Primary Tumor Location Research Articles

The Profile of Sinonasal Tumors with Orbital Involvement in Dr. M. Djamil General Hospital, Padang, Indonesia: A 10-Year Overview

Background: Sinonasal tumors are rare tumors, either malignant or benign, that vary greatly based on the origin and primary tumor location in the sinonasal tract. The close anatomical relationship between the sinonasal tract and the orbital cavity makes orbital involvement very common (50%-80%) in sinonasal tumors, and this indicates a negative prognostic factor in sinonasal malignancy. The purpose of this study is to demonstrate the profile of sinonasal tumors with orbital involvement in our center.
 Methods: Retrospective study from oncology subdivision files and medical records from January 2011 – December 2020. Collected data including age, gender, the clinical manifestations of orbital involvement, primary location, histopathology, and management of sinonasal tumors.
 Results: There were 35 patients examined by the oncology subdivision either directly came or consulted from the ENT department, consisting of 18 (51.4%) males and 17 (48.6%) females. The age of patients ranged from 11 to 83 years old. with the most common age groups being 41-50 and 51-60 (25.7% in each age group). The majority of the patients (77.1%) had presented with proptosis. Maxillary sinus was the most common (45.7%) primary site of tumors, and squamous cell carcinoma was the most common (51.4%) histopathology found. Most of the patients (37.1%) were treated with a combination of chemotherapy and radiotherapy.
 Conclusion: Orbital involvement commonly occurs in malignant sinonasal tumors with proptosis as a major clinical presentation. A combination of chemotherapy and radiotherapy was the most common practice management because the tumors were unresectable at the time of presentation.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P=0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P=0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P=0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P=0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P<0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P<0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P=0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P<0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P=0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P=0.164). In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Development and validation of a novel model to predict recurrence-free survival and melanoma-specific survival after sentinel lymph node biopsy in patients with melanoma: an international, retrospective, multicentre analysis

The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage. Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve [AUC]) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia). The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3-7·8) in the development cohort and 5·0 years (2·2-8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0-75·1) and 5-year melanoma-specific survival was 86·5% (85·3-87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6-67·7) and 83·3% (82·0-84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78-0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79-0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71-0·75) and 0·76 (0·74-0·78), respectively. Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas. Erasmus Medical Centre Cancer Institute.

A prediction model for lung metastases in patients with indeterminate pulmonary nodules in newly diagnosed colorectal cancer

IntroductionMultidisciplinary teams treating patients with newly diagnosed Colorectal Cancer (CRC) often encounter the appearance of Indeterminate Pulmonary Nodules (IPNs) that warrants follow–up with repetitive medical imaging and anxiety for patients. We determined the incidence of IPNs in patients with newly diagnosed CRC and developed and validated a model for individualized risk prediction of IPNs being lung metastases. Material and methodsNewly diagnosed CRC who underwent surgery between November 2011 to June 2014 were included to create the risk model, developed using both clinical experience and statistical selection. Discrimination and calibration slopes of the risk score were evaluated in an independent temporal validation sample. A nomogram is presented to assist clinicians in estimating an individual risk score. ResultsOut of 2111 CRC patients staged with chest CT, 204 (9.6%) had IPNs and 54/204 (26%) had lung metastases. We identified 4 predictors: “location of primary tumour”, “pathological nodal stage”, “size of the largest nodule” and “extrapulmonary synchronous metastases at diagnosis”. Discrimination of the final model in the validation sample was demonstrated by the difference in mean predicted risk between progressed cases en non-progressed cases (49% versus 21%, p = <0.001). ConclusionA prediction model with 4 clinical risk factors can be used to assist multidisciplinary teams in the prediction of individualized risk of lung metastases and imaging strategy in patients with IPNs and newly diagnosed colorectal cancer. The model performed well in new patients not included in the model development.

Clinicopathologic comparison of basal cell carcinoma among a diverse patient population in Los Angeles County.

