Efficacy Of Radiotherapy Research Articles

Non-coding RNAs modulation in breast cancer radioresponse: mechanisms and therapeutic implications.

Breast cancer is the most frequent type of cancer in women, with significant incidence and fatality rates. Radiation therapy is an important therapeutic option for breast cancer patients. However, tumor cells' resistance to radiation can limit therapy efficacy, resulting in recurrence and death. Non-coding RNAs (ncRNAs) are aclass of small RNA molecules that do not translate into proteins but can affect the translation of target mRNA. Several investigations on breast cancer have demonstrated abnormal expression of ncRNAs in response to radiation. Non-coding RNAs are essential in controlling numerous processes such as DNA damage response, cancer stem cell pathways, cell cycle regulation, cell death, and inflammation. Dysregulation of ncRNAs after irradiation influences radiosensitivity or radioresistance of breast cancer cells. Understanding the molecular mechanisms underlying Radiation response can lead to innovative treatment ways to reduce breast cancer radioresistance and increase radiotherapy's efficacy. This review summarizes current research on ncRNA dysregulation following irradiation and analyzes ncRNAs' function and mechanism in modifying breast cancer cell radiosensitivity and radioresistance.

SPIN1 accelerates tumorigenesis and confers radioresistance in non-small cell lung cancer by orchestrating the FOXO3a/FOXM1 axis.

Despite the importance of radiation therapy as a nonsurgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern because of poor patient response and outcomes. Therefore, it is crucial to identify novel targets to increase the effectiveness of radiotherapy and investigate the mechanisms underlying radioresistance. Previously, we demonstrated that Spindlin 1 (SPIN1) was related to tumour initiation and progression. In this study, we found that SPIN1 expression was higher in NSCLC tissues and cell lines than in the corresponding controls. SPIN1 overexpression in NSCLC patients was closely correlated with disease progression and poor prognosis. Functionally, SPIN1 depletion inhibited cell proliferation, decreased the percentage of cells in the G2/M phase and suppressed cell migration and invasion. Moreover, SPIN1 knockdown decreased the clonogenic capacity, impaired double-strand break (DSB) repair and increased NSCLC radiosensitivity. Mechanistically, forkhead box M1 (FOXM1) was identified as a key downstream effector of SPIN1 in NSCLC cells. Furthermore, SPIN1 was found to facilitate MDM2-mediated FOXO3a ubiquitination and degradation, leading to FOXM1 upregulation. Moreover, restoration of FOXM1 expression markedly abolished the inhibitory effects and increased radiosensitivity induced by SPIN1 depletion. These results indicate that the SPIN1-MDM2-FOXO3a/FOXM1 signalling axis is essential for NSCLC progression and radioresistance and could serve as a therapeutic target for increasing radiotherapy efficacy.

Effects of a novel HDAC6-selective inhibitor's radiosensitization on cancer cells.

The radiation sensitivity of tumor cells is a critical determinant of their therapeutic response to radiotherapy. Histone deacetylase 6 (HDAC6), beyond its known role in modulating tubulin acetylation and influencing cell motility, is also involved in the DNA damage response, potentially enhancing tumor cell radiosensitivity. Targeted HDAC6 inhibitors have shown substantial promise in preclinical studies aimed at increasing radiosensitivity and inhibiting cellular migration. A new HDAC inhibitor, named OXHA, was designed by substituting the phenyl cap of SAHA with an N,5-diphenyloxazole-2-carboxamide group. The inhibitory activity of OXHA was evaluated via in vitro enzymatic assays. Its effects on tumor cell migration and radiosensitization potential were assessed using scratch wound healing assays, micronucleus formation, and clonogenic survival assays. Enzymatic assays confirmed OXHA's selective inhibition of HDAC6. Compared to SAHA, OXHA significantly increased α-tubulin acetylation while minimally impacting histone H3 acetylation, indicating a high selectivity for HDAC6. In combination with X-ray irradiation, OXHA markedly impaired wound healing in A549 and HepG2 cells, enhanced micronucleus formation, and reduced clonogenic survival across multiple tumor lines. OXHA exhibits potent and selective HDAC6 inhibition, effectively impeding tumor cell migration and enhancing radiosensitivity across multiple cell lines. These findings suggest that OXHA has strong potential as a therapeutic strategy to improve radiotherapy efficacy.

