Synchronous Metastases Research Articles

Aggressive surgical intervention may improve prognosis in patients with ovarian metastasis from colorectal cancer.

The current study aimed to investigate the prognostic clinicopathological factors of synchronous and metachronous ovarian metastasis (OM) from colorectal cancer (CRC) in patients with and without oophorectomy. Female patients with OM from CRC who underwent primary tumor resection at our institution from January 2013 to December 2020 were evaluated. Of 661 female patients, 22 (3.3%) were diagnosed with OM. Among 22 patients with OM, 12 underwent OM resection. Twenty (91%) patients had extra OM upon diagnosis. Thirteen (59%) patients in the non-surgery group had peritoneal dissemination at surgery or on computed tomography scan or positron emission tomography-computed tomography. Two patients in the OM surgery group had emergency surgery because of abdominal pain. Four patients had postoperative complications, and the median duration of hospital admission was 16.5days. The median survival time from OM diagnosis to mortality was 20.9months. Then, the association between the clinicopathological factors and overall survival (OS) was investigated. Tumor location and surgery were found to be related to OS (p = 0.03, 0.006, respectively) in the univariate analysis. However, only surgery was associated with OS (p = 0.02) in the multivariate analysis. Surgery is an important prognostic clinicopathological factor of OM from CRC. OM tumors should be resected because OM surgery is less likely to cause complications and symptoms.

Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.

Stage IV Rectal Cancer and Timing of Surgical Approach.

Liver metastases are seen in at least 60% of patients with colorectal cancer at some point during the course of their disease. The management of both primary and liver disease is uniquely challenging in rectal cancer due to competing treatments and complex sequence of treatments depending on the clinical presentation of disease. Recently, several novel concepts are shaping new treatment paradigms, including changes in timing, sequence, and duration of therapies combined with potential deescalation of treatment components. Overall, the treatment of this clinical scenario mandates multidisciplinary evaluation and personalization of care; however, there is still considerable debate regarding the timing of liver metastasectomy in the context of the overall treatment plan. Herein, we will discuss the current literature on management of rectal cancer with synchronous liver metastasis, current treatment approaches with respect to chemotherapy, and role of hepatic artery infusion therapy.

The map of bone metastasis in nasopharyngeal carcinoma: A real-world study.

The aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC). This study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi-squared test, Wilcoxon rank sum test, and Kaplan-Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression. Cohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p < 0.05). Patients with SBM had better overall survival (42.2 months, 95% CI: 33.9-50.7) than patients with MBM (24.9 months, 95% CI: 22.2-28.7). Age at bone metastasis detection, metastasis to other organs, and more bone metastasis locations were associated with worse prognosis. The majority of MBMs occurred at 7 to 18 months after NPC diagnosis. Radiotherapy does not modify the metastatic patterns of NPC bone metastases. Patients with SBM tend to have metastasis to the cervical vertebra, which is close to the nasopharynx. Paying more attention to bone metastases during follow-up in the first 2 years after an NPC diagnosis.

R1 Classic and Combined Approaches in Surgical Strategies for Management of Synchronous Colorectal Liver Metastasis

R1 Classic and Combined Approaches in Surgical Strategies for Management of Synchronous Colorectal Liver Metastasis

Efficacy of chemotherapy combined with surgical resection for gastric cancer with synchronous ovarian metastasis: A propensity score matching analysis.

Ovarian metastasis from gastric cancer (GC) is characterized by aggressive biological behavior and poor outcome. Currently, there is no standard treatment mode for such patients. Thus, we evaluated the efficacy of conversion therapy in patients with synchronous ovarian metastasis from GC in this study. About 219 GC patients with ovarian metastasis in 2011-2020 were enrolled. Two groups were established based on the different treatment: the conversion therapy group (chemotherapy combined with surgical resection, CS group) and the non-conversion therapy group (NCS group). Propensity score matching (PSM) was used to analyze the efficacy of different treatment modes on the prognosis of these patients. Ninety-two patients were included according to PSM results, with 46 patients each in CS and NCS groups. The median overall survival (OS) in the CS group was notably better than that in the NCS group (p < 0.001). Twenty-six patients (56.52%) in the CS group achieved R0 resection, and they had a better prognosis (p = 0.003). Compared with patients who underwent simultaneous gastrectomy and ovarian metastasectomy (CSb group), those who underwent ovarian metastasectomy before systemic chemotherapy (CSa group) had a higher R0 resection rate (p = 0.016) and longer survival time (p = 0.002). A total of 38 patients (41.30%) across both groups received hyperthermic intraperitoneal chemotherapy (HIPEC), and these patients had a better survival (p = 0.043). The conversion therapy is safe and effective for patients with synchronous ovarian metastasis from GC and can improve their prognosis. However, our results need to be confirmed by more randomized controlled clinical studies.

