An ultra-long-acting L-asparaginase synergizes with an immune checkpoint inhibitor in starvation-immunotherapy of metastatic solid tumors.

Metastasis stands as the primary contributor to mortality associated with tumors. Chemotherapy and immunotherapy are frequently utilized in the management of metastatic solid tumors. Nevertheless, these therapeutic modalities are linked to serious adverse effects and limited effectiveness in preventing metastasis. Here, we report a novel therapeutic strategy named starvation-immunotherapy, wherein an immune checkpoint inhibitor is combined with an ultra-long-acting L-asparaginase that is a fusion protein comprising L-asparaginase (ASNase) and an elastin-like polypeptide (ELP), termed ASNase-ELP. ASNase-ELP's thermosensitivity enables it to generate an in-situ depot following an intratumoral injection, yielding increased dose tolerance, improved pharmacokinetics, sustained release, optimized biodistribution, and augmented tumor retention compared to free ASNase. As a result, in murine models of oral cancer, melanoma, and cervical cancer, the antitumor efficacy of ASNase-ELP by selectively and sustainably depleting L-asparagine essential for tumor cell survival was substantially superior to that of ASNase or Cisplatin, a first-line anti-solid tumor medicine, without any observable adverse effects. Furthermore, the combination of ASNase-ELP and an immune checkpoint inhibitor was more effective than either therapy alone in impeding melanoma metastasis. Overall, the synergistic strategy of starvation-immunotherapy holds excellent promise in reshaping the therapeutic landscape of refractory metastatic tumors and offering a new alternative for next-generation oncology treatments.

A Novel Ultrasound-Based Radiomics Model for the Preoperative Prediction of Lymph Node Metastasis in Cervical Cancer.

OBJECTIVE: The purpose of this retrospective study was to establish a combined model based on ultrasound (US)-radiomics and clinical factors to predict preoperative lymph node metastasis (LNM) in cervical cancer (CC) patients non-invasively. METHODS: A total of 131 CC patients who had cervical lesions found by transvaginal sonography (TVS) from the First Affiliated Hospital of Anhui Medical University (Hefei, China) were retrospectively analyzed. The clinical independent predictors were selected using univariate and multivariate logistic regression analysis. US-radiomics features were extracted from US images; after selecting the most significant features by univariate analysis, Spearman's correlation analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm; four machine-learning classification algorithms were used to build the US-radiomics model. Fivefold cross-validation was then used to test the performance of the model and compare the ability of the clinical, US-radiomics and combined models to predict LNM in CC patients. RESULTS: Red blood cell, platelet and squamous cell carcinoma-associated antigen were independent clinical predictors of LNM (+) in CC patients. eXtreme Gradient Boosting performed the best among the four machine-learning classification algorithms. Fivefold cross-validation confirmed that eXtreme Gradient Boosting indeed performs the best, with average area under the curve values in the training and validation sets of 0.897 and 0.898. In the three prediction models, both the US-radiomics model and the combined model showed good predictive efficacy, with average area under the curve values in the training and validation sets of 0.897, 0.898 and 0.912, 0.905, respectively. CONCLUSION: US-radiomics features combined with clinical factors can preoperatively predict LNM in CC patients non-invasively.

A modern approach to multiple pulmonary resections in children with recurrent metastatic pulmonary disease.

Implications of repeated resections of pulmonary metastasis (PM) are not well documented in the modern era. Fifteen children underwent two (n = 8), three (n = 3), or four or more (n = 3) resections (total = 38 procedures), most commonly for osteosarcoma (71%). Operative approach included muscle-sparing thoracotomy (71%), non-muscle-sparing thoracotomy (18%), and video-assisted thoracoscopy (11%). Median resected nodules per procedure was four (range = 1-95). Prolonged air leaks were the most common postoperative complication (29%). Median hospital stay was 4 days, and no children were discharged with or have required oxygen. Event-free survival is 67% at median follow-up time of 54 months, with an overall survival rate of 64%. Repeat resection of PM appears to be well tolerated, without prolonged hospital stays or compromised pulmonary function.

Lymph node evaluation and nodal metastasis prediction in epithelial ovarian cancers: A retrospective study.

