Search Results (287)

Background: Soft tissue sarcomas (STSs) are rare and heterogeneous malignancies requiring a multidisciplinary approach to diagnosis and treatment. Advances in surgical techniques, chemotherapy, and radiotherapy have improved survival rates but often result in significant functional impairments, particularly in patients undergoing limb-sparing procedures. Rehabilitation is crucial for restoring mobility and independence, with recent studies emphasizing the importance of personalized rehabilitation protocols tailored to specific surgical interventions. Quantitative assessments, such as 3D motion capture and surface electromyography, provide objective insights into gait performance and motor function, enabling more precise rehabilitation strategies to optimize recovery. Methods: This study evaluated gait performance in 21 patients with lower-limb impairment following limb-sparing surgery for STS. Patients underwent two instrumented gait assessments using marker-based 3D motion capture and surface electromyography to measure spatiotemporal gait parameters, joint kinematics, and muscle activity. Independence in the activity of daily living was assessed with the modified Barthel Index in both timepoints. Results: Following rehabilitation, patients demonstrated significant improvements in functional independence, as reflected by an increase in the modified Barthel Index (p < 0.001). Gait analysis revealed increased walking speed, stride length, cadence, and improved joint range of motion at the hip, knee, and ankle, though electromyographic analysis showed no statistically significant differences in muscle activation patterns or co-contraction indices. Conclusions: These findings underscore the importance of a rehabilitation programs personalized on gait strategies. A deeper understanding of motor adaptations based on sarcoma location and surgical approach could further refine rehabilitation protocols, ultimately enhancing patient outcomes and quality of life. Full article

Objectives: This study aimed to assess the precision of dose delivery to the target in adaptive carbon ion radiotherapy (CIRT) for locally advanced non-small cell lung cancer (LA-NSCLC) in cumulative dosimetry. Methods: Forty-six patients who received CIRT were included (64 Gy[relative biological effectiveness, RBE] in 16 fractions) with treatment plan computed tomography (CT) and weekly CT scans. Offline adaptive radiotherapy (ART) was administered if the dose distribution significantly worsened. Daily doses were calculated from weekly CTs and integrated into plan CT scans using deformable image registration. The dosimetry parameters were compared between the as-scheduled plan and adaptive replan in patients receiving ART. Survival outcomes and toxicity were compared between the ART and non-ART groups. Results: ART was implemented for 27 patients in whom adaptive replans significantly increased the median V_98% of the clinical tumor volume from 96.5% to 98.1% and D_98% from 60.5 to 62.7 Gy(RBE) compared with the as-scheduled plans (p < 0.001). The conformity and uniformity of the dose distribution improved (p < 0.001), with no significant differences in the doses to normal tissues (lungs, heart, esophagus, and spinal cord) from the as-scheduled plans (p > 0.05). The ART and non-ART groups demonstrated comparable local control, progression-free survival, and overall survival (p > 0.05). No grade 3 or higher radiation-related toxicities were observed. Conclusions: ART enhanced target dose coverage while maintaining acceptable normal tissue exposure, supporting weekly CT monitoring integration during CIRT for the timely intervention for anatomical variations, ensuring precise dose delivery in LA-NSCLC. Full article

Introduction/Background: Patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR) after neoadjuvant chemo-radiotherapy (NCRT) are a privileged group because of the favorable progression of their disease. However, their follow-up patterns after surgery are similar to those of other groups with worse prognosis, with the consequent psychological and economic impact. Methods: This is a retrospective observational multicenter study with data obtained from the Spanish Rectal Cancer Project. Patients with LARC who underwent surgery with curative intent after NCRT and achieved pCR were selected. The last follow-up update was conducted in December 2021. A conditional survival model was used to analyze oncological outcomes during follow-up. Recurrence-free survival (RFS) was analyzed for the entire cohort of patients and for those who survived at one, two, and three years. Results: A total of 815 patients from 32 hospitals were included. Their mean age was 65.1 years, and 36.1% of them were women. Of the 815 patients, 35 died or experienced recurrence (local or systemic) in the first postoperative year, and 780 were included in the conditional survival analysis one year after surgery. The probability of RFS at 5 years was 86.5% in the whole cohort and 89.4%, 92.9%, and 95.2% for survivors at one, two, and three years, respectively. The probability of recurrence in these same groups was 6.5%, 4.3%, 1.8%, and 0.6%. Conclusions: Follow-up of patients with LARC and pCR after NCRT followed by surgery could be adapted based on conditional survival data showing that the probability of RFS increases as patients remain recurrence-free, and recurrences more than 3 years after treatment are exceptional. Full article

