The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

Recent trends of characteristics and treatments in adults with newly diagnosed brain metastases.

OBJECTIVE: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. METHODS: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. RESULTS: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. CONCLUSIONS: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Prognostic role of 11C-choline PET/CT scan in patients with metastatic castrate resistant prostate cancer undergoing primary docetaxel chemotherapy.

BACKGROUND: We sought to assess the prognostic utility of 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy. METHODS: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C-choline PET/CT scans at baseline (before chemotherapy), mid-course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool-corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot. RESULTS: Percent change in blood pool-corrected SUVmax on mid-course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99-1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool-corrected SUVmax on mid-course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool-corrected SUVmax (OR: 3.56, 95% CI: 1.04-16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0-52.7 months), compared to 9.4 months (95% CI: 6.9-13.0 months) in the incomplete response group (p = .0005). CONCLUSIONS: Our study showed that mid-course and posttherapy 11C-choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C-choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC.

Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy.

OBJECTIVE: After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms. METHODS: Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years. RESULTS: Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p < 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p < 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (>0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p < 0.001). CONCLUSION: Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

Overall and progression-free survival of Afro-Caribbean men with metastatic castration-resistant prostate cancer (mCRPC).

INTRODUCTION: Several studies in the Caucasian population have shown the benefit of using docetaxel, abiraterone, or enzalutamide for patients with metastatic prostate cancer at the castration-resistant stage (mCRPC). However, there are no strong data for men of African ancestry. The objective of this study was to estimate the overall and progression-free survival of patients according to these treatments at the mCRPC stage. PATIENTS AND METHODS: This was a monocentric retrospective study that consecutively included 211 men with mCRPC between June 1, 2009 and August 31, 2020. The primary end point was overall survival (OS). The secondary end point was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. RESULTS: The present study included 180 patients for analyses. There was no difference in OS (log-rank test = 0.73), with a median follow-up of 20.7 months, regardless of the treatment administered in the first line. Men with mCRPC who received hormonotherapy (abiraterone or enzalutamide) showed better progression-free survival than those who received docetaxel (log-rank test = 0.004), with a particular interest for abiraterone hazard ratio (HR) = 0.51 (95% confidence interval: 0.39-0.67). The patient characteristics were similar, except for bone lesions, irrespective of the treatment administered in the first line. After univariate then multivariate analysis, only World Health Organization status and metastases at diagnosis were significantly associated with progression. CONCLUSION: Our results suggest the use of hormonotherapy (abiraterone or enzalutamide) with a tendency for abiraterone in first line for men with African ancestry at the mCRPC stage.

Revisiting the AJCC staging system of adrenocortical carcinoma.

OBJECTIVE: To evaluate the performance characteristics of AJCC 7th and 8th staging systems among patients with adrenal cortical carcinoma. METHODS: Surveillance, Epidemiology, and End Results (SEER) 18-registry was accessed and patients with adrenocortical carcinoma who were diagnosed 2010-2015 with complete information about AJCC 7th staging system were included. AJCC 8th staging system information was then reconstructed for each patient using available TNM staging variables. Kaplan-Meier overall survival estimates, multivariable Cox regression analysis, and concordance index (C-statistic) were used to examine the performance characteristics of both staging systems. RESULTS: A total of 574 patients with a diagnosis of adrenocortical carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, overall survival was compared among different AJCC stages for both versions; and the P value was significant (< 0.001) for both comparisons. C-statistic was then calculated for both staging systems and the results were as follows: for AJCC 7th version: 0.726 (95% CI 0.683-0.769); and for AJCC 8th version: 0.745 (95% CI 0.704-0.786). Patients with M1 disease (stage IV according to AJCC 8th edition) were then divided according to the extent of distant metastases into single versus multiple sites of metastases. Using Kaplan-Meier survival estimates, patients with a single site of metastases have better overall survival (P = 0.006). A C-statistic for a hypothetical modification of AJCC 8th staging system subdividing stage IV patients into IVA and IVB based on the number of metastatic sites was: 0.753 (95% CI 0.713-0.794). CONCLUSIONS: There is a minimal difference in the prognostic performance between both versions of the AJCC staging system. Subdivision of stage IV cancer into stage IVA and IVB (according to the number of organs with metastatic deposits) should be considered in subsequent versions of adrenocortical carcinoma staging.

Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial.

Importance: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene. Objective: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes. Design, Setting, and Participants: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021. Interventions: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care. Main Outcomes and Measures: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available. Results: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P = .02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P = .002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P = .002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P = .009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P = .003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P = .006). Conclusions and Relevance: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03249090.

Cell-cycle risk score more accurately determines the risk for metastases and death in prostatectomy patients compared with clinical features alone.

BACKGROUND: Prostate cancer treatment aims to prevent metastases and disease-specific mortality. Pathologic parameters have limited ability to predict these outcomes, but biomarkers can improve risk discrimination. We evaluated the ability of cell-cycle progression and combined cell-cycle risk scores to predict metastases and disease-specific mortality after prostatectomy. METHODS: Eligibility included (1) treatment with radical prostatectomy (1985-1997); (2) cell-cycle progression score; (3) preoperative prostate-specific antigen; (4) no neoadjuvant therapy; and (5) clinical follow-up (N = 360). Cancer of the prostate risk assessment postsurgical score was combined with cell cycle progression into the prespecified combined cell-cycle risk score. Hazard ratios (HRs) are reported per unit score. RESULTS: In total, 11% (41/360) developed metastases and 9% (33/360) experienced disease-specific mortality. Combined cell-cycle risk score predicted metastases and disease-specific mortality post-radical prostatectomy (p < 1 × 10-8 ). Adjusting for cancer of the prostate risk assessment postsurgical score, the combined cell-cycle risk score remained a predictor of metastases (HR = 3.03 [95% confidence interval (CI): 1.49, 6.20]; p = .003] and disease-specific mortality (HR = 3.40 [95% CI: 1.52, 7.59]; p = .004). Of patients with biochemical recurrence, 25% (41/163) developed metastases. Cancer of the prostate risk assessment postsurgical score was predictive of metastases postbiochemical recurrence but was improved by the addition of cell cycle progression (HR = 1.70 [95% CI: 1.14, 2.53]; p = .012). The combined cell-cycle risk was also prognostic of metastases post-biochemical recurrence (HR = 1.56 [95% CI: 1.20, 2.03]; p = .001). CONCLUSION: Combined cell-cycle risk and cell cycle progression scores predict metastases and disease-specific mortality post-radical prostatectomy and should help identify patients at greatest risk of treatment failure who might benefit from earlier intervention.

Improvement in overall and cancer-specific survival in contemporary, metastatic prostate cancer chemotherapy exposed patients.

INTRODUCTION: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void. MATERIALS AND METHODS: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses. RESULTS: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001). CONCLUSIONS: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.

The role of histopathological and biochemical parameters for predicting metastatic disease on 68 Ga-PSMA-11 PET in prostate cancer.

BACKGROUND: The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on 68 Ga-PSMA PET images. METHODS: Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent 68 Ga-PSMA-11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as "PET positive" and "PET negative" according to the presence of pathologic extraprostatic PSMA involvement. "PET positive" patients were additionally divided into two groups: oligometastatic (1-3 metastatic lesion) and multimetastatic (>3 metastatic lesions). RESULTS: The mean age of patients was 66.8 ± 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in "PET positive" group compared to "PET negative" group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low-intermediate risk groups (ISUP 1-3 and total PSA ≤ 20 ng/ml and PSAD < 0.15 ng/ml/cc). This ratio was 46% in the high-risk group (ISUP 4-5 or total PSA > 20 ng/ml or PSAD ≥ 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively; with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05). CONCLUSIONS: In this study, 68 Ga-PSMA-11 PET positivity was significantly higher in the high-risk patient group than in the low-intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP and tumor ratio in biopsy specimens can be used to identify high-risk patients.

