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14 pages, 1113 KB  
Article
Retrospective Monocentric Analysis of Carmustine Wafer Implantation in Recurrent Glioblastoma: Impact on Survival and Key Prognostic Factors
by Naomi Houedjissin, Franziska Staub-Bartelt, Michael Sabel, Julia Steinmann, Hannah Fischer and Marion Rapp
Curr. Oncol. 2026, 33(5), 238; https://doi.org/10.3390/curroncol33050238 - 22 Apr 2026
Viewed by 181
Abstract
Objective: The implantation of biodegradable carmustine (BCNU) wafers is a treatment option for recurrent high-grade glioma (HGG), but its efficacy is debated. We evaluated its impact on overall survival (OS) and survival after recurrence (SAR) considering recurrence timing after first-line treatment. Methods: In [...] Read more.
Objective: The implantation of biodegradable carmustine (BCNU) wafers is a treatment option for recurrent high-grade glioma (HGG), but its efficacy is debated. We evaluated its impact on overall survival (OS) and survival after recurrence (SAR) considering recurrence timing after first-line treatment. Methods: In this single-center retrospective study, we analyzed patients who underwent surgery for glioblastoma (GBM) recurrence following initial diagnosis (pre- and post-WHO classification 2016) between 2007 and 2022. All patients received standard first-line therapy, including maximal safe resection, radiotherapy with concomitant temozolomide, and adjuvant temozolomide. Recurrent GBM treatment involves resection, with or without adjuvant chemo- and/or radiotherapy. Patients who received carmustine wafer implantation (CWI) during resection were compared to those without wafer placement. Recurrences were classified by timing relative to first-line therapy: (1) post-radiochemotherapy, pre-adjuvant temozolomide; (2) during adjuvant temozolomide; (3) during prolonged temozolomide; (4) >1 month after completion of all therapy. Primary endpoints were OS and SAR, with prognostic factors analyzed. Results: A total of 176 patients were enrolled, with 59.7% (105/176) receiving CWI. Recurrence treatment included surgery without adjuvant therapy in 23.3% (41/176) of cases (26.7% of CWI+ and 18.3% of CWI−), adjuvant chemotherapy in 39.8% (70/176) (41% of CWI+ and 38% of CWI−), radiotherapy in 7.4% (13/176) (7.6% of CWI+ and 7% of CWI−), and combined radiochemotherapy in 29.5% (52/176) (24.8% of CWI+ and 36.6% of CWI−). No significant differences were found between groups in age (p = 0.684), residual tumor volume after initial (p = 0.988) or recurrence surgery (p = 0.356), MGMT status (p = 0.766) and KPS post 1st-line-therapy (p = 0.833). Median OS was 20 months [range 18–24] for CWI+ and 22 months [range 20–27] for CWI− (p = 0.487). The median SAR was 10 months [range 8–12] for CWI+ and 12 months [range 10–13] for CWI− (p = 0.252). Later recurrence (type 4) significantly correlated with prolonged OS (HR 0.16, 95% CI: 0.04–0.66, p = 0.011). Age (p < 0.001), MGMT methylation (p = 0.017), and smaller residual tumor volume post-recurrence surgery (p = 0.008) were also associated with longer survival. Conclusions: CWI did not significantly improve OS or SAR in recurrent GBM patients. However, younger age, MGMT methylation, smaller residual tumor volume, and later recurrence were linked to better survival outcomes, underscoring their prognostic importance. Full article
(This article belongs to the Special Issue Glioblastoma: Symptoms, Causes, Treatment and Prognosis)
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31 pages, 1166 KB  
Article
Survival in Men Treated for Lung Cancer: A Single-Center Retrospective Cohort Study in Poland
by Magdalena Królikowska-Jerużalska, Magdalena Kurkiewicz, Aleksandra Moździerz, Anna Rzepecka-Stojko and Jerzy Stojko
Healthcare 2026, 14(7), 970; https://doi.org/10.3390/healthcare14070970 - 7 Apr 2026
Viewed by 493
Abstract
Introduction: Lung cancer remains the leading cause of cancer-related mortality among men in Poland. Prognosis is generally poor, largely due to late diagnosis at advanced stages and the aggressive biological nature of the disease. Aim: This study aimed to evaluate the effectiveness of [...] Read more.
