Naphthalene Diimide-Based Polycyclic Conjugated Molecule Composite CoFe2O4 Nanohybrids for Photoacoustic Imaging-Mediated Photo-/Sonic Therapy.

The complex and harsh tumor microenvironment imped the efficacy of single-modality tumor therapy. With the advantages of biosafety, organic/inorganic nanohybrids have attracted more and more interest of researchers, and it is critical to investigate the development of highly efficient nanohybrids for multimodality combination therapy of cancers. Herein, a naphthalene diimide-based polycyclic conjugated molecule (NDI-S) is designed and synthesized, which has broader light absorption in the near infrared (NIR) region, outstanding photothermal conversion ability, and excellent photostability. Inorganic CoFe2O4 is synthesized via a solvothermal technique, which can produce much more reactive oxygen species (ROS) as a sonosensitizer when activated by ultrasonic (US). NDI-S and CoFe2O4 are then nanoprecipitated to create the organic/inorganic nanohybrids, NDI-S@CoFe2O4. According to the results of in vitro and in vivo experiments, NDI-S@CoFe2O4 can serve as a multifunctional nanoplatform for multimodal treatment of tumors in combination with photothermal/photodynamic/sonodynamic- therapy under the guidance of photoacoustic imaging, which provides a new vision of the development of organic/inorganic nanohybrids for cancer theranostics.

Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy characterized by advanced disease at diagnosis and a poor prognosis. Despite multimodal therapeutic approaches that include surgery, radiotherapy, and chemotherapy, an optimal treatment strategy remains elusive. Current developments in targeted therapies and immunotherapy offer promising avenues for improved outcomes, particularly for BRAF-mutant patients. However, challenges remain regarding overcoming drug resistance and developing effective treatments for BRAF-wild-type tumors. This comprehensive review examines the clinical and biological features of ATC, outlines the current standards of care, and discusses recent developments with a focus on the evolving role of radiotherapy. Moreover, it emphasizes the necessity of a multidisciplinary approach and highlights the urgent need for further research to better understand ATC pathogenesis and identify new therapeutic targets. Collaborative efforts, including large-scale clinical trials, are essential for translating these findings into improved patient outcomes.

Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma.

Medulloblastoma (MB) comprises four broad molecular subgroups, namely wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively, with subgroup-specific developmental origins, unique genetic profiles, distinct clinico-demographic characteristics, and diverse clinical outcomes. This is a retrospective audit of clinical outcomes in molecularly confirmed WNT-MB patients treated with maximal safe resection followed by postoperative standard-of-care risk-stratified adjuvant radio(chemo)therapy at a tertiary-care comprehensive cancer centre. Of the 74 WNT-MB patients registered in a neuro-oncology unit between 2004 to 2020, 7 patients accrued on a prospective clinical trial of treatment deintensification were excluded, leaving 67 patients that constitute the present study cohort. The median age at presentation was 12 years, with a male preponderance (2:1). The survival analysis was restricted to 61 patients and excluded 6 patients (1 postoperative mortality plus 5 without adequate details of treatment or outcomes). At a median follow-up of 72 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.7% and 91.2%, respectively. Traditional high-risk features, large residual tumour (≥1.5 cm2), and leptomeningeal metastases (M+) did not significantly impact upon survival in this molecularly characterized WNT-MB cohort treated with risk-stratified contemporary multimodality therapy. The lack of a prognostic impact of conventional high-risk features suggests the need for refined risk stratification and potential deintensification of therapy.

Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma.