Primary Tumor Resection Plus Chemotherapy versus Chemotherapy Alone for Colorectal Cancer Patients with Synchronous Bone Metastasis.

Background and Objective: Colorectal cancer (CRC) bone metastasis (BM), particularly synchronous metastasis, is infrequent and has a poor prognosis. Radical surgery for CRC with BM is challenging, and chemotherapy is the standard treatment. However, it is unclear whether combining chemotherapy with primary tumor resection (PTR) yields greater survival benefits than chemotherapy alone, as no relevant reports exist. Material and Methods: The Surveillance, Epidemiology, and End Results (SEER) database provided data on 1662 CRC patients with bone metastasis between 2010 and 2018, who were divided into two groups: chemotherapy combined with PTR and chemotherapy alone. Survival distributions were compared using the log-rank test, and survival estimates were obtained using the Kaplan-Meier method. A Cox proportional multivariate regression analysis was conducted to estimate the survival benefit of chemotherapy combined with PTR while controlling for additional prognostic factors. Results: The chemotherapy only group consisted of 1277 patients (76.8%), while the chemotherapy combined with PTR group contained 385 patients (23.2%). Patients who received chemotherapy combined with PTR had a significantly higher 1-year survival rate (60.7%) and 2-year survival rate (32.7%) compared to those who only received chemotherapy (43.8% and 18.4%, respectively; p < 0.0001). Independent prognostic factors identified by Cox proportional analysis were age, location of the primary tumor, type of tumor, M stage, metastasectomy and PTR. Patients who received chemotherapy combined with PTR had a significantly improved prognosis (HR 0.586, 95% CI 0.497-0.691, p < 0.0001). All subgroups demonstrated a survival advantage for patients who received chemotherapy in combination with PTR. Conclusions: Our findings suggest that patients with BM from CRC may benefit from chemotherapy combined with PTR. Our analysis also identified age, location of the primary tumor, type of tumor, M stage, metastasectomy, and PTR as independent prognostic risk factors for CRC patients with synchronous BM.

Assessing synchronous ovarian metastasis in gastric cancer patients using a clinical-radiomics nomogram based on baseline abdominal contrast-enhanced CT: a two-center study

BackgroundTo build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases.MethodsPathologically confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model.ResultsThe nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts.ConclusionsThis pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.

Analysis of the effect of clinical and laboratory parameters on survival in patients with metastatic renal cell cancer with intermediate prognosis according to IMDC (International mRCC Database Consortium)

