Combination Of Radiotherapy Research Articles

Clinical characteristics and prognosis of brain metastasis in locally advanced rectal cancer

Objective: To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC). Methods: The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan-Meier method was used for survival analysis. Results: We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4-112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2-21.8) months. Conclusion: The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Efficacy and safety of bevacizumab combined with temozolomide in the treatment of glioma a systematic review and meta-analysis of clinical trials.

Glioma is the most common malignant brain tumor in neurosurgery. Bevacizumab (BEV) is a monoclonal antibody that inhibits tumors by inhibiting vascular endothelial growth factor and reducing tumor angiogenesis. To evaluate the efficacy and safety of BEV combined with temozolomide (TMZ) in glioma, we performed a meta-analysis. PubMed, Embase, The Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing survival outcomes between TMZ combined with BEV and TMZ alone as well as cohort studies were included in our study. The primary outcome measures analyzed were overall survival (OS) and progression-free survival (PFS). A total of six randomized controlled trials and four cohort studies with a total of 2515 patients were included in our meta-analysis. The results of meta-analysis suggested that there were no significant improvements in overall survival, but the combination of TMZ and BEV prolonged progression-free survival, improved overall response rate (ORR), and increased the incidence of some adverse reactions, compared with TMZ alone. Subgroup analysis suggested sex, recursive partitioning analysis (RPA) grade, MGMT gene status and radiotherapy combination did not affect the improvement of OS with the combination of the two drugs, and RPA grade did not affect the improvement of PFS with the combination of the two drugs. The combination of TMZ and BEV can improve PFS as well as ORR in patients and has no benefit on OS. At the same time, the adverse reactions during the combination of the two drugs were acceptable.

In-depth exploration of the focus issues of TKI combined with radiotherapy for EGFR-mutant lung adenocarcinoma patients with brain metastasis: a systematic analysis based on literature metrology, meta-analysis, and real-world observational data

BackgroundThere is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate.MethodsWe initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs).Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021.ResultsThe bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69–0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61–0.82; P < 0.001) of the combination therapy were significantly prolonged. Finally, 168 EGFR-mutated BM advanced LAC patients in the real world were verified, and the median iPFS of the combination therapy (n = 88 and EGFR-TKIs alone (n = 80) were 16.0 and 9.0 months, respectively, (P < 0.001). The median OS was 29.0 and 27.0 months, respectively, with no dramatic difference (P = 0.188).ConclusionsResearch on EGFR-mutant LAC brain metastasis has turned towards exploring optimal treatment strategies for this condition. Our meta-analysis and real-world data analysis consistently demonstrate that combination therapy offers a substantial improvement in patient survival compared to EGFR-TKI monotherapy. Notably, among patients undergoing salvage radiotherapy (RT), our subgroup analysis reveals that those initially treated with third-generation TKIs experience more significant benefits than those treated with first- or second-generation TKIs.

Genomic biomarkers predict response to combined ATR inhibition and radiotherapy.

For decades, chemoradiosensitization with checkpoint kinase inhibitors has been proposed but largely unexplored. A recent study reports the novel ATR kinase inhibitor, RP-3500, synergizes with radiation to control Atm-/- tumors in vivo. RP-3500 did not radiosensitize wild-type or Brca-1 deficient tumors, highlighting the need for a genotype-tailored approach.

IN VIVO APPLICATION OF LOCAL DRUG DELIVERY SYSTEMS AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL/TERATOID/RHABOID TUMOURS

Abstract AIMS Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas, but to the best of our knowledge, not for the treatment of paediatric cerebellar tumours. Here we report the applicability of an LDDS against medulloblastoma group 3 (MB3) and atypical teratoid/rhaboid tumours (AT/RT), both of which are associated with poor prognoses. METHOD We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)- poly(ethyleneglycol) (PECE) hydrogel, which has been investigated with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and AT/RT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and AT/RT intracranial xenograft surgical resection models. RESULTS The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement, including long-term survivors. Against AT/RT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm. CONCLUSION The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For AT/RT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection - Update 1.

