Search Results (653)

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above zero > 0) between baseline [¹⁸F]FDG PET/CT metrics before the first treatment course and reirradiation. Material/Methods: Forty-seven patients who underwent thoracic reirradiation with curative intent at our institute between 2013 and 2021 met the inclusion criteria. All patients had histologically verified NSCLC, ECOG (Eastern Cooperative Oncology Group) ≤ 2, and underwent [¹⁸F]FDG PET/CT for initial staging and re-staging before primary radiotherapy and reirradiation, respectively. The time interval between radiation treatments was at least nine months. Quantitative metabolic volume and intensity parameters were measured before first irradiation and before reirradiation, and the difference above zero (>0; delta change) between them was statistically correlated to locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Results: Patients were followed for a median time of 33 months after reirradiation. The median OS was 21.8 months (95%-CI: 16.3–27.3), the median PFS was 12 months (95%-CI: 6.7–17.3), and the median LRC was 13 months (95%-CI: 9.0–17.0). Multivariate analysis revealed that the delta changes in SULpeak, SUVmax, and SULmax of the lymph nodes significantly impacted OS (SULpeak p = 0.017; SUVmax p = 0.006; SULmax p = 0.006), PFS (SULpeak p = 0.010; SUVmax p = 0.009; SULmax p = 0.009), and LRC (SULpeak p < 0.001; SUVmax p = 0.003; SULmax p = 0.003). Conclusions: Delta changes in SULpeak, SUVmax, and SULmax of the metastatic lymph nodes significantly impacted all clinical endpoints (OS, PFS and LRC) in recurrent NSCLC patients treated with reirradiation. Hence, these imaging biomarkers could be helpful with regard to patient selection in this challenging clinical situation. Full article

Gastric cancer remains the fourth leading cause of cancer-related mortality worldwide. Advanced disease is associated with a poor prognosis, emphasizing the critical importance of early diagnosis through endoscopy. In addition to prognosis, disease extent also plays a pivotal role in guiding management strategies. Therefore, accurate locoregional staging (T and N staging) is vital for optimal prognostic and therapeutic planning. Endoscopic ultrasound (EUS) has long been an essential tool in this regard, with computed tomography (CT) and, more recently, positron emission tomography–computed tomography (PET–CT) serving as alternative imaging modalities. EUS is particularly valuable in the assessment of early gastric cancer, defined as tumor invasion confined to the mucosa or submucosa. These tumors are increasingly managed by endoscopic resection techniques offering improved post-treatment quality of life. EUS has also recently been utilized in the restaging process after neoadjuvant chemotherapy, aiding in the evaluation of tumor resectability and prognosis. Its performance may be further enhanced through the application of emerging techniques such as contrast-enhanced endosonography, EUS elastography, and artificial intelligence systems. In advanced, unresectable disease, complications such as gastric outlet obstruction (GOO) severely impact patient quality of life. In this setting, EUS-guided gastroenterostomy (EUS-GE) offers a less invasive alternative to surgical gastrojejunostomy. This review summarizes and critically analyzes the role of EUS in the context of gastric cancer, highlighting its applications across different stages of the disease and evaluating its performance relative to other diagnostic modalities. Full article

Desmoid tumors are rare, deep-seated myofibroblastic tumors with an unpredictable course, ranging from spontaneous regression to infiltrative growth and locally aggressive behavior, but without metastatic potential. Over the past few decades, advances in understanding their natural history, underlying molecular pathways, and patient care priorities have shifted the treatment paradigm from upfront surgical resection to initial active surveillance, with further treatment dictated by continuous disease progression or associated symptoms. However, there are still specific scenarios where surgery continues to play an important role in locoregional treatment and symptom control. This article will focus on current treatment strategies and surgical indications in adult patients with desmoid tumors, emphasizing patient selection, anatomic site-specific considerations, and surgical technique. Understanding the nuanced role of surgery within the growing treatment landscape is key for individualized patient care in a multidisciplinary setting to optimize quality of life and long-term outcomes. Full article