Basal cell carcinoma (BCC) is the most common malignancy in the United States. The majority of cases are identified in Non-Hispanic Whites (NHW) and are far less demonstrated in patients of colour (POC). However, the Hispanic population represents a large and growing proportion of the US population, and skin cancer diagnoses in Hispanics are rising. Thus, the goal of this study is to examine clinicopathologic differences between BCC in Hispanics versus NHW. A retrospective chart review of Hispanic and NHW patients with BCC at Los Angeles County+USC Medical Center from January 2018 to March 2020 was performed. In total, 101 BCC samples from the first 100 patients identified of Hispanic ancestry, as well as 50 BCC samples identified from the first 50 patients identifying as NHW, were included for analysis. Patient characteristics (age, sex, medical history, and ethnicity), as well as tumour characteristics (location, subtype, tumour depth, and perineural invasion), were collected. We used between subjects t-tests for continuous variables, and chi-square tests for categorical variables. In total, 151 specimens were collected amongst 122 subjects (79 Hispanics and 43 NHW patients). Among NHW, the majority of patients (74.4%) were men, but among the Hispanic population, the majority (68.4%) were female (p<0.001). Prior history of other skin cancer was more common among NHW (67.4%) than Hispanics (31.6%) (p=<0.001). The Hispanic population had a significantly higher proportion of head and neck tumours (p=0.0004) but a lower proportion of extremity tumours (p=0.001) compared to NHW. Pigmented BCC was significantly more common among Hispanic patients (p<0.01). Finally, within the Hispanic group, there was a significant association between sex and histology (p=0.004), with Hispanic men demonstrating more aggressive mix histology compared to Hispanic women. Our study supports the notion that BCC disparities occur among POC compared to NHW. This includes variations in epidemiologic factors such as sex and past medical history, primary tumour location, and pathologic characteristics. Further research should be conducted to identify additional differences in skin cancer presentation in POC to reduce the gaps in skin cancer knowledge and care.

Abstract 6400: Tislelizumab combined with XELOX as a neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinomas: A prospective, phase II trial

Abstract Background: Combing anti-PD-(L)1 antibody with chemotherapy in neoadjuvant therapy of gastric/gastroesophageal junction (G/GEJ) adenocarcinomas is a promising strategy, but clinical data are remain insufficient. Whether immunotherapy biomarkers in previous studies (TMB, MSI, PD-L1, etc.) have equivalent predictive value for G/GEJ remains to be verified. In this phase II clinical trial of tislelizumab in combination with chemotherapy, potential therapy-related biomarkers in tumor samples, and changes in the tumor microenvironment during treatment were analyzed, and a predictive model for efficacy was developed. Methods: This was a prospective, single-center, single-arm, phase II trial. Patients with G/GEJ adenocarcinomas (stage cT3-4aN+M0) were treated with PD-1 inhibitor tislelizumab in combination with oxaliplatin plus capecitabine (XELOX) as neoadjuvant treatment for 2 or 3 cycles. The primary endpoint was the major pathological response (MPR). The secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, and safety. Tumor samples underwent RNA-sequencing (Amoy Diagnostics Co Ltd, Xiamen, China), to identify potential biomarkers, and a predictive model was developed to explore factors influencing tumor response and survival. Results: 28 patients were enrolled; mean age was 59.5 years (SD = 8.2), 19 (67.9%) patients were male; 14 (50.0%) patients with primary tumor location in the stomach, and 14 (50.0%) patients with primary tumor location in the GEJ. All patients were EB virus negative. Except one patient with PMS2 loss, 27 patients were pMMR. Nine (32.1%) patients achieved MPR after treatment, with four (14.3%) of them achieved pCR. The R0 resection rate was 96.4%, with 14 (50.0%) patients achieved objective response. No serious adverse events were reported. The most common grade 2 TRAEs during neoadjuvant treatment were anemia (5 of 28, 17.86%) and nausea (3 of 28, 10.71%). Analysis of differentially expressed genes revealed enrichment of the antigen processing and presentation pathway in the MPR group, while the TGF-β signaling pathway was enriched in the non-MPR group. Notably, the differential immune microenvironment analysis also uncovered significant differences in the TGF-β signature between the MPR and non-MPR groups. Additionally, a therapeutic response prediction model (HT score) was developed with an AUC of 0.98 (0.932-1) in the training set, and its performance was validated in publicly available datasets. Conclusion: Tislelizumab combined with XELOX holds promise as a neoadjuvant therapy for resectable G/GEJ adenocarcinomas, especially for EBV- and pMMR population, offering a well-tolerated safety profile. Moreover, the HT score has the potential to predict treatment efficacy in this regimen. Trial registration numbers: NCT05507658 and NCT05508399. Citation Format: Haikun Zhou, Tao Han, Lei Tuo, Qingchuan Yang, Ruiqi Gao, Pengfei Yu, Jiangpeng Wei, Changbin Zhu, Jin Wang, Peng Cheng, Xiang Kang, Sihui Pi, Hui Liu, Xiaoxi Pan, Xiaohua Li, Gang Ji. Tislelizumab combined with XELOX as a neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinomas: A prospective, phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6400.

