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20 pages, 1103 KB  
Review
Navigating the Role of Radiotherapy for Extremity Soft Tissue Sarcomas
by Emmy Nyqvist, Christina Linder-Stragliotto, Jenny Lofgren and Panagiotis Tsagkozis
Biomedicines 2026, 14(8), 1744; https://doi.org/10.3390/biomedicines14081744 - 2 Aug 2026
Viewed by 365
Abstract
Background/Objectives: The basis for treatment of sarcoma is surgical resection. However, since the introduction of limb salvage surgery, guidelines recommend radiation as a complement to surgery for high-grade sarcomas. The aim of the present narrative review was to provide a comprehensive update [...] Read more.
Background/Objectives: The basis for treatment of sarcoma is surgical resection. However, since the introduction of limb salvage surgery, guidelines recommend radiation as a complement to surgery for high-grade sarcomas. The aim of the present narrative review was to provide a comprehensive update about the role of surgery and radiotherapy (RT) for extremity soft tissue sarcoma (ESTS), to increase both surgeons’ and oncologists’ understanding of radiation as an adjuvant to sarcoma surgery and to illuminate areas of uncertainty that requires further research. Methods: A search on PubMed using relevant MeSH terms was performed, focusing on original research, meta-analyses and review articles. Related articles were identified through snowballing. Results: The support for the use of radiotherapy in conjunction with limb salvage is strong. Complication profiles differ between pre- and postoperative RT and attempts to further limit these are both technological and surgical. Preoperative radiotherapy provides the best results regarding long-term complications so far. Hypo-fractionation is showing promise, but awaiting long-term results for complications remains an area of research rather than clinical practice. Particle beam therapy and internal radiation show effects on control, but due to technical and availability issues, their role is mainly in previously irradiated or inoperable tumors. Conclusions: Upcoming research into adjusted deliveries, doses and planning is anticipated. To further personalize treatment, studies into sarcoma subtypes are indicated. Full article
(This article belongs to the Special Issue Update on Cancer Therapy)
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17 pages, 15329 KB  
Article
Effects of Combining Immune-Priming Sub-Lethal Low-Dose Radiation with 4-1BB Activation and Gal-3 Blockade in In Vitro and Preclinical Group-3 Medulloblastoma Models
by Arabinda Das, Connor Stephenson, Daniel G. McDonald, Julian E. Bailes, David Cachia and Ramin Eskandari
Cancers 2026, 18(12), 1890; https://doi.org/10.3390/cancers18121890 - 10 Jun 2026
Viewed by 507
Abstract
Background/Objectives: Pediatric group 3 (G3) medulloblastomas (MB) are therapy resistant and have a significantly worse prognosis than the other MB subtypes. Aggressive radiation/chemotherapy improves survival, but potential long-term comorbidities include neurocognitive deficits. In previous work, we demonstrated that low-dose X-ray radiation (LDXR) acts [...] Read more.
Background/Objectives: Pediatric group 3 (G3) medulloblastomas (MB) are therapy resistant and have a significantly worse prognosis than the other MB subtypes. Aggressive radiation/chemotherapy improves survival, but potential long-term comorbidities include neurocognitive deficits. In previous work, we demonstrated that low-dose X-ray radiation (LDXR) acts as an immunological adjuvant. Recent studies have demonstrated that galectin-3 (Gal-3) expression in MB tumors accelerates M2 macrophage infiltration and restricts T cell receptor (TCR)-mediated signaling. Immunotherapy with an agonistic anti-4-1BB monoclonal antibody (mAb) activates CD8+ T cells, promoting their survival and acquisition of potent cytolytic properties. Building on these findings, we hypothesized that immune priming via sublethal LDXR, combined with a Gal-3 inhibitor and an anti-4-1BB mAb, would boost anti-tumor effects, resulting in survival benefits. Methods: We tested this hypothesis in vitro in co-cultures of human MB cells and in vivo, in an immunocompetent G3MB mouse model (MP1). Treatment effects were assessed using Western blot, flow cytometry, hematoxylin and eosin (H&E) staining, immunofluorescence imaging, and analysis of cytokine and chemokine expression. Results: Our data demonstrated higher Gal-3 expression in MB patient-derived tumor tissue than in non-tumor tissue. LDXR modulated major histocompatibility complex molecules, and, combined with a Gal-3 inhibitor and an anti-4-1BB mAb, altered T-cell/tumor-cell interactions, enhanced T-cell-mediated MB cell death, and shifted cytokine production to drive microglial polarization toward the M1 subtype. Furthermore, H&E-stained tumor sections showed a ~70% reduction in tumor size compared with untreated controls. Conclusions: These preclinical findings suggest that combining immune priming with sublethal LDXR, Gal-3 inhibition, and 4-1BB activation may be an effective treatment strategy for G3MB. Full article
(This article belongs to the Section Cancer Therapy)
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18 pages, 587 KB  
Systematic Review
Adjuvant Radiotherapy Following Surgical Excision of Keloids: A Systematic Review of Dose, Fractionation, and Recurrence
by Monika Wojarska, Klaudia Kokot, Wiktoria Borzyszkowska, Patryk Boczar, Zuzanna Zalewska, Adrianna Kuryk, Julia Wojciechowska and Jerzy Jankau
Life 2026, 16(5), 770; https://doi.org/10.3390/life16050770 - 3 May 2026
Viewed by 1378
Abstract
Keloids are pathological scars originating from connective tissue characterized by excessive growth that extends beyond the original edges of the wound. They occur significantly more often in skin areas exposed to increased mechanical tension during the wound-healing process and up to fifteen times [...] Read more.
