ONCOGENE PANEL SEQUENCING ANALYSIS IDENTIFIES CANDIDATE ACTIONABLE GENES IN ADVANCED WELL-DIFFERENTIATED GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS.

Objective: To report the rate of candidate actionable somatic mutations in patients with locally advanced and metastatic gastro-enteropancreatic (GEP) neuroendocrine tumors (NET) and of other genetic alterations that may be associated with tumorigenesis. Methods: A phase II mutation targeted therapy trial was conducted in patients with advanced well-differentiated G1/G2 GEP-NET. Mutations found in the mTOR pathway-associated genes led to treatment with the mTOR inhibitor everolimus, and were defined as actionable. Tumor deoxyribonucleic acid (DNA) from GEP-NET were sequenced and compared with germline DNA, using the OncoVAR-NET assay, designed for hybrid capture sequencing of 500 tumor suppressor genes and oncogenes. Somatic variants were called and copy-number (CN) variant analysis was performed. Results: Thirty patients (14 small-intestine, 8 pancreatic, 3 unknown primary NET, and 5 of other primary sites) harbored 37 lesions (4 patients had DNA of multiple lesions sequenced). Only 2 patients with sporadic NET (n = 26) had an actionable mutation leading to treatment with everolimus. Driver somatic mutations were detected in 18 of 30 patients (21/37 lesions sequenced). In the remaining samples without a driver mutation, CN alterations were found in 11/16 tumors (10/12 patients), including CN loss of chromosome (Chr) 18 (P<.05), CN gain of Chr 5, and loss of Chr 13. CN losses in Chr 18 were more common in patients without driver mutations detected. Pronounced genetic heterogeneity was detected in patients with multiple lesions sequenced. Conclusion: Genome-wide DNA sequencing may identify candidate actionable genes and lead to the identification of novel target genes for advanced well-differentiated GEP-NET. Abbreviations: Chr = chromosome; CN = copy number; DNA = deoxyribonucleic acid; FDA = Food and Drug Administration; GEP = gastro-enteropancreatic; MEN-1 = multiple endocrine neoplasia syndrome type 1; mTOR = mammalian target of rapamycin; NET = neuroendocrine tumor; PFS = progression-free survival; PNET = pancreatic neuroendocrine tumors; SINET = small-intestine neuroendocrine tumor.

A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin.

OBJECTIVE: Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer. DESIGN: An open-label Simon two-stage phase II trial. PATIENTS AND MEASUREMENTS: Valproic acid was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid-stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake. RESULTS: Thirteen patients with a median age of 66 years (50-78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hürthle cell carcinoma. None of the 10 patients who completed the 10-week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression. CONCLUSIONS: Valproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin.

Feasibility of Radio-Guided Surgery with 68Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors.

BACKGROUND: Surgery is the only definitive therapy for gastro-entero-pancreatic neuroendocrine tumors (GEPNETs), and achieving complete tumor resection is an important prognostic factor. Radiopharmaceuticals such as (68)Ga-DOTA peptides have been developed that offer superior accuracy for localization of GEPNETs. The study aim was to determine the feasibility of radio-guided surgery (RGS) using (68)Ga-DOTATATE in patients with primary and recurrent GEPNETs. METHODS: Fourteen patients with GEPNETs were enrolled onto a prospective study to determine the feasibility of RGS with (68)Ga-DOTATATE. Findings from preoperative imaging, intraoperative exploration, RGS, and pathology were analyzed. RESULTS: The median decay corrected target count rate was 172.6 (range 28.15-2341) for tumors, with a tumor-to-background ratio (TBR) of 4.46 (range 1.6-43.56). The median lesion size was 1.55 (range 0.5-15) cm. There was no significant correlation between preoperative imaging maximum standardized uptake value (SUVmax) of the lesions and TBR (Spearman r = - 0.01, p = 0.9), TBR and tumor size (Spearman r = 0.29, p = 0.14), and SUVmax and tumor size (Spearman r = 0.22, p = 0.28). The probe showed correct identification for gastric and small intestine neuroendocrine tumor (NET), including lymph node metastasis in 17 (81.0 %) of 21 cases, with a median TBR of 3.5 (1.6-40.2). For pancreatic NETs and lymph node metastasis, 16 (66.7 %) of 24 were correctly identified by RGS. CONCLUSIONS: Our study shows that RGS with (68)Ga-DOTATATE is feasible and correctly confirms bowel NETs and metastatic mesenteric lymph nodes. Further studies are needed to determine the benefit of RGS with (68)Ga-DOTATATE.

