Primary Tumor Research Articles

Identifying timing and risk factors for early recurrence of resectable rectal cancer: A single center retrospective study

BACKGROUND Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute. AIM To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor. METHODS Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan–Meier method and Cox proportional hazards modeling. RESULTS We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R ² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006). CONCLUSION RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.

Abstract B140: Further evaluation of social determinants of health including association of neighborhood disadvantage and population density with severity of activity- and mood- related interference in primary brain tumor patients

Abstract Purpose: Growing evidence links living in rural or socioeconomically disadvantaged areas with worse outcomes in cancer patients. Our previous work indicated that growing up in a rural area and experiencing food insecurity in childhood are associated with more severe activity and mood-related interference from symptoms in the primary brain tumor (PBT) population. This study investigates the association of current neighborhood deprivation and population density with activity- and mood-related interference in a cross-sectional cohort of 555 patients with a PBT enrolled in a natural history study (NCT03251989). Methods: National Area Deprivation Index (ADI) and population density were dichotomized into more (>40) and less (<40) disadvantaged and urbanized (>1,000 persons/sq mi) and non-urbanized (<1,000 persons/sq mi). Activity- and mood-related interference was stratified into none/mild (0-1) and moderate/severe (2-10). Logistic regression was used to test univariate and multivariate associations of moderate/severe activity- and mood-related interference with demographic and clinical variables. Bonferroni-Holm was implemented to adjust for multiple comparisons (p < 0.001) in univariate analyses. We used backwards elimination multivariate analyses to fit the final model. Variables were included modeling when univariate p <0.10. Results: The sample included more males (57%), median age 49 (range 18-85), living in more disadvantage neighborhoods (25%), and primarily in urbanized areas (61%). The majority (74%) had high grade tumors, most commonly glioblastoma (39%), with 49% with tumor recurrence, and 21% on active treatment. Univariate analysis showed neither ADI nor population density was significantly associated with activity-related interference (ADI OR=1.35, 95% CI [0.85, 2.13]; population density OR=1.20, 95% CI [0.80, 1.79]) or mood-related interference (ADI OR=0.85, 95% CI [0.52, 1.38]; population density OR=1.19, 95% CI [0.78, 1.81]). In the multivariate analyses tumor diagnosis (OR=0.92 CI [0.53, 1.58]) growing up in a non-urbanized area (OR=1.56 CI [1.02, 2.40]), not having enough to eat when growing up (OR=2.50 CI [1.13, 5.54], and number of surgeries (OR=1.50 CI [1.00, 2.23]) remained associated with moderate/severe activity-related interference with ADI, and similar results were found in the population density model. Tumor recurrence (OR=1.77 CI [1.17, 2.66]) and comorbidities (OR=0.53 CI [0.33, 0.85]) were associated with moderate/severe mood-related interference with ADI and similar results were found in the population density model. Conclusions: Although activity- and mood-related interference were not associated with current ADI or population density, activity-related interference was significantly related to early life social variables including growing up in a rural area and not having enough to eat growing up. This study may be foundational for future study directions exploring other social deprivation factors early life or current that contributes to more interference in the PBT population. Citation Format: Tara S. Davis, Bennett A. McIver, Kimberly Reinhart, Elizabeth Vera, Vivian A. Guedes, Macy L. Stockdill, Orieta Celiku, Terri S. Armstrong, Michelle L. Wright. Further evaluation of social determinants of health including association of neighborhood disadvantage and population density with severity of activity- and mood- related interference in primary brain tumor patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B140.

