Adjuvant Chemoradiotherapy Research Articles

Adjuvant chemoradiotherapy plus PD-1 inhibitor for pN3 gastric cancer: a randomized, multicenter, Phase III trial.

D2 surgery followed by adjuvant chemotherapy has been established as the standard of care for patients with locally advanced gastric cancer in Asian countries. However, its efficacy is still unsatisfactory, especially for pathological N3 disease. The RACING trial is a randomized, multicenter, Phase III trial designed to compare the efficacy and safety of chemotherapy alone versus chemotherapy in combination with PD-1 inhibitor and radiotherapy in patients with pN3 gastric or gastroesophageal junction adenocarcinoma. A total of 433 patients will be assigned at a 1:1 ratio to the two arms. The primary end point is the 3-year disease-free survival rate. The secondary end points include the 3-year overall survival rate, 3-year local recurrence-free survival rate, treatment-related adverse events and quality of life.Clinical Trial Registration: NCT04997837 (ClinicalTrials.gov).

Primary dedifferentiated liposarcoma of the gallbladder: a case report and literature review

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

The Impact of Timing of Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma on Patient Overall Survival: A Multi-centre Retrospective Study

Abstract Background The optimal timing of initiating adjuvant temozolomide (TMZ) chemoradiotherapy after surgery in patients with glioblastoma is contentious. This study aimed to determine whether the timing of adjuvant treatment affects their overall survival (OS). Methods Consecutive adult patients with histologically-confirmed newly-diagnosed glioblastoma treated with adjuvant TMZ chemoradiotherapy across all neurosurgical centers in Hong Kong between 2006 and 2020 were analyzed. The surgery-to-chemoradiotherapy (S-CRT) interval was defined as the date of the first surgery to the date of initiation of adjuvant TMZ chemoradiotherapy. Results Four-hundred and seventy-two patients were reviewed. The median S-CRT interval was 41 days (IQR: 33-48) and the mOS was 16.7 months (95% CI: 15.9-18.2). The median age was 58 years (IQR: 50-63). Multivariable Cox regression with restricted cubic splines identified a non-linear relationship between the S-CRT interval and mOS. Post-hoc analysis-derived S-CRT intervals revealed that early CRT (< 5 weeks; adjusted hazard radio (aHR): 1.11; 95% CI 0.90-1.37) or late CRT (> 9 to 12 weeks; aHR 1.07; 95% CI 0.67-1.71) were not significantly associated with OS. Subgroup analyses for extent of resection (EOR) and pMGMT methylation status revealed no significant difference in treatment timing on OS. Conclusion The timing of adjuvant TMZ chemoradiotherapy if commenced within 12 weeks after glioblastoma diagnosis did not influence OS, regardless of EOR or pMGMT methylation status. Clinical judgement should be exercised in optimizing the timing of initiating adjuvant therapy.

Phase II Trial of Induction Chemotherapy for Advanced Sinonasal Squamous Cell Carcinoma.

Outcomes after primary surgery for advanced sinonasal squamous cell carcinoma (SCC) are poor. We tested whether induction chemotherapy (IC) can improve disease control or organ preservation. A phase II trial evaluated previously untreated patients with stage II-IV, M0 sinonasal SCC. Patients received IC with docetaxel, cisplatin, and fluorouracil, followed by chemoradiotherapy (CRT) for responders and surgery with adjuvant radiotherapy or CRT for non-responders. The primary endpoints were overall response rate (ORR) and locoregional control (LRC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), organ preservation, and treatment toxicity. Of the 31 patients enrolled between 2008 and 2020, 28 were evaluated for efficacy. Disease was T4a, T4b, and N+ in 57%, 21%, and 36% of patients, respectively. The ORR was 82.1%; 17.9% of patients had stable disease, and 0% had progressive disease. Grade 3 and 4 adverse events (AE) occurred in 54% and 18% of patients, respectively; there were no Grade 5 AEs. The 2-year LRC and PFS rates were 64.3% (95% CI 40.4-77.6) and 52.4% (95% CI 32.3-69.0), respectively. The median PFS was 25.8 months. The median OS was 47.4 months, with a 2-year OS rate of 69.4% (95% CI 44.9-80.4). No survival difference was observed between surgery versus CRT (hazard ratio 1.07, 95% CI 0.9-3.84). Of patients alive at 2 years, 63% achieved organ preservation, avoiding maxillectomy (38%), craniotomy (13%), or orbital exenteration (38%). IC and response-directed treatment achieved promising disease control and added organ preservation for patients with advanced sinonasal SCC.

