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The study presents a transcriptomics‐based liquid biopsy approach for early recurrence detection in locally advanced gastric cancer (LAGC). Four mRNA biomarkers (AGTR1, DNER, EPHA7, and SUSD5) linked to recurrence are identified through transcriptomic data analysis. A Risk Stratification Assessment (RSA) model combining these biomarkers with clinical features showed superior predictive accuracy for postoperative recurrence, with AUCs of 0.919 and 0.935 in surgical and liquid biopsy validation cohorts, respectively. Functional studies using human gastric cancer cell lines AGS and HGC‐27 demonstrated that silencing the identified mRNA panel genes impaired cell migration, invasion, and proliferation. In vivo experiments further showed reduced tumor growth, metastasis, and lymphangiogenesis in mice, possibly mediated by the cAMP signaling pathway. This non‐invasive approach offers significant potential for enhancing recurrence detection and enabling personalized treatment strategies, thereby improving patient outcomes in the management of LAGC. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian, fallopian tube, and primary peritoneal cancers are often diagnosed at advanced stages due to nonspecific symptoms. This makes early detection challenging and impacts patient outcomes. This study sought to clarify the role of HE4 and CA125 in the follow-up of ovarian cancer patients and, potentially, improve early detection and management of recurrences. By monitoring changes in these markers over time, the researchers hoped to find a more reliable way to identify cancer recurrence before it is visible on CT scans. The findings suggest that tracking increases in these markers can predict a relapse earlier than CT scans, potentially allowing for earlier treatment. Further research is required to refine follow-up strategies and enhance outcomes for ovarian cancer patients. Background: Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives: The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4's role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values' accuracy for early relapse detection. Methods: In this multicenter prospective cohort study, 117 eligible patients with Stage III–IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3–4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results: During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions: The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Circulating tumor (ctDNA) can be used to detect residual disease after cancer treatment. Detecting low-level ctDNA is challenging, due to the limited number of recoverable ctDNA fragments at any target loci. In response, we applied tumor-informed whole-genome sequencing (WGS), leveraging thousands of mutations for ctDNA detection. Performance was evaluated in serial plasma samples (n = 1283) from 144 stage III colorectal cancer patients. Tumor/normal WGS was used to establish a patient-specific mutational fingerprint, which was searched for in 20x WGS plasma profiles. For reproducibility, paired aliquots of 172 plasma samples were analyzed in two independent laboratories. De novo variant calling was performed for serial plasma samples with a ctDNA level > 10 % (n = 17) to explore genomic evolution. WGS-based ctDNA detection was prognostic of recurrence: post-operation (Hazard ratio [HR] 6.75, 95 %CI 3.18–14.3, p < 0.001), post-adjuvant chemotherapy (HR 28.9, 95 %CI 10.1–82.8; p < 0.001), and during surveillance (HR 22.8, 95 %CI 13.7–37.9, p < 0.0001). The 3-year cumulative incidence of ctDNA detection in recurrence patients was 95 %. ctDNA was detected a median of 8.7 months before radiological recurrence. The independently analyzed plasma aliquots showed excellent agreement (Cohens Kappa=0.9, r = 0.99). Genomic characterization of serial plasma revealed significant evolution in mutations and copy number alterations, and the timing of mutational processes, such as 5-fluorouracil-induced mutations. Our study supports the use of WGS for sensitive ctDNA detection and demonstrates that post-treatment ctDNA detection is highly prognostic of recurrence. Furthermore, plasma WGS can identify genomic differences distinguishing the primary tumor and relapsing metastasis, and monitor treatment-induced genomic changes. • Whole-genome sequencing [WGS, 20x] of 1283 plasma samples from 144 CRC patients • Plasma WGS highly prognostic at landmark timepoints assessing minimal residual disease • Serial analysis showed 95 % cumulative ctDNA detection in recurrence patients • ctDNA was detected median 8.7 months prior to recurrence detection by imaging • Excellent reproducibility of the full approach across two independent laboratories [ABSTRACT FROM AUTHOR]