Abstract 4979: Genomic profiling of early-onset metastatic colorectal cancer based on tumor sample location

Abstract Background: Here, we describe analyses towards identifying and comparing genetic variations between the primary and metastatic sites in early-onset metastatic colorectal cancer patients. Methods: We selected patients with early-onset metastatic colorectal cancer (under 50 years old) using data from the American Association for Cancer Research Project GENIE (version 14.1). We used the Fisher exact test to compare genetic mutations between the primary tumor and metastatic sites, complemented by the Benjamini-Hochberg adjustment method. Results: In a total of 1,791 patients with early-onset metastatic colorectal cancer, 27.1% had tumor samples from metastatic sites, while the majority, 72.9%, were from the primary tumor location. The most common mutations found were in the TP53 gene (77.6%), followed by APC (76.0%), KRAS (42.4%), and PIK3CA (19.0%). Notably, the metastatic samples had a significantly higher occurrence of SMAD4 mutations compared to their primary site counterparts (20.8% vs. 14.0%, p&amp;lt;0.001, q&amp;lt;0.001). Conversely, the primary tumor samples exhibited higher frequencies of TCF7L2 and ARID1A mutations (16.9% vs. 10.6%, p&amp;lt;0.001, q&amp;lt;0.001, and 13.0% vs. 6.4%, p&amp;lt;0.001, q&amp;lt;0.001, respectively). Conclusion: Determining the specific genes responsible for the formation of metastatic tumors is crucial for a deeper understanding of the disease's underlying biology in early-onset metastatic colorectal cancer. Such genomic details are crucial to pave the way to the discovery of potential biomarkers for diagnosis and the development of new cancer therapeutics. Citation Format: Muhammet Ozer, Suleyman Y. Goksu, Busra Bacik Goksu, Nina N. Sanford, Amy Jones, Nilesh Verma, Syed Kazmi. Genomic profiling of early-onset metastatic colorectal cancer based on tumor sample location [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4979.

Abstract 3779: Genomic and clinical characterization of metastatic patterns using real-word data from a large cohort of colorectal cancer patients