RADT-23. MOLECULAR PROFILING OF GLIOMAS: INSIGHTS INTO RADIONECROSIS AND PSEUDOPROGRESSION THROUGH NEXT-GENERATION SEQUENCING

Abstract BACKGROUND Gliomas, the most common primary tumors of the CNS, presenting diagnostic and therapeutic challenges due to their heterogeneity. Next-generation sequencing (NGS) enhances diagnostic precision by identifying genetic alterations, guiding accurate diagnosis and personalized treatment strategies. Post-treatment complications such as radionecrosis and pseudoprogression present additional diagnostic difficulties, often mimicking tumor recurrence. This study aimed to evaluate the association between genetic alterations detected by NGS and treatment-related complications. METHODS This retrospective study analyzed data from electronic medical records at a Brazilian Radiation Therapy Department (2018-2023). The study included patients with gliomas who underwent surgical resection followed by adjuvant radiochemotherapy and subsequently developed complications such as radionecrosis and pseudoprogression. Genetic alterations detected by the HSL 500 (NGS) test were evaluated for their association with these complications using Fisher’s Exact Test. RESULTS Out of 192 patients treated for glioma, 46 (23.96%) experienced treatment-related complications, with 20 patients having available NGS test results. Among these, eight cases were identified as pseudoprogression, fifteen as radionecrosis, with three patients presenting both conditions. All 20 patients with NGS results were diagnosed with high-grade gliomas, eight of whom underwent reirradiation, resulting in two cases of radionecrosis post-reirradiation. Although no statistically significant association was found between genetic alterations and radionecrosis or pseudoprogression, specific mutations were prevalent in each group. In radionecrosis cases, the most common mutations were TERT promoter (c.1-124C>T) (n=9, p=0.613) and EGFR amplification (n=8, p=1.0). In pseudoprogression, frequent mutations included TERT promoter (c.1-124C>T) (n=6, p=0.642), EGFR (n=5, p=0.67), PTEN (n=4, p=1.0), NF1 (n=2, p=0.537), and P53 (n=2, p=0.197). CONCLUSION Molecular testing for glioma characterization is crucial for diagnosis and prognosis, aiding in understanding treatment-related complications. Strategies to avoid radionecrosis and pseudoprogression are vital to improve patient quality of life, especially in high-grade gliomas. Further studies are needed to confirm these trends and explore clinical relevance of mutations.

DDEL-16. MICROMESH FOR REVAMPING THE ‘COLD’ TUMOR MICROENVIRONMENT IN GLIOBLASTOMA IMMUNOTHERAPY

Abstract High-grade gliomas have poor prognoses with limited treatment options, typically maximal safe resection and adjuvant radiochemotherapy. Novel therapies often face challenges due to low brain penetrance and poor bioavailability. To address these issues, a conformable, compartmentalized polymeric implant called microMESH has been developed. microMESH provides localized, sustained release of drugs, small inhibitors, antibodies, and nanomedicines, enabling novel therapeutic combinations. When applied to the tumor margins, microMESH adheres to the tissue, releasing its therapeutic cargo over weeks and reducing systemic toxicity. Its biocompatibility, cytotoxicity, and anti-tumor efficacy were tested on murine cancer cells (CT-2A) and orthotopic glioblastoma syngeneic models. Exposing primary bone marrow-derived monocytes (BMDM) to CT-2A conditioned medium increased the expression of anti-inflammatory cytokines (IL-10 and IL-4) by 2 times without significantly affecting the pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), indicating that CT-2A cells tend to establish an immunosuppressive ‘cold’ tumor microenvironment. Next, the co-incubation of CT-2A cells with BMDM followed by the administration of the immune checkpoint inhibitor aCD47 resulted in a cancer cell viability drop by 50% already at 50 μg/ml aCD47 after 1 day. Additionally, pre-treatment with docetaxel (DTXL) further decreased cell viability, suggesting a synergism between aCD47 and the chemotherapeutic drug. Flow cytometry showed that 50 nM DTXL at 3 days post-incubation was responsible for a strong translocation of the ‘immunogenic dell death’ protein calreticulin on the cell membrane, potentially explaining the synergism. Over 2 months, the intracranially deployed microMESH biodegraded without inducing any toxic effect. In orthotopic CT-2A tumors, aCD47/DTXL–microMESH (0.75 mg/kg, single intracranial application) showed a 40-day survival compared to 22 days for iv DTXL (3 mg/kg qod), 24 days for ip aCD47 (5 mg/kg qod), and 18 days for untreated mice. microMESH helped identify and enabled novel combination therapies directly at the tumor bed, demonstrating superior efficacy over systemic therapies.