Long-Term Outcome of Bilateral Laparoscopic Adrenalectomy Measured by Disease-Specific Questionnaire in a Unique Group of Patients with Cushing's Syndrome.

BACKGROUND: Laparoscopic bilateral adrenalectomy (LBA) is recommended for patients with bilateral adrenal disease and occult or unresectable ectopic Cushing's syndrome (CS). There are limited data on long-term outcomes after LBA, partly due to the lack of disease-specific tools for the measurement of impact on patients' health and quality of life. METHODS: We used a disease-specific questionnaire covering all major clinicopathologic characteristics of CS. We compared the outcome from LBA to a control group of 60 patients who had thyroidectomy (matched for age, gender, and time of surgery, 2:1 control-to-CS). RESULTS: Twenty-eight patients (20 women and 8 men) underwent LBA for CS. Of them, 24 patients (86 %) provided responses to our questionnaire. Ninety-two percent of patients' responses indicated a significant improvement of general Cushing's physical features with complete resolution reported in 59 % of responses. Significant improvement of associated biochemical abnormalities and comorbidities was reported in 83 % of patients' responses including complete reversal in 58 %. Significant improvement in emotional-behavioral symptoms was reported in 84 % of patients' responses with complete recovery in 53 %. All patients expressed satisfaction with LBA and significant improvement in their general health and self-reported quality of life. All of the improvements after LBA were statistically significant compared with the control group. CONCLUSIONS: Our disease-specific questionnaire enables a clearer understanding of the association between the clinical, metabolic, and emotional-behavioral features of CS, its treatment with LBA, and long-term impact on patient-reported quality of life. This disease-specific questionnaire may be useful for future studies in patients with CS.

Preoperative Imaging Features are Associated with Surgical Complications Following Carotid Body Tumor Resection.

BACKGROUND: Surgical resection remains the treatment of choice for carotid body tumors (CBTs). Although perioperative complications such as carotid artery injury and neurological deficits occur infrequently, they can be devastating. The aim of this study was to evaluate whether clinical factors or preoperative imaging findings can accurately predict perioperative complications. METHODS: Twenty CBTs were resected from 19 patients. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) of the neck were used to measure the degree of circumferential involvement of the CBT to the internal carotid artery (ICA), carotid artery narrowing, tumor length, tumor volume, and the distance from the tip of the C2 dens to the superior aspect of the CBT (dens-CBT). Operative reports and Shamblin classification (I-III) of each tumor were independently reviewed. Preoperative imaging features were compared to perioperative cranial nerve injury (CNI), rates of carotid artery injury, and major carotid artery repairs, as well as Shamblin classifications≥II. RESULTS: CNI was associated with a high-lying CBT (dens-CBT=1.8 vs. 2.9 cm, p<0.01). All four patients with CNI had a dens-CBT of <3 cm. Neither tumor length and tumor volume nor the involvement of the ICA (≥180° as measured by CT or MRI) was associated with CNI, carotid artery injury, major carotid artery repair, or Shamblin II or III classification. No carotid artery narrowing was observed in any of the cases. CONCLUSIONS: Preoperative measurement of the dens-CBT is helpful in identifying CBTs at risk for CNI after surgical resection.

Endovascular hypogastric artery preservation during endovascular aneurysm repair: a review of current techniques and devices.

