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The approval of radiation oncology care by insurance companies is burdensome for providers. In this topic discussion, we attempt to provide practical recommendations for how to deal with peer-to-peer phone calls as well as how to improve the timeliness and quality of subsequent letters of appeal.
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INTRODUCTION: Zanzalintinib (XL092) is a next-generation anti-VEGFR-related multi-targeted TKI that exhibits immunomodulatory effects. AREAS COVERED: This review explores preclinical and clinical data, along with the future directions associated with zanzalintinib and its combination with immune checkpoint inhibitors (ICIs). EXPERT OPINION: In addition to its anti-VEGFR activity, zanzalintinib demonstrates potential synergistic effects with ICIs through its immunomodulatory impact, attributed to its inhibition of MET and TAM kinases. Recent preclinical studies provide compelling evidence supporting this synergistic potential. Furthermore, a recent phase 1 dose escalation study confirmed the tolerability of the zanzalintinib and anti-PDL1 combination without major safety concerns.Multiple ongoing clinical trials are investigating the combination of zanzalintinib and ICIs across various solid tumor types, including phase 3 studies for renal cell carcinoma, colorectal, and head and neck cancer. These trials aim to elucidate the therapeutic role of this new-generation TKI and ICI combination.However, the identification of reliable predictive biomarkers for the zanzalintinib and ICI combination presents significant challenges. Given the intricate nature of their mechanistic rationale and the difficulties in identifying reliable biomarkers for combined anti-angiogenesis and ICI therapies, addressing this challenge remains a priority for ongoing and future research.
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There has been a controversy about the predictive value of tissue-TMB-H for immune checkpoint inhibitors (ICIs) with limited data regarding blood-TMB (bTMB) in GI tumors. We aim to evaluate the predictive value of bTMB compared with MSI-H in GI tumors. Patients with unresectable/metastatic GI cancer, harboring either MSS with bTMB-H (≥10 mut/Mb) or dMMR/MSI-H who received ICI were included. We compared ICIs' efficacy between MSS-bTMB-H (N=45) versus MSI-H (N=50) in GI tumors. Ninety-five patients were identified with the majority having colorectal (49.5%) or esophagogastric (34.7%) cancers. MSS-bTMB-H group had more esophagogastric cancer and later-line ICI recipients, with no significant differences in other known prognostic variables. At a median follow-up of 9.4 months, MSI-H group showed superior ORR (58.0% vs. 26.7%), DCR (84.0% vs. 42.2%), DoR (not-reached vs. 7.6 mo), PFS (22.5 vs. 3.8 mo), and OS (Not-reached vs. 10.1 mo) compared with MSS-bTMB-H. Multivariable analysis showed that MSI-H was an independent favorable factor over MSS-bTMB-H for PFS (HR=0.31, CI 0.15-0.63, P=0.001) and OS (HR=0.33, CI 0.14-0.80, P=0.014). MSI-H group showed favorable outcomes compared with MSS-bTMB-16+ (ORR: 58.0% vs. 26.9%; DCR: 84.0% vs. 42.3%; PFS:22.5 vs. 4.0 mo) and MSS-bTMB-20+ (ORR: 58.0% vs. 31.6%; DCR: 84.0% vs. 42.1%; PFS:22.5 vs. 3.2 mo). There was no difference between MSS-bTMB10-15 compared with MSS-bTMB-16+ in ORR, DCR, and PFS, or between MSS-bTMB10-19 compared with MSS-bTMB20+. Regardless of bTMB cutoff at 10, 16, or 20, bTMB-H did not appear to be a predictive biomarker in MSS GI tumors in this retrospective analysis.
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Significance: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology. Aim: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods. Approach: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84 pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention. Results: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features. Conclusions: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.