Efficacy of palliative hemostatic radiotherapy for tumor bleeding and pain relief in locally advanced pelvic gynecological malignancies.

The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains atherapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy. We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief. In total, 40patients with amedian planning target volume of 804 cm3 were treated with amedian total dose of 39 Gy in 13fractions, resulting in 6‑month and 1‑year local control rates of 66.9 and 60.8%, respectively. No higher-grade (>gradeIII) acute RT-induced toxicity appeared. Complete cessation of bleeding was achieved in 80.0% of all patients after amedian of 16days and pain relief was documented in 60.9% at first follow-up. 37.5% of the women required ablood transfusion and 25% an additional tamponade with local hemostatic agents. Successful stopping of bleeding was significantly less frequent in patients receiving anticoagulation concurrently with radiation and in the case of infield re-irradiation. Patients with ahigher total RT dose had cessation of bleeding significantly more often, with acut-off value of at least EQD2 (α/β = 10) = 36 Gy. The applied RT technique and planning target volume had no significant influence on the occurrence of bleeding cessation. Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in tumor bleeding and pain relief.

Long-term outcomes and prognostic factors of short-course radiotherapy (SCRT) in rectal cancer: a monocentric retrospective study.

To evaluate efficacy and tolerance of short-course radiotherapy (SCRT) prior to possible chemotherapy (CHT) and surgery in 64 patients with locally advanced rectal cancer, in terms of acute and early late toxicity and survival outcomes with prognostic factors. Sixty-four patients affected by rectal tumor were treated from 2008 to 2023 radiation therapy, with a total dose of 25Gy in 5 fractions. The Kaplan-Meier method was used to estimate the rates of overall survival (OS), cancer specific survival (CSS), local control (LC), disease free survival (DFS) and metastasis free survival (MFS). Univariate analysis for prognostic factors was performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios. Toxicity assessment has been considered in acute and in early late for gastrointestinal (GI), genitourinary (GU) districts. Median follow-up was 49.6months. The median OS was 65months with 1-year, 2-year and 5-year OS at 90.6%, 77.7% and 60% respectively. CSS at the 1-year, 2-year and 5-year was 98.3%, 96.2% and 86.2% respectively. LC at 1-year, 2-year and 5-year was 93.4%, 89.4% and 87.2% respectively. DFS at the 1-year, 2-year and 5-year was 93.4%, 89% and 87% respectively. The status of lymph nodes at diagnosis was a prognostic factor in term of LC and DFS. Acute GI toxicity was G1 in 10 (15.6%) patients. Five (7.8%) patients had a G1 acute GU toxicity. Fifteen (23.4%) patients developed chronic GI toxicities. SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

RADT-08. THIRD RECURRENT WHO 1 SPINAL MENINGIOMAS. CASE SERIES AND CLINICAL OUTCOMES FOLLOWING SURGERY OR DEFINITIVE RADIOTHERAPY

Abstract INTRODUCTION Spinal meningiomas (SM) account for approximately 1.2–12.7% of all meningiomas and 25% of spinal cord tumors. Most are benign (WHO grade 1), but a small percentage are atypical (WHO grade 2) or anaplastic (WHO grade 3). These tumors are typically solitary and non-invasive with low recurrence rates post-surgery. This study aims to compare the efficacy of definitive radiotherapy (RT) versus third surgery for recurrent SM WHO grade 1, focusing on local control, progression-free survival (PFS), and toxicity. METHODS A retrospective review approved by the Institutional Review Board included patients diagnosed with recurrent SM WHO grade 1 who underwent second surgery between 2008-2020. Patients who received radiation after the first surgery or upgraded to WHO grade 2 or 3 were excluded. Data on demographics, tumor characteristics, surgical techniques, and radiation therapy details were analyzed using descriptive and inferential statistics. RESULTS The study included 48 cases of third progression SM WHO grade 1. The median age was 53 years, and 70.8% were female. Tumor locations were primarily thoracic (75%). There was no significant difference in PFS between the third surgery and RT groups, with 36-month PFS rates of 77.4% and 76.4%, respectively. RT-related toxicities were manageable, and neurological improvements were noted in both groups, with more pronounced improvements in the surgical group. RT showed better pain control outcomes. CONCLUSION Both definitive RT and third surgery are effective for managing recurrent SM WHO grade 1, with comparable PFS. RT is a viable alternative, especially for high-risk surgical patients, providing effective pain control and manageable toxicities. Further studies with larger cohorts and longer follow-ups are recommended to validate these findings and refine treatment protocols for recurrent SM, ultimately improving patient outcomes and quality of life.