Abstract C154: Clinical, genomic, and socioeconomic factors underlying low survival rates from colorectal cancer in African American patients

Abstract Background: Colorectal cancer (CRC) patients of African ancestry (AFR) have higher incidence, higher mortality, and shorter overall survival (OS) than patients of non-African ancestry (non-AFR) in the United States. This disparity is likely due to a combination of clinical, genomic, and socioeconomic factors. We investigated real-world data of patients from a single tertiary cancer center to delineate the contribution of each of those variables. Methods: We analyzed data from 3,995 CRC patients, including 247 AFR and 3,748 non-AFR patients, diagnosed after 2014 and treated at Memorial Sloan Kettering Cancer Center. Every patient had a specimen sequenced with MSK-IMPACT, a targeted DNA sequencing assay that identifies genomic alterations in 341-505 genes. Genetic ancestry was determined using previously published methods by our group. Clinical annotations included sex, age at diagnosis (Dx), stage at Dx, and tumor location. Billing records were used to identify the type of insurance per patient and estimate their Yost Index (YI), a location-dependent socioeconomic status (SES) percentile score based on household incomes, house values, rent, poverty, education, and employment statistics. A multivariate cox proportional hazards model was used to assess the association between clinical variables (stage at Dx, age at Dx, sex, primary tumor location), genomic features (MSI status, BRAF, APC, SMAD4 alterations, chromosome 20Q amplifications), SES (YI) and OS. Propensity score matching (PSM) was performed using all features included in the multivariate model to assess outcome differences after matching for clinical, genomic, and socioeconomic variables. OS was measured in months from time of Dx to last follow-up and compared using the log-rank test. Results: AFR patients had worse OS compared to non-AFR patients (median OS: AFR, 44.9 vs. non-AFR, 64.3, p<0.001). AFR patients were younger at Dx (median 53 vs. 57 yo, p<0.001), had higher rates of right-sided tumors (41.1% vs. 30.2%, p<0.001), and less often had microsatellite unstable (MSI) tumors (5.26% vs 10.0%, p=0.014). Among microsatellite stable cases, AFR patients had a higher frequency of KRAS (57.1% vs. 44.7%, p=0.004) and a lower frequency of BRAF mutations (4.3% vs. 7.7%, p=0.069). Medicaid was more frequent among AFR patients (10.12% vs. 4.87%, p<0.001). AFR patients had lower SES (median YI 42 vs. 17, p<0.001). In a multivariate model accounting for clinical, genomic and socioeconomic features, AFR ancestry remained associated with worse outcomes (HR: 1.35, p = 0.007). AFR patients also had significantly shorter OS than the set of non-AFR patients matched for clinical, genomic, and socioeconomic features (5-yr OS was 31.6% for AFR vs 45.7% for non-AFR, log-rank p-value = 0.014). Conclusions: Colorectal cancer patients of AFR ancestry had significantly shorter OS than patients of other ancestries after accounting for basic clinical, genomic, and socioeconomic variables. Further research is needed in order to understand the causes of this disparity. Citation Format: Sharafudeen D. Abubakar, Henry Walch, Xuechun Bai, Tejiri Agbamu, Michele Waters, Kanika Arora, Farheen Shah, Christopher Fong, Justin Jee, Hannah Williams, Michael F Berger, Karuna Ganesh, Julio Garcia- Aguilar, Nikolaus Schultz, Rona Yaeger, Walid K Chatila, Francisco Sanchez-Vega. Clinical, genomic, and socioeconomic factors underlying low survival rates from colorectal cancer in African American patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C154.

The RAS/BRAF genes status in patients with colorectal cancer (review)

Colorectal cancer (CRC) is the third in prevalence among oncological diseases worldwide and second in the structure of oncological mortality. Genetic assessment of CRC is a necessary stage during selecting further treatment for patients. Many studies demonstrate a diverse distribution of mutations in the KRAS, NRAS, and BRAF genes in CRC. A critical literature review was conducted in order to systematize data on the mutational profile and genetic heterogeneity of these driver mutations in Russian patients with CRC. Articles were searched for in open databases. Totally 17 Russian studies and 3 English meta-analyses were analyzed for comparison with Russian data. Mutations in the KRAS, NRAS, and BRAF genes, according to Russian and international studies, are found in 40 %, 4 %, and 7 % in CRC patients, respectively. The frequency and specific localization of mutations may depend on the geographical location and nationality of the cohort. High intertumoral and intratumoral heterogeneity in CRC, especially in KRAS gene mutations, significantly influences the choice of further therapy and underscores the need for more detailed study of the mutational profile of the primary tumor, affected lymph nodes, and distant metastases. In Russia, several molecular genetic methods are used to determine somatic mutations in CRC with different sensitivity and specificity, the most common is real-time PCR. More accurate diagnostic methods include digital droplet PCR, Sanger sequencing, and next-generation sequencing, but each method has its limitations that must be considered when planning diagnostics and research. The promising directions in personalized oncology is the study of gene copy number variations, which may contribute to the development of new methods for treating CRC in the future. Despite the large number of studies, some aspects of the mutational profile of CRC in Russian studies remain poorly understood, which is why further research is needed on patients with colorectal cancer in Russia.

