Distant Metastatic Sites Research Articles

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Patterns of initial distant metastases in 151 patients undergoing surveillance for treated Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is associated with high rates of recurrence and distant metastatic progression. Current guidelines for surveillance imaging are not evidence based. Better characterization of the pattern of distant metastatic spread will better inform surveillance and facilitate earlier detection of metastases. This retrospective study aimed to assess potential relationships between primary tumour site and site of initial distant metastasis, time to distant metastasis, overall survival (OS) and MCC-specific death (MSD). Patients with local or regional (Stage I-III) disease who were treated with curative intent and progressed to Stage IV were included in this study (n = 151). Fisher's exact test was used to assess differences in patterns of initial distant metastases based on primary tumour site. Time to initial distant metastasis was calculated from date of MCC diagnosis. OS and MSD were calculated from date of initial distant metastasis to date of death from any or MCC-related causes, respectively. Of 151 patients included in analysis, 89 (58.9%) had a single initial distant metastatic site, and 62 (41.1%) had multiple sites. Patients with upper limb primary tumours were significantly less likely to develop distant lymph node or liver metastases (p = 0.02 and 0.04, respectively). Median time to distant metastasis was 11 months (IQR 6.7-17.9 months). Median OS was 15.3 months, and was shorter for patients with liver (7.0 months, p = 0.0004) or bone metastases (8.9 months, p < 0.0001). Using skin/soft tissue metastasis as a reference group, patients with multiple metastatic sites had significantly higher hazards of MSD (HR = 3.46 univariate, 3.77 multivariate analysis). Time to distant metastasis, OS and MSD did not differ by viral status. Sites of initial distant metastasis are related to primary tumour sites and survival outcomes. Because patients often have multiple initial metastases, full-body cross-sectional rather than region-specific imaging may facilitate earlier detection of metastatic disease.

Deciphering Breast Cancer Metastasis Cascade: A Systems Biology Approach Integrating Transcriptome and Interactome Insights for Target Discovery.

Breast cancer is the lead cause of cancer-related deaths among women globally. Breast cancer metastasis is a complex and still inadequately understood process and a key dimension of mortality attendant to breast cancer. This study reports dysregulated genes across metastatic stages and tissues, shedding light on their molecular interplay in disease pathogenesis and new possibilities for drug discovery. Comprehensive analyses of gene expression data from primary breast tumor, circulating tumor cells, and distant metastatic sites in the brain, lung, liver, and bone were conducted. Genes dysregulated across multiple stages and tissues were identified as metastatic cascade genes, and are further classified based on functional associations with metastasis-related mechanisms. Their interactions with HUB genes in interactome networks were scrutinized, followed by pathway enrichment analysis. Validation for their potential as targets included assessments for survival, druggability, prognostic marker status, secretome annotation, protein expression, and cell type marker association. Results displayed critical genes in the metastatic cascade and those specific to metastatic sites, revealing the involvement of the collagen degradation and assembly of collagen fibrils and other multimeric structure pathways in driving metastasis. Notably, pivotal cascade genes FABP4, CXCL12, APOD, and IGF1 emerged with high metastatic potential, linked to significant druggability and survival scores, establishing them as potential molecular targets. The significance of this research lies in its potential to uncover novel biomarkers for early detection, therapeutic targets, and a deeper understanding of the molecular mechanisms underpinning the metastatic cascade in breast cancer, and with an eye to precision/personalized medicine.

Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models.

Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.

Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database.

Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.

Metastatic profiles and survival differences between infiltrating ductal carcinoma and infiltrating lobular carcinoma in invasive breast cancer