NCOG-49. EFFICACY OF POSTOPERATIVE RADIOTHERAPY AFTER GROSS TOTAL RESECTION FOR INTRACRANIAL SOLITARY FIBROUS TUMORS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND The efficacy of postoperative radiotherapy (PORT) after gross total resection (GTR) for intracranial solitary fibrous tumors (SFT) remains unclear as previous studies yielded inconsistent results. Therefore, this study aimed to clarify this uncertainty using a comprehensive meta-analysis. By evaluating and synthesizing data from relevant studies, we sought to investigate the role of PORT, as compared with surgery alone, in survival outcomes after GTR of intracranial SFT. METHODS We conducted a systematic literature search, adhering to PRISMA guidelines, using Medline, Embase, and the Cochrane Library to identify relevant literature. The outcomes of interest included progression-free survival (PFS), overall survival (OS), and metastasis-free survival (MFS) at 3, 5, and 10 years, respectively. Differences between the two cohorts (GTR+PORT vs. GTR only) were estimated by calculating the hazard ratios. Results. Twelve studies, including data from 419 patients (PORT, n = 225 vs. surgery only, n = 194), were selected for meta-analysis. Pooled hazard ratios revealed that the PORT cohort showed sustained superiority in both PFS and OS over the surgery-only cohort after GTR of the tumor. These results were consistent with those of a subgroup analysis that focused on grade 2 and 3 intracranial SFT. However, no significant improvement was observed in MFS with PORT addition. Conclusion. The present study underscores the importance of PORT in enhancing the PFS and OS of patients with intracranial SFT after GTR. These findings suggest that PORT should be considered an effective treatment strategy for all patients with intracranial SFT, irrespective of the extent of resection.

DDDR-46. TARGETING TRANSGLUTAMINASE 2 (TGM2) ENHANCES SENSITIVITY OF GLIOBLASTOMA CELL LINES TO RADIOTHERAPY AND TEMOZOLOMIDE

Abstract Glioblastoma (GBM), the most aggressive and common primary brain tumor in adults, remains highly resistant to conventional therapeutics, including radiation therapy (RT), largely due to its molecular heterogeneity. Few biomarkers have been identified that successfully guide or predict treatment response. Transglutaminase 2 (TGM2), a ubiquitous multifunctional enzyme involved in numerous signal transduction pathways related to tumorigenesis, has recently been suggested to drive chemoradioresistance. Here, we investigate the effects of disrupting TGM2 by pharmacologic inhibition or CRISPR knockout (TGM2-KO) on GBM cell’s response to RT and Temozolomide (TMZ) chemotherapy. Using western blotting and clonogenic assays, we show that the allosteric TGM2 inhibitor, GK921, stabilizes p53 expression and impedes reproductive ability at IC50 and IC25 concentrations. TGM2-KO and GK921 (at IC10 and lower) sensitized GBM cell lines to RT with almost equivalent efficacy, resulting in a 2- to 3-fold suppression of clonal expansion compared to scramble controls or irradiation alone. We also demonstrate increased sensitivity of GBM cell lines to TMZ upon inhibition of TGM2 by GK921. Our findings indicate that the use of TGM2 inhibitors, such as GK921, could enhance the efficacy of RT and the potency of TMZ, positioning TGM2 as a promising therapeutic target that may improve standard treatment of GBM cells expressing TGM2.

Enhancing low-dose radiotherapy efficacy with PARP inhibitors via FBL-mediated oxidative stress response in colorectal cancer.