Reporting standards in randomized controlled trials involving neuro-oncology caregivers: A systematic review report from the RANO-Cares working group

Abstract BACKGROUND Family caregivers in neuro-oncology (e.g., spouse, family member, friend to a patient) have high unmet support needs, yet intervention trials and effective support options are scarce. The Response Assessment in Neuro-Oncology (RANO-) Cares working group investigated the methodological quality of neuro-oncology caregiver outcomes reporting in randomized controlled trials (RCTs). METHODS A systematic review was performed to evaluate to what extent RCTs assessing outcomes of caregivers of adult primary brain tumor patients adhere to minimum reporting standards. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life Research (ISOQOL) criteria for patient-reported outcome (PRO) reporting was used. Risk of bias was assessed per RCT. RESULTS Fifteen publications from 11 unique RCTs included 676 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on caregiver outcomes as a primary aim, of which eight (80%) satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two (40%) met ≥2/3 of applicable key criteria. Criteria often not reported adequately included sample size calculations (reported adequately in n=8, 53%), participant flow (n=9, 60%) window for data collection (n=1, 6%), and extent of (n=10, 66%), reasons for (n=9, 60%), and statistical approaches in dealing with (n=4, 26%) missing data. CONCLUSION Whilst there are opportunities to enhance reporting standards, RCTs that include neuro-oncology caregiver outcomes generally adhere to high quality reporting standards, and have low risk of bias, indicating good potential to impact clinical practice.

Video-Assisted Thoracoscopic Carinal Resection and Reconstruction in A Case of Primary Tracheal Tumor

Video-Assisted Thoracoscopic Carinal Resection and Reconstruction in A Case of Primary Tracheal Tumor

A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress

Glioblastoma is a Grade 4 primary brain tumor defined by therapy resistance, diffuse infiltration, and near-uniform lethality. The underlying mechanisms are unknown, and no treatment has been curative. Using a recently developed creatine kinase inhibitor (CKi), we explored the role of this inhibitor on GBM biology in vitro. While CKi minimally impacted GBM cell proliferation and viability, it significantly affected migration. In established GBM cell lines and patient-derived xenografts, CKi ablated both the migration and invasion of GBM cells. CKi also hindered radiation-induced migration. RNA-seq revealed a decrease in invasion-related genes, with an unexpected increase in glutathione metabolism and ferroptosis protection genes post-CKi treatment. The effects of CKi could be reversed by the addition of cell-permeable glutathione. Carbon-13 metabolite tracing indicated heightened glutathione biosynthesis post-CKi treatment. Combinatorial CKi blockade and glutathione inhibition or ferroptosis activation abrogated cell survival. Our data demonstrated that CKi perturbs promigratory and anti-ferroptotic roles in GBM, identifying the creatine kinase axis as a druggable target for GBM treatment.

