Larger Tumor Volume Research Articles

A comprehensive correlation of the KI-67 proliferation index to patient´s, imaging and tumor features and its value in predicting long-term course of patients with newly diagnosed intracranial meningiomas.

To analyze the correlation of KI-67-Proliferation Index (KI-67-PI) with preoperative patients and MRI characteristics, WHO grading, histological subtype and long-term-course of patients with newly diagnosed intracranial meningiomas (IM). In this single-center retrospective study, all consecutive patients with IM were analyzed from January 2007 to August 2019. Patient´s demographics (age, sex), imaging parameters (location, volume, edema, necrosis), and tumor features (WHO grade, histology) were assessed and correlated with KI-67-PI. Long-term data were retrieved from patient's last follow-up visits. This study included 463 IM in 457 surgically treated patients. Males exhibited a higher KI-67-PI than females (7.31 ± 0.22 vs. 5.37 ± 0.53; p < 0.01, Mann-Whitney U Test). Age positively correlated with KI-67-PI in both sexes (p < 0.01, Spearman), with older patients having a higher KI-67-PI. KI-67-PI was significantly higher in convexity IM compared to frontobasal IM (7.15 ± 5.56 vs. 4.66 ± 2.94; p < 0.05, ANOVA, Tukey´s HSD), while no difference in KI-67-PI expression was found when other locations were compared to each other (Tukey´s HSD). Higher KI-67-PI was significantly correlated with larger tumor volume (p < 0.01, Spearman), larger tumor necrosis and larger peritumoral edema (p < 0.01, Kruskal-Wallis). Patients with recurrent IM had a significantly higher KI-67-PI than patients without recurrence (8.24 ± 5.88 vs. 5.14 ± 3.53; p < 0.01, ANOVA, Tukey´s HSD) during a mean follow-up period of 80.92 ± 38.1months. Atypical and anaplastic IM exhibited significantly higher KI-67-PI compared to all other WHO grade 1 histological subtypes (12.09 ± 0.73 vs. 4.51 ± 0.13; p < 0.01, Kruskal-Wallis test) and KI-67-PI was significantly higher in anaplastic IM compared to atypical meningioma (19.67 ± 1.41 vs. 11.01 ± 0.38; p < 0.01, ANOVA). Higher KI-67-PI is not only associated with atypical and anaplastic subtypes of IM, but is also significantly higher in males, positively correlates with patients age, larger tumor volume, lager peritumoral edema and necrosis on preoperative MRI and predicts tumor recurrence. Therefore, KI-67-PI may serve as a decision indicator for adjuvant treatment in patients with IM.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies

PurposeIntracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal.MethodsA retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed.ResultsA total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001).ConclusionThis study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

The clinical practice and dosimetric outcome of the manual adaptive planning during definitive radiotherapy for cervical cancer

ProposeTo evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy.Methods and materialsEighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis.ResultsThe CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors.ConclusionWe found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.

Levels of circulating tumor DNA correlate with tumor volume in gastro-intestinal stromal tumors: an exploratory long-term follow-up study.

Patients with gastro-intestinal stromal tumors (GISTs) undergoing tyrosine kinase inhibitor therapy are monitored with regular computed tomography (CT) scans, exposing patients to cumulative radiation. This exploratory study aimed to evaluate circulating tumor DNA (ctDNA) testing to monitor treatment response and compare changes in ctDNA levels with RECIST 1.1 and total tumor volume measurements. Between 2014 and 2021, six patients with KIT proto-oncogene, receptor tyrosine kinase (KIT) exon-11-mutated GIST from whom long-term plasma samples were collected prospectively were included in the study. ctDNA levels of relevant plasma samples were determined using the KIT exon 11 digital droplet PCR drop-off assay. Tumor volume measurements were performed using a semi-automated approach. In total, 94 of 130 clinically relevant ctDNA samples were analyzed. Upon successful treatment response, ctDNA became undetectable in all patients. At progressive disease, ctDNA was detectable in five out of six patients. Higher levels of ctDNA correlated with larger tumor volumes. Undetectable ctDNA at the time of progressive disease on imaging was consistent with lower tumor volumes compared to those with detectable ctDNA. In summary, ctDNA levels seem to correlate with total tumor volume at the time of progressive disease. Our exploratory study shows promise for including ctDNA testing in treatment follow-up.

