Search Results (303)

Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our understanding of sinonasal EMP by reviewing the recent literature and presenting a case series from our clinical experience. Materials and Methods: A systematic review of published cases of sinonasal EMP from 2000 to 2023 was conducted using the PubMed database, yielding 28 eligible cases. Additionally, we retrospectively analyzed three patients diagnosed and treated at our institutions. Inclusion criteria included histologically and immunohistochemically confirmed EMP without evidence of systemic multiple myeloma. Data on demographics, tumor location, symptoms, treatment, and outcomes were collected and analyzed descriptively. Results: Sinonasal EMP most commonly presented with unilateral nasal obstruction and epistaxis. Tumors were primarily located in the nasal cavity and paranasal sinuses, often extending beyond a single anatomical site. In the literature cohort, the most frequent treatment was combined surgery and radiotherapy (35.71%), followed by radiotherapy alone (17.86%). Recurrence was reported in 10.71% of cases, and 7.14% of patients died due to disease progression. All three patients in our case series underwent surgical excision; two received postoperative radiotherapy. No recurrences or progression to multiple myeloma were observed during follow-up (12–24 months). Conclusions: Sinonasal EMP is a rare but radiosensitive tumor with a favorable prognosis when treated with surgery and/or radiotherapy. Early diagnosis, histopathological confirmation, and exclusion of systemic disease are essential. Multidisciplinary management and long-term follow-up are critical due to the risk of recurrence and transformation into multiple myeloma. Full article

Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics. Full article

Radiotherapy (RT) continues to be a fundamental component in the management of non-small cell lung cancer (NSCLC). Nevertheless, some NSCLC patients do not attain optimal therapeutic outcomes due to the emergence of radioresistance. Improving the effectiveness of RT in NSCLC necessitates a thorough comprehension of the mechanisms that lead to radioresistance. This review delineates various potential mechanisms of radioresistance in NSCLC, encompassing augmented DNA damage repair, cell cycle dysregulation, cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), tumor hypoxia, an immunosuppressive tumor microenvironment (TME), dysregulation of cell death pathways, metabolic reprogramming, exosome-mediated signaling, genetic mutations, aberrant activation of signaling pathways, and epigenetic modifications. In addition, this study explores various novel strategies aimed at enhancing the radiosensitivity of NSCLC and provides a concise overview of potential biomarkers predictive of RT response, which may contribute to the development of innovative combination therapies to address radioresistance and improve patient outcomes. Full article

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements in radiotherapy techniques like IMRT and VMAT, some patients still experience acute and late side effects. Current treatment protocols do not account for individual variability in normal-tissue radiosensitivity, highlighting the need for predictive tools and a personalised treatment approach. Genetic factors and molecular regulators like microRNAs (miRNAs) contribute to these variations by influencing DNA repair, inflammation, and apoptosis. This review explores potential biomarkers of radiotoxicity, focusing on immune-related factors such as IL-6 and TGF-β1, SNPs influencing radiosensitivity, miRNAs involved in radiation responses, and functional assays including the radiation-induced lymphocyte apoptosis (RILA) test. These approaches offer promising tools for identifying radiosensitive patients and enabling risk-adapted radiotherapy. Full article

Background/Objectives: NPC is a radiosensitive malignancy with high recurrence rates despite therapeutic advances. This study aimed to identify radiologic and metabolic predictors of recurrence in newly diagnosed NPC by integrating MRI and ¹⁸F-FDG PET/CT parameters. Methods: Fifty-two patients with biopsy-proven, previously untreated NPC who underwent pre-treatment MRI and ¹⁸F-FDG PET/CT were retrospectively analyzed. Local tumor features, nodal status, and response patterns were evaluated using MRI and PET/CT-derived metrics: SUVmax, SUVmean, SUVpeak, MTV, and TLG. The post-treatment MRI response was categorized into six patterns. Univariate and multivariate analyses were performed to identify independent predictors. Results: Recurrence occurred in 27% of patients. Based on the multivariate analysis, PNI, extensive PPS invasion, GTV, and metastatic LN count were identified as independent predictors of recurrence (PNI: OR = 1.60, p = 0.029; PPS: OR = 1.23, p = 0.027; GTV: OR = 1.08, p = 0.042; LN count: OR = 1.20, p = 0.031). PNI and PPS invasion were significantly associated with local failure (HR = 8.21, p = 0.008 and HR = 3.52, p = 0.043, respectively). GTV was independently associated with an increased risk of local (HR = 1.14, p = 0.021) and distant recurrence (HR = 1.19, p = 0.024). The presence of metastatic disease at diagnosis (HR = 6.27, p = 0.027) and a higher LN count (HR = 1.17, p = 0.028) were also linked to distant failure. Conclusions: Imaging-derived predictors including GTV, PNI, LN burden, and MRI-based response patterns demonstrate prognostic value for disease recurrence in NPC and may guide risk-adapted treatment strategies. Full article

