Multimodal Treatment Approach Research Articles

Chronic Thromboembolic Pulmonary Hypertension

Abstract: While the majority of patients have complete resolution of their acute pulmonary embolism (PE) after an adequate course of anticoagulation, some patients remain symptomatic with evidence of chronic PE. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Chronic Thromboembolic Pulmonary Disease (CTEPD) are terms that describe symptomatic patients with chronic thromboembolic occlusions of the pulmonary arteries with or without pulmonary hypertension, respectively. Here, we review the definitions, epidemiology, pathobiology, diagnosis and management of CTEPH. The chronic PE in CTEPH is essentially a scar in the pulmonary vasculature and is accompanied by a pulmonary arteriolar vasculopathy. Ventilation-perfusion scanning is the most sensitive screening test for CTEPH, and diagnosis must be confirmed by right heart catheterization (RHC). Treatment decisions require a multidisciplinary team and guidance from additional imaging, usually CT or pulmonary angiography. While pulmonary endarterectomy (PEA) to remove the chronic PE surgically is still the first-line treatment for appropriate candidates, there is an expanding role for balloon pulmonary angioplasty (BPA) and medical treatment, as well as multimodality treatment approaches that incorporate all of those options. New imaging modalities and treatment strategies hold the promise to improve our care and management of CTEPH patients in the future.

Conservative Management of Occipital Neuralgia Supported by Physical Therapy: A Review of Available Research and Mechanistic Rationale to Guide Treatment.

Conservative management is consistently recommended as a first line intervention for occipital neuralgia (ON); however, there is limited clinical research regarding conservative intervention for ON. This lack of research may lead to underutilization or unwarranted variability in conservative treatment. This article provides mechanism-based guidance for conservative management of ON as a component of a multimodal treatment approach, and discusses the role of the physical therapist in the care team. It also highlights opportunities for further research to refine conservative management of this condition. Published research on conservative interventions specific to ON is limited to very low-quality evidence for the use of TENS. The contemporary shift toward precision pain management emphasizing treatment based on a patient's constellation of clinical features-a phenotype-rather than solely a diagnosis provides more personalized and specifically targeted pain treatment. This paradigm can guide treatment in cases where diagnosis-specific research is lacking and can be used to inform conservative treatment in this case. Various conservative interventions have demonstrated efficacy in treating many of the symptoms and accepted etiologies of ON. Conservative interventions provided by a physical therapist including exercise, manual therapy, posture and biomechanical training, TENS, patient education, and desensitization have mechanistic justification to treat symptoms and causes of ON. Physical therapists have adequate time and skill to provide such progressive and iterative interventions and should be included in a multimodal treatment plan for ON. Further research is required to determine appropriate dosing, sequencing, and progression of conservative treatments.

Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).

LBA1 Background: The most effective multimodal approach for treatment of resectable locally advanced esophageal adenocarcinoma (EAC) is under debate. A prior ranking question is if neoadjuvant chemoradiation therapy or perioperative chemotherapy is superior. ESOPEC (NCT02509286) is a multicenter prospective randomized trial comparing neoadjuvant CROSS (41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative FLOT (5-FU/ leucovorin/oxaliplatin/docetaxel) and surgery for the curative treatment of EAC. Methods: Patients with cT1 cN+ cM0 or cT2-4a cNany cM0 resectable EAC were eligible. The primary endpoint is overall survival (OS; 90% power; hazard ratio [HR] 0.645, 218 events needed; one sided significance level of 2.5%). Analysis is by intention-to-treat in all randomized patients. The effect of treatment on OS is estimated using Cox regression stratified by study site, and including N stage (N0, N+), and age as covariates. Results: Between Feb 2016 and Apr 2020, 438 patients from 25 sites in Germany were randomly assigned to two treatment groups (221 FLOT; 217 CROSS). Baseline characteristics (male sex 89.3%, median age 63 [range 30-86], cT3/4 80.5%; cN+ 79.7%) were well balanced between both arms. Neoadjuvant treatment was started in 403 patients (207 FLOT; 196 CROSS). Surgery was done in 371 patients (191 FLOT; 180 CROSS). R0 resection was achieved in 351 patients (180 FLOT; 171 CROSS). 90 days postsurgical mortality was 4.3% (3.2% FLOT; 5.6% CROSS). After a median follow up of 55 months, 218 patients had died (97 FLOT; 121 CROSS). Median OS was 66 (95% CI 36 – not estimable) months in the FLOT arm, and 37 (95% CI 28 – 43) months in the CROSS arm. The 3-year OS rates were 57.4% (95% CI 50.1 – 64.0%) for FLOT and 50.7% (95% CI 43.5 – 57.5%) for CROSS (HR 0.70, 95% CI 0.53-0.92, p=0.012). In 359 patients with available tumor regression status, pathological complete response was achieved in 35 (19.3%, 95%-CI 13.9 – 25.9%) in FLOT and in 24 (13.5%, 95%-CI 8.8 – 19.4%) in CROSS. Conclusions: Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS. Funding: The trial was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 264590883. Clinical trial information: NCT02509286 .