BackgroundIn this study, we conducted a comprehensive evaluation of metastatic profiles and survival outcomes in patients with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) treated at our university hospital center. MethodsWe collected and analyzed data from all patients diagnosed with invasive breast cancer at our center between January 1, 2007, and 31 December 2014. We specifically compared three subgroups: patients with IDC, patients with ILC and patients with mixed carcinoma, which is a combination of IDC and ILC. ResultsAmong the 1963 patients treated for invasive breast cancer in our center during the study period, 1435 had IDC, 466 had ILC, and 59 had mixed carcinoma. The incidence of patients with at least one positive axillary lymph node differed significantly: 40 % for IDC, 36 % for ILC, and 45 % for mixed carcinoma (p = 0.001). However, there was no significant difference in the mean number of positive nodes (p = 0.1633). The occurrence of distant metastases was lower in patients with ILC (p = 0.04), particularly in the case of brain metastases (p = 0.01), although there was no difference in bone or visceral metastatic sites. Patients with ILC exhibited a longer mean time to metastasis from the initial diagnosis of invasive breast carcinoma. Overall survival (p = 0.0525) and survival without locoregional recurrence (p = 0.026) were significantly different. Specifically, the 5-year overall survival rates for IDC, ILC, and mixed carcinoma were approximately 95 %. Distance metastatic-free survival at 5 years was 85 % for IDC, 91 % for ILC, and 87 % for mixed carcinoma (p = 0.00506). ConclusionOur findings indicate variations in the distribution of distant metastatic sites among patients with IDC, ILC, and mixed carcinoma, as well as differences in survival outcomes. This study sheds light on the unique characteristics and clinical implications associated with these two distinct subtypes of invasive breast cancer.

Immune evasion in lung metastasis of leiomyosarcoma: upregulation of EPCAM inhibits CD8+ T cell infiltration

BackgroundLeiomyosarcomas are among the most common histological types of soft tissue sarcoma (STS), with no effective treatment available for advanced patients. Lung metastasis, the most common site of distant metastasis, is the primary prognostic factor. We analysed the immune environment targeting lung metastasis of STS to explore new targets for immunotherapy.MethodsWe analysed the immune environment of primary and lung metastases in 38 patients with STS using immunohistochemistry. Next, we performed gene expression analyses on primary and lung metastatic tissues from six patients with leiomyosarcoma. Using human leiomyosarcoma cell lines, the effects of the identified genes on immune cells were assessed in vitro.ResultsImmunohistochemistry showed a significant decrease in CD8+ cells in the lung metastases of leiomyosarcoma. Among the genes upregulated in lung metastases, epithelial cellular adhesion molecule (EPCAM) showed the strongest negative correlation with the number of CD8+ cells. Transwell assay results showed that the migration of CD8+ T cells was significantly increased in the conditioned media obtained after inhibition or knock down of EPCAM.ConclusionsEPCAM was upregulated in lung metastases of leiomyosarcoma, suggesting inhibition of CD8+ T cell migration. Our findings suggest that EPCAM could serve as a potential novel therapeutic target for leiomyosarcoma.

Short-term and long-term results of robot-assisted esophagectomy in cT3br/T4b esophageal cancer at initial diagnosis: Comparison with conventional thoracoscopic surgery.

284 Background: Conversion surgery in patients with locally advanced esophageal cancer that is not resectable at first time and has responded to prior therapy remains unclear. Recently, the usefulness of RAMIE for locally advanced esophageal cancer has begun to be discussed. In this study, we first analyzed the short- and long-term results of RAMIE, then examined the results of conversion RAMIE in T3br/T4b patients, and compared them with those of conversion using conventional MIE. Methods: Short-term and long-term postoperative outcomes were analyzed in 203 cases of robot-assisted esophageal cancer resection between 2020/1 and 2023/08. In addition, 33 patients with T3br/T4b who were initially diagnosed with cT3br/T4b and who underwent RAMIE after prior treatment were selected and compared to 48 cT3br/T4b cases with conventional MIE performed at the same time. Results: The mean age of RAMIE patients was 66.2 years, male to female ratio 170:33, preoperative treatment including NAC 150:53, and Clinical Stage I:II:III:IV 41:27:97:38. Surgical outcomes included thoracic surgery time of 200.3 min and total blood loss of 154.4 ml. Perioperative outcomes were Clavien-Dindo Grade 1 or higher: suture failure 4.4%, pneumonia 13.3%, and recurrent nerve palsy 16.7%. Long-term prognostic analysis (MST: 483.6days) showed 3yOS:97.6/94.1/80.3/70.9% and 3yDFS:96.2/87.2/66.2/52.4% in cStage I/II/III/IV. Especially in cStage II/III patients, 3yOS: 81.5%, 3yDFS: 71.4%. Long-term outcomes were not significantly different from those of conventional thoracoscopic procedures performed at the same time. Perioperative outcomes in cT3br/cT4b patients at initial presentation were pneumonia: 18.1%, recurrent nerve palsy rate: 12.1% (excluding complicated resection cases), and these 3yOS:66.2% and 3yDFS:48.7%. The 3yOS:52.7% and 3yDFS:40.3% of cT3br/T4b cases in the usual MIE showed a favorable trend in RAMIE (p=002). Of the 38 patients with recurrence after RAMIE surgery, 19 were local/regional and 19 were distant. Of these, 5/6/5/3 were brain/lung/liver/LN+others as the first site of distant metastasis. Conclusions: The short- and long-term results of RAMIE in our department, including T3br/T4, were described, and the short-term and long-term results of RAMIE were considered acceptable. In terms of recurrence, local/regional disease control was considered to be relatively good.

