Larger Tumor Volume Research Articles

Descriptive Statistics for Patients with Glioblastoma Associated with Germline Mismatch Repair Gene Mutation

<h3>Purpose/Objective(s)</h3> Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is a genetic mismatch repair mutation associated with increased risk for development of glioblastoma (GBM). There is a paucity of data describing the clinical outcomes of GBM patients with HNPCC. We aim to describe tumor characteristics, treatment patterns, and outcomes. <h3>Materials/Methods</h3> IRB approved retrospective review of consecutive patients with a diagnosis of both HNPCC and GBM at a single institution. <h3>Results</h3> Nine patients with a diagnosis of HNPCC and GBM were treated at a single institution from 2001-2022. Six patients were male. Median age at GBM diagnosis was 61 (range 21-84). Median follow up from the time of GBM diagnosis was 7.83 months. Eight patients had prior malignancies: n=7 with colon adenocarcinoma, n=1 with Burkitt lymphoma. Two patients had active synchronous cancers with GBM. The most common presenting symptoms were facial droop (n=3) and cognitive changes (n=2). Others include headache, gait change, visual field defect, and seizures with n=1 each. All patients underwent surgery: n=2 gross total resection, n=4 subtotal resection, and n=3 biopsy alone. There were 3 temporal lobe, 3 parietal lobe, 2 frontal lobe, and 1 frontoparietal lobe tumors. Two patients had multifocal disease at diagnosis. One patient had a giant cell variant GBM. Seven patients had MSH6 mutations and 2 had MSH2 mutations. Two patients progressed rapidly after surgery and were unable to receive RT. Seven patients received adjuvant radiation therapy (RT): n=5 received concurrent TMZ- 1 with concurrent bevacizumab, 5-fluorouracil, and leucovorin due to synchronous metastatic colon cancer, 1 received no chemotherapy. The most common dose and fractionation schedules were 60 Gy in 30 fractions (fx) (n=3), 40.05 Gy in 15 fx (n=3), and n=1 received 30 Gy in 10 fx due to poor performance status and large tumor volume. One patient received proton therapy for active MS, n=8 received IMRT. Two patients initiated tumor treating fields following RT completion. The median time to progression after RT was 3.35 months, and all progressed within the radiation field. Median survival from diagnosis was 6.5 months (range 1.2-15.5). No patients received immune checkpoint inhibitors. One patient was alive at the time of data collection. Seven died due to GBM progression, and n=1 died from progression of a synchronous malignancy. <h3>Conclusion</h3> In this small series, patients with mismatch repair mutation associated glioblastoma had especially poor outcomes and a rapidly progressive disease course.

Phantom Study of the Optimum Irradiation Angle for Proton Beam Therapy in Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> Passive proton beam therapy (PPBT) for hepatocellular carcinoma (HCC) has a higher local control rate than surgery or photon beam therapy. Moreover, it is attracting attention as one of the new treatment options. In the PPBT planning, the selection of the beam angle is determined according to the subjective judgment of the planner. Therefore, there are differences in the dose distribution depending on the planner. It has not yet been clarified which the irradiation angle can be selected to reduce unnecessary dose on the organ-at-risks and maintain the target coverage. The purpose of this study was to determining the optimal beam angle for liver S8 lesions. <h3>Materials/Methods</h3> The subjects were fifty-four treatment plans for HCC located in S8 irradiated using PPBT during the period of 2012.6-2021.3 at the National Cancer Center Hospital East. Tumor sizes were aggregated from the subjects. Clinical Target Volume (CTV) of the subject's liver ranged from 4 cm3 to 1370 cm3. Tumor sizes ranged from 132 cm to 655 cm3. From these results, the average CTV were represented on a virtual phantom, the dose distribution using PPBT was optimized using two irradiation angles. For the calculation of the optimum irradiation angle, the combination of the two beams rotated every 10 degrees and the best dose distribution was considered to be the optimum angle. The Conformity Index (CI) and Homogeneity Index (HI) of the CTV and the V30 (%) of the liver were calculated using the Dose volume histogram (DVH). <h3>Results</h3> The combination of beam angles showing 1 in the Conformity Index was 360 ° and 250 °, 350 ° and 230 °, 260 ° and 190 ° for small tumor volumes. Homogeneity Index and V30 averaged 1.06 and 28.0%, respectively. At the time of large tumor volume, it was 350 ° and 270 °, 350 ° and 250 °, 250 ° and 170 °. Homogeneity Index and V30 averaged 1.07 and 47.6%, respectively. The treatment schemes beam-arranged with a 70 ° difference in angle between the two beams were the most homogeneous with respect to the target. A significant difference was found in Conformity Index when compared to the most heterogeneous 190 ° difference (p <0.05). <h3>Conclusion</h3> Based on our findings, we recommend using a 2-beam configuration with a beam tilted by approximately 70 ° between the two beams for passive irradiation of hepatocellular carcinoma located in S8. This has the potential to achieve a uniform dose distribution within the target and at the same time reduce the hepatic dose. However, it should be noted that there is a difference in dose increase / decrease depending on the positional relationship of organs and tumors. Further treatment planning studies on aspects of respiration and organ movement need to be conducted.

