Background: Differentiated thyroid cancer (DTC) in children and adolescents is a rare but significant malignancy, often presenting at more advanced stages compared to adults, although it is associated with favorable long-term outcomes. This study aimed to identify prognostic factors and perform risk stratification with the goal of identifying low-risk patients who would benefit from a less radical treatment approach. Methods: This retrospective cohort study included patients aged 21 years and younger with DTC treated at the Institute for Oncology and Radiology of Serbia between 1980 and 2024. Results: The study analyzed 99 patients (39 children, 60 adolescents) with a median follow-up of 15.6 years (range: 0.6–43.6 years). No significant differences in long-term outcomes were observed between children and adolescents. Multivariate regression analysis identified a total number of more than 10.5 positive lymph nodes and extrathyroidal tumor extension as independent predictors of adverse events and event-free interval (EFI). Using these prognostic factors, patients were stratified into three groups: low-risk (no risk factors), intermediate-risk (one of two risk factors), and high-risk (both risk factors). Statistically significant differences in EFI were observed among the three groups. Notably, none of the patients in the low-risk group had evidence of disease after treatment. Patients classified as having no evidence of disease after treatment demonstrated significantly better EFI compared to those with evidence of disease. Conclusions: Our findings highlight the importance of meticulous risk stratification in predicting long-term outcomes and might serve as a basis for developing personalized therapeutic strategies. Identifying low-risk patients who may benefit from a less aggressive treatment approach while ensuring optimal treatment and follow-up for high-risk patients remains a central objective in the modern management of DTC.

Background: Single-agent pembrolizumab represents a standard of care in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC) with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%. Real-world evidence is of increasing importance in oncology, as clinical trial inclusion criteria may not be truly reflective of the patient population seen in daily clinical practice. Methods: We performed a prospective–retrospective single-center study including 121 patients who received pembrolizumab as a first-line therapy for mNSCLC with a PD-L1 TPS ≥ 50%. Our aims were to make a comparison with published clinical trial results by assessing the efficacy and safety of pembrolizumab monotherapy in our population. We collected patient demographics, clinical characteristics of the disease, and treatment outcomes, including efficacy and safety. Results: A total of 121 patients were included, with a median follow-up of 40.77 months. The median progression-free survival in the real world (rwPFS) was 20.73 months (95% CI 12.24–29.22), and the median overall survival (OS) was 29.30 months (95% CI 16.57–42.04). Immune-mediated adverse events (irAEs) occurred in 42% of patients, with serious events (grade 3 or more) occurring in 12%. ECOG PS 2, male gender, squamous histology, pleural and visceral metastases, and treatment with corticosteroids prior to initiation of pembrolizumab were found to be negative predictors for overall survival, while the occurrence of irAEs was the predictor of longer survival. Conclusions: This study provides further real-world insights into the efficacy of pembrolizumab in a heterogeneous patient population with advanced NSCLC in a single center in Serbia. It also confirmed the value of good ECOS PS and the occurrence of irAEs as predictors of favorable outcomes.

Background/Objectives: Multiple primary malignancies (MPMs) are defined as the occurrence of two or more independent primary tumors in the same patient, histologically distinct and not of metastatic origin. Patients treated for Hodgkin's lymphoma (HL) carry an increased risk of developing secondary malignancies, especially after chemotherapy and radiotherapy. The synchronous occurrence of breast and kidney carcinoma in this population is extremely rare. Methods: We present a 41-year-old female patient with a history of HL treated at the age of 23 with ABVD chemotherapy and supradiaphragmatic radiotherapy. Results: During staging for a newly diagnosed breast tumor (ER+/PR+/HER2+, pT1cN0), an incidental renal mass was identified and histologically confirmed as clear cell renal cell carcinoma (pT1aNxMx, G2). A multidisciplinary team performed simultaneous partial breast resection with sentinel lymph node biopsy and nephrectomy. The postoperative course was uneventful, and adjuvant systemic therapy was initiated according to oncological guidelines. Conclusions: Synchronous malignancies in HL survivors pose a clinical challenge, as they must be distinguished from metastatic disease and require coordinated therapeutic planning. Risk factors include prior radiotherapy, chemotherapy, genetic predisposition, and family history. This case highlights the importance of long-term surveillance of HL survivors, particularly young women, due to their elevated risk of secondary malignancies. Synchronous breast and kidney carcinomas after HL therapy are extremely rare and demand an integrated multidisciplinary approach. Early recognition and coordinated therapy are crucial for optimizing outcomes and contributing to a better understanding of the etiology and pathogenesis of multiple primary malignancies.

