Primary tumor resection for asymptomatic colorectal cancer patients with synchronous unresectable metastases: a meta-analysis of randomized controlled trials and case-matched studies.

PURPOSE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC. METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome. RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009). CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.

Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

Detection of Carcinoma-Associated Fibroblasts Derived from Mesothelial Cells via Mesothelial-to-Mesenchymal Transition in Primary Ovarian Carcinomas.

Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread.

Carcinoma en cuirasse in a middle-aged woman with a unique spoke-wheel presentation: A case report.

Carcinoma en cuirasse is a rare form of cutaneous metastasis characterized by the spread of a primary malignant tumor to the skin, most commonly associated with breast cancer in women. It may present as papulonodular lesions, erysipeloid, sclerodermiform infiltration, or en cuirassed, typically appearing months or years after the initial diagnosis of the primary malignancy. Diagnosis of carcinoma en cuirasse can be challenging, but histology can help distinguish it from other skin conditions. Treatment options for carcinoma en cuirasse are not well-defined due to the limited number of reported cases. Here, we report a case of a 30-year-old female, who presented with invasive ductal carcinoma which presented as carcinoma en cuirasse with a spoke-wheel pattern over the course of 6 months.

Epidemiological trends of synovial sarcoma by primary tumor sites in the US from 2000 to 2020.

BACKGROUND: Synovial sarcoma (SS) is a rare soft-tissue cancer. Existing literature encompasses Surveillance, Epidemiology, and End Results (SEER) data-based research on SS explaining the incidence-prevalence in general, by subtypes, and by age at diagnosis. Therefore, this study aimed to fill in the gap of knowledge about measures of disease occurrence and burden of SS by tumor site using the SEER database. METHODS: In this cross-sectional study, primary SS patients were selected from SEER 17 Registries, Nov. 2021 (2000-2020) using ICD-O-3 codes 9040, 9041, 9042, and 9043. Patients with additional cancers were excluded. The primary tumor site was categorized into (1) head/neck, (2) internal thorax, (3) abdomen/pelvis, (4) upper extremity, and (5) lower extremity using ICD-10CM codes. Five outcomes were analyzed: age-adjusted incidence rate, 5-year limited-duration prevalence rate, incidence-based mortality, case-fatality rate, and overall survival. RESULTS: From 2000-2020, the overall age-adjusted incidence rate was 0.15 per 100,000; the 5-year limited duration prevalence rate was 0.56 per 100,000; and the incidence-based mortality rate was 0.06 per 100,000 people. The case-fatality and 5-year OS rates were 39.2 % and 62.9 %, respectively. Lower extremity had the highest incidence of 0.07 (estimated 1166 cases), prevalence of 0.36 (estimated 224 cases), and mortality rate of 0.025 (estimated 429 deaths) per 100,000. The other four locations had much closer rates with each other. Intrathoracic SS had the highest case-fatality rate of 71.5 % (148/207) and lowest 5-year OS of 26.0 % (95 % CI: 19.6 %, 32.9 %) than other sites. CONCLUSION: Based on the measures of disease frequency, the most common primary tumor site is the lower extremity, followed by the upper extremity, abdomen/pelvis, internal thorax, and head/neck. The least favorable primary location is the internal thorax. Those with a primary location of the upper extremity have the longest overall survival, followed by the head/neck, lower extremity, abdomen/pelvis, and internal thorax.

Diagnostic Performances of PET/CT Using Fibroblast Activation Protein Inhibitors in Patients with Primary and Metastatic Liver Tumors: A Comprehensive Literature Review.

PET/CT using radiolabeled fibroblast activation protein inhibitors (FAPIs) is a promising diagnostic tool in oncology, especially when non-increased and/or physiologically high [18F]FDG uptake (as in liver parenchyma) is observed. We aimed to review the role of PET/CT using radiolabeled FAPIs in primary and/or metastatic liver lesions, and to compare their performances with more "conventional" radiopharmaceuticals. A search algorithm based on the terms "FAPI" AND ("hepatic" OR "liver") was applied, with the last update on 1st January 2024. Out of 177 articles retrieved, 76 studies reporting on the diagnostic application of radiolabeled FAPI PET/CT in at least one patient harboring primary or metastatic liver lesion(s) were fully analyzed. Although there was some heterogeneity in clinical conditions and/or study methodology, PET/CT with radiolabeled FAPIs showed an excellent performance in common primary liver malignancies (hepatocarcinoma, intrahepatic cholangiocarcinoma) and liver metastases (mostly from the gastrointestinal tract and lungs). A higher tumor-to-background ratio for FAPIs than for [18F]FDG was found in primary and metastatic liver lesions, due to lower background activity. Despite limited clinical evidence, radiolabeled FAPIs may be used to assess the suitability and effectiveness of FAPI-derived therapeutic agents such as [177Lu]Lu-FAPI. However, future prospective research on a wider population is needed to confirm the excellent performance.