RADT-24. WALLERIAN DEGENERATION OF THE CORTICOSPINAL TRACT IN GLIOMAS: A RETROSPECTIVE ANALYSIS AND A SYSTEMATIC REVIEW OF MOTOR FUNCTION IN ELOQUENT AREAS POST-RADIATION THERAPY. HOW IMPORTANT IS MOTOR FUNCTION FOR PATIENTS WITH GLIOMAS IN RADIATION THERAPY?

Abstract BACKGROUND The quality of life for patients with gliomas is significantly impacted by tumor characteristics, treatment modalities, and radiation dosages. Variability in radiotherapy protocols and differences in tissue tolerance necessitate a detailed risk-benefit assessment, especially in eloquent brain areas responsible for motor functions. METHODS A retrospective analysis of electronic medical records from a Brazilian Radiation Therapy Department (2018-2023) was conducted. Patients with gliomas who underwent surgical resection and adjuvant radiochemotherapy, subsequently developing Wallerian Degeneration of the Corticospinal Tract (WDCT), were included. Additionally, a systematic search was performed in PubMed, Embase, and Cochrane databases, focusing on radiotherapy in eloquent areas and evaluating motor function. Of the 1,064 studies identified, 11 underwent full-text review by two independent examiners. RESULTS Among 192 glioma patients, 13 (6.77%) developed WDCT, all with high-grade gliomas, including 3 post-reirradiation cases. Retrospective dosimetric analysis of the corticospinal tract was performed for two patients who had tractography. Patient 1, with right frontoparietal tumor, had an ipsilateral corticospinal tract volume of 10.6 cm³, a max dose of 62.81 Gy, and 0.5 cc receiving 62.2 Gy; the contralateral tract volume was 18.5 cm³, with 0.5 cc receiving 51 Gy. Patient 2, with right frontal tumor, had an ipsilateral corticospinal tract volume of 31.1 cm³, a max dose of 42.76 Gy, and 0.5 cc receiving 42.37 Gy; the contralateral tract volume was 30.3 cm³, with 0.5 cc receiving 24.19 Gy. The systematic review identified 5 studies reporting pre- and post-radiotherapy motor outcomes in eloquent areas, with 4 focusing exclusively on gliomas. However, heterogeneity in radiotherapy techniques and outcome assessments precluded a meta-analysis. CONCLUSION Motor function in glioma patients undergoing radiation therapy remains an underexplored area. Future studies should focus on standardized assessments of functional outcomes to establish dose constraints and optimize treatment protocols, thus improving the quality of life for glioma patients.

