Multimodal Treatment Research Articles

Parameningeal Rhabdomyosarcoma: Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 Study.

Parameningeal (PM) site is an unfavorable characteristic in rhabdomyosarcoma (RMS). We described the treatment and outcome for patients with PM RMS and investigated the prognostic value of risk factors. We scored PM site by originating site and by highest risk extension. Patients with PM RMS were treated within the European pediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study with risk-adapted, multi-modal treatment. Three-hundred-eighty-one patients with PM RMS were included. Radiotherapy was administered in 359 patients (77 with surgery). After a median follow-up of 75 months, 5-year event-free survival was 60% (95% confidence interval (CI) 55%-65%), 5-year overall survival was 65% (95% CI 60%-70%). The outcome for patients with PM RMS has not improved in comparison to previous historical studies, despite the more rigorous application of radiotherapy (94% of patients). Signs of meningeal involvement, PM site, and age at diagnosis remained prognostic risk factors. EudraCT number 2005-000217-35.

Liver transplantation for gastroenteropancreatic neuroendocrine liver metastasis: optimal patient selection and perioperative management in the era of multimodal treatments.

Gastroenteropancreatic neuroendocrine tumors (NET) often metastasize to the liver. Although curative liver resection provides a favorable prognosis for patients with neuroendocrine liver metastasis (NELM), with a 5-year survival rate of 70-80%, recurrence is almost inevitable, mainly in the remnant liver. In Western countries, liver transplantation (LT) has been performed in patients with NELM, with the objective of complete removal of macro- and micro-NELMs. However, prognosis had been unsatisfactory, with 5-year overall survival and recurrence-free survival rates of approximately 50 and 30%, respectively. In 2007, the Milan criteria were proposed as indications for LT for NELM. The criteria included: (1) confirmed histology of NET-G1 or G2; (2) a primary tumor drained by the portal system and all extrahepatic diseases removed with curative resection before LT; (3) liver involvement ≤50%; (4) good response or stable disease for at least 6months before LT; (5) age ≤ 55years. A subsequent report demonstrated outstanding LT outcomes for NELM within the Milan criteria, with 5-year overall survival and recurrence rates of 97 and 13%, respectively. In Japan, living donor LT (LDLT) for NELM has been performed sporadically in only 16 patients by 2021 in Japan; however, no consensus has been reached on the indications or perioperative management of LDLT. This article presents the outcomes of these 16 patients who underwent LDLT in Japan and reviews the literature to clarify optimal indications and perioperative management of LDLT for NELM in the era of novel multimodal treatments.

COMPLEXITY OF PITUITARY ADENOMA SURGERY

Introduction Pituitary adenomas are the most common intraselllar tumors, representing 16% of all intracranial lesions. Although the symptomatology is very complex, it requires a multimodal treatment plan, in order to cover all corners of this combined pathology. Mostly the treatment is surgical, hormonal or combined. The transnazosphenoidal corridor offers a optimal visualitation of the anatomic location (via microscope or endoscope) but also comes with a variety of morbidities, one of the most important being the cerebrospinalfluid fistula (CSF leak). Objective We effectuated a retrospective cohort study in which we included patients with pituitary adenoma who were operated in the Clinic of Neurosurgery from Targu-Mures Emergency County Hospital between January 2018 and April 2024 with full documentation, including complications (apoplexy, infections, CSF fistula etc.). Results A total of 45 patients passed the inclusion criteria with a predominance of female patients (60%, n=27) with a mean age of 55.77 years. Analizing the clinical and paraclinical data, there were 39 patients with macroadenoma (vs. microadenoma n=6), with the dominant symptomatology being headache (86.66%) and visual disturbances (66.66%). In 32 cases the transnazosphenoidal (TSS) approach was used (1 case endoscopic and 31 cases microscopic), in 10 cases pure transcranian with modified pterional or subfrontal craniotomy and in 3 cases there was a combined approach. Postoperative complications were encountered in 8 cases (17.77%), and death in 1 case. 6 patients presented postoperative CSF fistula. In 16 cases we encountered postoperative Diabetes Insipidus with a significant difference in the tumor volume favoring this manifestation (p=0.0001). There was no significance found between the volume of the tumor and postoperative CSF leak (p=0.665). In 31 cases (68.88%) the TSS approach was used and the closing of the sphenoid sinus and cranial base was effectuated in a classic manner with fat, fascia and muscle; in additional cases specified glues were used. Conclusions Our study wants to reflect on the importance of anterior/middle cranial base closure, taking into account the possible postoperative complications. It is important to be aware of the technique of different nasoseptal flaps in order to prevent CSF fistula and reduce postoperative complications.

