Metastasis Death Research Articles

The crosstalk between exosomal miRNA and ferroptosis: A narrative review.

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive and negative regulation of it. For example, increased levels of reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it is not dependent on caspases, but is dependent on iron. Exosomes are membrane-bound vesicles with a size of about 30 to 150nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, and proteins, which are genetically similar to their cells of origin. Exosomes are found in all bodily fluids, including blood, saliva, and urine. Cells often release exosomes after their fusion with the cell membrane. They play an important role in immune regulation and cell-cell communication. miRNAs, which are noncoding RNAs with a length of about 18 to 24 nucleotides, are involved in regulating gene expression after transcription. Emerging data suggests that exosomal miRNAs are implicated in various pathophysiological mechanisms of cells, including metastasis, drug resistance, and cell death. In addition, functional studies have indicated that exosomal miRNAs can play a key role in the modulation of cell death by regulating ferroptosis. Therefore, in this review, given the importance of exosomal miRNAs in ferroptosis, we decided to elucidate the relationship between exosomal miRNAs and ferroptosis in various diseases.

Chirurgie pour tumeurs phyllodes du sein : la dénomination d’une tumeur phyllode géante est-elle justifiée ?

In Africa, rare publications have focused on phyllodes tumors (PTs). The aim of our study is to describe the special feature of PTs surgery. Retrospective and descriptive study of 11 cases of PT operated from January 1, 2015 to March 31, 2023 at the medical-surgical clinic in Teaching Hospital Center of Sylvanus Olympio of Lome. The patients had a breast ultrasonography with or without mammography and core needle biopsy. Epidemiological, clinical and therapeutic data were record. The follow up was regularly at 1 month, 3 months and every 6 months. The PT was 4.9% of breast tumors operated on. The mean age was 29years (range 18 to 61). The 20-30 age group was the most represented in 5 cases. Self-examination of a breast nodule, breast pain, and fear of cancer were noted in 11, 4, and 2 cases, respectively. The mean time to admission was 8 months (range 6 to 18). The mean tumor size was 6.4cm (range 3-11). Breast-conserving surgery was performed in 10 patients and mastectomy in 1 case with R1 resection. We noted necrosis of the areola and nipple plate. The histopathology types are classified into benign (3), intermediate (6) and malignant (2). R1 resection noted local recurrence, then metastatic recurrence and death at 16months. TPs were described as giant (size greater than 5cm). There is no preset technique to apply. Conservative surgery is our preference while respecting a Ro margin, a breast remaining aesthetic and a lower scar price.

Oncologic outcomes for invasive squamous cell carcinoma with a clinically resolved biopsy site managed by watchful waiting: A retrospective cohort study.

Treatment of cutaneous squamous cell carcinoma largely involves surgical excision. Few studies have examined oncologic outcomes of tumors managed by watchful waiting when the lesion appears resolved after the biopsy site has healed. To describe oncologic outcomes for patients diagnosed with cutaneous squamous cell carcinoma that was determined clinically resolved at follow-up and subsequently managed by watchful waiting. This retrospective cohort included pathology proven cases of cutaneous squamous cell carcinoma occurring from 1/1/2013 to 4/31/2023. Each required documented clinical resolution more than 4 weeks after biopsy, management by watchful waiting, and at least 12 months of follow-up. Of 148 tumors managed by watchful waiting, there were two cases of local recurrence, and no cases of nodal metastasis, distant metastasis, or disease specific death. Log-rank test found significant risk of recurrence in immunocompromised participants (HR=12.87, p=0.0193) and those with rheumatologic disease (HR=16.18, p=0.0075). Retrospective, single-center design. The recurrence rate in this cohort compares favorably to reported recurrence rates for surgically managed cutaneous squamous cell carcinoma. In select cases, watchful waiting may be a reasonable management option for low-risk lesions that appear clinically resolved after healing of the biopsy site.

Long-term outcomes of endoscopic submucosal dissection for T1b colorectal cancer.

