Search Results (289)

Background: The prognostic impact of therapy-induced neutropenia in patients receiving definitive chemoradiotherapy for locally advanced thoracic esophageal cancer (EC) remains inadequately characterized. This study aimed to evaluate the association between grade 3–4 neutropenia and survival outcomes following docetaxel–cisplatin–5-fluorouracil (DCF) combined with radiotherapy (DCF-RT). Methods: Fifty patients with locally advanced thoracic EC were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m² (day 1), CDDP at 60 mg/m² (day 1), and 5-FU at 600 mg/m² (days 1 to 4), administered every four weeks for two cycles in combination with radiotherapy (60 Gy in 30 fractions). Toxicities were assessed using the Common Terminology Criteria for Adverse Events. Overall survival (OS), progression-free survival (PFS), locoregional control and distant metastasis-free survival were compared by neutropenia grade. Results: Grade 3–4 neutropenia occurred in 80% (95% CI: 66.3–90.0) of patients. The OS rate was significantly lower in those with grade 3–4 neutropenia than in those with grade 0–2 (p = 0.006). Multivariate analysis identified grade 3–4 neutropenia (HR 3.77; 95% CI: 1.35–10.56) and complete response (CR) (HR 0.47; 95% CI: 0.25–0.87) as independent prognostic factors for OS among patients who received definitive CRT. Among 38 patients with recurrence or residual disease, those with grade 3–4 neutropenia exhibited significantly greater reductions in lymphocyte counts at recurrence versus pretreatment (p = 0.012) compared with those with grade 0–2 neutropenia. Conclusions: Therapy-induced neutropenia is an independent prognostic factor for OS in locally advanced thoracic EC patients undergoing definitive DCF-RT. It may also serve as a predictor of insufficient lymphocyte recovery following chemoradiation. Full article

Background/Objectives: Management of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) varies between systemic immunotherapy and locoregional approaches. We compared atezolizumab plus bevacizumab (Atezo–Bev) with locoregional therapy in treatment-naïve patients. Methods: We conducted a retrospective cohort study of patients with image- or biopsy-proven HCC and MVI, Child–Pugh A/B, and ECOG 0–1 who received first-line Atezo–Bev or locoregional therapy (transarterial chemoembolization [TACE] with or without external-beam radiotherapy [RT]). Inverse probability of treatment weighting (IPTW) minimized baseline imbalances. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Modified RECIST assessed radiologic response, and major adverse events were classified using Society of Interventional Radiology criteria. Results: We analyzed 475 patients (Atezo–Bev, n = 191; locoregional therapy, n = 284). Baseline characteristics were similar, and IPTW achieved covariate balance. Median OS was 9.3 months with Atezo–Bev and 10.8 months with locoregional therapy; after IPTW, OS remained comparable (hazard ratio [HR] 0.95; 95% CI 0.76–1.19; p = 0.635). Median PFS was 6.0 versus 4.1 months, favoring Atezo–Bev; this persisted after IPTW (HR 0.64; 95% CI 0.52–0.79; p < 0.001). Objective response rates were similar (45% vs. 48%; p = 0.49). Major adverse events occurred in 11% of patients in both groups. Subgroup analyses showed no OS differences and a consistent PFS advantage with Atezo–Bev. Conclusions: In HCC with MVI, first-line Atezo–Bev achieved longer PFS than locoregional therapy, with comparable OS and safety, supporting Atezo–Bev as a valid and effective first-line option for disease control while locoregional modalities remain relevant within multidisciplinary care. Full article