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Imágenes Hiperespectrales , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Imágenes Hiperespectrales/métodos , Algoritmos , Microscopía/métodos , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patología , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
BACKGROUND: IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower grade gliomas is unclear. METHODS: We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grade 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling. RESULTS: We identified six trials with 1,204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95%CI 0.62-0.97], P=.03) but not OS (HR:0.87 [95%CI 0.64-1.18], P=.17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95%CI 0.42-0.64], P<.001) and PFS (HR=0.47 [95%CI 0.39-0.57], P<.001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion. CONCLUSIONS: Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.
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INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (ALCL) has been rapidly rising in the US and around the world, leading to a mandated "black-box" label on all silicone- and saline-filled implants by the Food and Drug Administration (FDA). Because regulatory decisions in the US and around the world have been influenced primarily by risk estimates derived from cancer registries, it is important to determine their validity in identifying cases of ALCL. METHOD: We reviewed all cases of ALCL submitted to the New York State Cancer Registry from a large comprehensive cancer center in New York City from 2007 to 2019. To determine the possibility of misdiagnosis or under-diagnosis of ALCL cases reported to cancer registries, we accessed the sensitivity and specificity of the ICD-O-3 codes 9714 (ALCL) and 9702 (Mature T-cell lymphoma, not otherwise specified [T-NOS]) to identify pathologically-proven ALCL. RESULTS: We reviewed 2286,164 pathology reports from 47,466 unique patients with primary cancers. Twenty-eight cases of histologically-proven ALCL were identified. The sensitivity and specificity of the ICD-O-3 code 9714 (ALCL) were 82% and 100%, respectively. The sensitivity of the combined codes 9714/9702 (ALCL/T-NOS) was 96% and the specificity was 44%. CONCLUSION: Previous epidemiological studies that influenced regulatory decisions by the FDA may have systematically underestimated the risk of ALCL by at least 20%. We encourage updated global risk estimates of breast ALCL using methods that ensure adequate case ascertainment.
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Implantes de Mama , Linfoma Anaplásico de Células Grandes , Sistema de Registros , Humanos , Linfoma Anaplásico de Células Grandes/epidemiología , Linfoma Anaplásico de Células Grandes/etiología , Linfoma Anaplásico de Células Grandes/diagnóstico , Femenino , Implantes de Mama/efectos adversos , Persona de Mediana Edad , Adulto , Ciudad de Nueva York/epidemiología , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/epidemiología , Sensibilidad y EspecificidadRESUMEN
While minimally invasive laparoscopic surgery can help reduce blood loss, reduce hospital time, and shorten recovery time compared to open surgery, it has the disadvantages of limited field of view and difficulty in locating subsurface targets. Our proposed solution applies an augmented reality (AR) system to overlay pre-operative images, such as those from magnetic resonance imaging (MRI), onto the target organ in the user's real-world environment. Our system can provide critical information regarding the location of subsurface lesions to guide surgical procedures in real time. An infrared motion tracking camera system was employed to obtain real-time position data of the patient and surgical instruments. To perform hologram registration, fiducial markers were used to track and map virtual coordinates to the real world. In this study, phantom models of each organ were constructed to test the reliability and accuracy of the AR-guided laparoscopic system. Root mean square error (RMSE) was used to evaluate the targeting accuracy of the laparoscopic interventional procedure. Our results demonstrated a registration error of 2.42 ± 0.79 mm and a procedural targeting error of 4.17 ± 1.63 mm using our AR-guided laparoscopic system that will be further refined for potential clinical procedures.
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The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.
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Neoplasias Colorrectales , Nivel de Atención , Humanos , Neoplasias Colorrectales/terapia , Manejo de la Enfermedad , Terapia Combinada , Calidad de Vida , Estadificación de NeoplasiasRESUMEN
Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50-64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62-0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52-1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence.