Endoscopic submucosal dissection (ESD) is a standardized procedure for intramucosal and slightly invasive submucosal colorectal cancers (CRC). However, the role of ESD for T1b (depth of submucosal invasion: ≥1,000 μm) CRC remains unclear. This study aimed to investigate the long-term efficacy and safety of ESD for T1b CRC. This study involved 50 patients with T1b CRC who underwent ESD, including 31 who received subsequent surgery (ESD + surgery group) and 19 who reported comorbidities or refused subsequent surgery (ESD-alone group). The clinical outcomes, lymph node metastasis (LNM) rate, and recurrence and survival rates were determined. All the patients achieved en-bloc resection, and 41 patients achieved R0 resection. The mean tumor diameter was 31.2 ± 11.9 mm. LNM was detected in 3 (6%) cases, demonstrating high-grade tumor budding (Bd 2/3) and invasion depth of >1,500 um. LNM was significantly correlated with tumor budding (P = 0.030). The overall median follow-up period was 41.00 ± 27.69 months and 33.16 ± 19.05 months in the ESD-alone and ESD + surgery groups, respectively (P = 0.241). Two patients in the ESD group had local recurrence and two patients died. Patients in the ESD + surgery group reported no local recurrence, distant metastasis, or disease-related death. Recurrence (P = 0.074) and survival rates (P = 0.072) were not significantly different between the two groups. The LNM rate was exceedingly low in patients with T1b. ESD is an effective and safe method for these patients. The necessity of additional surgical treatment after ESD should be comprehensively determined following the patient's characteristics.

CAR-T cell therapy for breast cancer: Current status and future perspective.

Within the expanding therapeutic landscape for breast cancer (BC), metastatic breast cancer (MBC) remains virtually incurable and tend to develop resistance to conventional treatments ultimately leading to metastatic progression and death. Cellular immunotherapy (CI), particularly chimeric antigen receptor-engineered T (CAR-T) cells, has emerged as a promising approach for addressing this challenge. In the wake of their striking efficacy against hematological cancers, CAR-T cells have also been used where the clinical need is greatest - in patients with aggressive BCs. Unfortunately, current outcomes fall considerably short of replicating that success, primarily owing to the scarcity of tumor-specific antigens and the immunosuppressive microenvironment within BC. Herein, we provide an up-to-date overview of both preclinical and clinical data concerning the application of CAR-T cell therapy in BC. By surveying the existing literature, we discuss the prevailing constrains of this therapeutic approach and overview possible strategies to advance it in the context of breast malignancies. Possible approaches include employing synthetic biology to refine antigen targeting and mitigate off-target toxicity, utilizing logic-gated CAR constructs to enhance specificity, and leveraging armored CARs to remodel the tumor micro-environment. Temporal and spatial regulation of CAR-T cells using inducible gene switches and external triggers further improves safety and functionality. In addition, promoting T cell homing through chemokine receptor engineering and enhancing manufacturing processes with universal CAR platforms expand therapeutic applicability. These innovations not only address antigen escape and T cell exhaustion but also optimize the efficacy and safety profile of CAR-T cell therapy. We, therefore, outline a trajectory wherein CAR-T cells may evolve from a promising experimental approach to a standard modality in BC therapy.

Perineural Invasion for Risk Stratification in Cutaneous Squamous Cell Carcinoma: A Scoping Review.