EPID-18. PATTERNS OF CARE AND CLINICAL OUTCOMES OF PATIENTS WITH GLIOBLASTOMA FROM 2005-2020: A REAL-WORLD ANALYSIS

Abstract BACKGROUND Survival for glioblastoma (GBM) remains low, with disparities affecting outcomes. Standard of care (SoC) includes surgery and adjuvant chemoradiation. This study explores demographics, treatment patterns, and outcomes of GBM patients in the United States. METHODS A retrospective study was conducted on patients with GBM in the National Cancer Database for GBM patients between 2005-2020 according to ESMO Guidance for Reporting Oncology Real-World (GROW). Trends were analyzed with descriptive statistics and X2-test between time periods: 2005-08, 2009-12, 2013-16, and 2017-20. Predictors of SoC receipt were analyzed with multivariate logistic regression. Median overall survival (mOS) estimated using Kaplan-Meier and Cox regression models. Adjustment made using demographic, socioeconomic, and clinical factors. Outcomes reported as (Odds Ratio [OR]/Hazard Ratio [HR] 95% Confidence Interval) per STROBE guidelines. RESULTS Of 104,697 GBM patients, 42.5% were female. 91.2% White, 5.7% Black, and 2.0% were Asian. 5.3% were Hispanic. Median age was 65 years (IQR:57-73). Percentage of patients ≥65 years increased from 48.8% in 2005-08 to 54.0% in 2017-20. 56.5% of patients received SoC. SoC usage increased over time: 2009-12 (OR:1.26, 1.21-1.31, P<0.001) vs 2013-16 (OR:1.36, 1.31-1.41, P<0.001) vs 2017-20 (OR:1.51, 1.45-1.57 P<0.001). Females (OR:0.91, 0.89-0.93 P<0.001), Black (OR:0.81, 0.77-0.86 P<0.001), and Hispanics (OR:0.92, 0.86-0.97, P=0.004) were less likely to receive SoC than males, White, and non-Hispanics. Privately insured were more likely to receive SoC than Medicare (OR:0.83, 0.80-0.87, P<0.001), Medicaid (OR:0.68, 0.64-0.71, P<0.001), and uninsured patients (OR:0.60, 0.55-0.64, P<0.001). SoC recipients had mOS of 14.6 months (14.5-14.8) vs 4.8 (4.7-4.9) for non-recipients (P<0.001). Compared to 2005-08, survival improved over time: 2017-20 (HR:0.83, 0.82-0.85, P<0.001) vs 2013-16 (HR:0.88, 0.86-0.89, P<0.001) vs 2009-12 (HR:0.93, 0.91-0.94, P<0.001). CONCLUSIONS Receipt of SoC has risen with significant increase in survival. However, female, Black, and Hispanic patients were less likely to receive SoC. Targeted efforts are warranted to mitigate disparities.

DISP-02. SOCIOECONOMIC FACTORS INFLUENCE OVERALL SURVIVAL IN CHEMORADIATION-TREATED NEWLY DIAGNOSED WHO GRADE 4 GLIOBLASTOMA

Abstract Social determinants of health are known to influence health outcomes, yet the interactive effects of patient-specific socioeconomic variables on overall survival remain poorly characterized in patients with glioblastoma (GBM). We aimed to assess socioeconomic factors associated with overall survival in a clinically homogenous GBM population. Patients with newly diagnosed isocitrate dehydrogenase wild-type glioblastoma, who underwent maximal safe resection of contrast-enhanced (CE) and non-contrast enhanced tissue (NC) tissue with adjuvant chemoradiation from 1997-2017 were selected for inclusion. Socioeconomic factors were collected through retrospective chart review. Variables associated with overall survival on univariate cox proportional hazards models (p<0.05) were selected for multivariate analysis. 272 patients (42.6% female, 14.3% minority) were included. On univariate logistic regression, older age (HR: 1.23, p<0.001), greater residual CE tissue (HR: 3.95, p<0.001), were associated with reduced survival. Greater extent of resection NCE tissue (HR 0.94, p=0.028), higher postoperative KPS (HR 0.89, p=0.034), and unemployment (HR: 0.67, p=0.022), were associated with longer overall survival. On multivariate analysis, age was associated with reduced survival (HR: 1.31, p<0.001), while unemployment (HR:0.69, p=0.049) was associated with longer overall survival. Subgroup multivariate analyses was performed dividing patients into those <65 (n=185, 45% female, 11.9% minority, 48% employed) and those ≥65 (n=87, 37% female, 14% minority, 20% employed). In the <65 cohort, protective factors included retirement (HR: 0.49 p=0.004), and unemployment (HR:.57, p=0.006). Older age (HR: 1.03, p=0.004), and greater residual CE tissue (HR: 1.16, p=0.03) continued to be associated with poorer survival. No variables correlated with outcomes in the ≥65 cohort. Active employment was associated with reduced survival in GBM patients treated with standard care, potentially serving as a proxy for access to subsequent treatment.