OGC SO15 - Utility of radiological re-staging following neo-adjuvant chemotherapy and its impact on oncological outcomes in resectable gastric adenocarcinoma

Abstract Background The current perioperative chemotherapy regimen that comprises the multimodal treatment strategy for gastric cancer consists of Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel. Despite improvement in outcomes at a population level, real-world data suggests that ≤40% of patients show a poor/no response to the neoadjuvant phase of treatment. Identification of these poor/non-responders may facilitate a re-evaluation of their treatment strategy and prevent potentially futile surgery. Radiological re-staging following neoadjuvant treatment is routinely performed despite its debatable accuracy and benefits. This study aimed to define the accuracy of radiological re-staging and its impact on survival following neoadjuvant treatment for resectable GC. Method Patients with resectable gastric cancer who completed 4 cycles of neoadjuvant FLOT and underwent resectional surgery with curative intent between 2018 and 2022 were retrospectively identified. All patients were clinically staged with gastroscopy, CT and staging laparoscopy. The index radiological/clinical stage at diagnosis was compared to the radiological re-staging following neoadjuvant treatment. Patient were re-staged with either a CT or PET-CT. Both were then compared with the final pathological stage to assess for correlation between the radiological and pathological stage. A survival analysis was then performed to evaluate the impact of radiological-pathological staging discrepancy on overall survival Results A total of 65 consecutive patients met the inclusion criteria of this study. On comparison of the index clinical stage with the radiological re-stage post-neoadjuvant treatment, 71% had concordant stages, 25% were downstaged, and 4% were upstaged. On comparison of the index clinical stage with the final pathological stage, 35% had concordant stages, 38% were upstaged and 27% were down staged (Cohen kappa = -0.224, 95% CI -0.390, -0.058). Discrepancy between clinical stage and radiological re-stage did not influence survival. However, discrepancy between clinical and pathological stage highlighted survival differences where upstaged patients had reduced survival (p = 0.018). Conclusion The accuracy of clinical staging compared to final pathological staging in the setting of aggressive tumour biology remains undefined. Radiological re-staging following neoadjuvant treatment proves to be an unreliable tool for assessing treatment response and does not predict long-term survival outcomes. These findings highlight the importance of accurate staging and the need for more precise methods of evaluating treatment response. This may enhance decision-making, individualise treatment regimens, and improve patient outcomes.

β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers

Despite advances in cancer treatment, current cancer incidence and prevalence still demand multimodal treatments to enhance survival and clinical outcomes. Drugs used in cardiology, such as β-blockers and statins have gained attention for their potential roles in oncology. This review focused on their possible complementary use in solid tumors, including breast, colorectal, lung, and prostate cancers. The involvement of the autonomic nervous system in promoting tumor growth can be disrupted by β-blockers, potentially hindering cancer progression. Statins, known for their pleiotropic effects, may also inhibit cancer growth by reducing cholesterol availability, a key factor in cell proliferation. We will provide an update on the impact of these therapies on cancer treatment and surveillance, discuss the underlying mechanisms, and explore their effects on the heart, contributing to the growing field of cardio-oncology.