Microscopic perineural invasion (mPNI) is a histopathological characteristic that can be found in cutaneous squamous cell carcinoma (cSCC). In the eighth edition of the American Joint Committee on Cancer (AJCC), mPNI defined as the involvement of nerves ≥0.1 mm and nerves deeper than the dermis is included in risk stratification of cSCC. The question remains whether other mPNI features are important for optimal cSCC staging. We aimed to summarize the evidence from published studies on the independent association between various mPNI features and the risk of recurrence, metastasis and disease-specific death in patients with cSCC. Embase, PubMed, and Web of Science were searched from January 2023 to February 2024 to identify studies that reported the prognostic impact of mPNI features in patients ≥18 years with histopathologically verified cSCC. Data on study and tumour characteristics were extracted. Nineteen studies met the inclusion criteria and evaluated one or more mPNI features in cSCC including nerve diameter, the extent of mPNI, the number of affected nerves, and depth of mPNI. Two studies provided evidence that "mPNI ≥0.1 mm" and "mPNI deeper than the dermis" are significantly and independently associated with poor prognosis after correction for other mPNI features and high-risk factors. One of these studies additionally identified "involvement of ≥3 nerves" as an independent and significant predictor of higher risk of local recurrence (HR, 2.17; 95% CI: 1.03-4.56; p = 0.04). Besides "nerve diameter of ≥0.1 mm" and "depth of mPNI involvement," "involvement of multiple nerves" was found to be an independent risk factor for poor prognosis and should also be considered for appropriate risk stratification.

Expression of HECTD2 predicts peritoneal metastasis of gastric cancer and reconstructs immune microenvironment

Peritoneal metastasis (PM) is a common metastasis site and death cause of gastric cancer, which is a complex biological process, but there is currently a lack of effective prediction and treatment targets. In this study, we first analyzed the differential gene expression of gastric cancer patients with or without peritoneal metastasis, and identified the HECT domain E3 ubiquitin protein ligase 2 (HECTD2) as the core gene of PM in gastric cancer. The current study shows that the role of HECTD2 in tumor is contradictory. In this study, our results show that the low expression of HECTD2 indicates that the survival rate of overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), and disease-free survival (DFS) are better, and can be used as an important component of prognostic indicators. In addition, through pathway enrichment analysis, we found that HECTD2 was mainly involved in metastasis related pathways such as extracellular matrix remodeling and cell adhesion in gastric cancer, and high expression of HECTD2 could activate epithelial-mesenchymal transition (EMT) metastasis related pathways in gastric cancer. In regulating the metastasis of gastric cancer cells, HECTD2 can also change the surrounding microenvironment, induce the enrichment of interstitial components and build an immune microenvironment conducive to tumor progression, while patients with low expression of HECTD2 may be more likely to benefit from immunotherapy. In conclusion, HECTD2 may be a novel biomarker for the diagnosis and prognosis of peritoneal metastasis of gastric cancer, providing basis for the mechanism of peritoneal metastasis of cancer and clinical medication.

Abstract B019: Clinical and molecular correlates of circulating tumor DNA (ctDNA) dynamics in breast tumors resistant to neoadjuvant therapy (NAT)