Adherence to active surveillance in patients with stage 1 testicular cancers may be influenced by factors affecting capacity and motivation to attend appointments. The aims of this study were to assess adherence to active surveillance and analyze factors which may impact adherence. A retrospective cohort study was conducted in patients diagnosed with stage 1 testicular cancer between 2005 and 2020, and managed with active surveillance at 3 institutions in South Western Sydney, Australia. Adherence with active surveillance was followed to 2023 and patients were subsequently classified into 3 groups: "Optimal," "Adequate" or "Loss to follow-up" (LTFU). Factors for adherence were analyzed using multivariable logistic regression. Disease recurrence was analyzed using multivariable Cox regression. In 125 patients, adherence with active surveillance was assessed as "Optimal" in 64 (51%), "Adequate" in 14 (11%), and LTFU in 47 (38%). Multivariable analysis demonstrated that patients had higher odds of being in the "Optimal" or "Adequate" categories if they were from a culturally and linguistically diverse background (OR 4.86, P =.026), nonsmokers (OR 7.63, P =.0002), not employed (OR 4.93, P =.0085), had a partner (OR 2.74, P =.0326), or were diagnosed after June 2016 (OR 5.22, P =.0016). Recurrence occurred in 21 patients (17%). The risk of recurrence increased with the presence of multiple pathological risk factors (HR 5.77, P =.0032), if patients were unemployed (HR 2.57, P =.032), or if they had "Optimal" or "Adequate" adherence (HR 12.74, P =.0136). Adherence with active surveillance was poorer in this cohort of stage 1 testicular cancer patients. Patients from culturally and linguistically diverse backgrounds and those who were nonsmokers, unemployed, with a partner, and later date of diagnosis, were more likely to be adherent with active surveillance. Adherence with active surveillance for stage 1 testicular cancer is often suboptimal. This retrospective study assessed adherence to active surveillance and analyzed factors impacting adherence. This cohort had a high rate of loss to follow-up of 38%. Significant risk factors for nonadherence included being from nonculturally and linguistically diverse background, employment, smoking, single relationship status, and earlier date of diagnosis. [ABSTRACT FROM AUTHOR]

BackgroundAmino acid transport imaging with 18F-FDOPA PET is increasingly used for detection of glioblastoma recurrence. However, a standardized image interpretation for 18F-FDOPA brain PET studies has not yet been established. This study compares visual and semiquantitative analysis parameters for detection of tumor recurrence and correlates them with progression-free survival (PFS).MethodsOne-hundred ten patients (72 male:38 female) with suspected tumor recurrence who underwent 18F-FDOPA PET imaging were studied. PET scans were analyzed visually (5-point scale) and semiquantitatively (lesion-to-striatum- and lesion- to-normal-brain-tissue ratios using both SUV(mean) and SUV(max)). Accuracies for recurrence detection were calculated using histopathology and clinical follow-up for validation. Receiving operator characteristic and Kaplan-Meier survival analysis were performed to derive imaging-based prediction of PFS and overall survival (OS).ResultsAccuracies for detection of glioblastoma recurrence were similar for visual (82%) and semiquantitative (range, 77%-82%) analysis. Both visual and semiquantitative indices were significant predictors of PFS, with mean lesion-to normal brain tissue ratios providing the best discriminator (mean survival, 39.4 vs 9.3 months; P < .001). None of the investigated parameters was predictive for OS.ConclusionsBoth visual and semiquantitative indices detected glioblastoma recurrence with high accuracy and were predictive for PFS. Lesion-to-normal-tissue ratios were the best discriminators of PFS; however, none of the investigated parameters predicted OS. These retrospectively established analysis parameters need to be confirmed prospectively.