Transarterial Chemoembolization in Locally Advanced Rectal Cancer: A Systematic Review

Background: Locally advanced rectal cancer (LARC) presents a significant treatment challenge. Transarterial chemoembolization (TACE) has emerged as a potential adjunctive treatment, offering targeted delivery of chemotherapeutic agents to the tumor site, minimizing systemic exposure. This systematic review aims to assess the current literature on this novel technique and evaluate the safety and efficacy profile of TACE in treating this complex cohort of patients. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, and Cochrane Library, to identify studies evaluating TACE in LARC. Inclusion criteria encompassed clinical trials, cohort studies, and case series reporting on outcomes such as tumor response rate, overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results: A total of eight studies involving 543 patients met the inclusion criteria. The studies varied in design, with five prospective and three retrospective studies. A higher prevalence of male participants (68.7%) was noted, with a median age of 60.3 years. The studies primarily evaluated the efficacy and safety of TACE in LARC treatment. Pathological response rates, tumor reduction, and survival outcomes varied across studies, with TACE showing promise in reducing tumor size, improving survival, and controlling metastasis. Major complications were rare, reported in 6.0% of cases. Conclusions: TACE is a promising therapeutic option for patients with LARC, demonstrating favorable tumor response rates and manageable toxicity profiles. Further large-scale, randomized controlled trials are warranted to confirm these findings and better define the role of TACE in the multimodal treatment of LARC.

The Evolving Role of Neoadjuvant Radiation Therapy in Pancreatic Adenocarcinoma

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

TMET-23. MASS SPECTROMETRY-BASED METABOLIC PROFILING AND IMAGING OF ASTROCYTE AND GLIOBLASTOMA INVASIVE MARGIN CELLS

Abstract Despite multimodal treatment, 90% of patients diagnosed with isocitrate dehydrogenase (IDH) wild-type glioblastoma experience tumour recurrence within 5 years. Poor prognosis is in considerable part attributed to the ability of cancer cells to infiltrate a healthy brain. We hypothesise that metabolic changes underpinning cellular crosstalk between astrocytes and glioblastoma cells isolated from the invasive margin within a physiologically representative in-vitro tumour microenvironment may reveal therapeutic targets to prevent or delay glioblastoma recurrence. This study used advanced analytical techniques to establish baseline metabolomic profiles for eGFP-tagged primary glioblastoma cells isolated from the invasive margin and healthy human cortical astrocytes. Liquid chromatography-mass spectrometry (LC-MS) enabled detailed analysis of biochemical pathways, and Atmospheric Pressure-Matrix Assisted Laser Desorption/Ionisation (AP-MALDI) imaging offered spatial localization of metabolites, critical for mapping their distribution within tumour microenvironments. Metabolites were extracted using a biphasic method (methanol:chloroform:water) for LC-MS analysis, and metabolic profiling was conducted using a ZIC-pHILIC column coupled with a Q-Exactive Orbitrap Mass Spectrometer. Additionally, AP-MALDI imaging facilitated the generation of high-resolution spatial distribution maps of selected metabolites, achieving a resolution of 10 µm. Both multivariate and univariate statistical analyses were applied to identify significant metabolic alterations. Metabolic profiling identified distinct pathways altered in glioblastoma cells compared to astrocytes, including alterations in aspartate, glycine and serine, and lipid metabolism. High-resolution imaging outlined the spatial distribution of metabolites involved in these pathways, revealing regions of metabolic heterogeneity. Furthermore, this methodology facilitated an expanded identification range of essential biomolecules, notably lipids and amino acids, thereby augmenting our understanding of their dynamic functions across diverse cellular contexts. By leveraging the complementary strengths of LC-MS and AP-MALDI imaging, this research enhances our understanding of spatial metabolite distribution in glioblastoma cells isolated from the invasive margin and suggests potential applications in patient tissue, offering a deeper exploration of disease mechanisms.

