Early Detection Of Recurrent Disease Research Articles

From Diagnosis to Remission Navigating Innovative Tumor Markers and Uncovering Hidden Risk in Breast Cancer Care, a Review Article.

Breast cancer is a leading cause of cancer-related deaths worldwide, and its management requires a multi-disciplinary approach. This review article aims to provide an overview of the use of tumor markers in breast cancer diagnosis, prognosis, and treatment monitoring, as well as the assessment of risk for recurrence and the development of second primary tumors. The article also discusses the challenges associated with the interpretation of tumor marker results and the integration of risk assessment tools into clinical practice. Overall, the review provides a comprehensive overview of the current state of knowledge on tumor markers and risk assessment in breast cancer care, and offers insights into how these tools can be used to optimize patient outcomes. Method: This review article was conducted by searching electronic databases such as PubMed, Medline, and Scopus, using a combination of keywords related to breast cancer, tumor markers, risk assessment, and clinical management. The search was limited to articles published in English language, and the final selection was based on the relevance and quality of the studies. Tumor markers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 are important in breast cancer diagnosis, prognosis, and treatment. They can be used to guide treatment decisions, monitor response to therapy, and detect recurrence. Risk assessment tools such as Adjuvant! Online and PREDICT can also provide valuable information for clinicians and patients in making informed decisions regarding treatment and follow-up. However, the interpretation of tumor marker results and the integration of risk assessment tools into clinical practice requires careful consideration and collaboration between the multidisciplinary team. Conclusion: The review highlights the potential benefits and limitations of tumor markers in breast cancer care, including their ability to predict risk, monitor treatment response, and facilitate early detection of disease recurrence. However, the use of these markers must be balanced against their potential for false-positive and false-negative results, as well as the need for careful interpretation and clinical context.

A rare case of medullary carcinoma

Medullary thyroid cancer (MTC) accounts for 5–10 % of all thyroid cancers. Most cases (75 %) are sporadic, but the proportion of patients with MTC and a familial predisposition syndrome is the highest among those with any hereditary cancer syndrome (about 25 %), and this possibility should be considered when examining a patient with MTC. Familial syndromes include multiple endocrine neoplasia (MEN) 2A, MEN 2B, and non-MEN familial MTC (familial MTC). Familial MTC syndromes occur in approximately one case per 30,000 of the population. Reduced penetrance and clinical variability are well-established features of many monogenic disorders, particularly phenotypes associated with the RET proto-oncogene. They require an individual assessment of the pathogenic effects and clinical significance of any identified new sequence of the RET va­riant as prerequisites for individual genetic counseling and planning of medical monitoring and treatment. Diagnostic criteria for the disease have been outlined, molecular and genetic aspects have been discussed, and the determination of treatment and further observation has been addressed. The article describes a clinical case of a rare variant of MTC. Treatment of this pathology with radical extrafascial thyroidectomy is under consideration. Given the ineffectiveness of radioiodine and chemotherapy, the main task in the treatment of MTC is early diagnosis, radical surgical intervention, and active monitoring aimed at early detection of disease recurrence. When planning prophylactic thyroidectomy, it is recommended to focus on the stratification of the level of RET gene mutations and the timing of prophylactic thyroidectomy proposed by the American Thyroid Association. The introduction of molecular genetic research into clinical practice for the purpose of diagnosing MTC allows for the objective assessment of the genetic lineage of the disease within a biological family. A timely diagnosis of MTC makes it possible to prescribe an adequate treatment at the stage of preclinical manifestations of the disease, which can significantly increase the quality and duration of life.

Identification of a serum-based microRNA signature that detects recurrent oral squamous cell carcinoma before it is clinically evident

BackgroundSurvival rates for oral squamous cell carcinoma (OSCC) have remained poor for decades, a fact largely attributable to late-stage diagnoses and high recurrence rates. We report analysis of serum miRNA expression in samples from patients with high-risk oral lesions (HRL, including OSCC/carcinoma in situ lesions) and healthy non-cancer controls, with the aim of non-invasively detecting primary or recurrent disease before it is clinically evident.MethodsDiscovery, test, and validation sets were defined from a total of 468 serum samples (305 HRL and 163 control samples). Samples were analysed using multiple qRT-PCR platforms.ResultsA two-miRNA classifier comprised of miR-125b-5p and miR-342-3p was defined following discovery and test analyses. Analysis in an independent validation cohort reported sensitivity and specificity of ~74% for this classifier. Significantly, when this classifier was applied to serial serum samples taken from patients both before treatment and during post-treatment surveillance, it identified recurrence an average of 15 months prior to clinical presentation.ConclusionsThese results indicate this serum miRNA classifier is effective as a simple, non-invasive monitoring tool for earlier detection of recurrent disease when lesions are typically smaller and amenable to a wider array of treatment options to improve survival.

Follow-Up after Curative Surgical Treatment of Soft-Tissue Sarcoma for Early Detection of Recurrence: Which Patients Have More or Fewer Visits than Advised in Guidelines?