Over the last quarter of a century, fluorine-18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) has revolutionized the diagnostic algorithm of ovarian cancer, impacting on the initial disease evaluation including staging and surgical planning, treatment response assessment and prognostication, to the most important role in detection of recurrent disease. The role of FDG PET/CT is expanding with the adoption of new therapeutic agents. Other non-FDG tracers have been explored with fibroblast activation protein inhibitor being promising. Novel tracers may provide the basis for future theragnostic work. This article will review the evolution and impact of PET/CT in ovarian cancer management., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Early detection of metastatic colorectal cancer, at initial diagnosis or during routine surveillance, can improve survival outcomes. Current routine investigations, including CEA and CT, have limited sensitivity and specificity. Recent studies of colorectal cancer cohorts under post surgery surveillance indicate circulating tumor DNA (ctDNA) evidence of recurrence can occur many months before clinical detection. Another possible role for ctDNA is in the further assessment of indeterminate findings on standard CEA or CT investigations. To further explore this potential, we undertook a prospective study. Further investigation, including FDG‐PET imaging, was at clinician discretion, blinded to ctDNA analysis. Forty‐nine patients were enrolled. Analyzed here are the 45 patients with an evaluable blood sample of whom 6 had an isolated elevated CEA, 30 had indeterminate CT findings, and 9 had both. FDG‐PET scans were performed in 30 patients. Fourteen of 45 patients (31%) had detectable ctDNA. At completion of the planned 2 year follow‐up, recurrence has occurred in 21 (47%) patients. Detectable ctDNA at study entry was associated with inferior relapse free survival (HR 4.85, p < 0.0001). Where FDG‐PET scan was normal/equivocal (n = 15, 50%) 1 of 1 with detectable ctDNA versus 3 of 14 with undetectable ctDNA ultimately had recurrence confirmed. In summary, for colorectal cancer patients with indeterminate findings on routine investigations, ctDNA detection increases the probability that the findings indicate metastatic disease, including in a nonpredefined subset that also underwent FDG‐PET imaging. Further studies of the value of ctDNA analysis during patient surveillance are warranted. What's new? Colorectal cancer (CRC) patients undergoing routine surveillance frequently present with findings considered indeterminate for recurrence following standard workup with computed tomography scanning and carcinoembryonic antigen testing. Here, circulating tumor DNA (ctDNA) was examined as a potential tool for further assessment of indeterminate CRC cases. Of 45 patients included in the analysis, 14 had detectable ctDNA at study entry. With a minimum 2 years follow‐up, positive ctDNA analysis was significantly associated with inferior relapse‐free survival. The findings identify ctDNA as a predictor of CRC recurrence and highlight its potential as an adjunct or routine test in CRC surveillance. [ABSTRACT FROM AUTHOR]

Background: Regular history assessments and physical examination with annual breast imaging have been recommended as the standard surveillance protocol for breast cancer patients who underwent curative-intent therapy. Based on randomized studies conducted in the 2000s, surveillance with regular chest or abdominal imaging, chemistry panels, or tumor marker measurements does not improve survival in such patients. Given the remarkable recent improvements of systemic therapy, we hypothesized that more intensive surveillance may lead to early detection and improve treatment outcomes in the modern era., Methods: We retrospectively evaluated the follow-up strategies and benefits of investigations used in usual practice. Breast cancer patients who had initial adjuvant therapy were recruited and classified according to the receipt of standard follow-up (history, physical examination, and annual breast imaging) or alternative follow-up (surveillance with at least annual chest or abdominal imaging or biannual liver function testing). The primary outcome was overall survival. Secondary outcomes included disease-free survival and the indicator of recurrence detection., Results: Of 412 recruited patients, 213 (51.7%) and 199 patients (49.3%) were included in the standard follow-up group and alternative follow-up group, respectively. Among 90 patients (21%) with disease recurrence, the most frequent indicators of recurrence were newly reported symptoms or physical examination abnormalities (64%), followed by abnormal breast imaging (23%) and abnormal chest X-ray (10%). After a median follow-up of 85 months, approximately 90% of patients remained alive after 5 years in both groups. The mean overall survival was similar between the standard and alternative follow-up groups (154.5 months vs. 151.9 months, p = 0.54). There was no difference in terms of the proportion of interval visits, specific cancer treatment received, and disease-free survival., Conclusion: Standard follow-up with history assessments, physical examination, and annual breast imaging remains the recommended surveillance strategy in the modern era. Alternative follow-up strategy did not improve oncologic outcomes.

Transsphenoidal surgery (TSS) is first-line treatment for Cushing's disease (CD), a devastating disorder of hypercortisolism resulting from overproduction of adrenocorticotropic hormone by a pituitary adenoma. Surgical success rates vary widely and disease may recur years after remission is achieved. Recognizing CD recurrence can be challenging; although there is general acceptance among endocrinologists that patients need lifelong follow-up, there are currently no standardized monitoring guidelines. To begin addressing this need we created a novel, systematic algorithm by integrating information from literature on relapse rates in surgically-treated CD patients and our own clinical experiences. Reported recurrence rates range from 3 to 47 % (mean time to recurrence 16-49 months), emphasizing the need for careful post-surgical patient monitoring. We recommend that patients with post-operative serum cortisol <2 µg/dL (measured 2-3 days post-surgery) be monitored semiannually for 3 years and annually thereafter. Patients with post-operative cortisol between 2 and 5 µg/dL may experience persistent or subclinical CD and should be evaluated every 2-3 months until biochemical control is achieved or additional treatment is initiated. Post-operative cortisol >5 µg/dL often signifies persistent disease and second-line treatment (e.g., immediate repeat pituitary surgery, radiotherapy, and/or medical therapy) may be considered. This follow-up algorithm aims to (a) enable early diagnosis and treatment of recurrent CD, thereby minimizing the detrimental effects of hypercortisolism, and (b) begin addressing the need for standardized guidelines for vigilant monitoring of CD patients treated by TSS, as demonstrated by the reported rates of recurrence. [ABSTRACT FROM AUTHOR]