Introduction: Radiation-induced breast angiosarcoma (RIBAS) is a rare adverse event associated with postoperative breast irradiation. The data from the literature indicate that RIBAS occurs in less than 0.3% of patients treated with adjuvant radiotherapy for breast cancer. Given the rarity, diverse clinical presentation, poor prognosis, and lack of consensus on the management, this study aimed to present experiences of our specialized cancer center with RIBAS, in terms of the incidence, presentation, management, and outcomes. Methods: We reviewed the medical records of 10,834 breast cancer patients treated at the Institute for Oncology and Radiology of Serbia between January 2013 and June 2024 to detect patients that had breast-conserving surgery, followed by postoperative irradiation, and developed angiosarcoma in the irradiated area at least 3 years after radiotherapy, without distant metastases. The incidence, latency period, management, and treatment outcomes were analyzed. Results: A total of nine female patients with RIBAS were identified and included in this study. The median age at RIBAS diagnosis was 64 years (range: 36–68), with a median latency of 64 months (95% CI > 57) from irradiation to diagnosis. The mean tumor size was 55 mm (SD 32.78). Patients were followed for a median of 30 months (range: 7–40) after initial RIBAS surgery. Local recurrence occurred in seven patients (77.8%), with five undergoing re-do surgery with curative intent. Three patients developed distant metastases during follow-up. The median overall survival (OS) was 31 months (95% CI > 30), with a 3-year survival rate of 15.2% (95% CI 2.5–91.6%). The median local recurrence-free interval was 10 months (95% CI > 3). Median OS after RIBAS local recurrence and after breast cancer treatment was 17 months (95% CI > 15) and 108 months (95% CI > 88), respectively. Conclusions: RIBAS is a rare but increasingly prevalent adverse event associated with BC irradiation, marked by an aggressive disease course and high relapse rates. Awareness, prompt diagnosis, and a radical surgical approach with wide clear margins are critical for improving patients’ outcomes.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of PD-L1, EGFR and AR expression in TNBC promotion and progression. To that end, we analyzed the immunohistochemical expression of these genes in 125 TNBC patients and their relation to clinicopathological parameters and survival. An elevated expression of PD-L1 was significantly correlated with higher tumor and nuclear grade, while a low expression was correlated with loco-regional recurrence without any influence on survival. Contrary to this, the expression of AR showed a positive impact on the DFI and a negative association with tumor grade. Furthermore, PD-L1 and AR demonstrated simultaneous expression, and further co-expression analysis revealed that a positive expression of PD-L1/AR notably correlates with tumor and nuclear grade and has a significant impact on a longer DFI and OS, while a negative PD-L1/AR expression is significantly associated with metastases. Therefore, our results suggest that positive PD-L1/AR expression is beneficial for TNBC patients. In addition, an elevated expression of EGFR contributes to metastases and a worse DFI and OS. In conclusion, we think that low PD-L1/low AR/high EGFR expression followed by high Ki67 expression constitutes a ‘high risk’ profile of TNBC.

BACKGROUND:Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS:In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS:Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION:Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING:None.

Background: Serum calcitonin (Ct) levels in medullary thyroid carcinoma (MTC) usually correlate with tumor size and disease extent. Majority of surgeons recommend total thyroidectomy (TT) and central neck dissection (CND) in proven or suspected MTC, but the extent of lateral neck dissection (LND) remains controversial. The aim of this study was to analyze usefulness of sentinel lymph node (SLN) biopsy with methylene blue dye (MBD) for intraoperative lymph node (LN) staging and selection of clinically N0 (cN0) patients with micro-MTCs and serum Ct level below 1000pg/ml for one-time LND, along with TT and CND.

Background: The aim of this study was to analyze esthetic outcomes of breast conserving surgery (BCS) after neoadjuvant treatment (NAT) by patients’ self-assessment.

Abstract Phyllodes tumors of the breast can be benign, malignant, or borderline. Benign and borderline tumors are rare tumor types that have a positive outlook and high survival rate, while the risk of recurrence is typical for malignant breast tumors. Giant phyllodes tumors are larger than 10 cm in diameter and demand a serious diagnostic and treatment approach. In this study we present a case of a female patient treated for an exulcerated breast carcinoma- a giant borderline phyllodes tumor of the breast. The patient presented to the department for the right breast lump with ulcerated skin and nipple abnormalities. The core biopsy was performed and the patient was diagnosed with a benign tumor. Simple mastectomy was performed and final histopathological report revealed a borderline phyllodes tumor. Diagnosis and treatment of a giant phyllodes tumor remain a great challenge for the surgeons. Establishing the preoperative diagnosis based on histopathological findings is imperative to disease management. Surgery is the mainstay of treatment and mastectomy has been the traditional procedure; in cases where suspicious findings in the axilla are revealed, radical mastectomy is performed and the axilla is to be dissected.