TMIC-87. ICAM-1 REGULATE EXTRACELLULAR VESICLE-MEDIATED IMMUNOSUPPRESSIVE MONOCYTE IN HUMAN GLIOBLASTOMA CELL

Abstract Glioblastoma is the most common malignant primary brain tumor and is universally fatal. Treatment involves maximal safe resection with adjuvant chemoradiation. Poor prognosis in glioblastoma is multifactorial, and local and systemic immunosuppression is an important factor. Extracellular vesicles (EVs) are small, membrane-bound particles released by cells into the external environment. They play a key role in intercellular communication. In glioblastomas, EVs regulate immunosuppression through induction of myeloid-derived suppressor cells (MDSCs) in a process dependent on the PD-1/PD-L1 and IL-6 axes. Primary cilia are microtubule-based organelles that play crucial roles in various cellular processes and signal transduction cascades. We recently showed that primary cilia modulate IL-6 expression and consequently, MDSC induction. Comparative proteomic analysis of EVs derived from human glioblastoma cells devoid of cilia showed loss of ICAM-1 expression compared to control glioblastoma cells. ICAM-1 (Intercellular Adhesion Molecule-1) is a cell surface glycoprotein that mediates cell-cell adhesion and immune responses. In this study, we showed that depletion of primary cilia in human glioblastoma cells result in increased PD-L1 but loss of IL-6 and ICAM-1. RNAi-meidated loss of ICAM-1 was synergistic with primary cilia depletion in preventing MDSC inductionn normal human monocytes exposed to glioblastoma-derived EVs. Exogenous IFN-g was sufficient to restore IL-6 levels and MDSC induction despite loss of primary cilia and ICAM-1 suggesting that primary cilia act upstream of IFN-g, IL-6 and ICAM-1 in glioblastoma-mediated MDSC induction. This study is the first to connect primary cilia signal transduction to IL-6 and ICAM-1 expression and to MDSC induction. The evidence suggests a potential parallel primary cilia regulatory cascade independent of the PD-L1 axis that controls tumor-mediated immunosuppression. These results may inform novel therapeutic strategies aimed at increasing efficacy of immunotherapy in the glioblastoma and other neoplastic processes.

SURG-02. ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMA WITH LEPTOMENINGEAL DISSEMINATION PRESENTING WITH CRANIAL NEUROPATHY IN AN ADULT PATIENT: ILLUSTRATIVE CASE AND REVIEW OF THE LITERATURE

Abstract INTRODUCTION Anaplastic pleomorphic xanthoastrocytomas (APXA) are very rare, grade III malignant astrocytic glial neoplasms first described as a distinct entity in the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). They are generally seen in pediatric and young adult patients as supratentorial lesions with both solid and cystic components and have a high propensity for recurrence despite local treatment. APXAs occasionally demonstrate leptomeningeal dissemination (LMD) but extremely seldom at the time of diagnosis. They are typically treated via surgical resection with adjuvant chemoradiation, although there is no standard of care for adjuvant therapy. Case Presentation: The authors describe the case of a 37-year-old male with a history of seizures since age 11 who presented with four months of worsening headache, increasingly frequent seizures, and diplopia with right cranial nerve III palsy. Imaging at the time of diagnosis of his seizure disorder as a child demonstrated a small left temporal lesion, which remained stable on imaging for over 20 years and was never biopsied, however MRI at current presentation showed significant interval enlargement with intralesional hemorrhage and leptomeningeal enhancement involving the left temporal and parietal lobes, left internal auditory canal, and right oculomotor nerve. He underwent surgical resection with gross total resection achieved and pathology revealed WHO Grade III pleomorphic xanthoastrocytoma with ATG7::RAF1 fusion, 9p21 deletion, and TERT promoter mutation on next generation sequencing. This was followed by adjuvant whole brain radiation with boost and treatment with MEK inhibitor cobimetinib. His postoperative course was remarkable for intermittent speech difficulty and improving right third nerve palsy. CONCLUSION We describe the unusual presentation of an already exceedingly rare primary CNS tumor, namely APXA in an adult patient with LMD and cranial neuropathy at the time of diagnosis, and detail tailored adjuvant therapy based on genomic profiling.

DDDR-45. INVESTIGATING TEMOZOLOMIDE RESISTANCE IN GLIOBLASTOMA USING A CLINICALLY RELEVANT DOSING REGIMEN

Abstract The standard of care of management for glioblastoma, the most common primary malignant brain tumor in adults, involves maximal safe surgical resection followed by adjuvant chemoradiotherapy and six cycles of adjuvant temozolomide (TMZ). Approximately half of all treated patients develop chemoresistance to TMZ. The evolution of chemoresistance to temozolomide in vitro has historically involved continuous exposure to drug, as opposed to clinical dosing schedules, which involve five days of treatment followed by 23 days of recovery. Thus, in this study, we examined the emergence of chemoresistance to TMZ in vitro, using a clinical dosing regimen. Temozolomide dose response to RN1, an MGMT promoter unmethylated, IDH-wildtype, patient-derived glioblastoma cell line, was determined using cell titer glo. Cells were treated with TMZ for five days, followed by 23 days of recovery, in cycles. In each subsequent cycle, the dose of TMZ used was adjusted to previous cycle’s IC50, the concentration at which 50% of cell growth is inhibited. This protocol was repeated over three rounds. Cells treated with TMZ, as compared to the DMSO-treated control population, gradually acquired chemoresistance with a continuous increase in IC50. Our protocol therefore highlights how a clinically relevant dosing regimen may help capture the trajectory by which chemoresistance emerges, also allowing for the exploration of the molecular mechanisms underlying this phenomenon.