Background/aim: Post-treatment surveillance of patients with squamous cell oropharyngeal carcinoma (SCOPC) consists of routine follow-up visits for 5 years. It has been suggested that this program is inefficient for finding recurrences and increasing survival. The primary study objective was to investigate how recurrences after treatment for SCOPC were detected, i.e., at routine follow-up visits, at patient-initiated visits, or incidentally. The secondary objective was to investigate whether 2-year survival after diagnosis of recurrence depended on the manner of detection., Patients and Methods: Patients with recurrences from SCOPC between 1988 and 2018 were included. Survival was analysed by the Kaplan-Meier method with log-rank test., Results: A total of 75 patients were included. Almost one-third were alive 2 years after the diagnosis of recurrence. Recurrences were detected at routine follow-up visits in 50.7%, at patient-initiated visits in 42.7% and 6.6% were found incidentally. There was an increased survival in the patient-initiated group, but this was not significant., Conclusion: The majority of recurrences in both groups compared were amenable to curative treatment., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Context: Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC)., Objective, Design, Setting: This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC., Patients and Methods: 135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography-mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard., Results: Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine "steroid fingerprint" at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%)., Conclusion: Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence., (© Endocrine Society 2019.)

Background/aim: Current guidelines derived from a pre-human papilloma virus (HPV) era in oropharyngeal cancer do not recommend routine surveillance imaging. We aimed to analyze the method of recurrence detection in HPV+ disease to determine a role for follow-up imaging., Patients and Methods: All HPV+ and HPV- oropharyngeal cancer patients treated at our institution from 2005-2016 with biopsy-proven recurrence were identified and their method of recurrence detection was analyzed., Results: A total of 16 HPV+ oropharyngeal cancer patients were identified to have recurrence, 12 (75%) of which experienced distant recurrence and 13 (81.3%) were detected asymptomatically with imaging at a median time of 19.7 months after initial treatment and verifying no residual disease. Twelve (75%) detections were with PET-CT. While HPV- patients (17 patients) also have a high rate of asymptomatic detection (16 patients, 94.1%), their 3-year post-recurrence survival was significantly lower at 6.5% compared to 83.6% for the HPV+ group (p<0.01)., Conclusion: In HPV+ patients, a large proportion of failures are asymptomatic distant metastases, which occur beyond 6 months following treatment completion, and are detected with whole body imaging alone. In light of long term post-recurrence survival observed, this preliminary data suggests that routine surveillance imaging should be further studied for HPV+ disease., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The purpose of this article is to summarize the evidence for the value of PET/CT for the management of patients with head and neck squamous cell cancer and suggest best clinical practices., Conclusion: FDG PET/CT is a valuable imaging tool for identifying unknown primary tumors in patients with known cervical node metastases leading to management change and is the standard of care for the initial staging of stage III and IV head and neck squamous cell carcinomas (HNSCCs), for assessing therapy response when performed at least 12 weeks after chemoradiation therapy, and for avoiding unnecessary planned neck dissection. Neck dissection is avoided if PET/CT findings are negative-regardless of the size of the residual neck nodes-because survival outcomes are not compromised. FDG PET/CT is valuable in detecting recurrences and metastases during follow-up when suspected because of clinical symptoms and serves as a prognostic marker for patient survival outcomes, for 5 years. Using FDG PET/CT for routine surveillance of HNSCC after 6 months of treatment without any clinical suspicion should be discouraged.

Objective: The purpose of this article is to summarize the evidence regarding the role of FDG PET/CT in treatment response assessment and surveillance of lung cancer and to provide suggested best practices., Conclusion: FDG PET/CT is a valuable imaging tool for assessing treatment response for patients with lung cancer, though evidence for its comparative effectiveness with chest CT is still evolving. FDG PET/CT is most useful when there is clinical suspicion or other evidence for disease recurrence or metastases. The sequencing, cost analysis, and comparative effectiveness of FDG PET/CT and conventional imaging modalities in the follow-up setting need to be investigated.