Objective: To identify consensus regarding lymph node (LN) evaluation in epithelial ovarian cancer (EOC). The objective of the present study was to evaluate surgico-pathological findings, LN involvement, and the prediction of LN metastasis via preoperative imaging and intraoperative assessment in women with EOC. Materials and Methods: Women with EOC who underwent cytoreductive surgery (CRS) between Jan 2019 to June 2022 were included. The distribution of histology, stage, and LN metastasis was studied. The predictive value of serum cancer antigen (CA)-125, instead of and radiologically and surgically enlarged LNs with final LN histopathology was studied. Results: A total of 96 women with EOCs underwent CRS. Fifty women (52%) underwent primary CRS and 46 women (48%) underwent interval CRS. Seventy-five women (78.13%) with EOC underwent pelvic and/or para-aortic lymphadenectomy, out of which 23 (30.67%) were histologically positive. High-grade serous carcinoma was the commonest (n=55, 73.33%) histology. The majority of women, 56 (74.67%) were stage III or IV at presentation. Complete cytoreduction was achieved in 59 (78.66%) patients. The receiver operating characteristics curve showed a cutoff for CA-125 of 1360 U/mL (area under the curve 0.702, p=0.002) for LN metastases. Both radiologically and surgically enlarged LNs significantly predicted LN metastasis on histopathology (p=0.02 and 0.006 respectively). The combined sensitivity, specificity, positive predictive value and negative predictive value of both contrast enhanced computed tomography (CECT) and surgically enlarged LNs were 78.26%, 57.69%, 45%, and 85.71%, respectively. Conclusion: Serous histology, high-grade tumors, highCA-125 levels, and suspicious LNs on CECT or during surgery were significantly associated with LN metastasis. However, considering the false-negative rate of 21.74%, the combination of radiologically and surgically enlarged LNs cannot be used as the sole surrogate marker for lymphadenectomy.

Curcumin blunts epithelial-mesenchymal transition to alleviate invasion and metastasis of prostate cancer through the JARID1D demethylation.

Prostate cancer (PCa) is one of the most common and prevalent cancers in men worldwide. The majority of PCa-related deaths result from metastasis rather than primary tumors. Several studies have focused on the relationship between male-specific genes encoded on the Y chromosome and PCa metastasis; however, the relationship between the male specific protein encoded on the Y chromosome and tumor suppression has not been fully clarified. Here, we report a male specific protein of this type, the histone H3 lysine 4 (H3K4) demethylase JARID1D, which has the ability to inhibit the gene expression program related to cell invasion, and can thus form a phenotype that inhibits the invasion of PCa cells. However, JARID1D exhibits low expression level in advanced PCa, and which is related to rapid invasion and metastasis in patients with PCa. Curcumin, as a multi-target drug, can enhance the expression and demethylation activity of JARID1D, affect the androgen receptor (AR) and epithelial-mesenchymal transition (EMT) signaling cascade, and inhibit the metastatic potential of castration resistant cancer (CRPC). These findings suggest that using curcumin to increase the expression and demethylation activity of JARID1D may be a feasible strategy to inhibit PCa metastasis by regulating EMT and AR.

Efficacy and safety of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pancreatic cancer peritoneal metastasis.

OBJECTIVES: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. METHODS: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). RESULTS: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. CONCLUSIONS: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.

Bilateral breast metastases from anaplastic lymphoma kinase-positive lung cancer in a male: a case report.

BACKGROUND: Distant metastases from lung cancer are commonly found in the brain, bone, and liver. Metastases to the breast from non-mammary malignancies are extremely rare, and their clinical presentations remain unclear. CASE PRESENTATION: We herein report a case of bilateral breast metastases from anaplastic lymphoma kinase-positive advanced lung cancer in a 51-year-old Japanese male patient. During the course of systemic treatment for advanced lung cancer, computed tomography revealed bilateral breast enlargement without contrast enhancement, a finding consistent with gynecomastia. While other metastatic lesions responded to chemotherapy, both breast masses grew vertically like nodules. The breast masses were immunohistochemically diagnosed as metastases from lung cancer and were removed surgically. Simultaneous bilateral breast metastases from malignancies of other organs, like ones in this case, have rarely been described. CONCLUSIONS: It is important to keep in mind that breast metastases from nonmammary malignancies are a possible explanation for unusual breast findings in a patient with a history of malignancies.

Current knowledge of antisense long non-coding RNA in the occurrence and prognosis of skull base tumors.