Abstract Background: Colorectal cancers (CRCs) can exhibit disparate metastatic patterns that affect outcomes. We investigated associations between genomic features and organ-specific metastatic tropism and we compared the frequency of actionable alterations detected in patients undergoing longitudinal clinical sequencing. Methods: We analyzed data for 6574 tumors from 6153 CRC patients, including 4510 primary and 2064 metastatic specimens. All patients had microsatellite stable (MSS) disease and were treated at Memorial Sloan Kettering. Paired primary and metastatic samples were available for 203 patients. Tumors were sequenced with MSK-IMPACT, a targeted DNA sequencing assay that identifies genomic alterations in 341-505 genes. Clinical annotations included sex, stage at diagnosis (Dx), and primary tumor location. History of metastatic disease was automatically retrieved from radiology reports using validated natural language processing methods; time to specific-site metastasis was modeled with Cox regression. False discovery rate (FDR) was used to correct for multiple hypothesis testing. The OncoKB knowledge base was used to identify clinically actionable alterations. Results: Liver (n=1068, 51.7%), peritoneal (n=269, 13.0%) and lung metastases (n=263, 12.7%) accounted for the majority of non-primary sequenced specimens. The frequency of actionable alterations (OncoKB Level≥3A) did not vary between unmatched metastatic and primary samples (12.3% vs 11.4%, p=0.302). In primary tumor samples from patients with localized disease at the time of diagnosis, TGFB pathway alterations were associated with increased risk of metastasis to the brain (HR=2.41, p=0.028), bone (HR=2.10, p&amp;lt;0.001), peritoneum (HR=1.82, p=0.001) and liver (HR=1.42, p=0.049). Alterations in the RAS pathway were associated with increased risk of lung (HR=1.47, p=0.009), peritoneum (HR=1.54, p=0.021) and liver (HR=1.44, p=0.026) metastases. By contrast, WNT pathway alterations were associated with a lower risk of developing lung (HR=0.69, p=0.033) and peritoneal metastasis (HR=0.68, p=0.081). Among patients with paired primary and metastatic samples, no significant difference was observed between the frequency of clinically actionable alterations in primary vs. metastatic specimens (16.7% vs. 18.2%, p=0.794). Presence of metastases-private or primary-private alterations did not correlate with site-specific metastasis risk. Conclusions: The risk of developing metastatic disease and organ-specific dissemination might be linked to genomic abnormalities detectable at the localized stage. No significant difference in the frequency of actionable alterations was observed between primary and metastatic CRC samples. Citation Format: Paolo Manca, Ayush V. Kris, Henry Walch, Christopher Fong, Justin Jee, Karl Pichotta, Nikolaus Schultz, Walid K. Chatila, Rona Yaeger, Francisco Sanchez-Vega. Genomic and clinical characterization of metastatic patterns using real-word data from a large cohort of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3779.

Abstract 925: Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection

Abstract Introduction: Anti-EGFR monoclonal antibody plus doublet chemotherapy is the mainstay of first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Some of these patients might undergo secondary resection. However, there is no standardized suggestion on whether colorectal cancer liver metastasis patients should keep target therapy after secondary resection. NCCN guidelines suggest chemotherapy only in patients receiving primary liver resection. Whether we could spare the use of target therapy after secondary resection is the main aim of our study. Methods: Using Taiwan's National Health Insurance Research Database, we established a cohort of KRAS wild-type mCRC patients treated with first-line anti-EGFR therapy plus doublet chemotherapy between 2013 and 2018. Secondary surgery was defined as either resection of liver metastases or radiofrequency ablation. Results: 5694 stage IV mCRC patients received anti-EGFR MAb plus doublet chemotherapy as a first-line treatment between 2013 and 2018. 174 patients were enrolled in the final analysis, with 153 continuing anti-EGFR MAb after secondary resection and 21 patients without anti-EGFR MAb. Compared with those who without anti-EGFR therapy after secondary resection, patients who continued anti-EGFR MAb exhibited significantly longer overall survival (OS; median, 43.8 vs. 31.9 months, p = 0.031) but not in time to treatment failure (TTF; median, 22.2 vs. 26.6 months, p = 0.841). The OS benefits of continuing anti-EGFR MAb remained regardless of left-sided or right-sided primary tumors (40.9 vs. 43.0 months, p = 0.980). The patient cohort from 2016 to 2018 showed more prolonged survival than from 2012 to 2015 (not reached vs. 40.450, p = 0.0305). TTF has no statistical difference when considering patient cohort or primary tumor location. In multivariate analyses, continuing first-line anti-EGFR MAb therapy after secondary resection remained an independent predictor of longer OS. Conclusion: For mCRC patients who received secondary resection after first-line anti-EGFR and doublet chemotherapy, continuing anti-EGFR MAb after resection was associated with significantly longer OS regardless of primary tumor sidedness. Citation Format: Yao-Yu Hsieh, Chin-Wen Tsai, T-CARE Group, Yi-Hsieh Liang. Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 925.

