ethics is a scientific enterprise and has an important role to play in political decision making on life-sciences issues.