Chimeric antigen receptor (CAR)-T-cell therapy has revolutionised haematological cancer treatment. However, its application in solid tumours remains significantly limited by the immunosuppressive tumour microenvironment (TME), poor antigen specificity, and physical barriers to infiltration. This review explores a compelling question: can CAR-T cells be adapted to overcome immunosuppression in solid tumours effectively? We provide an in-depth analysis of the immunological, metabolic, and structural challenges posed by the TME and critically evaluate emerging engineering strategies designed to enhance CAR-T cells’ persistence, targeting, and function. These include metabolic reprogramming, hypoxia-responsive constructs, checkpoint-resistant designs, and innovative delivery techniques such as locoregional administration and nanotechnology-assisted targeting. We highlight promising preclinical and early clinical studies demonstrating that armoured CAR-T cells secreting cytokines like interleukin (IL)-12 and IL-18 can reprogram the TME, restoring antitumour immunity. Moreover, we examine synergistic combination therapies that integrate CAR-T cells with immune checkpoint inhibitors, radiotherapy, oncolytic viruses, and epigenetic modulators. Special attention is given to personalised strategies, such as bispecific targeting and precision delivery to tumour-associated vasculature or stromal elements, which are showing encouraging results in overcoming resistance mechanisms. This review aims not only to synthesise current advancements but also to ignite optimism in the potential of CAR-T-cell therapy to breach the immunological fortress of solid tumours. As we enter a new era of synthetic immunology, this evolving landscape offers hope for durable remissions and novel treatment paradigms. For clinicians, researchers, and biotech innovators, this paper provides a roadmap toward transforming a therapeutic dream into clinical reality. Full article

Gastric cancer remains a significant global health challenge, with regional and demographic disparities in incidence, mortality, and treatment outcomes. Despite advances in screening and early detection, prognosis remains poor for many patients, particularly those with advanced disease. Recent insights into DNA damage response pathways have uncovered critical molecular vulnerabilities in gastric tumors, including frequent TP53 mutations, ARID1A loss, ATM deficiency, and oncogene-driven replication stress, which render these cancers highly dependent on the ATR–CHK1 axis for survival. This review synthesizes current clinical and preclinical evidence on ATR and CHK1 inhibitors as therapeutic strategies in gastric cancer. Emphasis is placed on synthetic lethality, immune modulation, and the potential for combination regimens with chemotherapy, radiotherapy, or immune checkpoint blockade. Mechanisms of resistance, including transcription-associated replication stress modulation and bypass signaling networks, are discussed, alongside strategies to predict and overcome therapeutic failure. The review also highlights the importance of biomarker-guided patient selection, adaptive dosing to reduce toxicity, and refined pharmacodynamic monitoring to enhance therapeutic precision. Collectively, these insights support the rational integration of ATR–CHK1 inhibitors into clinical protocols for biomarker-defined gastric cancer subsets and underscore their promise Full article

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared. Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.5 Gy/15 fractions with concurrent capecitabine) for LAPC. Gray’s test and Cox proportional regression analyses were performed to identify factors associated with local failure (LF) and overall survival (OS). Results: A total of 211 patients (SMART, n = 91; HART, n = 120) were evaluated, and none had surgery. Median follow-up after SMART and HART was 27.0 and 40.0 months, respectively (p < 0.0002). SMART achieved higher gross tumor volume (GTV) coverage and greater hotspots. Two-year LF after SMART and HART was 6.5% and 32.9% (p < 0.001), while two-year OS was 31.0% vs. 35.3% (p = 0.056), respectively. LF was associated with SMART vs. HART (HR 5.389, 95% CI: 1.298–21.975; p = 0.021) and induction mFOLFIRINOX vs. non-mFOLFIRINOX (HR 2.067, 95% CI 1.038–4.052; p = 0.047), while OS was associated with CA19-9 decrease > 40% (HR 0.725, 95% CI 0.515–0.996; p = 0.046) and GTV V120% (HR 1.022, 95% CI 1.006–1.037; p = 0.015). Acute grade > 3 toxicity was similar (3.3% vs. 5.8%; p = 0.390), while late grade > 3 toxicity was less common after SMART (2.2% vs. 9.2%; p = 0.037). Conclusions: Ablative SMART and HART both achieve favorable oncologic outcomes for LAPC with minimal toxicity. We did not observe an OS difference, although technical advantages of SMART might improve target coverage and reduce LF. Full article

Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer requiring adjuvant radiation with external beams were enrolled. Five patients underwent radiation therapy targeting the pelvic disease and positive lymph nodes, with doses of 50.4 Gy in twenty-eight fractions and a subsequent stereotactic boost on the vaginal vault at a dose of 5 Gy in a single fraction. One patient was administered 30 Gy in five fractions to the vaginal vault. These patients underwent external beam RT following the implantation of three 0.40 × 10 mm gold fiducial markers (FMs). Our IGRT strategy involved real-time 2D kV image-based monitoring of the fiducial markers during the treatment delivery as a surrogate of the vaginal cuff. To explore the potential role of FMs throughout the treatment process, we analyzed cine movies of the 2D kV-triggered images during delivery, as well as the image registration between pre- and post-treatment CBCT scans and the planning CT (pCT). Each CBCT used to trigger fraction delivery was segmented to define the rectum, bladder, and vaginal cuff. We calculated a standard metric to assess the similarity among the images (Dice index). Results: All the patients completed radiotherapy and experienced good tolerance without any reported acute or long-term toxicity. We did not observe any loss of FMs during or before treatment. A total of twenty CBCTs were analyzed across ten fractions. The observed trend showed a relatively emptier bladder compared to the simulation phase, with the bladder filling during the delivery. This resulted in a final median Dice similarity coefficient (DSC) of 0.90, indicating strong performance. The rectum reproducibility revealed greater variability, negatively affecting the quality of the delivery. Only in two patients, FMs showed intrafractional shift > 5 mm, probably associated with considerable rectal volume changes. Target coverage was preserved due to a safe CTV-to-PTV margin (10 mm). Conclusions: In our preliminary study, CBCT in combination with the use of fiducial markers to guide the delivery proved to be a feasible method for IGRT both before and during the treatment of post-operative gynecological cancer. In particular, this approach seems to be promising in selected patients to facilitate the use of SBRT instead of BRT (brachytherapy), thanks to margin reduction and adaptive strategies to optimize dose delivery while minimizing toxicity. A larger sample of patients is needed to confirm our results. Full article

Anal cancer is a rare malignancy with rising incidence. Definitive treatment with radiation and concurrent chemotherapy represent the standard of care for patients with non-metastatic disease. Advances in radiation delivery through the use of intensity-modulated radiotherapy have significantly reduced the toxic effects of treatment. Adaptive radiotherapy (ART) has emerged as a strategy to further enhance treatment precision and individualize therapy in response to patient-specific changes during the course of chemoradiotherapy. The rationale for ART in anal cancer stems from the recognition that significant anatomic and tumor changes can occur throughout the 5–6-week treatment course, including tumor shrinkage, weight loss, and variable rectal/bladder filling. This review discusses the role of ART in contemporary anal cancer management. We overview the principles of ART, delineate the technical workflows (including both computed tomography (CT) and MR-guided approaches), and examine how adaptive techniques are applied in treatment planning and delivery. We also review the clinical evidence to date, including dosimetric studies and emerging clinical trial data on ART in anal cancer, particularly its impact on outcomes and toxicity. Full article