Abstract Purpose: We examined the utility of serial ctDNA testing for refining risk stratification of NAT- resistant tumors (RTs, defined as residual cancer burden, RCB-II/III) and predicting early treatment response. We also characterized the molecular correlates of ctDNA dynamics in RTs to elucidate the mechanisms associated with increased metastatic potential. Methods: We performed serial ctDNA testing using a tumor-informed personalized assay (SignateraTM, Natera Inc.) in 723 patients (pts) with high-risk early-stage breast cancer receiving NAT (I-SPY2). Tumors were stratified according to RCB class and ctDNA dynamics (clearance patterns), and the distant recurrence-free survival (DRFS) between groups was compared. We examined the predictive value of ctDNA dynamics using the RCB index (the continuous measure of RCB) as the response endpoint. Serial whole exome sequencing (WES), gene expression profiling (GEP), and reverse-phase protein analysis (RPPA) data were analyzed to elucidate the molecular biology of RTs. Results: Of the 723 pts, 300 (41%) had hormone receptor (HR)+HER2-, 237 (33%) triple-negative (TN), and 186 (26%) HER2+ breast cancers with pretreatment ctDNA-positivity rates of 76%, 92%, and 77%, respectively. 321 (45%) pts had responding tumors (RCB-0/I), and 55% had RTs: RCB-II (n=255) and RCB-III (n=132). CtDNA dynamics revealed heterogeneity in the metastatic potential of RTs, including tumors with a reduced propensity to metastasize (persistent ctDNAneg and early clearance). Failure to clear ctDNA after NAT was associated with an increased risk of metastatic recurrence and death (3-yr DRFS rates: no clearance=35% vs. persistent ctDNAneg=98%, p<0.001). Early clearance of ctDNA, 3 weeks after treatment initiation, skewed the distributions toward lower RCB indices (favorable response), including in arms containing immune checkpoint inhibitors. Of the 387 RTs, 316 had ctDNA data post-NAT, of which only 51 (16%) were ctDNA+. We hypothesized that changes in the mutational landscape during NAT could have impacted the detection of patient-specific ctDNA targets selected from WES of pretreatment tumors. However, serial WES (n=100) of RTs showed that these targets remained detectable in solid tissue over time, even in persistent ctDNAneg. To investigate the biology of persistent ctDNA positivity, we used logistic regression to analyze serial GEP (n=174) and RPPA (n=98) data in RTs that were ctDNA+ at pretreatment, comparing those with ctDNA clearance by surgery vs. those that remained ctDNA+. We found subtype- specific associations: In HR+HER2-, failure to clear ctDNA during NAT was associated with low pretreatment ER/AR, high early on-treatment proliferation, and low HER2-signaling after NAT, while in TN, fewer associations were observed; these included high pretreatment levels of MYC and proliferation. Conclusions: ctDNA dynamics refined risk stratification of RTs and enabled early prediction of treatment response. Understanding the molecular profiles of RTs based on ctDNA dynamics could aid treatment selection to overcome resistance to NAT. Citation Format: Mark Jesus M. Magbanua, Denise M. Wolf, Samuel Rivera-Hinojosa, Ziad Ahmed, Nayelis A. Manon, Rosalyn Sayaman, Antony Tin, Ekaterina Kalashnikova, Lamorna Brown Swigart, Gillian L. Hirst, Christina Yau, Wen Li, Claudine Isaacs, Rebecca A. Shatsky, Amy L. Delson, Charuta C. Palsuledesai, Angel Rodriguez, Minetta C. Liu, Paula R. Pohlmann, Laura J. Esserman, Hope S. Rugo, Angela DeMichele, Laura van 't Veer. Clinical and molecular correlates of circulating tumor DNA (ctDNA) dynamics in breast tumors resistant to neoadjuvant therapy (NAT) [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B019.

The abscopal effects of sonodynamic therapy in cancer.

The abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death. To expand our understanding of abscopal effects of SDT, we have summarised the preclinical studies that have found SDT-induced abscopal responses across various cancer models, using diverse combination strategies with nanomaterials, microbubbles, chemotherapy, and immune checkpoint inhibitors. Additionally, we shed light on the molecular and immunological mechanisms underpinning SDT-induced primary and metastatic tumour cell death, as well as the role and efficacy of different sonosensitisers. Notably, the observed abscopal effects underscore the need for continued investigation into the SDT-induced 'vaccine-effect' as a potential strategy for enhancing systemic anti-tumour immunity and combating metastatic disease. The results of the first SDT human clinical trials are much awaited and are hoped to enable the further evaluation of the safety and efficacy of SDT, paving the way for future studies specifically designed to explore the potential of translating SDT-induced abscopal effects into clinical reality.

Prostate-Specific Antigen Stratification for Predicting Advanced Prostate Cancer Events in Men Approaching Age Limits for Recommended Screening.