Introduction. Most patients with metastatic renal cell carcinoma (mRCC) who received systemic therapy are classified into as intermediate risk group according to the International mRCC Database Consortium (IMDC) assessment. However, survival differs in patients with one and two unfavourable prognostic risk factors.Objective. To analyze the impact of possible clinical and laboratory parameters on survival in mRCC patients with intermediate prognosis according to IMDC in the presence of one or two unfavourable prognostic risk factors.Materials &amp; methods. A retrospective analysis of data from 316 mRCC patients with intermediate prognosis receiving systemic therapy was carried out. The presence and effect on survival of the following laboratory parameters were compared: hemoglobin, neutrophil count, LDH, platelet count, alkaline phosphatase, serum calcium level, ESR, and emphasis was also placed on the time of metastases appearance. Overall survival (OS), post-progression survival (PPS), and 3- and 5-year survival were evaluated.Results. The overall 3- and 5-year survival rate for subgroups with one and two unfavourable prognostic risk factors were 85.2% ± 1.8% and 58.1 ± 1.6%; 79.1% ± 1.7% and 35.6  1.6%, respectively (p &lt; 0.001). Three- and 5-year PPS for both subgroups amounted to 66.1% ± 1.6% and 21.8% ± 1.4%; 45.2% ± 1.5% and 12.2% ± 1.3%, respectively (p &lt; 0.001). Median for OS was 61 and 51 months and PPS was 50 and 32 months respectively (p &lt;0.001). No statistically significant difference was found in the frequency of gradations of the investigated laboratory indicators with a predictive effect on prognosis, depending on the number of a unfavourable prognostic risk factors. There were also no significant differences in survival rates when laboratory parameters deviated from the normal, except for hemoglobin: OS in patients with one prognostic factor is significantly higher with normal hemoglobin (p &lt; 0.05). In the future, considering the absence of influence of the selected factors on survival rates with their obvious significant differences in patients with one and two prognostic factors, the influence of the time of appearance of metastases (synchronous / metachronous) was analysed: all survival parameters were significantly worse in patients with synchronous metastases. Furthermore, OS in patients with metachronous metastases with the same relapse-free period was significantly better in patients with one prognostic factor according to IMDC.Conclusions. The presence of one or two prognostic factors significantly affects the indicators of 3 and 5-year overall survival and PPS in patients with an intermediate prognosis of mRCC, while laboratory parameters do not affect survival, except for hemoglobin levels, the time of metastases appearance has a significant effect, and the time of metastases appearance has a significant effect.

Prediction of synchronous distant metastasis of primary pancreatic ductal adenocarcinoma using the radiomics features derived from 18F-FDG PET and MRI

To explore the potential of the joint radiomics analysis of positron-emission tomography (PET) and magnetic resonance imaging (MRI) of primary tumours for predicting the risk of synchronous distant metastasis (SDM) in patients with pancreatic ductal adenocarcinoma (PDAC). 18F-FDG PET and MRI images of PDAC patients from January 2011 to December 2020 were collected retrospectively. Patients (n=66) who received 18F-FDG PET/CT and MRI were included in a development group. Patients (n=25) scanned with hybrid PET/MRI were incorporated in an external test group. A radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm to select PET-MRI radiomics features of primary PDAC tumours. A radiomics nomogram was developed by combining the radiomics signature and important clinical indicators using univariate and multivariate analysis to assess patients' metastasis risk. The nomogram was verified with the employment of an external test group. Regarding the development cohort, the radiomics nomogram was found to be better for predicting the risk of distant metastasis (area under the curve [AUC]: 0.93, sensitivity: 87%, specificity: 85%) than the clinical model (AUC: 0.70, p<0.001; sensitivity:70%, specificity: 65%) and the radiomics signature (AUC: 0.89, p>0.05; sensitivity: 65%, specificity:100%). Concerning the external test cohort, the radiomics nomogram yielded an AUC of 0.85. PET-MRI based radiomics analysis exhibited effective prediction of the risk of SDM for preoperative PDAC patients and may offer complementary information and provide hints for cancer staging.

Clinical relevance of biomarker discordance between primary breast cancers and synchronous axillary lymph node metastases

Clinical decision-making for patients with breast cancer (BC) is still primarily based on biomarker characteristics of the primary tumor, together with the evaluation of synchronous axillary lymph node metastasis (LNM). In this study, we investigated the prevalence of discordance in the biomarkers and surrogate subtyping between the primary BC and the LNM, and whether subsequent changes would have altered clinical treatment recommendations. In this retrospective study, 94 patients treated for unifocal primary BC and synchronous LNM at Sahlgrenska UniversityHospital during 2018 were included. Estrogen (ER) and progesterone (PR) receptor, Ki67, and HER2 status were assessed in the primary tumor and LNM using immunohistochemistry. Discordances between the primary tumor and the LNM were analyzed for each individual biomarker and surrogate subtyping. The concordance between the primary tumor and the LNM for ER, PR, Ki67, and HER2 status was 98.9%, 89.4%, 72.3%, and 95.8%, respectively. Discordance in surrogate subtyping was found in 28.7% of the tumors and matched LNMs, the majority (81.5%) of which changed to a more favorable subtype in the LNM; most commonly from Luminal B to Luminal A (48.6%). No changes in surrogate subtyping were detected where ER or HER2 status changed from negativity in the BC to positivity in the LNM, thereby showing no additional value in performing immunohistochemistry on the LNM from a treatment decision-making perspective. However, large studies need to be performed that test both the primary BCs and synchronous LNMs for more accurate diagnostics.

Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

Minimally invasive vs. open approach to the simultaneous treatment of colorectal tumors with synchronous liver metastasis: a single center, propensity-score matched analysis from Mayo clinic

BackgroundOpen combined resections of colorectal primary tumors and synchronous liver metastases have become common in selected cases. However, evidences favoring a minimally invasive (MIS) approach are still limited. The aim of this study is to evaluate the outcomes of MIS vs. open synchronous liver and colorectal resections. Methods384 cases of synchronous colorectal and liver resections performed at one institution were identified during the study period. MIS vs open approach were compared after a propensity score matching; surgical outcomes were analyzed. ResultsMIS cases featured longer operative time (399 vs 300 min, p < 0.001), fewer blood loss (200 vs 500 ml, p = 0.003), and shorter hospitalization (median LOS 4 vs 6 days, p = 0.001). No difference was observed between the two groups for use of Pringle maneuver (p = 0.083), intraoperative blood transfusion (p = 0.061), achievement of negative colorectal (p = 0.176) and liver margins (p = 1.000), postoperative complications (p = 1.000) and significant (Clavien-Dindo ≥ 3a) complications (p = 0.817), delay of adjuvant therapy due to complications (p = 0.555), 30- and 90-day mortality. ConclusionSynchronous colorectal and liver metastases resections via a minimally-invasive approach in high-volume centers with appropriate expertise result in significantly lower blood loss and length of stay despite longer operative time in comparison to open, with no oncological inferiority.

Detection of the high-risk factors for synchronous bone metastasis in tonsillar squamous cell carcinoma.

To analyze the risk factors for synchronous bone metastases (BM) in patients with tonsillar squamous cell carcinomas. Tonsillar carcinomas patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2013. We examined the association between risk factors and synchronous BM using Chi-squared tests. Predictors of survival rates were assessed using univariate and multivariate analyses. A total of 5752 patients were analyzed, which including 35 patients (0.6%) with synchronous BM, and 5717 patients without synchronous BM (99.4%). Multivariate logistic regression analysis showed that Caucasian, lower T or N classification were associated with a significantly lower risk of BM (P < 0.05, respectively). Elderly not married non-Caucasian patients with highly differentiated disease, higher T or N classification, multiple sites of metastases and no surgical therapy to primary tumor were more likely to reduce life expectancy. By analyzing data from a large cohort, Caucasian, lower T or N classification were associated with a significantly lower risk of BM. Elderly not married non-Caucasian patients with highly differentiated disease, higher T or N classification, multiple sites of metastases and no surgical therapy to primary tumor were more likely to reduce life expectancy. More accurate assessments of BM will be imperative for early diagnosis and treatment in non-Caucasian tonsillar carcinoma patients who harbored with higher T or N classification.

Lateral neck dissection for the treatment of synchronous and metachronous lateral neck metastasis of N1b papillary thyroid cancer.

Metachronous lateral neck recurrence after thyroidectomy for N1b papillary thyroid cancer is accompanied by high morbidity and increased difficulty of reoperation. From the perspective of recurrence, the objective of this study was to compare patients who underwent metachronous lateral neck dissection (mLND) despite initial thyroidectomy and patients who underwent synchronous lateral neck dissection (sLND) for papillary thyroid cancer and analyze the risk factors for recurrence after mLND. This retrospective study involved 1,760 patients who underwent lateral neck dissection for papillary thyroid cancer at the Gangnam Severance Hospital, a tertiary medical center in Korea, from June 2005 to December 2016. The primary outcome was structural recurrence, and secondary outcome measures were risk factors of recurrence in the mLND group. A total of 1,613 patients underwent thyroidectomy and sLND at diagnosis. In 147 patients, thyroidectomy alone was performed at the time of diagnosis, and mLND was performed when recurrence to the lateral neck lymph node was confirmed. During a median follow-up of 102.1 months, 110 (6.3%) patients experienced a recurrence. There was no significant difference in the recurrence between the sLND and mLND groups (6.1% vs 8.2%, P=.32). The period from lateral neck dissection to recurrence was longer in the mLND group than in the sLND group (113.6 ± 39.4 months vs 87.0 ± 33.8 months, respectively, P<.001). Age ≥50 years (adjusted HR=5.209, 95% CI=1.359-19.964; P=.02), tumor size >1.45cm (adjusted HR=4.022, 95% CI=1.036-15.611; P=.04), and lymph node ratio in the lateral compartment (adjusted HR=4.043, 95% CI=1.079-15.148; P=.04) were independent variables predictive of recurrence after mLND. mLND is suitable for treating lateral neck recurrence in patients with N1b papillary thyroid cancer who previously underwent thyroidectomy. Lateral neck recurrence after treatment in patients who underwent mLND was predicted by age, tumor size, and lymph node ratio in the lateral compartment.