Background: We evaluated the utility of HNSCC LN R2* relaxation times to infer the oxygenation status of LN non-invasively at baseline and when breathing air and 100% oxygen to predict chemoradiotherapeutic locoregional response at 2 years. Hypoxia within LNs has been associated with poorer outcomes following CRT. Deoxyhaemoglobin decreases MRI transverse relaxation time (T2*) (lengthening inverse, R2*). Methods: A total of 54 patients underwent 1.5T-MRI before CRT. Conventional MR sequences were supplemented with T2* sequences breathing both air and 100% oxygen; pathological nodes identified in consensus were volumetrically contoured to T2* parametric maps. Results: Patients followed-up with for >2 years were categorised by multidisciplinary consensus into post-therapy complete local response (CR; n = 32/54) and local nodal disease relapse (RD; n = 22/54). Our data demonstrated, by R2*, that nodes that sustained post-therapy CR are significantly more hypoxic compared with relapsing nodes and paradoxically demonstrate a significant increase in hypoxia on 100% oxygen. Pre-treatment LN short axis diameter, various qualitative descriptors of malignancy, and quantitative DWI were not useful in discriminating successful response to CRT. Conclusions: This study demonstrates that a significant differential response to 100% oxygen and higher baseline R2* LN measurements could be exploited in risk stratification prior to CRT, and future work could be directed towards understanding the contrast mechanisms of R2* imaging, underpinning the observed differences in the context of hypoxia. Full article

Background/Objectives: Liver metastases are common among patients with breast cancer and have a poor prognosis if left untreated. The aim of this systematic review is to evaluate and compare chemoembolization (TACE) versus radioembolization (TARE) treatments in patients with breast cancer liver-dominant metastases in terms of overall survival (OS), local tumor control (LC), and toxicity. Methods: The S.P.I.D.E.R framework was used to address the clinical question. A systematic literature search using PubMed and Scopus was performed to identify full articles evaluating the efficacy of TACE and TARE in patients with liver metastases from breast cancer. Results: The literature search resulted in 10 articles for TACE, 13 articles for TARE and 1 for combined TACE/TARE, totaling 462 patients for the TACE group and 627 for the TARE group. The median LC was 68.7% for TACE and 78.9% for TARE. The median OS was 15.3 months for TACE and 11.9 for TARE. Progression at three months was 32.5% for TACE and 20.6% for TARE. Conclusions: The included studies were heterogeneous, varying widely in design, patient selection, and therapeutic protocols. Nonetheless, this systematic review suggests that locoregional therapies are effective in the treatment of liver metastases in patients with breast cancer and may improve tumor burden, alleviate symptoms and extend overall survival. The median LC of the liver metastases at three months was higher in the TARE group compared to TACE. However, the TARE group showed lower OS rates after treatment. Full article

Background/Objectives: Image-guided adaptive brachytherapy is a standard modality in the treatment of locally advanced cervical cancer. However, the availability of isotope-based brachytherapy is limited in countries with lower resources. The objective of this study is to report the first institutional dosimetric and clinical data on intracavitary electronic brachytherapy. Methods: A total of 25 patients with histologically proven cervical cancer stage IB-IVA were treated with concurrent chemoradiotherapy and electronic brachytherapy. The patients were followed up for a median of 12 months (range 6–24). Toxicity was evaluated by the radiation oncologist and gynecologist on each visit and scored by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: All patients completed the treatment successfully with a median overall treatment time (OTT) of 52 days (range 39–89). The desired target coverage was achieved in all patients, and the dose limits for the organs at risk were achieved in 88% of the patients. No Grade 3 toxicities occurred. A total of 84% of the patients achieved local control in the cervix, and a complete response was noted in 72% of the patients. Conclusions: Electronic brachytherapy provides the option to deliver a high dose of radiation to the uterine cervix without leading to severe toxicity. Further improvements to the treatment protocol could provide better locoregional and systemic control of the disease. Studies with larger cohorts and longer follow-up are necessary. Full article

Background: With aging populations, the incidence of squamous cell carcinoma of the head and neck (SCCHN) among elderly patients is increasing. Although adjuvant radiotherapy or chemoradiation is a well-established component of multimodal treatment, elderly patients remain underrepresented in clinical trials. This study evaluates the feasibility of adjuvant radiotherapy and chemoradiation in patients over 70 years with SCCHN and explores the correlation between treatment feasibility and various comorbidity scores. Methods: We retrospectively analyzed patients over 70 years of age who received adjuvant radiotherapy or chemoradiation at the University Hospital Regensburg between 2004 and 2018. A total of 71 patients, with a median age of 75 years, were included. The majority were classified as UICC stage IVa. Median follow-up was 27 months. Results: Sixty-two patients completed treatment without interruption, and sixty-five received at least 95% of the prescribed radiation dose. The median total dose was 64 Gy. Acute toxicity of grade III or IV (CTC) occurred in 37 patients. Local tumor control rates were 99% at 12 months, 88% at 24 months, and 76% at 5 years. Overall survival rates were 87% at 12 months, 67% at 24 months, and 41% at 60 months, with a median overall survival of 51 months. The Elixhauser Comorbidity Score showed significant predictive value for treatment feasibility (p = 0.006). Conclusions: Adjuvant radiotherapy and chemoradiation are feasible and effective treatment options for elderly patients with SCCHN. The favorable local and locoregional control rates reported here suggest, in line with other recent reports in the literature, that age alone should not be a justification for treatment de-intensification. Full article