The standard of care for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment, however, the predictive significance of most of the targets for treatment in systemic cancer are less well established in central nervous system (CNS) tumors . In 2023 the EANO Guideline Committee presented evidence based recommendations for rational testing of molecular targets for targeted treatments. From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit; despite regulatory approvals for tumor agnostic treatment of NTRK gene fusions and high Tumor Mutational Burden (TMB) for patients with adult brain tumors, the evidence of clinical benefit for patients was still limited . This guideline has a modular structure, allowing regular updating of individual sections and adding new ones. The present version (Update 1) presents a review of the rationale of testing for PTEN, H3F3A, MTAP, RET and IDH, and presents an update of the text on TMB high and mismatch repair deficiency. It also presents an overview of therapeutic yield of routine next generation sequencing for mutations and fusion detection. The supplement accompanying this version contains the in depth review of all targets, whereas in the main manuscript the final recommendations of the revised and new targets are presented. Updates will be made on a regular basis.

A combination of lymphatic drug delivery of anti-CTLA-4 antibody and local radiotherapy for solid-tumor treatment.

The combination of radiotherapy and immunotherapy is a promising approach that has been shown in clinical trials to improve significantly survival and response rates compared with monotherapy against solid tumor. Since anti-CTLA-4 antibodies block immunosuppressive signals mainly in the lymph nodes (LNs), efficient drug delivery to the lymphatic system is desirable. However, the immune checkpoint inhibitors, especially anti-CTLA-4 are currently administered intravenously (i.v.), resulting in limited efficacy in controlling solid tumor and inhibiting metastases, and the method of administration has not been optimized. Here, we show that a combination of local radiotherapy and administration of anti-CTLA-4 antibodies using a lymphatic drug delivery system (LDDS) suppresses solid tumor and metastases. We compared the efficacy of LDDS-based immunotherapy or radioimmunotherapy with i.v. administration in a solid-tumor model created by subcutaneous inoculation into LN-swollen mice with osteosarcoma cells. Tumor-bearing mice were divided into various groups (no treatment, immunotherapy [i.v. or LDDS], radiotherapy, and radioimmunotherapy [i.v. or LDDS]) and were observed for 28 days. Immunotherapy was administered with a cumulative dose of 10 mg/kg of anti-CTLA-4 monoclonal antibody, and radiotherapy was administered with a cumulative 8 Gy of fractionated X-ray irradiation. For immunotherapy alone, LDDS provided slight tumor growth inhibition but did not inhibit distant metastasis. For radioimmunotherapy, however, tumor growth was delayed and distant metastasis was suppressed compared with radiotherapy alone. In particular, the LDDS group achieved a high tumor-suppressive effect with T cell-mediated immune activity, indicating the efficacy of LDDS in radioimmunotherapy.

7826 The Identification of an Activating ESR1 Mutation in an Aggressive Prolactinoma Enabled the Use of Personalized Treatment

