Time, cost, ethical, and regulatory considerations surrounding in vivo testing methods render them insufficient to meet existing and future chemical safety testing demands. There is a need for the development of in vitro and in silico alternatives to replace traditional in vivo methods for inhalation toxicity assessment. Exposures of differentiated airway epithelial cultures to gases or aerosols at the air-liquid interface (ALI) can assess tissue responses and in vitro to in vivo extrapolation can align in vitro exposure levels with in-life exposures expected to give similar tissue exposures. Because the airway epithelium varies along its length, with various regions composed of different cell types, we have introduced a known toxic vapor to five human-derived, differentiated, in vitro airway epithelial cell culture models-MucilAir of nasal, tracheal, or bronchial origin, SmallAir, and EpiAlveolar-representing five regions of the airway epithelium-nasal, tracheal, bronchial, bronchiolar, and alveolar. We have monitored toxicity in these cultures 24 h after acute exposure using an assay for transepithelial conductance (for epithelial barrier integrity) and the lactate dehydrogenase (LDH) release assay (for cytotoxicity). Our vapor of choice in these experiments was 1,3-dichloropropene (1,3-DCP). Finally, we have developed an airway dosimetry model for 1,3-DCP vapor to predict in vivo external exposure scenarios that would produce toxic local tissue concentrations as determined by in vitro experiments. Measured in vitro points of departure (PoDs) for all tested cell culture models were similar. Calculated rat equivalent inhaled concentrations varied by model according to position of the modeled tissue within the airway, with nasal respiratory tissue being the most proximal and most sensitive tissue, and alveolar epithelium being the most distal and least sensitive tissue. These predictions are qualitatively in accordance with empirically determined in vivo PoDs. The predicted PoD concentrations were close to, but slightly higher than, PoDs determined by in vivo subchronic studies.

The optimal radiotherapy technique for patients requiring both breasts or chest walls simultaneous irradiation with or without regional nodal irradiation is currently under investigation. In the last decade several publications present case reports and case series of patients treated with adjuvant radiotherapy in both breasts or chest walls for synchronous bilateral breast cancer (SBBC) with modern radiotherapy techniques. This article presents a systematic review of relevant literature as well as a case report of a SBBC patient who received bilateral chest wall radiotherapy with regional nodal irradiation at our institution with Truebeam - Edge Linear Accelerator. Solid evidence is provided that the practice of avoiding adjuvant radiotherapy in SBBC out of fear of toxicity with older radiotherapy techniques is outdated. Modern techniques can safely and effectively deliver treatment to patients requiring both sides irradiation and even in mastectomy patients in need of regional nodal irradiation.

BACKGROUND: Uncertainty in the dose-response of low dose radiation raised concern of an increased cancer incidence in Sweden after the Chernobyl Nuclear Power Plant (NPP) accident.
METHODS: A closed cohort was created of all males ≥18 years of age living in the Northern Sweden in 1986. In total 826,400 individuals were enrolled including 40,874 hunters. A nested case-control design was used with five controls randomly selected for each cancer case matched on year of diagnosis and year of birth. Individual absorbed colon dose was calculated 1986 to 2015. Allowing for a 5-year latency period Hazard Ratios (HR) per mGy with 95% Confidence Intervals (95% CI) were calculated in a conditional logistic regression adjusted by rural/non-rural living, length of education and pre-Chernobyl cancer incidence 1980 to 1985. A total of 127,109 cancer cases occurred from 1 January 1991 to 31 December 2015. Cancer was classified in: 1) Organ-specific (stomach, colon, liver, lung, prostate, urinary bladder, thyroid and leukaemia), 2) Other and 3) Not previously associated to ionizing radiation.
RESULTS: The average colon dose in cases was 1.77 mGy compared to controls 1.73 mGy. Hunters average colon dose was 2.32 mGy. Organ-specific cancers showed the highest HR per mGy both in the full cohort, adj HR 1.019 (1.014-1.024) and the hunter subcohort, adj HR 1.014 (1.001-1.027) during follow-up 1991 to 2015. Other cancer and Not previously associated with ionizing radiation showed lower HR per mGy. Therefore, the adj HR per mGy for Total cancer, 1.013 (1.009-1.017) was explained by Organ-specific cancer. Increased adj HR per mGy was seen in stomach, colon and prostate cancer, respectively in the full cohort and lung cancer in hunters.
CONCLUSIONS: Some cancer sites previously associated with ionizing radiation showed a positive adjusted HR per mGy both in the full cohort and in the hunter subcohort.