Therapeutic Effect of Curcumol on Chronic Atrophic Gastritis (CAG) and Gastric Cancer Is Achieved by Downregulating SDF-1α/CXCR4/VEGF Expression.

CAG is an essential procession of the transformation from gastritis into gastric cancer. A series of timely moves of diagnosis, treatment, and monitoring towards CAG to anticipate the potential population at risk of gastric cancer is an effective means to prevent gastric cancer occurrence. The main active monomer in Fuzheng Huowei Decoction is Curcumol, which is an indispensable ingredient in the treatment to CAG and gastric cancer. In this study, the CAG model, in vitro cultured gastric cancer cells, and participating nude mice were treated with Curcumol, and alterations in SDF-1α/CXCR4/VEGF expression were estimated using the assays of immunohistochemistry and Western blot. MTT, flow cytometry, transwell, HE staining, and tumor volume determination were applied for the verification of the regulatory effects of Curcumol on CAG and gastric cancer cells. The results showed that the expressions of VEGF, SDF-1α, CXCR4, and CD34 decreased in our CAG model with Curcumol treatment. Curcumol is in procession of an inhibitory effect toward the activity, migration, and invasion of gastric cancer cells, and it would also result in gastric cancer cells' apoptosis. We subsequently added SDF-1α overexpressing lentivirus to the Curcumol-treated group and found that the expressions of SDF-1α, CXCR4, and VEGF protein increased, and the inhibitory effect of Curcumol on gastric cancer cells was withdrawn. Our nude mouse experiment showed that Curcumol + SDF-1α group ended up with the largest tumor volume, while Fuzheng Huowei + NC group was with the smallest tumor volume. In conclusion, Curcumol is able to effectively protect the gastric tissue and suppress gastric cancer cells' viability. Curcumol functions as a therapeutic factor in chronic atrophic gastritis and gastric cancer by downregulating SDF-1α/CXCR4/VEGF expression.

Spinal Nerve Sheath Tumors: Factors Associated with Postoperative Residual and Recurrent Tumors: A Single-Center Experience

Spinal schwannomas (SSs) are usually benign tumors with a good prognosis when treated by surgical excision. However, complete resection can be complicated by factors such as the tumor location and configuration. In the present study, we sought to identify the factors associated with incomplete surgical resection (residual) and the factors associated with tumor recurrence. We performed a retrospective review of 113 cases of SSs treated surgically from 2008 to2021. Of the 113 SSs, 102 were benign and 2 were malignant nerve sheath tumors. Of the 102 benign SSs, gross total resection (GTR) was performed for 87, with 8 displaying residual and 7, recurrent tumor. We found a significantly higher ratio of cervical and sacral tumors (P= 0.008 and P= 0.004, respectively), dumbbell and foraminal configurations (P < 0.0001 and P= 0.0006, respectively), and larger tumor volumes (P= 0.003) in the residual and recurrent cohorts compared with the GTR cohort. A second operation was performed for 2 patients in the residual and 4 patients in the recurrent cohorts. The total complication rate was 6%. We found that most benign SSs will be amenable to GTR (85% of cases), with an excellent prognosis. The patients with residual or recurrent tumor were more likely to have had a cervical or sacral location, a dumbbell or foraminal configuration, and a larger tumor volume. Except for 1 new SS and 1 recurrent tumor that had necessitated a lateral approach, the remainder had been treated using a posterior approach. At surgery, ultrasonography of the canal is advisable to ensure that the intra- and extraspinal components of dumbbell lesions have both been entirely removed.

