Metastatic Pattern Research Articles

Risk factors and pattern of metastatic recurrence after endoscopic resection with additional treatment for esophageal cancer.

Although esophageal cancers invading the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic resection (ER) are associated with a risk of lymph node metastasis, details of metastatic recurrence after additional treatment remain unknown. We aimed to identify the risk factors for metastatic recurrence and recurrence patterns in patients receiving additional treatment after ER for esophageal cancer. Between 2006 and 2017, patients with pT1a-MM/pT1b-SM esophageal cancer who underwent ER with additional treatment (esophagectomy, chemoradiotherapy [CRT], and radiation therapy) at 21 institutions in Japan were enrolled. We evaluated the risk factors for metastatic recurrence after ER with additional treatment. Subsequently, the rate and pattern (locoregional or distant) of metastatic recurrence were investigated for each additional treatment. Of the 220 patients who received additional treatment, 57, 125, and 38 underwent esophagectomy, CRT, and radiation therapy, respectively. In the multivariate analysis, lymphatic invasion was the sole risk factor for metastatic recurrence after additional treatment (hazard ratio, 3.50; P = 0.029). Although the risk of metastatic recurrence with additional esophagectomy was similar to that with CRT (hazard ratio, 1.01; P = 0.986), the rate of locoregional recurrence tended to be higher with additional esophagectomy (80.0% (4/5) vs. 36.4% (4/11)), leading to a better prognosis in patients with metastatic recurrence after additional esophagectomy than CRT (survival rate, 80.0% (4/5) vs. 9.1% (1/11)). Patients with lymphatic invasion have a high risk of metastatic recurrence after ER with additional treatment for pT1a-MM/pT1b-SM esophageal cancer. Additional esophagectomy may result in a better prognosis after metastatic recurrence.

Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.

Establishment of a Transplantation Model of PDAC-Derived Liver Metastases

BackgroundThe highly metastatic nature of pancreatic ductal adenocarcinoma (PDAC) and the difficulty to achieve favorable patient outcomes emphasize the need for novel therapeutic solutions. For preclinical evaluations, genetically engineered mouse models are often used to mimic human PDAC but frequently fail to replicate synchronous development and metastatic spread. This study aimed to develop a transplantation model to achieve synchronous and homogenous PDAC growth with controlled metastatic patterns in the liver.MethodsTo generate an orthotopic PDAC model, the DT6606 cell line was injected into the pancreas head of C57BL/6 mice, and their survival was monitored over time. To generate a heterotopic transplantation model, growing doses of three PDAC cell lines (DT6606, DT6606lm, and K8484) were injected into the portal vein of mice. Magnetic resonance imaging (MRI) was used to monitor metastatic progression, and histologic analysis was performed.ResultsOrthotopically injected mice succumbed to the tumor within an 11-week period (average survival time, 78.2 ± 4.45 days). Post-mortem examinations failed to identify liver metastasis. In the intraportal model, 2 × 105 DT6606 cells resulted in an absence of liver metastases by day 21, whereas 5 × 104 DT6606lm cells and 7 × 104 K8484 cells resulted in steady metastatic growth. Higher doses caused significant metastatic liver involvement. The use of K8484 cells ensured the growth of tumors closely resembling the histopathologic characteristics of human PDAC.ConclusionsThis report details the authors’ efforts to establish an “optimal” murine model for inducing metastatic PDAC, which is critical for advancing our understanding of the disease and developing more effective treatments.

The impact of metastatic sites on survival Rates and predictors of extended survival in patients with metastatic pancreatic cancer

Background objectivesThe aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. MethodsWe examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016–2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. ResultsMedian overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). ConclusionWhile synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

Nodal Metastases in Stage 3 Head and Neck Melanoma: Patterns of Metastases and Patterns of Failure.