Predictive Modeling of Long-Term Prognosis After Resection in Typical Pulmonary Carcinoid: A Machine Learning Perspective.

Typical Pulmonary Carcinoid (TPC) is defined by its slow growth, frequently necessitating surgical intervention. Despite this, the long-term outcomes following tumor resection are not well understood. This study examined the factors impacting Overall Survival (OS) in patients with TPC, leveraging data from the Surveillance, Epidemiology, and End Results database spanning from 2000 to 2018. We employed Lasso-Cox analysis to identify prognostic features and developed various models using Random Forest, XGBoost, and Cox regression algorithms. Subsequently, we assessed model performance using metrics such as Area Under the Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA). Among the 2687 patients, we identified five clinical features significantly affecting OS. Notably, the Random Forest model exhibited strong performance, achieving 5- and 7-year AUC values of 0.744/0.757 in the training set and 0.715/0.740 in the validation set, respectively, outperforming other models. Additionally, we developed a web-based platform aimed at facilitating easy access to the model. This study presents a machine learning model and a web-based support system for healthcare professionals, assisting in personalized treatment decisions for patients with TPC post-tumor resection.

No survival benefit of primary tumor resection for non-small cell lung cancer patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with pleural dissemination are generally contraindicated for surgery. This study aimed to investigate the survival benefits of primary tumor resection for NSCLC patients with unexpectedly detected pleural disseminated nodules during thoracotomy in the era of targeted therapy. METHODS: Of the 4984 patients with NSCLC who underwent surgery without induction therapy between 2000 and 2021, we retrospectively evaluated 90 (1.8%) patients with unexpectedly detected pleural disseminated nodule. Survival analyses were performed with Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: Among the evaluated patients, 58 were male, the median age was 67, and 77 (86%) were diagnosed with adenocarcinoma. Exploratory thoracotomy was performed in 21 (23%), and primary tumor resection was performed in 69 (77%) patients, including pneumonectomy in four, lobectomy in 39, and sublobar resection in 26. Epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement were detected in 33 (37%) and 4 (4%) cases, respectively. Among them, 31 patients received targeted therapy. The overall survival (OS) was not significantly different between patients with primary tumor resection and exploratory thoracotomy (5-year OS rate: 30.2% vs. 27.8%, p = 0.81). Multivariable analysis revealed that sex (p = 0.02) and targeted therapy (p < 0.01) were independent prognostic factors for OS. Survival outcomes in patients who received targeted therapy were significantly better regardless of primary tumor resection. CONCLUSIONS: Primary tumor resection might not affect the survival in NSCLC patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Survival outcomes according to the tumor location and prognostic factor in metastatic rectal cancer: a multicenter retrospective cohort study.

Background & aims: Prognostic factors of metastatic rectal cancer are not well known. We aim to determine prognostic factors affecting survival for metastatic rectal cancer patients and also to investigate the effect of tumor localization on overall survival. Methods: Metastatic rectal cancer patients who received treatment in 5 different centers between 2012 and 2022 were included. Prognostic factors for survival were evaluated using univariate and multivariate analysis. The statistical methods included Pearson's chi-square test, Fisher exact test, Log-rank test, and Cox regression model. Results: A total of 283 patients with metastatic rectal cancer were included in the study. The median OS was not significantly different among the three groups (upper rectum 30.1 months, middle rectum 28.3 months, and low rectum cancer 24.8 months; log-rank p = 0.25). In univariate analysis, Grade 3, ECOG performance status 2, the presence of multiple metastatic sites, the presence of KRAS mutation, the presence of liver metastases, the presence of nonregional lymph node metastases, and the presence of bone metastases were significant predictors of poor survival. In multivariate analysis, Grade 3, ECOG performance status 2, and the presence of multiple metastatic sites were determined as indicators of worse prognosis. Conclusion: Our findings, primary tumor location did not affect survival in metastatic rectal cancer. The most important factors affecting survival were multiple metastatic sites, tumor grade, and ECOG performance status.

Endovascular Treatment for Primary Tumor Hemorrhage in Oropharyngeal Carcinoma: A Report of Two Cases.

Acute arterial hemorrhage is a damaging and sometimes lethal complication that occurs in patients with head and neck cancer. However, achieving hemostasis can be challenging because of the difficulty in applying pressure in the throat and oral cavity. In this context, endovascular treatment (ET) has been performed in recent years. This report aims to describe the benefits of ET for acute bleeding. Additionally, our findings emphasize the importance of early diagnosis and treatment of tumor-related bleeding, not only for immediate life-saving benefits but also for the potential resumption of irradiation and chemotherapy, which can lead to favorable long-term prognoses in some instances. We describe two cases of primary tumor bleeding where treatment was successful with ET. Neurosurgeons performed these treatments, and effective hemostasis was achieved in both cases. No complications or rebleeding were observed. ET is a better option for hemorrhage from oropharyngeal tumors than for hemorrhage from the main trunk of the carotid artery. The efficacy of ET is dependent on the vessels involved, and early identification of the culprit artery can predict the prognosis. ET should be considered an option for acute arterial hemorrhage in head and neck cancer.