The different clonal origins of metachronous and synchronous metastases

BackgroundMetastases are the leading cause of mortality in cancer patients. Linear and parallel are the two prominent models of metastatic progression. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The aim of the study was to determine whether synchronous metastases (SM) and metachronous metastases (MM) differ only in lead-time or stem from different biological processes.Materials and methodsWe retrospectively studied the chest CTs of 791 patients inflicted by eleven malignancy types that were treated in our institution in the years 2010–2020. Patient’s population included 396 with SM and 395 with MM. The diameter of 15,427 lung metastases was measured. Clonal origin was deduced from the linear/parallel ratio (LPR)-a computerized analysis of metastases diameters. LPR of 1 suggests pure linear dissemination and − 1 pure parallel.ResultsPatients with MM were significantly older (average of 62.9 vs 60.7 years, p = 0.02), and higher percentage of them were males (58.7% vs 51.1%, p = 0.03). Median overall survival of patients with MM and SM was remarkably similar (23 months and 26 months respectively, p = 0.774) when calculated from the time of metastases diagnosis. Parallel dissemination (LPR ≤ 0) was found in 35.4% of patients with MM compared to only 19.8% of the patients with SM (p < 0.00001).ConclusionPatients with SM and MM differ in demography and in clonal origin. Different therapeutic approaches may be considered in these two conditions.

Prognostic impact of R1 resection margin in synchronous and simultaneous colorectal liver metastasis resection: a retrospective cohort study

BackgroundA margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM.MethodsA total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching.ResultsThe R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival.ConclusionsThe R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era.

Comparison of genetic variation between primary colorectal cancer and metastatic peritoneal cancer.

Among cancer metastases by primary colorectal cancer (CRC), peritoneal metastasis is the second most common metastatic lesion after liver metastasis. In treating metastatic CRC, it is very important to differentiate targeted-therapy and chemotherapy according to the characteristics of each lesion because the genetic variation of the primary and metastatic lesions are different. However, there are few studies of genetic characteristics on peritoneal metastasis caused by primary CRC, so molecular-level studies are continuously required. We propose an appropriate peritoneal metastasis treatment policy by identifying the genetic characteristics between primary CRC and synchronous peritoneal metastatic lesions. Primary CRC and synchronous peritoneal metastasis samples were analyzed in pairs from six patients using Comprehensive Cancer Panel (409 cancer-related genes, Thermo Fisher Scientific, USA) and next-generation sequencing (NGS). The mutations were commonly found on the KMT2C and THBS1 genes in both primary CRC and peritoneal metastasis. The PDE4DIP gene was mutated in all cases except for on a sample of peritoneal metastasis. As a result of analysis using the mutation database, we confirmed that the gene mutations of primary CRC and the peritoneal metastasis derived from it showed the same tendency, although we did not accompany the gene expression level or epigenetic study. It is thought that the treatment policy through molecular genetic testing of primary CRC can also be applied to peritoneal metastasis treatment. Our study is expected to be the basis for further peritoneal metastasis research.