Stage 3 patients with clinically positive nodal metastasis are treated with therapeutic neck dissection and adjuvant systemic therapy. The aim of our study was to examined the predictability of pre-operative CT as a nodal drainage assessment tool. Retrospective review of all patients with clinically positive head and neck cutaneous melanoma between 2010 and 2019. Clinical disease was diagnosed as radiological suspicious, biopsy-proven node. A pre-operative CT evaluation for nodal metastasis was compared to pathology report. A total of 53 patients were included. Forty patients (75.5%) were males with a mean age of 59 (SD 15.52). The majority of patients (26.4%) had an unknown primary site. The most common sites for primary were the cheek in eight patients (15.1%) followed by forehead (9.4%) and lateral neck (9.4%). Preoperative CT predicted nodal disease in 84.6% of cases. The primary region that mainly failed from the previously described clinical prediction was the upper anterior neck with 83.3% parotid involvement. A total of 10 patients (18.9%) were diagnosis with non-clinical nodes on pathology with a median non-clinical node of 1 (range 1-2). Of them, 9 (90%) were in the same clinical levels detected by CT. Pre-operative CT was associated with a neck level accuracy of 98.1%. Stage 3 head and neck melanoma with clinically positive nodal metastasis that are eligible for an adjuvant systemic treatment, may benefit from a highly selective neck dissection according to their pre-operative imaging studies. This should be further evaluated in a large-scale clinical trial. 3 Laryngoscope, 134:4292-4297, 2024.

Nodal metastasis and value of neck dissection in T1/2 oropharyngeal and hypopharyngeal carcinomas

Due to heterogeneous data, the indication for elective neck dissection (END) in patients with squamous cell carcinoma of the hypopharynx and oropharynx (HPSCC and OPSCC) in stages T1/2N0 is somewhat unclear. Therefore, in this multicenter study, we performed detailed analysis of the metastatic behavior of HPSCC and OPSCC. The nodal metastatic patterns of 262 HPSCC and OPSCC patients who had undergone surgery was retrospectively investigated. In addition, recurrence-free and overall survival were recorded. Furthermore, a systematic literature review on the topic was completed. In patients with HPSCC, a discrepancy between clinical and pathologic N status was recorded in 62.1% of patients vs. 52.4% for p16- OPSCC, and 43.6% for p16+ OPSCC. The occult metastasis rate in cT1/2cN0 primary tumors was 38.9% for HPSCC vs. 17.8% (p16- OPSCC) and 11.1% (p16+ OPSCC). Contralateral metastases occurred in 22.2% of cases for HPSCC at stages cT1/2cN0, compared to only 9.1% for p16- OPSCC, and 0% for p16+ OPSCC patients.Patients with p16+ OPSCC had better recurrence-free and overall survival than p16- OPSCC and HPSCC patients. A direct association between patient survival and the extent of neck surgical therapy could not be demonstrated in our patients. Patients with HPSCC are at risk for bilateral neck metastases from stage cT1/2cN0, justifying bilateral END. Patients with T1/2 OPSCC present with occult metastases ipsilaterally in >20% of cases; however, the risk for contralateral occult metastasis is <10%. Hence, in strictly lateralized cT1/2CN0 tumors, omission of contralateral END may be considered.

Association of mutational status with metastatic pattern, race, ethnicity, and overall survival (OS) in leiomyosarcoma (LMS).

e23553 Background: LMS, one of the most common soft tissue sarcomas, can arise from the uterus, retroperitoneum, vessels, or extremities. It is unclear if the metastatic pattern and potentially the mutational status differs among the different types of LMS. We investigated the association between sites of metastases, mutations, race, ethnicity, and OS in different LMS types. Methods: This single-center retrospective study evaluated patients with biopsy-proven LMS that underwent genomic testing between January 2009 and May 2023. Association between genomic profile, sites of metastases, types of LMS (extremity, retroperitoneal, uterine, vascular), self-reported race and ethnicity was performed using Fisher’s exact test. Survival curves for self-reported race and ethnicity, mutations, sites of metastases, and types of LMS were estimated using the Kaplan-Meier method and compared with a log-rank test. Cox proportional hazard regression models were used to examine the association between OS with types of LMS, self-reported race and ethnicity, mutational status, and sites of metastases. Results: The study included 110 subjects (F/M:81/29; median age 57 years, 99/110 with metastatic disease). 27/110 (25%) subjects self-reported as Hispanic, and 27/110 (25%) as Black. The most common type of LMS was uterine (50/110, 45%), followed by retroperitoneal (27/110, 25%), extremities (23/110, 21%) and vascular (10/110, 9%). The most common mutation was TP53 (74/110, 67%), followed by RB1 (24/110, 22%). ER/PR expression was present in 25/110 subjects (23%). The lungs were the most common site of metastasis (79/99, 80%), followed by the liver (37/99, 37%), and pelvis (29/99, 29%). Peritoneal and pelvic metastases were more common in uterine LMS (p = 0.0001 and 0.002, respectively). Liver metastases were more common in retroperitoneal LMS (p = 0.03). TP53 mutation was more common in vascular LMS (p = 0.03), whereas intermediate/high tumor burden was more common in LMS arising from the extremities (p = 0.004). BRCA1/2 mutations were more common in subjects with liver (p = 0.02) and intramuscular metastases (p = 0.04). Pleural metastases (11/99, 11%) were associated with lower OS (Risk Ratio: 2.7; 95% CI: 1.13, 6.32; p = 0.02). ATRX mutation (17/110, 15%) was more common in Hispanic subjects (p = 0.005), in which it was associated with lower OS (p = 0.0007). Conclusions: The mutational status and metastatic pattern of LMS varies based on the LMS types, and potentially provides prognostic data. In our sample, OS was reduced in Hispanic subjects with ATRX mutation, and the presence of pleural metastases was also independently associated with shorter OS.