Abstract 4976: The impact of obesity on survival in epithelial gynecological tumors

Abstract Background: The impact of obesity on the survival of patients with epithelial gynecological tumors is not yet clear. We aim to elucidate the impact of body mass index (BMI) on epithelial gynecological tumors in a large tertiary center at Saudi Arabia. Methods: We retrospectively reviewed the medical files of all patients with pathologically confirmed epithelial gynecological tumors at our center. Then, we assessed the difference in overall survival (OS) according to primary tumor location, BMI, stage at presentation, and performance status (PS) at presentation using log-rank tests. Results: 400 patients were included in the analysis. The mean age at diagnosis was 56.1±13 years. 242 (60.5%) patients were diagnosed with uterine carcinomas, 137 (34.3%) with ovarian carcinomas, and 21 (5.3%) with cervical carcinomas. 278 (69.5%) patients were obese at presentation, 74 (18.5%) were overweight, 43 (10.8%) were within normal range, and 7 (1.8%) were underweight. The PS at presentation was 0, 1, 2, 3, and 4 in 351 (87.8%), 17 (4.3%), 10 (2.5%), 16 (4%), and 6 (1.5%) patients, respectively. Cervical cancer was associated with long OS, while ovarian cancers demonstrated poor prognosis (p=0.0159). There was no difference in OS between different BMI groups (p=0.072). Patients with stage 4 cancers had significantly shorter OS (p&amp;lt;0.0001). Patients with PS 4 at presentation was associated with the worst prognosis (p&amp;lt;0.0001). Interpretation: Shorter OS was associated with ovarian carcinomas, advanced staging, and poor PS at presentation. BMI classification had no impact on OS. Further studies are needed to confirm our findings. Citation Format: Ahmed Badran, Mahmoud Elshenawy, Waleed Fallatah, Abdullaah K. Hinkston, Saad S. Ali, Mohammed Ali Omar, Abdulaziz M. Alaklabi, Hytham M. Abdalla, Tarek Z. Arabi, Belal N. Sabbah, Hamed Alhusaini. The impact of obesity on survival in epithelial gynecological tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4976.

Abstract 3467: Tumor immune and microbial characteristics of colorectal cancer according to age at diagnosis and detailed anatomical location