Despite the improvement in endovascular techniques, one aspect of aneurysmal disease that continues to be challenging is the management of aortoiliac aneurysms. Sacrificing the hypogastric artery (HGA) for effective treatment is not without sequelae, which may include buttocks claudication, colonic ischemia, spinal cord ischemia, as well as buttock and scrotal necrosis. This should be taken into consideration particularly in patients with previous intervention or potential additional future interventions. This review describes the current endovascular techniques for preservation of HGA perfusion.

Localized Colitis Associated With Cholecystectomy in Multiple Sclerosis Patient Treated With Ocrelizumab.

Our understanding of multiple sclerosis (MS) has led to the development of new therapeutic strategies, including ocrelizumab, a third-generation humanized anti-CD20 antibody. Ocrelizumab is largely well tolerated with favorable effectiveness, however, it has been associated with reports of colitis presenting weeks to months following infusion. We present a case of severe localized colitis in the setting of recent surgery and chronic ocrelizumab use. High-dose IV hydrocortisone was initiated, and the patient showed gradual improvement. Repeat imaging after discharge showed near-complete resolution of the patient's condition. This case aims to increase awareness of possible postoperative severe localized colitis in MS patients on Ocrevus.

Unusual presentation and treatment of spontaneous celiac artery dissection.

The management options of an isolated celiac artery dissection include medical, open surgical, and endovascular techniques. Which strategy is chosen depends on the severity of the dissection, collateral circulation to the liver, the patient's hemodynamic status, and the surgeon's expertise. We describe an unusual case of celiac artery dissection involving splenic and hepatic arteries complicated by hemorrhage. The patient was successfully treated by coil embolization of the splenic and gastric branches. Hepatic arterial blood flow was preserved with a stent graft extending from the origin of the gastroduodenal artery to the orifice of the celiac artery.

Synchronous Acute Appendicitis and Acute Cholecystitis: A Case Report.

Acute cholecystitis (AC) and acute appendicitis (AA), independently, are among the most commonly diagnosed conditions in the emergency department (ED). However, their synchronous presentation is very rare. Here, we present a 31-year-old man with worsening right flank abdominal pain, nausea, and vomiting. Physical examination results were significant for moderate to severe right upper abdominal quadrant pain with a positive Murphy's sign and right lower quadrant pain with rebound. Workup in the ED revealed leukocytosis with a left shift, and the abdominal ultrasound and computerized tomography scan showed AA and AC. A literature review revealed a paucity of publications on concomitant AA and AC. Reporting new cases will contribute to improving our understanding of the biology, natural history, and management of this rare pathological combination.

Gallbladder Cancer or Diffuse Xanthogranulomatous Cholecystitis: A Case of Management Dilemma During Elective Cholecystectomy With Unexpected Severe Mass-Like Pericholecystic Fibrosis and Inflammation.

A 52-year-old man was scheduled to undergo an elective laparoscopic cholecystectomy for an increasingly symptomatic cholelithiasis. The pre-operative diagnosis was established clinically and confirmed with ultrasonography (US), showing gallstones and thickened gallbladder wall. Intraoperatively, extensive dense adhesions of the omentum to the entire subdiaphragmatic surface of the liver and the diaphragm were encountered. The adhesions of the omentum and colon were completely obscuring the Morrison's space with cartilage-like consistency at the supposed anatomical projection of the gallbladder fundus. Due to these unexpected pathological findings and uncertain disease biology, a decision was made to abort and re-schedule the surgery after obtained tissue biopsy results, magnetic resonance cholangiopancreatography (MRCP), and tumor markers carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and alpha fetoprotein (AFP) were available. CA 19-9 was found elevated 10-fold, while AFP and CEA levels were within normal limits. A follow-up cholecystectomy was performed, and final pathology revealed diffuse xanthogranulomatous cholecystitis (XC) and extensive inflammatory changes, adhesions, and fibrosis and no malignancy. The patient tolerated the procedure well and was discharged home on day two after surgery. His follow-up examination was unremarkable. Distinguishing between XC and gallbladder carcinoma is important to appropriately guide management and treatment.

An Unusual Presentation of Occult Small-Cell Neuroendocrine Carcinoma as Acalculous Cholecystitis With Widespread Liver Metastasis.