NCOG-16. A PROSPECTIVE OBSERVATIONAL STUDY OF CLINICAL PROFILE, COURSE AND OUTCOME OF PRIMARY BRAIN TUMOR AT A TERTIARY CARE CENTER

Abstract Primary brain tumors include tumor arising from neuro-epithelial cells, cranial nerves, meninges, germ cells, pituitary gland, and blood-forming organs. These tumors can present with either generalized or focal signs and symptoms.General symptoms are due to raised intracranial pressure (headache, vomiting). Focal symptoms are due to the compression of a structure or destruction (focal neurological deficits). The aim of this study is to analyze the clinical profiles of pediatric and adult brain tumor patients. Data of primary brain tumor patients who were diagnosed from 1st December 2019 to December 2021 were prospectively collected and analysed. In our study of 61 patients, the majority of patients had GBM (32.8%) and astrocytoma (31.1%) and medulloblastoma (11.5%). Less common histologies ependymomas (9.8%), meningioma (6.6%), brain stem glioma (3.3%), oligodendrogliomas (3.3%) and germinoma (1.6%). Out of 19 astrocytomas, 10 were of low grade (1 or 2), while 9 were of high grade (3 or 4).The majority (61.7%) of gliomas were of high grade, while the remaining 38.3% were of low grade. The majority (57.5%) of patients received multimodal treatment,26.2%received dual modality (surgery and RT), while the remaining 16.3% received single modality, either surgery or RT. Most (86.9%) of the patients treated with radiotherapy as a part of a single or multimodal treatment. A significant percentage of patients (77.1%) received concurrent and adjuvant temozolamide-based chemotherapy. Primary brain tumors have a different profile in pediatric patients. Among pediatric patients, the median age was 11.8 years, with male predominance. This study concludes that primary brain tumors have a different profile among adults and pediatric patients, with the majority of patients achieving a response to the first line therapy with an overall good tolerance for therapy.

PATH-66. MOLECULAR FEATURES RELATED TO LONG-TERM SURVIVAL IN GLIOBLASTOMA

Abstract Glioblastoma Multiforme (GBM) remains the most common malignant primary brain tumor in adults, with a dismal prognosis that rarely exceeds beyond 2 years of survival despite multimodal treatment. While small fractions of GBM patients seem to display extended survival, the underlying mechanisms for this peculiarity remain largely unknown. Previously published investigations of long-term survivors (LTS) usually incorporate small numbers of patients, non-uniform definition of LTS and rarely provide a comprehensive molecular analysis. With advances in multi-omics technologies and their integration with disease diagnostics, numerous prognostic molecular markers have been proposed. So far, only O6-methylguanine-DNA-methyltransferase (MGMT) gene promotor hypermethylation was linked to outcome and therapy response. We aim to investigate omics characteristics associated with LTS. Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients, >18 years old, operated and treated at our institution between 2013 and 2020 and living ≥5 years post-diagnosis (LTS = 62) or 1-2 years (STS = 62) were identified. Clinical and demographic characteristics were matched. Tumor tissues was analyzed with targeted next generation sequencing (NGS) and compared between LTS and STS. In addition, methylation analysis was done for all LTS. Results will be presented. We hope to shed a broader light on the molecular drivers behind the LTS in GBM patients, that will provide prognostic markers and potential targets for novel treatments.

PATH-67. THE ROLE OF STATUS OF HER-2, ESTROGEN-RECEPTOR, BRCA 1, AND BRCA 2, IN THE INCIDENCE OF BRAIN METASTASIS IN BREAST CANCER