Manual medicine as part of a multimodal treatment approach to nociplastic pain

Manual medicine as part of a multimodal treatment approach to nociplastic pain

Formula diets for weight loss - chances and challenges

Formula diets, through the use of industrially manufactured meal replacement products, lead to effective and rapid weight reduction and improvement in obesity-associated comorbidities. The specific composition of these meal replacement products simplifies the adherence to calorie goals and ensures the supply of essential nutrients during significant energy restriction. Despite numerous potential applications, evidence from randomized controlled studies, and simplicity in practical implementation, challenges persist. Monotony and social restrictions complicate adherence and acceptance. The use of formula diets for sustainable weight loss requires integration into a multimodal treatment approach with the goal of long-term changes in eating and activity behaviour. This includes accompanying nutritional counselling, promotion of physical activity, evaluation of adjuvant pharmacological or interventional therapies, as well as psychological support. The development of new incretin-based anti-obesity medications has opened another application field for formula products. There is optimization potential in expanding the product range and combining it with digital applications to enhance acceptance and reach a larger patient group.

Intravitreal chemotherapy (IVC) in retinoblastoma: A study of clinical variables and ocular preservation outcomes.

10059 Background: Retinoblastoma, a primary intraocular malignancy, poses unique challenges in preserving life and vision. This retrospective study aims to analyze the impact of IVC in a population of retinoblastoma patients. The primary objective to avoid external radiotherapy, a recognized risk factor for second neoplasms, particularly in germline retinoblastoma cases. Methods: We conducted an analysis of retinoblastoma patients from 2011 to 2024. Clinical variables, including sex, age, laterality, intraocular retinoblastoma staging, and therapies employed, were prospectively documented. Results: The study included 59 patients (37 male; 22 female). Thirty-three percent of patients had unilateral tumors and an average age of 28 months at diagnosis, and 67% had bilateral tumors with an average age of 15 months. Sixty-one eyes were treated and classified at diagnosis as follow: 6 (9.8%) in groups A and B, 10(18%) in group C, 37(64%) in group D, 6(11%) in group E, and 2(3%) without initial information. IVC was administered as part of a multimodal treatment approach. A total of 203 cycles of IVC were performed, averaging 3.4 cycles per patient. Melphalan was used in 39% of cycles, followed by the combination of melphalan and topotecan in 35%, and topotecan alone in 26%. Seven of 61 (11.5%) were enucleated. Three of 61 eyes (4.9%) received radiotherapy. Control of vitreous seeds and vision preservation were achieved in 57/61 eyes (93%). No grade 3 or 4 adverse events occurred. Conclusions: IVC emerges as a crucial component in the management of retinoblastoma, offering a viable alternative to external radiotherapy. The analysis highlights the importance of this approach in preserving ocular integrity, thereby avoiding enucleation and reducing the risk of second neoplasms, particularly in germline retinoblastoma patients.

Application of artificial intelligence to hepatobiliary cancer clinical outcomes research

The rapid evolution of modern technology has made artificial intelligence (AI) an important emerging tool in healthcare. AI, which is a broad field of computer science, can be used to develop systems or machines equipped with the ability to tackle tasks that traditionally necessitate human intelligence. AI can be used to perform multifaceted tasks that involve the synthesis of large amounts of data with the generation of solutions, algorithms, and decision support tools. Various AI approaches, including machine learning (ML) and natural language processing (NLP), are increasingly being used to analyze vast healthcare datasets. In addition, visual AI has the potential to revolutionize surgery and the intraoperative experience for surgeons through augmented reality enhancing surgical navigation in real-time. Specific applications of AI in hepatobiliary tumors such as hepatocellular carcinoma and biliary tract cancer can improve patient diagnosis, prognostic risk stratification, as well as treatment allocation based on ML-based models. The integration of radiomics data and AI models can also improve clinical decision making. We herein review how AI may be of particular interest in the care of patients with complex cancers, such as hepatobiliary tumors, as these patients often require a multimodal treatment approach.