P.103 Automated pituitary adenoma segmentation for radiosurgery with deep learning-based model

Background: Pituitary adenomas are treated with endoscopic surgery, while stereotactic radiosurgery addresses complex cases. Our study highlights AI’s role in accurate segmentation, improving treatment planning workflow efficiency Methods: In a retrospective study at Na Homolce Hospital (January 2010 to October 2022), SRS for pituitary adenomas was analyzed. Data were split 80:20 for training and validation. Using nnU-net, a medical image segmentation tool, a model predicted precise tumor, optic nerve, and pituitary gland segmentation. Accuracy was evaluated quantitatively with Dice similarity coefficient and qualitatively by human experts. The study explored the impact of tumor volume and hormonal activity status on segmentation accuracy. Results: The study comprised 582 and 146 patients in training and validation sets, respectively. The model achieved Dice similarity coefficients of 83.1% (tumor), 62.9% (normal gland), and 78.0% (optic nerve). Expert assessments deemed 41% directly applicable, 31.5% needing minor adjustments, and 27.4% unsuitable for clinical use. Larger tumor volume and non-functioning adenomas correlated with higher accuracy. Including T2 weighted scans improved DSC for optic nerve and normal gland. Conclusions: The study showcases deep learning’s potential in automating pituitary adenoma segmentation from MRI data, particularly excelling in large, hormonally inactive macroadenomas. Encourages collaborative use with clinicians for improved neurosurgical patient care.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia. HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

A Rare Tumor of Scalp - Giant Multiple Cellular Histiocytofibroma

Histiocytofibroma or dermatofibroma is a rare benign cutaneous tumor present preferentially in the dermis. Histiocytofibroma is most frequent benign tumor, but some specific morphological forms may present local recurrences and can cause lymph node and visceral metastases. The trunk and limbs represent the most classically described topography, other locations are known like face and scalp. Histiocytofibroma is most often present as a unique lesion: papule or nodule, giant form is not common and it is characterized by a large tumor volume (5 cm or more). The cellular histological variant is a rare subtype. We report a case of a 56-year-old male patient with no particular past medical history, who presented with a fronto-parietal cutaneous large tumor evolved for 2 years, gradually increasing in volume, measuring 7 cm in diameter, with regular contours, flesh colored, and peripheral vascularization on the surface of the lesion, it was firm and adherent to bone plane at palpation, along with seven other small lesions, the largest of which was 2 cm. The CT scan did not show any bone invasion. Surgical management consisted of large excision with 1 cm free margins. histological and immunohistochemical findings were in favor of cellular histiocytofibroma. The substance loss was covered by skin graft after complete budding. A 26 months follow up results were good without recurrence.

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd wasreported. The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation2023B. Three different Lmin values were investigated and specified for the seven boost fractions: , and . To compare the LETd optimized against reference plans, LETd and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( range uncertainty and setup uncertainty along the main three axes). The optimization method with resulted in an optimal LETd distribution with an average increase of (and ) in the CTV-HD by ( ) (and ( )), without significant difference in the RBE-weighted dose. By allowing over- and under-dosage in the target, the (and ) can be increased by ( ) (and ( )), using the optimization parameters . The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to referenceplans. Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE-weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects duringtreatment.