Abstract Disclosure: T. Paes: None. J.B. Mebarak: None. J. C. Magnotto: None. G. A. Stamatiades: None. Y. Kuang: None. C. Paweletz: None. E.R. Laws: None. R.S. Carroll: None. R. Jeselsohn: None. D. R. Mohan: None. A. Marcondes Lerario: None. W. L. Bi: None. D. A. Reardon: None. D. M. Meredith: None. U.B. Kaiser: None. A. Abreu: None. Introduction: Prolactinomas are benign tumors typically treated with dopamine agonists; few progress on medical therapy, through unclear molecular mechanisms. Although the SF3B1 mutation has been identified in one study as a driver of aggressive prolactinomas, in most cases no genetic mutations have been reported. We aimed to identify genetic alterations associated with prolactinomas using a gene panel. Method and Results: Oncopanel, a massively parallel sequencing panel, was performed to identify genomic variants and copy number variation (CNV) in a cohort of 21 patients with prolactinomas. No SF3B1 pathogenic variants were identified in this cohort. A MEN1 mutation was detected in a macroadenoma resistant to dopamine agonist. In a case of an extremely aggressive prolactinoma diagnosed in a 49-year-old woman, a somatic ESR1 [encoding estrogen receptor alpha (ERα)] mutation (ESR1Y537S) was identified in tissue from the patient’s fourth surgery. Using droplet digital PCR (ddPCR), ESR1Y537S was also detected in circulating cell-free DNA. We aimed to investigate whether ESR1Y537S may have driven initial tumor formation, or whether it was acquired as the tumor progressed. To this end, Sanger sequencing and ddPCR analyses of DNA from the first two resected tumors were performed and failed to identify ESR1Y537S. In the CNV analysis, the ESR1-mutated prolactinoma had the highest number of CNVs, compared to the rest of the cohort. Despite efforts to control tumor growth with multiple therapeutic modalities, the mutated prolactinoma had progressively enlarged post-menopausally, with invasion of surrounding structures. ESR1Y537S is a hotspot mutation in metastatic breast cancer. In breast cancer cells, ESR1Y537S activates the ERα independent of ligand binding, resulting in high cell proliferation and conferring resistance to classic hormonal treatment in ER-positive breast cancer. Elacestrant, a second-line ER degrader, increases overall free-survival in patients with resistant breast cancer and ESR1Y537S. Given the lack of response to multimodality therapy, off-label elacestrant was initiated after the third cycle of radiotherapy was completed in the patient with the aggressive prolactinoma. The combination of radiotherapy with this personalized treatment targeting ESR1 activity (elacestrant) was able to control tumor growth and significantly reduce prolactin levels. Conclusion:ESR1 regulates lactotroph differentiation and proliferation, possibly contributing to prolactinoma tumorigenesis. Our data support a role for ESR1Y537S in this prolactinoma’s unusually aggressive behavior in the postmenopausal setting. Molecular profiling revealing the mutation (ESR1Y537S) allowed the patient to receive a targeted therapy which, together with radiotherapy, resulted in a decrease in prolactin levels and a remarkable improvement in disease control. Presentation: 6/2/2024

Iron oxide nanoparticles as potential agents for combined radiotherapy

Background. Iron oxide nanoparticles (NP) represent a promising theranostic platform for combined radiotherapy: the reactivity of iron oxide enhances oxidative stress of tumor cells associated with irradiation while magnetic properties may provide additional feature as controlled delivery.Aim. To study the potency of heparinized iron oxide NP in experimental antitumor therapy.Materials and methods. The synthesis of iron oxide NP was carried out by chemical precipitation followed by magnetic separation, the resulting sol was stabilized with heparin. For each batch of newly synthesized particles, the hydrodynamic diameter was determined, IR spectrometry, X-ray diffraction analysis, and scanning electron microscopy were performed. The MX-7 tumor model of rhabdomyosarcoma chosen for the study was transplanted into female C3HA mice; NP were administered intratumorally or intravenously, once a day, according to the “5–2–5” scheme. Fractional irradiation (1–2 Gy / fraction; 1.3±0.15 Gy / min) was carried out after NP administration.Increasing life expectancy (ILE), the degree of tumor growth inhibition (TGI), a pathomorphological assessment of the lung, liver, spleen and tumor node was carried out for all experimental mice.Results. As a result of the study, it was found that when administered intratumorally, heparinized iron oxide NP are retained inside the tumor, providing a moderate additive effect, compared with isolated radiotherapy in the first week of irradiation (TGI = 40 % (day 6), TFD = 10 Gy, p &lt;0.05), however, with an increase in tumor volume by the end of the second week, the treatment regimen was not more effective than radiotherapy. with a combination of radiotherapy and intravenous administration of NP, the effect was observed within two weeks (TGI = 43 % (day 6), TGI = 29 % (day 14), TFD = 10 Gy; p &lt;0.05; ILE = 54 %, TFD = 20Gy; p &lt;0.05).Conclusion. The studied iron oxide nanopreparation enhanced capacity of radiation therapy to inhibit tumor growth when administered intravenouslyin experimental mice with rhabdomyosarcoma and irradiated subsequently.