Background/Objectives. Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC). The receptor tyrosine kinase EPHA3 is a critical driver for NEPC. It is overexpressed in PCa, particularly in androgen-independent and neuroendocrine subtypes. EPHA3 activates c-Myc signaling to enhance EZH2 expression, promoting histone H3K27 trimethylation. The neural transcription factor BRN2 functions upstream of both EZH2 and ASCL1. The latter regulates the Notch pathway ligand DLL3, thereby orchestrating neuroendocrine differentiation. Elevated expression of classical neuroendocrine markers CHGA and SYP is characteristic of the NEPC phenotype. This study reports the novel usage of the olive phenolic S-(-)-hydroxyoleocanthal (HOC, oleacein) to effectively control NEPC by targeting the EPHA3–BRN2–EZH2–ASCL1–DLL3–SYP–CHGA oncogenic network. Methods. Cell viability assays were conducted to assess in vitro effects. To model NEPC progression and recurrence, NCI-H660-Luc cells were xenografted into male athymic nude mice. RNA-sequencing was performed to compare the differentially expressed genes between placebo control and treated tumors. Results. HOC significantly attenuated the proliferation of NEPC NCI-H660 cells in vitro. Daily oral administration of HOC at 10 mg/kg body weight markedly suppressed the progression of NEPC NCI-H660-Luc tumors. Continued HOC treatments after surgical excision of the primary tumors substantially reduced locoregional recurrence. HOC significantly downregulated the expression of EPHA3, BRN2, EZH2, ASCL1, DLL3, SYP, and CHGA in treated primary and recurrence tumors versus placebo control. Conclusions. These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC. Full article

Background/Objectives. Prostate cancer (PCa) is among the leading causes of death from cancer in men. Frequent use of androgen receptor inhibitors induces PCa transdifferentiation, leading to poorly differentiated neuroendocrine PCa (NEPC). ROR2 is critical for NEPC pathogenesis by activating ASCL1, promoting lineage plasticity. Protein lysine methylation mediated by N-lysine methyltransferases SMYD2 and its downstream effector EZH2 upregulates the NEPC marker ASCL1 and enhances c-MET signaling, promoting PCa aggression. Epidemiological studies suggest a lower incidence of certain malignancies in Mediterranean populations due to their intake of an olive-phenolics-rich diet. Methods. Cell viability, gene knockdown, and immunoblotting were used for in vitro analyses. A nude mouse NEPC xenograft model evaluated the anti-tumor efficacy of purified and crude oleocanthal. Xenograft tumors were subjected to RNA-seq, qPCR, and Western blot analyses, with clinical validation performed using tissue microarrays. Results. A tissue microarray analysis showed that SMYD2 expression was significantly elevated in PCa tissues with higher IHS versus normal prostate tissue cores. The olive phenolic S–(–)–oleocanthal (OC) suppressed the de novo NEPC NCI-H660 cells proliferation. Male athymic nude mice xenografted with the NCI-H660-Luc cells were used to assess OC effects on de novo NEPC progression and recurrence. Male NSG mice transplanted with LuCaP 93 PDX tumor tissues generated a heterogeneous in vivo model used to assess OC effects against t-NEPC progression. Daily oral 10 mg/kg OC administration significantly suppressed the NCI-H660-Luc tumor progression and locoregional recurrence after primary tumor surgical excision. OC treatments effectively suppressed the progression of LuCaP 93 PDX tumors. OC-treated tumors revealed downregulation of ROR2, ASCL1, SMYD2, and EZH2, as well as activated c-MET levels versus the placebo control. RNA sequencing of the collected treated NEPC tumors showed that OC disrupted NEPC splicing, translation, growth factor signaling, and neuronal differentiation. Conclusions. This study’s findings validate OC as a novel lead entity for NEPC management by targeting the ROR2-ASCL1-SMYD2-EZH2-c-MET axis. Full article