Self-shielding gyroscopic radiosurgery (GRS) represents a technical innovation in the field of stereotactic radiosurgery. GRS does not require a radiation vault and is optimized for radiosurgical treatments. Reports on its usage are limited. We describe the first clinical experience of GRS at our institution to assess the application of GRS in the treatment of cranial tumors. Moreover, we perform a dosimetric comparison to robotic radiosurgery (RRS) with vestibular schwannoma (VS) GRS patients.
Patients who were treated with GRS between July and November 2021 were included. Patient, tumor, and dosimetric characteristics were retrospectively summarized and analyzed.
Forty-one patients with 48 intracranial tumors were included. Tumor entities mostly comprised VS, brain metastases, and meningiomas. The median prescription dose and isodose line were 13.5 Gy and 50.0% for benign neoplasia versus 20 Gy and 60.0% for malignant tumors, respectively. The mean planning target volume was 1.5 cubic centimeters. All patients received a single-fraction treatment without encountering any technical setup difficulties. Treatment plan comparisons with RRS revealed comparable plan characteristics, dose gradients, and organs at risk doses. Significant differences were detected concerning the new conformity index and number of monitor units per treatment (both P < 0.01).
This case series provides more evidence on the usage of self-shielding GRS in the management of cranial tumors. Dosimetric comparisons for VS cases revealed mostly equivalent dosimetric characteristics to RRS. Further clinical and physical analyses for GRS are underway.

One of the treatment options for recurrent brain metastases is surgical resection combined with intracranial brachytherapy. GammaTile® (GT) (GT Medical Technologies, Tempe, Arizona) is a tile-shaped permanent brachytherapy device with cesium 131 (131Cs) seeds embedded within a collagen carrier. We report a case of treating a patient with recurrent brain metastases with GT and demonstrate a dosimetric modeling method.

UNASSIGNED: Primary cardiac paragangliomas are rare tumors. Metastatic disease is even rarer. Surgical management is technically challenging, and sometimes even impossible. Available therapeutic modalities for metastatic disease include external beam radiation therapy as well as systemic treatments, namely 131I-MIBG and more recently, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. To our knowledge, this is the first case of progressive unresectable cardiac paraganglioma with intracardiac extension treated with dosimetry based personalized PRRT to be reported. This case is of particular interest since it documents for the first time the efficacy, and especially the safety of the 177Lu-DOTATATE PRRT in this precarious context for which therapeutic options are limited.
UNASSIGNED: A 47-year-old man with no medical history consulted for rapidly decreasing exercise tolerance. The investigation demonstrated an unresectable progressing metastatic cardiac paraganglioma with intracardiac extension. The patient was treated with personalized 177Lu-DOTATATE PRRT and showed complete symptomatic and partial anatomical responses, with a progression-free survival of 13 months.
UNASSIGNED: PRRT with 177Lu-DOTATATE should be considered for inoperable cardiac paraganglioma. No major hemodynamic complications were experienced. Therapy resulted in safety and substantially improved quality of life.

Background: The patient benefit from a diagnostic nuclear medicine procedure far outweighs the associated radiation risk. This benefit/risk ratio assumes a properly administered radiopharmaceutical. However, a significant diagnostic radiopharmaceutical extravasation can confound the procedure in many ways. We identified three current extravasation hypotheses espoused by medical societies, advisory committees, and hundreds of individual members of the nuclear medicine community: diagnostic extravasations do not cause harm, do not result in high absorbed dose to tissue, and require complex dosimetry methods that are not readily available in nuclear medicine centers. We tested these hypotheses against a framework of current knowledge, recent developments, and original research. We conducted a literature review, searched regulatory databases, examined five clinical cases of extravasated patients, and performed dosimetry on those extravasations to test these globally accepted hypotheses. Results: A literature review found 58 peer-reviewed documents suggesting patient harm. Adverse event/vigilance report database reviews for extravasations were conducted and revealed 38 adverse events which listed diagnostic radiopharmaceutical extravasation as a factor, despite a regulatory exemption for required reporting. In our own case material, assessment of care was evaluated for five extravasated patients who underwent repeat imaging. Findings reflected results of literature review and included mis- or non-identification of lesions, underestimation of Standardized Uptake Values (SUVs) by 19-73%, classification of scans as non-diagnostic, and the need to repeat imaging with the associated additional radiation exposure, inconvenience, or delays in care. Dosimetry was performed for the same five cases of diagnostic radiopharmaceutical extravasation. Absorbed doses to 5 cm3 of tissue were between 1.1 and 8.7 Gy, and shallow dose equivalent for 10 cm2 of skin was as high as 4.2 Sv. Conclusions: Our findings suggest that significant extravasations can or have caused patient harm and can irradiate patients\' tissue with doses that exceed medical event reporting limits and deterministic effect thresholds. Therefore, diagnostic radiopharmaceutical injections should be monitored, and dosimetry of extravasated tissue should be performed in certain cases where thresholds are thought to have been exceeded. Process improvement efforts should be implemented to reduce the frequency of extravasation in nuclear medicine.