P01.17.A Role of preoperative assessment in predicting tumor induced plasticity in patients with diffuse gliomas

Abstract Background When diffuse gliomas (DG) affect the brain′s potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor-brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganisation in these patients. Material and Methods FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG). This standardized radiological tool was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language preoperative assessments were performed in all patients before the direct cortical/subcortical brain mapping. The distance between eloquent spots and tumor margins was registered and measured on the neuronavigation system. Tumours containing eloquent points within hyperintense area on FLAIR sequences (cortical or subcortical) were considered eloquent. Eloquent points within 5-10 mm from the FLAIR signal margin were considered peritumoral, while beyond 10 mm from the FLAIR signal were considered outside the tumour area. Pre and postoperative images (3 months after the operation) were merged to detect eventual residual tumour. Clinical, radiological, and topographical variables and intraoperative findings were used for correlation and logistic regression analyses. Results 84.6% of our patients displayed neuropsychological symptoms at the preoperative assessment. Eloquent tumors were detected in 75% of the cases. Impaired NPS functions were correlated with more invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2 /A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Group comparison between younger and older patients (cut-off at 38 years old based on ROC curves) showed a significative difference in the number of intratumoral cortical eloquent spots (p &amp;lt; .05) and the number of peritumoral cortical eloquent spots (p &amp;lt; .001). Conclusion Preoperative NPS impairment was linked with high risk of eloquent tumors. Epilepsy and language impairment were linked with specific tumor locations while peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.

The role of the serum 25-OH vitamin D level on detecting prostate cancer in men with elevated prostate-specific antigen levels

We aimed to determine whether vitamin D levels before prostate biopsy have diagnostic value for clinically significant prostate cancer. The study cohort included patients who underwent prostate biopsy. A total of 224 patients were enrolled in our study and serum vitamin D levels were measured from February 2016 to December 2019 in routine laboratory tests. To determine the relationship between vitamin D levels and aggressiveness of prostate cancer, we used logistic multivariate analysis. Based on the histopathological results of patients who underwent radical prostatectomy, the serum vitamin D level was significantly lower with the large tumor volume group. In the univariate analysis, the prostate cancer diagnosis rate was associated with low vitamin D levels. Low vitamin D level is negatively correlated with clinically significant prostate cancer (biopsy Gleason score of 7 or higher) in the univariate (Odds ratio [OR], 0.955; P < 0.001) and multivariate (OR, 0.944; P = 0.027) analyses. In conclusion, we found that the incidence of clinically significant prostate cancer might related to low vitamin D level in the Asian population. In the future, a larger population and prospective study are needed.

The Clinical Significance of Either Extraprostatic Extension or Microscopic Bladder Neck Invasion Alone Versus Both in Men With pT3a Prostate Cancer Undergoing Radical Prostatectomy: A Proposal for a New pT3a Subclassification.

The prognosis of prostate cancers exhibiting extraprostatic extension [other than bladder or seminal vesicle invasion (EPE)] and/or microscopic bladder neck invasion (mBNI) is variable, and further risk stratification is required. We herein assessed radical prostatectomy findings and long-term oncologic outcomes in consecutive 957 patients with pT3a disease. The patient cohort was divided into 4 groups, focal EPE (F-EPE) only (n=177; 18.5%), nonfocal/established (E-EPE) only (n=634; 66.2%), mBNI only (n=51; 5.3%). The rate of positive surgical margin and estimated volume of tumor were significantly higher in patients with both EPE and mBNI than in those with either. In addition, compared with F-EPE or mBNI only, E-EPE only was significantly associated with higher Grade Group, lymph node metastasis, and larger tumor volume. Kaplan-Meier analysis revealed a comparable prognosis after prostatectomy between those showing F-EPE only versus mBNI only ( P =0.986), and these 2 cohorts were combined for further analysis. Then, patients showing E-EPE only had a significantly higher or lower risk of progression compared with those showing F-EPE or mBNI only ( P <0.001) or both EPE and mBNI ( P <0.001), respectively. These significant differences in progression-free survival were also seen in subgroups, including those with or without undergoing adjuvant therapy before recurrence and those showing no lymph node metastasis. In multivariate analysis, F-EPE or mBNI only (hazard ratio=0.524, P =0.003) or both EPE and mBNI (hazard ratio=1.465, P =0.039) (vs. E-EPE only) showed significance for progression. Based on these findings, we propose a novel pT3a subclassification, pT3a1 (F-EPE or mBNI alone), pT3a2 (E-EPE alone), and pT3a3 (both EPE and mBNI).

Imaging characteristics of orbital peripheral nerve sheath tumors: Analysis of 34 cases.