Abstract Breast cancer (BC) is the most diagnosed tumor in women and the second-leading cause of brain metastasis (BM), with a prevalence ranging from 10-36%. According to the Epidemiological Strategy and Medical Economics research program, advanced BC patients face an estimated 25% risk of developing BM within 2-3 years after the initial diagnosis. The frequency of BM is significantly increased by the primary tumor profile, including larger tumors, higher nuclear grade, HER-2 positivity, estrogen-receptor negativity, and triple-negative status. A gap remains in the classification of the BM site relative to primary tumor biomarkers, and the absence of multimodality treatment methodologies poses challenges to survival rates and quality of life in BC patients. This retrospective cross-sectional study at Aga Khan University Hospital identified 52 cases of brain metastasis secondary to breast cancer over a 10-year period. The median age of patients was 55 years, ranging from 32 to 78 years. Primary breast tumors were predominantly high-grade ductal carcinomas (65%), followed by lobular carcinomas (25%) and other rare histological types (10%). Secondary brain metastases were primarily located in the cerebrum (60%), cerebellum (25%), and brainstem (15%). Tumor profiles indicated a significant correlation between HER-2 positivity and the development of brain metastasis, with 70% of HER-2 positive patients presenting with extensive brain metastasis. Tumor progression varied, with a median time to brain metastasis of 2.5 years from the initial breast cancer diagnosis. Despite aggressive multimodality treatments, including surgery, radiation, and chemotherapy, the overall prognosis remained poor. The study found that early detection of HER-2 positive and triple-negative tumors could potentially delay the progression of brain metastasis through targeted therapies. Mortality rates in this cohort were high, with a median survival of 8 months following the diagnosis of brain metastasis. These findings underscore the need for improved diagnostic, preventive, and therapeutic strategies to manage brain metastasis in breast cancer patients.

SURG-41. OPTIMIZING PATIENT OUTCOMES IN PETROCLIVAL MENINGIOMA TREATMENT: EVALUATING SURGICAL, RADIOSURGICAL, RADIOTHERAPY AND COMBINED TREATMENT APPROACHES

Abstract Petroclival meningiomas pose a formidable challenge due to their proximity to critical neurovascular structures, necessitating complex surgical interventions with a high risk of complications. Stereotactic radiosurgery (SRS) offers an alternative or complementary treatment option, yet the optimal treatment strategy remains undefined. We aimed to evaluate the local control rates following surgical resection, radiotherapy, and SRS for petroclival meningiomas and to assess the incidence of cranial nerve palsies associated with each treatment modality. This retrospective study reviewed medical records of patients treated for petroclival meningiomas at Stanford University between 1980-April 2024. Pre- and post-treatment radiological data were analyzed to assess local control. Cranial nerve function was evaluated pre- and post-treatment, and at last follow-up. A total of 171 patients (129 females; median age 54.65 years) diagnosed with petroclival meningioma were identified. Treatment modalities included: 31 patients underwent surgical resection alone, 27 received SRS alone, 11 received radiotherapy alone, 36 underwent combined surgical resection and SRS, 28 received combined surgical resection and radiotherapy, 9 were treated with a triad of surgical resection, SRS, and radiotherapy, and 29 were managed with serial imaging alone. The percentage change of tumor volume from diagnosis to follow-up for these groups was -55.6%, 28.9%, 73.0%, -64.9%, -12.0%, 35.3%, and -8.8%, respectively. The incidence of new cranial nerve palsies was highest (68%) in patients who underwent surgical resection. The percentage of worsening pre-existing palsies was greater in patients receiving single-modality non-surgical treatment. Surgery, radiotherapy, and SRS demonstrated promising local control rates for specific patient cohorts with petroclival meningiomas. Patients receiving combination therapies generally fared better than those receiving single-modality treatments, with surgery followed by SRS yielding the best outcome. The incidence of cranial nerve palsies was lower following SRS and radiotherapy compared to surgery. Future research should focus on refining multi-modal treatment strategies to minimize complications and improve patient quality of life.

Nanotechnology for Nasopharyngeal Cancer Therapy and Improving Drug Stability and Biodistribution

AbstractNasopharyngeal cancer (NPC) is a challenging malignancy with a poor prognosis due to late diagnosis and resistance to conventional treatments. Nanotechnology offers promising solutions to address these limitations by enabling targeted drug delivery, enhancing therapeutic efficacy, and facilitating multimodal treatment strategies. By leveraging the unique properties of nanomaterials and nanocarrier systems, innovative approaches for early detection, targeted treatment, and multimodal therapy can be developed, paving the way for more effective and personalized management of NPC. This review provides a comprehensive overview of recent developments and applications of nanotechnology in NPC therapy, focusing on improving drug stability, biodistribution, and targeted delivery to NPC tumors.