Abstract Background: Colorectal cancer is a heterogeneous disease, exhibiting spectra of tumor characteristics that vary across age at diagnosis and anatomical location. We hypothesized that tumor immune and microbial characteristics of colorectal cancer might change with age at diagnosis and detailed anatomical location. Methods: We utilized a pooled dataset of colorectal cancer cases (N= 958 to1413 depending on variables) with available immune cell density or microbial data in the Nurses' Health Study, Health Professionals Follow-up Study, and Ontario Familial Colon Cancer Registry. We examined whether there were statistically significant trends in tumor immune and microbial according to age at diagnosis and detailed primary tumor location (cecum, ascending, hepatic flexure, transverse, splenic flexure, descending, sigmoid, rectosigmoid, rectum) using Spearman’s correlation test. The densities of immune cells were determined by using multiplex immunofluorescence, including T cells (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3) and macrophages (CD68, M1-like, and M2-like) in tumor intraepithelial and stromal regions. We conducted stratified analyses by microsatellite instability (MSI) status. Results: The density of memory (both CD4+ and CD8+) T cells in tumor epithelial areas continuously increased as age at diagnosis increased (P for trend &amp;lt;0.005). Compared to later-onset colorectal cancer, early-onset colorectal cancer had a lower density of memory T-cells. With respect to tumor site, CD3+CD4+ and CD3+CD8+ T densities in tumor epithelial areas were highest in the cecum compared to other subsites, and there was a statistically significant decreasing trend from the cecum to rectum (P for trend &amp;lt;0.005). We also observed significant decreasing trends for CD68+, M1-like, and M2-like macrophage densities in combined tumor (intraepithelial and stromal) regions from the cecum to rectum (P for trend &amp;lt;0.005). The proportion of F. nucleatum-positive colorectal cancers gradually decreased from the cecum to rectum (P for trend &amp;lt;0.005). Similar trends were observed in separate analyses in non-MSI-high cases. Conclusions: This study suggests that certain tumor immune and microbial characteristics in the tumor microenvironment, specifically T cell and macrophage densities and Fusobacterium nucleatum positivity, change gradually according to age at diagnosis and/or detailed anatomical location. Age and anatomical location spectra in tumor immune and microbial characteristics will shed light on the etiology of colorectal cancer (including early-onset colorectal cancer), leading to better-personalized cancer prevention and treatment. Citation Format: Tomotaka Ugai, Yasutoshi Takashima, Yuxue Zhong, Juha P. Väyrynen, Daniel Buchanan, Jeroen Huyghe, Li Hsu, Conghui Qu, Sushma Thomas, Claire Thomas, Steve Gallinger, Robert Grant, Ulrike Peters, Amanda I. Phipps, Jonathan Nowak, Shuji Ogino. Tumor immune and microbial characteristics of colorectal cancer according to age at diagnosis and detailed anatomical location [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3467.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BackgroundKRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. MethodsAll patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. ResultsThe analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01–2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06–1.91). ConclusionsKRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

Added value of DCER-features to clinicopathologic model for predicting metachronous metastases in rectal cancer patients.

The study aimed to investigate whether dynamic contrast-enhanced MRI parameters and preoperative radiological features (DCER-Features) add value to the clinicopathologic model for predicting metachronous metastases in rectal cancer patients. From January 2014 to December 2020, 859 patients in the PACS system were retrospectively screened. Of the initial 722 patients with surgically confirmed rectal cancer and no synchronous metastases, 579 patients were excluded for various reasons such as lack of clinicopathological or radiological information. 143 patients were finally included in this study. And 73 Patients of them developed metachronous metastasis within five years. After stepwise multiple regression analyses, we constructed three distinct models. Model 1 was developed solely based on clinicopathological factors, and model 2 incorporated clinicopathological characteristics along with DCE-MRI parameters. Finally, model 3 was built on all available factors, including clinicopathological characteristics, DCE-MRI parameters, and radiological features based on rectal magnetic resonance imaging. The radiological features assessed in this study encompass tumor imaging staging, location, and circumferential resection margin (CRM) for primary tumors, as well as the number of visible lymph nodes and suspected metastatic lymph nodes. Receiver operating characteristic (ROC) and decision curve analysis (DCA) were conducted to evaluate whether the diagnostic efficiency was improved. The performance of model 3 (including clinicopathologic characteristics and DCER-Features) was the best (AUC: 0.856, 95% CI 0.778-0.886), whereas it was 0.796 (95% CI 0.720-0.828) for model 2 and 0.709 (95% CI 0.612-0.778) for model 1 (DeLong test: model 1 vs model 2, p = 0.004; model 2 vs model 3, p = 0.037; model 1 vs model 3, p < 0.001). The decision curves indicated that the net benefit of model 3 was higher than the other two models at each referral threshold. The calibration plot of the three models revealed an excellent predictive accuracy. This study suggests that DCER-Features have added value for the clinicopathological model to predict metachronous metastasis in patients with rectal cancers.

Nomogram Based on US and Clinicopathologic Characteristics: Axillary Nodal Evaluation Following Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer

BackgroundTo develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and MethodsIn this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. ResultsAxillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. ConclusionNomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.

Comparison of oncological and functional outcomes in Lower-limb osteosarcoma pediatric patients: a large single-center retrospective cohort study.