BACKGROUNDPeripheral nerve sheath tumors (PNSTs), a rare group of neoplasms in the orbit, comprise only 4% of all orbital tumors. At present, there are very few studies detailing the features of these tumors identified using imaging technology. AIMTo compare the differences in location, morphology, magnetic resonance imaging (MRI) signal intensity/computed tomography (CT) value, and enhancement degree of tumors of different pathological PNSTs types.METHODSClinical, pathological, CT, and MRI data were analyzed retrospectively in 34 patients with periorbital sheath tumors diagnosed using histopathology from January 2013 to August 2021.RESULTSAmong 34 cases of orbital peripheral nerve sheath tumors, 21 were schwannomas, 12 were neurofibromas, and 1 was a plexiform neurofibroma. Common clinical symptoms presented by patients with these types of tumors include eyelid swelling, exophthalmos, and limited eye movement. Schwannomas mostly occur in the intramuscular space with small tumor volume and rare bone involvement. Neurofibromas develop in the extrapyramidal space with larger tumor volume and more bone involvement. Radiologically, schwannomas and neurofibromas are characterized by regular morphology and uneven density and signal. One case of plexiform neurofibroma showed tortuous and diffuse growth along the nerve, with a worm-like appearance on imaging.CONCLUSIONDifferent pathological types of orbital peripheral nerve sheath tumors have unique imaging characteristics. Comprehensive consideration of the patient's clinical and imaging manifestations is of great value in the diagnosis of orbital peripheral nerve sheath tumors.

Impact of radiation dose to the immune cells in unresectable or stage III non-small cell lung cancer in the durvalumab era

Background/purposeHigher estimated radiation doses to immune cells (EDIC) have correlated with worse overall survival (OS) in patients with locally-advanced non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, which established consolidative durvalumab as standard-of-care. Here, we examine the prognostic impact of EDIC in the durvalumab era. Materials/methodsThis single-institution, multi-center study included patients with unresectable stage II/III NSCLC treated with chemoradiation followed by durvalumab. Associations between EDIC [analyzed continuously and categorically (≤6 Gy vs > 6 Gy)] and OS, progression-free survival (PFS), and locoregional control (LRC) were evaluated by Kaplan-Meier and Cox proportional methods. Results100 patients were included with median follow-up of 23.7 months. The EDIC > 6 Gy group had a significantly greater percentage of stage IIIB/IIIC disease (76.0 % vs 32.6 %; p < 0.001) and larger tumor volumes (170 cc vs 42 cc; p < 0.001). There were no differences in early durvalumab discontinuation from toxicity (24.1 % vs 15.2 %; p = 0.27). Median OS was shorter among the EDIC > 6 Gy group (29.6 months vs not reached; p < 0.001). On multivariate analysis, EDIC > 6 Gy correlated with worse OS (HR: 4.15, 95 %CI: 1.52–11.33; p = 0.006), PFS (HR: 3.79; 95 %CI: 1.80–8.0; p < 0.001), and LRC (HR: 2.66, 95 %CI: 1.15–6.18; p = 0.023). Analyzed as a continuous variable, higher EDIC was associated with worse OS (HR: 1.34; 95 %CI: 1.16–1.57; p < 0.001), PFS (HR: 1.52; 95 %CI: 1.29–1.79; p < 0.001), and LRC (HR: 1.34, 95 %CI: 1.13–1.60; p = 0.007). ConclusionsIn the immunotherapy era, EDIC is an independent predictor of OS and disease control in locally advanced NSCLC, warranting investigation into techniques to reduce dose to the immune compartment.

Herophilus-Galen line as a predictor of extent of resection in the occipital interhemispheric transtentorial approach to pineal tumors in children.

The goals of this study were to evaluate the extent of resection (EOR) obtained with an occipital interhemispheric transtentorial approach (OITA) in a series of pediatric patients with pineal region tumors and to define preoperative radiological factors predictive of the EOR. This is a retrospective cohort study of a series of pediatric patients with pineal tumors who underwent surgery through a microsurgical OITA performed by the senior author during the period from January 2006 to January 2020. The tumor volume was measured preoperatively, and then on sagittal midline cuts the authors identified the most cranial point of the torcular Herophili (defined as the "Herophilus point") and the lowest point of the inferior profile of the vein of Galen (defined as the "Galen point"). The line joining these two points (defined as the "Herophilus-Galen line" [H-G line]) was used to identify the "Herophilus-Galen plane" (H-G plane) perpendicular to the sagittal plane. Tumor volumes located below and above this plane were measured. EOR was evaluated by measuring residual tumor volume visible on T1 volumetric injected sequences of immediate postoperative MRI. Thirty patients were selected for study inclusion. The preoperative mean tumor volume was 15.120 cm3 (range 0.129-104.3 cm3). The mean volumes were 2.717 cm3 (range 0-31 cm3) above the H-G plane and 12.40 cm3 (median 5.27 cm3, range 0.12-72.87 cm3) below the H-G plane. Three patients underwent only biopsy. Of the remaining 27 patients, gross-total resection (GTR; 100% tumor volume) was achieved in 20 patients (74%). In the remaining 7 patients, the mean residual tumor volume was 7.3 cm3 (range 0.26-17.88 cm3). In 3 of these patients, GTR was accomplished after further surgical procedures (1 in 2 patients, 3 in 1 patient) for an overall GTR rate of 85.18%. Larger tumor volume was significantly associated with incomplete resection (p < 0.001). A tumor volume ≤ 2 cm3 above the H-G plane (p = 0.003), linear extension ≤ 1 mm above the H-G line, and pineal histology were predictive of GTR at first OITA procedure (p = 0.001). The H-G line is an intuitive, easy-to-use, and reliable indicator of the superior anatomical limit of visibility during the microsurgical OITA. This anatomical landmark may be useful as a predictor of EOR for pineal tumors performed through this approach. The main limitations of this study are the small number of patients and the exclusively pediatric age of the patient population.