OPINION STATEMENT: The integration of targeted therapy into the multimodal management of craniopharyngiomas represents a significant advancement in the field of neuro-oncology. Historically, the management of these tumors has been challenging due to their proximity to vital brain structures, necessitating a delicate balance between tumor control and the preservation of neurological function. Traditional treatment modalities, such as surgical resection and radiation, while effective, carry their own set of risks, including potential damage to surrounding healthy tissues and the potential for long-term side effects. Recent insights into the molecular biology of craniopharyngiomas, particularly the discovery of the BRAF V600E mutation in nearly all papillary craniopharyngiomas, have paved the way for a targeted systemic treatment approach. However, advances have been limited for adamantinomatous craniopharyngiomas. The success of BRAF/MEK inhibitors in clinical trials underscores the potential of these targeted therapies not only to control tumor growth but also to reduce the need for more invasive treatments, potentially minimizing treatment-related complications. However, the introduction of these novel therapies also brings forth new challenges, such as determining the optimal timing, sequencing, and duration of targeted treatments. Furthermore, there are open questions regarding which specific BRAF/MEK inhibitors to use, the potential need for combination therapy, and the strategies for managing intolerable adverse events. Finally, ensuring equitable access to these therapies, especially in healthcare systems with limited resources, is crucial to prevent widening healthcare disparities. In conclusion, targeted therapy with BRAF/MEK inhibitors holds great promise for improving outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. However, additional research is needed to address the questions that remain about its optimal use and integration into comprehensive treatment plans.

Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study.

BACKGROUND: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. METHODS/DESIGN: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. RESULT: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. CONCLUSION: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. TRIAL REGISTRATION: ChiCTR2200057179.

ASO Practice Guidelines Series: Management of Resectable, Borderline Resectable, and Locally Advanced Pancreas Cancer.

Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma.

[New and Established Multimodal Therapeutic Strategies in Advanced Rectal Cancer].

INTRODUCTION: Locally advanced rectal cancer has a high risk of local recurrence which can be reduced by multimodal therapy. Neoadjuvant radiotherapy or radiochemotherapy has been established. Nevertheless, this has not proved to improve overall survival. The benefit of adjuvant chemotherapy after neoadjuvant radiotherapy or radiochemotherapy remains unclear. Current studies are investigating total neoadjuvant therapy with different sequences of radiotherapy and chemotherapy followed by rectal resection. This procedure shows high pathologic complete remissions up to 28 % as well as an improvement in disease-free and metastasis-free survival. Under study conditions, in case of clinical complete remission, watchful waiting with close follow-up and surgery can be considered only in case of local tumor recurrence.

A Case of Bilateral Vertebral Artery Dissecting Aneurysm Treated With Multimodality Therapy Under Superficial Temporal Artery Assistance-Posterior Cerebral Artery Bypass.

A ruptured bilateral vertebral artery dissecting aneurysm (BVDA) is a challenging vascular disorder. Trapping surgery with bypass assistance could be a potential treatment; however, there is a risk of ischemic complications. Recently, endovascular treatment has been reported, but its long-term outcomes remain uncertain. The patient was a 57-year-old male who presented with subarachnoid hemorrhage. Digital subtraction angiography showed a dilated dominant left vertebral artery (VA) and a narrowed right VA, suggesting a BVDA. First, we performed a right superficial temporal artery-superior cerebellar artery (STA-SCA) insurance bypass. We then performed proximal clipping of the left vertebral VA. The pulsation of the STA-SCA bypass disappeared on day 6. Three-dimensional computed tomography angiography (3DCTA) showed the emergence of a fusiform aneurysm and proximal stenosis of the contralateral VA. On day 31, we performed a superficial temporal artery-posterior cerebral artery (STA-PCA) insurance bypass. Stent-assisted coil embolization was planned for two days after the STA-PCA bypass. However, preoperative angiography showed progression of right proximal VA stenosis, and stenting appeared impossible. There was no change in somatosensory evoked potential (SEP), and angiography showed sufficient retrograde blood flow to the posterior circulation during the right VA balloon occlusion test (BOT). Therefore, internal trapping of the right VA was performed. Postoperative angiography showed perfect patency of the left STA-PCA bypass and retrograde blood flow to the posterior circulation. There was no additional neurological deficit after endovascular treatment. Multimodality therapy could be a potential treatment for bilateral VA dissection.

A New Strategy to Elevate Absorptivity of AIEgens for Intensified NIR-II Emission and Synergized Multimodality Therapy.