Background: As demonstrated by the PACIFIC trial, biomarker-driven patient selection is crucial. While treatment based on programmed death ligand-1 (PD-L1) and mutational status have become routine, tests for biomarkers available from pretherapeutic blood samples are currently a topic of scientific interest. Methods: This analysis was conducted on patients from the ALLSTAR RWD study, which is a nationwide, prospective registry for inoperable non-small cell lung cancer (NSCLC) stage III. Patients were amenable if they had a full routine pre-treatment blood sample, from which the following biomarkers were extracted: neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), derived monocyte-to-lymphocyte ratio (dMLR) and lactate dehydrogenase (LDH) levels. The intention was to find a cutoff for each of these biomarkers to predict locoregional control (LRC), progression-free survival (PFS) and overall survival (OS). Results: MLR and dMLR demonstrated their predictive potential with cutoff values of 0.665 and 0.945, respectively. Stratifying the whole cohort by means of these cutoffs demonstrated significantly better locoregional control for patients below the threshold, both in the whole cohort (N = 175; 55.7% vs. 75.5%; p-value = 0.018) and in the Durvalumab subgroup (N = 106; 57.5% vs. 77.3%; p-value = 0.030). Similar findings were observed for PFS in the whole cohort (N = 175; 20.5% vs. 56.1%; p-value p < 0.001) and in the Durvalumab subgroup (N = 106; 31.2% vs. 64.6%, p-value < 0.001). dMLR could also significantly predict PFS (N = 173; 17.4% vs. 56.3%; p-value < 0.001), which was corroborated in the Durvalumab subgroup (N = 108; 23.1% vs. 64.1%; p-value = 0.003). Conclusions: This explorative analysis demonstrates the predictive potential of MLR and dMLR for LRC and PFS. These blood biomarkers can be readily integrated into clinical routines since they are easily available. Full article

Background: Recent trials, including JCOG0802/WJOG4607L and CALGB140503, have confirmed the oncological adequacy of segmentectomy for early-stage non-small-cell lung cancer (NSCLC). This shift emphasizes the preservation of pulmonary function and minimal invasiveness. Robot-assisted thoracic surgery (RATS) offers enhanced anatomical precision and potentially improves segmentectomy outcomes. Methods: We reviewed the current evidence comparing sublobar resection and lobectomy for early-stage NSCLC, focusing on RATS segmentectomy. Clinical trials, perioperative and long-term outcomes, technical innovations, and patient selection criteria were analyzed. Comparative data among RATS, video-assisted thoracoscopic surgery (VATS), and open approaches were synthesized, including the emerging roles of AI and 3D imaging. Results: Segmentectomy yields survival outcomes equivalent or superior to lobectomy for stage IA peripheral NSCLC ≤2 cm, with better pulmonary function despite higher locoregional recurrence. RATS enhances visualization, dexterity, and ergonomics, thereby enabling precise dissection and lymph node assessment. Compared to VATS and open surgery, RATS shows lower conversion rates, reduced pain, and comparable oncological control. Innovations, such as indocyanine green imaging, 3D modeling, and AI-guided navigation, support margin accuracy and personalized care. Conclusions: Segmentectomy has redefined the surgical standards for early-stage NSCLC. RATS maximizes the minimally invasive benefits by combining oncological safety and functional preservation. Its technical precision facilitates complex resections and integration with digital planning tools to advance personalized thoracic surgery. RATS represents the next evolution of minimally invasive thoracic surgery, redefining the balance between oncological safety and functional preservation in early-stage NSCLC. Full article