Metastatic relapse of stage I-III breast cancer in New Zealand.

PURPOSE: This study aims to investigate the factors that influence the risk of metastatic relapse in women presenting with stage I-III breast cancer in New Zealand. METHODS: The study included women diagnosed with stage I-III breast cancer. Cumulative incidence of distant metastatic relapse was examined with the Kaplan-Meier method by cancer stage and subtype. Cox proportional hazards models were used to estimate the adjusted hazard ratio of developing recurrent metastatic breast cancer by cancer stage and biomarker subtype after adjustment for other factors. RESULTS: A total of 17,543 eligible women were identified. The 5-year cumulative incidence of metastatic recurrence was 3.7% for stage I, 13.3% for stage II and 30.9% for stage III disease. The adjusted hazard ratios (HR) of stage II and stage III breast cancer developing metastatic disease were 2.07 and 4.82 compared to stage I. The adjusted risk of distant metastatic relapse was highest for luminal B HER2- cancers (adjusted HR: 1.59 compared to luminal A disease). Higher grade cancers were associated with a higher risk of metastases. After adjustment, women aged 60-69 years and Asian women had the lowest risk of distant metastatic relapse. CONCLUSIONS: The prognosis of women with locally invasive breast cancer differs greatly with the chance of developing metastatic disease depending on the stage of disease at diagnosis and the subtype. Grade of disease at diagnosis was also important. Maori or Pacific ethnicity did not influence the risk of developing metastatic disease, although Asian women seemed less likely to develop metastases.

Seeding metastases: The role and clinical utility of circulating tumour cells.

Peripheral human blood is a readily-accessible source of patient material in which circulating tumour cells (CTCs) can be found. Their isolation and characterization holds the potential to provide prognostic value for various solid cancers. Enumeration of CTCs from blood is becoming a common practice in informing prognosis and may guide therapy decisions. It is further recognized that enumeration alone does not capture perspective on the heterogeneity of tumours and varying functional abilities of the CTCs to interact with the secondary microenvironment. Characterizing the isolated CTCs further, in particular assessing their functional abilities, can track molecular changes in the disease progress. As a step towards identifying a suite of functional features of CTCs that could aid in clinical decisions, developing a CTC isolation technique based on extracellular matrix (ECM) interactions may provide a more solid foundation for isolating the cells of interest. Techniques based on size, charge, density, and single biomarkers are not sufficient as they underutilize other characteristics of cancer cells. The ability of cancer cells to interact with ECM proteins presents an opportunity to utilize their full character in capturing, and also allows assessment of the features that reveal how cells might behave at secondary sites during metastasis. This article will review some common techniques and recent advances in CTC capture technologies. It will further explore the heterogeneity of the CTC population, challenges they experience in their metastatic journey, and the advantages of utilizing an ECM-based platform for CTC capture. Lastly, we will discuss how tailored ECM approaches may present an optimal platform to capture an influential heterogeneous population of CTCs.

Development and validation of a prognostic scoring model for mortality risk stratification in patients with recurrent or metastatic gastric carcinoma.

BACKGROUND: Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma. METHODS: Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts. RESULTS: Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts. CONCLUSION: The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

Evaluation and Management of Colorectal Cancer Hepatic Metastases.

CASE SUMMARY: A 65-year-old man presents with new liver lesions on surveillance imaging 2 years after a right hemicolectomy for cecal adenocarcinoma. The primary tumor was pT3N1, microsatellite stable, and KRAS wild type. He completed adjuvant FOLFOX. His CEA level is 22 ng/mL. There are two 1.5-cm lesions in the right lobe near the dome of the liver and a 4-cm lesion in segment II. No luminal recurrence is detected endoscopically, and there is no evidence of peritoneal or pulmonary disease.

Paratesticular tumors. A clinicopathological study from a single tertiary hospital in North India.