Our goal was to quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men. We used a random sample of patients in the US Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary end point was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at 3 time points. PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk. In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

Retinoblastoma with and without Extraocular Tumor Extension: A Global Comparative Study of 3435 Patients

PurposeTo study the treatment, and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). DesignMulticenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naïve patients. Cases with microscopic orbital extension detected post-enucleation were excluded from the study. ParticipantsA total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE Intervention(s)Chemotherapy, enucleation, exenteration, radiotherapy. Main outcomes(s)Systemic metastasis and death. ResultsOf the 3435 RB patients included in this study, 309 (9%) were from low-income countries, 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from low-income countries, 197 (6%) lower middle-income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (p=0.0001). The outcomes were statistically significant for RB-EOE compared to RB-w/o-EOE: systemic metastasis (32% vs 4% respectively; p=0.0001) and metastasis-related death (63% vs 6% respectively; p=0.0001). Multimodal treatment was the most common form of treatment (n=177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n=97; 30%). Adjuvant external beam radiotherapy after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan-Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk for death from RB-EOE was greater in patients aged >4 years than <2 years (hazard ratio (HR)=2.912; p<0.001) and for unimodal (surgery or intravenous chemotherapy) and bimodal (surgery and intravenous chemotherapy) treatment than trimodal treatment (surgery, intravenous chemotherapy and external beam radiotherapy) (HR=2.023; p=0.004 and HR 1.819; p=0.027 respectively). ConclusionRetinoblastoma with extraocular tumor extension is associated with a higher risk for metastasis and death. Patients with RB-EOE are likely to benefit from trimodal treatment (intravenous chemotherapy, surgery, and external beam radiotherapy) rather than treatment protocols excluding external beam radiotherapy.

Clinicopathological and molecular characteristics of microsecretory adenocarcinoma in salivary gland

Objective: To investigate the clinicopathological, immunohistochemical, and molecular genetic characteristics of microsecretory adenocarcinoma (MSA) of the salivary gland, and to improve the understanding of this rare tumor. Methods: Cases originally diagnosed as MSA at the Department of Oral Pathology, the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine were retrospectively collected. The cases of polymorphous adenocarcinoma and adenocarcinoma, not otherwise specified from January 2000 to January 2020 were reviewed to identify potential misdiagnosed MSA cases. Clinicopathological analysis and follow-up of all confirmed MSA cases were performed, and relevant literature was reviewed. Results: A total of 4 MSA cases were identified, including 2 screened from the polymorphous adenocarcinoma cohort. Of the 4 MSA patients, 3 were male and 1 was female, with an average age of 53 years (range, 37-67 years). Three cases occurred in the palate, and one in the buccal region. The clinical manifestation was usually a slow-growing painless mass. Tumors were generally small, with a maximum diameter ranging from 0.7 to 1.8 cm (average, 1.2 cm). Microscopically, the tumor was unencapsulated and showed an infiltrative growth pattern. The tumor cells appeared small in size and showed bland, cubic and flattened cytological features, forming microcystic lumens and glandular tubes. Significant basophilic secretions were seen in the lumens. Between the tumor nests there was fibro-myxoid stroma. Immunohistochemistry showed diffusely or partially positive staining for cytokeratin 7, S-100, SOX-10, p63 and vimentin and negative staining for p40, mammaglobin, and calponin. The proliferation index of Ki-67 was relatively low (1%-3%). Four MSA cases all harbored SS18 gene rearrangement as shown by fluorescence in situ hybridization (FISH), including 2 cases with MEF2C::SS18 fusion gene through RNA-targeted next generation sequencing. All 4 patients underwent surgical resection without any adjuvant treatments. Three patients were followed up for a period of 2 to 203 months. No tumor recurrence, metastasis, or disease-related death was found. Conclusions: Salivary gland MSA is a novel and rare low-grade carcinoma with unique and consistent histological morphology, immunophenotype, and molecular changes. Immunohistochemical staining and SS18 break apart FISH are useful for the diagnosis of the tumor with atypical morphology and high-grade transformation.

Incidence, Risk Factors, Organism Types, and Outcomes of Catheter-Related Bloodstream Infections in Hemodialysis Patients.