Reconstruction options for infection-related defects : Plastic surgery armamentarium

The occurrence of infections has always been feared in all surgical disciplines. Plastic reconstructive surgery faces the challenge of treating infection-related defects on apatient-specific basis, which requires amultidisciplinary treatment concept. Satisfactory treatment success can only be achieved through radical debridement for infection cleansing, optimization of the perfusion situation paired with targeted anti-infective treatment and, if necessary, with soft tissue reconstruction by plastic surgery. This article presents the current possibilities of plastic and reconstructive surgery with respect to the reconstruction of infection-related defects. Proven and reliable strategies are presented and supplemented by promising experimental approaches. Due to the often multilayered defect situation caused by infections, from the epidermis to cancellous bone, the entire armamentarium of plastic and reconstructive surgery is used for reconstruction. The early involvement of plastic surgery in the treatment of infections and the interdisciplinary and multimodal treatment approach have proven their worth in the treatment of complex infection situations.

Treatment strategies for recurrent rectal cancer

Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop alocal relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as aresult of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains achallenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent.

Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities.

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced-stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post-surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced-stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

The impact of tumor budding and single-cell invasion on survival in patients with stage III/IV locally advanced oral squamous cell carcinoma- results from a prospective cohort study.

Tumor budding (TB) refers to the presence of small clusters of tumor cells at the invasive front of a malignant tumor. Single tumor cell invasion (SCI) is an extreme variant of TB, in which individual loose tumor cells are present at the invasive front. Both TB and SCI are important histomorphologic risk factors postulated to indicate loss of cellular cohesion. In this study, we investigated the influence of TB and SCI on different survival outcomes in patients with locally advanced oral squamous cell carcinoma (OSCC). We included 129 patients with locally advanced OSCC (pT3-4) from a single-center, prospectively maintained cohort. We examined the association of TB and SCI with the presence of occult lymph node metastasis using a logistic regression model. Survival probabilities were estimated using the Kaplan-Meier method and cumulative incidence functions. The association of TB and SCI on overall survival (OS), oral cancer-specific survival (OCSS), and local recurrence-free survival (LRFS) was investigated using Cox's proportional hazards regression models. TB was detected in 98 (76%) of the tumors, while SCI was observed in 66 (51%) patients. There was a significant association between TB and the occurrence of occult lymph node metastasis (OR=3.33, CI: 1.21-10.0). On multivariate analysis, TB had no detectable impact on survival outcomes. However, SCI showed a higher risk for local recurrence (Hazards ratio (HR): 3.33, CI: 1.19 - 9.27). This study demonstrates that TB and SCI in locally advanced OSCC function as an independent risk factor for occult lymph node metastases, as well as local recurrences. Both histomorphologic risk factors could serve as an additional parameter for stratifying therapy and escalating multimodal treatment approaches.

Combination of calretinin, MALAT1, and GAS5 as a potential prognostic biomarker to predict disease progression in surgically treated mesothelioma patients

BackgroundThe role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival. MethodsBetween 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival. ResultsMALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %. ConclusionMALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.

Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy.

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

Therapeutic Response to PRRNT in a Rare Case of Metastatic Renal Neuroendocrine Carcinoma

AbstractNeuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.

Adjunctive bevacizumab therapy in an equine corneal stromal invasive squamous cell carcinoma with a 53-months follow-up.

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.

Treatment strategies for borderline resectable pancreatic neuroendocrine tumors: a narrative review.