Introduction: Lung cancer remains the leading cause of cancer-related mortality among men in Poland. Prognosis is generally poor, largely due to late diagnosis at advanced stages and the aggressive biological nature of the disease. Aim: This study aimed to evaluate the effectiveness of various treatment modalities and determine their impact on overall survival in male patients diagnosed with small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Methods: This retrospective cohort study analyzed 1431 men (mean age: 61.5 years) treated at the Katowice Oncology Center in Poland between 2002 and 2012. Overall survival was assessed using the Kaplan–Meier method and multivariable Cox proportional hazards regression. Evaluated prognostic factors included clinical stage, surgical intervention (partial or total lung resection), first-line treatment regimen, and the number of treatment cycles. Results: Survival probabilities declined progressively with advancing clinical stage for both SCLC and NSCLC. Patients who underwent surgical resection demonstrated significantly longer survival compared to non-surgically treated patients (p < 0.001). Furthermore, combined radiochemotherapy yielded superior therapeutic outcomes compared to chemotherapy alone. In the non-surgical NSCLC cohort, first-line treatment with platinum derivatives combined with gemcitabine resulted in the highest 1-year survival rate compared to other pharmacological schemes. Discussion: The high mortality observed within the first 12 months post diagnosis reflects the late-stage presentation common during the study period. The findings align with established oncological principles, confirming that surgical resection and multimodal therapies offer the greatest survival advantages for eligible patients. Conclusions: Survival rates for both SCLC and NSCLC are overwhelmingly dictated by early diagnosis and the feasibility of surgical resection. Improving long-term outcomes depends heavily on implementing effective lung cancer screening programs to detect the disease at operable stages and utilizing optimized combined treatment protocols. Full article
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12 pages, 276 KB  
Article
Development of an Enomogram to Predict the Rate of Loco-Regional Control After Radio-Chemotherapy and Interventional Radiotherapy in Cervical Cancer
by Valentina Lancellotta, Maria Concetta La Milia, Rosa Autorino, Enrico Rosa, Bruno Fionda, Pierpaolo Dragonetti, Leonardo Bannoni, Raffaella Michela Rinaldi, Viola De Luca, Gerardina Stimato, Angeles Rovirosa, Alessio Giuseppe Morganti, Gabriella Macchia, Benedetta Gui, Nicolò Bizzarri, Anna Fagotti, Luca Tagliaferri and Maria Antonietta Gambacorta
Cancers 2026, 18(7), 1096; https://doi.org/10.3390/cancers18071096 - 27 Mar 2026
Viewed by 548
Abstract
Objective: This study aimed to explore the association between magnetic resonance imaging (MRI)-derived volumetric parameters and oncological outcomes, and to develop an exploratory predictive model based on these variables in patients treated with radio-chemotherapy followed by interventional radiotherapy (modern brachytherapy). Methods: [...] Read more.
Objective: This study aimed to explore the association between magnetic resonance imaging (MRI)-derived volumetric parameters and oncological outcomes, and to develop an exploratory predictive model based on these variables in patients treated with radio-chemotherapy followed by interventional radiotherapy (modern brachytherapy). Methods: Between 2021 and 2024, 300 patients with cervical cancer were included. Treatment was pelvic external beam radiotherapy with platinum-based chemotherapy followed by interventional radiotherapy boost. Volumetric MRI variables for each patient were collected. Time-to-event analyses were performed using Cox proportional hazards regression models. Model performance was assessed using Harrell’s concordance index (C-index). Internal validation was performed using bootstrap resampling. Based on the final multivariable Cox models, an interactive web-based nomogram was developed as an exploratory tool to visualize model-derived associations. Results: Median tumor volume decreased from 69.4 cm3 at diagnosis to 2.2 cm3 at the time of pre-interventional radiotherapy MRI, with a median reduction rate of 96.5%. Tumor volume at diagnosis, pre-interventional radiotherapy residual tumor volume, and tumor volume reduction rate were significantly associated with loco-regional relapse and distant metastases in Cox regression analyses. These findings were consistent across univariate and multivariable models. Internal validation confirmed the stability of the model estimates. Conclusions: MRI-derived volumetric parameters are associated with oncological outcomes in patients with locally advanced cervical cancer and may contribute to early risk stratification. The proposed model should be considered exploratory and hypothesis-generating and requires external validation before any potential clinical application. Full article
(This article belongs to the Special Issue Brachytherapy in the Treatment of Gynaecological Malignancies)
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23 pages, 614 KB  
Review
Bioactive Hydrogels and Scaffolds for Oral Mucosal Regeneration After Oral Squamous Cell Carcinoma Therapy: A Comprehensive Review
by Alina Ormenisan, Andreea Bors, Liana Beresescu, Despina Luciana Bereczki-Temistocle and Gabriela Felicia Beresescu
Medicina 2026, 62(3), 558; https://doi.org/10.3390/medicina62030558 - 17 Mar 2026
Viewed by 663
Abstract
Oral squamous cell carcinoma (OSCC) therapy frequently produces acute and chronic injury to the oral mucosa, including surgical lining defects and radiochemotherapy-associated oral mucositis (OM). Beyond pain and ulceration, these injuries compromise nutrition, speech, oral hygiene, and feasibility of dental/implant rehabilitation, and may [...] Read more.