Background Patients undergoing hemodialysis for End-Stage Renal Disease (ESRD) are at risk for Hemodialysis Catheter-Related Bloodstream Infections (CRBSIs). This study evaluates the incidence, risk factors, organism types, and outcomes of CRBSI in adult patients on maintenance hemodialysis at King Faisal Hospital, Rwanda. Methods This was a prospective cohort study of adult patients with end-stage renal disease undergoing hemodialysis via central venous hemodialysis catheters at King Faisal Hospital, Rwanda. Upon receiving the IRB approval, 81 eligible patients, women, and men aged between 19 and 74, were enrolled. Restricted Mean Survival Time (RMST) analysis evaluated the risk factors for CRBSI. The statistical significance was determined using p-values, with a cut-off of 0.05. Results The incidence of CRBSI was found to be 0.78 episodes per 1,000 catheter-days. Acute hemodialysis catheter type and anemia were associated with increased risk for CRBSI, with a P-value less than 0.05. In addition, all CRBSI cases were due to bacteria, with 52.63% gram-negative and 47.37% gram-positive. Out of 19 CRBSI events,nine cases (47.37%) required hospitalization with a median duration of seven days. Approximately half of the CRBSIs required catheter removal. No metastatic infection or death was noted. Conclusion The present study demonstrated that our hemodialysis unit has an incidence of 0.78 episodes per 1,000 catheter-days. Catheter type and anemia were significantly associated with CRBSI.

Progress in Research of Nanotherapeutics for Overcoming Multidrug Resistance in Cancer.

Chemotherapy has been widely applied in oncotherapy. However, the development of multidrug resistance (MDR) has diminished the effectiveness of anticancer drugs against tumor cells. Such resistance often results in tumor recurrence, metastasis, and patient death. Fortunately, nanoparticle-based drug delivery systems provide a promising strategy by codelivery of multiple drugs and MDR reversal agents and the skillful, flexible, smart modification of drug targets. Such systems have demonstrated the ability to bypass the ABC transporter biological efflux mechanisms due to drug resistance. Hence, how to deliver drugs and exert potential antitumor effects have been successfully explored, applied, and developed. Furthermore, to overcome multidrug resistance, nanoparticle-based systems have been developed due to their good therapeutic effect, low side effects, and high tumor metastasis inhibition. In view of this, we systematically discuss the molecular mechanisms and therapeutic strategies of MDR from nanotherapeutics. Finally, we summarize intriguing ideas and future trends for further research in overcoming MDR.

Retinoblastoma Outcomes Based on the 8th Edition American Joint Committee on Cancer Pathological Classification in 1411 Patients

PurposeTo evaluate the outcomes of retinoblastoma (RB) based on the 8th edition of the American Joint Committee on Cancer (AJCC) pathological classification in a global cohort of patients. DesignRetrospective, multicentre, intercontinental collaborative study Participants1411 patients Intervention(s)Primary enucleation with/without adjuvant chemotherapy/radiotherapy Main outcomes(s)Orbital tumor recurrence, tumor-related metastasis, tumor-related death ResultsBased on the 8th edition AJCC pathological classification, 645 (46%) eyes belonged to pT1, 164 (11%) to pT2, 493 (35%) to pT3, and 109 (8%) to pT4 categories. At a mean follow-up of 38 months (median, 35 months; <1-149 months), orbital tumor recurrence was seen in 8 (1%), 5 (3%), 22 (4%) and 25 (23%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related metastasis was seen in 7 (1%), 5 (3%), 40 (8%), and 46 (43%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related death was seen in 12 (2%), 7 (4%), 64 (13%), and 64 (59%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively. Multivariate Cox proportional hazards analysis of outcomes revealed pT category and adjuvant therapy as independent predictors of outcomes. Categories pT3b (p=0.005), pT3c (p<0.001), pT3d (p<0.001), and pT4 (p<0.001) had a greater hazard for orbital recurrence; categories pT2a (p=0.015), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related metastasis; and categories pT2a (p=0.068), pT2b (p=0.004), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related death when compared to the pT1 category. Patients who did not receive adjuvant therapy had greater hazards of orbital tumor recurrence in categories pT3b (p=0.005), pT3c (p=0.003), and pT4 (p=0.002); greater hazards of tumor-related metastasis in categories pT3a (p=0.001), pT3b (p=0.01), pT3c (p=0.001), and pT4 (p=0.007); and tumor-related death in categories pT3a (p<0.001), pT3b (p=0.009), pT3c (p=0.018), and pT4 (p<0.001) when compared to those who received adjuvant therapy. ConclusionThe 8th edition AJCC pathological classification predicts outcomes in patients undergoing primary enucleation for RB, and adjuvant therapy is associated with a lower risk of orbital recurrence, tumor-related metastasis, and tumor-related death in the pT3 and pT4 categories.