Sub-optimal placement of both intracavitary devices and interstitial needles is a relatively common occurrence in cervical brachytherapy, which may reduce the accuracy of dose distribution and contribute to adverse toxicities. To mitigate complications, improve target dose coverage, and verify proper device placement, implants may be placed under real-time image guidance. Traditionally, transrectal ultrasound has been used for needle guidance. However, we have utilized transabdominal ultrasound (TA-US) in our brachytherapy center. The purpose of this pictorial essay was to provide a pictorial description of TA-US technique, present a retrospective review of our preliminary outcomes adopting TA-US into routine practice, and to discuss the advantages of real-time ultrasound image guidance for placement of intrauterine tandem and interstitial needles.

Differentiated thyroid cancer patients with significantly elevated or rapidly rising serum thyroglobulin (Tg) levels and negative diagnostic radioiodine scans (DxScan) often present a therapeutic dilemma in deciding whether or not to administer an 131I treatment. In this report, we describe a novel two-step approach of a 30 mCi 131I exploratory scan before a dosimetric 131I therapy to help \"un-blind\" the treating physician of the benefit/risk ratio of a further \"blind\" 131I treatment. A 51-year-old man presented with rising Tg levels, a negative DxScan, and a history of widely metastatic follicular thyroid cancer. He had undergone total thyroidectomy, remnant ablation with 3.8 GBq (103.5 mCi) of 131I, Gammaknife®, and treatment with 12.1 GBq (326 mCi) of 131I for multiple metastases. However, at 19 months after the treatments, his Tg levels continued to rise, and scans demonstrated no evidence of radioiodine-avid metastatic disease. In anticipation of a \"blind\" 131I treatment, the medical team and the patient opted for a 30 mCi exploratory scan. The total dosimetrically guided prescribed activity (DGPA) was decided based on the whole-body dosimetry. The patient was first given 30 mCi of 131I, and the exploratory scan was performed 22 h later, which demonstrated 131I uptake in the left lung, left humeral head, T10, and right proximal thigh muscle. Based on the positive exploratory scan, the remainder of the DGPA was administered within several hours after the scan. On the post-DGPA treatment scan performed at 5-7 days, the lesions seen on the ~ 22 h exploratory scan were confirmed, and an additional lesion was observed in the left kidney. The 30 mCi exploratory scan suggested the potential for a response in the radioiodine-avid lesions despite a negative diagnostic scan. This method allows 131I treatment to be administered to patients who may have a greater potential for a therapeutic response while avoiding unwarranted side effects in those patients with nonavid disease.

The risks of radiation exposure in orthopaedic surgery have become a topic of increasing interest in the setting of widespread fluoroscopy use and concern for an increased prevalence of breast cancer among female orthopaedic surgeons. The aim of this national study of 31 female orthopaedic surgeons was to achieve a deeper understanding of fluoroscopic use in the OR and its associated exposure to radiation, by comparing female orthopaedic trauma and arthroplasty surgeons.
A total of 31 surgeons wore dosimeters for 10 operating days each to track cumulative radiation exposure. Surgeons were not asked to modify their practice in any way, with no requirement that the operating days had to be chosen with the knowledge that fluoroscopy would be used. Participants were also asked to fill out a form at the end of each day, detailing the number of cases that day, the number of hours spent in the OR, and the total amount of time using fluoroscopy.
Trauma surgeons received significantly higher radiation doses in the OR (p=0.01) and reported longer use of fluoroscopy (p<0.001). Trauma surgeons also spent more time per day in the OR and had more cases per day compared to arthroplasty surgeons, but this difference was not significant. Radiation dose penetrating through protective equipment remained minimal.
Although the female trauma surgeons in the study operated longer and performed more procedures per day, the higher radiation exposure was best explained by the amount of time fluoroscopy is used in the OR. The fluoroscopic times in this study therefore may be a useful self-assessment tool for attending trauma and arthroplasty surgeons. Awareness of these differences will hopefully increase an individual surgeon\'s mindfulness toward the length of fluoroscopy use in each case, regardless of orthopaedic subspecialty.Level of Evidence: IV.