CNSC-50. PRIMARY INTRACRANIAL CONGENITAL GLIOBLASTOMA (PICG): A SYSTEMATIC REVIEW OF CASE REPORTS FROM 2000 TO 2023

Abstract BACKGROUND AND OBJECTIVE The most commonly reported congenital intracranial space occupying lesions are teratoma, glioma and neuroblastoma. Primary intracranial congenital glioblastoma (PICG) is one of the most lethal and extremely rare neoplasms. Most pediatricians and gynecologists are unable to detect it congenitally, posing an ominous risk of spread and disease severity. We aim to determine the clinical manifestations, number of reported cases, radiological findings and neuro-oncological management of PICG. MATERIALS AND METHODS A comprehensive literature search using PubMed Central and Google Scholar was done, retrieving 17 case reports and five case series of 31 patients with PICG and included using the Preferred Reporting items for Systematic Reviews and Meta-Analyses guidelines, published between 2000 and 2023. RESULTS The mean age at presentation was 86.00 ± 88.36 days, with both genders affected equally, i.e. 45.16%. The most common symptoms and signs at presentation were seizures (38.70%) and hydrocephalus (51.61%), respectively. Left hemispheric (48.38%), with frontoparietal involvement (16.12%) was the frequently affected site. MRI findings were suggestive of low intensity signal significant of hemorrhage or calcification and a heterogenous mass in 35.58% and 32.25% cases, respectively. Gross total resection (GTR) was achievable in 48.38% patients. Glial fibrillary acid protein and vimentin were positive in 45.16% and 29.03% cases, respectively. Intraoperative mortality and recurrence were noted in 25.80% and 9.68% of patients, respectively. The average follow up duration was 20.57 months. CONCLUSION PICG has an extremely aggressive course of natural progression. Congenital presentation and its lack of awareness among clinicians is itself a challenge for disease management. Adjuvant chemo-radiotherapy has proven fruitful along with GTR. Post-operative CSF diversion is warranted.

RADT-16. ADJUVANT CHEMO-RADIATION THERAPY AS A RISK FACTOR FOR POSTOPERATIVE HYDROCEPHALUS FOLLOWING RESECTION OF HIGH-GRADE GLIOMA: A PROPENSITY-MATCHED CASE SERIES

Abstract The discovery of the neural glymphatic network in the past decade has significant implications for clinical investigations on hydrocephalus. With emerging understanding of how meningeal lymphatics and perivascular pathways impact cerebrospinal fluid dynamics, it is conceivable that inflammatory and fibrotic changes induced by radiation and chemotherapy may contribute to the pathogenesis of postoperative hydrocephalus, a well-documented sequela of resective neurosurgery. This study investigates differences in adjuvant chemo-radiation therapy patterns between patients who develop hydrocephalus following high-grade glioma resection and those who do not experience this postoperative complication. A retrospective chart review identified 328 adult patients who underwent tumor resection at our institution between 2010-2020, of which 257 had high-grade gliomas. Demographic and clinical data were collected, including resection history and adjuvant chemotherapy and radiation history. Propensity Score Matching generated comparative cohorts (n=27) using covariates sex, age at first surgery, surgery type, tumor location, extent of first resection, tumor-associated seizures, ventricular opening, number of additional resective surgeries, and pre-surgical Karnofsky Performance Scale score. Independent t-tests assessed differences in adjunctive chemo-radiation trends between patients who developed hydrocephalus within 3 years postoperatively and those who did not. 27 of 257 patients (10.5%) who underwent resection for high-grade glioma developed hydrocephalus within 3 years of their first surgery. Patients who developed hydrocephalus were more likely to have initiated the Stupp protocol(P=0.004), completed the Stupp protocol(P=0.02), and undertaken multiple cycles of the Stupp protocol(P=0.0004). Additionally, these patients had a smaller time window between surgery and adjuvant chemo-radiotherapy initiation than patients who did not develop hydrocephalus (P=0.02). Importantly, engagement in other clinical trial regimens with chemotherapy or radiation therapy did not differ significantly between groups(P=0.08, P=0.49, respectively). Shortened time to initiation of chemo-radiation therapy postoperatively and increased number of chemo-radiation cycles may increase a patient’s susceptibility to develop postoperative hydrocephalus following resection of high-grade glioma.