Large ventricular myxoma causing inflow and outflow obstruction of the right ventricle; A Case Report

BackgroundMyxomas are the most common primary benign heart tumors, typically found in the left atrium, with only 2–4% occurring in the right ventricle. Clinical presentations vary widely, including congestive heart failure and systemic embolic phenomena. This case report describes a rare right ventricular myxoma causing both inflow and outflow obstruction, presenting as progressive exertional dyspnea.Case PresentationA 23-year-old male presented with two weeks of worsening exertional dyspnea. He was stable but tachypneic with a systolic murmur over the tricuspid area. Elevated erythrocyte sedimentation rate (ESR) and C-Reactive protein (CRP) were noted, while other lab tests were normal. Imaging, including echocardiography and chest tomography scan (CT) revealed a 4 × 3.8 × 4.6 cm mass in the right ventricle extending to the pulmonary trunk. Surgical resection via right ventriculotomy was performed, and histopathology confirmed myxoma. The patient recovered uneventfully.ConclusionRight ventricular myxomas, though rare, can cause significant obstruction and present with diverse symptoms. Timely diagnosis using imaging techniques like echocardiography is crucial. Surgical resection remains the definitive treatment, offering excellent outcomes and low recurrence rates. Early intervention is vital to prevent serious complications and ensure favorable patient prognosis.

Management and follow-up strategies for patients with head and neck paraganglioma

Abstract Objective Head-neck paragangliomas (HNPGLs) are rare tumors with approximately half arising due to germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx). Patients with HNPGL have heterogenous propensity to recur and metastasize. Thus, we aim to assess prevalence and predictors of recurrent (RD) and/or metastatic disease in patients with and without SDHx-related HNPGLs. Design and methods This cross-sectional study used retrospective data of 214 patients enrolled in six referral centers. Data included sex, age, primary tumor treatment, location, and size, biochemical phenotype, germline PVs, presence of RD (locoregional or new tumor), and/or metastasis. Results Patients with and without SDHx-related HNPGLs showed 74% and 40% prevalence of RD, respectively. Patients without SDHx-related HNPGLs presented with recurrent tumors only in head-neck regions. The only independent predictor for RD in the entire cohort was presence of SDHx PVs. Metastatic prevalence reached 9-13%. For patients with SDHx-related HNPGLs, large tumor size (>2.3cm, OR:50.0, CI:2.6-977.6), young age at initial diagnosis (<42years, OR:27.3, CI:1.8-407.2), and presence of SDHB PV (OR:15.6; CI:1.5-164.8) were independent predictors of metastasis. For patients without SDHx-related HNPGLs, only carotid-body location was an independent predictor of metastasis (OR:18.9, CI:2.0-182.5). Conclusions Patients without SDHx-related HNPGLs require long-term follow-up due to high prevalence of RD with imaging largely restricted to head-neck regions. As carotid-body HNPGLs have the highest metastatic risk among sporadic tumors, radical treatment with frequent follow-up is suggested until population-based data are available. Importantly, patients with SDHx-related HNPGLs might benefit from early radical treatment when tumors are still small to reduce metastatic risk.

Robotic and Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Multicenter Study From Saudi Arabia.

Peritoneal metastasis (PM) is a common evolution of abdominal tumors. Without aggressive multimodal treatment, it is associated with a poor prognosis. The aim of this study is to present a multicenter results from Saudi Arabia on minimally invasive CRS and HIIPEC. A retrospective analysis of a prospective maintained multicenter database was queried for all patients treated with laparoscopic or robotic CRS and HIPEC between 2019 and 2024 in Saudi Arabia. Surgical and oncological outcome was analyzed. Eleven consecutive patients underwent minimally invasive CRS and HIPEC between 2019 and 2024. Eight patients (72.7%) were operated by laparoscopy, one of them by single port access and three patients (27.3%) were operated robotically. Six patients (54.5%) were female. Median age was 42 (29-64). Primary tumor was PMP from the appendix, colon, and MCM in 6 (54.5%), 4 (36.4%), and 1 (9.1%) respectively. The median duration to complete the surgical procedure for all patients was 330 (230-580) min and for robotic CRS the median docking time was 570 (330-580) min. Median PCI was 2 (1-7) and completeness Cytoreduction (CC score 0) was achieved in the all patients (100%). Median hospital stay was 8 days (3-20). Four patients had one night postoperative ICU stay. Major morbidity (CTCAE) 3 and 4 occurred in three patients (27.3%) (Port site hernia, bleeding, and wound infection). No readmission to the hospital and no 90 days mortalities. The minimally invasive approach by laparoscopy or robot is a feasible and promising option for CRS and HIPEC. It reduces the hospital stay, early return to intended oncological treatment (RIOT). Further prospective clinical studies are needed to evaluate this approach.