Small-cell neuroendocrine carcinoma, often classified as small-cell lung carcinoma (SCLC) type, is an aggressive neuroendocrine tumor with early metastatic potential that can lead to unexpected patient presentations. We report the case of a 69-year-old man who presented to the emergency department with worsening right upper abdominal pain, nausea, and vomiting for the past several days. The clinical picture and the workup, including the complete metabolic panel and complete blood count, were highly suggestive of acute cholecystitis with transaminitis and direct hyperbilirubinemia. The ultrasound and magnetic resonance cholangiopancreatography of the abdomen revealed a diffusely hyperdense and hypertrophic liver without evidence of choledocholithiasis. After initial resuscitation, the patient underwent laparoscopic cholecystectomy. Intraoperative findings were consistent with diffuse miliary liver metastatic disease of unknown etiology, rigid liver parenchyma, an extremely frail gallbladder wall, and mild ascites. A biopsy of the liver and cholecystectomy were performed. The final pathology revealed metastatic SCLC to the liver and widespread intravascular tumor emboli, causing diffuse ischemia of the entire gallbladder wall. The patient's postoperative course was marked by the development of foudroyant liver insufficiency and worsening severe type B lactic acidosis.

Hypothyroidism Presenting as Adynamic Ileus Mimicking a Mechanical Small Bowel Obstruction: A Diagnostic and Management Dilemma.

Patients who present with nausea, vomiting, constipation, and abdominal pain typically undergo workups for small bowel obstruction (SBO). SBO is commonly caused by mechanical obstruction due to adhesions, inflammatory conditions, or malignancies. Hypothyroidism is primarily associated with decreased basal metabolic rate and rarely, in severe cases, gastrointestinal motility dysfunction. We report a case of a 44-year-old man who presented to the emergency department with abdominal pain, nausea, and vomiting. The workup, including computed tomography, showed a small bowel feces sign, highly suspicious for a mechanical SBO. His past medical history was significant for a poorly controlled hypothyroidism due to Hashimoto's thyroiditis with a markedly elevated thyroid stimulating hormone (TSH) level. He had no prior surgical history, and his family history was significant for a suspected inflammatory bowel disease (IBD) in his son. The patient failed initial resuscitative nonoperative management and underwent exploratory laparoscopy that revealed diffusely dilated small bowel loops with no obvious cause of mechanical obstruction. Inflammatory markers for IBD were found to be negative, and the patient's gastrointestinal motility gradually improved with daily intravenous levothyroxine.

Small Bowel Perforation Due to Rare Metastasis From Stage IV Lung Adenocarcinoma.

Lung adenocarcinoma commonly metastasizes to the lymph nodes, bone, nervous system, liver, respiratory system, and adrenal gland. Metastasis to the small bowel is extremely rare and the literature deals mostly with few published case reports. We present a case of a 70-year-old male with a previous history of stage IV lung adenocarcinoma with brain and liver metastases treated with radiotherapy and chemotherapy. He presented to the emergency department with peritonitis and sepsis due to bowel perforation. He underwent an emergency exploratory laparotomy and small bowel resection. Surgical pathology revealed metastatic lung adenocarcinoma as the cause of bowel perforation. He tolerated and recovered from surgery well and was discharged on postoperative day 7. On one-month follow-up as an outpatient, he was doing well and had no complications or complaints from his recent surgery.

Synchronous papillary-medullary thyroid microcarcinoma: a case report.