SURG-21. DEVELOPMENT AND VALIDATION OF A CLINICAL RISK SCORE FOR POSTOPERATIVE OUTCOME IN NEWLY DIAGNOSED GLIOBLASTOMA: A REPORT OF THE RANORESECT GROUP

Abstract BACKGROUND Following resection or biopsy, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aim to make use of our RANO classification for extent of resection (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool. METHODS The RANO resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model was prognostically verified in a separate external validation cohort. RESULTS Our training cohort compromised 1003 patients with newly diagnosed IDH-wildtype glioblastoma, including 744 patients who underwent adjuvant radiochemotherapy (TMZ/RT→TMZ). Residual tumor, MGMT promotor methylation status, age, and KPS were prognostic of overall survival and forwarded into regression tree analysis. By combining eleven terminal nodes and individually weighting the prognostic factors, an additive scale (range, 0-9 points) integrating these four variables distinguished patients with low (0-2 points), intermediate (3-5 points), and high risk (6-9 points) for poor postoperative outcome (median overall survival: 24 vs. 16 vs. 6 months; p<0.01). The presence of the three risk groups was confirmed in the subgroups of patients treated with or without RT/TMZ→TMZ. The prognostic value of the risk score was verified in a external single-center validation cohort of newly diagnosed glioblastoma (n = 258, p<0.01). Compared to previously postulated models, goodness-of-fit measurements were superior for our score. CONCLUSIONS The novel RANO risk score serves as an easy-to-use, yet highly prognostic tool for postoperative patient stratification prior to further therapy. The score may serve to guide patient management and reduce imbalances between study arms in prospective trials.

CTNI-52. EXPEDITED CHEMORADIATION AFTER LASER INTERSTITIAL THERMAL THERAPY (LITT) IS FEASIBLE AND SAFE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND High-grade gliomas (HGG) are incurable primary brain tumors. Laser Interstitial Thermal Therapy (LITT) has emerged as an alternative to surgery for select patients. Hyperthermia can improve the efficacy of radiation and chemotherapy. Shortening the time between LITT and chemoradiation may maximize their biological and clinical benefits. This clinical trial evaluated the safety and feasibility of expediting chemoradiation after biopsy and LITT in patients with newly-diagnosed HGG. METHODS Patients with suspected HGG were enrolled. Those with pathologic confirmation of HGG and deemed appropriate candidates for LITT and chemoradiation were considered evaluable. Participants underwent 6 weeks of adjuvant chemoradiation within seven days of LITT. Endpoints were assessed until the completion of radiation, and included the occurrence of wound dehiscence; new, treatment-refractory seizures; cerebral edema; and completion of planned radiotherapy. RESULTS Fifteen patients with suspected HGG were enrolled and ten were considered evaluable. All ten patients were diagnosed with glioblastoma (GBM, IDHwt). Five patients were deemed unevaluable: four patients with other CNS tumors and one GBM patient who developed grade 4 postoperative edema. Of ten evaluable patients, the median age was 60.2 years (IQR: 51.0, 69.4), and median preoperative KPS was 90 (IQR: 90, 80). The median time between LITT and the initiation of chemoradiation was seven days. There were no occurrences of significant protocol-related adverse events. CONCLUSIONS Accelerated initiation of chemoradiation after biopsy and LITT is safe and feasible for patients with newly diagnosed HGG. A larger study is needed to assess potential synergy of hyperthermia and chemoradiation to improve survival.

Assessment of Professional Practices in the Care Pathway of Patients with Upper Aerodigestive Tract Cancer in a University Hospital.