Short-term and long-term survival outcomes in patients with invasive lobular carcinoma vs. invasive ductal carcinoma of the breast.

e12564 Background: Invasive lobular carcinoma (ILC) accounts for 10% of all invasive breast cancer and has distinct histological and biological features compared to the most common breast cancer histological subtype, invasive ductal carcinoma (IDC). ILC is more endocrine sensitive and chemotherapy resistant than IDC and has a different metastatic pattern. There is lack of conclusive data on the differences in survival outcomes between ILC and IDC. We aimed to assess the short-term and long-term survival outcomes in patients with ILC and IDC in a large population database. Methods: This is a retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results database. We included women &gt; 18 years with stage I-III ILC or IDC diagnosed from 1992-2020. Multivariable logistic regression was used to assess factors associated with different treatment modalities in patients with IDC vs. ILC. We estimated breast cancer-specific survival (BCSS) using Kaplan-Meier methods and their survival rates were compared using the log-rank test. We analyzed BCSS at different time points using a cox regression model with time-varying coefficients. Results: 343,397 patients with IDC and 39,859 patients with ILC were included in this study. Patients with ILC were older (63.0 ± 12.5 years vs. 59.2 ± 13.5 years, p&lt;0.001). There were more non-Hispanic white patients with ILC vs. IDC (76% vs. 67%, p&lt;0.001). Patients with ILC had more advanced disease: more stage III disease (16% vs. 11%, p&lt;0.001), more T3-T4 disease (15% vs. 6%, p&lt;0.001), and more N2-N3 disease (12% vs. 9%, p&lt;0.001). Patients with ILC also had a higher frequency of hormone receptor positive disease (97% vs. 81%, p&lt;0.001). Fewer patients with ILC had grade 3-4 tumors (9% vs. 36%, p&lt;0.001). Our multivariate analysis showed that compared to patients with IDC, patients with ILC were more likely to undergo mastectomy (OR=1.85, p &lt; 0.001) and radiation (OR=1.20, p&lt;0.001), but less likely to receive chemotherapy (OR= 0.92, p&lt;0.001). After adjusting for clinicopathological features, treatment modalities, and socioeconomic variables; compared to patients with IDC, patients with ILC had better BCSS in the first five years (HR=0.71, p &lt;0.001), but worse BCSS in later years (HR=1.30, p&lt;0.001 in year 6-10; HR=1.75, p&lt;0.001 in year 11-15; HR=2.17, p&lt;0.001 in year 16-20). Annual hazard models show that IDC peaked at recurrence in the first 5 years after diagnoses, and the hazard rate declines gradually after that. ILC peaked at recurrence in the first 5 years after diagnosis with minimal decrease in hazard rates after that. Conclusions: BCSS of patients with ILC is better in early years but worse in later years compared to patients with IDC. Future studies are needed to identify predictors of late relapses in ILC, and novel therapeutic strategies are required for these patients.