Comparative effectiveness of primary tumor resection versus chemotherapy in patients with asymptomatic unresectable metastatic colorectal cancer: a retrospective cohort study using the target trial emulation framework.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Tumor desmoplasia outperforms preoperative serum calcitonin as surgical biomarker in sporadic medullary thyroid cancer.

BACKGROUND: Conceptually, thyroid tumor desmoplasia may be better suited for excluding node metastases in sporadic MTC than preoperative serum calcitonin levels. METHODS: This analysis included 181 patients with unilateral sporadic MTC graded on the 7-grade desmoplasia scale after thyroidectomy and neck dissection. RESULTS: When thyroid tumor desmoplasia reached 1% and ≥50%, node metastases increased from 0% to 7% (median of 0 metastases) and 83% (median of 7.5 metastases), microscopic lymphatic invasion from 0% to 3% and 35%, extrathyroid extension from 0% to 5% and 22%, and extranodal growth from 0% to 0% and 44%, whereas biochemical cure declined from 100% to 95% and 25%. Thyroid tumor diameters and basal calcitonin overlapped widely among the seven desmoplasia groups, precluding differentiation by thyroid tumor size or serum calcitonin levels. CONCLUSIONS: Thyroid tumor desmoplasia, unlike serum calcitonin levels, discriminates extremely well between node-negative and node-positive sporadic MTC, opening new avenues for precision surgery.

Impact of primary tumor resection in the management of metastatic well-differentiated neuroendocrine tumors of the small bowel and pancreas.

Patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NET) often present with advanced disease. Primary tumor resection (PTR) in the setting of unresectable metastatic disease is controversial. Most studies evaluating the impact of PTR on overall survival (OS) have been performed using large population-based databases, with limited treatment related data. This study aims to determine whether PTR improves OS and progression-free survival (PFS) in patients with metastatic well-differentiated GEP-NET. This is a retrospective single-institution study of patients with metastatic well-differentiated GEP-NET between 1978 and 2021. The primary outcome was OS. The secondary outcome was PFS. Chi-squared tests and Cox regression were used to perform univariate and multivariate analyses (MVA). OS and PFS were estimated using the Kaplan-Meier method and log-rank test. Between 1978 and 2021, 505 patients presented with metastatic NET, 151 of whom had well-differentiated GEP-NET. PTR was performed in 31 PNET and 77 SBNET patients. PTR was associated with improved median OS for PNET (136 vs. 61 months, p = .003) and SBNET (not reached vs. 79 months, p<.001). On MVA, only higher grade (HR 3.70, 95%CI 1.49-9.17) and PTR (HR 0.21, 95%CI 0.08-0.53) influenced OS. PTR resulted in longer median PFS for patients with SBNET (46 vs. 28 months, p = .03) and a trend toward longer median PFS for patients with PNET (20 vs. 13 months, p = .07). In patients with metastatic well-differentiated GEP-NET, PTR is associated with improved OS and may be associated with improved PFS and should be considered in a multidisciplinary setting. Future prospective studies are needed to validate these findings.

Transition to a mesenchymal state in neuroblastoma may be characterized by a high expression of GD2 and by the acquisition of immune escape from NK cells.

Background: Neuroblastoma (NB) is characterized by both adrenergic (ADRN) and undifferentiated mesenchymal (MES) subsets. The ganglioside sialic acid-containing glycosphingolipid (GD2) is widely overexpressed on tumors of neuroectodermal origin promoting malignant phenotypes. MES cells are greatly enriched in post-therapy and relapsing tumors and are characterized by decreased expression of GD2. This event may cause failure of GD2-based immunotherapy. NK cells represent a key innate cell subset able to efficiently kill tumors. However, the tumor microenvironment (TME) that includes tumor cells and tumor-associated (TA) cells could inhibit their effector function. Methods: We studied eight NB primary cultures that, in comparison with commercial cell lines, more faithfully reflect the tumor cell characteristics. We studied four primary NB-MES cell cultures and two pairs of MES/ADRN (691 and 717) primary cultures, derived from the same patient. In particular, in the six human NB primary cultures, we assessed their phenotype, the expression of GD2, and the enzymes that control its expression, as well as their interactions with NK cells, using flow cytometry, RT-qPCR, and cytotoxicity assays. Results: We identified mature (CD105+/CD133-) and undifferentiated (CD133+/CD105-) NB subsets that express high levels of the MES transcripts WWTR1 and SIX4. In addition, undifferentiated MES cells display a strong resistance to NK-mediated killing. On the contrary, mature NB-MES cells display an intermediate resistance to NK-mediated killing and exhibit some immunomodulatory capacities on NK cells but do not inhibit their cytolytic activity. Notably, independent from their undifferentiated or mature phenotype, NB-MES cells express GD2 that can be further upregulated in undifferentiated NB-MES cells upon co-culture with NK cells, leading to the generation of mature mesenchymal GD2bright neuroblasts. Concerning 691 and 717, they show high levels of GD2 and resistance to NK cell-mediated killing that can be overcome by the administration of dinutuximab beta, the anti-GD2 monoclonal antibody applied in the clinic. Conclusions: NB is a heterogeneous tumor representing a further hurdle in NB immunotherapy. However, different from what was reported with NB commercial cells and independent of their MES/ADRN phenotype, the expression of GD2 and its displayed sensitivity to anti-GD2 mAb ADCC indicated the possible effectiveness of anti-GD2 immunotherapy.