Impact of site of metastases in pancreatic ductal adenocarcinoma.

708 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a 5-year survival rate of 3%. We examined the clinical significance of the metastatic site on outcomes in mPDAC using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We analyzed the data on mPDAC from SEER database from 2010-2020 and categorized into three groups: mPDAC with, liver-only (LO) metastasis (mets), multi-organ mets including the liver (IL), and multi-organ mets excluding the liver (EL). Patient demographics and disease characteristics were summarized using the mean for continuous variables and proportions for categorical variables. Overall survival (OS) was calculated from time of diagnosis to death or censored at a loss to follow-up. The survival curve was plotted using the Kaplan-Meier method and log-rank p-value was reported. The Cox regression model was used to study the association of site of distant metastasis on overall survival, controlling for potential confounders (age, race, treatment, etc.) Results: We identified 22642 patients with mPDAC; 15844, 4250, and 2548 with LO, IL, EL mets respectively. The mean age at diagnosis was 66 years with the majority being white (78.4%), non-Hispanic (87.1%), and from metropolitan counties (88.5%). The median OS was 4 months, 3 months, and 6 months (log-rank p&lt;0.001) for LO, IL, and EL groups respectively, with 2-year survival being 4.84%, 2.56% and 7.89% respectively (log-rank p&lt;0.001). Multivariate analysis showed a higher risk of mortality in LO (31.5%, hazards ratio (HR)=1.315, p&lt;0.001) and IL groups (69.2% HR=1.692, p&lt;0.001) than EL group (Table). Conclusions: The site of distant metastasis is an independent prognostic factor for survival in patients with mPDAC, with liver-only mets or multi-organ mets including liver having worse OS than extrahepatic mets. [Table: see text]

The efficacy and safety of conversion therapy after initial systemic chemotherapy in advanced esophageal cancer with distant metastases: A multicenter retrospective observational study.

310 Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated. Results: From 22 institutions, 149 patients were enrolled. As defined, all patients received systemic chemotherapy as an initial treatment. The distant metastatic sites in para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial treatment, 116 patients underwent surgery and 33 patients received CRT as conversion therapy. Of 116 patients who underwent conversion surgery, the incidence rate of postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%, respectively. R0 resection was obtained in 87%. Regarding the non-hematological toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hematologic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p = 0.112). Pathological responders showed a significantly longer OS than non-responders (3y-OS, 56.4% vs 36.1%, p = 0.010). The distribution or number of distant metastases were not identified as prognostic factors. Conclusions: This study showed that conversion therapy for ESCC patients with distant metastasis could be conducted safely and have a favorable prognosis. Since its survival benefit would depend on the pathological response, it is important to develop an indicator to predict pathological response before surgery and carefully select appropriate candidates of conversion therapy in ESCC.

Timing of primary tumor resection after systemic chemotherapy initiation among patients with metastatic colon cancer.