TMIC-11. THE EFFECTIVENESS OF VALPROIC ACID IN COMBINATION WITH TEMOZOLOMIDE FOR TREATMENT OF HIGH-GRADE GLIOMAS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND High-grade gliomas (HGGs) rapidly progress with a high recurrence rate and poor prognosis despite standard multimodal treatment. Valproic acid (VPA), a histone deacetylase inhibitor, sensitizes HGG to radiochemotherapy along with having potential anti-cancer mechanisms and augmenting the growth inhibitory effect of Temozolomide (TMZ). This study explores the effectiveness of VPA in combination with TMZ for treating patients with HGG. METHODS A comprehensive literature search was performed on PubMed, Scopus, Embase, and Web of Science databases and identified relevant studies (case-control, cohort, RCTs) comparing the synergistic effect of VPA during TMZ to TMZ without VPA. We investigated median overall survival (OS), Progression-free survival (PFS), and baseline MGMT methylation status to evaluate this relationship. RESULTS Our systematic review encompassed 9 studies involving 4,097 patients with HGGs (seven cohorts, one case-control, and one RCT). The pooled analysis of median OS demonstrated no statistical significance difference between VPA during TMZ and TMZ alone (MD=-3.97; 95%CI=-8.43-0.49; p=0.08). However, sub-analysis showed a statistically significant effect in studies with sample size <100 (MD=-5.06; 95%CI=-9.32,-0.80; p<0.02), and 100-200 (MD=-7.07; 95%CI=-13.15,-1.00; p<0.02), and those conducted before 2015 (MD=-5.62, 95%CI=-9.08,-2.17, p<0.01). On meta-regression analysis, no statistical significance (RC=0.82,95% CI=0.39,-2.03, p=0.18) was observed, indicating that the study year is not associated with the intervention. A separate analysis of 3 studies also showed no significant variance in the baseline percentage of patients without MGMT methylation (log OR=-0.35, 95%CI=-1.02,-0.32, p=0.30) when administering VPA during TMZ treatment (n=67) compared to TMZ alone (n=409). Additionally, VPA during TMZ does not significantly affect PFS (MD=-3.54; 95% CI=-10.18-3.10, p=0.30) compared to TMZ alone. CONCLUSIONS The concurrent use of VPA with TMZ shows no significant effect on OS and PFS, nor does it show any variance in the baseline MGMT methylation status compared to TMZ alone. However, smaller sample sizes show a significant effect. Thus, our findings emphasize the imperative for additional research aimed at refining clinical outcomes.

EXTH-41. COMBINATION TREATMENT WITH RAF/MEK AND FAK INHIBITION ENHANCES TUMOR GROWTH INHIBITION IN MENINGIOMA

Abstract BACKGROUND Patients with meningiomas who have progressed after multimodal treatments face a significant shortage of viable therapeutic options. Recent advancements in the molecular understanding of meningiomas have identified the FAK and RAF/MEK signaling pathways as potential promising targets for progressive meningiomas. METHODS In vitro, we tested two human meningioma cell lines, IOMM-Lee (NF2 wild-type and CDKN2A loss) and CH157-MN (NF2 mutant). The cells were plated in Matrigel-coated wells, treated with defactinib (FAK inhibitor), VS-6766 (RAF/MEK inhibitor, avutometinib) and the combination over a 7-day period and assessed for cell viability using the CellTiter-Glo 3D assay. In vivo, we tested the efficacy of the FAK inhibitor VS-4718 (possessing favorable pharmacokinetic properties in mice) and RAF/MEK inhibitor VS-6766, both given daily via oral gavage, in athymic nude mice bearing IOMM-Lee or CH157-MN tumors. RESULTS In the matrigel assay, VS-6766 suppressed IOMM-Lee and CH157-MN cells in a dose dependent manner. The drug combination was mostly additive in IOMM-Lee cells. However, CH157-MN cells showed a strong synergistic response across all drug concentrations tested. In the IOMM-Lee flank tumor model, VS-4718 alone had no effect, while VS-6766 alone or in combination significantly reduced tumor growth and extended median survival from 25 days to 47 days (p < 0.05). In the CH157 flank tumor model, VS-4718 monotherapy did not affect tumor growth or survival, but VS-6766 monotherapy slowed tumor growth and increased median survival from 10 days to 31 days (p < 0.001). Combining both drugs further reduced tumor growth and extended median survival to 42 days (p < 0.001). CONCLUSION Treatment with FAK and RAF/MEK inhibitors showed synergistic or combination effects in the NF2 mutant CH157-MN model in vitro and in vivo. RAF/MEK inhibitor monotherapy was effective for the IOMM-Lee model (NF2 wild-type), without clear benefit of combining with the FAK inhibitor. Investigations in intracranial tumor models are underway.