The effectiveness of radiotherapy in colorectal cancer (CRC) relies on its ability to induce cell death via the generation of reactive oxygen species (ROS). However, genes responsible for mitigating oxidative stress can impede radiotherapy's efficacy. In this study, we elucidate a significant association between the nucleolar protein Fibrillarin (FBL) and the oxidative stress response in CRC tumors. Our findings reveal elevated expression of FBL in colorectal cancer, which positively correlates with oxidative stress levels. Mechanistically, FBL demonstrates direct accumulation at DNA damage sites under the regulation of PARP1. Specifically, the N-terminal GAR domain of FBL is susceptible to PARylation by PARP1, enabling FBL to recognize PARylated proteins. The accumulation of damaged FBL plays a pivotal role in facilitating short-patched base excision repair by recruiting Ligase III and disassociating PCNA and FEN1. Moreover, tumors with heightened FBL expression exhibit reduced DNA damage levels but increased sensitivity to combined low-dose radiotherapy and olaparib treatment. This underscores the potential of leveraging PARP inhibitors to augment radiotherapy sensitivity in CRC cases characterized by elevated FBL expression, offering a promising therapeutic avenue.

Magnetic resonance imaging-guided single-fraction preoperative radiotherapy for early-stage breast cancer (the RICE trial): feasibility study

BackgroundOver the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer.MethodsThe RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac.The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI.ConclusionThe RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.

Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells

Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data from esophageal squamous cell carcinoma (ESCC) samples. Radioresistant ESCC cell lines were generated to explore the functional role of CCNG1. Various techniques, including gene knockdown, flow cytometry, and apoptosis assays, were utilized to evaluate alterations in radiosensitivity, cell cycle progression, and cell survival in response to CCNG1 modulation. Elevated CCNG1 expression was associated with poor clinical outcomes in ESCC patients and contributed to various malignant phenotypes in ESCC cells. In radioresistant ESCC cell lines, CCNG1 knockdown markedly increased radiosensitivity, as demonstrated by enhanced G2/M phase arrest and apoptosis following radiation exposure. CellChat analysis indicated a correlation between CCNG1 and the Wnt/β-catenin signaling pathway, while western blot (WB) analysis confirmed that CCNG1 functions as a downstream effector of Wnt/β-catenin. Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes.

Efficacy and safety of tyrosine kinase inhibitors with thoracic radiotherapy for patients with oncogene-mutated non-small cell lung cancer: a meta-analysis.

Tyrosine Kinase Inhibitors (TKIs) is an important therapy for patients with oncogene-mutated Non-Small Cell Lung Cancer (NSCLC). However, acquired resistance remains a major challenge. The efficacy of TKIs plus thoracic radiotherapy (RT) in oncogene-mutated NSCLC patients is uncertain. Therefore, we performed a meta-analysis to comprehensively evaluate the efficacy and safety of thoracic RT plus TKIs in oncogene-mutated NSCLC patients. The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane Library. Studies comparing the efficacy and safety of TKIs plus RT with TKIs alone in oncogene-mutated NSCLC patients were included in this analysis. Outcomes were median progression-free survival (mPFS), median overall survival (mOS), and incidence of adverse events (AEs). This analysis performed a subgroup analysis of the efficacy of first-line TKIs in combination with RT. This meta-analysis included 12 studies with 2936 patients (n = 823 patients with TKIs plus thoracic RT, n = 2113 patients with TKIs alone). The results showed that patients who received treatment with TKIs plus thoracic RT were associated with superior mPFS and mOS than those who were treated with TKIs alone (hazard ratio [HR]: 0.42, 95% CI 0.30-0.59, p < 0.00001; HR: 0.56, 95% CI 0.41-0.70, p < 0.00001, respectively). Subgroup analyses showed that TKIs plus thoracic RT as first-line treatment was associated with better mPFS and OS (HR: 0.37, 95% CI 0.26-0.52, p < 0.00001; HR: 0.47, 95% CI 0.31-0.70, p = 0.0002, respectively). Although the combination of TKIs with thoracic RT was associated with an increased risk of total AEs (odds ratio [OR]: 1.17, 95% CI 1.06-1.29, P = 0.002), there was no significant difference in serious AEs (grade ≥ 3) (OR: 1.06, 95% CI 0.58-1.92, P = 0.86). The most frequently occurring radiation-related AEs were radiation pneumonitis, radiation esophagitis, and radiation dermatitis, with overall rates of 41.3%, 15.4%, and 11.1%, respectively. The incidence of severe radiation pneumonitis and radiation esophagitis was 4.5% and 6.2%, respectively. In comparison to TKIs alone, TKIs plus thoracic RT are associated with survival benefits, especially as a first-line treatment option. Although TKIs plus thoracic RT may increase the risk of total AEs, it did not increase the risk of severe AEs. Therefore, TKIs plus thoracic RT may be a promising therapeutic regimen for oncogene-mutated NSCLC patients.