65 Background: In patients with resectable, metastatic colon cancer, the optimal timing of definitive resection of the primary tumor after initiation of chemotherapy remains unclear. Our goal is to identify factors that influence the interval between chemotherapy and definitive surgical management, and its impact on overall survival. We hypothesize that patients with shorter chemotherapy-to-surgery intervals (less than 60 days or about 2 months) compared to 61-180 days (2-6 months) or greater than 180 days (&gt; 6 months), will have the worst overall survival. Methods: We conducted a retrospective analysis of all patients diagnosed with metastatic colon cancer from 2004-2016 who underwent resection of both primary tumor and distant metastatic site from the National Cancer Database (NCDB). Among those who received chemotherapy prior to surgery, we calculated the interval days between initiation of chemotherapy and primary tumor resection. Descriptive analysis, logistic regression, and overall survival was performed comparing patients with chemotherapy-to-surgery intervals of &lt;60, 60-180, and &gt;180 days. Results: A total of 2,238 patients were included, of which 143 (6%), 1446 (65%), and 649 (29%) were in the &lt;60, 60-180, and &gt;180 days groups, respectively. Similar distribution of patients across groups was observed for age, gender, insurance status, income, education level, distance travel, and Charlson-Deyo scores. Poorly differentiated tumors were more frequent in the &lt;60 days group (12% vs 2-9% for other grades, p=0.001) as well as presence of lymphovascular invasion (8% vs 4%, p = 0.006). The odds of receiving care at an academic facility were lower in the &lt;60 days group (OR: 0.52, 95% CI 0.273-0.994). Overall survival was significantly reduced in the &lt;60 days group compared to 60-180 days (HR= 0.562, 95% C: 0.38-0.82). Conclusions: In this retrospective study from a national database, shorter chemotherapy-to-surgery interval (&lt;60 days) was associated with poorly differentiated tumors and lymphovascular invasion. The odds of receiving surgery in &lt;60 days of receiving chemotherapy was lower in academic/research facilities. A reduction in overall survival was observed in the shorter interval (&lt;60 days) group compared to longer intervals. More research is needed to define the optimal chemotherapy-surgery interval and factors that influence this.

Unusual metastases of papillary thyroid carcinoma: a case report and review of literature

Papillary thyroid carcinoma comprise approximately 80 % of all thyroid cancers. It has generally a good prognosis, and distant spread is rare. Common sites of distant metastasis include lung and bone. Whatever the pleural and breast metastasis are exceedingly rare. Their presence portends a dismal prognosis and a shorter median survival. We recently experienced a case of 60 -year-old women with pleural and breast metastasis of papillary thyroid carcinoma. We report this case with a review of the literature.

Abstract A018: Exercise stimulates anti-tumoral immunity in metastatic PDAC

Abstract The majority of pancreatic ductal adenocarcinoma (PDAC) patients are metastatic at presentation with limited treatment options and a poor overall 5-year survival of 3%. The liver is the predominant site of distant metastasis in PDAC. Our group has previously shown that aerobic exercise can inhibit tumorigenesis in a primary PDAC mouse model by promoting anti-tumor immunity, however, the effects of exercise in the metastatic setting have not been explored. As such, we developed a model of PDAC liver metastasis by isolating primary pancreatic and liver metastatic cell lines from 18–20-week-old LSL-KRasG12D/+; LSL-Trp53R172H/+; p48Cre; Rosa26LSL-tdTomato/+ (KPCTpancreas or KPCTliver, respectively) mice. KPCTpancreas cells were surgically implanted into the pancreata of syngeneic wild-type mice. One week after pancreatic implantation, KPCTliver cells were implanted into the liver either by direct injection into the parenchyma or via the portal vein. The portal vein method enables us to account for the extravasation step of the metastatic cascade, while the direct parenchymal injection offers a less invasive surgery. Both models preserve the spleen, which is the largest secondary lymphoid organ and essential to the immune response. Treadmill running was initiated in the aerobic exercise cohort 5 days per week for 2 weeks or mice were allowed to rest. Endpoint analysis revealed that aerobic exercise treatment decreased tumor burden in both primary tumors and liver metastasis as measured by tumor weights and tdTomato fluorescence imaging when compared to the rested controls. Immune profiling of the liver metastases revealed elevated IL-15Rɑ+ CD8+ T cells as well as CD19+ B cells in the exercise cohort. While identification of IL-15Rɑ+ CD8+ T cells is consistent with the immune changes we have previously reported in the primary pancreatic tumor of exercised mice, the latter changes reveal organ specific immune cell recruitment not observed in the primary pancreatic tumor of exercised mice. The combined immune profiling and phenotypic changes suggest that aerobic exercise reduces PDAC metastatic growth by modulating systemic and intra-tumoral immunity. The induction of an anti-tumorigenic immune response by aerobic exercise could open avenues for potential pharmacological intervention in downstream pathways to aid in the treatment of metastatic PDAC. Citation Format: Mansour E. Riachi, Carolina G. Alcantara Hirsch, Erica Ma, Beny Shapiro, Ammar Javed, Christopher L. Wolfgang, Dafna Bar-Sagi. Exercise stimulates anti-tumoral immunity in metastatic PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A018.