Antisense long non-coding RNA (AS-lncRNA) represents a novel class of RNA molecules. In recent years, it has been discovered that AS-lncRNAs play crucial roles in various biological processes, particularly in the onset and progression of tumors. Skull base tumors, originating from the base of the brain, exhibit specific expression patterns of AS-lncRNA which correlate significantly with clinical characteristics. This makes AS-lncRNA a promising candidate as a tumor marker. Functional studies have revealed that AS-lncRNAs can regulate gene expression by acting as miRNA sponges and interacting with RBPs. Consequently, they play pivotal roles in tumor cell cycle, apoptosis, angiogenesis, invasion, and metastasis processes. Further exploration into the mechanisms of AS-lncRNA in tumors holds substantial theoretical significance for deeper insights into the etiology, pathogenesis, and RNA dynamics of skull base tumors. Moreover, AS-lncRNA could serve as molecular markers or potential targets for early diagnosis. Their potential extends to efficacy assessment, prognosis prediction, and gene therapy, suggesting broad clinical applications. In summary, AS-lncRNA emerges as a promising molecular marker implicated in the onset and progression of skull base tumors.

A case report on the atypical metastatic pathway of prostate cancer to the kidney and stomach.

Prostate cancer rarely metastasizes to the stomach and kidneys. We report a 73-year-old male with such spread, highlighting significant clinical challenges. Initially diagnosed via biopsy and imaging, he received hormone therapy and cytoreductive radical prostatectomy. Despite initial management, the cancer progressed to metastatic castration-resistant prostate cancer, with gastric and renal metastases confirmed by imaging and biopsy. This case emphasizes the need for awareness of rare metastatic sites, comprehensive diagnostic evaluations, and further research into these atypical metastases to improve patient outcomes and develop better treatment strategies for managing advanced prostate cancer effectively.

Identification of Biomarkers Associated With Paget's Disease of Bone and Bone Metastasis From Breast Cancer Patients.

BACKGROUND: The bone is among the most frequently chosen sites for the metastatic spread of breast cancer. The prediction of biomarkers for BM (Bone Metastasis) and PDB (Paget's disease of bone) initiated from breast cancer could be critically important in categorizing individuals with a higher risk and providing targeted treatment for PDB and BM. AIMS: This research aims to investigate the common key candidate biomarkers that contribute to BM-BCa (Bone metastasis of breast cancer) and PDB by employing network decomposition and functional enrichment studies. METHODS AND RESULTS: This research analyzed high-throughput transcriptome sequencing (RNA-Seq). For this work, the dataset (GSE121677) was downloaded from GEO (Gene Expression Omnibus), and DEGs were identified using Galaxy and R script 4.3. Using STRING (Search Tool for the Retrieval of Interacting Genes), high-throughput research created a protein-protein interaction network (PPIN). The BM-PDB-interactome was created using Cytoscape 3.9.1 and PDB biomarkers, with the top 3% DEGs from BM-BCa. Functional Enrichment Analysis (Funrich 3.1.3) and DAVID 6.8 performed functional and gene set enrichment analysis (GSEA) of putatively essential biomarkers. TCGA (The Cancer Genome Atlas) validated the discovered genes. Based on our research, we identified 1262 DEGs; among these DEGs, 431 genes were upregulated, and 831 genes were downregulated. During the third growth of the interactome, 20 more genes were pinned to the BM-PDB interactome. RAC2, PIAS1, EP300, EIF2S1, and LRP6 are among the additional 25% of genes identified to interact with the BM-PDB interactome. To corroborate the findings of the research presented, additional functional and gene set enrichment analyses have been performed. CONCLUSION: Of the five reported genes (RAC2, PIAS1, EP300, EIF2S1, and LRP6), RAC2 was identified to function as the common key potential biomarker in the BM-PDB interactome analysis and validated by TCGA in the study presented.

Diagnostic difficulties in the differentiation between an ovarian metastatic low­grade appendiceal mucinous neoplasm and primary ovarian mucinous cancer: A case report and literature review.