Patient characteristics, treatment patterns and early trends of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) use by US urologists and oncologists.

e17048 Background: 177Lu-PSMA-617 was approved by the US Food and Drug Administration in March 2022 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This study describes characteristics of patients treated with 177Lu-PSMA-617, treatment patterns and early trends in 177Lu-PSMA-617 utilization by US urologists (URO) and medical oncologists (ONC). Methods: This retrospective cohort study identified adult patients with ≥1 claim for 177Lu-PSMA-617 between 3/1/22 and 6/30/23 (first claim = index date) from the IQVIA open-source pharmacy and medical claims database. Patients were grouped by the physician specialty of the treating/referring physician. Patient characteristics were assessed within the 6 months prior to 177Lu-PSMA-617 initiation. Prior prostate cancer treatments were assessed over all available pre-index data. Results: Overall 1,394 patientstreated with 177Lu-PSMA-617 were identified during the first 16 months post-approval; 76.9% treated by an ONC and 23.1% treated by a URO. The mean age overall was 72.1 years; most patients were aged 65 and older (ONC, 83.3%; URO, 84.8%). Most patients had bone metastases (ONC, 88.0%; URO, 86.3%) and over one-third had visceral metastases (ONC, 34.6%; URO 35.7%). URO treated a higher proportion of patients with only lymph node metastases (5.9%) than oncologists (2.6%). Prior to 177Lu-PSMA-617, the vast majority of patients received ARPI and/or taxanes (ONC, 88.2%; URO, 89.4%). Use of 177Lu-PSMA-617 has steadily increased over the 16 months since approval with over five times as many patients being treated by ONC and URO in the first half of 2023. Conclusions: This is the first large-scale study describing 177Lu-PSMA-617 patient characteristics, prostatic cancer metastatic distribution, treatment patterns, and utilization trends by prescriber type (ONC and URO). This study highlights how URO are playing a pivotal role in management of post-taxane mCRPC patients receiving 177Lu-PSMA-617. As additional data with 177Lu-PSMA-617 becomes available, we anticipate the role of URO to significantly evolve with the potential for earlier use of 177Lu-PSMA-617 for pre-taxane mCRPC patients.

Biologic and prognostic significance of HER2-low and ER-low expressions in de novo metastatic breast cancer.

e13170 Background: It is unclear whether ER-low-positive (ER-low) and HER2-low-positive (HER2-low) biomarkers, as new biological subtypes, have different biological and clinicopathological characteristics in de novo metastatic breast cancer (dnMBC). Per ASCO/CAP guidelines, tumors were defined as HER2-low-positive (HER2-low) if they had an HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and HER2-0 if they had an HER2 IHC score of 0; ER-low refers to the tumor IHC staining of 1%-10%, if the staining is less than 1%, it is defined as ER-0. This study aimed to investigate whether ER-low and HER2-low expressions is associated with clinicopathologic characteristics and prognosis among patients with de novo metastatic breast cancer. The study was approved by the Ethics Committee of Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types, histopathological report and survival data. According to ASCO/CAP guideline recommendations, patient-specific histopathological results were classified, and IHC-based breast cancer markers, mainly including ER-low and HER2-low, were evaluated and analyzed. Median survival time (MST) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. All statistical analyses were performed using Stata 18.0. Results: A total of 518 patients (median age of 53 years) were included in this study, including 194 patients with HER2-low, 201 patients with HER2-low, 36 patients with ER-low, and 179 patients with ER-0. Expression of HER2-low was significantly more common among ER-positive tumors (excluding the ER-low) compared with HER2-0 tumors (71.1% vs. 62.2%; P &lt; .001). The MST in the HER2-low cohort was longer than that in the HER2-0 cohort (40 vs. 30 months; HR,0.65; 95% CI, 0.52-0.82, p=.0001); while the MST of ER-low cohort was slightly longer than that of the ER-0 cohort (27 vs. 20 months; HR,0.75; 95% CI, 0.51-1.11, p=.231), but there was no statistical difference. Notably, in the metastasis pattern cohort, HER2-low showed a significantly higher MST compared with HER2-0 (P&lt;.001), with a MST of up to 68 months for bone-only metastases. There was no significant difference in MST between ER-low and ER-0 regardless of whether patients received endocrine therapy (P=.135). Conclusions: In the present study, for dnMBC patients, ER-low expression has similar biological and clinical outcome characteristics as ER-0. However, unlike HER2-0, HER2-low expression may predict a survival benefit in bone-only metastases.

Oncological Outcomes and Patterns of Recurrence after the Surgical Resection of an Invasive Intraductal Papillary Mucinous Neoplasm versus Primary Pancreatic Ductal Adenocarcinoma: An Analysis from the German Cancer Registry Group of the Society of German Tumor Centers.

Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The available literature has shown controversial results regarding prognosis and clinical outcomes after the resection of invasive IPMN. This study aims to characterize the oncologic outcomes and metastatic progression pattern after the resection of non-metastatic invasive IPMN. Data were obtained from 24 clinical cancer registries participating in the German Cancer Registry Group of the Society of German Tumor Centers (ADT). Patients with invasive IPMN (n = 217) as well as PDAC (n = 5794) between 2000 and 2021 were included and compared regarding oncological outcomes. Invasive IPMN was significantly smaller in size (p < 0.001) and of a lower tumor grade (p < 0.001), with fewer lymph node metastases (p < 0.001), lymphangiosis (p < 0.001), and consequently a higher R0 resection rate (88 vs. 74%) compared to PDAC. Moreover, invasive IPMN was associated with fewer local (11 vs. 15%) and distant recurrences (29 vs. 46%) and metastasized more frequently in the lungs only (26% vs. 14%). Invasive IPMN was associated with a longer median OS (29 vs. 19 months) and DFS (31 vs. 15 months) compared to PDAC and stayed independently prognostic in multivariable analyses. These survival differences were most pronounced in early tumor stages. Interestingly, postoperative chemotherapy was not associated with improved overall survival in surgically resected invasive IPMN. Invasive IPMN is a rare pancreatic entity with increasing incidence in Germany. It is associated with favorable histopathological features at the time of resection and longer OS and DFS compared to PDAC, particularly before the locoregional spread has occurred. Invasive IPMNs are associated with lung-only metastasis. The benefit of postoperative chemotherapy after the resection of invasive IPMN remains uncertain.

Anatomical Patterns of Nodal Spread in Unilateral Papillary and Medullary Thyroid Cancer.

Background: Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This study sought to delineate patterns of central and lateral neck involvement in unilateral papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). Methods: This was a retrospective correlative analysis of nodal patterns in surgical specimens from patients with unilateral PTC or MTC who had undergone thyroidectomy with at least ipsilateral central neck dissection between November 1994 and January 2024 at a tertiary referral center. Results: Included were 833 patients with unilateral PTC and 640 patients with unilateral MTC. Simultaneous presence or absence of node metastases was noted in ipsilateral central and lateral neck compartments in 76.6-78.1% of patients with PTC (both node positive in 27.0-54.7% and both node negative in 23.4-49.6%) and 77.3-80.0% of patients with MTC (both node positive in 26.6-33.2% and both node negative in 44.1-53.4%). Only one ipsilateral neck compartment was node positive in 21.9-23.4% of patients with PTC and 20.0-22.7% of patients with MTC. The ipsilateral central, but not the ipsilateral lateral compartment, was node positive in 8.8-16.9% with PTC and 8.6-8.8% of patients with MTC, whereas the ipsilateral lateral, but not the ipsilateral central compartment, was node positive in 6.5-13.1% with PTC and 11.3-14.1% with MTC. Ipsilateral lateral neck involvement sparing the ipsilateral central neck was 1.5-2 times more frequent in patients with node positive MTC than patients with node positive PTC (24.2-25.2% vs. 12.9-17.1%). Greater numbers of node metastases in the ipsilateral central neck compartment were associated with more frequent involvement of the ipsilateral lateral, contralateral central, and contralateral lateral neck compartments. Thyroid tumor diameter intensified nodal spread without changing nodal spread patterns. Conclusions: These histopathological findings, which need to be interpreted in light of the respective tumor biology, offer an unprecedented glimpse at the metastatic patterns of unilateral PTC and MTC. Customizing neck dissection to the patterns of nodal spread, considering operative status (initial vs. reoperative surgery) and experience with neck dissection, may require more frequent concomitant dissections of ipsilateral central and ipsilateral lateral neck compartments.

Efficacy of Cytoreductive Surgery (CRS) + HIPEC in Gastric Cancer with Peritoneal Metastasis: Systematic Review and Meta-Analysis.

Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8-28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9-8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (-1.8954 (95% CI: -2.5761 to -1.2146; p < 0.001). CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.

The Incidence of Distant Metastases in Patients with Pleural Mesothelioma Screened for a Multimodal Approach: How Much Staging Do We Really Need?