Keloids are pathological scars originating from connective tissue characterized by excessive growth that extends beyond the original edges of the wound. They occur significantly more often in skin areas exposed to increased mechanical tension during the wound-healing process and up to fifteen times more frequently in individuals with darker skin pigmentation. The underlying mechanism of keloid formation is driven by an inflammatory response triggered by skin injury extending into the reticular dermis, leading to fibroblast accumulation and neovascularization. The management of keloids remains challenging, as the recurrence rate is high when surgical excision is performed as a standalone treatment. Evidence indicates that combining surgical resection with adjunctive modalities results in superior clinical outcomes and may significantly lower recurrence rates compared with monotherapy. Adjuvant radiotherapy plays a key role in this approach, as it has been shown to reduce recurrence rates to below 10%, primarily through suppression of inflammation and inhibition of fibroblast activity. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A systematic search of the PubMed and Web of Science databases identified 22 studies comprising more than 2219 patients treated with surgical excision followed by postoperative radiotherapy. Reported recurrence rates ranged from 1.6% to 55.2% and were influenced by total radiation dose, fractionation schedule, radiotherapy technique, and duration of follow-up. Despite its proven effectiveness when combined with surgery, radiotherapy has certain limitations, including the lack of standardized guidelines regarding dose, fractionation, and timing of administration. Most reported adverse effects were mild to moderate and localized to the treated area, while a direct causal relationship between postoperative radiotherapy and secondary malignancy development could not be established. The variability in treatment protocols highlights the need for further studies to support more effective, evidence-based decision-making in the treatment of keloids. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
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16 pages, 2376 KB  
Article
Initial Evaluation of Feasibility and Cutaneous Toxicity of Electron FLASH Radiotherapy Using a Standard-of-Care Fractionation Scheme in a Porcine Skin Model
by Elise Konradsson, Kevin Liu, Safee Baig, Susanne Je-Han Lin, Alan Hernandez Lopez, Brett Velasquez, Stephanie Mayor, Kayla Samuel, Traci Viscarra, Krystal Garrow, Erica J. Moore, William Norton, Jody Swain, Ziyi Li, Albert C. Koong, Steven H. Lin, Emil Schüler and Devarati Mitra
Cancers 2026, 18(6), 1009; https://doi.org/10.3390/cancers18061009 - 20 Mar 2026
Viewed by 941
Abstract
Background/Objectives: FLASH radiotherapy (RT) has shown potential to reduce normal tissue toxicity compared with conventional (CONV) RT while maintaining tumor control. FLASH RT is characterized by ultra-high dose rate delivery, commonly using mean dose rates ≥ 40 Gy/s and sub-second delivery times. Most [...] Read more.