High-efficiency absorptivity is crucial for the construction of high-performance luminescent materials, especially the long-wavelength near-infrared II (NIR-II) materials; thus seeking an efficient and universal strategy to elevate the absorptivity is extremely important but is still an intractable challenge. In this work, a simple but efficient design strategy is discovered, involving the introduction of gold(I) unit that could effectively elevate the absorptivity of aggregation-induced-emission luminogens (AIEgens). As a result of the efficient elevation of absorptivity, the representative AIE-active TBTP-Au shows more superior NIR-II (1220 nm) luminescence, much higher photothermal conversion efficiency, and unique intracellular reactive oxygen species (ROS) generating ability compared with that of the TBTP ligand. Taking advantage of these improvements, the fabricated tumor-targeting TBTP-Au-cRGD nanoparticles achieve specific NIR-II tumorous imaging in vivo and exert high-efficiency cancer therapy via the synergistic chemotherapy and photothermal therapy. Thus, this work provides a new and efficient strategy to construct high-absorption luminescent materials and demonstrates the great potential of gold(I)-based AIEgens as multifunctional theranostic agents.

Trends in Surgical Management of Esophageal Cancer.

BACKGROUND: Management of esophageal cancer has changed to a combined modality approach over the past two decades due to poor outcome. Recently, multimodal treatment has become the standard practice. The aim of this study was to evaluate the changing trends in management and outcomes of esophagectomy over 15 years from a single center in Nepal. METHODS: Patients with squamous cell carcinoma and adenocarcinoma of esophagus/ gastroesophageal junction who underwent surgery between 2001-2018 were analyzed. Patients were grouped into three successive 5-year periods. RESULTS: 547 patients underwent esophagectomy during 2001-2018. There was increased trend of neoadjuvant treatment from 9-13% to 52% (p<.001) and minimally invasive surgery (MIS) from 0% to 80% (p<.001). 30-day mortality decreased from 8% to 1% (p=.01). The 5-overall survival was 24% which increased from 17% to 27% (p=.003). CONCLUSIONS: Long term outcome has improved over last 15 years with decreasing mortality which appears to be due to incorporation of MIS and neoadjuvant treatment.

Current Management of Stage IIIA (N2) Non-Small-Cell Lung Cancer: Role of Perioperative Immunotherapy, and Tyrosine Kinase Inhibitors.

There have been numerous recent advances in the treatmetn of stage IIIA non-small cell lung cancer. The most significant involve the addition of targeted therapies adn immune checkpoint inhibitors into perioperative care. These exciting advances are improving survival in this challenging patient population, but some-decade old controveries around the definition of resectability, prognositic importance of tumor response to induction therapy, and the role of pneumonectomy persist.

Effect of Health Disparities on Refusal of Trimodality Therapy in Localized Esophageal Adenocarcinoma: A Propensity Score Matched Analysis of the National Cancer Database.

BACKGROUND: Factors associated with refusal of multimodality therapy in patients with localized esophageal adenocarcinoma (EA) remain unknown. We hypothesized that sociodemographic disparities affect decision to pursue optimal trimodally therapy for patients with EA. METHODS: NCDB for esophageal cancer (2004-2017) was utilized. Included were patients diagnosed with cT3-T4 cN0 or cTany N1-3 EA of the mid-lower esophagus. Annual institutional esophagectomy volumes were categorized as low (<20/year) and high (≥20/year). Conditional logistic regression was used to identify predictors of refusal of offered treatment. Kaplan Meier method was used to compare survival. RESULTS: 13 091 patients met selection criteria, mean age was 62.4 ± 9.6 years and 11 581 (88.5%) were males. 633 (4.8%) patients refused at least one component of recommended treatment (chemotherapy, radiation, and esophagectomy), most commonly refusal of surgery (N = 554, 4.2%). On multivariable analysis, factors predictive of treatment refusal included older age, female gender, black race, no insurance, low income (below poverty), mid-esophageal tumors, and treatment at low-volume centers. Patients who were recommended treatment but refused had significantly worse survival than those who adhered to treatment (median 23.1 ± 1.1 vs. 32.1 ± 1.2 months; P < .001). CONCLUSIONS: In this study, sociodemographic disparities and center volume were among factors predictive of therapy refusal in patients with localized esophageal adenocarcinoma. While understanding potential reasons for treatment refusal is critical, this data suggests that socioeconomic variables may drive patient decisions.