Radiographic Differentiation of Secretory Meningiomas and WHO Grade 2 Meningiomas: When Atypical Features Are Not Always Predictive of Atypical Tumors

Secretory meningioma (SM) is a rare subtype of World Health Organization (WHO) grade 1 meningioma, associated with significant peritumoral brain edema (PTBE). Because of this, SM may be mistaken preoperatively to be a WHO grade 2 meningioma (G2M). In this study, we identified radiographic features to differentiate these 2 tumor types preoperatively to help inform surgical decision-making. We performed a retrospective review of all patients with histologically confirmed intracranial SM and G2M at a single institution from 2000 to 2019. Relevant clinic, demographic and radiographic data were collected. We performed a stepwise multivariable logistic regression to identify independent predictors of SM. A total of 43 SM and 140 G2M patients were included in this study. In multivariable analysis, severe PTBE, meaning edema size greater than tumor size (odds ratio [OR] 4.44, P= 0.01), tumor hyperintensity on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging sequences (OR 7.80, P= 0.002), and higher normalized apparent diffusion coefficient (nADC) values (OR 1.54, P < 0.001) were strong predictors of SM. Conversely, larger tumor volume (OR 1.79 per 10 mL volumeincrease, P < 0.001) and cystic component (OR 12.50, P= 0.007) correlated with G2M. In this study, we found that preoperative FLAIR hyperintensity, severe PTBE, and higher nADC values correlated with SM pathology, and larger size and cystic component were associated with G2M. Accurate identification of SM on preoperative imaging may provide surgeons useful information in decision-making.

Abstract 6165: DARC/ACKR1 expression is associated with immune landscape changes among triple negative breast tumors

Abstract Recent work defining the immune landscape across breast cancer (BC) subtypes have revealed that TNBC tumors have increased immunogenicity, and these increases in immune cell infiltration are associated with better prognosis and outcomes. Our recent work has proposed the Duffy Antigen Receptor for Chemokines (DARC), as a potential driver of immune regulation in breast tumors. DARC/ACKR1 is an atypical chemokine receptor that promiscuously binds both pro-inflammatory CC and pro-angiogenic CXC class chemokines and plays a role in chemokine gradient establishment both in circulation, and at sites of inflammation via chemokine transcytosis. In the BC context, we and others have reported DARC/ACKR1 protein expression on breast tumor epithelial cells by IHC and have also shown a range of gene expression in breast tumors from bulk RNAseq data in the TCGA cohort. Specifically, alongside CIBERSORT deconvolution of tumor associated immune cell populations, we have shown a strong positive correlation between DARC/ACKR1 gene expression and total tumor-associated leukocyte (TAL) abundance across all BC subtypes. To investigate the role of DARC/ACKR1 specifically in the TNBC tumor microenvironment (TME), we have analyzed (1) in silico bulk RNAseq data from two independent TNBC cohorts, (2) imaging mass cytometry data from TNBC patients and (3) murine model of DARC/ACKR1 BC progression in a basal-like BC transgenic mouse model. Our in silico data shows strong positive correlation of DARC/ACKR1 expression and TAL abundance, when DARC/ACKR1 expression is both dichotomized and analyzed as a continuous variable. Immune cell populations increasing with DARC/ACKR1 expression include B cell, T cell, monocyte and macrophage populations, which was consistent with our previous findings across all BC subtypes. IMC analysis of TNBC FFPE sections to determine protein expression of various immune and structural markers on the single-cell level between DARC/ACKR1 high or low expressing tumors show cells from DARC/ACKR1 high expressing tumors clustered distinctly from DARC/ACKR1 low expressing tumors. Image analysis also revealed increased infiltration among our DARC/ACKR1 high tumors. Finally, our murine model of DARC/ACKR1 in TNBC, shows that tumor development followed similar disease progression as human BC, following early through late-stage disease. DARC/ACKR1 deficient mice were found to have larger tumor volume and more palpable tumors, where DARC/ACKR1 expressing mice show co-localization of DARC and immune cell expression. This is the first work to describe the role of DARC/ACKR1 in the TNBC TME in bulk tumor transcriptomic data, spatial single-cell protein level data, and murine BC tumor model. Further investigation of factors that drive immune response in TNBC tumors, like DARC/ACKR1, may lead the way to novel therapeutic options or biomarkers for better outcomes for women with TNBC. Citation Format: Rachel Martini, Kiel Telesford, Brittany Lord, Hiranmayi Ravichandran, Olivier Elemento, Nancy Manley, Michele Monteil, Lisa Newman, Upender Manne, Clayton Yates, Melissa B. Davis. DARC/ACKR1 expression is associated with immune landscape changes among triple negative breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6165.

Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy

BackgroundThe prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT).MethodsFive hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume.ResultsThe volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume.ConclusionsOutcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.

The Significant Role of Tumor Volume on the Surgical Approach Choice, Surgical Complexity, and Postoperative Complications in Renal Cell Carcinoma With Venous Tumor Thrombus From a Large Chinese Center Experience.

ObjectiveTo explore the role of tumor volume (TV) on surgical approach choice, surgical complexity, and postoperative complications in patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus.MethodFrom January 2014 to January 2020, we retrospectively analyzed the clinical data of 132 patients who underwent radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT). Primary renal tumor volume (PRTV), renal vein tumor thrombus volume (RVTTV), inferior vena cava tumor thrombus volume (IVCTTV), and total tumor thrombus volume (TTTV) were measured with the help of an internationally recognized 3D volume measurement software. The patients were divided into three groups according to the tumor volume within the inferior vena cava (IVC). Group 1 included 48 patients with IVCTTV between 0 and 15 cm3 (36.6%), group 2 included 38 patients with IVCTTV between 16 and 30 cm3 (28%), and group 3 included 46 patients with IVCTTV above 30 cm3 (35%). The three IVCTTV groups, as well as four different volume groups, were compared in terms of surgical approach choice, surgical complexity, and postoperative complications. One-way ANOVA and a non-parametric test were used to compare the clinicopathological characteristics and distribution differences between the three groups.ResultThis study found significant differences among the three groups in the proportion of open surgery (P < 0.001), operation time (P < 0.044), intraoperative bleeding (P < 0.001), and postoperative complications (P < 0.001). When the four different volumes were compared, we found that for higher volumes IVCTTV and TTTV, open surgery is used more often compared with laparoscopic surgery (P < 0.001). In addition, with the increase in renal vein tumor thrombus volume, inferior vena cava tumor thrombus volume, and total tumor thrombus volume, the operation time also increased. Finally, with the increase in tumor thrombus volume and total tumor thrombus volume, the amount of intraoperative bleeding increased.ConclusionWith the increase in tumor volume, the proportion of open surgery and the incidence of postoperative complications increased. In addition, larger tumor volume prolongs operation time, increases intraoperative blood loss, and makes the surgery more complicated.

Patient-reported cognitive function before and after glioma surgery

BackgroundLittle is known about the extent to which glioma patients experience subjective changes in cognitive function following surgery. We sought to assess patient-reported cognitive function before and after glioma surgery and explore potential factors associated with cognitive change.MethodsIn a prospective population-based study, patient-reported cognitive function was measured in 182 patients undergoing primary surgery for diffuse glioma (141 high-grade gliomas (HGG) and 41 low-grade gliomas (LGG)) by using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 cognitive function subscale preoperatively and at 1 and 6 months postoperatively. Binomial logistic regression models were used to assess factors possibly associated with patient-reported cognitive changes.ResultsIn the HGG group, the mean cognitive function score increased from 70.9 (95% 66.6, 75.2) preoperatively to 85.1 (95% CI 81.2, 89.0) (p < 0.001) and 83.3 (95% CI 79.1, 87.6) (p < 0.001) at 1 and 6 months postoperatively, respectively. In the LGG group, the mean score was 80.9 (95% CI 74.4, 87.4) preoperatively and remained stable at postoperative follow-ups. Females reported lower scores than males. At an individual level, both improvement and deterioration in cognitive scores were frequently seen in LGG and HGG patients after surgery. Preoperative use of corticosteroids and large tumor volume were predictors for cognitive improvement at 1 month postoperatively. No predictors were identified for cognitive improvement at 6 months and worsening at 1 and 6 months.ConclusionMany glioma patients experience perioperative subjective changes in cognitive function after surgery. At group level, HGG patients reported improved cognitive function after surgery, while LGG patients reported stable cognitive function. Preoperative use of corticosteroids and large tumor volume were independently associated with postoperative improvement.

Long Non-Coding RNA ZEB2-AS1 Promotes Hepatocellular Carcinoma Progression by Regulating The miR-582-5p/FOXC1 Axis.