Background/Objectives: FLASH radiotherapy (RT) has shown potential to reduce normal tissue toxicity compared with conventional (CONV) RT while maintaining tumor control. FLASH RT is characterized by ultra-high dose rate delivery, commonly using mean dose rates ≥ 40 Gy/s and sub-second delivery times. Most preclinical studies have used single-fraction regimens, leaving the feasibility and normal tissue impact of clinically relevant fractionation largely unexplored. We evaluated electron FLASH RT given in a standard five-fraction regimen to a porcine skin model, simulating adjuvant treatment workflow for high-risk cutaneous melanoma. Method: Three Yorkshire–Landrace swine received paired five-fraction electron irradiations to dorsolateral skin using either FLASH RT (mean dose rates 175–246 Gy/s) or CONV RT (8 Gy/min). Radiation was delivered with a 9-MeV electron beam; field diameters of 4, 7, or 10 cm; and doses of 5 × 6, 5 × 7, or 5 × 8 Gy. Dosimetry was validated with several dosimeters and real-time beam monitoring, confirming dose accuracy within 3%. Skin toxicity was assessed over 22–24 weeks using clinical grading, erythema spectrophotometry, and histopathologic evaluation. Results: FLASH RT was well tolerated at 5 × 6 Gy and 5 × 7 Gy, with no significant differences in peak radiation dermatitis, erythema index, or histologic damage compared with CONV RT. At 5 × 8 Gy, both modalities caused unacceptable toxicity, including moist desquamation and necrosis. No volume-dependent effects were observed. Conclusions: Although a FLASH-specific normal tissue sparing effect was not observed, this study demonstrates the technical feasibility and safety of delivering fractionated electron FLASH RT in a large animal model using a clinically relevant workflow. These findings support further investigation of physical beam parameters and biological modifiers, such as tissue oxygenation, and inform the clinical translation of fractionated FLASH RT for cutaneous malignancies. Full article
(This article belongs to the Section Cancer Therapy)
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12 pages, 4684 KB  
Case Report
A Perplexing Plexopathy After Pembrolizumab Therapy in Early-Stage Triple-Negative Breast Cancer
by Toluwalogo Baiyewun, Brian McNamara, Emily Aherne, Alex James Bryan, Julie Twomey, Sorcha NiLoingsigh, Bolanle Ofi, Derek Power and Seamus O’Reilly
Curr. Oncol. 2026, 33(2), 125; https://doi.org/10.3390/curroncol33020125 - 20 Feb 2026
Cited by 1 | Viewed by 1476
Abstract
Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing [...] Read more.
Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing strategies. As the use of immunotherapy expands, recognizing toxicity from recurrence and optimizing response-adapted approaches are essential to balance cure with quality of survival. Case Presentation: A 38-year-old pregnant woman with a distant history of uveitis and psoriasis was discovered to have pregnancy-associated TNBC. Postnatally, she was treated with neoadjuvant chemotherapy and pembrolizumab, followed by wire-guided left breast wide local excision and sentinel lymph node biopsy of the left axilla. After surgery, residual cancer was noted. She continued adjuvant pembrolizumab and adjuvant radiotherapy 40.05 Gy/15 fr to the breast and nodes, followed by a 13.35 Gy/5 fr boost to the tumour bed (breast). Despite a persistent residual tumour, pembrolizumab was continued as per protocol in a response-agnostic manner. At the end of one year of adjuvant pembrolizumab, she developed progressive numbness and weakness in the ipsilateral arm, initially raising suspicion for local recurrence. Comprehensive MRI and PET-CT imaging did not identify recurrent tumour or new metastatic disease. Electromyography confirmed a lower-trunk brachial plexopathy without a structural cause. An immune-mediated process was diagnosed by a process of elimination. Despite treatment with 1st-line high-dose corticosteroids and 2nd-line intravenous immunoglobulin (IVIG), improvement was limited. Therapeutic plasmapheresis led to marked functional recovery and symptom resolution 20 months later. Discussion: Four main challenges are identified: (1) the diagnostic difficulty in identifying local recurrence or radiation injury from immune-related neuropathy; (2) the emerging therapeutic role of plasmapheresis in steroid-refractory irAEs; (3) the possible inconsistencies between rare toxicities observed in clinical trials vs. clinical practice; and (4) the limitations in response in adjuvant therapy, particularly in patients with coexisting AI conditions. Conclusions: Early recognition and accurate distinction from tumour recurrence, as well as support for plasmapheresis as a potential option in steroid-refractory presentations, have been shown to improve patient survival and symptom reduction. With increasing use of immunotherapy, real-world toxicity data, predictive biomarkers, and personalized treatment strategies are urgently needed to balance cure with long-term functional outcomes. Full article
(This article belongs to the Section Breast Cancer)
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18 pages, 2602 KB  
Article
Racial and Ethnic Disparities in Second Primary Lung Cancer After Breast Radiotherapy: A SEER Cohort Analysis (2000–2022)
by Fares A. Qtaishat, Mohammad Hamad, Adham Musa, Theeb Natsheh, Othman Al-Barghouthi, Basil A. Abusalameh, Anas A. Younis, Hamzeh Al-Qarallah, Sara Qutaishat, Matthew P. Banegas, H. Irene Su, Winta T. Mehtsun and Tala Al-Rousan
Cancers 2026, 18(4), 635; https://doi.org/10.3390/cancers18040635 - 15 Feb 2026
Viewed by 1446
Abstract
Background: Adjuvant radiation therapy for breast cancer improves survival but may expose thoracic organs to low-dose radiation, increasing the risk of second primary lung cancer (SPLC). Racial and ethnic disparities and social factors influencing SPLC risk remain underexplored. Objectives: We quantified racial and [...] Read more.