Stereotactic body radiotherapy (SBRT) delivers ablative radiation doses with sub-millimeter precision. Radiogenomic studies, meanwhile, provide insights into how tumor-intrinsic genetic factors influence responses to such high-dose treatments. This review explores the radiobiological mechanisms underpinning SBRT efficacy, emphasizing the roles of DNA damage response (DDR) pathways, tumor suppressor gene alterations, and inflammatory signaling in shaping tumor radiosensitivity or resistance. SBRT induces complex DNA double-strand breaks (DSBs) that robustly activate DDR signaling cascades, particularly via the ATM and ATR kinases. Tumors with proficient DNA repair capabilities often resist SBRT, whereas deficiencies in key repair genes can render them more susceptible to radiation-induced cytotoxicity. Mutations in tumor suppressor genes may impair p53-dependent apoptosis and disrupt cell cycle checkpoints, allowing malignant cells to evade radiation-induced cell death. Furthermore, SBRT provokes the release of pro-inflammatory cytokines and activates innate immune pathways, potentially leading to immunogenic cell death and reshaping the tumor microenvironment. Radiogenomic profiling has identified genomic alterations and molecular signatures associated with differential responses to SBRT and immune activation. These insights open avenues for precision radiotherapy approaches, including the use of genomic biomarkers for patient selection, the integration of SBRT with DDR inhibitors or immunotherapies, and the customization of treatment plans based on individual tumor genotypes and immune landscapes. Ultimately, these strategies aim to enhance SBRT efficacy and improve clinical outcomes through biologically tailored treatment. This review provides a comprehensive summary of current knowledge on the genetic determinants of response to stereotactic radiotherapy and discusses their implications for personalized cancer treatment. Full article

Background and Objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC). Methods: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous. Results: Twelve studies (n = 1354 unique patients, median sample = 73, range 22–735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a “butyrate-rich” baseline profile was 44% (95% CI 35–54) versus 21% (95% CI 15–29) in controls (I² = 18%). Conclusions: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment. Full article

Radiotherapy resistance represents a critical aspect of cancer treatment, and molecular characterization is needed to explore the pathways and mechanisms involved. DNA repair, hypoxia, metabolic reprogramming, apoptosis, tumor microenvironment modulation, and activation of cancer stem cells are the primary mechanisms that regulate radioresistance, and understanding their complex interactions is essential for planning the correct therapeutic strategy. Proteomics has emerged as a key approach in precision medicine to study tumor heterogeneity and treatment response in cancer patients. The integration of mass spectrometry-based techniques with bioinformatics has enabled high-throughput, quantitative analyses to identify biomarkers, pathways, and new potential therapeutic targets. This review highlights recent advances in proteomic technologies and their application in identifying biomarkers predictive of radiosensitivity and radioresistance in different tumors, including head and neck, breast, lung, and prostate cancers. Sample variability, data interpretation, and the translation of findings into clinical practice remain challenging elements of proteomics. However, technological advancements support its application in a wide range of topics, allowing a comprehensive approach to radiobiology, which helps overcome radiation resistance. Ultimately, incorporating proteomics into the radiotherapy workflow offers significant potential for enhancing treatment efficacy, minimizing toxicity, and guiding precision oncology strategies. Full article

At the intersection of nanotechnology and cancer biology, gold nanoparticles (AuNPs) have emerged as more than passive carriers—they are active agents capable of reshaping cellular fate. Among their most promising attributes is the potential to modulate apoptosis and autophagy, two intricately linked pathways that determine tumor response to stress, damage, and treatment. Apoptosis serves as the principal mechanism of programmed cell death, while autophagy offers a dualistic role—preserving survival under transient stress or contributing to cell death under sustained insult. Thus, understanding how these mechanisms interact—and how AuNPs influence this crosstalk—may be key to unlocking more effective oncologic therapies. This review explores the molecular interplay between apoptosis and autophagy in cancer and evaluates how AuNPs impact these pathways. By enhancing radiosensitization in radiation therapy and improving drug delivery and chemotherapeutic precision, AuNPs offer a unique strategy to circumvent resistance in aggressive or refractory tumors towards shaping their biological behavior and cellular pathways and, therefore, forming a patient-centered personalized therapeutic potential. Yet, clinical translation remains challenging. The dynamic physicochemical nature of AuNPs makes their biological behavior highly context-dependent. Combined with the complexity of apoptotic and autophagic signaling and tumor heterogeneity, this creates a triad of profound intricacy. However, within this complexity lies therapeutic opportunity. Framing AuNPs, apoptosis, and autophagy as a synergistic axis may enable mechanism-informed, adaptable, and patient-specific cancer therapies. This paradigm shift invites a more strategic integration of nanotechnology with molecular oncology, advancing the frontier of precision medicine. Full article

