Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry.

BACKGROUND: The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE. RESULTS: A total of 32 administrations of [177Lu]Lu-DOTA-TATE (7.4 GBq/session) carried out by a physician and a nurse, were studied. In total, two physicians and four nurses were independently monitored with cumulative (passive) and/or real-time (active) dosemeters. Extremity, eye lens and whole-body doses were evaluated in terms of the dosimetric quantities Hp(0.07), Hp(3) and Hp(10), respectively. It was obtained that lead aprons reduced dose rates and whole-body doses by 71% and 69% for the physicians, respectively, and by 56% and 68% for the nurses. On average, normalised Hp(10) values of 0.65 ± 0.18 µSv/GBq were obtained with active dosimetry, which is generally consistent with passive dosemeters. For physicians, the median of the maximum normalised Hp(0.07) values was 41.5 µSv/GBq on the non-dominant hand and 45.2 µSv/GBq on the dominant hand. For nurses 15.4 µSv/GBq on the non-dominant and 13.9 µSv/GBq on the dominant hand. The ratio or correction factor between the maximum dose measured on the hand and the dose measured on the base of the middle/ring finger of the non-dominant hand resulted in a factor of 5/6 for the physicians and 3/4 for the nurses. Finally, maximum normalised Hp(3) doses resulted in 2.02 µSv/GBq for physicians and 1.76 µSv/GBq for nurses. CONCLUSIONS: If appropriate safety measures are taken, the administration of [177Lu]Lu-DOTA-TATE is a safe procedure for workers. However, regular monitoring is recommended to ensure that the annual dose limits are not exceeded.

Occupational radiation exposure assessment during the management of [68Ga]Ga-DOTA-TOC.

BACKGROUND: Since it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters. RESULTS: The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study. CONCLUSIONS: Imaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.

Efficacy and safety of Nivolumab in older patients with pretreated lung cancer: A subgroup analysis of the Galician lung cancer group.

BACKGROUND: Nivolumab is an anti PD1 immunotherapy drug approved for advanced Non-Small Cell Lung Cancer (NSCLC) patients who previously received at least one prior line of treatment. Older patients are often not represented in clinical trials and drugs with acceptable safety profiles are necessary. We aim to report the efficacy and safety profile of Nivolumab in the real-world older subgroup of the Galician lung cancer group study. PATIENTS AND METHODS: We retrospectively reviewed 188 advanced NSCLC patients treated with at least one prior therapy. We collected data from patients who were ≥70 years old treated with Nivolumab in second or subsequent lines. Patient characteristics, treatment efficacy (overall survival, progression-free survival, and response rate), and safety profile were reported. RESULTS: Thirty-eight patients aged ≥70 years were included in the subgroup analysis. The median age was 74.5 years, a high percentage of patients were males (95%), most had a Performance Status of 1 (79%) and only 13% were non-smokers. The predominant histology was adenocarcinoma (53%), and 18% of patients received 2 or more lines. The median Progression-Free Survival was 7.53 months (CI 4.3-17.3, p = 0.15) and the median Overall Survival was 14.85 months (CI 10.5-20.7, p = 0.44). The objective response rate was 42%. No new adverse events were reported in comparison to a global population. CONCLUSIONS: The efficacy and safety profile of Nivolumab in advanced NSCLC patients treated with at least one prior therapy and age ≥70 years old can be overlapped to a global population. Further prospective trials are needed to define and confirm these results.

Assessing Immunotherapy with Functional and Molecular Imaging and Radiomics.

Immunotherapy is changing the treatment paradigm for cancer and has introduced new challenges in medical imaging. Because not all patients benefit from immunotherapy, pretreatment imaging should be performed to identify not only prognostic factors but also factors that allow prediction of response to immunotherapy. Follow-up studies must allow detection of nonresponders, without confusion of pseudoprogression with real progression to prevent premature discontinuation of treatment that can benefit the patient. Conventional imaging techniques and classic tumor response criteria are limited for the evaluation of the unusual patterns of response that arise from the specific mechanisms of action of immunotherapy, so advanced imaging methods must be developed to overcome these shortcomings. The authors present the fundamentals of the tumor immune microenvironment and immunotherapy and how they influence imaging findings. They also discuss advances in functional and molecular imaging techniques for the assessment of immunotherapy in clinical practice, including their use to characterize immune phenotypes, assess patient prognosis and response to therapy, and evaluate immune-related adverse events. Finally, the development of radiomics and radiogenomics in these therapies and the future role of imaging biomarkers for immunotherapy are discussed. Online supplemental material is available for this article. ©RSNA, 2020.

Real world data of nivolumab for previously treated non-small cell lung cancer patients: a Galician lung cancer group clinical experience.

BACKGROUND: Recently, immunotherapy has changed the standard of treatment in non-small cell lung cancer (NSCLC). Outside clinical trials, data of real life is lacking. This is an observational study that represents the real world experience with nivolumab in pretreated NSCLC. METHODS: Eligibility criteria included, histologically confirmed NSCLC, stage IIIB and IV, evaluable disease and at least one prior therapy. Patients received nivolumab until progressive disease (PD) or unacceptable toxicity. The main aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The secondary aim was to perform subgroup analysis by clinical features. RESULTS: From August of 2015 to January of 2017, 188 patients were enrolled. The patients demographics were: median age 58 years, 144 male; 17 never smoker and 171 former/current smoker; 112 adenocarcinoma, 66 squamous-cell carcinoma and 10 not otherwise specified (NOS); 61 stage IIIB and 127 stage IV; 15 performance status (PS) 0, 154 PS 1 and 19 PS 2; 5 epidermal growth factor receptor (EGFR) and 1 anaplastic lymphoma kinase (ALK); 42 with central nervous system (CNS) metastases; and 71 received 2 or more prior therapy lines. Of the 188 patients enrolled, 25 (13.3%) were not evaluated, 3 (1.6%) had complete response (CR), 45 (23.9%) partial response (PR), 48 (25.5%) disease stabilization (DS) and 67 (35.6%) PD. The median of progression-free survival (PFS) was 4.83 months (95% CI, 3.6-5.9) and overall survival (OS) was 12.85 months (95% CI, 9.07-16.62). The subgroup analysis revealed statistical significance in OS for patients with CNS metastases 14.8 months (95% CI, 11.5-17.3) vs. 5.09 months (95% CI, 0.3-9.8) and also PS 0 [not reached (NR)] vs. PS 1 11.7 months vs. PS 2 3.4 months (95% CI, 2.3-4.4). The safety profile was in accordance with the literature data. CONCLUSIONS: This study represents the real word experience with nivolumab and the results are consistent with previously reported in clinical trials. PS 2 and the presence of CNS metastases are associated with poor prognosis.

Unsuspected uterine metastasis of breast carcinoma diagnosed by 18F-FDG PET/CT.

A 50-year-old woman with a history of bilateral lobular carcinoma of the breast in 1995 and 2001 was treated with mastectomy, axillary lymphadenectomy, chemotherapy, and hormone therapy which achieved a complete response. In 2009, the patient developed a progressive elevation of tumor markers. A CT scan was performed showing no suspicious malignant lesions. She was referred for (18)F-FDG PET/CT and the images revealed highly increased tracer uptake in the uterus suggestive of malignancy. The patient underwent hysterectomy with bilateral double adnexectomy and a histopathological diagnosis of massive carcinomatous infiltration of breast lobular carcinoma was done.