Prognostic Nomogram for Liver Metastatic Colon Cancer Based on Histological Type, Tumor Differentiation, and Tumor Deposit: A TRIPOD Compliant Large-Scale Survival Study

ObjectiveA proportional hazard model was applied to develop a large-scale prognostic model and nomogram incorporating clinicopathological characteristics, histological type, tumor differentiation grade, and tumor deposit count to provide clinicians and patients diagnosed with colon cancer liver metastases (CLM) a more comprehensive and practical outcome measure.MethodsUsing the Transparent Reporting of multivariable prediction models for individual Prognosis or Diagnosis (TRIPOD) guidelines, this study identified 14,697 patients diagnosed with CLM from 1975 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) 21 registry database. Patients were divided into a modeling group (n=9800), an internal validation group (n=4897) using computerized randomization. An independent external validation cohort (n=60) was obtained. Univariable and multivariate Cox analyses were performed to identify prognostic predictors for overall survival (OS). Subsequently, the nomogram was constructed, and the verification was undertaken by receiver operating curves (AUC) and calibration curves.ResultsHistological type, tumor differentiation grade, and tumor deposit count were independent prognostic predictors for CLM. The nomogram consisted of age, sex, primary site, T category, N category, metastasis of bone, brain or lung, surgery, and chemotherapy. The model achieved excellent prediction power on both internal (mean AUC=0.811) and external validation (mean AUC=0.727), respectively, which were significantly higher than the American Joint Committee on Cancer (AJCC) TNM system.ConclusionThis study proposes a prognostic nomogram for predicting 1- and 2-year survival based on histopathological and population-based data of CLM patients developed using TRIPOD guidelines. Compared with the TNM stage, our nomogram has better consistency and calibration for predicting the OS of CLM patients.

Efficacy of Targeted Radionuclide Therapy Using [131I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma

Purpose: To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance. Methods: For TRT, we used a melanin radiotracer ([131I]ICF01012) currently in phase 1 clinical trial (NCT03784625). TRT alone or combined with MEKi was evaluated in three-dimensional melanoma spheroid models of human BRAFV600E SK-MEL-3, murine NRASQ61K 1007, and WT B16F10 melanomas. TRT in vivo biodistribution, dosimetry, efficiency, and molecular mechanisms were studied using the C57BL/6J-NRASQ61K 1007 syngeneic model. Results: TRT cooperated with MEKi to increase apoptosis in both BRAF- and NRAS-mutant spheroids. NRASQ61K spheroids were highly radiosensitive towards [131I]ICF01012-TRT. In mice bearing NRASQ61K 1007 melanoma, [131I]ICF01012 induced a significant extended survival (92 vs. 44 days, p < 0.0001), associated with a 93-Gy tumor deposit, and reduced lymph-node metastases. Comparative transcriptomic analyses confirmed a decrease in mitosis, proliferation, and metastasis signatures in TRT-treated vs. control tumors and suggest that TRT acts through an increase in oxidation and inflammation and P53 activation. Conclusion: Our data suggest that [131I]ICF01012-TRT and MEKi combination could be of benefit for advanced pigmented BRAF-mutant melanoma care and that [131I]ICF01012 alone could constitute a new potential NRAS-mutant melanoma treatment.

Predicting Survival Outcome of Patients With Colorectal Cancer and Only Lung Metastasis: A Population-Based Real-World Study

Background: Patients with metastatic colorectal cancer (mCRC) have a poor prognosis, but lung metastasis (LM) generally has a relatively desirable survival outcome. However, clinicians have had few tools for estimating the probability of survival in patients with colorectal cancer (CRC) and only LM (OLM). The present study aimed to develop nomograms estimating survival probability for patients with CRC and OLM.Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database of patients with CRC between 2010 and 2014 were retrieved for retrospective analysis. Patients with OLM diagnosed between 2010 and 2014, except for 2012 (n = 1,118) were used to conduct multivariate Cox analysis to identify independent prognostic factors. Nomograms estimating 1- and 3-year overall survival (OS) and cancer-specific survival (CSS) were developed. The nomograms were internally validated for concordance index (C-index), calibration plots, receiver operating characteristic (ROC) curves, and were also externally validated with independent patients diagnosed in 2012 (n = 261).Results: Age, marital status, tumor location, tumor size, T and N stage, CEA, tumor deposit, histological grade, primary or metastatic tumor surgery, chemotherapy, radiotherapy, and income were found to be independently associated with OS and/or CSS. The nomograms were constructed based on these prognostic factors. The C-index were high in internal validation (0.736 for OS and 0.741 for CSS) and external validation (0.656 for OS and 0.663 for CSS). Internal and external calibration plots and ROC curves demonstrated a good agreement between actual observation and nomogram prediction.Conclusions: The nomograms individually predict OS and CSS of patients with CRC and OLM and could aid in the personalized prognostic evaluation and clinical decision-making.

Metachronous Mesorectal Recurrence after Colectomy for Ascending Colon Cancer

Background: An isolated metachronous recurrence in the mesorectum from a primary ascending colon cancer is a rare finding that has not been previously reported. This may represent a form of retroperitoneal spread, sometimes referred to as “drop metastasis,” which is an uncommon mechanism for metachronous recurrence. Case Presentation: A 38-year-old male presented to the Emergency Department in January of 2018 with profound anemia. A colonoscopy revealed innumerable colonic polyps. He reported having multiple family members diagnosed with colon cancer and was subsequently diagnosed with familial adenomatous polyposis with rectal sparing. Total abdominal colectomy with ileorectal anastomosis was performed, revealing a T3N1a adenocarcinoma of the ascending colon. The patient subsequently underwent 12 cycles of adjuvant FOLFOX. Surveillance imaging in late 2019 revealed a suspicious mass in the superior perirectal soft tissue without any other sites of potential disease. Completion proctectomy was performed in January 2020, 2 years after the initial resection. Pathology revealed a mesorectal tumor deposit located 1.5 cm distal to the ileorectal anastomosis. No evidence of mucosal involvement or nodal metastasis was identified. Conclusion: Isolated mesorectal recurrence is a rare and previously unreported clinical finding following resection of an ascending colon cancer with an ileorectal anastomosis. This likely represents a form of retroperitoneal spread.

The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery

Background. The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. Method. Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. Results. X-tile plots identified 3 (P<0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P<0.001, P=0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P<0.001). Conclusion. More TD count (TD count≥4) was significantly associated with poor disease-specific survival in CRC patients.