Low-grade appendiceal mucinous neoplasm (LAMN) is a tumor that primarily originates from the appendix and belongs to the family of appendiceal mucinous neoplasms (AMNs). In 50% of female patients, AMNs (particularly LAMNs) have a tendency to metastasize to organs in the genital tract, where the neoplasm can mimic the features of primary ovarian mucinous cancer (POMC). The present case report reviewed the difficulties in differentiating between these two types of tumors. In the present case report, a 61-year-old female patient was admitted to the Second Department of Gynecological Surgery and Gynecological Oncology, University Clinical Hospital no. 4 at Lublin Medical University (Lublin, Poland) with the diagnosis of a right ovarian mass. After performing ultrasound and computed tomography (CT) scans and laboratory analysis, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy and resection of the Douglas peritoneum. Notably, the postoperative pathological assessment revealed LAMN with metastases to the right ovary and omentum. Immunohistochemically, cytokeratin 20 and caudal type homeobox 2 both stained positively, whereas paired box gene 8 stained negatively. After surgery, the patient received the recommended hyperthermic intraperitoneal chemotherapy at the Department of Surgical Oncology at Lublin Medical University. After 1 year, a CT scan was performed, which indicated no evidence of recurrent disease. In conclusion, observations from the present case report suggest that gynecologists should be conscious of the possibility of malignancies of gastrointestinal origin in cases of ovarian tumors instead of making direct assumptions of POMC. If the mucinous mass involves the base of the appendix or if there is a suspicion of positive margins, then cytoreductive surgery and right-sided hemicolectomy must be performed. In addition, identifying the origin of mucinous tumors in the right ovary and/or the appendix requires the histopathological examination of a panel of markers using immunohistochemistry.

Breast cancer metastasizing to salivary glands: Systematic review.

Distant metastasis to salivary glands is a very rare event and most often associated with primary malignancies of the skin. Only 1-4% of all salivary gland tumours manifest with metastasis. Carcinomas of the breast, lung, kidney and prostate are those primaries that may also potentially metastasize to salivary glands. Literature has documented several studies analysing metastatic tumours in the oral region. However, very little research work has been published to date to analyse solely the Breast cancer metastasizing to the salivary glands. Thus, this review was conducted to examine the published cases of Breast cancer metastasizing to salivary glands from March 1975 to March 2023. An electronic search of the published literature was performed without publication year limitation in PubMed/ Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research Gate databases, using mesh keywords like ('Breast cancer' OR 'Breast carcinoma') AND ('Metastasis' OR 'Metastases'), And ('Salivary glands' OR 'Parotid gland' OR 'Submandibular gland' OR 'Sublingual gland'). We also searched all related journals manually. The reference list of all articles was also checked. Our research revealed a total of 48 relevant papers with 55 patients. Parotid was the most predominantly affected salivary gland. 14.5% of patients died with a mean survival time of 7 months. It can be concluded from this research that Breast cancer metastasizing to salivary glands is a rare occurrence. Careful evaluation of these cases is needed in order to raise awareness of these lesions and gain a better understanding of their characteristics.

Leptomeningeal metastases in prostate cancer: A review of the current literature.

Leptomeningeal metastasis/leptomeningeal carcinomatosis (LMC; terms used interchangeably) is an inflammatory complication of primary tumors that involves the spread of the disease to the meninges (specifically the arachnoid and pia maters) and spinal cord. In the United States, approximately 110,000 new cases are diagnosed each year, and the prognosis is usually poor. Complications of LMC include cognitive impairment, cranial nerve dysfunction, ischemic stroke, and mortality. The survival times of untreated and treated LMC are approximately 4-6 weeks and 2-4 months, respectively. Leptomeningeal carcinomatoses are usually metastatic cancers that spread to the central nervous system. Although lung and breast cancers have a clearly defined relationship with LMC, it remains unclear whether prostate cancer (PC) is also directly associated with LMC. To determine whether such association exists, we conducted a PubMed review of the literature on patients with PC with coexisting LMCs. Our search yielded 23 case reports of patients with preexisting PC who developed LMC. In addition, 2 retrospective cohort studies were examined. Various findings were identified in the revised cases and studies. The first 3 findings were related to the progression of the disease: patients presenting with neurological disease symptoms were in remission from PC for 7 years on average, LMCs tended to occur after other cancer diagnoses, and the disease had already rapidly progressed by the time the symptoms were present. Regarding diagnosis, the major finding was that most LMCs were detected by magnetic resonance imaging (which does not detect early dissemination), and it was suggested that single-photon emission computed tomography or positron emission tomography imaging could be used for earlier detection. Finally, in terms of treatment, the main finding was that treatment was palliative rather than curative and that prognosis remained poor despite treatment. On the basis of these results, we recommend for individuals with risk factors, such as high-grade PC and hormonal PC, to be evaluated on a case-by-case basis for increased surveillance of LMC development.

Comparison of Peritoneal Cytology Results Before and After Resection in Gastric Cancer Patients.