EXTH-81. A RARE CASE OF RELENTLESSLY PROGRESSIVE METASTATIC PINEOCYTOMA MANAGED WITH SEQUENTIAL MULTIMODAL THERAPY

Abstract BACKGROUND Pineocytoma is a rare pineal parenchymal WHO grade 1 tumor, typically well-managed with surgical resection alone. With gross total resection (GTR), 91% 1-year and 84% 5-year survival rates have been reported. Recurrent pineocytoma is rare and optimal management in that setting is unknown, in part owing to the rarity of the condition. METHODS We report an atypical course of pineocytoma in a 58-year-old male involving metastatic disease. RESULTS A pineal mass was identified upon MRI of the brain obtained for vision changes. Patient underwent GTR, pathology was consistent with pineocytoma, WHO grade 1. Ki-67 labeling index was low at 1-2%. Despite low-grade pathology, two years later, surveillance imaging demonstrated recurrence in the pineal region and a second lesion in the right thalamus. The patient underwent gamma knife surgery (GKRS) to both lesions. Three years later, he developed three new lesions in the right cerebellum and again underwent GKRS. Subsequent surveillance imaging identified new lesions in the right cerebellum and along ventricular walls, treated with further GKRS. Nine years after initial diagnosis, focal nodular leptomeningeal metastases were discovered, along with progression at the primary tumor site. Patient was treated with GKRS to the nodular deposits followed by pembrolizumab. Further disease progression as noted despite immunotherapy. Patient was treated with 6 cycles of temozolomide chemotherapy and at further progression 3 cycles of lomustine. Upon additional progression, further radiation therapy was administered with bevacizumab to reduce risk of radiation necrosis. Patient remains on surveillance 13 years after initial diagnosis with visual changes and mild headache representing only clinical issues. CONCLUSIONS Although exceedingly rare, pineocytoma is capable of metastasizing to brain parenchyma and the leptomeninges, as demonstrated in our patient. However, our case demonstrates prolonged survival is possible even in the setting of relentlessly progressive metastatic disease with utilization of multimodality treatment.

Brain Metastasis in Pediatric Patients with Osteosarcoma

Background: Brain metastases in pediatric osteosarcoma are infrequent but associated with a dire prognosis. Methods: This retrospective study examined six pediatric patients at Johns Hopkins Hospital who developed brain metastases from osteosarcoma between April 2015 and November 2023. Results: Median survival post-brain metastasis was 2.5 months. The patients underwent various treatments, including chemotherapy, surgery, and radiation. Despite these interventions, outcomes were uniformly fatal. Notably, one patient survived over 13 months post-brain metastasis with a treatment regimen of cabozantinib and nivolumab along with surgical resection and radiation, highlighting the potential efficacy of multimodal treatment regimens. This case demonstrated changes in the immune microenvironment, hinting at an anti-tumoral response, although no histologic response was observed. Conclusions: These findings emphasize the critical need for vigilant clinical monitoring, especially in patients with new neurological symptoms. The study highlights the diagnostic challenges and the rapid progression of brain metastases, underscoring the necessity for further research. Prospective studies and clinical trials focusing on novel therapeutic strategies are essential to improve outcomes. Disease biology studies examining tumor features across primary, pulmonary, and brain metastatic sites may offer insights into the mechanisms of metastasis and potential therapeutic targets, providing a foundation for better management of this devastating complication.