[Local resection of small intestine neuroendocrine neoplasms (SI-NEN) : Current principles]. / Lokale Resektion von neuroendokrinen Tumoren des Dünndarms (SI-NEN) : Aktuelle Prinzipien.

BACKGROUND: Neuroendocrine tumors of the small bowel (small intestine neuroendocrine neoplasms, SI-NEN) are the most frequent tumors of the small intestine and approximately 30-40% are still surgically treatable with curative intent at the time of diagnosis. Certain surgical principles must be followed for optimal oncological outcomes and good postoperative quality of life. METHODS: Based on international guidelines and own experiences, the locoregional surgical treatment of SI-NENs is presented. RESULTS: Locoregional SI-NENs should always be resected if technically feasible, as only this approach can achieve a long-term cure and even small primary tumors (< 10 mm) often already show lymphatic metastasis. The resectability of SI-NENs and their difficulty depend on the extent of lymphatic metastasis, which should be assessed based on preoperative imaging of the extent around the superior mesenteric artery. Currently, the surgical gold standard for SI-NENs is open surgery with bidigital palpation of the entire small intestine followed by primary tumor resection via small bowel segment resection, right hemicolectomy or ileocecal resection and vessel-sparing, and therefore organ-preserving lymphadenectomy (≥ 8 lymph nodes). The guidelines consider that laparoscopic or robotic approaches are justified only for early stages of SI-NENs. CONCLUSION: Guideline-compliant surgical treatment of locoregional SI-NEN enables recurrence-free long-term survival with good quality of life.

The prognostic value of lymph node to primary tumor standardized uptake value ratio in cancer patients: a meta-analysis.

OBJECTIVE: The lymph node to primary tumor standardized uptake value ratio (NTR) is an innovative parameter derived from positron emission tomography/computed tomography (PET/CT) scans that captures the intricate relationship between primary tumors and associated lymph nodes. This meta-analysis aimed to investigate the prognostic value of NTR in cancer patients. METHODS: A systematic search of PubMed, Cochrane, and Embase databases was conducted to identify studies investigating the association between NTR and survival outcomes in cancer patients. The pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twelve studies comprising a total of 2037 patients were included in the meta-analysis. Elevated NTR was significantly associated with worse overall survival aHR (2.21, 95% CI 1.63 to 2.99), disease-free survival aHR (3.27, 95% CI 2.12 to 5.05), and distant metastasis-free survival aHR (2.07, 95% CI 1.55 to 2.78) in cancer patients. Subgroup analyses by cancer type showed consistent results across various malignancies, including head and neck squamous cell carcinoma, endometrial carcinoma, lung cancer, breast cancer, and nasopharyngeal carcinoma. CONCLUSIONS: This meta-analysis provides evidence for a significant association between elevated NTR and worse survival outcomes in cancer patients. Elevated NTR may serve as a useful prognostic biomarker for cancer patients and could potentially be used to guide treatment decisions and monitor disease progression. Future studies should aim to validate these findings in larger and more diverse patient populations and investigate the underlying mechanisms for the observed association between NTR and survival outcomes.

The prognostic significance of primary tumor site in vulvar cancer: a population-based cohort study.

OBJECTIVE: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. METHODS: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan-Meier analyses and Cox proportional hazards regression analyses. RESULTS: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27-2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47-3.85; p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan-Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). CONCLUSION: Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

Stability and variability of molecular subtypes: comparative analysis of primary and metastatic triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are lacking. METHODS: We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC (eTNBC) and 415 metastatic TNBC (mTNBC) patients] who were treated at Fudan University Shanghai Cancer Center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes. RESULTS: The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1% (47/465). The median overall survival (OS) in the mTNBC cohort was 27.2 months [95% confidence interval (CI), 24.4-30.2 months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like (MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial. CONCLUSIONS: Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.

Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.