OBJECTIVE: Peritoneal cytology is used to detect the peritoneal spread of gastric cancer and to assess survival rate. The aim of this study was to compare the risk factors, recurrence, and survival of gastric cancer patients with positive and negative peritoneal cytology before and after resection. MATERIALS AND METHODS: Patients with gastric cancer who underwent elective surgery were retrospectively analysed. The study covered a period between September 2018 and September 2020. After applying the exclusion criteria, 57 patients were included in the study. For the purpose of this study, peritoneal cytology was taken from the same three intra-abdominal regions before and after resection from patients with operable gastric cancer. RESULTS: Of the 57 patients included in the study, 36 (63.2%) were male patients and 21 (36.8%) were female patients. Preoperative or postoperative malignant cytology was detected in 12 patients (21.1%). Tumour diameter was larger in patients with preoperatively detected malignant cytology than in the patients with postoperatively positive malignant cytology (66.67 mm vs. 44.44 mm) (p = 0.006). The recurrence rate was higher in patients with preoperative and postoperative positive cytology than in those with negative cytology (p = 0.019). The survival of patients with preoperative malignant cytology was worse than the survival of patients with preoperative benign cytology (p = 0.011). A significant correlation was found between lymphovascular invasion (+), perineural invasion (+), T4, Stage 3 disease, number of malignant lymph nodes, and preoperative cytology positivity (p <0.05). CONCLUSION: In our study, we found that the preoperative cytology positivity is associated with lymphovascular invasion positivity, perineural invasion positivity, T4 tumour, Stage 3 disease, and the number of malignant lymph nodes. Postoperative positive cytology was not associated with the same variables. Because of the significant associations in preoperative positivity, fluid samples should be obtained immediately after the abdomen is open and before the tumour is manipulated. If possible, fluid samples should be taken from different quadrants, but if the sample is to be taken from a single quadrant, it should be taken from the pelvis.

Gastrointestinal Metastases From Lobular Breast Carcinoma: A Literature Review.

Invasive lobular carcinoma (ILC) represents a rare subtype of breast carcinoma, originating from the lobule. Unlike ductal carcinoma, ILC does not express E-cadherin and thus can metastasize to uncommon sites. We aimed to investigate the clinicopathological characteristics of the rare subgroup of ILC patients with gastrointestinal (GI) metastases. A PubMed search was undertaken using the terms "Lobular Breast Carcinoma" AND "Gastrointestinal Metastasis." We identified 169 cases, with metachronous GI metastatic disease being approximately twice as common as synchronous GI metastases. The median age at initial diagnosis was 56.7 years (24-88). The majority of patients were hormonal receptor-positive and only a small minority was HER2-positive. The appearance of a gastrointestinal lesion was often the mode of revelation of ILC. Differential diagnosis from primary gastrointestinal cancer is sometimes challenging, especially in the case of signet-ring cell carcinoma. The median time from breast cancer diagnosis to GI metastases was 6.5 years (0-33). Most common metastatic sites include the stomach, colon, and rectum, in order of decreasing frequency, whereas metastases were found in every part of the digestive tract. In conclusion, metastases of ILC can arise in the gastrointestinal tract and they should be managed similarly to metastatic breast cancer.

Surgical resection and neoadjuvant therapy in patients with gastric cancer and ovarian metastasis: A real-world study.

BACKGROUND: Regarding when to treat gastric cancer and ovarian metastasis (GCOM) and whether to have metastatic resection surgery, there is presently debate on a global scale. The purpose of this research is to examine, in real-world patients with GCOM, the survival rates and efficacy of metastatic vs non-metastasized resection. AIM: To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM. METHODS: This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People's Hospital from June 2009 to July 2023. The diagnosis of all patients was confirmed by pathology. The primary study endpoints included overall survival (OS), ovarian survival, OS after surgery (OSAS), disease-free survival (DFS), differences in efficacy. RESULTS: This study had 41 patients in total. The surgical group (n = 27) exhibited significantly longer median OS (mOS) and median overall months (mOM) compared to the nonoperative group (n = 14) (mOS: 23.0 vs 6.9 months, P = 0.015; mOM: 18.3 vs 3.8 months, P = 0.001). However, there were no significant differences observed in mOS, mOM, median OSAS (mOSAS), and median DFS (mDFS) between patients in the surgical resection plus neoadjuvant therapy group (n = 11) and those who surgical resection without neoadjuvant therapy group (n = 16) (mOS: 26.1 months vs 21.8 months, P = 0.189; mOM: 19.8 vs 15.2 months, P = 0.424; mOSAS: 13.9 vs 8.7 months, P = 0.661, mDFS: 5.1 vs 8.2 months, P = 0.589). CONCLUSION: Compared to the non-surgical group, the surgical group's survival duration and efficacy are noticeably longer. The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.

Treatment strategy and therapy based on immune response in patients with gastric cancers.

In this editorial, we highlight the significance of a retrospective study "Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis" performed by Liu et al. The authors utilized data collected from gastric cancer (GC) patients and assessed immunotherapy effectiveness and survival status. They found significant differences in treatment response. Because immunotherapy seems to be a beneficial strategy for advanced GC patients, stratification of the data based on metastasis status may further improve treatment strategies.

Consideration on immunotherapy of liver metastases of malignant tumors.

In this editorial, we comment on the article "Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis" by Liu et al that was published in the recent issue of the World Journal of Gastrointestinal Surgery. It has prompted us to think and summarize some thoughts on immunotherapy for malignant tumor liver metastasis. Immunotherapy plays a crucial role in the treatment of malignant tumors; however, the presence of liver metastases in advanced tumors may impact its efficacy. Although patients with liver metastases can still benefit from immunotherapy, multiple clinical studies have indicated that, compared to other sites of metastasis, liver metastases may diminish the effectiveness of immunotherapy. The efficacy of immune checkpoint inhibitors in patients with liver metastases often fails to reach the ideal level, primarily due to the liver metastases exploiting the host's peripheral immune tolerance mechanisms to promote systemic CD8(+) T cell exhaustion, resulting in a systemic immune-tolerant environment. This article aims to summarize the reasons for the decreased efficacy of immunotherapy following liver metastasis in various malignant tumors and propose potential clinical strategies for management.

Immunotherapy for gastric cancer and liver metastasis: Is it time to bid farewell.

Patients with metastatic gastric cancer have a grim prognosis. Palliative chemotherapy offers a limited survival improvement, but recent advancements in immunotherapy have sparked hope. However, the effectiveness of immunotherapy in patients with liver metastases remains debated. This article reviews a recent study by Liu et al and evaluates conflicting evidence on the impact of liver metastases on response to immunotherapy in metastatic gastric cancer. While some studies suggest no significant difference in treatment response based on liver involvement, others report varied response rates. The present study, a retrospective analysis of 48 patients by Liu et al, examines this issue and concludes that immunotherapy is less effective in patients with liver metastases. Despite methodological limitations and a small sample size, the study contributes to the ongoing discourse. The nuanced response to immunotherapy in certain patients underscores the importance of understanding the tumor microenvironment, immune cell infiltration, and the expression of immune checkpoints. Rather than dismissing immunotherapy for patients with gastric cancer and liver metastases, a shift towards personalized treatment strategies and a more profound understanding of tumor-specific biomarkers is essential. By unraveling the molecular intricacies of individual cases, clinicians may tailor more effective and customized treatments, offering a glimmer of hope for this challenging patient group.

Is pulsed saturation transfer sufficient for differentiating radiation necrosis from tumor progression in brain metastases?

Background: Stereotactic radiosurgery (SRS) for the treatment of brain metastases delivers a high dose of radiation with excellent local control but comes with the risk of radiation necrosis (RN), which can be difficult to distinguish from tumor progression (TP). Magnetization transfer (MT) and chemical exchange saturation transfer (CEST) are promising techniques for distinguishing RN from TP in brain metastases. Previous studies used a 2D continuous-wave (ie, block radiofrequency [RF] saturation) MT/CEST approach. The purpose of this study is to investigate a 3D pulsed saturation MT/CEST approach with perfusion MRI for distinguishing RN from TP in brain metastases. Methods: The study included 73 patients scanned with MT/CEST MRI previously treated with SRS or fractionated SRS who developed enhancing lesions with uncertain diagnoses of RN or TP. Perfusion MRI was acquired in 49 of 73 patients. Clinical outcomes were determined by at least 6 months of follow-up or via pathologic confirmation (in 20% of the lesions). Results: Univariable logistic regression resulted in significant variables of the quantitative MT parameter 1/(RA·T2A), with 5.9 ±â€…2.7 for RN and 6.5 ±â€…2.9 for TP. The highest AUC of 75% was obtained using a multivariable logistic regression model for MT/CEST parameters, which included the CEST parameters of AREXAmide,0.625µT (P = .013), AREXNOE,0.625µT (P = .008), 1/(RA·T2A) (P = .004), and T1 (P = .004). The perfusion rCBV parameter did not reach significance. Conclusions: Pulsed saturation transfer was sufficient for achieving a multivariable AUC of 75% for differentiating between RN and TP in brain metastases, but had lower AUCs compared to previous studies that used a block RF approach.