Introduction: The incidence of NSCLC increases with age, with a median of approximately 70 years at diagnosis. Historically, treatment strategies for locally advanced cancers have been developed predominantly in younger populations, often excluding elderly patients who may present with multiple comorbidities, severely impaired lung function, or decreased performance status, leading to a lack of age-relevant clinical data. Therefore, we performed a subanalysis of real-world data from the ALLSTAR study to investigate the impact of durvalumab and the radiation regimen (sequential versus concurrent) on clinical outcome in elderly patients with unresectable stage III NSCLC. Methods: We included a total of 171 patients in this subanalysis. All patients were diagnosed with unresectable stage III NSCLC. Patients were divided into two age groups, ≥70 (41%) and <70 years (59%). All of them received curative chemoradiotherapy with (66%) or without (34%) durvalumab. Results: Patients were followed up for a median time of 25.1 months (range: 3.3–52.1). In the elderly group, patients who did not receive durvalumab consolidation had a median PFS of 17 months (95%-CI: 12.4—not reached) and a higher risk of progression (HR = 2.2; 95%-CI: 1–4.6) than those treated with durvalumab, which had a median PFS of 37 months (95%-CI: 24.5—not reached). This difference was statistically significant (log rank p = 0.026). Moreover, the Cox model yielded a hazard ratio suggesting a higher risk of locoregional (HR = 3.8; 95%-CI: 1.28–11.48; log rank p-value =0.01) as well as local recurrence (HR = 5.5: 95%-CI: 1.67–18.1: p-value =0.002) in patients who received sequential chemoradiotherapy compared to those with concomitant chemoradiotherapy in the same age group. In an exploratory analysis based on a Mann–Whitney U test, we did not find significant difference in toxicity between the two age groups. Conclusions: Durvalumab was associated with prolonged progression-free survival, while concomitant radiotherapy showed a trend towards improvement in locoregional and local control in patients aged ≥70. There was no significant difference in treatment toxicity found in the exploratory Mann–Whitney U analysis between the two age groups. Full article

Background/Objectives: Immune checkpoint inhibitor (ICI)-based combinations are the standard first-line therapy for unresectable hepatocellular carcinoma (HCC). A major challenge is the early identification of patients with primary progression (1st-PD) and those who experience early progression despite initial disease control (2nd-PD). This study evaluated whether very early treatment changes in alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) could serve as predictors of treatment response during atezolizumab plus bevacizumab (Atz + Bev) therapy. Methods: A total of 147 patients treated with Atz + Bev were retrospectively analyzed. Serum tumor markers were measured approximately every 3 weeks, and radiologic responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 at week 6 (first evaluation) and again at a median of 14.8 weeks (second evaluation). Results: At the first evaluation, 32 patients achieved a partial response, 81 showed stable disease, and 25 had progression. In the week 3 landmark analysis, early increases in AFP (ratio ≥ 1.4) or DCP (ratio ≥ 1.0) identified patients who would experience primary radiologic progression, with a clear separation in landmark progression-free survival (PFS) (3.4 vs. 13.1 months; p < 0.001). Among the 109 patients with disease control at week 6, 92 maintained control and 17 progressed at the second evaluation. In the week 9 landmark cohort, modest rises in AFP (ratio ≥ 1.1) or DCP (ratio ≥ 1.5) identified individuals at risk for early secondary progression, again showing marked differences in landmark PFS (3.8 vs. 14.0 months; p < 0.001). Conclusions: The dynamic monitoring of AFP and DCP provides a simple framework for biomarker-based responder selection and adaptive treatment optimization during Atz + Bev therapy. Clinically actionable thresholds at weeks 3 and 9 may support timely treatment switching and the integration of locoregional strategies, enabling personalized, biomarker-guided management to improve outcomes in unresectable HCC. Full article