Prostate cancer cell lines are particularly clinically homogenous, mostly representing metastatic states rather than localized disease. While there has been significant work in the development of additional models, few have been created without oncogenic transformation. We derived a primary prostate cancer cell line from a patient with localized Gleason 7 prostate cancer—designated CaB34—which spontaneously immortalized. We leveraged CaB34 to generate a paired radioresistant subline, CaB34-CF, using a clinically relevant fractionated radiotherapy schedule. These two paired cell lines were investigated extensively to determine their molecular characteristics and therapy responses. Both CaB34 and CaB34-CF express prostate-specific markers, including KRT18, NKX3.1, and AMACR. Multi-omic analyses using RNAseq and shotgun proteomics identified NNMT as the most significantly dysregulated component in CaB34-CF. A bioinformatic analysis determined that NNMT was more abundant within prostate tumors compared to benign prostate, suggesting a role in tumor progression. Knockdown studies of NNMT demonstrated significant radiosensitization of CaB34-CF cells, which was largely a result of increased radiation-induced cellular senescence. Growth as 3D organoids was significantly higher in the CaB34-CF line, and demonstrated a less structured pattern of expression of cytokeratin markers. Radiosensitization with NNMT siRNA was recapitulated in a 3D organoid clonogenic assay in CaB34-CF cells. Our research provides a paired primary model of treatment-naïve and radioresistant disease to address mechanisms of therapy resistance, while expanding the repertoire of localized prostate cancer cell lines for the research community. In addition, our findings present NNMT as a potential therapeutic target for sensitization of radioresistant disease. Full article

Stereotactic radiotherapy (SBRT) and radiofrequency ablation (RFA) are common ablative techniques for lung metastases. A retrospective review of all patients treated with either modality at a single institution between 2011 and 2019 was conducted. Baseline characteristics and outcomes were compared. Local and distant progression, and overall survival were estimated using the Kaplan–Meier method. Univariable analysis was carried out using Cox regression; this was followed by multivariable modelling. In total, 106 patients treated with RFA and 70 treated with SBRT were identified. Tumours treated with SBRT were larger (median size 18 mm vs. 11 mm) and primarily oligometastatic (91.4% vs. 20%). Median progression-free survival (PFS) was 12.5 months for SBRT and 7.9 months for RFA (p = 0.009). Median OS was similar (p = 0.66). In multivariable analysis, lesion size > 20 mm was predictive of adverse local PFS (p = 0.001), PFS (p = 0.0034) and OS (p = 0.001). A statistically significant interaction effect suggested that RFA was associated with better local PFS within colorectal primary patients (p = 0.035). This study highlights differences in patient selection and outcomes for RFA or SBRT in the treatment of lung metastases at our institution. Future studies for SBRT should focus on the optimum dose schedules required for different histologies. For less-radiosensitive tumours, RFA may offer a superior alternative where dose-escalated SBRT is not possible. Full article

Background/Objectives: In recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), the overall prognosis is poor, and systemic treatment options remain limited. While precision therapy approaches have revolutionized treatment strategies in several tumor types, molecularly informed therapies in R/M HNSCC are rare, primarily due to the low number of actionable genetic alterations identified through next-generation sequencing (NGS) panels. There is an urgent need to establish precision therapy approaches in R/M HNSCC using innovative predictive testing. Methods: We report the case of a 43-year-old patient with recurrent oral cancer who was extensively pretreated and comprehensively characterized using both descriptive and functional testing. Results: NGS revealed no targetable alterations. A tumor tissue slice radiosensitivity assay suggested radioresistance, arguing against re-irradiation. Kinome profiling identified upregulated Src-family kinases (SFK), and SFK inhibition reduced kinase activity in vitro. Most notably, mRNA analysis demonstrated high Trop-2 overexpression, confirmed by immunohistochemistry (3+ in 100% of tumor cells). Following six cycles of the Trop-2-directed antibody–drug conjugate Sacituzumab govitecan (SG), the patient had an impressive clinical response. Conclusions: Tumor characterization beyond genetic profiling can identify novel treatment options in therapy-refractory HNSCC. This is the first report of “real-world” data on promising antitumor efficacy of SG in a heavily pretreated oral cancer patient with Trop-2 overexpression. Consistent with the findings of the Basket TROPiCS-03 study, SG appears to be a promising novel therapy option for R/M HNSCC after failure of immunotherapy and chemotherapy, particularly in patients with Trop-2 overexpression. Full article