Prognostic factors for lacrimal gland adenoid cystic carcinoma: a retrospective study in Chinese patients.

To explore the prognostic factors for lacrimal gland adenoid cystic carcinoma (LGACC) in Chinese patients. Clinical and histopathological data were reviewed in patients with pathologically confirmed LGACC. Local recurrence, metastasis, and disease-specific death were the main outcome measures. Univariate and multivariate analyses were performed by the Kaplan-Meier method and a Cox proportional hazard model. This retrospective cohort study included 45 patients with pathologically confirmed LGACC between January 2008 and June 2022. Tumor (T) classification (P=0.005), nodal metastasis (N) classification (P=0.018) and positive margin (P=0.008) were independent risk factors of recurrence; T (P=0.013) and N (P=0.003) classification and the basaloid tumor type (P=0.032) were independent risk factors for metastasis; T classification (P<0.001) was an independent factor of death of disease. In the further analysis, the durations from first surgery to radiotherapy is correlated with metastatic risk in LGACC patients with basaloid component (P=0.022). Histological subtype should be emphasized when evaluating prognosis and guiding treatment. Timely radiotherapy may reduce the risk of metastasis in patients with basaloid component.

Eyelid/Periocular Sebaceous Gland Carcinoma in 500 Eyes: Analysis Based on 8th Edition American Joint Cancer Committee Classification

PurposeTo analyze the presentation and outcomes of eyelid and periocular sebaceous gland carcinoma (SGC) based on prognostic stage of the 8th edition of American Joint Committee on Cancer (AJCC) classification. DesignRetrospective clinical cohort study Methods• Setting: Quaternary referral center• Study population: 500 eyes of 499 patients with SGC• Intervention: Excisional biopsy, chemotherapy, Orbital exenteration• Main outcome measures: Tumor recurrence, lymph node metastasis, systemic metastasis, and death based on AJCC prognostic staging ResultsThe mean age at presentation with SGC was 57 years (55 years; range, 26 to 82 years). Based on the 8th edition of AJCC classification, tumors belonged to Stage 0 (n=13, 3%), I (n=158, 32%), II (n=269, 54%), III (n=48, 9%), and IV (n=12, 2%). At a mean follow-up of 26 months (median, 10 months; range, <1 to 192 months), tumor recurrence, lymph node metastasis, systemic metastasis, and disease-related death were seen in 39 (10%), 65 (16%), 33 (8%), and 33 (8%) patients respectively. Tumor recurrence rates did not differ significantly between the stages (p=0.472). The 5-year Kaplan-Meier estimates of regional lymph node metastasis, systemic metastasis, and metastasis-related death were higher for stage II (12%, 11%, and 12%, respectively), III (69%, 25%, and 42%, respectively) and IV (70%, 100%, and 100%, respectively) compared to stage I (0%, 6%, and 6%, respectively). Cox proportional analysis revealed a greater hazard ratio (HR) for lymph node metastasis in stage II (HR, 3.498; 95% CI, 0.200 to 10.200; p<0.022), III (HR, 95% CI, 24.836; 8.733 to 70.631; p<0.001), and IV (HR, 53.731; 95% CI, 15.418 to 187.253; p<0.001), systemic metastasis in stage III (HR. 13.895; 95% CI, 3.871 to 49.874; p<0.001) and IV (HR, 81.465; 95% CI, 22.267 to 298.051; p<0.001) and for disease-related death in stage III (HR, 9.182; 95% CI, 2.743 to 30.728; p<0.001) and IV (HR, 85.237; 95% CI, 25.331 to 287.422; p<0.001), compared to stage I. ConclusionThe prognostic staging of the 8th edition AJCC classification predicts the prognosis of patients with eyelid and periocular SGC, which worsens with the advancing stage. The high incidence of lymph node and systemic metastasis accounts for mortality in these patients.