OBJECTIVE: Paratesticular tumors (PTT) are rare and form a heterogenous group, ranging from benign to malignant high grade sarcomas. This study was undertaken to describe the clinicopathological spectrum of PTTs received over a 20-year period. METHODS: All primary and secondary PTTs diagnosed from 2000 to 2019 in the pathology department of a tertiary care hospital in North India were retrospectively reviewed. Gross, histopathological features and immunohistochemistry (IHC) findings were correlated with clinical details. RESULTS: A total of 169 intra-scrotal tumors were diagnosed during the study period, out of which there were 30 PTTs (in 27 patients) comprising 17.75%. Age range was 4 to 85 years (median 58 years). Benign PTTs were the commonest (n = 21, 70%), followed by metastasis to the paratesticular region (n = 6, 20%) and then primary malignant PTTs (n = 3, 10%). The commonest benign PTT was lipoma (n = 16, 76.19%), followed by adenomatoid tumor (n = 3, 14.28%) with one case each (4.76%) of cellular angiofibroma and hemangioma. Among primary malignant PTT, there were two cases of rhabdomyosarcoma, and one case of biphasic malignant mesothelioma. Metastatic tumors included four cases of prostatic adenocarcinoma, and one case each of pancreatic signet ring cell carcinoma and clear cell renal cell carcinoma. CONCLUSION: PTTs show a wide clinicopathological spectrum. Benign PTTs are commoner than malignant PTTs. Meticulous grossing and histopathological examination supplemented by IHC is essential for an accurate diagnosis of this heterogenous class of tumors, which influences the role of adjuvant therapy and patient prognosis.

Probing Cancer Metastasis at a Single-Cell Level with a Raman-Functionalized Anionic Probe.

Cancer metastasis is the primary reason for cancer-related deaths, yet there is no technique capable of detecting it due to cancer pathogenesis. Current cancer diagnosis methods evaluate tumor samples as a whole/pooled sample process loses heterogeneous information in the metastasis state. Hence, it is not suitable for metastatic cancer detection. In order to gain complete information on metastasis, it is desirable to develop a nondestructive detection method that can evaluate metastatic cells with sensitivity down to single-cell resolution. Here we demonstrated self-functionalized anionic quantum probes for in vitro metastatic cancer detection at a single-cell concentration. We achieved this by incorporating a nondestructive SERS ability within the generated probes by integrating anionic surface species and NIR plasmon resonance. To the best of our knowledge, this was the first time that metastatic cancer cells were detected through their neoplastic transformations. With reliable diagnostic information at the single-cell sensitivity in an in vitro state, we successfully discriminated against cancer malignancy states.

Distant metastasis of salivary gland cancer: Incidence, management, and outcomes.

BACKGROUND: Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment. METHODS: Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM. RESULTS: Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003). CONCLUSIONS: In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival.

Designing a Rational Follow-Up Schedule for Patients with Extremity Soft Tissue Sarcoma.

PURPOSE: The risk of tumor recurrence after resection of soft tissue sarcoma (STS) necessitates surveillance in follow-up. The objective of this study was to determine the frequency/timing of metastasis and local recurrence following treatment for soft tissue sarcoma, and to use these data to justify an evidence-based follow-up schedule. METHODS: Utilizing a prospective database, a retrospective single center review was performed of all patients with minimum 2-year follow-up after resection of a localized extremity STS. Kaplan-Meier estimates were used to calculate the incidence of local recurrence and metastases on an annual basis for 10 years. RESULTS: We identified a total of 230 low-grade, 626 intermediate-grade and 940 high-grade extremity STS and a total of 721 events, 150 local recurrences and 571 metastases. Based on tumor size and grade, follow-up cohorts were developed that had similar metastatic risk. Using pre-determined thresholds for metastatic event, a follow-up schedule was established for each cohort. CONCLUSION: Based on our results we recommend that patients with small low-grade tumors undergo annual follow-up for 5 years following definitive local treatment. Patients with large low-grade tumors, small intermediate-grade and small high-grade tumors should have follow-up every 6 months for the first 2 years, then yearly to 10 years. Only patients with large intermediate- or high-grade tumors require follow-up every 3 months for the first 2 years, then every 6 months for years 3-5, followed by annually until 10 years.