Background: Adjuvant radiation therapy for breast cancer improves survival but may expose thoracic organs to low-dose radiation, increasing the risk of second primary lung cancer (SPLC). Racial and ethnic disparities and social factors influencing SPLC risk remain underexplored. Objectives: We quantified racial and ethnic differences in SPLC incidence and survival among radiotherapy-treated breast cancer survivors and assessed the potential protective role of marital status. Methods: Using SEER-17 (2000–2022), we identified patients with first primary breast cancer receiving radiotherapy, excluding those who died within two months. Standardized incidence ratios (SIRs) assessed observed versus expected SPLC cases by race and ethnicity and marital status, and five-year overall survival (OS) after SPLC and mean age at death were calculated. Racial categories included White, Black, Asian or Pacific Islander (API), and American Indian or Alaska Native (AI/AN); ethnicity was categorized as Hispanic or non-Hispanic. Results: Among 558,493 patients, 6674 developed SPLC (1.19%). Risk varied significantly by race (p < 0.05). AI/AN patients had the highest overall risk (SIR 1.82), particularly 12–59 months and ≥120 months post-treatment. Black (SIR 1.21) and API (SIR 1.23) survivors had sustained elevated risk, while White survivors showed no overall increase (SIR 0.96) and Hispanic survivors had lower risk (SIR 0.72). Married individuals had 12% lower SPLC incidence (SIR 0.88). Five-year overall survival after SPLC was 28.0%, with significant variation by race and ethnicity (p = 0.002). API (32.2%) and AI/AN (32.5%) patients had the highest survival, followed by White (28.0%) and Black patients (25.6%). Married patients had higher five-year survival (31.8% vs. 25.0%) and older mean age at death (64.3 vs. 48.6 years) compared to unmarried patients. Conclusions: SPLC risk and prognosis after breast radiotherapy differ by race, ethnicity, and marital status. These findings highlight the importance of context-aware survivorship counseling and support the consideration of personalized lung cancer screening for breast cancer survivors. Full article
(This article belongs to the Special Issue Health Disparities and Outcomes in Cancer Survivors)
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15 pages, 574 KB  
Systematic Review
Proton Beam Therapy in Gynecological Cancers: A Systematic Review of Indications, Complications, and Limitations
by Vito Andrea Capozzi, Giulia Martignon, Elisa Scarpelli, Alessandra De Finis, Stefano Restaino, Giuseppe Vizzielli and Roberto Berretta
Medicina 2026, 62(2), 334; https://doi.org/10.3390/medicina62020334 - 6 Feb 2026
Cited by 2 | Viewed by 1455
Abstract
Background and Objectives: Gynecological cancers frequently require radiation therapy (RT) in primary, adjuvant, or salvage settings. However, photon-based RT is associated with non-negligible toxicity, and treatment of pelvic recurrences after prior irradiation remains challenging. Proton beam therapy (PBT), due to its favorable [...] Read more.