ObjectivesLong non-coding RNAs (lncRNAs) feature prominently in tumors. Reportedly, lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) is aberrantly expressed in a variety of tumors. The present study was aimed to explore ZEB2-AS1 functions and determine mechanism in hepatocellular carcinoma (HCC) progression. Materials and Methods In this experimental study, expressions of ZEB2-AS1, microRNA (miR)-582-5p and forkhead box C1 (FOXC1) mRNA in HCC tissues and cell lines were detected via quantitative reveres transcription polymerase chain reaction (qRT-PCR). After establishing gain- and loss-of-functions models, cell counting kit-8, 5-bromo-2’-deoxyuridine (BrdU), Transwell assays and flow cytometry analysis were conducted to examine HCC cell multiplication, migration, invasion and apoptosis, respectively. The targeted relationship between miR-582- 5p and ZEB2-AS1 was verified via dual-luciferase reporter gene assay. Western blot was utilized for detecting FOXC1 expression in HCC cells after selectively regulating ZEB2-AS1 and miR-582-5p. Results In HCC tissues and cells, ZEB2-AS1 expression was increased. High ZEB2-AS1 expression was related to relatively large tumor volume, increased tumor-node-metastasis (TNM) stage and positive lymph node metastasis of the patients. ZEB2-AS1 overexpression facilitated HCC cell multiplication, migration, invasion and suppressed apoptosis, while ZEB2-AS1 knock-down caused the opposite effects. It was also confirmed that ZEB2-AS1 could competitively bind with miR-582-5p to repress its expression, and indirectly up-regulate FOXC1 expression level in HCC cells. ConclusionThe current study revealed that ZEB2-AS1 was over-expressed in HCC tissues and cells. It also upregulated FOXC1, through sponging miR-582-5p, to promote HCC progression. This provides new perspectives for elucidating the pathogenesis of HCC.

Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma via repressing IGF-1R-PI3K-NF-κB signaling pathway.

Increasing studies have found that long noncoding RNAs (lncRNAs) contribute to regulating tumor progression. This study explores the expression characteristics, effects, and related mechanisms of lncRNA IGF1R antisense imprinted non-protein coding RNA (IRAIN) in glioma. Quantitative real-time PCR (qRT-PCR) was implemented to testify the IRAIN profile in glioma tissues and paracancerous tissues, and the link between the IRAIN level and the clinicopathological indicators of glioma was analyzed. IRAIN overexpression and knockdown cell models were constructed in glioma cells. Cell proliferation was verified by the colony formation experiment, while flow cytometry was implemented to monitor apoptosis. Transwell assay was performed to examine cell invasion and migration. Western blot (WB) was adopted to compare the profiles of the apoptosis-related proteins (Bax, Bcl2, and Caspase3) and IGF-1R-PI3K-NF-κB pathway. IRAIN was down-regulated in glioma tissues (compared with adjacent normal tissues), and the low IRAIN expression was significantly linked with the larger tumor volume and higher pathological stages. Functionally, overexpressing IRAIN abated glioma cell proliferation, invasion, and migration, promoted apoptosis, and attenuated IGF-1R-PI3K-NF-κB expression and temozolomide (TMZ) resistance, which was also confirmed in the xenograft tumor experiment. The WB result showed that overexpressing IRAIN inactivated the IGF-1R-PI3K-NF-κB pathway. Additionally, the IGF-1R knockdown model was established in U251 cells. Si-IGF-1R induced cell proliferation inhibition, promoted cell death, and reduced cell migration and TMZ resistance, whereas Si-IGF-1R+IRAIN group showed no additional effects on glioma cells compared with the Si-IGF-1R group. IRAIN repressed glioma development and TMZ resistance by inactivating the IGF-1R-PI3K-NF-κB axis.

Applying 3D-Printed Templates in High-Dose-Rate Brachytherapy for Cervix Cancer: Simplified Needle Insertion for Optimized Dosimetry