Epoxymicheliolide Reduces Radiation-Induced Senescence and Extracellular Matrix Formation by Disrupting NF-κB and TGF-β/SMAD Pathways in Lung Cancer.

Lung cancer is a major cause of cancer-related mortality, and radiotherapy is often limited by tumor resistance and side effects. This study explores whether epoxymicheliolide (ECL), a compound from feverfew, can enhance radiotherapy efficacy in lung cancer. We tested ECL on A549 and PC-9 lung cancer cell lines to evaluate its effect on x-ray irradiation. We measured apoptosis, NF-κB pathway inhibition, TGF-β secretion reduction, and epithelial-mesenchymal transition suppression. Invivo, C57BL/6 mice with lung tumors received ECL and radiotherapy. ECL enhanced the antiproliferative effects of x-ray irradiation, induced apoptosis in senescent cells, inhibited the NF-κB pathway, reduced TGF-β levels, and suppressed epithelial-mesenchymal transition. ECL also inhibited tumor growth and improved survival in mice. ECL is a promising adjunct to radiotherapy for lung cancer, improving treatment outcomes by targeting multiple tumor progression mechanisms. It offers potential for enhanced management of lung cancer.

Hyperthermia reduces cancer cell invasion and combats chemoresistance and immune evasion in human bladder cancer.

Bladder cancer (BC) is a common malignancy and its most prevalent type is urothelial carcinoma, which accounts for ~90% of all cases of BC. The current treatment options for BC are limited, which necessitates the development of alternative treatment strategies. Hyperthermia (HT), as an adjuvant cancer therapy, is known to improve the efficacy of chemotherapy or radiotherapy. The present study aimed to investigate the anti‑tumor effects of HT on cell survival, invasiveness, chemoresistance and immune evasion in human BC cell lines (5637, T24 and UMUC3). Calcein AM staining was performed to analyze the cytotoxicity of natural killer (NK) cells against human BC cells following HT treatment. Cell migration and invasion affected by HT were analyzed using Transwell migration and invasion assays. It was found that HT inhibited the proliferation of BC cells by downregulating the phosphorylation of protein kinase B. Moreover, HT effectively enhanced the sensitivity of BC cells to the chemotherapy drug cisplatin (DDP) and reduced the chemoresistance of DDP‑resistant cells by downregulating the expression of cadherin‑11. It was further demonstrated that HT inhibited the migration and invasion of BC cells and enhanced the cytotoxic effects of NK cells. In summary, the antineoplastic effects of HT were mediated through three main mechanisms: Enhancement of the chemosensitivity of BC cells and mitigation of DDP‑induced chemoresistance, suppression of the invasive potential of BC cells and reinforcement of the anticancer response of NK cells. Thus, HT appears to be a promising adjunctive therapy for human BC.

Recent Advances in Silica-Based Nanomaterials for Enhanced Tumor Imaging and Therapy.

Cancer remains a formidable challenge, inflicting profound physical, psychological, and financial burdens on patients. In this context, silica-based nanomaterials have garnered significant attention for their potential in tumor imaging and therapy owing to their exceptional properties, such as biocompatibility, customizable porosity, and versatile functionalization capabilities. This review meticulously examines the latest advancements in the application of silica-based nanomaterials for tumor imaging and therapy. It underscores their potential in enhancing various cancer imaging modalities, including fluorescence imaging, magnetic resonance imaging, computed tomography, positron emission tomography, ultrasound imaging, and multimodal imaging approaches. Moreover, the review delves into their therapeutic efficacy in chemotherapy, radiotherapy, phototherapy, immunotherapy, gas therapy, sonodynamic therapy, chemodynamic therapy, starvation therapy, and gene therapy. Critical evaluations of the biosafety profiles and degradation pathways of these nanomaterials within biological environments are also presented. By discussing the current challenges and prospects, this review aims to provide a nuanced perspective on the clinical translation of silica-based nanomaterials, thereby highlighting their promise in revolutionizing cancer diagnostics, enabling real-time monitoring of therapeutic responses, and advancing personalized medicine.