Background/Objectives: Over the past few years, high-dose radioembolization (≥150 Gy) has become widely adopted for the treatment of primary liver cancer, while evidence for its application in hepatic metastases is still limited. The aim of this study was to evaluate the safety and efficacy of high-dose transarterial radioembolization (TARE) in patients with hepatic metastases using resin Yttrium-90 (⁹⁰Y) microspheres. Methods: In this retrospective analysis, patients who were treated with high-dose TARE for hepatic metastases with ⁹⁰Y resin microspheres between May 2019 and April 2025 were included. The primary outcomes were treatment efficacy and toxicity assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Treatment efficacy was evaluated based on radiological response according to Response Evaluation Criteria in Solid Tumors version 1.1, time to progression and overall survival (OS). Secondary outcomes included ⁹⁰Y PET/CT post-treatment voxel-based local deposition model dosimetry and its relations to response. Results: A total of 15 patients were included, with hepatic metastases originating from colorectal cancer (n = 11, 73.3%), neuroendocrine tumor (n = 3, 20%) and breast cancer (n = 1, 6.7%). Seven patients (47.7%) had undergone one or multiple prior loco(regional) liver treatments and 13 (86.7%) patients had prior systemic therapy. The median mean tumor absorbed dose was 160.7 Gy (IQR 127.6–245.0 Gy), and the median normal liver parenchyma dose was 40.3 Gy (IQR 21.7–52.3 Gy). Disease control was achieved in all patients, with partial response in 10 patients (66.7%) and stable disease in 5 patients (33.3%) after 3 months. The median OS was 26.5 months (95% CI 24.5 months to no estimate). Two patients (13.3%) experienced grade 3 laboratory toxicity. No grade 4 or 5 toxicities were observed. Conclusions: High-dose TARE with ⁹⁰Y resin microspheres resulted in a high disease control rate and demonstrated a favorable safety profile, even in this heavily pretreated cohort. Full article

Background: Considering the increased need to deliver adjuvant radiotherapy (RT) after pleurectomy/decortication (P/D) for malignant pleural mesothelioma (MPM) without exceeding the tolerance of the adjacent normal tissue, new advanced RT technologies have been developed. However, radiation to the whole hemithorax presents a challenge because of the increased risk of toxicity occurring with two intact radiosensitive lungs. The aim of this study is to systematically review the literature in order to assess the role of radiotherapy after P/D for MPM, based on the evidence published so far. Methods: We conducted this systematic review according to PRISMA guidelines and registered in an international public register of systematic review (PROSPERO). A PubMed and Cochrane database search was performed to identify articles published from 2005 to 2024 regarding the role of adjuvant radiotherapy after P/D for MPM. We included only level I–III-evidence studies according to the Oxford Centre for Evidence-Based Medicine’s guidance. Results: We selected 11 level II studies. Based on published reports, delivery of high-dose external beam ‘conventional’ RT to the entire hemithorax is not recommended in a P/D setting and hemithoracic intensity-modulated radiotherapy (IMRT) may be considered an encouraging and reasonable therapeutic option, leading to excellent loco-regional control and survival results. Conclusions: Data and experience strongly support that the ideal platform to define potential indication of the adjuvant RT is a multidisciplinary team. Moreover, given the technical difficulty of IMRT treatment, we recommend considering this treatment in experienced centers with dedicated protocols for MPM due to their ability to detect and manage side effects resulting from the disease and the treatment as well as to ensure the best and the latest treatment plan for each patient. Full article

Background: Head and neck carcinomas represent a heterogeneous group of aggressive malignancies with often poor prognosis and high recurrence rates. In recent years, the identification and characterization of cancer stem cells (CSCs) within these tumors have profoundly reshaped our understanding of tumorigenesis, resistance mechanisms, and metastatic potential in this anatomical district. Cancer stem cells (CSCs) play a central role in therapeutic resistance, recurrence, and metastatic progression in head and neck squamous cell carcinoma (HNSCC), particularly within the anatomically complex maxillofacial region. This review has synthesized recent advances in CSC biology, including marker heterogeneity, stemness-associated pathways, and interactions with the tumor microenvironment. Methods: A narrative review of the available literature was conducted, focusing on studies dealing with cancer stem cells in head and neck carcinoma and their implications for maxillofacial surgery. Results: We have critically examined emerging systemic and locoregional CSC-targeted therapies, highlighting inhibitors of Notch, Wnt/β-catenin, Hedgehog, and Hippo/YAP pathways, ALDH and ABC transporter inhibitors, autophagy modulators, nanoparticle-based delivery systems, and CSC-directed immunotherapies. The implications of these approaches for surgical planning, resection margins, and postoperative disease control in maxillofacial oncology have been discussed. To enhance clarity and analytical value, we have incorporated two comprehensive tables summarizing CSC markers and therapeutic strategies. Collectively, the evidence indicates that integrating CSC-oriented diagnostics and therapeutics into multimodal management may improve long-term outcomes for patients with maxillofacial HNSCC. Conclusions: This review highlights the critical need for integrating CSC-focused research into clinical practice to develop more effective, personalized, and durable treatment strategies. Such an approach could enhance oncologic control, reduce recurrence, and improve functional outcomes for patients undergoing complex oncologic procedures in the maxillofacial region. Full article