Background: Papillary thyroid carcinoma is the most common type of thyroid carcinoma, making up 85-90% of all thyroid carcinomas. Medullary thyroid carcinoma is the third most common type of thyroid carcinoma, making up less than 5% of all thyroid carcinomas. However, synchronous papillary-medullary thyroid carcinoma is exceedingly rare and has not been well described historically. There have been fewer than 40 cases reported in the current literature. Case Description: In this case report we present a 65-year-old man with synchronous papillary-medullary thyroid carcinoma. A 65-year-old man presented with a symptomatic multinodular thyroid goiter. Ultrasound (US) confirmed bilateral thyroid nodules, and he was initially managed nonoperatively. Fine needle aspiration (FNA) biopsy of the left dominant nodule revealed atypia of undetermined significance (AUS) (Bethesda class III). Further assessment of the FNA specimen with ThyGeNEXT® (mutation panel) revealed no mutations and the ThyraMIR® (microRNA risk classifier) was negative, which classified the results as very highly likely to be benign. Due to worsening local compressive symptoms, a total thyroidectomy was performed. Final surgical pathology revealed incidental multicentric, multifocal micropapillary carcinoma foci from (0.1 to 0.5 cm), and a 0.3 cm medullary carcinoma in the left thyroid lobe on the background of nodular hyperplasia. Conclusions: Synchronous papillary-medullary thyroid carcinoma is a rare finding that should be considered in patients with symptomatic multinodular thyroid goiters. It is important to report this case to increase awareness and improve our understanding and management of these unusual carcinomas in the future.

The functional neuroanatomy of dystonia.

Dystonia is a neurological disorder characterized by involuntary twisting movements and postures. There are many different clinical manifestations, and many different causes. The neuroanatomical substrates for dystonia are only partly understood. Although the traditional view localizes dystonia to basal ganglia circuits, there is increasing recognition that this view is inadequate for accommodating a substantial portion of available clinical and experimental evidence. A model in which several brain regions play a role in a network better accommodates the evidence. This network model accommodates neuropathological and neuroimaging evidence that dystonia may be associated with abnormalities in multiple different brain regions. It also accommodates animal studies showing that dystonic movements arise with manipulations of different brain regions. It is consistent with neurophysiological evidence suggesting defects in neural inhibitory processes, sensorimotor integration, and maladaptive plasticity. Finally, it may explain neurosurgical experience showing that targeting the basal ganglia is effective only for certain subpopulations of dystonia. Most importantly, the network model provides many new and testable hypotheses with direct relevance for new treatment strategies that go beyond the basal ganglia. This article is part of a Special Issue entitled "Advances in dystonia".

Chasing "shadows": discovering the subtleties of sestamibi scans to facilitate minimally invasive parathyroidectomy.

BACKGROUND: With the advent of sestamibi scans, high-resolution ultrasonography (US), and intraoperative intact parathyroid hormone (PTH) measurements, minimally invasive parathyroidectomy (MIP) is considered the standard of care for patients with primary hyperparathyroidism (PHPT). Preoperative imaging, however, can be negative more than 20% of the time. METHODS: We chose to examine one surgeon's experience with patients who presented with PHPT and negative or indeterminate preoperative imaging from July 1993 to September 2009. A retrospective review of a parathyroid surgery database and patient records was conducted to collect the following information: patient age and sex; calcium and PTH levels; sestamibi and US results; and operative reports. Each sestamibi scan had been re-reviewed preoperatively by the surgeon with a nuclear medicine physician. The study cohort included patients with negative or indeterminate sestamibi results and a negative or no US report in which the surgeon was able to identify a "shadow" or subtlety on sestamibi and plan an MIP. RESULTS: A total of 126 patients had a negative or indeterminate sestamibi scan and a negative or no US report. "Shadows" or subtleties were found in 18 of 44 (41%) of the cases with a negative sestamibi and in 62 of 82 (76%) of cases with an indeterminate sestamibi scan. For these 80 cases a MIP was planned. In all, 7 of 80 (9%) were converted to a bilateral exploration. The remaining 46 patients underwent a planned bilateral exploration. Cure rates were comparable: 99% in the study group compared to 97% in the group who underwent a planned or converted bilateral exploration. CONCLUSIONS: With careful preoperative re-review of a negative or indeterminate sestamibi scan and the identification of subtleties in patients with a negative preoperative US scan, a successful MIP can be performed 91% of the time with a 98% cure rate.

Perforated Colon Cancer Associated With Post-operative Recurrent Bowel Perforations.