Abstract PO2-07-04: Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity

Abstract Background: Traditionally, multi-focal breast cancer results in mastectomy. The Alliance Trial offers a paradigm shift in surgical options available for multi-focal breast cancer patients in the context of adjuvant chemotherapy. In the trial, patients with multi-focal disease (&amp;lt; 3 tumors) who underwent breast conservation surgery (BCS) were found to have similar outcomes to patients undergoing mastectomy. BCS for large volume tumors ( &amp;gt;30%) has been cited as having a high potential for cosmetic defect, and hence represents a typical upper limit for potential tissue removal in BCS. Here, we evaluated a patient cohort to better understand the economic impact of the Alliance trial and further categorize patients that would most benefit without suffering cosmetic impact. We employed a novel computational technology to quantify the ratio of tumor size to breast tissue volume. Methods: Using a publicly available, single site cohort (n=243, DUMC) of breast cancer patients that underwent mastectomy, we segmented the tumors using our TumorSight Viz software platform. This platform uses artificial intelligence to segment the tumor and surrounding tissues and allows for a volumetric and morphologic assessment in 3D space. We then applied relevant inclusion/exclusion criteria from the Alliance Trial to the cohort (Saha et al, 2018). In trial eligible patients, we used TumorSight Viz to create a convex hull (CH) around the multi-focal disease using dilations of 1 cm and 2 cm. The volume of the CH, corresponding to proposed surgical extirpation, and the overall breast volume (BV) were then computationally assessed in 3D. The ratio of CH to BV (CH:BV) was calculated and a cutoff of 30% (high potential for cosmetic deformity) was applied. A cost analysis was then carried out. We determined the aggregate per annum savings that could potentially be realized by transforming a subset of mastectomies to BCS by tabulating total costs of mastectomy+reconstruction vs. BCS+WBI (whole-breast irradiation), as well as adjusted for relative rates of adjuvant therapy (~80%) across the nationwide patient population. Results: We found that 19.3% of adjuvant mastectomy patients were eligible for BCS based on Alliance Trial criteria. Of those, 68% had tumor CH:BV &amp;lt; 30% when using a 1 cm dilation around the tumor. When using a 2 cm dilation, 56% had tumor CH:BV &amp;lt; 30%. Together, these results indicate that of all adjuvant mastectomy patients, an estimated 10.8-13.1% are eligible for BCS based on volumetric measures of cosmetically acceptable breast tissue removal. Our economic analysis of BCS vs. mastectomy revealed an estimated $28,500 cost savings for patients with private insurance, suggesting that both decreased costs and improved quality-of-life (QOL) can be mutually aligned. By assessing the nationwide number of patients receiving adjuvant therapy for breast cancer, alongside the percentage potentially eligible for BCS using the above cosmetic defect analysis, we estimate that BCS conversion from mastectomy offers to provide a net savings of $300-350 million annually. Conclusion: The Alliance Trial guidelines unveiled the potential option of BCS in ~20% of patients with multi-focal disease in our cohort, demonstrating considerable cost-savings. Computational tools can further differentiate individuals who may not be best candidates for BCS in this setting, ensuring high QOL and informed decision-making. Citation Format: John Pfeiffer, Matthew Biancalana, Dorys Lopez-Ramos, Bradley Feiger, Anuja Antony. Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-07-04.

TNF-α can promote membrane invasion by activating the MAPK/MMP9 signaling pathway through autocrine in bone-invasive pituitary adenoma.

A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone-invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear. We performed transcriptome microarrays on specimens of bone-invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF-α through plasmids, then validated the effects of TNF-α on GH3 cells and verified the efficacy of the TNF-α inhibitor SPD304. Finally, the effects of TNF-α were validated in invivo experiments. Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF-α, MMP9, and p-p38 is higher in BIPAs than in NIPAs. Overexpression of TNF-α elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF-α overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. Invivo experiments confirm that the TNF-α overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF-α overexpression. Bone-invasive pituitary adenoma secretes higher levels of TNF-α, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF-α and may be applied in the clinical treatment of bone-invasive pituitary adenoma.

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy

PurposeHepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors.MethodsIn this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child–Pugh score (CPS) progression was also explored.ResultsSBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2‑Gy fractions with α/β 10 Gy (EQD2α/β10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose–response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/β3–8 dose to the liver (12.8–12.6) with a 10% likelihood of ncRILD.ConclusionSBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61–73.1 Gy, coupled with a mean liver dose under 12.6–12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Hypoxia-mediated attenuation of EGLN2 inhibition of the NF-κB signaling pathway leads to the formation of a loop between HIF-1α and MUC1-C promoting chemoresistance in bladder cancer.