Treating pediatric osteosarcoma in long bones is challenging due to skeletal immaturity, which restricts the generalizability of insights derived from adult patients. Are there disparities in outcomes? How should surgical protocols be tailored for children of varying ages? What are the specific postoperative complications? A large single-center retrospective cohort study of 345 patients under 14 years old with lower-limb osteosarcoma treated in our department since 2000 was conducted to address these inquiries. A retrospective analysis of 345 pediatric patients with lower-limb osteosarcoma admitted to our department between 2000 and 2019 was conducted. Clinical and functional outcomes were compared based on age groups, surgical methods, type of prosthesis, and primary tumor location. Patients were divided into the low-age group (≤10y old) and the high-age group (>10y old). Overall survival rate (OS), progressionfree survival rate (PFS), and prosthesis survival rate were assessed using Kaplan-Meier curves, nonparametric survival analysis (log-rank test), and Univariate cox regression were used for comparison. The incidence of complications, local relapse rate (LRR), metastasis rate, final limb-salvage, and amputation rate, and Musculoskeletal Tumor Society (MSTS) score of different independent groups were further evaluated using χ2 test or Fisher's exact test, and t -test was employed to evaluate the measurement data. The average age of the patients was 11.10±2.32 years ranging from 4 to 14y, with an average follow-up duration of 48.17 months. The 5, 10, and 15-year OS rates were 50.3%, 43.8%, and 37.9%, respectively. The progression-free survival rate was 44.8% at 5 years and 41.1% at 10 years. The final limb salvage rate was 61.45%, while the final amputation rate was 38.55%. The low-age group had a higher amputation rate compared with the high-age group (48.00% vs. 33.18%, P =0.009). The overall LRR was 9.28%, and the incidence of metastasis was 28.99%. The LRR of the limb-salvage group was higher than the amputation group ( P =0.004). The low-age group experienced more prosthesis-related complications than the high-age group ( P =0.001). The most common prosthesis-related complication in the low-age group was soft-tissue failure, while the periprosthetic infection was most frequent in the high-age group. The high-age group had a higher cumulative prosthesis survival compared with the low-age group ( P =0.0097). Modular prosthesis showed better MSTS scores and higher cumulative prosthetic survival than expandable prosthesis in pediatric patients ( P <0.05). Limb preservation in pediatric patients becomes increasingly efficacious with advancing age, while consideration of amputation is warranted for younger patients. The prevailing postoperative complications associated with prosthesis encompass soft tissue failure and periprosthetic infection. Younger patients diagnosed with lower limb osteosarcoma exhibit a heightened amputation rate and a greater incidence of prosthesis-related complications.

Analysis of prognostic factors and the role of epilepsy in neurosurgical patients with brain metastases.

Brain metastases (BMs) represent the most frequent brain tumors in adults. The identification of key prognostic factors is essential for choosing the therapeutic strategy tailored to each patient. Epilepsy can precede several months of other clinical presentations of BMs. This work aimed to study the impact of epilepsy and other prognostic factors on BMs patients' survival. This retrospective study included 51 patients diagnosed with BMs and who underwent neurosurgery between 2010 and 2021. The impact of BM features and patient's clinical characteristics on the overall survival (OS) was analyzed through uni- and multivariate analysis. The average OS was 25.98 months and differed according to the histology of the primary tumor. The primary tumor localization and the presence of extracranial metastases had a statistically significant impact on the OS, and patients with single BM showed a superior OS to those with multifocal lesions. The localization of BMs in the temporal lobe correlated with the highest OS. The OS was significantly higher in patients who presented seizures in their clinical onset and in those who had better post-surgical Karnofsky performance status, no post-surgical complications, and who underwent post-surgical treatment. Our study has highlighted prognostically favorable patient and tumor factors. Among those, a clinical onset with epileptic seizures can help identify brain metastasis hitherto silent. This could lead to immediate diagnostic-therapeutic interventions with more aggressive therapies after appropriate multidisciplinary evaluation.

Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study).

The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.

A prediction nomogram for perineural invasion in colorectal cancer patients: a retrospective study

BackgroundPerineural invasion (PNI), as the fifth recognized pathway for the spread and metastasis of colorectal cancer (CRC), has increasingly garnered widespread attention. The preoperative identification of whether colorectal cancer (CRC) patients exhibit PNI can assist clinical practitioners in enhancing preoperative decision-making, including determining the necessity of neoadjuvant therapy and the appropriateness of surgical resection. The primary objective of this study is to construct and validate a preoperative predictive model for assessing the risk of perineural invasion (PNI) in patients diagnosed with colorectal cancer (CRC).Materials and methodsA total of 335 patients diagnosed with colorectal cancer (CRC) at a single medical center were subject to random allocation, with 221 individuals assigned to a training dataset and 114 to a validation dataset, maintaining a ratio of 2:1. Comprehensive preoperative clinical and pathological data were meticulously gathered for analysis. Initial exploration involved conducting univariate logistic regression analysis, with subsequent inclusion of variables demonstrating a significance level of p < 0.05 into the multivariate logistic regression analysis, aiming to ascertain independent predictive factors, all while maintaining a p-value threshold of less than 0.05. From the culmination of these factors, a nomogram was meticulously devised. Rigorous evaluation of this nomogram's precision and reliability encompassed Receiver Operating Characteristic (ROC) curve analysis, calibration curve assessment, and Decision Curve Analysis (DCA). The robustness and accuracy were further fortified through application of the bootstrap method, which entailed 1000 independent dataset samplings to perform discrimination and calibration procedures.ResultsThe results of multivariate logistic regression analysis unveiled independent risk factors for perineural invasion (PNI) in patients diagnosed with colorectal cancer (CRC). These factors included tumor histological differentiation (grade) (OR = 0.15, 95% CI = 0.03–0.74, p = 0.02), primary tumor location (OR = 2.49, 95% CI = 1.21–5.12, p = 0.013), gross tumor type (OR = 0.42, 95% CI = 0.22–0.81, p = 0.01), N staging in CT (OR = 3.44, 95% CI = 1.74–6.80, p < 0.001), carcinoembryonic antigen (CEA) level (OR = 3.13, 95% CI = 1.60–6.13, p = 0.001), and platelet-to-lymphocyte ratio (PLR) (OR = 2.07, 95% CI = 1.08–3.96, p = 0.028).These findings formed the basis for constructing a predictive nomogram, which exhibited an impressive area under the receiver operating characteristic (ROC) curve (AUC) of 0.772 (95% CI, 0.712–0.833). The Hosmer–Lemeshow test confirmed the model's excellent fit (p = 0.47), and the calibration curve demonstrated consistent performance. Furthermore, decision curve analysis (DCA) underscored a substantial net benefit across the risk range of 13% to 85%, reaffirming the nomogram's reliability through rigorous internal validation.ConclusionWe have formulated a highly reliable nomogram that provides valuable assistance to clinical practitioners in preoperatively assessing the likelihood of perineural invasion (PNI) among colorectal cancer (CRC) patients. This tool holds significant potential in offering guidance for treatment strategy formulation.

Proximal Humerus Reconstruction for Bone Sarcomas: A Critical Analysis.

» The proximal humerus is a common location for primary bone tumors, and the goal of surgical care is to obtain a negative margin resection and subsequent reconstruction of the proximal humerus to allow for shoulder function.» The current evidence supports the use of reverse total shoulder arthroplasty over hemiarthroplasty when reconstructing the proximal humerus after resection of a bone sarcoma if the axillary nerve can be preserved.» There is a lack of high-quality data comparing allograft prosthetic composite (APC) with endoprosthetic reconstruction of the proximal humerus.» Reverse APC should be performed using an allograft with donor rotator cuff to allow for soft-tissue repair of the donor and host rotator cuff, leading to improvements in shoulder motion compared with an endoprosthesis.

Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.