Colon perforation is a major life-threatening condition associated with high morbidity and mortality, which often develops secondary to complicated diverticulitis and, less commonly, colon cancer. We describe the case of a 51-year-old female who had perforated colon cancer with concurrent diverticulosis. Based on history, physical exam, laboratory, and computed tomography (CT) findings on initial presentation, the patient was diagnosed with acute complicated diverticulitis. Despite medical treatment, the patient's condition worsened, warranting exploratory laparotomy and a left hemicolectomy with transverse end colostomy creation. Surgical pathology revealed stage IIIC colon cancer without evidence of diverticulitis. The patient underwent eight cycles of adjuvant chemotherapy with FOLFOX (folinic acid, fluorouracil, and oxaliplatin). Over the next year, the patient experienced recurrent bowel perforations requiring repeated surgeries. Perforations were identified in both the small and large bowel on different occasions. Even though neither presented with a clear etiology, possible ischemic, infectious, erosive, and iatrogenic etiologies were on the differential. Our case exemplifies the mounting complications we should be wary of when performing repeated invasive abdominal operations.

Primary versus secondary nature of mesenteric neuroendocrine tumours.

Neuroendocrine tumours (NETs) are rare group of malignancy that originate from neuroendocrine cells present throughout the body. Most patients with NET first present with symptoms associated with metastasis, and up to 20% of patients have unknown primary site of tumour. Most common metastatic sites for small intestine NETs (SI-NETs) are the locoregional lymph nodes and liver. Although mesenteric metastasis through direct extension or lymphatic spread from SI-NETs is common, mesenteric extranodal involvement is extremely rare, and its biology and primary versus secondary nature are not well understood. Due to their small size and location, SI-NETs are frequently undetected on anatomical imaging or indium-111-pentetreotide single-photon emission computed tomography/CT (Octreoscan) and are difficult to be found via endoscopy. Gallium-68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate positron emission tomography (68Ga-DOTATATE PET)/CT has been increasingly used for accurate staging, unknown primary tumour site localisation and appropriate management planning. We present a case of an incidentally found mesenteric NET with occult SI-NETs localised preoperatively by 68Ga-DOTATATE PET/CT.

Incidental Adrenal Mass in a Patient With Surgically Treated Lung Adenocarcinoma.

Adrenal metastases are not uncommon in patients with widespread metastatic lung cancer. Isolated metachronous adrenal metastases in cases of surgically treated lung cancer without long-term evidence of disease are rare and may pose a diagnostic and treatment dilemma. The current literature suggests that in such cases, adrenalectomy provides better median and overall survival rates. This case presents an incidentally discovered isolated adrenal mass in a patient with a past medical history of lung adenocarcinoma that was surgically removed three years before metastasis discovery. The patient successfully underwent adrenalectomy and was disease-free with no apparent complications at her three-month follow-up visit. The case highlights the importance of long-term radiographic surveillance after surgical resection of lung adenocarcinoma for the prompt diagnosis and timely treatment of metachronous metastases.

Prospects for Radiopharmaceuticals as Effective and Safe Therapeutics in Oncology and Challenges of Tumor Resistance to Radiotherapy.

The rapid advances in nuclear medicine have resulted in significant advantages for the field of oncology. The focus is on the application of radiopharmaceuticals as therapeuticals. In addition, the latest developments in cell biology (the understanding of the cell structure, function, metabolism, genetics, signaling, transformation) have given a strong scientific boost to radiation oncology. In this regard, the article discusses what is soon going to be a new jump in radiation oncology based on the already accumulated considerable knowledge at the cellular level about the mechanisms of cell transformation and tumor progression, cell response to radiation, cell resistance to apoptosis and radiation and cell radio-sensitivity. The mechanisms of resistance of tumor cells to radiation and the genetically determined individual sensitivity to radiation in patients (which creates the risk of radiation-induced acute and late side effects) are the 2 major challenges to overcome in modern nuclear medicine. The paper focuses on these problems and makes a detailed summary of the significance of the differences in the ionizing properties of radiopharmaceuticals and the principle of their application in radiation oncology that will shed additional light on how to make the anti-cancer radiotherapies more efficient and safe, giving some ideas for optimizations.