The expression pattern of MUC1-C in tumors is closely linked to tumor progression; however, its specific mechanism remains unclear. The expression of MUC1-C in cancer and adjacent normal tissues was detected using immunohistochemistry and Western blot. The IC50 of cells to gemcitabine was determined using the CCK8 assay. The effects of hypoxia and MUC1-C on the behavioral and metabolic characteristics of bladder cancer cells were investigated. Gene expression was assessed through Western blot and polymerase chain reaction. The relationship between the genes was analyzed by co-immunoprecipitation, immunofluorescence and Western blot. Finally, the role of the EGLN2 and NF-κB signaling pathways in the interaction between MUC1-C and hypoxia-inducible factor-1α (HIF-1α) was investigated. MUC1-C expression is significantly higher in bladder cancer tissues than in adjacent normal tissues, particularly in large-volume tumors, and is closely correlated with clinical features such as tumor grade. Tumor volume-mediated hypoxia resulted in increased expression of MUC1-C and HIF-1α in bladder cancer cells. Under stimulation of hypoxia, the inhibitory effect of EGLN2 on the NF-κB signaling pathway was weakened, allowing NF-κB to promote the positive feedback formation of MUC1-C and HIF-1α. Simultaneously, EGLN2-mediated degradation of HIF-1α was reduced. This ultimately led to elevated HIF-1α-mediated downstream gene expression, promoting increased glucose uptake and glycolysis, and ultimately resulting in heightened chemotherapy resistance and malignancy.

HPV-Related Multiphenotypic Sinonasal Carcinoma: A Clinicoradiological Series of 3 Cases With Full Endoscopic Surgical Outcome.

Context: Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC), formerly known as HPV-related carcinoma with adenoid cystic like features, is a rare tumor subtype with unusual correlation between radiological, histopathological, and surgical findings. The shared histological characteristics with other sinonasal tumors make the diagnosis challenging. Optimal surgical and oncological treatments for this rare condition remains to be clearly defined. Methods: The objective of the study was to describe the unique characteristics and endoscopic surgical treatment of this rare tumor. In this retrospective case series, all patients with an HMSC diagnosis treated in our tertiary center were selected. Results: Three HMSC cases were identified, including 2 male and 1 female patients. All cases originated from the posterior nasal cavity. One case presented with a tumor of 8.9 cm × 6.4 cm × 8.7 cm, which is the largest tumor volume described to date. All patients received exclusively endoscopic surgical treatment, followed by adjuvant radiation therapy. No patient showed clinical or radiological sign of disease recurrence, or regional or distant metastasis, with a follow-up ranging from 9 months to 4 years. In 2 cases, initial diagnoses incorrectly suggested adenoid cystic or basaloid squamous cell carcinoma. HPV-DNA testing confirmed the presence of HPV in all cases, with identification of strains 16 and 18. Conclusion and Relevance: HMSC represents a newly identified diagnosis that constitutes a significant challenge for both clinicians and pathologists. It is crucial to acknowledge its indolent clinical course and the apparent contradiction between aggressive radiological features and the noninvasive nature of surgical findings. Skull base surgeons should be aware that, despite these complexities, endoscopic treatment is achievable in the majority of cases. This understanding is essential for the effective management of HMSC.

Refining the predictive value of preoperative apparent diffusion coefficient (ADC) by whole-tumor analysis for facial nerve outcomes in vestibular schwannomas.

Apparent diffusion coefficient (ADC) in MRI has been shown to correlate with postoperative House-Brackmann (HB) scores in patients with vestibular schwannoma despite limited methodology. To rectify limitations of single region of interest (ROI) sampling, we hypothesize that whole-tumor ADC histogram analysis will refine the predictive value of this preoperative biomarker related to postoperative facial nerve function. Of 155 patients who underwent resection of vestibular schwannoma (2014-2020), 125 patients were included with requisite clinical and radiographic data. After volumetric analysis and whole-tumor ADC histogram, regression tree analysis identified ADC cutoff for significant differences in HB grade. Outcomes were extent of resection, facial nerve function, hospital length of stay (LOS), and complications. Regression tree analysis defined three quantitative ADC groups (× 10-6 mm2/s) as high (> 2248.77; HB 1.7), mid (1468.44-2248.77; HB 3.1), and low (< 1468.44; HB 2.3) range (p 0.04). The mid-range ADC group had significantly worse postoperative HB scores and longer hospital LOS. Large tumor volume was independently predictive of lower rates of gross total resection (p <0.0001), higher postoperative HB score (p 0.002), higher rate of complications (p 0.04), and longer LOS (p 0.003). Whole-tumor histogram yielded a robust regression tree analysis that defined three ADC groups with significantly different facial nerve outcomes. This likely reflects tumor heterogeneity better than solid-tumor ROI sampling. Whole-tumor ADC warrants further study as a useful radiographic biomarker in patients with vestibular schwannoma who are considering surgical resection.