PURPOSE The incidence of histologically proven lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) reaches 80%. According to different guidelines surgical management in clinically N0 (cN0) patients with PTC remains controversial. The purpose of this study was to investigate if sentinel lymph node biopsy (SLNb) using methylene blue dye is accurate in the detection of LNM in the lateral neck compartment in cN0 patients with PTC. METHODS Enrolled were 153 cN0 patients with PTC. All underwent total thyroidectomy with central neck dissection and SLNb in the lateral neck compartment, using methylene blue dye as marker. Selective modified radical neck dissection was performed in cases of metastatic SLNs. RESULTS Neck LNMs were histologically verified in 40.9% of the cases. Predictive factors for LNM were: males, younger than 45 years, tumors greater than 1cm, capsular and vascular invasion. The central neck compartment of LNM was predictive for lateral LNM in 80.5% of the cases. LNM were confirmed in 24% of SLNs in the lateral neck compartment, which were over 56% predictive of LNM to other dissected lateral LN. SLN identification rate (IR) was 91.8%. Sensitivity, specificity, positive value (PPV) and negative predictive value (NPV) were 85.7, 96.7, 88.3 and 95.9%, respectively. The overall accuracy of the method was 94.3%, with probability of 91.2% (ROC AUC, 95% CI; 84.2-98.3). CONCLUSION The proposed method of SLN biopsy using methylene blue dye is feasible, safe and accurate in the detection of LNM in the lateral neck compartment and may help in the decision to perform selective modified radical neck dissection in cN0 patients with PTC.

Introduction: Metastatic tumors are the most frequent tumors of the heart with the melanoma metastasis being the most frequent. In cases of a cardiac tamponade or a low cardiac output syndrome due to the position of the tumor it could lead to an acute life-threatening condition for the patient. Case report: We present a case of a successfully treated metastatic cardiac melanoma in a lifesaving cardiac surgery. A 42-year-old woman was admitted to the emergency department of the Clinical Center of Serbia in a critical state with signs of tricuspid orifice obstruction with a tumor mass. Her previous medical history showed that she had an adequate surgical excision of the melanoma in the right lumbar region at the age of 39. An emergency cardiac surgery was performed with the resection of the tumor and the atrial wall. The postoperative course was uneventful and a HP exam once again confirmed the same type of melanoma as previously diagnosed. The patient was alive and well on followup exams for 4 months when she was diagnosed with metastatic tumor masses in the pelvis with ascites and melanosis of the entire skin followed by lethal outcome 5 months after the cardiac surgery. Conclusion: Surgical resection of metastatic cardiac melanoma can be safe and effective in an emergency scenario, especially in the case of solitary metastasis. It can be performed with excellent results and very few postoperative complications. however, due to the nature of the principal disease, the long-term survival rate remains low, giving the surgery a place in palliative treatment.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The aim of this prospective study was to analyze accuracy of sentinel lymph node biopsy with methylene blue dye for intraoperative detection of lateral metastases in clinically N0M0 medullary microcarcinomas with calcitonin <1,000 pg/mL and selection of true-positive patients for one-time therapeutic lateral dissection. In addition to total thyroidectomy and central neck dissection, all patients had bilateral sentinel biopsy of jugulo-carotid regions after methylene blue injection to decide upon necessity for lateral dissection. If sentinels were benign on frozen section, additional non-sentinels were extirpated, with no further lateral dissection. If sentinels were malignant, one-time lateral dissection was performed. 20 patients were included in this study. Hereditary disease form was observed in 3/20 (15%) of patients with RET proto-oncogene mutation C634F; remaining 17/20 (85%) were negative for germline mutations. There were no allergic reactions to methylene blue and identification rate of sentinels was 100%. In total, 2/20 (10%) cN0 patients had lymphonodal metastases, thus were reclassified as pN1b. Remaining 18/20 (90%) were classified pN0 based on standard pathohistology. Frozen section findings on sentinels were 100% match with standard pathohistology, and there were no skip metastases in lateral compartments. Sensitivity, specificity and accuracy of sentinel biopsy method with methylene dye and frozen section were 100%. Dzodic's sentinel lymph node biopsy method can be used for intraoperative assessment of lateral compartments and optimization of initial surgery of medullary microcarcinomas with calcitonin <1,000 pg/mL. This way, cN0 patients with sentinel metastases can receive one-time lateral dissection, and those without benefit from less extensive surgery.