Clinical Characteristics and Multimodality Therapy Outcomes in 304 Pediatric Patients with Cerebral Arteriovenous Malformations.

BACKGROUND: Clinical follow-up data of pediatric patients with cerebral arteriovenous malformations (AVMs) are limited. This study investigated the characteristics of AVMs in children and analyzed the clinical outcomes of multimodality therapy in pediatric patients with AVMs at a single center. METHODS: This retrospective study included consecutive patients diagnosed with AVMs at our institution between August 2008 and June 2018. Data on demographic characteristics, AVM features, and clinical outcomes were collected. Patients aged <18 years at admission were defined as children. RESULTS: Overall, 1009 patients with AVMs were included, with 304 (30.1%) patients aged <18 years. AVMs in pediatric patients were more likely to present with intracranial hemorrhage, mostly located in deep areas of the brain. A small nidus, exclusively deep drainage, and deep AVM location were associated with hemorrhage in children; Kaplan-Meier analysis revealed that patients with ruptured AVMs had a higher risk of developing a follow-up hemorrhage than those with unruptured AVMs. Among 290 children who were followed up, the multivariate regression analysis showed that a higher pretreatment modified Rankin Scale score, deep AVM location, and conservative treatment were significantly associated with unfavorable outcomes. CONCLUSIONS: In pediatric patients, AVMs were more likely to present with intracranial hemorrhage than that in adults. Hemorrhagic presentation in children was associated with a small nidus, exclusively deep drainage, and deep AVM location. Pediatric patients with ruptured AVMs had significantly higher risks of follow-up hemorrhage than those with unruptured AVMs. Our clinical results suggest that nonconservative treatment is better for pediatric patients with AVMs.

Improving outcomes in malignant pleural mesothelioma in an integrated health care system.

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor that should be managed by an experienced surgical and multidisciplinary group. Our objective was to determine the impact of proficient surgeons and MPM bi-disciplinary review on outcomes of patients with MPM. Methods: Through this cohort study, electronic medical records of 368 adult patients with MPM from 1/1/2009 to 12/31/2020 were reviewed and compared before and after MPM surgeries were regionalized to specialized surgeons and bi-disciplinary review of MPM patient treatment options. We used the Kaplan-Meier method and log-rank tests to compare survival rates by period, by treatment type, and by stage. Patients were followed from cancer diagnosis date until they died or end of study follow-up, whichever occurred first. We also conducted Cox proportional hazards regression model to examine the overall survival (OS) with adjustments for age, histology, stage, and Charlson comorbidity index (CCI). Results: Despite similar staging, more patients received any MPM directed treatment from 2015-2020 compared with those patients from 2009-2014. Specifically, there was an increase in patients who received pleurectomy/decortication (PD) from 2015-2020 compared to those who received PD in 2009-2014. Patients with similar age, CCI, stage, and histology had an increase in OS of 12 months with multimodality therapy (surgery, systemic therapy, +/- radiation) compared to those patients who received no treatment. Conclusions: Consolidating mesothelioma surgery to a specialized surgical team and regular bi-disciplinary review of MPM cases to determine appropriate multimodality therapy, increases the incorporation of surgical treatments in the management of patients with MPM.

Multimodality Therapy in Patients With Primary Pericardial Mesothelioma.

INTRODUCTION: Primary pericardial mesothelioma (PPM) has no accepted standard-of-care treatment options with management and outcomes often extrapolated from diffuse pleural mesothelioma. Disease-specific research is needed to better define PPM. We report our institutional experience with PPM highlighting the potential role for multimodality therapy. METHODS: Patients with PPM diagnosed by a multidisciplinary team of medical oncologists, thoracic surgeons, thoracic pathologists, and radiologists between January 2011 and January 2022 were followed to February 2022. Clinicopathologic features and treatment outcomes were annotated. Overall survival (OS) was defined from the date of pathologic diagnosis. RESULTS: The median age at diagnosis of the 12 patients identified with having PPM was 51 (range: 21-71) years old. Most patients were of female sex (n = 8; 67%), 75% of the samples were epithelioid (n = 9), and 25% were nonepithelioid (two sarcomatoid and one biphasic). Most cases (92%, 11 of 12) had expression of at least two mesothelial markers on immunohistochemistry. The median OS of the cohort was 25.9 months. Five patients had an OS greater than 12 months; four of whom received pericardial radiation. Three of the patients who received radiation did so as part of a trimodality approach (surgical resection, adjuvant chemotherapy, and radiation); the OS for patients who received trimodality therapy was 70.3 months versus 8.2 months for those who did not. CONCLUSIONS: PPM represents a distinct disease with no universally accepted treatment options. Our findings suggest that trimodality therapy may improve outcomes in selected patients with PPM.

Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds.

The aggressive and recurrent nature of glioblastoma is multifactorial and has been attributed to its biological heterogeneity, dysfunctional metabolic signaling pathways, rigid blood-brain barrier, inherent resistance to standard therapy due to the stemness property of the gliomas cells, immunosuppressive tumor microenvironment, hypoxia and neoangiogenesis which are very well orchestrated and create the tumor's own highly pro-tumorigenic milieu. Once the relay of events starts amongst these components, eventually it becomes difficult to control the cascade using only the balanced contemporary care of treatment consisting of maximal resection, radiotherapy and chemotherapy with temozolamide. Over the past few decades, implementation of contemporary treatment modalities has shown benefit to some extent, but no significant overall survival benefit is achieved. Therefore, there is an unmet need for advanced multifaceted combinatorial strategies. Recent advances in molecular biology, development of innovative therapeutics and novel delivery platforms over the years has resulted in a paradigm shift in gliomas therapeutics. Decades of research has led to emergence of several treatment molecules, including immunotherapies such as immune checkpoint blockade, oncolytic virotherapy, adoptive cell therapy, nanoparticles, CED and BNCT, each with the unique proficiency to overcome the mentioned challenges, present research. Recent years are seeing innovative combinatorial strategies to overcome the multifactorial resistance put forth by the GBM cell and its TME. This review discusses the contemporary and the investigational combinatorial strategies being employed to treat GBM and summarizes the evidence accumulated till date.

Glioblastoma is a form of brain tumor which typically leads to death in almost all patients. Over the last two decades, traditional treatment strategies such as surgery, radiotherapy and chemotherapy have been combined as standard therapy. Together, these aggressive treatment strategies have provided modest survival benefit with acceptable toxicity. However, relapse is the invariable norm resulting in death in the overwhelming majority of patients. Relapse occurs due to multiple factors such as inability of drugs to cross blood­brain barrier, immunosuppressive tumor microenvironment, stemness nature of glioma cells, tumor heterogeneity and enhanced hypoxia and angiogenic factors. Therefore, there is an urgent need to develop an innovative treatment approach to treat glioblastoma. Recently, several treatment strategies known as immunotherapies including CAR T cell therapy, dendritic cell vaccines, immune checkpoints blockade and oncolytic virus, nano particles and gene editing/silencing technology have demonstrated promising results in preclinical and few clinical trials. Furthermore, to increase the efficacy of these novel strategies, combinatorial approaches are being implemented for the treatment. This includes CAR T cell therapy in combination with small molecules, immune checkpoint inhibitors and oncolytic virus and nanoparticles plus gene editing, silencing or immune checkpoints inhibitors. These treatments have shown exciting results in preclinical settings and few of these trials are in progress. The review summarizes these combinatorial novel approaches and discusses them in detail.

Retroperitoneal Sarcomas: Histology Is Everything.

Retroperitoneal sarcomas (RPS) are a rare subset of soft tissue sarcoma that are composed of only a few histologic subtypes, each with a distinct tumor biology, clinical presentation, preferred treatment strategy, recurrence risk, and surveillance plan. In the modern era of precision medicine, our understanding of the implications of subtype tumor biology and anatomic location has led to a more nuanced, histology-specific approach to therapy, including surgery, neoadjuvant radiation therapy, and/or chemotherapy. This article provides a summary of recent updates to the management of RPS.