Background: Transarterial radioembolization (TARE) with Yttrium-90 microspheres is an established therapy for unresectable hepatocellular carcinoma (HCC). However, its clinical efficacy compared to transarterial chemoembolization (TACE) remains unclear. Methods: We retrospectively reviewed 279 consecutive patients undergoing TARE (n = 104) or TACE (n = 175) at four tertiary centers. Patients with metastatic disease, locally advanced HCC, or Child–Pugh (CP) C were excluded. Data on treatment, adverse events, survival outcomes (median overall survival [mOS], and objective response rates [by modified Response Evaluation Criteria in Solid Tumors; mRECIST]) were collected. Results: The median follow-up of the cohort was 27 months (IQR 13–50), the mean age was 67.6 ± 10.1 years, and 207 (74.2%) were male. The cohort was balanced in age, performance status, CP class, and HCC etiology. Maximum tumor diameter was significantly larger in the TARE cohort compared to the TACE cohort (4.4 vs. 3.1 cm, p < 0.001), including within the BCLC 0/A (4.2 vs. 2.7 cm, p = 0.001) and BCLC B (5.0 vs. 4.0 cm, p = 0.049) subgroups. The mOS was longer with TACE (37 vs. 22 months; hazard ratio [HR] 1.65, 95% CI: 1.19–2.29, p = 0.002). In BCLC 0/A patients, TACE yielded longer mOS (60 vs. 25 months; HR 2.35, 95% CI: 1.17–4.69; p = 0.016). In BCLC B, mOS was longer with TACE (32 vs. 20 months), but was not statistically significant (HR 1.39, 95% CI: 0.96–2.03, p = 0.080). In BCLC 0/A, complete response rates were higher with TACE (43.2% vs. 34.3%, p = 0.012). Hepatic decompensation was more frequent with TARE- (26.0%) than with TACE-treated patients (13.7%, p = 0.010). Conclusions: TACE demonstrated superior survival outcomes over TARE, particularly in early-stage disease. These results advocate for a more nuanced selection of embolization therapies in these patients. Full article

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and remains one of the leading causes of cancer-related mortality. Its incidence continues to rise worldwide, and it is currently the fastest-growing cancer by incidence in the United States. HCC most often arises in the context of chronic liver disease, particularly cirrhosis. While chronic viral hepatitis (hepatitis B and C) has traditionally been the primary etiologic factor, recent advances in antiviral therapies and prevention strategies have shifted the epidemiological landscape. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease are increasingly prominent risk factors, especially in Western populations. This shift underscores the need for targeted risk factor modification, improved early detection, and enhanced surveillance protocols. The management of HCC necessitates a multidisciplinary approach, incorporating locoregional therapies, surgical resection, liver transplantation, and systemic therapies for advanced-stage disease. Recent advances in systemic treatments, including immune checkpoint inhibitors and combination therapies, have transformed the therapeutic landscape. Despite these developments, significant challenges persist in optimizing treatment, identifying predictive biomarkers, and personalizing therapy. Ongoing research is focused on refining molecular classifications and advancing precision medicine strategies to improve outcomes. This review provides a comprehensive overview of the etiology, surveillance strategies, diagnostic approaches, molecular features, and current treatment modalities for HCC. Full article