PDOC-10 LIMITATIONS IN POST OPERATIVE- ADJUVANT CARE OF PATIENTS WITH BRAIN TUMOURS-A CASE OF SUPRATENTORIAL MEDULLOBLASTOMA IN A PAEDIATRIC PATIENT

Abstract OBJECTIVE To highlight the challenges and limitations in accessing post-operative adjuvant care of patients with brain tumours in Zimbabwe and implications on patient outcomes and to discuss potential strategies to overcome these challenges. METHODS This is a case report on a 6 year old patient with a supratentorial medulloblastoma to demonstrate the challenges encountered on accessing post-operative adjuvant care at a Central hospital in Harare. RESULTS The patient had a near total resection of the tumour done and was managed in the Intensive care unit for 1 week. HE was discharged to the general ward for another week and eventually referred to the paediatric oncologists after a histological diagnosis of a supratentorial medulloblastoma was made. Patient received cycles of chemotherapy but failed to raise money for adjuvant radiotherapy. Patient returned 5 months later with the tumour having recurred. CONCLUSION Limitations in post-operative adjuvant care may have a negative impact on the overall patient outcomes, in this case lack of access to radiotherapy. Medulloblastomas are responsive to radiotherapy and their prognosis improves significantly with a combination of surgical resection and radiotherapy. Addressing these limitations at different levels involving government and non-governmental organizations helps in mitigating inaccessibility of radiotherapy to radio-sensitive brain tumours patients after surgical resection. This case report brings out the urgent need to implement cheaper and sustainable options to address challenges in post-operative adjuvant care in order to get good patient outcomes.

PDOC-12 PEDIATRIC BRAIN TUMOR INCIDENCE, AND TREATMENT MODALITY AT KILIMANJARO CHRISTIAN MEDICAL CENTER

Abstract INTRODUCTION Pediatric brain tumors (PBT) a significant health concern, they are the primary cause of cancer-related deaths among children. PBTs in Low- and Middle-Income Countries are diagnosed late due to insufficient resources. This abstract describes Pediatric Brain tumor incidence and treatment modalities at Kilimanjaro Christian Medical Center (KCMC) Cancer Care Center (CCC), Moshi, Tanzania from December 2016 to March 2024. METHOD Data on pediatric patients treated at the CCC between Dec. 2016 and March 2024, were analyzed. Inclusion criteria were a primary brain tumor and patients aged 0-19 at the time of diagnosis. All patients were previously diagnosed by computer tomography/ magnetic resonance imaging. Variables retrospectively collected from patient’s medical records were: demographic characteristics (age, gender, Place of residence, and insurance status), previous history of malignant diseases, incidence date, and treatment modality. RESULTS Total of 748 cases of pedeatric cancer were diagnosed at CCC. Of all the pediatric cancers diagnosed, brain cancer accounted for 22(2.9%). Out of these cases of brain cancer, 63.6% were males and 36.4% were females.Majority of them came within the Kilimanjaro region. 41% were palliated while 59% had a curative intent at the time of diagnosis, 22.7% died between December 2016 to March 2024.Embryonal tumors were (40.9%) with a breakdown that includes 6 Medulloblastoma and 3 cases of Craniopharyngioma (teratoid/rhabdoid), gliomas (36.4%) with sub-types such as Ependymoma, Anaplastic Astrocytoma, Pilocytic Astrocytoma, Pineocytoma, Stem glioma, and Tectal glioma, unspecified cases (13.6%), and Pineoblastoma were (9.1%). Surgery was used in 40.9% of cases, radiotherapy in 31.8%, and chemotherapy in 72.7%. Chemoradiotherapy was used in 31.8% of cases. 13.6% of cases utilized a combined approach, including chemotherapy, radiotherapy, and surgery. CONCLUSION PBT incidence at KCMC is 2.9%, improving access to screening, accurate diagnosis and treatment modalities are essential in identifying and managing PBT in our setting.