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Augmented reality (AR) has seen increased interest and attention for its application in surgical procedures. AR-guided surgical systems can overlay segmented anatomy from pre-operative imaging onto the user's environment to delineate hard-to-see structures and subsurface lesions intraoperatively. While previous works have utilized pre-operative imaging such as computed tomography or magnetic resonance images, registration methods still lack the ability to accurately register deformable anatomical structures without fiducial markers across modalities and dimensionalities. This is especially true of minimally invasive abdominal surgical techniques, which often employ a monocular laparoscope, due to inherent limitations. Surgical scene reconstruction is a critical component towards accurate registrations needed for AR-guided surgery and other downstream AR applications such as remote assistance or surgical simulation. In this work, we utilize a state-of-the-art (SOTA) deep-learning-based visual simultaneous localization and mapping (vSLAM) algorithm to generate a dense 3D reconstruction with camera pose estimations and depth maps from video obtained with a monocular laparoscope. The proposed method can robustly reconstruct surgical scenes using real-time data and provide camera pose estimations without stereo or additional sensors, which increases its usability and is less intrusive. We also demonstrate a framework to evaluate current vSLAM algorithms on non-Lambertian, low-texture surfaces and explore using its outputs on downstream tasks. We expect these evaluation methods can be utilized for the continual refinement of newer algorithms for AR-guided surgery.
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Our previous research studies have demonstrated the role of microRNA133b (miR133b) in healing the contused spinal cord when administered either intranasally or intravenously 24 h following an injury. While our data showed beneficial effects of exogenous miR133b delivered within hours of a spinal cord injury (SCI), the kinetics of endogenous miR133b levels in the contused spinal cord and rostral/caudal segments of the injury were not fully investigated. In this study, we examined the miR133b dysregulation in a mouse model of moderate unilateral contusion injury at the fifth cervical (C5) level. Between 30 min and 7 days post-injury, mice were euthanized and tissues were collected from different areas of the spinal cord, ipsilateral and contralateral prefrontal motor cortices, and off-targets such as lung and spleen. The endogenous level of miR133b was determined by RT-qPCR. We found that after SCI, (a) most changes in miR133b level were restricted to the injured area with very limited alterations in the rostral and caudal parts relative to the injury site, (b) acute changes in the endogenous levels were predominantly specific to the lesion site with delayed miR133b changes in the motor cortex, and (c) ipsilateral and contralateral hemispheres responded differently to unilateral SCI. Our results suggest that the therapeutic window for exogenous miR133b therapy begins earlier than 24 h post-injury and potentially lasts longer than 7 days.
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Médula Cervical , Contusiones , MicroARNs , Traumatismos de la Médula Espinal , Animales , Ratones , Contusiones/metabolismo , Modelos Animales de Enfermedad , MicroARNs/metabolismo , MicroARNs/uso terapéutico , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia , Médula Cervical/lesionesRESUMEN
The COVID-19 pandemic caused widespread disruptions in cancer care. We hypothesized that the greatest disruptions in diagnosis occurred in screen-detected cancers. We identified patients (≥18 years of age) with newly diagnosed cancer from 2019 to 2020 in the US National Cancer Database and calculated the change in proportion of early-stage to late-stage cancers using a weighted linear regression. Disruptions in early-stage diagnosis were greater than in late-stage diagnosis (17% vs 12.5%). Melanoma demonstrated the greatest relative decrease in early-stage vs late-stage diagnosis (22.9% vs 9.2%), whereas the decrease was similar for pancreatic cancer. Compared with breast cancer, cervical, melanoma, prostate, colorectal, and lung cancers showed the greatest disruptions in early-stage diagnosis. Uninsured patients experienced greater disruptions than privately insured patients. Disruptions in cancer diagnosis in 2020 had a larger impact on early-stage disease, particularly screen-detected cancers. Our study supports emerging evidence that primary care visits may play a critical role in early melanoma detection.