Oral Soft Tissue Metastasis from Breast Cancer as the Only Primary Source: Systematic Review.

Background Breast cancer is one of the most lethal neoplasms causing death. Oral cavity is the rare site of distant metastasis from breast cancer. Very little research has been conducted to date to analyze breast cancer as the sole primary source of metastasis to the oral soft tissues. The goal of this study was to examine the published cases of oral soft tissue metastasis from breast cancer as the only primary source to date. Methods 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 ("Oral soft tissues" OR "Tongue" OR "Palate" OR "Tonsil" OR "Buccal mucosa" OR "Floor of mouth" OR "Vestibule" OR "Salivary glands"). We also searched all related journals manually. The reference list of all articles was also checked. Results Our research revealed 88 relevant papers (September 1967-September 2023) with 96 patients in total. The most predominant oral soft tissues involved were salivary glands followed by the gingiva, tonsils, tongue, and buccal mucosa. A total of 23% of patients died with an average survival time of 1 to 15 months. Conclusions Oral soft tissue metastasis from breast cancer is a rare event and has a bad prognosis. More cases need to be published to raise awareness of these lesions.

Simultaneous laparoscopic liver metastasectomy and intersphincteric resection for neuroendocrine tumor of the rectum by natural orifice specimen extraction surgery.

Neuroendocrine tumors (NET) are relatively uncommon rectal neoplasms, and the liver is the most common site of distant metastasis. Simultaneous liver and colorectal resections by minimally invasive surgery and natural orifice specimen extraction are gaining popularity, reducing morbidity. We describe a case of rectal NET with liver metastasis operated simultaneously by laparoscopy with both specimens extracted via the anal canal. Transanal or transvaginal natural orifice specimen extraction surgery for suitable cases is underutilized and only isolated case reports for simultaneous resections exist.

Real-world progression in the survival of de novo Metastatic prostate cancer over the past decade

BackgroundThe impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. MethodsOur study involved 43,228 mPCa patients (2004–2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. ResultsPatients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. ConclusionThe survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.

Prognostic Indicators for Intracranial Metastases from Pancreatic Cancer: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis

ObjectiveThe natural history, treatment options, and clinical outcomes of pancreatic metastases to the brain remain largely unknown. Here, we seek to investigate characteristics that influence OS in pancreatic metastases to the brain. MethodsThis is a population-based retrospective study of OS in 508 patients with pancreatic metastases to the brain using the SEER database. Univariate and multivariate Cox regression analyses were utilized, and a predictive nomogram was developed. ResultsThere were 508 patients identified for this study, with a median OS of two months. In the univariate analysis, patients older than 65 years had significantly reduced OS (p<0.001). Patients with liver metastases (p<0.001) and liver and lung metastases (p<0.001) exhibited significantly reduced OS. Treatment of the primary tumor with chemotherapy only (p<0.001), radiation only (p=0.01), radiation and chemotherapy (p<0.001), and surgery only (p=0.01) were associated with increased OS. Resection of a distant metastasis site (p=0.009) and of a brain metastasis (p=0.03) were associated with increased OS. In the multivariable analysis, factors that remained significant included patient age (p=0.01), liver metastases (p<0.001), liver and lung metastases (p<0.001), treatment with chemotherapy (p<0.001), treatment with radiation and chemotherapy (p<0.001), and treatment with surgery and chemotherapy (p<0.001). The nomogram had a C-index of 0.766, suggesting congruence between the findings on the nomogram and the results in the internal verification. ConclusionsMedian OS is influenced by age, multiorgan metastases, and treatment of the primary tumor. These data highlight the marginal benefit of treatment, yet improved quality of life remains to be elucidated.

Clinical significance of baseline Epstein-Barr virus DNAfor recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survivaland objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s)or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900copies/ml) was related to shorter progression-freeand overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.

The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy.

With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers-HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren's classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.

Do resected colorectal cancer patients need early chest imaging? Impact of clinicopathologic characteristics on time to development of pulmonary metastases.

For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging. We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection. Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post-resection. We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.