Well-differentiated pancreatic neuroendocrine tumors (pNETs) are a group of rare, heterogeneous tumors that originate in the endocrine tissue of the pancreas and account for 1-2% of all pancreatic neoplasms. The majority of pNETs are non-functional and typically follow a more indolent course. Especially at early stages, the primary management of pNETs is surgical resection which is associated with relatively low rates of recurrence and excellent long-term prognosis. On the other hand, some patients will present with locally advanced primary tumors or low volume metastatic disease in which complete surgical resection may be more difficult to achieve and recurrence rates are significant. Unlike treatment of borderline resectable (BR) pancreatic adenocarcinoma, in which neoadjuvant treatment strategies are becoming standardized, borderline resectability is not a currently established terminology for pNETs and the optimal multidisciplinary treatment approach is poorly understood. We performed a literature search on PubMed, Google Scholar, and ClinicalTrials.gov using keywords, including 'pancreatic neuroendocrine tumor' and 'borderline resectable'. All studies and review articles in English with full text were considered. Each publication was independently reviewed. We introduce the concept of BR-pNETs, focusing on important criteria that should be included in their definition by balancing the feasibility of resection and the clinical utility of surgery. We suggest that extended resection, involving vascular reconstruction, adjacent organ resection, and/or liver metastasis, should be considered at experienced, high volume centers. Furthermore, we outline multidisciplinary treatment strategies, including systemic and locoregional treatment options, for optimizing outcomes for this growing patient population. Formalizing the definition of resectability in pNETs through multidisciplinary collaborative research will be important for standardizing the indications for multimodality treatment and aggressive surgical approaches for patients.

Effect of photobiomodulation therapy as a multimodal approach to treatment of dermal abrasions in cownose rays (Rhinoptera bonasus).

Photobiomodulation therapy (PBMT) has become increasingly utilized in the zoo and aquarium fields to treat ailments in various species; however, its use in teleosts and elasmobranchs is relatively underrepresented in the literature. This study examined the efficacy of PBMT as an adjunct treatment to reduce the healing time of dermal abrasions in cownose rays (Rhinoptera bonasus). Ten cownose rays were included in this study and separated into control (n = 5) and treatment groups (n = 5). Animals in both treatment and control groups received intramuscular injections of enrofloxacin every 72 h to provide broad-spectrum antibiotic coverage. Cownose rays in the treatment group additionally received PBMT using the Companion® CTC-12 unit using the large, noncontact head. Control group rays were subjected to identical handling without the use of PBMT. A total of 196 Joules were delivered at a power of 2 W based on a dose of 5 J/cm2 at each session. Observational analysis revealed a lack of appreciable difference in healing time between the treatment and control groups in the aforementioned settings; however, it is recommended that PBMT protocols should be re-evaluated if there is little to no response in healing after three to four sessions. PBMT use on acute superficial dermal abrasions in cownose rays was well-tolerated in this study and may have utility in a multimodal treatment approach to wound healing. This study also produced a wound scoring metric based on photographs captured at each treatment. Future studies should utilize increased fluence (J/cm2) and irradiance (W/cm2) and incorporate synchronous histological analysis and increased sample size.

Is there an indication for local treatment in metastasised hormone-sensitive prostate cancer?

In case of newly diagnosed metastasised hormone-sensitive prostate cancer, there are two indications for local treatment: to reduce or avoid local symptoms thus improving quality of life and prolonging survival in a subset of patients. Local treatment must be seen in a multimodal treatment approach and is not a replacement of systemic treatment. In the following review, we highlight the current literature for the different local treatment options, radiotherapy and radical prostatectomy, and try to give indications for which option should be offered to which patient.

Abstract 5799: Novel nanoparticle technology targets the delivery of polyIC to EGFR overexpressing cancers and induces a multimodal anti-tumor response