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COVID-19 , Detección Precoz del Cáncer , Melanoma , Estadificación de Neoplasias , Neoplasias , Pandemias , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Masculino , Femenino , Estados Unidos/epidemiología , Detección Precoz del Cáncer/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Melanoma/epidemiología , Melanoma/diagnóstico , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Pacientes no Asegurados/estadística & datos numéricos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Adulto , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Atención Primaria de Salud/estadística & datos numéricos , Seguro de Salud/estadística & datos numéricos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Diagnóstico Tardío/estadística & datos numéricos , Bases de Datos Factuales , SARS-CoV-2/aislamiento & purificación , Modelos LinealesRESUMEN
Hepatocellular carcinoma (HCC), a prevalent and often fatal liver cancer, presents significant treatment challenges, especially in its advanced stages. This article delves into the promising approach of combining immunotherapy, particularly immune checkpoint inhibitors, with radiation therapy, a cornerstone of HCC management. Our review synthesizes current preclinical and clinical research, highlighting the potential synergistic effects of this combinational treatment. Emerging evidence suggests that this synergy enhances tumor control and improves patient survival rates. The combination leverages the localized, tumor-targeting ability of radiation therapy and the systemic, immune-boosting effects of immunotherapy, potentially overcoming the limitations inherent in each treatment modality when used separately. This integrative approach is especially promising in addressing the complex tumor microenvironment of HCC. However, the treatment landscape is nuanced, with challenges such as patient-specific response variability and potential resistance to therapies. Future research directions should focus on refining these combination strategies, tailoring them to individual patient profiles, and understanding the underlying mechanisms that govern the interaction between immunotherapy and radiation therapy. Such advancements could significantly improve HCC management, setting new standards for patient care and treatment efficacy.
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The purpose of this paper is to summarize 3 methods for treating adrenal metastases with stereotactic body radiation therapy. This article is not meant to provide consensus guidelines but rather to present 4 practical examples of treatment techniques using different treatment platforms from 3 institutions.
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Neoplasias de las Glándulas Suprarrenales , Radiocirugia , Humanos , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/radioterapia , Radiocirugia/métodosRESUMEN
Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.
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Líquido Cefalorraquídeo , Canales Iónicos , Vasos Linfáticos , Animales , Ratones , Líquido Cefalorraquídeo/metabolismo , Hidrocefalia/genética , Canales Iónicos/metabolismo , Canales Iónicos/genética , Vasos Linfáticos/metabolismo , Mecanotransducción Celular/fisiología , Meninges/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Pirazinas , Tiadiazoles , HumanosRESUMEN
PURPOSE: Previous comparative effectiveness studies have not demonstrated a benefit of proton beam therapy (PBT) compared with intensity-modulated radiation therapy (IMRT) for prostate cancer. An updated comparison of GI and genitourinary (GU) toxicity is needed. METHODS: We investigated the SEER-Medicare linked database, identifying patients with localized prostate cancer diagnosed from 2010 to 2017. Procedure and diagnosis codes indicative of treatment-related toxicity were identified. As a sensitivity analysis, we also identified toxicity based only on procedure codes. Patients who underwent IMRT and PBT were matched 2:1 on the basis of clinical and sociodemographic characteristics. We then compared GI and GU toxicity at 6, 12, and 24 months after treatment. RESULTS: The final sample included 772 PBT patients matched to 1,544 IMRT patients. The frequency of GI toxicity for IMRT versus PBT was 3.5% versus 2.5% at 6 months (P = .18), 9.5% versus 10.2% at 12 months (P = .18), and 20.5% versus 23.4% at 24 months (P = .11). The frequency of only procedure codes indicative of GI toxicity for IMRT versus PBT was too low to be reported and not significantly different. The frequency of GU toxicity for IMRT versus PBT was 6.8% versus 5.7% (P = .30), 14.3% versus 12.2% (P = .13), and 28.2% versus 25.8% (P = .21) at 6, 12, and 24 months, respectively. When looking only at procedure codes, the frequency of GU toxicity for IMRT was 1.0% at 6 months, whereas it was too infrequent to report for PBT (P = .64). GU toxicity for IMRT versus PBT was 3.3% versus 2.1% (P = .10), and 8.7% versus 6.7% (P = .10) at 12 and 24 months, respectively. CONCLUSION: In this observational study, there were no statistically significant differences between PBT and IMRT in terms of GI or GU toxicity.