Radiotherapy efficacy and prognostic factors in hepatocellular carcinoma patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis

Radiotherapy efficacy and prognostic factors in hepatocellular carcinoma patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis

Impact of Myc-Altered Pathology on Radiotherapy Efficacy Among Patients with Relapsed/Refractory Large-B Cell Lymphoma: A Collaborative Study by XXX: Impact of double hit pathology on RT efficacy.

Presence of MYC and BCL2 translocations (i.e. double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. Patients with LBCL that received their first course of RT for relapsed/refractory (r/r) disease between 2008-2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per WHO (5th edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. 383 patients (102 DHL, 281 non-DHL, 44% curative) were treated to 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post stem cell transplant. Median biological equivalent dose (alpha/beta 10) was 28 Gy (range 3.2-60.0) for palliative and 46.9 Gy (range 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI 1.05-3.67,p=.03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). Relapsed/refractory LBCL remains radioresponsive with 60-80% response rate to RT. While DHL pathology does not appear to influence RT response, its presence is associated with higher rates of local recurrence, suggesting it may be more radioresistant.

Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial.

Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival. We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle. Patients were enrolled at 20 academic institutions in Australia, Canada, Italy, and the USA. Patients were randomly assigned to preoperative radiotherapy then surgery (control group) or preoperative pembrolizumab with radiotherapy (initiated 1-14 days after the first dose of pembrolizumab) then surgery and postoperative pembrolizumab (experimental group). Pembrolizumab (200 mg intravenously every 3 weeks) was administered as three neoadjuvant cycles (before, during, and after radiotherapy) and 14 or less adjuvant cycles. Primary endpoint was disease-free survival. This study is registered with ClincialTrials.gov (NCT03092323). Between Nov 18, 2017, and Nov 14, 2023, 143 participants were randomly assigned to treatment. A modified intention-to-treat analysis of 127 patients with median follow-up of 43 months showed that the experimental group (n=64) had significantly longer disease-free survival than the control group (n=63; log-rank one-sided p=0·035; hazard ratio [HR] 0·61; 90% CI 0·39-0·96). The 2-year disease-free survival increased by 15% with addition of pembrolizumab: 52% (90% CI 42-64) and 67% (90% CI 58-78) for the control and experimental groups, respectively. Disease-free survival was similarly improved with pembrolizumab for the intention-to-treat patient population (HR 0·61 [90% CI 0·39-0·95]). Grade 3 or higher adverse events occurred more frequently in the experimental group (56%) than the control group (31%). Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic sarcoma and pleomorphic or dedifferentiated liposarcoma of the extremity, which establishes a promising new treatment option for these patients. Stand Up to Cancer and Merck Sharp & Dohme.

Three-dimensional conformal radiation therapy with concurrent chemotherapy for stage III non-small cell lung cancer: protocol for a systematic review and meta-analysis

IntroductionLung cancer continues to be a common form of cancer worldwide and a primary contributor to cancer-related fatalities. Non-small cell lung cancer (NSCLC) is the most prevalent form, making up...

Primary orbital mesenchymal chondrosarcoma: clinicopathological characteristics and prognostic prediction

PurposeThis study aimed to analyze the clinicopathological characteristics of a rare malignant tumour, primary orbital mesenchymal chondrosarcoma (MCS), and identify the risk factors influencing its prognosis. MethodsA total of 15 patients with histologically confirmed primary orbital MCS were enrolled between April 2013 and October 2022. The relationships between clinicopathological features and outcomes, including recurrence and survival were analyzed. ResultsDuring the follow-up period, 9 patients (60%) experienced disease relapse, and 7 patients (46.7%) succumbed to the disease. Immunohistochemical analysis showed positive rates for SMA, CD-99, S-100, vimentin, and Bcl-2 at 60%, 60%, 53.3%, 100%, and 93.3%, respectively. The Ki67 index was positively associated with the recurrence and mortality rates. ConclusionOur study suggested that the Ki67 index could be a vital prognostic factor for MCS. Further follow-up studies are required to assess the efficacy of chemotherapy and radiotherapy in improving patient outcomes.