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers

BackgroundImmunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. MethodsWe retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. ResultsA total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74–22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). ConclusionsThe combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.

Immune checkpoint inhibitors with or without radiotherapy in metastatic non‑small cell lung cancer: A meta‑analysis and literature review.

The combination of immune checkpoint inhibitors (ICIs) and radiotherapy has shown promise in the treatment of metastatic non-small cell lung cancer (NSCLC). The present meta-analysis aimed to determine the efficacy and safety of combining radiotherapy (RT) ICIs for the treatment of metastatic NSCLC. PubMed, Google Scholar, the Cochrane Library and Web of Science databases were searched for relevant articles up to February 1, 2023. Post-therapy outcomes such as progression-free survival (PFS), complete response, partial response (PR), progressive disease (PD), stable disease and adverse events (AEs) were analyzed. The meta-analysis was performed using RevMan 5.4 software. A total of seven studies involving 682 patients were included (384 patients who received ICI + RT vs. RT and 298 patients who received ICI + RT vs. ICI alone). No significant difference in PFS was demonstrated between the ICI + RT group and the RT group (heterogeneity: χ2=2.35; df=1; P=0.13; I2=57% and test for overall effect: Z=0.10; P=0.92). Conversely, patients in the ICI alone group had significantly decreased PR rates (heterogeneity: Τ2=0.00; χ2=2.13; df=3; P=0.54; I2=0% and test for overall effect: Z=2.57; P=0.01) compared with patients in the ICI + RT group. The ICI + RT group also had significantly lower rates of PD (heterogeneity: Τ2=0.00; χ2=0.91; df=3; P=0.82; I2=0% and test for overall effect: Z=2.52; P=0.01) compared with the ICI alone group. Safety analysis revealed no significant difference between patients who received ICI + RT and those who received RT in terms of grade 1 or 2 AEs. In conclusion, the combination of ICIs + RT demonstrates promising efficacy and safety for patients with metastatic NSCLC. However, clinical trials that have tested this combination are lacking, which emphasizes the need for further research.

Polyploidy as an outcome of anticancer therapies and a contributing cause of their lack of efficacy

In addition to innate and gained resistance poliploidy of cancer cells is described as a mechanism responsible for lack of response or cancer relapses after initial patient recovery. Formation of these cells is induced by cyto- and genotoxic agents, which trigger endoreduplication, cytokinesis failure, cell fusion or canibalism. These processes lead to amplification of DNA, cell cycle arrest and escape from death. Cancer reinitiation results from depolyploidization by neosis, amitotic and meiotic-like divisions. In this paper we review the known mechanisms, which drive cancer cell transition to poliploidy, major features of these cells and their role in cancer progression. We also depict the current approaches, which target metabolic and signaling pathways that are crucial for survival and functioning of polyploid cells. The combination of chemotherapy and radiotherapy with agents capable of inhibiting or eliminating polyploid cells could substantially improve the success rate and efficacy of anticancer therapies.

Immune checkpoint inhibitors for the treatment of Tiple-negative breast cancer

Recently, the use of immune checkpoint inhibitors (ICIs) on triple negative breast cancer have been a hot research topic. immune checkpoints are vital as they prevent an immune response from being so strong that it kills healthy cells, which is unwanted. When T cell surface proteins bind to partner proteins (immune checkpoint proteins) on other cells, for instance tumor cells, immune checkpoints engage. When the checkpoint and immune checkpoint protein bind together, a signal is released to prevent the cancer from being killed by the immune system. ICIs work by stopping checkpoint proteins from binding with partner proteins, so the “off” signal was not sent, allowing the immune system to kill the cancer cells. In this review we will focus of the effect of ICI monotherapy, ICI with chemotherapy and ICI with radiotherapy. Results showed that ICI monotherapy, combination of ICIs and chemotherapy, and combination of ICI and radiotherapy have greatly improved ORR, PIS, and OS compared to the traditional chemotherapy. The combination therapy have also revealed a higher cost-effectiveness compared to ICI monotherapy.

Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY).

Smart radiotherapy biomaterials (SRBs) include seed and liquid biomaterials designed to be employed as fiducial markers during radiotherapy while also delivering therapeutic drug payloads to enhance treatment outcomes. In this study, we investigate a novel Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY) biomaterial, which can be loaded with immunoadjuvants (anti-CD40 monoclonal antibody or Caflanone (FBL-03G)) at the point of care. The CLARITY biomaterial was investigated in an animal model of pancreatic cancer using C57BL6 mice. Mice were imaged before and at different points of time post-treatment to evaluate the potential of CLARITY biomaterial to provide imaging contrast similar to fiducials. This study also used cadavers to assess CLARITY's potential to provide imaging contrast in humans. Results showed imaging contrast from computed tomography (CT) and magnetic resonance imaging (MRI) modalities for up to 30 days post-treatment, demonstrating potential for use as fiducials. A significant increase in survival (***, p = 0.0006) was observed for mice treated with CLARITY biomaterial loaded with immunoadjuvant for up to 10 weeks post-treatment compared to those without treatment. These initial results demonstrate the potential of CLARITY biomaterial to serve as a smart multifunctional radiotherapy biomaterial and provide the impetus for further development and optimization as a point-of-care technology for combination radiotherapy and immunotherapy.

CD39 inhibitor (POM-1) enhances radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells by promoting apoptosis through the Bax/Bcl-2/Caspase 9/Caspase 3 pathway

CD39 inhibitor (sodium polyoxotungstate, POM-1) has been reported to have antitumor effects. However, the synergistic effect of POM-1 with radiotherapy requires further elucidation. This study aimed to investigate the role and the molecular mechanism of POM-1 in esophageal squamous cell carcinoma (ESCC) radiosensitization. Firstly, the expression of CD39 in ESCC cells and normal esophageal epithelial cells were detected. Then radioresistant ESCC cells (Eca109R and KYSE150R) were constructed and CD39 expression was analyzed. Furthermore, the effect of POM-1 on radiosensitivity for parent cells and radioresistant cells were observed. Then, we analyzed the effect of POM-1 and CD39 siRNA on radiotherapy-induced apoptosis and determined whether POM-1 modulated the radioresistance of ESCC cells depending on the apoptotic signaling pathway. Finally, we validated the synergistic effect of POM-1 combined with radiotherapy in vivo. Our results showed that CD39 was highly expressed in ESCC cells and radioresistant ESCC cells (p < 0.05). POM-1 reduced radioresistance and proliferation of parent cells and radioresistant cells (p < 0.05). Further mechanistic exploration showed that inhibition of CD39 promoted radiation-induced apoptosis (p < 0.05). Bax knockdown reversed the effect of POM-1 on ESCC cells (p < 0.01). Animal experiments also validated that radiotherapy combined with POM-1 enhanced tumor inhibition in vivo (p < 0.05). These results suggested that POM-1 had synergistic effect with radiotherapy by enhancing cell apoptosis through Bax/Bcl-2 signal pathway in ESCC. The combination of POM-1 and radiotherapy is expected to enhance the anti-tumor effect in ESCC.

The effects of the ketogenic diet on cancer treatment: a narrative review.