Pleural mesothelioma (PM) is a very aggressive malignancy with a poor prognosis. Most patients receive systemic treatment only; however, some patients may benefit from multimodality treatment. A precise staging of patients undergoing multimodal treatment is mandatory. We investigated the pattern of metastasis in a cohort of patients screened for multimodal treatment to define the extent of staging examinations. Additionally, we investigated the occurrence of metastasis during follow-up. We investigated a single-center experience of 545 patients newly diagnosed and/or treated with PM between the years 2010 and 2022. Patients who were treated naïvely and had a whole set of imaging of the brain were included and further analyzed. A total of 54% of all patients with cerebral imaging had an available 18FDG-PET CT scan. We also recorded metastasis during treatment follow-up. There were 110 patients who had a whole set of imaging (CT = 89% and MRI = 11%) of the brain, and 54% of all patients with cerebral imaging had an available 18FDG-PET CT scan. We identified four patients with cerebral metastasis at the time of first diagnosis, which means that 5.4% of the cohort had cerebral metastasis and 13.3% of all patients in the subgroup with complete data of 18FDG-PET CT had distant non-cerebral metastasis. During the longitudinal follow-up, we found 11 patients with newly diagnosed metastases after a median time of 1.6 years (range: 2 months to 3.3 years) after first diagnosis without metastases. Distant metastases are more frequent in mesothelioma patients than previously thought. This implies that extensive staging is needed for patients selected for multimodal treatment, including brain imaging and 18FDG-PET CT.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma.

Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. To provide an updated overview of risk factors, prognosis, and management of CSRCC. A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.

Genomic landscape defines peritoneal metastatic pattern and related target of peritoneal metastasis in colorectal cancer.

The primary objective of this study is to develop a prediction model for peritoneal metastasis (PM) in colorectal cancer by integrating the genomic features of primary colorectal cancer, along with clinicopathological features. Concurrently, we aim to identify potential target implicated in the peritoneal dissemination of colorectal cancer through bioinformatics exploration and experimental validation. By analyzing the genomic landscape of primary colorectal cancer and clinicopathological features from 363 metastatic colorectal cancer patients, we identified 22 differently distributed variables, which were used for subsequent LASSO regression to construct a PM prediction model. The integrated model established by LASSO regression, which incorporated two clinicopathological variables and seven genomic variables, precisely discriminated PM cases (AUC 0.899; 95% CI 0.860-0.937) with good calibration (Hosmer-Lemeshow test p = .147). Model validation yielded AUCs of 0.898 (95% CI 0.896-0.899) and 0.704 (95% CI 0.622-0.787) internally and externally, respectively. Additionally, the peritoneal metastasis-related genomic signature (PGS), which was composed of the seven genes in the integrated model, has prognostic stratification capability for colorectal cancer. The divergent genomic landscape drives the driver genes of PM. Bioinformatic analysis concerning these driver genes indicated SERINC1 may be associated with PM. Subsequent experiments indicate that knocking down of SERINC1 functionally suppresses peritoneal dissemination, emphasizing its importance in CRCPM. In summary, the genomic landscape of primary cancer in colorectal cancer defines peritoneal metastatic pattern and reveals the potential target of SERINC1 for PM in colorectal cancer.

A comprehensive overview of metaplastic breast cancer: Features and treatments.

Metaplastic breast cancer is a rare, aggressive, and chemotherapy-resistant subtype of breast cancers, accounting for less than 1% of invasive breast cancers, characterized by adenocarcinoma with spindle cells, squamous epithelium, and/or mesenchymal tissue differentiation. The majority of metaplastic breast cancers exhibit the characteristics of triple-negative breast cancer and have unfavorable prognoses with a lower survival rate. This subtype often displays gene alterations in the PI3K/AKT pathway, Wnt/β-catenin pathway, and cell cycle dysregulation and demonstrates epithelial-mesenchymal transition, immune response changes, TP53 mutation, EGFR amplification, and so on. Currently, the optimal treatment of metaplastic breast cancer remains uncertain. This article provides a comprehensive review on the clinical features, molecular characteristics, invasion and metastasis patterns, and prognosis of metaplastic breast cancer, as well as recent advancements in treatment strategies.