Purpose: We aimed to study the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) in the treatment of unresectable hepatocellular carcinoma (HCC) with extrahepatic spread (EHS). Materials and Methods: A total of 323 patients with unresectable HCC received HAIC plus lipiodol microvascular embolization. HAIC was performed via puncture of the left subclavian artery with a temporary 4-French angio-catheter placed in the common/proper hepatic artery. The HAIC regimen consisted of a daily infusion of cisplatin (10 mg/m²), mitomycin-C (2 mg/m²), and leucovorin (15 mg/m²), administered over a period of 20–30 min, and then a 5-fluorouracil (5-FU, 100 mg/m²) infusion for the remaining of 22 h of each day, for five consecutive days. Before the temporary catheter was removed, 10 mL of ethiodized oil (Lipiodol, Guerbet, France) was injected to obtain a synergistic effect of chemoinfusion and lipiodol microvascular embolization. Treatment responses were evaluated based on mRECIST criteria. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients with EHS were compared to those without. Subgroup analyses of patients with and without major portal vein tumor thrombosis (PVTT) were performed both before and after propensity score matching (PSM). The survival analyses were conducted with the Kaplan–Meier method and compared using the log-rank test. All the statistical analyses were performed by SPSS (version 26.0). Result: The overall ORR was 59.1%. The median OS of the initial cohort and patients positive and negative for EHS were 16.3, 12.0, and 18.0 months, respectively (p = 0.002). In the subgroup analysis, there was no statistical difference in survival in patients with major PVTT between the with-EHS and without-EHS groups (13.0 vs. 15.0 months, p = 0.407). However, the median OS in patients with EHS was significantly shorter than those without EHS (11.4 vs. 19.4 months, p < 0.001) in the subgroup of non-major PVTT patients. After PSM, there were no significant survival differences between the EHS and non-EHS groups in any patient cohort or sub-cohort analysis. Conclusions: For unresectable HCC, controlling intrahepatic tumor progression through HAIC is more important than controlling extrahepatic tumor growth, especially in patients with major PVTT. Personalized locoregional HAIC can be performed in patients with EHS. Full article

Background: Sarcopenia assessed by skeletal muscle area (SMA) at the third lumbar vertebra (L3) is an established prognostic marker in many malignancies, including head and neck cancer (HNC). However, in HNC, L3 is rarely assessed. The prognostic value of myosteatosis, measured by skeletal muscle radiation attenuation (SMRA) remains largely unexplored. This study evaluated both muscle metrics at the third cervical vertebra (C3) for locoregional control (LRC) and overall survival (OS) in HNC. Methods: SMA and SMRA at C3 were quantified in CT scans of 904 HNC cases by a deep learning-based segmentation pipeline with manual verification. Cox proportional hazards models assessed associations with LRC and OS. Results: Median SMA was 36.64 cm² (IQR: 30.12–42.44). Median SMRA was 50.77 HU (IQR: 43.04–57.39). In multivariable analysis, lower SMA (HR 1.85, 95% CI: 1.19–2.88, p ≤  0.001) and lower SMRA (HR 1.76, 95% CI: 1.22–2.54, p < 0.001) were associated with lower LRC. For OS, lower SMA (HR 1.53, 95% CI:1.06–2.20, p = 0.02) and lower SMRA (HR 2.13, 95% CI: 1.58–2.88, p <  0.001) were associated with a worse outcome in multivariable analysis. Conclusions: Both SMRA and SMA assessed at C3 correlate with worse LRC and OS in HNC. Full article