In cervical cancer brachytherapy, adding interstitial needles to intracavitary applicators can enhance dosimetry by improving target coverage while limiting normal tissue dose. However, its use is limited to a subset of practitioners with appropriate technical skill. We designed tandem anchored radially guiding interstitial templates (TARGITs) with a 3-dimensional (3D) printing workflow to optimize needle placement and facilitate greater ease-of-use of intracavitary/interstitial (IC/IS) technique. This study compared dosimetry and procedure characteristics between tandem and ovoid (T&O) implants using TARGIT technique versus non-TARGIT technique. This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive radiation treatment for cervical cancer between February 2017 and January 2021. TARGIT technique was implemented from November 2019 onwards; all prior procedures involved non-TARGIT technique using a no needle or freehand needle approach. Target coverage, dose to organs at risk, and procedure times were evaluated and compared between TARGIT technique and non-TARGIT technique. The cohort included 70 patients with cervical cancer who underwent 302 T&O procedures: 68 (23%) with TARGIT technique and 234 (77%) with non-TARGIT technique, which included 133 no needle and 101 freehand needle implants. TARGIT implants involved longer average procedure times (+6.3 minutes, P < .0001). TARGIT implants achieved a higher mean high-risk clinical target volume V100% than non-TARGIT implants (+4.4%, P = .001), including for large tumors 30 cm3 or greater (+8.1%, P = .002). Average D90 was 4.6 Gy higher and average D98 was 3.2 Gy higher for TARGIT technique compared with non-TARGIT technique (P = .006 and P = .02). Total treatment doses to rectum, bowel, and bladder were not significantly different for TARGIT versus non-TARGIT technique. The 3D-printed TARGIT approach to T&O brachytherapy achieved greater tumor coverage while sparing normal tissues, particularly for large tumor volumes, with only a slight increase in average procedure time. TARGIT represents a creative technological solution for increasing accessibility of advanced IC/IS brachytherapy technique for cervical cancer definitive radiation treatment.

Elevated Serum Lactate in Glioma Patients: Associated Factors.

IntroductionSerum lactate levels in brain cancer patients correlate with tumor malignancy grading, and serum lactate has been suggested as a potential biomarker and prognostic factor. The purpose of this study was to identify potential sources of elevated serum lactate in patients with brain gliomas by examining factors of importance for serum lactate production and clearance.MethodsIn this cross-sectional study, data were collected from 261 glioma patients who underwent surgery from March 2011 to June 2015. We recorded patient gender, age, blood serum measures of lactate, glucose, pH, hemoglobin and base excess, patient health status, medications, and tumor characteristics. Patients with elevated and normal serum lactate levels were compared, and we explored if there were correlations between the variables. The association of serum lactate with the measured variables was investigated by simple and multivariable linear regression models.Results and DiscussionPatients with elevated serum lactate had higher blood glucose, larger tumor volumes, and more tumor edema; more often needed pressor medication during surgery; and more often received corticosteroid treatment. The investigated variables were highly correlated. Multivariable linear regression indicated that gender, tumor volume, Charlson Comorbidity Index, hyperglycemia, and corticosteroid treatment were associated with serum lactate levels. Histopathology was not an independent factor. In conclusion, comorbidities, hyperglycemia, and presurgical corticosteroid treatment exhibited the strongest association with serum lactate in glioma patients.

Early-onset adverse events after stereotactic radiosurgery for jugular foramen schwannoma: a mid-term follow-up single-center review of 46 cases

BackgroundRecently, stereotacitc radiosurgery (SRS) has been in the spotlight as an alternative therapeutic option for jugular foramen schwannomas (JFS). While most reported studies focus on the long-term efficacy and safety issues of SRS, none describe the early-onset adverse events (eAEs). We aimed to investigate the incidence, clinical characteristics, and mid-term outcomes of eAEs occurring within six months after SRS for JFS.MethodsIn this retrospective review, patients who underwent at least six months of follow-up were included among all patients with JFS who have performed SRS at our institution between July 2008 and November 2019. And eAEs were defined as a newly developed neurological deficit or aggravation of pre-existing symptoms during the first six months after SRS.ResultsForty-six patients were included in the analysis. The median follow-up period was 50 months (range 9–136). The overall tumor control rate was 91.3%, and the actuarial 3-, 5-, and 10-year progression-free survival rates were 97.8%, 93.8%, and 76.9%, respectively. Of the 46 patients, 16 had eAEs, and the median time to onset of eAEs was one month (range 1–6 months), and the predominant symptoms were lower cranial nerve dysfunctions. Thirteen of 16 patients showed improved eAE symptoms during the follow-up period, and the median resolution time was six months (range 1–52). In 11 (68.8%) of 16 patients with eAEs, transient expansions were observed with a mean of 3.6 months after the onset of eAEs, and the mean difference between the initial tumor volume and the transient expansion volume was more prominent in the patients with eAEs (3.2 cm3 vs. 1.0 cm3; p = 0.057). In univariate analysis, dumbbell-shaped tumors (OR 10.56; p = 0.004) and initial tumor volume (OR 1.32; p = 0.033) were significantly associated with the occurrence of eAEs.ConclusionsAlthough acute adverse events after SRS for JFS are not rare, these acute effects were not permanent and mostly improved with the steroid treatment. Dumbell-shaped and large-volume tumors are significant predictive factors for the occurrence of eAEs. And the transient expansion also seems to be closely related to eAEs. Therefore, clinicians need to be more cautious when treating these patients and closely monitor the occurrence of eAEs.