Background/Objectives: This study aims to present a structured clinical workflow for offline adaptive Biology-guided Radiotherapy (BgRT) using the RefleXion X1 PET-linac system, addressing challenges introduced by inter-treatment anatomical and biological changes. Methods: We propose a decision tree offline adaptation framework based on real-time assessments of Activity Concentration (AC), Normalized Target Signal (NTS), and bounded dose-volume histogram (bDVH%) metrics. Three offline strategies were developed: (1) preemptive adaptation for minor changes, (2) partial re-simulation for moderate changes, and (3) full re-simulation for major anatomical or metabolic alterations. Two clinical cases demonstrating strategies 1 and 2 are presented. Results: The preemptive adaptation strategy was applied in a case with early tumor shrinkage, maintaining delivery parameters within acceptable limits while updating contours and dose distribution. In the partial re-Simulation case, significant changes in PET signal necessitated a same-day PET functional modeling session and plan re-optimization, effectively restoring safe deliverability. Both cases showed reduced target volumes and improved OAR sparing without additional patient visits or tracer injections. Conclusions: Offline adaptive workflows for BgRT provide practical solutions to address inter-fractional changes in tumor structure and function. These strategies can help maintain the safety and accuracy of BgRT delivery and support clinical adoption of PET-guided radiotherapy, paving the way for future online adaptive capabilities. Full article

Background and Objectives: The COVID-19 pandemic disrupted cancer care, prompting adaptations to reduce patient exposure while preserving treatment efficacy. This retrospective observational study compared a weekly cisplatin and 5-fluorouracil (5-FU) regimen to the standard monthly regimen for neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Materials and Methods: This single-center retrospective study included 91 patients, divided into two cohorts: weekly chemotherapy (n = 30) and standard chemotherapy (n = 61). Treatment assignment was based on hospital policy changes during the pandemic, with weekly outpatient chemotherapy implemented after November 2022 to conserve inpatient resources. All patients received radiotherapy at 50 Gy in 25 fractions. The weekly regimen consisted of cisplatin 20 mg/m² and 5-FU 800 mg/m², administered over 1–2 h weekly, while the standard regimen administered the same doses over four consecutive days on weeks 1 and 5. Primary endpoints were pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: The response rates were similar between groups (weekly: 86.7% vs. standard: 90.2%; p = 0.724). The weekly regimen group showed a higher pCR (40.0% vs. 26.2%; p = 0.181) and significantly lower recurrence (26.7% vs. 52.5%; p = 0.020). Mortality was also reduced in the weekly group (6.7% vs. 34.4%; p = 0.004), though the follow-up duration was shorter (10.6 vs. 22.8 months; p < 0.001). Conclusions: In this retrospective observational study, weekly cisplatin and 5-FU demonstrated comparable efficacy to the standard regimen, with potential advantages in reducing recurrence and mortality. This modified approach may be a viable alternative for maintaining oncologic outcomes while minimizing the burden on healthcare systems during pandemic conditions, although prospective validation is needed. Full article

Background: The aim was to explore the association between coping strategies (CSs) and health-related quality of life (HRQoL) in breast cancer (BC) survivors and to analyze the role of relevant sociodemographic and clinical variables. Methods: A cross-sectional study involving 305 women under follow-up for surgically treated BC in Spain. CSs were measured using the Brief Coping Orientation to Problems Experienced Scale and the HRQoL with the Short-Form Health Survey (SF-12). Results: The mean age at BC diagnosis for participants was 57.4 years, with 60.3% of diagnoses at the local stage. Most frequent complementary treatments were radiotherapy (53.4%) and chemotherapy (33.1%). Adaptative CS scores were positively associated both with higher physical HRQoL (adjusted regression coefficient: 2.19; 95% confidence interval: 0.11; 4.27, p-value: 0.039) and mental HRQoL scores (coef.: 2.65: 95%CI: 0.25; 5.04, p-value: 0.030). Maladaptive CS scores were inversely associated with mental HRQoL scores (coef.: −3.92; 95%CI: −6.62; −1.22, p-value: 0.005). The effects were stronger among women with a favorable BC prognosis. Conclusions: Adaptive CSs positively affected the physical and mental HRQoL, while maladaptive CSs negatively affected the mental HRQoL. Therefore, psychosocial interventions that promote adaptive CSs and avoid maladaptive ones could improve the well-being of women with a favorable BC prognosis. Full article

Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments—including chemotherapy, radiotherapy, immunotherapy, and surgery—are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In contrast, peptide-based therapeutics offer a paradigm shift, combining high tumour-targeting precision with minimal off-target effects. Their low immunogenicity, multi-pathway modulation capabilities, and adaptability for diagnostics and therapy make them ideal candidates for advancing oncology care. Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., ¹⁸F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and ¹⁷⁷Lu-FAP-2286 integrating imaging and radiotherapy). Despite their promise, peptides face challenges like metabolic instability and short half-lives. Recent advances in structural engineering (e.g., cyclization and D-amino acid incorporation) and delivery systems (e.g., nanoparticles and PEGylation) have significantly enhanced their clinical potential. This review highlights peptide-based agents in development, showcasing their ability to improve early cancer detection, reduce metastasis, and enhance therapeutic efficacy with fewer adverse effects. Examples like CLP002 underscore their role in personalised medicine. By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology. Full article

Radiation therapy, a highly effective cancer treatment that targets cancer cells, may produce challenging side effects, including radiation-induced skin tissue injuries. The wound healing process involves complex cellular responses, with key phases including hemostasis, inflammation, proliferation, and remodeling. However, radiation-induced injuries disrupt this process, resulting in delayed healing, excessive scarring, and compromised tissue integrity. This review explores innovative approaches related to wound healing in post-radiotherapy defects, focusing on the integration of adipose-derived stem cells (ADSCs) in protein/polysaccharide bioengineered scaffolds. Such scaffolds, like hydrogels, sponges, or 3D-printed/bioprinted materials, provide a biocompatible and biomimetic environment that supports cell-to-cell and cell-to-matrix interactions. Various proteins and polysaccharides are discussed for beneficial properties and limitations, and their compatibility with ADSCs in wound healing applications. The potential of ADSCs-polymeric scaffold combinations in radiation-induced wound healing is investigated, alongside the mechanisms of cell proliferation, inflammation reduction, angiogenesis promotion, collagen formation, integrin binding, growth factor signaling, and activation of signaling pathways. New strategies to improve the therapeutic efficacy of ADSCs by integration in adaptive polymeric materials and designed scaffolds are highlighted, providing solutions for radiation-induced wounded skin, personalized care, faster tissue regeneration, and, ultimately, enhanced quality of the patients’ lives. 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: Non-ablative stereotactic body radiation therapy (SBRT) is commonly employed for locally advanced pancreatic cancer (LAPC) using computed tomography-guided radiotherapy (CTgRT) without online adaptive radiation therapy (oART). The safe delivery of ablative SBRT has been demonstrated using stereotactic magnetic resonance-guided online adaptive radiation therapy (SMART). We performed an in silico comparison of non-adapted CTgRT versus SMART to better understand the potential benefit of oART for ablative pancreatic SBRT. Methods: We retrospectively evaluated original and daily adapted SMART plans that were previously delivered for 20 consecutive LAPC cases (120 total plans across all patients) treated on a 0.35 T MR-linac prescribed to 50 Gy (gross disease) and 33 Gy (elective sites) simultaneously in five fractions. Six comparative CTgRT plans for each patient (one original, five daily treatment) were retrospectively generated with the same prescribed dose and planning parameters as the SMART plans assuming no oART availability. The impact of daily anatomic changes on CTgRT and SMART plans without oART was evaluated across each treatment day MRI scan acquired for SMART. Results: Ninety percent of cases involved the pancreatic head. No statistically significant differences were seen between CTgRT and SMART with respect to target coverage. Nearly all (96%) fractions planned on either CT or MRI platforms exceeded at least one GI organ at risk (OAR) constraint without oART. Significant differences favoring SMART over non-adaptive CTgRT were observed for the duodenum V35 Gy ≤ 0.5 cc (34.2 vs. 41.9 Gy, p = 0.0035) and duodenum V40 Gy ≤ 0.03 cc (37 vs. 52.5 Gy, p = 0.0006) constraints. Stomach V40 Gy trended towards significance favoring SMART (37 vs. 40.3 Gy, p = 0.057) while no significant differences were seen. Conclusions: This is the first study that quantifies the frequency and extent of GI OAR constraint violations that would occur during ablative five-fraction SBRT using SMART vs. CTgRT. GI OAR constraint violations are expected for most fractions without oART whereas all constraints can be achieved with oART. As such, these data suggest that oART should be required for ablative five-fraction pancreatic SBRT. Full article