Despite significant advances in therapy, cancer remains the top cause of death in parts of the globe. For many types of cancer, the typical treatment is a combination of surgery, chemotherapy, and radiotherapy. However, this conventional treatment is not successful on its own. As a consequence, innovative approaches that improve treatment efficacy are urgently needed. The ketogenic diet is a high-fat, moderate protein, and low-carbohydrate diet that appears to sensitize most cancers to conventional therapies by exploiting cancer cells' altered metabolism, making it an effective adjuvant cancer treatment alternative. This diet could decrease glucose metabolism while enhancing lipid metabolism, interfering with the Warburg effect, and inhibiting tumor cell proliferation. The anticancer impact of ketogenic diet has been established in numerous animal trials and clinical investigations on a wide range of tumor types, including glioblastoma, pancreatic cancer, head and neck cancer, breast cancer, invasive rectal cancer, ovarian cancer, and endometrial cancer. In this review, we discussed the various types of ketogenic diets, the mechanism of action for ketogenic diet as a cancer therapy, and the data gathered from continuing preclinical and clinical studies, intending to establish a solid theoretical foundation for future research.

EGFR-Tyrosine Kinase Inhibitor Combined with Radiotherapy in 105 Patients of Lung Adenocarcinoma with Brain Metastasis: A Retrospective Study of Prognostic Factor Analysis

Introduction: This study aimed to retrospectively analyse the response and prognosis factors for patients with lung adenocarcinoma exhibiting brain metastasis and epidermal growth factor receptor (EGFR) mutations, who were treated with a combination of EGFR-tyrosine kinase inhibitor (TKI) and brain radiotherapy (RT). Methods: Clinicopathological data of patients with lung adenocarcinoma were collected from January 2021 to January 2024 at the First Affiliated Hospital of Hebei North University. Statistical analysis was performed using SPSS version 26.0, with significance set at p < 0.05. Results: A total of 105 patients were included. The overall survival (OS) rates at 1, 2, and 3 years were 82.9%, 61.2%, and 33.7%, respectively. The progression-free survival 1 (PFS1) rates at 1, 2, and 3 years were 62.7%, 36.6%, and 22.1%, respectively. The progression-free survival 2 (PFS2) rates at 1, 2, and 3 years were 80.8%, 54.6%, and 31.4%, respectively. The median OS, PFS1, and PFS2 were 29.8, 18.0, and 28.1 months, respectively. Cox multivariate analysis identified gene mutation status and brain radiation dose as independent prognostic factors for OS. For PFS1, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors. Clinical stage, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors for PFS2. Conclusion: The combination of TKIs and brain RT is effective for patients with lung adenocarcinoma with EGFR mutations and brain metastases. Patients with exon 19 Del or exon 21 L858R mutations and brain radiation doses ≥40 Gy exhibit longer OS, PFS1, and PFS2. Additionally, complete remission + partial remission is associated with extended PFS1 and PFS2, while patients in stage IVA show longer PFS2.

Combination of immune checkpoint inhibitors and radiotherapy in locally advanced esophagogastric junction adenocarcinoma: A review

AbstractEsophagogastric adenocarcinoma (EGJ‐AC) poses a significant global health burden, characterized by high incidence rates and poor prognosis. Despite advancements in treatment modalities, including surgery, chemotherapy, and radiation therapy (RT), locally advanced EGJ‐AC management remains challenging. Various preclinical and clinical studies have provided insights into the synergistic effects of combining immune checkpoint inhibitors (ICIs) with RT, further supporting the combination therapy in EGJ‐AC. Immunotherapy, particularly ICIs, has emerged as a promising therapeutic approach in various malignancies, including EGJ‐AC. This narrative review aims to critically examine the rationale behind combining ICIs with standard treatment modalities, including RT or chemoradiotherapy, in the preoperative setting for locally advanced EGJ‐AC. A comprehensive literature search identified eight phase 2 randomized clinical trials evaluating the safety profile and oncologic outcomes of adding ICI agents to neoadjuvant chemoradiotherapy in this population. The results of enrolled trials show that the combination of ICIs with standard treatment modalities is a promising approach for improving survival and pathological response in patients with locally advanced EGJ‐AC. This combination treatment was associated with mostly grade 1–2 immune‐related toxicities, indicating its safety and tolerability. There were higher rates of complete or major pathologic responses compared to historical controls. Further studies, including large‐scale randomized controlled trials, are needed to address remaining questions regarding the efficacy, safety, and long‐term outcomes of combination therapy in this population.