Metabolomic characterization of human glioblastomas and patient plasma: a pilot study

Background Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling. Methods A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence. Results Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype. Conclusions In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.

EGFRVIII and EGFR targeted chimeric antigen receptor T cell therapy in glioblastoma

Glioblastoma is the most common primary brain tumor. Although there have been significant advances in surgical techniques, chemo and immunotherapies, and radiation therapy, outcomes continue to be devastating for these patients with minimal improvements in survival. Chimeric antigen receptor T cell therapy is a revolutionary approach that is a new pillar in the treatment of cancer. CAR T cell therapy has produced remarkable results in hematological malignancies; however, multiple limitations currently prevent it from being a first-line therapy, especially for solid tumors. Epidermal growth factor receptor is classically amplified in glioblastoma, and a variant, EGFR variant III, is expressed on glioblastoma, making it an exciting potential target for CAR T cell therapy. Although preclinical has exciting potential, clinical data has been heterogeneous. In this review, we assess the state of field of EGFR-targeted CAR T cells.

Successful outcome achieved with adjuvant chemotherapy with irinotecan plus cisplatin in rectal neuroendocrine carcinoma: a case report

BackgroundRectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin.Case presentationA 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence.ConclusionThis case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.

Epithelioid Trophoblastic Tumor Predominant Mixed Germ Cell Tumor of the Testis: A Case Report and Review of the Literature.

An epithelioid trophoblastic tumor is a rare form of gestational trophoblastic neoplasia that mostly affects the uterus and endocervix in female patients of the reproductive age group. The tumor is believed to arise from chorion leave-type intermediate trophoblast. The epithelioid trophoblastic tumor in men is extremely rare and mostly described in association with mixed germ cell tumors of the testis. It is more commonly identified at the metastatic sites than in the testis. The epithelioid trophoblastic tumor should be differentiated from placental site trophoblastic tumor and squamous cell carcinoma. The distinctive morphology and characteristic immunohistochemical staining pattern help differentiate epithelioid trophoblastic tumors from other neoplasms. Only 7 male patients with epithelioid trophoblastic tumors have been described to date. Of these 7 patients, 4 were in metastatic sites, 2 in the testis, and 1 in the lung without the involvement of the testis or retroperitoneum. The proportion of epithelioid trophoblastic tumors was only 5% in the 2 patients with testis involvement. Here, we report the third patient with a primary testicular epithelioid trophoblastic tumor in a young man. Further, this is the first report to document epithelioid trophoblastic tumor as dominant histology in a testicular germ cell tumor.

Effectiveness and Safety of mRNA Vaccines in the Therapy of Glioblastoma

Glioblastoma (GBM) is the most common and most malignant primary brain tumor, presenting significant treatment challenges due to its heterogeneity, invasiveness, and resistance to conventional therapies. Despite aggressive treatment protocols, the prognosis remains poor, with a median survival time of approximately 15 months. Recent advancements in mRNA vaccine technology, particularly the development of lipid nanoparticles (LNPs), have revitalized interest in mRNA-based therapies. These vaccines offer unique advantages, including rapid production, personalization based on tumor-specific mutations, and a strong induction of both humoral and cellular immune responses. mRNA vaccines have demonstrated potential in preclinical models, showing significant tumor regression and improved survival rates. Early-phase clinical trials have indicated that mRNA vaccines are safe and can induce robust immune responses in GBM patients. Combining mRNA vaccines with other immunotherapeutic approaches, such as checkpoint inhibitors, has shown synergistic effects, further enhancing their efficacy. However, challenges such as optimizing delivery systems and overcoming the immunosuppressive tumor microenvironment remain. Future research should focus on addressing these challenges and exploring combination therapies to maximize therapeutic benefits. Large-scale, randomized clinical trials are essential to validate the efficacy and safety of mRNA vaccines in GBM therapy. The potential to reshape the tumor microenvironment and establish long-term immunological memory underscores the transformative potential of mRNA vaccines in cancer immunotherapy.

Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets

Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth and a poor prognosis for patients. Despite advancements in treatment, the median survival time for GBM patients remains low. One of the crucial challenges in understanding and treating GBMs involves its remarkable cellular heterogeneity and adaptability. Central to the survival and proliferation of GBM cells is their ability to undergo metabolic reprogramming. Metabolic reprogramming is a process that allows cancer cells to alter their metabolism to meet the increased demands of rapid growth and to survive in the often oxygen- and nutrient-deficient tumor microenvironment. These changes in metabolism include the Warburg effect, alterations in several key metabolic pathways including glutamine metabolism, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, increased uptake and utilization of glutamine, and more. Despite the complexity and adaptability of GBM metabolism, a deeper understanding of its metabolic reprogramming offers hope for developing more effective therapeutic interventions against GBMs.

Stage IV gastric cancer with microsatellite instability–high achieving long-term survival by gastrectomy after nivolumab as third-line therapy: a case report and literature review

BackgroundThe prognosis for stage IV gastric cancer remains poor; however, the advent of immune checkpoint inhibitors (ICIs) such as nivolumab has increased the number of patients with long-term survival. Patients with microsatellite instability (MSI)–high gastric cancer have been recognized as a highly effective population for ICIs. Herein, we report a patient with MSI–high advanced gastric cancer treated with gastrectomy after the administration of nivolumab as third-line therapy.Case presentationA 73-year-old woman presented with a type 3 tumor in the lower part of the gastric body, which was diagnosed as gastric cancer through biopsy. Staging laparoscopy revealed that the tumor had invaded the pancreas and the posterior lobe of the transverse mesocolon, and disseminated nodules were found near the ligament of Treitz. After 4 courses of S-1 plus cisplatin therapy, laparoscopic gastrojejunal bypass was performed because of difficulty in oral intake. She received S-1 plus oxaliplatin therapy after a gastrojejunal bypass; however, her regional lymph nodes were enlarged. After six courses of paclitaxel plus ramucirumab as second-line chemotherapy, computed tomography (CT) showed exacerbation of peritoneal dissemination; thus, nivolumab was selected as the third-line therapy. The tumor was characterized by MSI–high. At 24 courses, CT and gastroscopy revealed a complete clinical response of the tumor; however, re-growth of the primary tumor was observed at 36 courses. The patient underwent distal gastrectomy with D1 + lymph node dissection, and received S-1 monotherapy as adjuvant therapy for 1 year. No recurrence was noted at 39 months after the surgery.ConclusionsWe report a patient with highly advanced gastric cancer with peritoneal dissemination, which worsened during second-line therapy and was successfully treated with gastrectomy after nivolumab administration as a third-line therapy. MSI–high gastric cancer is a target that should be actively considered for the administration of ICIs, such as nivolumab, and multidisciplinary treatment combined with chemotherapy and gastrectomy, including conversion surgery, can lead to patients’ long-term survival.

Utilizing machine learning algorithms for predicting risk factors for bone metastasis from right-sided colon carcinoma after complete mesocolic excision: a 10-year retrospective multicenter study

BackgroundBone metastasis (BM) occurs when colon cancer cells disseminate from the primary tumor site to the skeletal system via the bloodstream or lymphatic system. The emergence of such bone metastases typically heralds a significantly poor prognosis for the patient. This study's primary aim is to develop a machine learning model to identify patients at elevated risk of bone metastasis among those with right-sided colon cancer undergoing complete mesocolonectomy (CME).Patients and methodsThe study cohort comprised 1,151 individuals diagnosed with right-sided colon cancer, with a subset of 73 patients presenting with bone metastases originating from the colon. We used univariate and multivariate regression analyses as well as four machine learning algorithms to screen variables for 38 characteristic variables such as patient demographic characteristics and surgical information. The study employed four distinct machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), to develop the predictive model. Additionally, the model was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), while Shapley additive explanation (SHAP) was utilized to visualize and analyze the model.ResultsThe XGBoost algorithm performed the best performance among the four prediction models. In the training set, the XGBoost algorithm had an area under curve (AUC) value of 0.973 (0.953–0.994), an accuracy of 0.925 (0.913–0.936), a sensitivity of 0.921 (0.902–0.940), and a specificity of 0.908 (0.894–0.922). In the validation set, the XGBoost algorithm had an AUC value of 0.922 (0.833–0.995), an accuracy of 0.908 (0.889–0.926), a sensitivity of 0.924 (0.873–0.975), and a specificity of 0.883 (0.810–0.956). Furthermore, the AUC value of 0.83 for the external validation set suggests that the XGBoost prediction model possesses strong extrapolation capabilities. The results of SHAP analysis identified alkaline phosphatase (ALP) levels, tumor size, invasion depth, lymph node metastasis, lung metastasis, and postoperative neutrophil-to-lymphocyte ratio (NLR) levels as significant risk factors for BM from right-sided colon cancer subsequent to CME.ConclusionThe prediction model for BM from right-sided colon cancer developed using the XGBoost machine learning algorithm in this study is both highly precise and clinically valuable.

Diagnostic Accuracy of Circulating Tumor HPV DNA Testing in Patients With a Lateral Neck Mass

ImportanceThe most frequent presenting symptom for patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) is a lateral neck mass. Circulating tumor tissue–modified viral (TTMV)–HPV DNA is a unique biomarker produced by the fragmentation of HPV DNA during the degradation of HPV-associated tumors, and its detection and quantitation are currently being used as an adjunct to imaging in monitoring for disease recurrence and may have utility for diagnosis.ObjectiveTo measure the diagnostic characteristics of TTMV-HPV DNA compared with gold standard tissue biopsy for diagnosing HPV-OPSCC in patients presenting with an indeterminate lateral neck mass.Design, Setting, and ParticipantsThis prospective diagnostic test study enrolled patients 18 years or older who presented with a lateral neck mass to a large urban tertiary health care system from December 2021 to June 2023. Participants underwent standard-of-care testing to obtain a tissue diagnosis and a single TTMV-HPV DNA measurement.Main Outcomes and MeasuresThe primary outcome of interest was sensitivity, while specificity, positive predictive value, and negative predictive value were secondary end points. A subset analysis was performed comparing test performance metrics between TTMV-HPV DNA testing and fine-needle aspiration.ResultsA total of 138 patients were included, of whom 80 (58.0%) were men, with median age of 57.5 years (IQR, 43.3-67.0 years). Of 138 patients, 87 (63.0%) had neck masses in level 2 and 47 (34.1%) had HPV-OPSCC. TTMV-HPV DNA testing exhibited a sensitivity of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), specificity of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]), positive predictive value of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), and negative predictive value of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]).Conclusions and RelevanceIn this diagnostic study of patients presenting with a lateral neck mass, circulating TTMV-HPV DNA demonstrated excellent diagnostic test characteristics for the detection of HPV-OPSCC. Such testing may have particular utility for patients in whom obtaining adequate tissue is problematic, as is often the case with cystic neck masses and unknown primary tumors.

Glioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements

Glioma is the most common primary tumor of the central nervous system (CNS). Glioblastoma (GBM) is incurable with current treatment strategies. Additionally, the treatment of recurrent GBM (rGBM) is often referred to as terminal treatment, necessitating hospice-level care and management. The presence of the blood-brain barrier (BBB) gives GBM a more challenging or “cold” tumor microenvironment (TME) than that of other cancers and gloma stem cells (GSCs) play an important role in the TME remodeling, occurrence, development and recurrence of giloma. In this review, our primary focus will be on discussing the following topics: niche-associated GSCs and macrophages, new theories regarding GSC and TME involving pyroptosis and ferroptosis in GBM, metabolic adaptations of GSCs, the influence of the cold environment in GBM on immunotherapy, potential strategies to transform the cold GBM TME into a hot one, and the advancement of GBM immunotherapy and GBM models.