Incidence, survival, and associated factors estimation in osteosarcoma patients with lung metastasis: a single-center experience of 11 years in Tianjin, China

BackgroundOsteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis.MethodsFrom February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. The Cox proportional hazard regression analysis was performed to analyze the prognostic factors of all osteosarcoma patients and those patients with lung metastasis, respectively. Furthermore, risk factors for developing lung metastasis were identified in synchronous lung metastasis (SLM) and metachronous lung metastasis (MLM) patients.ResultsA total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteosarcoma was 70.0% and the survival months for patients with SLM and MLM were 33.3 ± 12.6 and 45.8 ± 7.4 months, respectively. The presence of lung metastasis was one of the independent prognostic factors for prognosis of osteosarcoma. In patients with lung metastasis, twenty-one (10.3%) showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) were diagnosed with lung metastases during the later course. T3 stage (OR = 11.415, 95%CI 1.362–95.677, P = 0.025) and bone metastasis (OR = 6.437, 95%CI 1.69–24.51, P = 0.006) were risk factors of SLM occurrence. Bone metastasis (OR = 1.842, 95%CI 1.053–3.224, P = 0.032), good necrosis (≥ 90%, OR = 0.032, 95%CI 0.050–0.412, P < 0.001), elevated Ki-67 (OR = 2.958, 95%CI 1.098–7.969, P = 0.032) and elevated LDH (OR = 1.791, 95%CI 1.020–3.146, P = 0.043) were proved to be independent risk factors for developing MLM.ConclusionThe overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.

Abstract IA006: Overcoming complex polyclonality for accurate clinical genotyping in metastatic prostate cancer

Abstract Background: De novo metastatic castration-sensitive prostate cancer (mCSPC) is highly aggressive, but the lack of routine tumor tissue in this setting hinders genomic stratification and jeopardizes precision oncology efforts. Accurate molecular profiling at diagnosis is important for future genomics-informed risk stratification strategies and biomarker-guided treatment. Currently, it is unclear the extent that intrapatient tumor heterogeneity impacts clinical cancer genotyping. Methods: We performed genomic profiling of 607 synchronous primary foci, metastatic lesions, and plasma cell-free DNA from a rare clinical trial cohort of 43 patients with de novo mCSPC who underwent radical prostatectomy at diagnosis. Surgery is not currently standard practice in this disease setting. All samples were subjected to targeted DNA sequencing using a bespoke prostate cancer-specific panel and a subset were also subjected to whole-exome sequencing. Results: Sequencing-derived tissue tumor fraction was highly heterogeneous between samples, and was below 40% across all foci in approximately 20% of patients, potentially precluding routine detection of key classes of clinically-relevant biomarkers. In samples with high tumor fraction, the genomic landscape of mCSPC closely resembled metastatic castration-resistant prostate cancer. In same-patient samples, intra-prostate heterogeneity in mutation, copy number, and whole-genome duplication was pervasive and affected tumor suppressor genes including PTEN, TP53, and RB1. Phylogenetic modeling demonstrated additional complexity in several patients driven by polyclonal metastatic seeding from the reservoir of primary populations. While the metastatic clones were often identified in the primary site, frequent discordance between select primary foci and synchronous metastases in clinically-relevant genes, plus highly variable per-sample tumor fraction, resulted in false genotyping of the dominant disease, when relying on a single tissue focus. However, in silico modeling demonstrated that analysis of multiple prostate diagnostic biopsy cores can rescue misassigned somatic genotypes. Conclusions: Our work reveals extensive polyclonality that undermines standard precision genotyping in de novo mCSPC, nominates practical strategies for improved biomarker profiling and genomics-informed risk stratification and offers deep biological insight into the relationship between primary and untreated metastases. Citation Format: Alexander W. Wyatt, Andrew J. Murtha, Evan Warner, Kim Van der Eecken, Edmond M. Kwan, Cameron Herberts, Joonatan Sipola, Sarah W.S. Ng, Xinyi E. Chen, Nicolette M. Fonseca, Elie Ritch, Elena Schönlau, Cecily Q. Bernales, Gráinne Donnellan, Kevin Beja, Amanda Wong, Sofie Verbeke, Nicolaas Lumen, Jo Van Dorpe, Bram De Laere, Matti Annala, Gillian Vandekerkhove, Piet Ost. Overcoming complex polyclonality for accurate clinical genotyping in metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA006.