Radiation therapy is a medical treatment that uses high doses of radiation to kill or damage cancer cells. It works by damaging the DNA within the cancer cells, ultimately causing cell death. Radiotherapy can be used as a primary treatment, adjuvant treatment in combination with surgery or chemotherapy or palliative treatment to relieve symptoms in advanced cancer stages. Radiation therapy is constantly improving in order to enhance the effect on cancer cells and reduce the side effects on healthy tissues. Our results clearly demonstrate that proton therapy and, even more, carbon ion therapy appear as promising alternatives to overcome the radioresistance of various tumors thanks to less dependency on oxygen and a better ability to kill cancer stem cells. Interestingly, hadrons also retain the advantages of radiosensitization approaches. These data confirm the great ability of hadrons to spare healthy tissue near the tumor via various mechanisms (reduced lymphopenia, bystander effect, etc.). Technology and machine improvements such as image-guided radiotherapy or particle therapies can improve treatment quality and efficacy (dose deposition and biological effect) in tumors while increasingly sparing healthy tissues. Radiation biology can help to understand how cancer cells resist radiation (hypoxia, DNA repair mechanisms, stem cell status, cell cycle position, etc.), how normal tissues may display sensitivity to radiation and how radiation effects can be increased with either radiosensitizers or accelerated particles. All these research topics are under investigation within the ARCHADE research community in France. By focusing on these areas, radiotherapy can become more effective, targeted and safe, enhancing the overall treatment experience and outcomes for cancer patients. Our goal is to provide biological evidence of the therapeutic advantages of hadrontherapy, according to the tumor characteristics. This article aims to give an updated view of our research in radiation biology within the frame of the French “ARCHADE association” and new perspectives on research and treatment with the C400 multi-ions accelerator prototype. Full article

Background/Objectives: Stereotactic body radiotherapy is frequently used in patients with adrenal metastases. Motion of adherent radiosensitive organs at risk (OARs) and tumors influence OAR toxicity and tumor control. Online-adaptive Magnetic Resonance-guided radiotherapy (MRgRT) can address and mitigate interfractional changes. However, the impact of intrafractional variations in adrenal MRgRT is unknown. Methods: A total of 23 patients with 24 adrenal metastases were treated with MRgRT. After daily plan adaptation and before beam application, an additional (preRT) 3d MRI was acquired. PreRT target volumes and OARs were retrospectively recontoured in 200 fractions. The delivered, online-adapted treatment plans, as well as non-adapted baseline plans, were calculated on these re-contoured structures to quantify the dosimetric impact of intrafractional variations on target volume coverage and OAR doses with and without online adaptation. Normal tissue complication probabilities (NTCPs) were calculated. Results: The median time between the two MRIs was 56.4 min. GTV and PTV coverage (dose to 95% of the PTV, D95%, and volume covered by 100% of the prescription dose, V100%) were significantly inferior in the preRT plans. GTV D_mean was significantly impaired in left-sided metastases, but not in right-sided metastases. Compared to non-adapted preRT plans, adapted preRT plans were still significantly superior for all GTV and PTV metrics. Intrafractional violations of OAR constraints were frequent. D0.5cc and the volume exposed to the near-maximum dose constraint were significantly higher in the preRT plans. The volume exposed to the D0.5cc constraints in single fractions escalated up to 1.5 cc for the esophagus, 3.2 cc for the stomach, 5.3 cc for the duodenum and 7.3 cc for the bowel. This led to significantly elevated NTCPs for the stomach, bowel and duodenum. Neither PTV D95%, nor gastrointestinal OAR maximum doses were significantly impaired by longer fraction duration. Conclusions: Intrafractional motion in adrenal MRgRT caused significant impairment of target volume coverage (D95% and V100%), potentially undermining local control. Frequent violation of gastrointestinal OAR constraints led to elevated NTCP. Compared to non-adaptive treatment, online adaptation still highly improved GTV and PTV coverage. Full article

Background/Objectives: The increasing prevalence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has necessitated a revaluation of therapeutic strategies. HPV-driven OPSCC differs from HPV-negative OPSCC due to its distinct molecular signatures, increased radiosensitivity, and better prognoses. However, despite these differences, treatment strategies have remained largely uniform, resulting in minimal reductions in morbidity and exposing HPV-positive patients to unnecessary toxicity. Monoclonal antibodies (mAbs) have become a promising therapeutic option due to their ability to target treatment with fewer systemic side effects. Immune checkpoint inhibitors (ICIs) such as pembrolizumab have shown efficacy in enhancing the immune response against tumors, while EGFR inhibitors like cetuximab offer an alternative modality. Current clinical trials aim to refine dosing regimens and identify combination strategies that may enhance therapeutic outcomes. Results: Despite promising evidence, several challenges hinder the widespread adoption of mAbs as a standard treatment for HPV-positive OPSCC in clinical practice. This review examines the current role of mAbs in HPV-positive OPSCC treatment, highlighting their limitations and future research directions. Conclusions: Further studies are needed to optimize patient selection, establish standardized treatment protocols, and investigate the long-term benefits of mAb-based therapies in this patient population. Full article