200 DWI and ADC Changes in Patients With Glioblastoma IDH-Wild Type Following Surgical Tumor Resection

INTRODUCTION: Current standard of care for glioblastoma (GBM) entails maximal tumor resection to achieve better outcomes while preserving neurological function. Early postoperative DWI has elucidated that peritumoral ischemia is common following glioma resection, but radiographic characteristics, risk factors, and outcomes have not been well described. METHODS: This retrospective cohort included 324 patients (18-86 years) who underwent surgical resection for glioblastoma IDH-wildtype between 2005 and 2022. All patients had structural MRI and DWI acquired preoperatively and within 72 hrs after resection. Areas of restricted diffusion on postoperative DWI were classified as rim, sector, mixed, or remote. RESULTS: Areas of restricted diffusion on postoperative DWI were found in 173 (53%) patients. 55 (32%) were rim-shaped, 103 (59%) sector-shaped, 10 (6%) mixed, and 5 (3%) remote. Preoperative tumor volume was positively correlated with areas of ischemia (p = 0.048), but peritumoral DWI was not correlated with decreased overall survival (OS) or Karnofsky Performance Score (KPS). In the full cohort analysis, gross total resection (GTR) correlated with improved OS compared to subtotal total resection (STR) (p = 0.016); however, subgroup analysis revealed that this survival benefit was exclusively found in patients without peritumoral infarction on DWI (21 months vs. 13 months, p = 0.043). CONCLUSIONS: Larger tumor volume was a risk factor for larger peritumoral infarction. The survival benefit of GTR was only seen in patients who did not experience postoperative peritumoral infarction, underscoring the importance of maximal safe tumor resection. Future study on specific causes of postoperative peritumoral infarctions may improve surgical management and outcomes in glioblastoma patients.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiation Therapy for Locally Advanced Lung Cancer

Real-time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiation therapy (o-ART) on the ETHOS system with image guided radiation therapy delivery on a Halcyon unit for conventional fractionated radiation therapy of locally advanced lung cancer (LALC). We analyzed 26 patients with LALC treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real-world clinic. Target coverage and organ at risk (OAR) doses were compared between adaptive plans (ADP) and nonadaptive scheduled plans (SCH). Planning robustness was evaluated by the frequency of preplanning goals achieved in ADP plans, stratified by tumor volume change. The AOD workflow was achievable within 30 minutes for most radiation fractions. Over the course of therapy, we observed an average 26.6% ± 23.3% reduction in internal target volume (ITV). Despite these changes, with o-ART, ITV and planning target volume (PTV) coverage (V100%) was 99.2% and 93.9% for all members of the cohort, respectively. This represented a 2.9% and 6.8% improvement over nonadaptive plans (P < .05), respectively. For tumors that grew >10%, V100% was 93.1% for o-ART and 76.4% for nonadaptive plans, representing a median 17.2% improvement in the PTV coverage (P < .05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in nonadaptive plans, this figure was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in the heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. The AOD workflow is efficient and robust in responding to anatomic changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiation therapy.

Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

Role of primary tumor volume and metastatic lymph node volume in response to curative effect of definitive radiotherapy for locally advanced head and neck cancer

BackgroundStudies have shown mixed results concerning the role of primary tumor volume (TV) and metastatic lymph node (NV) volume in response to the curative effect of definitive radiotherapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC).ObjectiveWe aimed to evaluate the impact of TV and NV on the efficacy of radical radiotherapy in LAHNSCC patients, with the goal of guiding individualized therapy.Patients and methodsPatients with LAHNSCC who received radical radiation therapy and were reexamined within 6 months post-therapy from January 2012 to December 2021 were selected. The volumes of the primary tumors and metastatic lymph nodes were calculated by software and then were divided into a large TV group vs small TV group and a large NV group vs small NV group according to the relationship with the median. Additionally, patients who received concurrent chemoradiotherapy (CCRT) or not were divided into the CCRT group and the radiotherapy (RT) group. Patients with lymph node metastasis were divided into node concurrent chemotherapy (N-CCRT) group and a node metastatic chemotherapy (N-RT) group according to whether they received concurrent chemotherapy or not. The volume shrinkage rate (VSR), objective response rate (ORR), local control rate (LCR) and overall survival (OS) were recorded and analyzed.Results96 patients were included in the primary tumor volume group, and 73 patients were included in the metastatic lymph node group. Receiver operating characteristic (ROC) curves were constructed for objective remission (OR) endpoints, and a volume threshold was defined for TV and NV patients. The threshold primary tumor volume was 32.45 cm3, and the threshold metastatic lymph node volume was 6.05 cm3.The primary TV shrinkage rates of the small TV and the large TV groups were basically the same, P = 0.801. Similarly, the ORR and LCR were not significantly different between the small TV group and the large TV group (PORR = 0.118, PLCR = 0.315). Additionally, the TV shrinkage rate did not significantly differ between the CCRT group and the RT group, P = 0.133. Additionally, there was no significant difference in ORR or LCR in CCRT group (PORR = 0.057, PLCR = 0.088). However, the metastatic lymph node volume shrinkage rate in the small NV group was significantly greater than that in the large NV group (P = 0.001). The ORR and LCR of the small NV subgroup were significantly greater than those of the large NV subgroup (PORR = 0.002, PLCR = 0.037). Moreover, compared with that of the N-RT group, the NV shrinkage rate of the N-CCRT group was 84.10 ± s3.11%, and the shrinkage rate was 70.76 ± s5.77% (P = 0.047). For the ORR and LCR, the N-CCRT group and N-RT group were significantly different (PORR = 0.030, PLCR = 0.037). The median OS of the whole group was 26 months. However, neither TV/NV nor concurrent chemotherapy seemed to influence OS.ConclusionPrimary tumor volume is not a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Nevertheless, metastatic lymph nodes are a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Patients with smaller lymph nodes have better local control.

Can we predict overall survival using machine learning algorithms at 3-months for brain metastases from non-small cell lung cancer after gamma knife radiosurgery?

Gamma knife radiosurgery (GRKS) is widely used for patients with brain metastases; however, predictions of overall survival (OS) within 3-months post-GKRS remain imprecise. Specifically, more than 10% of non-small cell lung cancer (NSCLC) patients died within 8 weeks of post-GKRS, indicating potential overtreatment. This study aims to predict OS within 3-months post-GKRS using machine learning algorithms, and to identify prognostic features in NSCLC patients. We selected 120 NSCLC patients who underwent GKRS at Chungbuk National University Hospital. They were randomly assigned to training group (n = 80) and testing group (n = 40) with 14 features considered. We used 3 machine learning (ML) algorithms (Decision tree, Random forest, and Boosted tree classifier) to predict OS within 3-months for NSCLC patients. And we extracted important features and permutation features. Data validation was verified by physician and medical physicist. The accuracy of the ML algorithms for predicting OS within 3-months was 77.5% for the decision tree, 72.5% for the random forest, and 70% for the boosted tree classifier. The important features commonly showed age, receiving chemotherapy, and pretreatment each algorithm. Additionally, the permutation features commonly showed tumor volume (>10 cc) and age as critical factors each algorithm. The decision tree algorithm exhibited the highest accuracy. Analysis of the decision tree visualized data revealed that patients aged (>71 years) with tumor volume (>10 cc) were increased risk of mortality within 3-months. The findings suggest that ML algorithms can effectively predict OS within 3-months and identify crucial features in NSCLC patients. For NSCLC patients with poor prognoses, old age, and large tumor volumes, GKRS may not be a desirable treatment.

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study

ObjectiveCosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. MethodsWe retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. ResultsCosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. ConclusionsThe clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.