Background: Functioning gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors that secrete biologically active hormones, leading to complex clinical syndromes such as carcinoid syndrome, VIPoma, glucagonoma, gastrinoma, insulinoma, and somatostatinoma. These syndromes frequently induce profound metabolic, gastrointestinal, and nutritional disturbances. Objective: This review aims to provide a comprehensive overview of the physiopathology of malnutrition in functioning GEP-NENs and to highlight nutritional and supportive care strategies, including how medical, surgical, and locoregional treatments can indirectly improve nutritional outcomes. Methods: We analyzed the current literature and clinical guidelines to identify key mechanisms of malnutrition across different functioning syndromes and their clinical manifestations. Nutritional recommendations and the impact of treatment modalities on nutritional status were summarized. Results: The pathophysiology of malnutrition in functioning NENs is multifactorial and syndrome-specific. Hormonal hypersecretion may cause diarrhea, electrolyte imbalances, catabolic states, steatorrhea, or hypoglycemia, among other effects. These lead to nutrient loss, malabsorption, or altered intake. Tailored dietary interventions, micronutrient supplementation (e.g., niacin, calcium, vitamin B12), and symptom-guided nutritional support are essential. Somatostatin analogs, PRRT, and cytoreductive approaches often contribute to symptom control, thereby enhancing nutritional status and patient quality of life. Conclusions: Malnutrition in functioning GEP-NENs is a significant clinical issue that requires early recognition and a multidisciplinary, individualized management plan. Integrating nutrition into the comprehensive care of these patients is essential to improve outcomes and quality of life. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with metabolic-dysfunction-associated steatohepatitis (MASH) and alcohol-related liver disease (ALD) emerging as major etiologies. This review explores the epidemiological trends, pathogenesis, and clinical management of HCC arising from MASH and ALD, highlighting both the shared and distinct mechanisms. MASH-HCC is driven by metabolic dysregulation, including obesity, insulin resistance, and lipotoxicity, with genetic polymorphisms such as PNPLA3 and TM6SF2 playing critical roles in disease progression. ALD-HCC, in contrast, is propelled by the toxic byproducts of ethanol metabolism, including acetaldehyde and reactive oxygen species, which induce chronic inflammation, and fibrosis. Both conditions also involve immune dysregulation, gut dysbiosis, and increased intestinal permeability, contributing to hepatic carcinogenesis. The review emphasizes that, while there is consensus regarding the screening of HCC in cirrhosis patients, there is lack of consensus on screening strategies for non-cirrhotic MASH patients who are also at risk for HCC. This underscores the importance of the early detection of cirrhosis using advanced diagnostic tools such as transient elastography and fibrosis scores. Current therapeutic approaches, ranging from surgical resection, liver transplantation, and locoregional therapies to systemic therapies like immune checkpoint inhibitors, are discussed, with an emphasis on the need for personalized treatment strategies. Finally, the review highlights future research priorities, including the development of novel biomarkers, exploration of the gut–liver axis, and deeper investigation of the interplay between genetic predisposition and environmental factors. By synthesizing these insights, the review aims to inform multidisciplinary approaches to reduce the global burden of MASH- and ALD-related HCC and improve patient outcomes. Full article

Background: The role of neoadjuvant endocrine therapy (NET) in patients with luminal tumors is still not well defined in everyday clinical practice. To assess the efficacy of combination NET, we analyzed the outcomes of fulvestrant and aromatase inhibitors (AI) in combination in a real-world population. Methods: This was a single-arm, retrospective longitudinal study of the total population of patients diagnosed with locoregionally advanced, clinical stage II-III, HR+ HER2-, luminal-type eBC, who were treated with the neoadjuvant combination of fulvestrant and AI between 2019 and 2024 at the Clinical University Hospital of Split, Croatia. Results: We enrolled 44 patients in the intention-to-treat (ITT) population, while 34 completed NET and surgery (per-protocol population; PPP). The median duration of NET was 11 months (interquartile range [IQR] of 9–16 months). The best radiological objective response rate (partial or complete response) was achieved by 30 (68.2%) in ITT, and 26 (76.5%) in PPP, defined by radiological examination, breast ultrasound, or MR. In the PPP, the minimal or moderate pathological response according to residual cancer burden (I or II) was observed in 29 (85.3%) patients. The median of absolute changes in Ki-67 was −5 (95% CI: −9 to 0), and the median of relative Ki67 changes was −40% (95% CI: −72% to 0%). Post-surgical Ki-67 was significantly predicted by initial Ki-67, positive lymph nodes, and time from diagnosis to the initiation of NET. Treatment was well tolerated, with no therapy discontinuation or dose reductions needed due to toxicity. The most commonly reported side effects included musculoskeletal pain (45.5%), asthenia (34.1%), and hot flashes (29.5%). Conclusions: Dual hormonal therapy with fulvestrant and AI is an active, easily given, non-toxic, promising neoadjuvant treatment in real-world patients with locally advanced luminal-type eBC who are not candidates for chemotherapy. Full article

Background/Objectives: Synchronous ipsilateral supraclavicular lymph node metastases (sISLMs) in breast cancer are rare and associated with poor prognosis. The optimal locoregional treatment strategy remains unclear, particularly regarding the role of supraclavicular lymph node dissection (SLND). Methods: We conducted a systematic review and network meta-analysis, including studies published up to end December 2023, to compare the outcomes of SLND combined with radiotherapy (RT) and systemic therapy (ST), SLND with ST alone, and ST alone, using RT + ST as the reference. Results: Ten studies involving 3346 patients were included for overall survival (OS) analysis, and six studies were included for disease-free survival (DFS). SLND + RT + ST showed similar OS and DFS compared to RT + ST. Sensitivity analyses revealed that SLND limited to level V improved OS (HR: 0.47, 95% CI: 0.29–0.77), while more extensive dissections (level V+) worsened outcomes (HR: 1.41, 95% CI: 1.10–1.80). Conclusions: These findings suggest that selective SLND may benefit certain patients, but broader application should be approached with caution pending results from future randomized trials. Full article