Oral squamous cell carcinoma (OSCC) therapy frequently produces acute and chronic injury to the oral mucosa, including surgical lining defects and radiochemotherapy-associated oral mucositis (OM). Beyond pain and ulceration, these injuries compromise nutrition, speech, oral hygiene, and feasibility of dental/implant rehabilitation, and may disrupt oncologic treatment delivery. The oral cavity imposes stringent constraints on regenerative biomaterials—continuous salivary flow, high microbial load, and repeated mechanical shear—such that clinical success depends on reliable mucoadhesion/wet adhesion, barrier function, mechanical compliance, and safe, spatially confined bioactivity. This PRISMA-informed evidence-mapped structured narrative review provides an evidence map and structured qualitative synthesis of hydrogel and scaffold platforms relevant to post-OSCC care, spanning clinically used mucoadhesive barrier formulations through emerging wet-adhesive multifunctional patches, acellular matrices, and tissue-engineered oral mucosa (TEOM) constructs. Clinically, the strongest evidence base remains barrier-forming gels and liquids that reduce OM pain and improve oral function during active therapy, establishing performance benchmarks for intraoral retention and patient-reported benefit. Preclinical studies are rapidly expanding toward multifunctional designs that integrate antimicrobial, anti-inflammatory, pro-epithelialization, and pro-angiogenic cues. However, a pervasive limitation is the inconsistent use of OSCC-relevant models (e.g., irradiated/xerostomic tissue beds), standardized functional endpoints (e.g., oral intake, durability under mastication, and neurosensory outcomes), and explicit oncologic safety evaluation, which severely compromises translational validity. For reconstructive applications, dermal matrices and early TEOM reports suggest feasibility for selected defects, but controlled comparative trials and scalable manufacturing pathways remain limited. Translational priorities include oncologic-by-design bioactivity (time-limited, locally confined cues), clinically anchored outcome reporting, and quality-by-design manufacturing aligned with device/combination/advanced-therapy regulatory requirements. Full article
(This article belongs to the Special Issue Regenerative Dentistry: A New Paradigm in Oral Health Care)
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13 pages, 422 KB  
Article
Predictors and Patterns of Recurrence After a Watchful Waiting Approach following Clinical Complete Response to Neoadjuvant Radiochemotherapy for Esophageal Cancer
by Sarah Gerber, Martin D. Berger, Hossein Hemmatazad, Pauline Aeschbacher, Dino Kröll, Daniel Candinas and Yves Borbély
Curr. Oncol. 2026, 33(3), 170; https://doi.org/10.3390/curroncol33030170 - 16 Mar 2026
Viewed by 453
Abstract
(1) Background: Treatment of esophageal cancer (EC) traditionally consists of neoadjuvant radiochemotherapy (RCT) followed by resection; however, esophagectomy is associated with substantial morbidity, particularly in patients with relevant comorbidities. Therefore, a watchful waiting (WW) strategy has been increasingly adopted for patients achieving a [...] Read more.
(1) Background: Treatment of esophageal cancer (EC) traditionally consists of neoadjuvant radiochemotherapy (RCT) followed by resection; however, esophagectomy is associated with substantial morbidity, particularly in patients with relevant comorbidities. Therefore, a watchful waiting (WW) strategy has been increasingly adopted for patients achieving a complete response to RCT. This study aimed to identify independent predictors and recurrence patterns in EC patients managed with WW. (2) Methods: We retrospectively analyzed all patients with potentially curable EC and complete response to RCT treated at a tertiary university hospital between 2014 and 2022. Comprehensive staging and restaging were performed using computed tomography, endoscopy with ultrasound and biopsies, and positron-emission tomography, followed by structured surveillance. Recurrence patterns and associated clinical and tumor-related factors were assessed using multivariate regression analysis. (3) Results: Among 50 included patients, 30 (60%) developed recurrence after a median of 202 days. Patients with initially nodal-negative disease did not develop distant recurrence, whereas nodal-positive patients showed metastatic recurrence in 26% and local regrowth in 16%. (4) Discussion: Adenocarcinoma, circumferential tumor extent greater than 50%, dysphagia, fatigue, and deterioration of general condition at restaging were independently associated with recurrence. These findings support risk-adapted surveillance and may facilitate personalized management in EC patients undergoing WW. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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21 pages, 3380 KB  
Article
Radiation Dose-Dependent and -Independent Pulmonary Infiltrates in Patients with High-Grade Pneumonitis After Radiochemotherapy and Durvalumab Consolidation for Stage III NSCLC
by Andreas Herz, Aymane Khouya, Maja Guberina, Martin Metzenmacher, Marcel Opitz, Christoph Pöttgen, Gerrit Fischedick, Hubertus Hautzel, Thomas Gauler, Ken Herrmann, Erik Büscher, Servet Bölükbas, Fabian Doerr, Natalie Baldes, Laura Valentina Klüner, Benedikt M. Schaarschmidt, Rüdiger Karpf-Wissel, Jane Winantea, Denise Bos, Verena Jendrossek, Emil Mladenov, Lena Gockeln, Mario Andre Hetzel, Florian Wirsdörfer, Martin Schuler, Martin Stuschke and Nika Guberinaadd Show full author list remove Hide full author list
Diagnostics 2026, 16(6), 827; https://doi.org/10.3390/diagnostics16060827 - 11 Mar 2026
Viewed by 569
Abstract
Background/Objectives: Analysis of the density and spatial distribution of pulmonary infiltrates of patients with high-grade (≥3) pneumonitis after radiochemotherapy and durvalumab consolidation (RT/CTx + IO) was performed in order to define dosimetric hallmarks of the development of infiltrates following this multimodality treatment. [...] Read more.
Background/Objectives: Analysis of the density and spatial distribution of pulmonary infiltrates of patients with high-grade (≥3) pneumonitis after radiochemotherapy and durvalumab consolidation (RT/CTx + IO) was performed in order to define dosimetric hallmarks of the development of infiltrates following this multimodality treatment. Methods: Consecutive patients treated with RT/CTx + IO for stage III NSCLC were retrospectively reviewed with respect to the occurrence of grade ≥ 3 pneumonitis. Lung infiltrates were contoured on follow-up CT scans acquired around the time of maximum pneumonitis expression. The applied dose distribution was overlaid with the follow-up CT using elastic deformation, and infiltrates were binned according to their density in density strata of 50 HU. The dose and density dependence of partial infiltrate volumes per unit lung volume was analyzed using a mixed fixed and random effect model adjusting for patient, density and dose-dependent random effects. Results: Six patients with grade ≥ 3 pneumonitis were identified from 132 patients treated with RT/CT + IO at a comprehensive cancer center. Partial volumes of lung infiltrates captured by follow-up CT with maximum pneumonitis expression ranged from 15.5 to 60.0% (median 39.8%). A significant, systematic dose–response relationship was found for partial lung infiltrate volumes per dose and density bin. A unimodal density distribution of partial lung infiltrate volumes was also found over the infiltrate density range of −1000 to 100 HU. This was determined using a mixed model that adjusted for random effects (p < 0.0001 for both effects, F-test). There was no interaction effect between systematic dose and infiltrate density dependence of the partial infiltrate volumes. The proportion of infiltrate volumes that are attributable to the systematic dose–response relation amounts to a mean of 16.6% of the total infiltrate volume per patient according to this model. Compared to patients with pneumonitis of grade ≤ 2, patients with high-risk pneumonitis had higher partial infiltrate volumes, particularly in the low-dose regions in five grade dose bins up to 20 Gy (AUC = 1.0, p < 0.0001, likelihood-ratio test). Conclusions: Dose-dependent and -independent partial lung infiltrate volumes were found in patients with high-grade pneumonitis after RT/CTx + IO. These results indicate that pneumonitis involves contributions from both radiochemotherapy-induced and immunotherapy-related mechanisms. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 591 KB  
Article
Acute Toxicities During Proton Therapy with or Without Simultaneous Chemotherapy in Pediatric CNS Tumors: A Retrospective Cohort Study
by Eicke Schuermann, Sarah Peters, Jonas E. Adolph, Julien Merta, Stefan Rutkowski, Michael C. Frühwald, Philipp Dammann, Hermann L. Müller, Christof M. Kramm, Gudrun Fleischhack, Beate Timmermann and Stephan Tippelt
Cancers 2026, 18(5), 859; https://doi.org/10.3390/cancers18050859 - 7 Mar 2026
Viewed by 525
Abstract
Background: Proton beam therapy (PBT) is a valuable alternative to photon radiotherapy of CNS tumors in children and adolescents. While most recent studies deal with the outcome or long-term side effects of PBT, the aim of this study was to investigate the feasibility [...] Read more.
Background: Proton beam therapy (PBT) is a valuable alternative to photon radiotherapy of CNS tumors in children and adolescents. While most recent studies deal with the outcome or long-term side effects of PBT, the aim of this study was to investigate the feasibility of PBT with a particular focus on the acute toxicity of a simultaneous radiochemotherapy (sPBCT). Patients and methods: We enrolled 199 children [median age 7.4 years (range, 0.9–17.9)], who received altogether 200 courses of PBT/sPBCT at initial diagnosis (n = 121) or at relapse (n = 79) with sPBCT in 52 (26%) courses. Data collection to PBT/sPBCT was based on the medical records and the KiProReg (Registry study of Standard Proton Therapy in Children at West German Proton Therapy Center) with a primarily descriptive-statistical and logistic regression analysis. Results: During PBT/sPBCT a total of n = 704 adverse events (AEs, mean 3.4 per course) were observed. Eighty-seven of them were graded as high-grade adverse events (HGAEs, Common Terminology Criteria for Adverse Eventº ≥3 (CTCAE)) which occurred in 67 (33.5%) PBT/sPBCT courses. HGAEs were in particular hematotoxicity (n = 43; 64.1%) and infections (n = 18; 26.8%). A significantly higher rate of HGAEs was documented in patients treated with sPBCT (n = 33/52; 63.5%) compared to those with PBT only (n = 34/148; 23.0%) (p = 0.001). In children with sPBCT, 15 (28.8%) patients could not receive the recommended dose or schedule of the planned chemotherapy (CTx) due to HGAEs, with the rate of planned CTx courses performed being significantly lower in patients receiving intensive intravenous CTx (p < 0.001). Interruptions of PBT and of simultaneous CTx were both significantly associated with the occurrence of infections [Odds ratios 3.002 (95% CI 1.005–8.971, p = 0.049) and 3.905 (95% CI 1.005–15.174, p = 0.049)]. Total discontinuation of treatment did not occur. Conclusions: Concurrent CTx during proton therapy is associated with a significant increased risk for HGAE occurrence and therapy interruptions requiring individual dose and schedule adjustments dependent on CTx intensity, very experienced interdisciplinary teams as well as intensive care and in-/out-patient oncology facilities on site. Full article
(This article belongs to the Special Issue Proton Therapy of Cancer Treatment)
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13 pages, 420 KB  
Article
Feasibility and Safety of Autologous Dendritic Cell Vaccination Combined with Radio-Chemotherapy in Newly Diagnosed Glioblastoma: A Retrospective Single-Center Series
by Inés Esparragosa Vázquez, Ascensión López-Díaz de Cerio, Susana Inoges, Javier Aristu, Pablo Domínguez, Reyes García-Eulate, Marta Calvo-Imirizaldu, Javier Arbizu, María E. Rodríguez-Ruiz, Pablo Irimia, Marta M. Alonso, Felipe Prósper, Ricardo Díez-Valle and Jaime Gállego Pérez-Larraya
Vaccines 2026, 14(2), 172; https://doi.org/10.3390/vaccines14020172 - 12 Feb 2026
Viewed by 803
Abstract
Background: The prognosis of glioblastoma (GBM) patients remains poor. Dendritic cell (DC) vaccination has been investigated as an immunotherapy option, mainly in early-phase clinical studies. Herein, we report the feasibility, safety, and descriptive clinical and radiological outcomes of a retrospective series of newly [...] Read more.
Background: The prognosis of glioblastoma (GBM) patients remains poor. Dendritic cell (DC) vaccination has been investigated as an immunotherapy option, mainly in early-phase clinical studies. Herein, we report the feasibility, safety, and descriptive clinical and radiological outcomes of a retrospective series of newly diagnosed GBM patients treated with standard radio-chemotherapy and autologous DC vaccination as compassionate use. Methods: We retrospectively reviewed the medical and radiological records of patients with newly diagnosed GBM who received autologous tumor lysate–pulsed DC vaccination in addition to standard-of-care treatment at a tertiary academic center between 2009 and 2017. Clinical data, treatment characteristics, adverse events, survival outcomes, and radiological responses were collected and analyzed descriptively. Results: Twenty-four patients were included. All patients underwent surgical resection and were further treated with autologous tumor lysate–DC vaccination and standard radio-chemotherapy. Histology of GBM was confirmed in all patients. The first vaccine was administered in 75% of patients after a median of 21 days (range: 6–30 days) following surgery and prior to radiotherapy initiation. DC vaccination was continued following radiotherapy at specific time points, with no observed significant adverse events. Median OS was 21.1 months (95% CI, 27.9–75.0 months), and median PFS was 10.3 months (95% CI, 15.6–26.6 months). Presence of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was associated with longer survival and higher 12-month PFS rates, consistent with its established prognostic value. Radiological responses were retrospectively assessed according to RANO and RANO 2.0 criteria. Conclusions: In this retrospective single-center series, autologous DC vaccination administered as compassionate use in combination with standard radio-chemotherapy was feasible and safe in routine clinical practice. Survival and radiological outcomes are reported descriptively and should be interpreted with caution given the absence of a control cohort. These findings support further prospective controlled studies to properly assess the clinical role of DC vaccination in newly diagnosed GBM. Full article
(This article belongs to the Special Issue The Era of Vaccines: Advancing Tumor Immunology and Immunotherapy)
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33 pages, 2243 KB  
Article
Nonlinear Smooth Sliding Mode Control Framework for a Tumor-Immune Dynamical System Under Combined Radio-Chemotherapy
by Muhammad Arsalan, Sadiq Muhammad and Muhammad Tariq Sadiq
Mathematics 2026, 14(3), 521; https://doi.org/10.3390/math14030521 - 1 Feb 2026
Viewed by 475
Abstract
Sliding mode control (SMC) is a robust nonlinear control framework that enforces system trajectories onto predefined manifolds, providing strong robustness guarantees against uncertainties. However, SMC inherently introduces unwanted transients or chattering in system state trajectories, which may cause issues especially for sensitive applications [...] Read more.
Sliding mode control (SMC) is a robust nonlinear control framework that enforces system trajectories onto predefined manifolds, providing strong robustness guarantees against uncertainties. However, SMC inherently introduces unwanted transients or chattering in system state trajectories, which may cause issues especially for sensitive applications such as regulation of drug administration. This paper proposes a multi-input smooth sliding mode control (MISSMC) strategy that combines radiotherapy and chemotherapy for a nonlinear tumor–immune dynamical system described by ordinary differential equations. The closed-loop system is first analyzed to establish key qualitative properties: all state variables remain positive and bounded, the sliding surfaces exhibit asymptotic convergence, and explicit analytical upper bounds on the cumulative therapy doses are derived under clinically motivated constraints. On this basis, a smooth hyperbolic-tangent sliding manifold and associated control law are designed to regulate the radiation and drug infusion rates. While the use of a hyperbolic-tangent smoothing function effectively suppresses chattering, it introduces a small steady-state error due to the presence of a boundary layer. To address this limitation, integral action is incorporated into the sliding surfaces, ensuring asymptotic convergence of tumor state and reducing residual steady-state error, while enhancing robustness against model uncertainties and parameter variations. Numerical simulations, based on a brain-tumor case study, show that the proposed smooth SMC markedly suppresses transient overshoots in both states and control inputs, while preserving effective tumor reduction. Compared with a conventional (non-smooth) SMC scheme, the MISSMC controller reduces baseline radiation and chemotherapy intensities on average by roughly 70%. Similarly, MISSMC lowers the overall cumulative doses on average by about 40%, without degrading the therapeutic outcome. The resulting integral smooth SMC framework therefore offers a rigorous nonlinear-systems approach to designing combined radio-chemotherapy protocols with guaranteed positivity, boundedness, and asymptotic stabilization of the closed-loop system, together with explicit bounds on the control inputs. Full article
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11 pages, 567 KB  
Article
Tumor Characterization Using [18F]FDG PET Radiomics in a PD-L1-Positive NSCLC Cohort
by Bernadett Erzsébet Kálmán, Agnieszka Bos-Liedke, Dániel Dezső, Ewelina Kaminska, Mateusz Matusewicz, Ferenc Budán, Domokos Mathe, János Girán, Dávid Sipos, Éva Pusztai, Árpád Boronkai and Zsombor Ritter
Pharmaceuticals 2026, 19(1), 103; https://doi.org/10.3390/ph19010103 - 7 Jan 2026
Viewed by 673
Abstract
Background: Durvalumab consolidation following radiochemotherapy is now the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). [18F]FDG PET/CT offers valuable insights not just for staging but also for tumor characterization via radiomics, which can potentially predict histology, [...] Read more.
Background: Durvalumab consolidation following radiochemotherapy is now the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). [18F]FDG PET/CT offers valuable insights not just for staging but also for tumor characterization via radiomics, which can potentially predict histology, immunophenotype, and prognosis. Methods: We conducted a retrospective analysis of [18F]FDG PET/CT scans from stage IIIA–IIIB NSCLC patients treated at the Clinical Centre, University of Pécs. All biopsy samples were classified histologically (squamous vs. adenocarcinoma) and tested for PD-L1. Lung tumors were segmented using MEDISO InterViewTM FUSION software (version 3.12.002.0000). with an SUVmax threshold of four. Imaging features were extracted and compared based on histology, PD-L1 status, and neutrophil-to-lymphocyte ratio (NLR)-based prognosis groups. Statistical analyses were performed with Jamovi (v2.6.44), using Shapiro–Wilk, t-test/ANOVA, Mann–Whitney/Kruskal–Wallis, or Chi-square tests as appropriate. Results: Fifty-six patients were included (38 PD-L1-positive, 18 -negative). Among PD-L1-positive cases, poor versus good NLR prognosis groups differed in maximum diameter (p = 0.046), short-zone emphasis (p = 0.026), and zone-length non-uniformity (p = 0.027). Focusing on PD-L1-positive squamous carcinoma, maximum diameter, metabolic tumor volume, busyness, and coarseness showed significant differences (all p < 0.05). SUVmax, mean SUV, SUVpeak, and complexity were higher in squamous than in adenocarcinoma subtypes. PD-L1-positive and -negative squamous tumors differed in zone percentage (p = 0.039) and long-zone high gray-level emphasis (p = 0.024), while no significant differences were observed among adenocarcinomas. Conclusions: [18F]FDG PET/CT radiomics showed potential for differentiating NSCLC histological subtypes and for identifying PD-L1-associated imaging patterns in squamous cell carcinoma. In addition, certain metabolic features were associated with NLR-based prognostic groups in PD-L1-positive patients. Full article
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15 pages, 5860 KB  
Article
The “Undefined and Ignored Normal Tissue” Bulboclitoral Complex in Locally Advanced Cervical Cancer Treated with Definitive Radiochemotherapy: Is It Not the Organ at Risk?
by Kamuran Ibis, Mahmut Hudai Aydin, Korhan Kokce, Leyla Suncak, Ozlem Guler Guniken, Can Ilgin, Deniz Bolukbas, Nezihe Seden Kucucuk and Inci Kizildag Yirgin
Medicina 2026, 62(1), 14; https://doi.org/10.3390/medicina62010014 - 21 Dec 2025
Viewed by 639
Abstract
Background and Objectives: The bulboclitoral complex (BCC) is an essential organ for female sexual health. However, it is not defined as an organ at risk in any guideline defining target volumes in radiotherapy of gynecological cancers, and there is no information about dose [...] Read more.
Background and Objectives: The bulboclitoral complex (BCC) is an essential organ for female sexual health. However, it is not defined as an organ at risk in any guideline defining target volumes in radiotherapy of gynecological cancers, and there is no information about dose constraint. Materials and Methods: Simulation computed tomography scans of 20 patients diagnosed with locally advanced cervical cancer were used retrospectively. The volumetric modulated arc therapy treatment plan with a total dose of 45 Gy in 25 fractions was created using the planning target volume (PTV)-standard, which was created without considering the BCC, and the PTV-BCC spared, which were contoured and included in the optimization. Bulboclitoral complex doses in PTV-standard and PTV-BCC spared plans were compared using the paired simple t test. Results: Median BCC volume was 17.6 cm3 (11.20–25.50). Bulboclitoral complex maximum dose (Dmax) was median 49.07 Gy (48.49–50.25) and 28.81 Gy (18.14–44.61) in the PTV-standard and PTV-BCC spared plans, respectively, and the BCC Dmax was statistically significantly lower in the PTV-BCC spared plan (p < 0.001). When comparing BCC percentage of volume receiving 45 Gy (V45), the median values for PTV-standard and PTV-BCC spared plans were 37.5% (13.3–82.6) and 0%, respectively (p ≤ 0.001). Conclusions: The bulboclitoral complex can be dosimetrically protected from radiation by contouring and optimizing it as an organ at risk in the radiotherapy plan. The clinical effects of protecting the BCC from radiation as an organ at risk on sexual health need to be investigated. Full article
(This article belongs to the Special Issue New Advances in Radiation Therapy)
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28 pages, 1773 KB  
Review
Heat Shock Protein Chaperome Is a Multi-Faceted Vector for Tumor Cell Migratory Activity, Invasion, and Metastasis
by Viacheslav Fedorov, Andrey Kurkin, Georgii Fofanov, Vitaliya Kaneva, Anna Kondratenko, Stephanie E. Combs and Maxim Shevtsov
Cells 2025, 14(23), 1837; https://doi.org/10.3390/cells14231837 - 21 Nov 2025
Viewed by 1329
Abstract
Heat shock proteins (HSPs), in particular, representatives of the HSP70 and HSP90 families, are the folding centers of cell proteins and have been proven to be overexpressed in various types of solid and hematological malignancies. With their involvement in a number of cellular [...] Read more.
Heat shock proteins (HSPs), in particular, representatives of the HSP70 and HSP90 families, are the folding centers of cell proteins and have been proven to be overexpressed in various types of solid and hematological malignancies. With their involvement in a number of cellular functions (e.g., protection from various stresses including radiochemotherapy, transport regulation, apoptotic signal inhibition, etc.), these chaperones are a valuable target for cancer progression research. However, recent focus has shifted to the HSP interaction network, which includes many molecules involved in cell migration and invasion pathways. Investigating the interplay between different co-chaperones and their effect on cell motility may help with establishing a palette of available diagnostic and therapeutic targets for highly invasive cancer types. In this review, we describe current models of the HSP functional cycle and recent studies proving links between these cycle regulators and contributions to cell migration. Based on detailed studies of various co-chaperones’ involvement in cancer progression, the network approach gives much necessary molecular context to previously established HSP functions. Full article
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10 pages, 904 KB  
Article
Impact of Hemoglobin Levels During Definite Chemoradiotherapy of Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma on Survival
by Sandy Hazko, Amed Ahmed, Robert Michael Hermann, Mathias Alexander Sonnhoff, Athanasia Warnecke, Frank Bruns, Robert Blach, Hans Christiansen and Jan-Niklas Becker
Medicina 2025, 61(11), 2027; https://doi.org/10.3390/medicina61112027 - 13 Nov 2025
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Abstract
Background and Objectives: This study aims to investigate the impact of hemoglobin (Hb) level changes during radiochemotherapy (RCT) on the survival of patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and Methods: A retrospective analysis was conducted [...] Read more.
Background and Objectives: This study aims to investigate the impact of hemoglobin (Hb) level changes during radiochemotherapy (RCT) on the survival of patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and Methods: A retrospective analysis was conducted on 97 patients with HNSCC, treated with definitive RCT between January 2016 and October 2021. Hb levels were monitored weekly during RCT. Kaplan–Meier and Cox regression analysis were performed. Results: There was a significant association between Hb levels at the end of RCT and overall survival (p < 0.01). Initial Hb levels and Hb level changes were not significantly associated with survival. In multivariate analysis, a lower body mass index (BMI) and Hb levels at week six were identified as significant prognostic factors. Conclusions: At the end of RCT, rather than baseline levels or changes during treatment, Hb levels are a significant prognostic factor for overall survival in patients with HNSCC. Full article
(This article belongs to the Section Oncology)
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15 pages, 248 KB  
Article
Neoadjuvant Radiochemotherapy Combined with Locoregional Hyperthermia in Locally Advanced Rectal Cancer: Feasibility and Tolerance of Short-Course Versus Long-Course Radiotherapy Schedules
by Laura Ferrera-Alayón, Bárbara Salas-Salas, Antonio Alayón-Afonso, Miguel Sánchez Carrascal, Laura López Molina, Rafael Alexis Hernández Santana, Hans Crezee and Marta Lloret Sáez-Bravo
Cancers 2025, 17(21), 3529; https://doi.org/10.3390/cancers17213529 - 31 Oct 2025
Cited by 1 | Viewed by 1060
Abstract
Background: Integrating deep regional hyperthermia (HT) with neoadjuvant chemoradiotherapy (CRT) may enhance treatment efficacy in locally advanced rectal cancer (LARC), yet feasibility and tolerance data remain scarce for both short-course (SCRT) and long-course (LCRT) radiotherapy (RT) regimens. Methods: In this single-center prospective observational [...] Read more.
Background: Integrating deep regional hyperthermia (HT) with neoadjuvant chemoradiotherapy (CRT) may enhance treatment efficacy in locally advanced rectal cancer (LARC), yet feasibility and tolerance data remain scarce for both short-course (SCRT) and long-course (LCRT) radiotherapy (RT) regimens. Methods: In this single-center prospective observational study, 67 LARC patients received neoadjuvant RT and chemotherapy (CT) combined with deep radiative HT using a phased-array system (ALBA 4D). Patients treated with SCRT (5 × 5 Gy) were prescribed two HT sessions; those treated with LCRT (25 × 2 Gy) were prescribed ten. HT planning was guided by dedicated software, and real-time thermometry ensured precise thermal delivery. Feasibility was defined as completion of ≥50% of prescribed sessions. Tolerance and toxicity were assessed with standardized clinical scales (QMHT, UMC, CTCAE v4.03). Results: HT was feasible in both groups: 100% of SCRT and 63.6% of LCRT patients completed ≥50% of prescribed sessions. In total, 243 sessions were delivered. Most symptoms were mild and transient, predominantly localized pain. No grade ≥3 HT-related toxicities occurred. All scheduled RT and surgery proceeded without delay. Median T50 was 40.3 °C (SCRT) and 40.4 °C (LCRT); the median RT-to-HT interval was 42 min in both groups. Conclusion: This first Spanish experience shows that deep radiative HT can be seamlessly integrated into both SCRT and LCRT neoadjuvant protocols for rectal cancer. High adherence, favorable tolerance, and reliable thermal control support clinical implementation. Any between-schedule observations are descriptive only; no formal comparative testing was performed. The study was not designed or powered to establish comparative effectiveness between SCRT and LCRT, and the sample size was insufficient to detect rare HT-specific adverse events. Full article
(This article belongs to the Section Methods and Technologies Development)
11 pages, 464 KB  
Article
Beyond Molecular Characterization: The Impact of Age-Adjusted Charlson Comorbidity Index in Glioblastoma Patients Treated with Radio or Radio-Chemotherapy
by Tamara Ius, Nicola Montemurro, Giuseppe Lombardi, Alberto D’Amico, Luisa Bellu, Alessandro Parisi, Francesco Martino, Giulia Lezzi, Giulia Gobitti, Giulia Gulino, Riccardo Morganti, Giuseppe Catapano, Francesco Acerbi, Luca Denaro, Francesco Pasqualetti and Marco Krengli
J. Clin. Med. 2025, 14(21), 7515; https://doi.org/10.3390/jcm14217515 - 23 Oct 2025
Viewed by 838
Abstract
Background: Glioblastoma (GBM) prognosis has been reported to be influenced by age and comorbidity in several investigations. Identifying factors that contribute to poor survival is crucial to optimizing and personalizing therapeutic strategies. In the present retrospective analysis, we investigated the impact of [...] Read more.
Background: Glioblastoma (GBM) prognosis has been reported to be influenced by age and comorbidity in several investigations. Identifying factors that contribute to poor survival is crucial to optimizing and personalizing therapeutic strategies. In the present retrospective analysis, we investigated the impact of GBM patient stratification using the age adjusted Charlson Comorbidity Index (ACCI). Methods: A total of 165 patients diagnosed with IDH wild-type GBM, treated with post-operative radio or radio-chemotherapy, were evaluated. To assess the impact of comorbidities, patients were stratified into two groups according to their ACCI scores: Group A (ACCI 0–2) and Group B (ACCI >2). The Cox proportional hazards model test was used to compare overall survival (OS) between the two groups of patients and determine whether the presence of comorbidities significantly affected outcomes. Primary and secondary endpoints were OS and progression free survival (PFS), respectively. Results: The median follow-up period was 36 months, and the median OS was 14 months (95% CI 12.4–15.5). The univariate analysis evidenced that patients in Group A had a significantly longer OS compared to those in Group B, with median OS times of 18 months (95% CI 16–20) and 12 months (95% CI 10.5–13.5), respectively (p = 0.015). The OS remained statistically significant in the multivariate analysis (p = 0.015). Conclusions: The results of this study indicate that ACCI may serve as an independent prognostic factor in patients with newly diagnosed GBM. Full article
(This article belongs to the Section Oncology)
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