Presentation and outcome of Gastric Cancer at a Tertiary Care Center

Introduction: Gastric cancer is the fifth most common cancer globally and the fourth leading cause of cancer-related deaths. Early-stage disease can be managed with endoscopic therapy or surgery, while advanced gastric cancer requires a multimodal treatment approach, including extensive lymphadenectomy. This study aims to evaluate the clinicodemographic profile and treatment outcomes of gastric cancer patients and to establish an effective therapeutic strategy. Methods: This retrospective descriptive cross-sectional study was conducted in the Department of Surgery at Shree Birendra Hospital. It included patients with gastric malignancies who had complete medical records. Data on patient history, AJCC staging, operative details, and postoperative findings were analyzed. Surgical choices were based on the clinical indication in each case. Clinicopathological characteristics and surgical outcomes were compared across tumor stages. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 24. Results: The study included 90 patients (62 males, 28 females) aged between 23 and 82 years. The most common clinical presentations were abdominal pain (58%), gastric outlet obstruction (18%), lump (5%), anemia (5%), and peritonitis (4%). Adenocarcinoma was the predominant histological type (87.78%). Curative surgery was performed on 73 patients (81.11%), while 17 patients (18.89%) underwent palliative procedures. Morbidity occurred in 16 patients (17.7%), primarily due to chest complications and sepsis, and mortality was recorded in 5 patients (5.5%). Conclusion: This study highlights the predominance of locally advanced gastric cancer in males, with distal gastric cancer and well-differentiated adenocarcinoma being the most common. Chest complications and sepsis were the leading causes of morbidity and mortality. No patients received perioperative chemotherapy, underscoring the need for updated treatment protocols to improve outcomes.

Validity of the Chronic Pain Grade Scale in nonspecific chronic low back pain

Higher pain grades are associated with high psychological burden and increase the risk for the persistence of chronic low back pain (CLBP). Previous results on the criterion validity of the Chronic Pain Grade Scale (CPGS) have been extended to the context of inpatient multidisciplinary orthopedic rehabilitation (MOR) and have been supplemented with additional psychosocial and work-related measures. In this multicenter study, psychological, work- and pain-related outcomes were examined among 1010 individuals with nonspecific CLBP (ICD-10: M51/53/54) prior to the beginning of an inpatient MOR stratified by pain grade (I-IV). Additionally, frequency distributions of scores regarding pain-specific self-efficacy, depression, and subjective prognosis of gainful employment by pain grade in patients were investigated. The CPGS differed between all pain grades in the psychological, work- and pain-related outcomes in the expected direction. In post hoc pairwise comparisons, gradeIV was significantly different from the lower grades. Patients with higher pain grades showed unfavorable levels in psychosocial parameters and more frequently scores in the clinical range than expected. These results confirm the criterion validity of the CPGS. The psychosocial risk pattern observed in higher pain grades supports the importance of conducting early pain-related and psychological diagnostic assessments and implementing systematic allocation to needs-based interdisciplinary multimodal treatments.

Recommendations for the use of nuclear medicine imaging in patients with neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid cancer in children. Despite intensive multimodality treatment, long-term survival of patients with high-risk NB, which comprises more than half of all cases, remains poor. Nuclear medicine is key in diagnosis, staging, response assessment and long-term follow-up of NB. The emergence of novel tracers and the increasing complexity of studies require updated guidelines for nuclear medicine imaging in NB. Standardising diagnostic techniques are essential for improving study comparability and ensuring test quality. This article aims to provide a comprehensive review of NB radionuclide diagnostic imaging, including its characteristics, accuracy, advantages, and limitations. It offers practical recommendations to multidisciplinary teams responsible for treating patients with NB. This review summarises the opinions of leading experts from the Neuroblastoma Spanish Group within the Spanish Society of Paediatric Haematology and Oncology (SEHOP) and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM).