Type Of Primary Tumor Research Articles

Glioma Stem Cells: Novel Data Obtained by Single-Cell Sequencing.

Glioma is the most common type of primary CNS tumor, composed of cells that resemble normal glial cells. Recent genetic studies have provided insight into the inter-tumoral heterogeneity of gliomas, resulting in the updated 2021 WHO classification of gliomas. Thorough understanding of inter-tumoral heterogeneity has already improved the prognosis and treatment outcomes of some types of gliomas. Currently, the challenge for researchers is to study the intratumoral cell heterogeneity of newly defined glioma subtypes. Cancer stem cells (CSCs) present in gliomas and many other tumors are an example of intratumoral heterogeneity of great importance. In this review, we discuss the modern concept of glioma stem cells and recent single-cell sequencing-driven progress in the research of intratumoral glioma cell heterogeneity. The particular emphasis was placed on the recently revealed variations of the cell composition of the subtypes of the adult-type diffuse gliomas, including astrocytoma, oligodendroglioma and glioblastoma. The novel data explain the inconsistencies in earlier glioma stem cell research and also provide insight into the development of more effective targeted therapy and the cell-based immunotherapy of gliomas. Separate sections are devoted to the description of single-cell sequencing approach and its role in the development of cell-based immunotherapies for glioma.

EXTH-60. ONCR-GBM, A NOVEL ARMED ONCOLYTIC HSV-1 VECTOR ENGINEERED FOR EFFICACY AND SAFETY IN GLIOBLASTOMA

Abstract Glioblastoma (GBM) is the most common type of primary brain tumor in adults, with a 5-year overall survival of only 7%. Oncolytic viruses are a promising and active area of research in GBM with the recent approval of an oncolytic HSV-1 vector, teserpaturev (Delytact, also known as G47Δ, Daiichi Sankyo) for recurrent GBM based on an overall survival of 92% at 1 year. G207, an HSV-1 vector more attenuated than teserpaturev, recently reported acceptable tolerability with evidence of responses in children with recurrent or progressive high-grade glioma. These vectors are not expressing any cDNA transgene that may enhance and prolong antitumor activity. We report here the development of ONCR-GBM, an oncolytic HSV-1 vector specifically engineered for safety using a microRNA attenuation strategy to limit viral replication in healthy cell type of the CNS. ONCR-GBM has been developed from a novel potently oncolytic strain of HSV-1 and optimized for infection of GBM tumor cells. Antitumor efficacy has been further enhanced through the expression of multiple payloads designed to modify the immunosuppressive tumor microenvironment of GBM. We previously reported that a vector expressing IL-12 and a PD-1 antagonist nanobody achieved > 90% survival after a single injection in the GL261-Nectin1 orthotopic model. This vector promoted immune cell recruitment and activation in tumors and protected surviving animals from a subsequent tumor rechallenge. Additional payloads selected for interfering with the immune suppressive stroma in GBM have been evaluated for potentiating the response of IL-12 and anti PD-1 expressing HSV-1. We will present the outcome of the in vivo screen, and the selection of the optimal combination of payloads featured in ONCR-GBM clinical candidate.

EPCO-05. DIFFERENTIAL MOLECULAR PROFILING OF IDH WILD TYPE GLIOBLASTOMA SURVIVORS REVEALS THE ASSOCIATION OF NEOANTIGEN QUALITY WITH EXCEPTIONAL LONG SURVIVAL

Abstract Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor. Despite intensive multimodal treatment, the prognosis of GBM patients is poor with the median overall survival under 15 months. Defining the genetic profiles of rare long-term GBM survivors may provide insights into the molecular basis of GBM progression. IDH mutations have been identified as a favorable prognostic factors, and define a clinically and molecularly distinct group of GBM. Additional molecular mechanisms underlying the prolonged survival in IDHwt GBM patients remained unclear. Therefore, we explored the molecular profiles of 71 IDHwt GBM homogeneously treated patients exhibiting disproportionate survival. The cohort included 36 short-term survivors that deceased within 1 year after diagnosis (median survival of 7 months) and 35 long-term survivors exhibiting an exceptional survival above 4 years (median survival of 88 months). The differential genetic landscape of short- and long-term IDHwt GBM survivors outlined similar mutation load and few differences in the frequency of recurrent alterations, including chromosomes 19 and 20 duplication significantly overrepresented in long-term survivors. To assess the potential impact of T lymphocyte neoantigen-mediated activation towards extended GBM survival, we inferred the restricted HLA binding affinity of the somatic mutations and applied the immune fitness model to accurately predict high-quality neoantigens. Although the general neoantigen burden remained unvaried between short- and long-term survivors, we found that the immune quality of the predicted neoantigens is significantly higher in the patients with exceptional long survival. Moreover, the immune deconvolution of the tumor microenvironment from the gene expression data indicated the presence of CD8+ T lymphocytes and pro-inflammatory macrophages in samples harboring high-quality neoantigens from long-term survivors. This study identified the neoantigen quality as a main distinctive feature of exceptionally long-term survivors supporting the key role of cellular-mediated immune response to restrict tumor progression in IDHwt GBM.

RADT-34. ANALYSIS OF A METHYLATION CLASS-GUIDED RADIOTHERAPY IN MENINGIOMA PATIENTS - AND THE PROSPECTIVE PHASE II MARCIE TRIAL WITH CARBON-ION BOOST RADIOTHERAPY

Abstract Meningiomas represent the most common primary brain tumor type, with a recurrence rate of approximately 20% following resection. Classification by molecular classes was demonstrated to be more accurate in identifying patients at high risk of disease progression in meningiomas, compared to WHO grading only. Novel radiotherapeutic modalities using protons or carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, enabling a higher local dose deposition while reducing the radiation dose for organs of risks. The prospective single-arm phase II - MARCIE trial investigated a bimodal radiotherapy using photons (50 Gy in 25 fractions) and a carbon-ions boost with 18 Gy (RBE) in 6 fractions. Local progression-free survival after 3 years was defined as primary endpoint. In total, 33 patients were recruited before termination of the trial. After 3 years, local progression free survival was estimated at 94.7% and overall survival at 89.8%. Serious adverse events in the form of radiation necrosis were observed in 3 cases, requiring a subsequent treatment with bevacizumab. Post-hoc DNA methylation profiling revealed that relapses occur more frequently in high-risk meningiomas following radiotherapy, compared to the intermediate risk-group, confirming the prognostic relevance of the methylation-based meningioma classifier.Subsequently, a retrospective matched-pair analysis was performed to compare irradiated (n > 100) and non-irradiated meningiomas, stratified into the molecular risk groups (ben, int, high). The clinical benefit of postoperative radiotherapy and dose escalation with regard to the local control are currently being assessed for the respective molecular meningioma classes. Postoperative, bimodal radiotherapy with carbon-ion boost represent an auspicious treatment modality with an excellent local tumor control following resection. Molecular risk stratification is crucial in identifying patients who might benefit from postoperative radiotherapy.

Non-colorectal liver metastases: A review of interventional and surgical treatment modalities.

Liver metastases (LM) occur in up to 90% either simultaneously with the diagnosis of the primary tumor or at a later time-point. While resection of colorectal LM and resection or transplantation of neuroendocrine LM is part of a standard therapy with a 5-year patient survival of up to 80%, resection of non-colorectal and non-neuroendocrine LM is still discussed controversially. The reason for it is the significantly lower survival benefit of all different tumor entities depending on the biological aggressiveness of the tumor. Randomized controlled trials are lacking. However, reviews of case series with ≥100 liver resections are available. They show a 5-year patient survival of up to 42% compared to only <5% in patients without treatment. Risk factors for poor survival include the type of primary tumor, a short interval between resection of the primary tumor and liver resection, extrahepatic manifestation of the tumor, number and size of the LM, and extent of liver resection. Overall, it has recently been shown that a good patient selection, the technical advances in surgical therapy and the use of a risk score to predict the prognosis lead to a significantly better outcome so that it is no longer justified not to offer liver resection to patients with non-colorectal, non- endocrine LM. Since modern therapy of LM is multimodal, the optimal therapeutic approach is decided individually by a multidisciplinary team consisting of visceral surgeons, oncologists, interventional radiologists and radiologists as part of a tumor board.

Analysis of prognostic factors in patients with brain metastases affecting survival

IntroductionBrain metastases (BM) are associated with dismal prognosis as they cause significant morbidity and affect the quality of life of patients. Management of BM depends on the following factors: age, patient performance, size and the number of lesions, location of the tumor, comorbidities, primary tumor type, and extracranial disease burden. In the present study, the pattern of occurrence, clinical characteristics, treatment outcome of brain metastases, and factors, tumor characteristics, and treatment that may impact BM patients’ overall survival were analyzed.MethodsRetrospective analysis of medical records of 116 patients with histologically proven primary site solid tumors with brain metastases was done in the present study. Clinicoradiological and pathological parameters were documented. The relationship between variables and outcome was assessed by univariate analysis using the Cox proportional regression model to reach a significance of p < 0.05, to determine independent predictors of overall survival.ResultsOne hundred sixteen patients of BM from various solid malignancies were included. Age ranged from 18 to 81 years (median 53.5). One hundred four patients received WBRT with a dose range of 8–40Gy/1–15fr, 7 received SRS with a dose of 18–24Gy depending on the size of the metastatic lesion, and 2 received SRT 27–33Gy/3fr. At the time of final analysis, 47 patients with BM had expired, 60 were lost to follow-up, and 9 were alive. Median survival was 8.25 (0.5–32.5 months) months. Female gender (χ2 = 8.423; p = 0.015), RPA I (χ2 = 9.353; p = 0.05), and metachronous BM (χ2 = 3.793; p = 0.03) were associated with better survival. Patients with age 41–50 years, adenocarcinoma lung histology, and supratentorial location survived more than 2 years but did not show any statistical significance.ConclusionBrain metastases portend a very dismal prognosis. Certain clinicoradiological and pathologic factors have been identified to affect survival. More prospective multicentric trials, with a larger sample size, need to be conducted to assess the benefit of radiation in patients with limited life expectancy and identify prognostic and predictive factors for survival.

Analysis of Prognostic Factors and Construction of Prognostic Models for Invasive Micropapillary Carcinoma of the Breast

To compare and analyze the clinical characteristics of invasive micropapillary carcinoma (IMPC) of the breast (IMPC-B) and invasive ductal carcinoma (IDC) of the breast (IDC-B) and establish a prognostic model of IMPC-B. We retrospectively analyzed data for patients diagnosed with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 and screened 581 patients with IMPC and 1325 patients with IDC. We compared age, race, laterality, tumor site, histological grade, type of surgery, radiation, chemotherapy, whether the first primary tumor, T stage, N stage, M stage, and molecular type between IMPC-B and IDC-B and draw survival curves of IMPC-B and IDC-B. The relationship between clinical factors and prognosis was investigated by univariate analysis using the Log-rank test and multivariate analysis of the Cox proportional hazards regression model. A risk scoring model was constructed based on independent risk factors to distinguish high-risk and low-risk patients; in addition, a nomogram was created to predict patient survival. There were differences between the two groups in the age of onset, race, tumor site, histological grade, type of surgery, N stage, and molecular type (p < 0.05). Overall survival was decreased in IMPC-B compared with IDC-B (p < 0.05). The prognosis of IMPC-B was significantly correlated with histological grade, whether the first primary tumor, type of surgery, radiotherapy, chemotherapy, T stage, and N stage. Based on the relationship between the above factors and overall survival prognosis, the risk score model we constructed can effectively distinguish high-risk and low-risk patients (p < 0.05). The established nomogram had better performance in predicting survival in patients with IMPC-B (C - index = 0.78). IMPC-B has a worse prognosis than IDC-B, with earlier age of onset, higher histological grade, and later N stage, and luminal breast cancer is the main type. The nomogram can well predict the prognosis of patients with IMPC-B, which has a high clinical reference value and provides a scientific basis for clinical treatment.

A New Scoring Tool to Estimate Post-Treatment Ambulatory Status after Radiotherapy of Metastatic Spinal Cord Compression

<h3>Purpose/Objective(s)</h3> To improve treatment personalization of patients irradiated for metastatic spinal cord compression (MSCC), a score predicting post-treatment ambulatory status after radiotherapy (RT) alone (without surgery) was presented in 2008. Since then, upfront decompressive surgery has become more popular, which may decrease the predictive value of this score. A new scoring tool may be helpful. <h3>Materials/Methods</h3> Data of 283 patients treated with RT alone for MSCC in three prospective trials since 2010 were re-evaluated. Dose-fractionation of RT and 12 factors were analyzed including age (<=67 <i>vs</i> >67 years), gender, tumor type (breast ca. <i>vs</i> prostate ca. <i>vs</i> myeloma/lymphoma <i>vs</i> lung ca. <i>vs</i> others), interval from tumor diagnosis to MSCC (<=6 <i>vs</i> >6 months), number of affected vertebrae (1-2 <i>vs</i> >=3), further bone lesions (no <i>vs</i> yes), visceral metastases (no <i>vs</i> yes), time developing motor deficits (<=7 <i>vs</i> >7 days), pre-RT ambulatory status (ambulatory without aid <i>vs</i> ambulatory with aid <i>vs</i> not ambulatory), performance score (ECOG-PS 1-2 <i>vs</i> 3-4), sensory deficits (no <i>vs</i> yes), and sphincter dysfunction (no <i>vs</i> yes). For each factor that achieved significance in the multivariate analysis (logistic regression model) after backward regression modelling, scoring points were calculated by dividing the post-RT ambulatory rates (in %) by 10. The scoring points of these factors were added for each patient. The new score was compared to the previous tool for prediction (positive predictive value, PPV) of ambulatory and non-ambulatory status after RT. <h3>Results</h3> In the multivariate analysis, primary tumor type (p=0.010), sensory deficits (p=0.002), sphincter dysfunction (p=0.017), pre-RT ambulatory status (p<0.001) and ECOG-PS (p<0.001) were significant; a trend was found for the time developing motor deficits (p=0.054). Five of these factors were included in the score and available for 278 patients. ECOG-PS was not included, since ambulatory status and ECOG-PS were confounding variables. For internal validation, bootstrapping with 1000 replications was used. Corrected C-statistic accounting for overfitting was 0.91, which demonstrated good predictive performance of the model. Based on post-RT ambulatory rates, three prognostic groups (25-29, 30-38 and 39-45 points) were designed with ambulatory rates of 11% (5/44), 64% (49/77) and 97% (152/157), respectively. Rates of local control of MSCC were 100%, 82% and 94% at 1 year, and 100%, 82% and 87% at 2 years. Survival rates were 20%, 21% and 55% at 1 year, and 13%, 12% and 39% at 2 years. PPVs of the new score to predict ambulatory and non-ambulatory status were 97% and 89% <i>vs</i> 98% and 79% when using the previous score. <h3>Conclusion</h3> The new score appeared more precise than the previous one in predicting non-ambulatory status after RT. Depending on survival prognosis, patients with <=38 points likely benefit from upfront surgery. Since patients of the 39-45 points group had very high rates of post-RT ambulatory status and local control, they may not require surgery.

Association of Baseline Symptom Burden and Survival among Patients with Brain Metastases at a Tertiary Cancer Center

<h3>Purpose/Objective(s)</h3> Brain metastases (BrM) commonly affect patients with solid malignancies and often correlate with significant symptomatology that profoundly impacts patients' quality of life (QOL). As systemic therapies increasingly improve extracranial disease control but lag in intracranial efficacy, a rising incidence of BrM persists. Thus, an urgent need exists to characterize the most common symptoms associated with BrM and to correlate these symptoms with survival. <h3>Materials/Methods</h3> We identified patients who received radiation therapy (RT) within 30 days of BrM diagnosis at a tertiary cancer center between 2017-2020 who prospectively completed the MD Anderson Symptom Instrument-Brain Tumor questionnaire (a validated instrument among patients with BrM for evaluation of 22 symptoms and 6 interference measures linked to daily functioning). Symptom severity score (range 0-10, with higher scores indicating more severe symptomatology) and interference score (range 0-10, with higher scores indicating greater compromise of activity-related/affective function), were compared via t-test or ANOVA by: age (>65 vs. ≤65), sex, Karnofsky performance status (KPS) (high, 90-100 vs. low, <90), Charlson co-morbidity index (CCI) (high, >2 vs. low, 0-2), primary tumor type (lung, breast, melanoma, other), and initial intracranial treatment strategy (surgical resection, stereotactic RT, or whole brain RT). Overall survival (OS) was assessed via Cox regression with the above co-variates; symptom severity and interference were evaluated in separate Cox models. <h3>Results</h3> A total of 101 patients were identified (median age=67 years, female=60%, primary lung cancer=45%). Mean symptom severity and interference scores at time of BrM diagnosis were 2.4 and 3.4, respectively. The most common severe (defined as a score >4) symptoms were: fatigue (47%), distress (40%), sleep disturbances (37%), drowsiness (35%), and sadness (32%). The most common high (score>4) interference measures were: enjoyment of life (47%), ability to work (44%), and walking (35%). Higher symptom severity was more common among females than males (2.8 vs 1.8, respectively; p=0.01); there were no significant differences in mean symptom severity or interference scores by age, KPS, CCI, or initial BrM treatment strategy. On Cox regression, higher symptom severity and higher interference scores were associated with worse OS (HR 1.30 per 1-point increase [95% CI, 1.11-1.51], p<0.001; and HR 1.18 per 1-point increase [95% CI 1.07-1.30], p=0.001, respectively); age, KPS, CCI, and other co-variates were not significantly associated with OS. <h3>Conclusion</h3> High symptom and interference burden is common among patients with BrM and associated with worse survival. Further work should investigate how improving symptoms, such as through palliative care interventions, may impact QOL trajectories and survival among the BrM patient population.

Long-Term Outcome Following Intensity-Modulated Radiotherapy Delivered Using Individualized Clinical Target Volume Delineation Based on Stepwise Spread Pattern of Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> The optimal method for clinical target volume delineation in nasopharyngeal carcinoma has not yet been determined. We have developed an individualized CTV delineation protocol based on the stepwise spread patterns of NPC. This study aimed to determine the long-term outcomes and toxicities in NPC patients receiving intensity-modulated radiotherapy with individualized CTV delineation. <h3>Materials/Methods</h3> We retrospectively reviewed the data of patients with newly diagnosed nondisseminated NPC who underwent IMRT using our individualized CTV delineation protocol. A total of 7,262 patients with NPC (79.3% patients in stage III-IVA) treated between April 2009 and December 2015 were included in this study. Dose–volume statistics, clinical outcomes, patterns of failures and toxicities were assessed. To analyze dose distribution of patients with or without local recurrence, propensity score matching (PSM) was performed to compare the dose between the two groups matched by age, sex, histological type, T category, N category, chemotherapy and gross tumor volume of primary tumor and enlarged retropharyngeal lymph nodes (GTVnx) in a 1:1 ratio. <h3>Results</h3> Median follow-up was 67.3 (range, 2.0-118.7) months. The 5-year local relapse–free survival, regional relapse–free survival, distant metastasis–free survival, progression–free survival, and overall survival rates were 93.6%, 94.4%, 86.8%, 77.8%, and 86.0%, respectively. In-field failure is the major locoregional failure pattern, accounting for 92.3% patients of local and 86% of regional recurrence. Age and T classification were independent prognostic for LRFS, DMFS, PFS, and OS in multivariate analysis. Late grade 3 toxicities were mild and included ear injury (1.8%), xerostomia (0.2%), dysphagia (0.2%), brain injury (0.2%), and trismus (0.1%). No grade 4 toxicity occurred during IMRT or follow-up. PSM analysis revealed no significant difference between minimum (P = 0.815), maximum (P = 0.595), and mean (P = 0.700) dose to the planning tumor volume of primary tumor and enlarged retropharyngeal lymph nodes (PTVnx) between patients with local recurrence and the matched patients without local recurrence. <h3>Conclusion</h3> Our stepwise CTV delineation protocol appears to be a promising strategy for improving outcomes in NPC.

A rare case report of recurrent atypical meningioma with multiple metastases treated with anti-PD-1 and anti-VEGF therapy

BackgroundMeningioma is the most common type of primary intracranial tumor with 0.1–1% of all primary meningiomas have been reported to develop into metastases. However, there is no proven therapeutic strategy for multiple metastases of meningiomas.Case presentationA 60-year-old female accepted total tumor resection of a right frontal lobe meningioma in September 2018, In October 2021, the patient was admitted to hospital because of cough and shortness of breath and diagnosed with metastatic meningiomas. The computed tomography (CT) scan revealed the presence of large masses in the right thoracic and abdominal cavity. After two cycles of anti-PD-1 and anti-VEGF treatment, the symptoms were relieved and the tumor was necrotic. Follow up to June 21, 2022, the patient has been given eleven cycles of the treatment every 3 weeks without tumor progression.ConclusionsThis case showed combined anti-PD-1 and anti-VEGF treatment stimulates peripheral blood immune cells to kill metastatic meningioma cells. Whether combined immunotherapy is more effective for metastatic meningioma needs further exploration.

Bilateral Wilms’ Tumor With Different Responses to Preoperative Chemotherapy

Wilms' tumor (WT) is a common type of primary renal tumor in the pediatric population that can equally affect both sides. Herein, we describe a case of bilateral Wilms' tumor (BWT) in a three-year-old male with different responses to preoperative chemotherapy in the two kidneys. The left kidney mass responded poorly to chemotherapy than the right kidney, which raised the suspicion of coexisting benign disease or congenital anomaly. However, it was ruled out by preoperative nuclear scan and ultrasound-guided frozen section biopsy taken from the left kidney mass. The report of a frozen section on hematoxylin and eosin (H&E) stain was positive for the small blue cell tumor. The patient was managed successfully with a total nephrectomy of the right kidney and nephron-sparing surgery (NSS) on the left kidney. The postoperative period was uneventful and was managed successfully with radiotherapy. Despite many challenges faced in the management of bilateral Wilms' tumor, surgery is the most preferable mode of therapy with chemotherapy and radiotherapy being effective in certain cases. The patient was followed up till no signs of recurrence or metastasis were observed.

Comparison of Diagnostic PET and 4D CT-Based Tumor Delineation for Oligometastatic Lung Tumors

<h3>Purpose/Objective(s)</h3> Stereotactic body raiation therapy (SBRT) is increasingly used to treat oligometastatic tumors. To account for internal motion, 4D-CT is commonly used for lung SBRT. Biology-guided radiotherapy (BgRT) is an emerging concept that may allow for reduction of treatment volumes using positron emission tomography (PET) signal guidance. Benchtop testing of BgRT technology suggests target delineation on a single respiratory phase with 5 mm biology-guided margin may be sufficient, however this has not been clinically validated. We tested our hypothesis that PET-based tumor delineation would result in smaller target volumes than 4D-CT. <h3>Materials/Methods</h3> We retrospectively reviewed a single-institution lung radiotherapy database to identify patients with oligometastatic lung tumors treated with ablative doses of biologically effective dose (BED10) >=100 Gy. We included patients treated from 2015-2020 with a diagnostic PET performed within 30 days of CT simulation. Tumors were contoured on the diagnostic PET using an auto-threshold of 40% of the lesion SUVmax, followed by manual editing to include CT-based tumor accounting for possible PET signal misregistration. A 5 mm isotropic expansion was applied to generate the planning target volume (PTV). We compared these to existing 4D CT-based tumor volumes accounting for internal motion and their associated PTVs. <h3>Results</h3> Of 102 patients with oligometastatic lung tumors, we included 13 patients with 15 lung tumors. There were 7 female and 6 male patients, with a median age of 72 (range 52 – 89) at the time of treatment. Primary tumor types included 4 colorectal, 2 head and neck, 1 non-small cell lung cancer, 1 melanoma, and 5 other cancer types. Patients were treated to 50 to 54 Gy in 3 to 5 fractions. Median time from diagnostic PET scan to CT simulation was 17 days (range 0 – 27). Median lesion diameter was 1.2 cm (IQR 0.9 – 1.7) with median SUVmax of 5.4 (IQR 4.0 – 7.7). Diagnostic PET-based tumor contours had a median volume of 2.5 cc (IQR 1.7 – 3.1 cc), whereas 4D CT-based tumor contours had a median volume of 3.0 cc (IQR 2.4 – 9.9 cc). Diagnostic PET-based PTV had a median volume of 10.4 cc (IQR 8.4 – 12.6 cc), whereas 4D CT-based PTV had a median volume of 11.8 cc (IQR 10.8 – 31.5). <h3>Conclusion</h3> Diagnostic PET-based tumor delineation resulted in smaller tumor and planning target volumes compared to 4D-based tumor delineation. This data will serve as a benchmark for future research focusing on imaging modality concordance and clinical impact of reduced biology-guided margins in BgRT for oligometastatic patients undergoing lung SBRT.

Impact of Dosimetric Factors on Local Failure in Patients with Spine Metastasis after Stereotactic Body Radiotherapy: A Multi-Institutional Study

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is increasingly utilized in the treatment of spine metastasis. Preliminary data suggest that higher doses may improve local control, but may also increase risk of toxicity including vertebral compression fracture (VCF). Our single institution study recently found that a minimum dose of at least 21 Gy to 80% of planning target volume (PTV D80%) in 2 fractions was associated with higher risk of VCF. The purpose of this study is to assess this variable's relationship with local failure (LF) and VCF in an international, multi-institutional cohort. <h3>Materials/Methods</h3> Patients with radiation naïve solid tumor spine metastases treated with SBRT at 5 international institutions from 2010 - 2020 were included. Patients with surgical stabilization were excluded. LF was defined per spine response assessment in neuro-oncology criteria. Variables examined included spinal instability neoplastic score (SINS) factors and dosimetric/volumetric characteristics of radiation planning. All fractionation scheme doses were converted to 2-fraction equivalent doses (2fxED) using the linear quadratic model with an alpha/beta of 3 and used in analyses of PTV D80%. Univariate and multivariate Cox proportional hazard models for LF and VCF were constructed using the Fine and Gray competing risk method. <h3>Results</h3> 357 vertebral segments from 234 patients were treated with SBRT. Common primary tumor types were prostate (n = 50, 22%), non-small cell lung cancer (n = 42, 18%), breast (n = 35, 15%), and kidney (n = 25, 11%). Most (n = 199 pts, 242 segments) were treated with 2 or 3 fractions with a median prescription dose of 24 Gy or 27 Gy, respectively (range: 14-45 Gy in 1-5 fractions). Median follow was 21.1 months (0.6-88.4 mo). LF was 12.6% and 18.1% at 1- and 2-years, respectively. Variables associated with increased LF on univariate analysis were lower PTV D80% at 2fxED ≤21 Gy (HR 0.36, 95% CI 0.20-0.65, p = 0.001) and lower prescription dose BED3 (HR 0.98 as continuous variable, CI 0.97-0.99, p = 0.03). On multivariate analysis, only PTV D80% at 2fxED ≤21 Gy remained associated with increased risk of LF (HR 0.46, CI 0.24-0.85, p = 0.01). VCF incidence was low, at 4.2% and 6.7% at 1- and 2-years, respectively. Higher SINS was predictive of VCF (HR 1.22, CI 1.1-1.36, p <0.001). Patients with higher PTVD80% at 2fxED>21 Gy had a higher, albeit non-significant, risk of VCF (HR 3.30, CI 0.80-13.6, p = 0.10), consistent with our previous single institution study. <h3>Conclusion</h3> This multi-institutional, international study suggests that a PTV D80% at 2fxED ≤21 Gy may increase the risk of LF, while >21 Gy may increase the likelihood of VCF. Prospective studies are needed to further explore this complex relationship and identify the dose/fractionation schedule that best balances local control with normal tissue toxicity including VCF.

Childhood Obesity: A Potential Key Factor in the Development of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a malignant primary tumor type of the central nervous system (CNS). This type of brain tumor is rare and is responsible for 12–15% of all brain tumors. The typical survival rate of GBM is only 12 to 14 months. GBM has a poor and unsatisfactory prognosis despite advances in research and therapeutic interventions via neurosurgery, radiation, and chemotherapy. The molecular heterogeneity, aggressive nature, and occurrence of drug-resistant cancer stem cells in GB restricts the therapeutic efficacy. Interestingly, the CNS tumors in children are the second most usual and persistent type of solid tumor. Since numerous research studies has shown the association between obesity and cancer, childhood obesity is one of the potential reasons behind the development of CNS tumors, including GBM. Obesity in children has almost reached epidemic rates in both developed and developing countries, harming children’s physical and mental health. Obese children are more likely to face obesity as adults and develop non-communicable diseases such as diabetes and cardiovascular disease as compared to adults with normal weight. However, the actual origin and cause of obesity are difficult to be pointed out, as it is assumed to be a disorder with numerous causes such as environmental factors, lifestyle, and cultural background. In this narrative review article, we discuss the various molecular and genetic drivers of obesity that can be targeted as potential contributing factors to fight the development of GBM in children.

A Novel System for Precise Grading of Glioma.

Gliomas are the most common type of primary brain tumors and one of the highest causes of mortality worldwide. Accurate grading of gliomas is of immense importance to administer proper treatment plans. In this paper, we develop a comprehensive non-invasive multimodal magnetic resonance (MR)-based computer-aided diagnostic (CAD) system to precisely differentiate between different grades of gliomas (Grades: I, II, III, and IV). A total of 99 patients with gliomas (M = 49, F = 50, age range = 1–79 years) were included after providing their informed consent to participate in this study. The proposed imaging-based glioma grading (GG-CAD) system utilizes three different MR imaging modalities, namely; contrast-enhanced T1-MR, T2-MR known as fluid-attenuated inversion-recovery (FLAIR), and diffusion-weighted (DW-MR) to extract the following imaging features: (i) morphological features based on constructing the histogram of oriented gradients (HOG) and estimating the glioma volume, (ii) first and second orders textural features by constructing histogram, gray-level run length matrix (GLRLM), and gray-level co-occurrence matrix (GLCM), (iii) functional features by estimating voxel-wise apparent diffusion coefficients (ADC) and contrast-enhancement slope. These features are then integrated together and processed using a Gini impurity-based selection approach to find the optimal set of significant features. The reduced significant features are then fed to a multi-layer perceptron artificial neural networks (MLP-ANN) classification model to obtain the final diagnosis of a glioma tumor as Grade I, II, III, or IV. The GG-CAD system was evaluated on the enrolled 99 gliomas (Grade I = 13, Grade II = 22, Grade III = 22, and Grade IV = 42) using a leave-one-subject-out (LOSO) and k-fold stratified (with k = 5 and 10) cross-validation approach. The GG-CAD achieved 0.96 ± 0.02 quadratic-weighted Cohen’s kappa and 95.8% ± 1.9% overall diagnostic accuracy at LOSO and an outstanding diagnostic performance at k = 10 and 5. Alternative classifiers, including RFs and SVM produced inferior results compared to the proposed MLP-ANN GG-CAD system. These findings demonstrate the feasibility of the proposed CAD system as a novel tool to objectively characterize gliomas using the comprehensive extracted and selected imaging features. The developed GG-CAD system holds promise to be used as a non-invasive diagnostic tool for Precise Grading of Glioma.

Clinical Observation of Asymptomatic Left Atrial Myxoma

Myxomas are the most common type of primary benign cardiac tumor in adults, with an incidence of about 0.2 % in the population at autopsy. Myxomas develop from multipotent mesenchyme and are usually an undifferentiated, pedunculated atrial mass attached to a fossa ovale on the left side of the atrial septum. Frequent asymptomatic course of the disease complicates timely diagnosis and treatment. The presented clinical observation demonstrates the accidental detection of left atrial myxoma in a 68-year-old patient with subsequent successful surgical intervention.

Biomedical applications of terahertz spectra in clinical and molecular pathology of human glioma

Gliomas are the most common type of primary tumor originating in the central nervous system of adults. Tumor histological type, pathological grade, and molecular pathology are significant prognosis and predictive factors. In this study, we were aiming to predict histological type and molecular pathological features based on terahertz time-domain spectroscopy technology. Nine gliomas with different grades, one meningioma, and one lymphoma were enrolled. There were significant differences in terahertz absorption coefficient between normal brain tissue, tumoral-periphery, and tumoral-center tissue in specific frequency bands (0.2–1.4 THz). Histological type, pathological grade, and glioma-specific biomarkers were closely related to the terahertz absorption coefficient in both tumoral-periphery and tumoral-center tissues. Interestingly, tumoral-periphery showed more obvious differences than tumoral-center tissues in almost all aspects. All the results show that the terahertz technology has potential application value in the intraoperative real-time glioma recognition and diagnosis of glioma histological and molecular pathological features.

The efficacy of immune checkpoint inhibitors in elderly patients: a meta-analysis and meta-regression

BackgroundImmune checkpoint inhibitor (ICI) therapy has improved patient survival in advanced cancers; however, the efficacy of ICIs in elderly patients is still elusive. This study assessed the efficacy of ICIs in elderly patients with advanced cancer in terms of overall survival (OS) and progression-free survival (PFS).Materials and methodsWe carried out a systematic review and identified 30 head-to-head phase II/III randomized controlled trials that compared immunotherapy with the standard of care in advanced solid tumor patients. The data on patients younger or over 65 years of age were indexed from PubMed-Medline, Embase, and Scopus and obtained for meta-analysis. The subgroup analyses were stratified by primary tumor type, line of treatment, or type of immunotherapy, and a meta-regression analysis was carried out after adjusting for all other variables.ResultsThe study included 17 476 patients, comprising 58% (10 119) younger (<65 years old) and 42% (7357) elderly (≥65 years old) patients. The hazard ratio (HR) for OS was 0.77 [95% confidence interval (CI) 0.70-0.85] and 0.77 (95% CI 0.70-0.85) in the younger and elderly groups, respectively, suggesting similar efficacies of ICIs in these two age groups. The subgroup analyses revealed no significant relationship between age and treatment outcomes, except for the PFS benefit in younger patients with melanoma than in elderly patients (HR 0.44 in younger patients versus 0.65 in elderly patients, P = 0.04). These results were further supported by meta-regression analysis, which showed no statistically significant difference in OS (P = 0.954) and PFS (P = 0.555) between the two age groups.ConclusionsThe findings suggest that age-associated impairments of the immune system did not affect the efficacy of ICIs in elderly patients compared to younger patients. Therefore, the choice of ICIs for elderly patients can be considered, regardless of chronological age.

Lanreotide Depot to Treat Gastroenteropancreatic Neuroendocrine Tumors in a US Community Oncology Setting: A Prospective, Observational Study.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can result in symptoms such as diarrhea, flushing, abdominal pain, and fatigue and are often associated with a significant disease burden and poor prognosis. This non-interventional, prospective, observational study evaluated the real-world safety and effectiveness of lanreotide depot, a somatostatin analog (SSA) used to treat GEP-NETs, in a community setting. In this prospective, non-interventional study (NCT02730104), adult patients with locally advanced (inoperable), metastatic GEP-NETs treated with lanreotide depot were evaluated by their physician every 6 months from enrollment for 24months. Clinically defined time to disease progression (TTDP) and overall survival (OS) were estimated for the total population and by primary tumor type (gastrointestinal [GI], pancreatic, unknown origin), and an exploratory analysis determined the rate of progression-free survival (PFS) at 12 and 24months. Patient satisfaction was evaluated via the Treatment Satisfaction Questionnaire for Medication (TSQM-9), and safety information was recorded. Of 99 patients, the 24-month PFS rate was 73.7% (95% confidence interval [CI] 63.1-81.7) and 24-month OS rate was 84.2% (95% CI 74.0-90.7). Median TTDP was not reached because few patients experienced disease progression during the study period. The majority of responding patients expressed satisfaction with treatment on each domain of the TSQM-9. Treatment-related adverse events (AEs) occurred in 19.2% of patients, while no serious AEs (SAEs) were related to the study drug. Lanreotide depot is an effective and well-tolerated treatment for GEP-NETs in the real-world community setting. ClinicalTrials.gov identifier, NCT02730104.