Introduction: Recent randomized evidence suggests that stage II–IV non metastatic esophageal adenocarcinoma is best managed with perioperative chemotherapy (CHT) and surgery. Intensification of neoadjuvant chemotherapy and radiochemotherapy are proposed before surgery in high-volume centers with the aim of increasing both systemic and locoregional control. However, few data comparing intensified RTCHT, CHT plus RTCHT and perioperative CHT with FLOT in real-life scenarios are available. Methods: This is a multicenter, retrospective series, including three cohorts of patients treated for esophageal adenocarcinoma: Cohort A: nRTCHT; Cohort B: TCF plus RTCHT, defined as triplet chemotherapy followed by dose-reduced triplet therapy + RT; Cohort C: perioperative chemotherapy with FLOT regimen. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were pathologic complete response (pCR), pathologic lymph-node complete response (ypN0), overall survival (OS), and perioperative acute toxicity. Results: From January 2013 to December 2023, 142 patients were identified. All patients received multimodal therapy with radical esophagectomy. A total of 95% of patients were male; the majority of patients presented with stage cT3cN1. A total of 63 patients were treated in Cohort A (31 cases with doublet 5FU-CDDP concurrent to 50.4 Gy and 32 cases with CROSS regimen), 36 in Cohort B, and 43 in Cohort C. After a median FU of 36 months, the 3-year DFS resulted 58.6%. pCR occurred in 26 cases (18.6%). Three-year OS had a value of 72%. At univariate analysis, ypN0 was related to better DFS; cN+ disease was related with worse OS. The treatment cohort did not impact survival outcomes; however, an effect on CR was shown, with pCR in 15% (A), 36.3% (B), 11% (C) of cases, respectively (χ: 0.008). A total of 67% of patients in Cohort B experienced a ypN0. Two treatment-related deaths occurred (one in Cohort A and one in C) with a slight increase in G3 toxicity in cohort C. Conclusions: In this real-life multicenter series, oncological results were adequate for all three neoadjuvant strategies. TCF plus RTCHT guaranteed a higher pCR and ypN0 rate without increasing toxicity. An intensified neoadjuvant schedule, such as TCF plus RTCHT, may be useful in cases where higher tumor and nodal responses are needed. Taken together, our data highlight that further investigation is warranted before abandoning radiotherapy-based neoadjuvant approaches in esophageal and GEJ adenocarcinoma. Full article

Background/Objectives: Recurrences of squamous cell carcinoma (SCC) at the base of the tongue (BoT) after primary radiochemotherapy (RT-CHT) are associated with low survival rates, poor functional outcomes, and high morbidity following salvage surgery. Transoral robotic surgery (TORS) has emerged as a less invasive alternative to open surgical approaches. This study aims to describe our clinical experience with TORS in patients with BoT SCC recurrence after RT-CHT, focusing on oncological outcomes—relapse-free survival (RFS) and disease-specific survival (DSS)—as well as functional outcomes, particularly swallowing function. Methods: We conducted a retrospective review of four patients who underwent salvage TORS for BoT recurrence between September 2013 and September 2014 at a single tertiary referral center. All patients had been previously treated with primary RT-CHT for oropharyngeal squamous cell carcinomas. Oncological events (recurrence, death) and functional endpoints (dietary limitations, MD Anderson Dysphagia Inventory [MDADI] scores) were retrieved from medical records. Results: Four patients were included. All achieved unrestricted oral intake by one month post-TORS, showing functional improvement compared to their preoperative status. Three of the four patients remained free of locoregional recurrence during follow-up. No major perioperative complications were reported. Conclusions: In selected patients with BoT SCC recurrence after primary RT-CHT, TORS may offer a viable and less morbid salvage treatment option with favorable early functional outcomes and acceptable oncologic control. Based on both our institutional experience and the supporting literature, we propose selection criteria to guide TORS indication in this clinical setting. Full article