A Prospective Observational Study on Patterns of Metastases and Clinical Profile of Carcinoma Cervix in Rural Population of Central India: A Tertiary Cancer Center Study

A Prospective Observational Study on Patterns of Metastases and Clinical Profile of Carcinoma Cervix in Rural Population of Central India: A Tertiary Cancer Center Study

Abstract PO4-04-05: HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations

Abstract Background: The exploration of heterogeneity in mBC has gained significant interest in optimizing therapeutic strategies. While the impact of differential HER2 IHC staining has been extensively studied in HER2-low neoplasms, limited data is available regarding IHC 2+ and IHC 3+ categories in HER2-pos mBC. The aim of our study is to compare, the clinical variables, metastatic patterns, and prognosis between patients classified as IHC 2+ and IHC 3+ in HER2-pos mBC. Methods: Pts with HER2 pos mBC, determined by HER2 IHC staining of 3+ or 2+ with amplification at the in situ hybridization assay, were selected from the GIM14 study database for analysis. Associations among variables were assessed by conducting logistic regression analyses. Additionally, prognostic factors for overall survival (OS) and time to treatment failure (TTF) were evaluated using both uni- and multi-variable Cox regression models. Results: A total of 766 HER2-pos mBC pts were included in the analysis. Among them, 302 (39%) had IHC score of 2+ and 464 (61%) had a IHC score of 3+. Central nervous system (CSN) metastases (mts) were observed in 68 (9%) pts (32% IHC 2+; 68% IHC 3+), lymph node (LN) mts in 330 (43%) pts (46% IHC 2+; 54% IHC 3+), lung (LU) mts in 182 (24%) pts (46% IHC 2+; 54% IHC 3+), liver (LI) mts in 227 (30%) pts (45% IHC 2+, 55% IHC 3+), skin (SK) mts in 68 (9%) pts (28% IHC 2+; 72% IHC 3+) and pleural (PL) mts in 40 (5%) pts (47% IHC 2+, 53% IHC 3+). In univariable (uni) analysis, IHC 3+ compared to IHC 2+ was significantly associated with SK mts (OR 1.76, P=0.043) and less likely to be associated with LI (OR 0.71, P=0.031), LU (OR 0.70, P =0.036), and LN (OR 0.63, P=0.002) mts. In multivariable (multi) analysis, LN mts maintained statistical significance (OR 0.62, P=0.004). In subgroup analysis, among IHC 3+ patients, factors associated with worse OS pts were neo Tx (HR 1.55, P=0.032), adjuvant radiotherapy (HR 1.34, P=0.042), neo ChT (HR 1.63, P=0.002), CNS mts (HR 1.98, P=0.002), and LI mts (HR 1.68, P&amp;lt; 0.0001). In multi analysis, CNS mts (HR 1.73, P=0.028) and LI mts (HR 1.47, P=0.017) remained prognostic for IHC 3+ subgroup. The only factor associated with worse OS in IHC 2+ pts was LI mts (HR 1.67, P=0.005). Multi analysis in the overall HER2-pos population identified neo chemotherapy (ChT) (HR 1.49, P=0.009), CNS mts (HR 1.53, P=0.003) and PL mts (HR 1.50, P=0.036) as negative prognostic factors for OS, while PL mts (HR 1.74, P=0.048) were associated with a shorter time to treatment failure (TTF). Conclusions: Our exploratory data revealed that HER2-pos mBC with a IHC score of 3+ is less likely to be associated with LN mts and with visceral mts. The site of mts has prognostic significance, as CNS mts are associated with worse OS in pts with an IHC score of 3+ pts, while LI mts are associated with worse OS in both IHC 2+ and 3+ subgroups. However, the IHC score itself (2+ or 3+) does not have independent prognostic value. The relationship between HER2 IHC staining and treatment outcomes requires further investigation to better understand its potential impact on clinical practice. Citation Format: Arianna Dri, Eva Blondeaux, Claudia Bighin, Simona Gasparro, Stefania Russo, Lorenzo Foffano, Palma Pugliese, Andrea Fontana, Enrico Cortesi, Antonella Ferzi, Ferdinando Riccardi, Valentina Sini, Luca Boni, Alessandra Fabi, Filippo Montemurro, Michelino De Laurentiis, Grazia Arpino, Lucia Del Mastro, Lorenzo Gerratana, Fabio Puglisi. HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-05.