The main objective of this study was to evaluate the alignment between treatment decisions made during multidisciplinary team meetings (MTMs) and the treatments received by patients with upper aerodigestive tract cancers. The secondary objective was to identify factors influencing potential discrepancies. This retrospective, single-center study was conducted at a tertiary referral center and included 147 patients diagnosed with squamous cell carcinoma of the upper aerodigestive tract. Patients were divided into two groups based on the match between MTM-decided and actual treatments. Multivariate analysis was performed to assess factors independently associated with discrepancies. Out of 147 patients, 28 (19%) received treatment that did not align with MTM decisions. Among these, eight died before treatment, one patient refused care, five received supportive care, five patients underwent surgery, three received radiotherapy alone, one patient underwent surgery and adjuvant radiochemotherapy, one patient underwent surgery and adjuvant radiotherapy alone, three patients received radiochemotherapy, and one patient received palliative chemotherapy. Independent significant factors associated with non-concordance included poor performance status (PS) and treatment not received at a tertiary reference center. Treatment shifts mainly involved downgrading from curative to palliative care. This study highlights the importance of patient health status in determining deviations from MTM decisions. Further efforts should focus on improving the integration of patient comorbidities and health status into MTM decision-making to optimize care delivery.

Establishment of a Novel Risk Stratification System Integrating Clinical and Pathological Parameters for Prognostication and Clinical Decision‐Making in Early‐Stage Cervical Cancer

ABSTRACTBackgroundHighly heterogeneity and inconsistency in terms of prognosis are widely identified for early‐stage cervical cancer (esCC). Herein, we aim to investigate for an intuitional risk stratification model for better prognostication and decision‐making in combination with clinical and pathological variables.MethodsWe enrolled 2071 CC patients with preoperative biopsy‐confirmed and clinically diagnosed with FIGO stage IA‐IIA who received radical hysterectomy from 2013 to 2018. Patients were randomly assigned to the training set (n = 1450) and internal validation set (n = 621), in a ratio of 7:3. We used recursive partitioning analysis (RPA) to develop a risk stratification model and assessed the ability of discrimination and calibration of the RPA‐derived model. The performances of the model were compared with the conventional FIGO 2018 and 9th edition T or N stage classifications.ResultsRPA divided patients into four risk groups with distinct survival: 5‐year OS for RPA I to IV were 98%, 95%, 85.5%, and 64.2%, respectively, in training cohort; and 99.5%, 93.2%, 85%, and 68.3% in internal validation cohort (log‐rank p < 0.001). Calibration curves confirmed that the RPA‐predicted survivals were in good agreement with the actual survivals. The RPA model outperformed the existing staging systems, with highest AUC for OS (training: 0.778 vs. 0.6–0.717; internal validation: 0.772 vs. 0.595–0.704; all p < 0.05), and C‐index for OS (training: 0.768 vs. 0.598–0.707; internal validation: 0.741 vs. 0.583–0.676; all p < 0.05). Importantly, there were associations between RPA groups and the efficacy of treatment regimens. No obvious discrepancy was observed among different treatment modalities in RPA I (p = 0.922), whereas significant survival improvements were identified in patients who received adjuvant chemoradiotherapy in RPA II–IV (p value were 0.028, 0.036, and 0.024, respectively).ConclusionWe presented a validated novel clinicopathological risk stratification signature for robust prognostication of esCC, which may be used for streamlining treatment strategies.

Definite Treatment Delay With Neoadjuvant Chemotherapy and Longitudinal Monitoring by Circulating Tumor DNA for Advanced Cervical Cancer During Pregnancy: A Case Series and Literature Review.

Previous studies mainly concentrate on neoadjuvant chemotherapy (NACT) for delivery delay in FIGO Stage IB1-IIIB cervical cancer during pregnancy to prevent early preterm delivery while not affecting maternal outcome. Here, we described two pregnant patients with FIGO Stage IIIC cervical cancer about their diagnosis, treatment, and outcome. Both patients underwent cesarean delivery, left enlarged lymph node dissection, and longitudinal monitoring by circulating tumor DNA. Our study suggested that pregnant patient was completely response to NACT, which was confirmed by ctDNA monitoring, followed by left pelvic enlarged lymph node dissection during cesarean section and adjuvant chemoradiotherapy postpartum. The infant grew normally, without any evidence of chemotherapy-related side effects after delivery. In pregnant women with advanced cervical cancer, longitudinal ctDNA monitoring might be able to evaluate maternal response to NACT and confirm if delivery delay to optimize fetal outcome would compacting the maternal outcomes or not. Cervical cancer may not transmit across the placental barrier and so it is safe for delayed delivery until fetal maturity in utero during pregnancy.

Efficacy and Low Toxicity of Normo-Fractionated Re-Irradiation with Combined Chemotherapy for Recurrent Glioblastoma-An Analysis of Treatment Response and Failure.

Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p < 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p < 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm3) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well.