Background and Objectives: Gynecological cancers frequently require radiation therapy (RT) in primary, adjuvant, or salvage settings. However, photon-based RT is associated with non-negligible toxicity, and treatment of pelvic recurrences after prior irradiation remains challenging. Proton beam therapy (PBT), due to its favorable dose distribution and reduced exposure of organs at risk (OARs), has emerged as a potential alternative, particularly in re-irradiation scenarios. Despite its expanding use in other malignancies, evidence supporting PBT in gynecologic cancers remains limited. This systematic review aims to investigate the use of PBT in gynecological cancers and its associated complications. Materials and Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. A comprehensive search (2000–2025) identified studies investigating PBT in gynecologic cancers. Eligible designs included randomized trials and prospective and retrospective series. Reported adverse events were categorized as GI, GU, or other, and only grade ≥3 CT-CAE complications were considered. Results: Of 580 records screened, 9 studies comprising 232 patients met inclusion criteria. Most patients were treated for endometrial (n = 147) or cervical (n = 75) cancer; 90 received chemotherapy. Overall, severe toxicity occurred in 15.2% of patients. GI complications ranged from 0–14% and GU from 0–33%. Complication rates were lowest in adjuvant or de novo treatment series (0–10%), whereas re-irradiation cohorts showed higher rates (up to 33% GU). Comparative studies suggested a possible advantage of PBT over IMRT, particularly for GI toxicity, though data remain limited. Conclusions: Severe GI and GU toxicity after PBT in gynecologic cancers appears infrequent, particularly in primary and adjuvant settings, though re-irradiation remains challenging. Current evidence is restricted to small and heterogeneous studies. Ongoing phase II trials will provide prospective data to clarify feasibility, toxicity, and long-term outcomes. Until then, PBT in gynecologic oncology should be regarded as investigational. Full article
(This article belongs to the Special Issue Gynecological Surgery: Bridging Research and Clinical Practice)
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11 pages, 801 KB  
Article
The Role of Dosimetric Parameters in Radiation Pneumonitis: A Functional Approach in Adjuvant Treatment of Malignant Pleural Mesothelioma
by Luca Dominici, Davide Franceschini, Mauro Loi, Ruggero Spoto, Antonio Marco Marzo, Beatrice Marini, Mariya Boyanova Ilieva, Nicola Lambri, Francesco La Fauci, Ciro Franzese and Marta Scorsetti
Cancers 2026, 18(3), 405; https://doi.org/10.3390/cancers18030405 - 27 Jan 2026
Viewed by 520
Abstract
Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm, the major cause of which is asbestos exposure. Adjuvant radiotherapy after pleurectomy/decortication (P/D) aims at reducing locoregional recurrence but is limited by the risk of radiation pneumonitis (RP). In this study, we attempted to [...] Read more.
Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm, the major cause of which is asbestos exposure. Adjuvant radiotherapy after pleurectomy/decortication (P/D) aims at reducing locoregional recurrence but is limited by the risk of radiation pneumonitis (RP). In this study, we attempted to evaluate the predictive value of conventional and functional dosimetric parameters in assessing RP risk. Methods: This retrospective study analyzed 68 patients with non-metastatic MPM treated with adjuvant radiotherapy after P/D. Dosimetric parameters, including V20, V5, and mean lung dose (MLD), were calculated for both total lung volume and functional lung volume (FLV), with emphysematous regions excluded based on CT imaging thresholds. Statistical analyses assessed correlations between these parameters and acute RP incidence. Results: Acute RP developed in 42% of patients, and 28% had moderate-to-severe (Grade 2–3) events. V20 and FCL_V20 were significantly associated with the risk of RP (p = 0.017 and p = 0.028, respectively). Predictive accuracy for conventional V20 (AUC = 0.668) and Functional Contralateral Lung V20 (FCL_V20) (AUC = 0.655) showed moderate efficacy, without further significant improvement in using functional parameters. A V20 threshold > 1.8% predicted severe RP with high specificity (89.8%). Conclusions: While functional lung delineation provides an alternative in dosimetry, conventional V20 is a robust predictor of RP. Optimization of dosimetric constraints, in an effort to reduce pulmonary toxicity in MPM patients, should be further combined with advanced radiotherapy techniques and biomarkers. Full article
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11 pages, 1233 KB  
Article
Impact of Unplanned Radiotherapy Interruptions and Prolonged Overall Treatment Time on Recurrence in Head and Neck Squamous-Cell Carcinoma: A Retrospective Analysis from a Single Institution
by Rabia S. Angiras, Dilson Lobo, Athiyamaan M. Senthiappan, Sourjya Banerjee, Srinivas Challapalli, Johan Sunny, Abhishek Krishna and Paul Simon
Onco 2026, 6(1), 8; https://doi.org/10.3390/onco6010008 - 17 Jan 2026
Cited by 1 | Viewed by 2243
Abstract
Introduction: Radiotherapy plays a critical role in the management of head and neck squamous-cell carcinoma (HNSCC); however, the influence of overall treatment time on patient outcomes remains an area of ongoing investigation. The use of radiation, either in conjunction with concurrent chemotherapy [...] Read more.
Introduction: Radiotherapy plays a critical role in the management of head and neck squamous-cell carcinoma (HNSCC); however, the influence of overall treatment time on patient outcomes remains an area of ongoing investigation. The use of radiation, either in conjunction with concurrent chemotherapy or on its own, is crucial when treating HNSCC. Despite the longstanding hypothesis that treatment gaps may adversely affect tumor response and overall survival, there is a paucity of literature on this particular area. This study aims to bridge the knowledge gap and assess the correlation of treatment gaps on recurrences in HNSCC patients. Materials and Methodology: This retrospective study is based on an analysis of data obtained from a single institution between 2017 and 2021. Patients were selected on the basis of the presence of treatment gaps. Data were extracted from medical records and analyzed to evaluate the association between overall treatment time and various patient and treatment-related factors. Various factors thought to contribute to treatment gaps, such as age, TNM Stage, radiation dose, and use of concurrent chemotherapy, were also examined. Results: A total of 212 patients with treatment gaps were evaluated. Of these, 80 individuals experienced recurrences. It was observed that compared to distant metastases, locoregional failure was more frequent (n = 2, 4.2% vs. n = 45, 95.74%). The patients underwent both adjuvant and definitive therapy and were treated with a dose range of 60–70 Gy and concurrent cisplatin chemotherapy. It was noticed that this cohort had a range of 4–43 days of treatment gaps. Notably, 19 out of 47 patients had treatment gaps ≤ 5 days, while 28 out of 47 had gaps exceeding 5 days. It was also observed that patients with treatment gaps of >5 days had poorer quality of life and overall survival. Conclusions: This study identified that the Overall Treatment Time (OTT) had a strong statistical correlation with the development of recurrences. Further, the age of the patient, presence of neutropenia and the duration of the treatment gap were also identified to significantly correlate with the chance of developing recurrences. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy: 2nd Edition)
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11 pages, 661 KB  
Systematic Review
The Role of Radiotherapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: State of the Art
by Marco Andolfi, Michele Salati and Majed Refai
J. Pers. Med. 2025, 15(12), 585; https://doi.org/10.3390/jpm15120585 - 1 Dec 2025
Viewed by 740
Abstract
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 [...] Read more.
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
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15 pages, 1966 KB  
Case Report
Online Adaptive Radiotherapy for Left-Sided Breast Cancer with Comprehensive Regional Nodal Coverage Including the Internal Mammary Chain: Case Report and Narrative Review
by Damir Vučinić, Matea Lekić, Mihaela Mlinarić, Giovanni Ursi, Nikola Šegedin, Vanda Leipold, Domagoj Kosmina, Hrvoje Kaučić, Karla Schwarz and Dragan Schwarz
Radiation 2025, 5(4), 34; https://doi.org/10.3390/radiation5040034 - 20 Nov 2025
Viewed by 2363
Abstract
Online adaptive radiotherapy mitigates errors in absorbed dose delivery due to daily anatomical changes during hypofractionated breast treatment, particularly when comprehensive nodal therapy includes the internal mammary chain. To illustrate this, we present a case of a 65-year-old woman with left-sided luminal B [...] Read more.
Online adaptive radiotherapy mitigates errors in absorbed dose delivery due to daily anatomical changes during hypofractionated breast treatment, particularly when comprehensive nodal therapy includes the internal mammary chain. To illustrate this, we present a case of a 65-year-old woman with left-sided luminal B invasive carcinoma, who underwent segmentectomy and level 1–2 dissection. Pathology revealed an 18 × 15 × 13 mm primary tumor with lymphovascular invasion, two of eleven axillary nodes positive, and intramammary metastasis, staged pT1cN1a. She received adjuvant docetaxel–cyclophosphamide followed by letrozole. Hypofractionated radiotherapy (40 Gy in 15 fractions) was administered in an inspiration breath-hold setting using a CBCT-guided online-adaptive platform. Adaptive planning improved V95% coverage over the planned treatment for all targets: on average, whole breast coverage increased from 88.4% to 96.3%, supraclavicular from 93.0% to 97.1%, axilla from 90.6% to 96.7%, and internal mammary from 91.8% to 95.9%. Organ-at-risk metrics remained within limits: the mean heart dose increased slightly (from an average of 0.12 Gy in scheduled to 0.15 Gy in adaptive plans). At the same time, the LAD D0.03 cm3 decreased, and the heart V4 Gy fell modestly (from 13.3% in the scheduled plan to 8.2% in the adaptive plan), reflecting low-dose redistribution without exceeding constraints. Lung and thyroid mean doses remained comparable. The patient tolerated treatment well, with no acute toxicity or local recurrence. This case highlights the importance of daily adaptation for complex left-sided radiation treatment involving internal mammary nodes, demonstrating target recovery without exceeding absorbed dose constraints and supporting future studies on control, toxicity, and quality of life. Full article
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23 pages, 2004 KB  
Review
Radiation Necrosis in Neuro-Oncology: Diagnostic Complexity and Precision Radiotherapy Strategies
by Laura Mittelman, James Duehr, Jacob S. Kazmi, Luis O. Vargas, Nora Donahue, John Chen, Sandra Leskinen, Shoaib A. Syed, A. Gabriella Wernicke and Randy S. D’Amico
Cancers 2025, 17(21), 3542; https://doi.org/10.3390/cancers17213542 - 1 Nov 2025
Cited by 8 | Viewed by 5727
Abstract
Background: Radiation necrosis (RN) is a delayed and potentially debilitating complication of radiotherapy for central nervous system (CNS) tumors. It presents significant diagnostic and therapeutic challenges due to the variable clinical manifestations and overlap with tumor recurrence. Although advances in radiotherapy have improved [...] Read more.
Background: Radiation necrosis (RN) is a delayed and potentially debilitating complication of radiotherapy for central nervous system (CNS) tumors. It presents significant diagnostic and therapeutic challenges due to the variable clinical manifestations and overlap with tumor recurrence. Although advances in radiotherapy have improved tumor control, RN remains incompletely understood and inadequately addressed. This narrative review synthesizes current evidence on RN pathophysiology, risk factors, diagnostic strategies, and management approaches. Methods: A literature search was conducted for English-language literature published between January 1990 and December 2024. Studies were included if they addressed RN incidence, diagnosis, treatment, or novel preventive strategies in CNS tumor populations. Relevant findings were synthesized to produce a narrative review summarizing pathophysiology, diagnostic challenges, and treatment strategies. Results: RN results from radiation-induced neurovascular injury, inflammation, and vessel permeability, with incidence ranging from 3 to 26% depending on tumor type, location, and treatment parameters. Risk is influenced by dose, fractionation, cumulative exposure, re-irradiation, and adjuvant therapies. Advanced modalities such as SRS, HFSRT, brachytherapy, proton therapy, and IORT reduce but do not eliminate RN risk. Diagnosis remains challenging despite advanced MRI and PET techniques, with histopathology as the gold standard. Management includes corticosteroids, bevacizumab, surgery, LITT, and experimental therapies. Connectomics-based planning shows promise in minimizing RN by sparing critical brain networks. Conclusions: RN is a clinically significant and multifactorial complication of CNS radiotherapy. Precision treatment modalities and advanced imaging have improved prevention and detection, but diagnostic uncertainty and recurrence risk persist. Integration of connectomics into treatment planning may offer future promise of a reduction in RN-related morbidity by preserving structural and functional network integrity. Full article
(This article belongs to the Special Issue Radiotherapy for the Management of Brain Metastases)
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30 pages, 387 KB  
Review
Radiotherapeutic Modalities and Advancements in the Treatment of Cutaneous Malignancies
by Noor Malik, Irini Yacoub, Kristin Hsieh, J. Isabelle Choi, Arpit Chhabra and Charles B. Simone
J. Clin. Med. 2025, 14(18), 6547; https://doi.org/10.3390/jcm14186547 - 17 Sep 2025
Cited by 2 | Viewed by 2975
Abstract
Cutaneous malignancies represent the most common cancers worldwide and pose a growing public health burden. While surgical excision remains the primary curative modality, radiotherapy offers an effective adjuvant therapy for high-risk histopathologic features and an established, organ-preserving alternative for patients with inoperable disease [...] Read more.
Cutaneous malignancies represent the most common cancers worldwide and pose a growing public health burden. While surgical excision remains the primary curative modality, radiotherapy offers an effective adjuvant therapy for high-risk histopathologic features and an established, organ-preserving alternative for patients with inoperable disease or lesions in cosmetically or functionally sensitive sites. Advances in radiotherapeutic techniques, including brachytherapy and proton therapy, have expanded the therapeutic armamentarium, allowing tailored treatment based on tumor depth, extent, and anatomical location. Contemporary evidence highlights favorable local control and toxicity outcomes with modern radiation therapy approaches, yet data remain fragmented, with most studies limited by small cohorts, heterogeneous methodologies, and limited follow-up durations. Furthermore, the role of radiotherapy in complex scenarios, such as perineural invasion, recurrent disease, and previously irradiated fields, continues to evolve. This review synthesizes the current literature on radiotherapeutic management of skin cancer, critically evaluates dosimetric and clinical outcomes across modalities, and identifies key gaps in evidence. Emphasis is placed on the need for prospective, multicenter investigations to better define comparative effectiveness, optimize dose-fractionation regimens, and integrate emerging technologies into clinical practice. Radiotherapy remains an indispensable modality in dermatological oncology, offering curative potential with preservation of cosmesis and function, yet its optimal utilization demands further high-quality research to refine patient selection and therapeutic strategies. Full article
(This article belongs to the Special Issue Skin Cancer: Prevention, Diagnosis and Treatment)
11 pages, 886 KB  
Communication
A Biological-Driven Approach to Explore Dose-Escalated Ultra-Hypofractionation in Breast Cancer Radiotherapy
by Marco Calvaruso, Denis Panizza, Riccardo Ray Colciago, Valeria Faccenda, Gaia Pucci, Elena De Ponti, Giusi Irma Forte, Giorgio Russo, Luigi Minafra and Stefano Arcangeli
Biomedicines 2025, 13(9), 2154; https://doi.org/10.3390/biomedicines13092154 - 4 Sep 2025
Cited by 2 | Viewed by 1651
Abstract
To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both [...] Read more.
To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model. Full article
(This article belongs to the Special Issue Latest Advancements in Radiotherapy)
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24 pages, 4816 KB  
Article
Formulation of Honokiol- and Magnolol-Loaded Nanoemulsions for Head and Neck Cancer Adjuvant Therapy: Evaluation of Radiation Sterilization Effects on Active Substance Properties
by Katarzyna Dominiak, Aleksandra Gostyńska-Stawna, Agnieszka Sobczak, Jarosław Paluszczak, Aneta Woźniak-Braszak, Mikołaj Baranowski, Paweł Bilski, Barbara Wicher, Ewa Tykarska, Anna Jelińska and Maciej Stawny
Int. J. Mol. Sci. 2025, 26(16), 8032; https://doi.org/10.3390/ijms26168032 - 20 Aug 2025
Cited by 6 | Viewed by 1741
Abstract
Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded [...] Read more.
Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded intravenous (IV) nanoemulsions using commercial lipid preparations with varying fatty acid compositions. The formulations were physicochemically characterized and evaluated in vitro using FaDu and SCC-040 HNSCC cell lines. HON and MAG were sterilized via ionizing radiation at doses of 25, 100, and 400 kGy. Their suitability for IV use was assessed through PXRD, DSC, TGA, EPR, FT-IR, NMR, and HPLC analyses. All formulations met safety criteria for IV administration, with mean droplet diameters below 241 nm and encapsulation efficiencies exceeding 95%. They significantly reduced cancer cell viability, with a synergistic effect observed in combined HON and MAG formulations compared to single-compound nanoemulsions. Clinoleic-based formulations showed enhanced anticancer efficacy, likely due to the pro-apoptotic properties of oleic acid. Notably, radiation sterilization at the standard 25 kGy dose preserved the thermal, crystalline, and structural stability of HON and MAG, whereas higher doses (400 kGy) induced degradation. Although free radicals were detected via EPR, their transient nature and rapid decay confirmed the method’s safety. HON/MAG-loaded nanoemulsions exhibited strong anticancer potential, while radiation sterilization at 25 kGy ensured sterility without compromising stability. These findings provide a preliminary in vitro basis for future in vivo studies investigating HON and MAG as potential adjuvant therapies for HNSCC. Full article
(This article belongs to the Special Issue Drug Discovery: Natural Products and Compounds)
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