Abstract Aberrant activation of epidermal growth factor receptor (EGFR) signaling pathways is associated with tumor growth and progression. EGFR overexpression occurs in various types of solid cancers and correlates with poor outcome. Unfortunately, the clinical benefit from EGFR-targeted therapies is usually short-lived, due to the development of resistance. TargImmune has developed first-in-class Targeted Apoptotic Immunomodulators (TAIMs), which harness the body’s anti-viral responses to treat solid tumors. Our novel nanoparticle platform technology, Ta:RNA , selectively delivers synthetic dsRNA, polyinosinic:polycytidylic acid (polyIC) to tumor cells that overexpress a target receptor. PolyIC and other pattern recognition receptor (PRR) agonists have been used as adjuvants or for intratumoral administration but have limited efficacy as single agents. TargImmune’s platform allows systemic delivery of dsRNA, tailoring the nanoparticles to various solid cancers by simply changing the targeting moiety. Here we describe EGFR-Ta:RNA, which is targeted to tumors that overexpress EGFR. EGFR-Ta:RNA does not inhibit EGFR per se, and therefore activation of alternative or downstream oncogenes is not expected to cause resistance. The mechanism of action of EGFR-targeted Ta:RNA nanoparticles was extensively studied in vitro and in vivo, using confocal imaging, large-scale RNA sequencing studies, Western blot analysis and ELISA assays. In vitro, EGFR-Ta:RNA potency and selectivity were established by comparing cells with high receptor and low receptor expression. Imaging studies showed that the nanoparticles are internalized selectively into EGFR-overexpressing cancer cells by receptor-mediated endocytosis. RNAseq studies revealed: (i) a common transcriptional signature in EGFR-Ta:RNA-treated tumours and cancer cells; (ii) enrichment in pathways related to anti-viral response, inflammation, type I interferon signaling, and NFΚB signaling; (iii) enrichment in genes coding for cytokines. Western blot analysis and ELISA assays confirmed that the mechanism of action of EGFR-Ta:RNA is mediated via the induction of PRR downstream signaling, which results in cytokine secretion, apoptosis and immune cell activation. The efficacy of EGFR-Ta:RNA was demonstrated in multiple animal models, including both xenograft and immunocompetent models. The pharmacodynamic effect, exemplified by target engagement and activation of PRR signaling in tumors, was verified in vivo. In conclusion, TargImmune’s EGFR-Ta:RNA nanoparticles deliver polyIC in a tumor-targeted manner to evoke PRR signaling, inducing targeted tumor cell apoptosis as well as immune cell recruitment and activation against the heterogenous tumor. EGFR-Ta:RNA represents a novel, multimodal treatment approach for EGFR overexpressing cancers. Citation Format: Derrick Broka, Caroline De Feyter, Shoshana Klein, Meera Saxena, Joerg Schreiber, Alexei Shir, Michal Skowicki, Yaakov Benenson, Alexander Levitzki, Cornelia G. Palivan, Esteban Pombo-Villar, Babette Schade, Maya Zigler. Novel nanoparticle technology targets the delivery of polyIC to EGFR overexpressing cancers and induces a multimodal anti-tumor response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5799.

Long-Term Survival in Patients with Oligometastatic Non-Small Cell Lung Cancer by a Multimodality Treatment-Comparison with Stage III Disease.

Background: In patients with oligometastatic NSCLC, a cT3-cT4 primary tumor or an cN2/cN3 lymph node status was reported to be associated with unfavorable outcome. The aim of this study was to assess the importance of definitive or neoadjuvant thoracic radiochemotherapy for long-term outcome of these patients in order to find more appropriate treatment schedules. Methods: Analysis of the West Cancer Centre (WTZ) institutional database from 08/2016 to 08/2020 was performed. Patients with primary synchronous OMD, all without actionable driver mutations, who received definitive thoracic radiochemotherapy (RCT) or neoadjuvant RCT followed by surgery (trimodality treatment) were included. Survival outcome is compared with stage III NSCLC. Results: Altogether, 272 patients received concurrent radiochemotherapy. Of those, 220 presented with stage III (158 with definitive RCT, 62 with trimodality approach). A total of 52 patients had OMD patients with cT3/cT4 or cN2/cN3 tumors. Overall survival (OS) at five years for OMD patients was 28.3% (95%-CI: 16.4-41.5%), which was not significantly different from OS of patients with stage III NSCLC treated with definitive or neoadjuvant RCT (34.9% (95%-CI: 27.4-42.8%)). However, the PFS of OMD patients at five years or last follow-up was significantly worse than that of stage III patients (13.0% vs. 24.3%, p = 0.0048). The latter was due to a higher cumulative incidence of distant metastases in OMD patients (50.2% vs. 20.4% at 48 months, p < 0.0001) in comparison to stage III patients. A cross-validated classifier that included severe comorbidity, ECOG performance status, gender and pre-treatment serum CRP level as the most important factors in the univariable analysis, was able to divide the OMD patient group into two equally sized groups with a four-year survival rate of 49.4% in the good prognosis group and 9.9% in the poor prognosis group (p = 0.0021). Laboratory chemistry and clinical parameters, in addition to imaging and high-precision therapies, can help to predict and improve prognosis. Conclusions: A multimodality treatment approach and local metastases-directed therapy in addition to chemoimmunotherapy can lead to good long-term survival in patients with cT3/cT4 or cN2/cN3 OMD NSCLC without severe comorbidities and in good performance status and is therefore recommended.