Impact of Tumor Pigmentation in 6934 Patients with Uveal Melanoma at a Single Center

PurposeTo evaluate clinical features and outcomes associated with degree of tumor pigmentation in patients with uveal melanoma (UM) of the choroid and ciliary body. DesignRetrospective observational study. Subjects6,934 consecutive patients with choroidal or ciliary body melanoma between 1971 and 2007 from a single ocular oncology center. MethodsData on patient demographics, tumor characteristics, treatment approach, and clinical outcomes were collected. Comparisons between pigmented (>80% pigmentation by surface area), partially pigmented (20-80%), and non-pigmented tumors (<20%) were performed using relevant hypothesis testing. Survival analyses for metastasis and melanoma-related death were conducted using the Kaplan-Meier method with log-rank tests for univariate comparisons. A multivariate Cox regression analysis was performed to assess the independent effects of multiple covariates on time-to-metastasis. Main Outcome MeasuresExtraocular extension, ocular melanocytosis, time to tumor recurrence, tumor location, and melanoma-related metastasis and death. ResultsThere were 6,934 eyes with UM and the degree of tumor pigmentation was classified as pigmented (n=3,762; 54%), partially pigmented (n=2,115; 31%) or non-pigmented (n=1,057; 15%). Pigmented UM was associated with extraocular extension (p<0.001), ocular melanocytosis (p=0.003), earlier tumor recurrence (p<0.001), and more anterior tumor epicenter location (ciliary body, and equator to ora serrata) (p<0.001). Pigmented UMs also exhibited the highest 10-year metastasis rate at 26%, compared to 19% for partially pigmented UMs and 16% for non-pigmented UMs (p<0.001). Kaplan-Meier survival curves demonstrated differences among the tumor pigmentation groups for melanoma-related metastasis (p<0.001) and melanoma-related death (p<0.001). Multivariate Cox regression analysis for melanoma-related metastasis showed that pigmented UMs had a 29% higher relative risk of developing metastasis compared to partially pigmented UMs (p=0.002) and a 54% higher relative risk of developing metastasis compared to non-pigmented UMs (p<0.001). ConclusionPigmented choroidal and ciliary body melanoma is more often associated with ocular melanocytosis, extraocular extension, anterior tumor epicenter, and earlier tumor recurrence. We also revealed that patients with pigmented UMs demonstrate a higher 10-year rate of metastatic disease and have decreased metastatic survival relative to partially pigmented and non-pigmented UMs.

Prognostic value of blood GRHL2 in patients with non-small-cell lung cancer after radiotherapy and chemotherapy.

Aim: We aimed to investigate the predictive value of the Grainyhead-like 2 (GRHL2) expression from circulating blood for recurrence, metastasis and overall death on patients with non-small-cell lung cancer (NSCLC).Materials & Methods: We collected blood samples from 122 patients who were admitted to our hospital for NSCLC.Results: Multivariable Cox proportional-hazards analysis in adjusted Model II showed that compared with GRHL2-negative expression, positive expression in patients with NSCLC was associated with increased death risk (HR=7.0, 95% CI: 2.1-20.9, p=0.03) and risk for composite end point (HR=8.2, 95% CI: 4.0-27.1, p <0.01).Conclusion: This study supported that elevated circulating GRHL2 expression might be considered as a candidate prognostic biomarker for poor prognosis among these NSCLC patients.

Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.