Follow-up (FU) in soft-tissue sarcoma (STS) patients is designed for early detection of disease recurrence. Current guidelines are not evidenced-based and not tailored to patient or tumor characteristics, so they remain debated, particularly given concerns about cost, radiation frequency, and over-testing. This study assesses the extent to which STS patients received guideline-concordant FU and to characterize which type of patients received more or fewer visits than advised. All STS patients surgically treated at the Leiden University Medical Center between 2000-2020 were included. For each patient, along with individual characteristics, all radiological examinations from FU start up to 5 years were included and compared to guidelines. Recurrence was defined as local/regional recurrence or metastasis. A total of 394 patients was included, of whom 250 patients had a high-grade tumor (63.5%). Only 24% of patients received the advised three FU visits in the first year. More FU visits were observed in younger patients and those diagnosed with a high-grade tumor. Among patients with a recurrence, 10% received fewer visits than advised, while 28% of patients without a recurrence received more visits than advised. A minority of STS patients received guideline-concordant FU visits, suggesting that clinicians seem to incorporate recurrence risk in decisions on FU frequency.

An approach to the management of recurrent metastatic squamous cell carcinoma of the anus: A case report

Introduction: Anal squamous cell carcinoma (ASCC) is an uncommon gastrointestinal cancer that is increasingly curable when diagnosed in early stages. Distant metastases are relatively uncommon. New technologies have been introduced for the early detection of disease recurrence across all solid tumors, but their role in ASCC has not been well described. We present a case of isolated metachronous metastasis to the lung from primary ASCC, without primary recurrence and the application of circulating tumor DNA (ctDNA) technology in management. Case Report: The patient is a 63-year-old female who presented with altered bowel habits, rectal bleeding and was found to have a 3×2 cm mass fixed to the anal sphincter on colonoscopy. Biopsy showed moderately differentiated invasive squamous cell carcinoma. Imaging revealed inguinal lymphadenopathy but was negative for distant metastases. She underwent definitive chemoradiotherapy without complications. Post-treatment surveillance scans were negative for residual disease or distant metastasis. Two years later, positron emission tomography (PET)/computed tomography (CT) scans revealed a 0.5 cm sub-pleural nodule which when repeated three months later grew to 0.7 cm. The nodule was then surgically resected. Histology was positive for metastatic squamous cell carcinoma, similar to the primary tumor. Given the dearth of data related to treatment in the setting of resected isolated metastatic disease we pursued ctDNA testing which was negative. Given this finding along with the clinical presentation, time to metastasis (two years) and absence of other evidence of recurrence we opted to monitor expectantly rather than administer systemic chemotherapy. Conclusion: Anal squamous cell carcinoma with metachronous distant metastasis is an unusual phenomenon. Treatment with chemotherapy in completely resected metastatic disease is controversial. Use of ctDNA technology may have a role in aiding in this complex decision making.

Circulating tumor DNA (ctDNA) and disease recurrence in early stage pancreatic cancer.

e16313 Background: Surgical resection with neoadjuvant and/or adjuvant chemotherapy remains to be the cornerstone in treatment for early-stage pancreatic adenocarcinoma. Disease recurrence after curative intent treatment remains to be very common, and early detection of disease recurrence remains challenging. Recent studies explored the role of ctDNA in guiding adjuvant treatment in colon cancer, but its role in pancreatic cancer remains unknown. Methods: Through comprehensive chart review, we identified patients who: 1. Diagnosed with early-stage pancreatic adenocarcinoma; 2. Underwent curative intent surgery at our institution from 2019 to 2021; 3. Have postoperative tissue informed ctDNA results with commercially available assay (Signatera, by Natera Inc). Results: A total of 14 patients, including 7 males and 7 females, were included in the study. Depending on location of tumor, types of surgery included Whipple procedure (N = 13) and distal pancreatectomy (N = 1). The median age at time of surgery was 62 years (Range: 41-83 years). Two patients received neoadjuvant chemotherapy, and 13 patients received adjuvant chemotherapy. Two patients also received adjuvant radiation. A total of 41 ctDNA readings were obtained. The median time from surgery to first ctDNA assay was 2.4 months. First post-op ctDNA was positive in 6 patients, all of whom received adjuvant chemotherapy but still experienced clinical recurrence after a median of 3.7 months. The median overall survival of those ctDNA+ patients was 11.4 months. In the remaining 8 patients, the median progression free survival was 14 months, with clinical recurrence being observed in 4 patients. Median overall survival was not reached at median follow up of 30.5 months (one patient died at 6 months without disease recurrence, and another died at 14 months with progressive disease). In the 4 patients who had clinical recurrence despite initially negative ctDNA, ctDNA turned positive 1 month before clinical recurrence in 1 patient. However, in the other 3 patients, recurrence occurred 3.1, 1.9 and 3.5 months after the most recent negative ctDNA result. Conclusions: Our study demonstrated that positive ctDNA reliably predicts clinical recurrence in early-stage pancreatic cancer after surgery, with a positive predictive value of 100%. Negative result appears to be less reliable. This may be explained by different shedding pattern and test sensitivity. Larger scale study is underway to further evaluate its role in determining prognosis and guiding adjuvant treatment.

The effect of anastomotic leakage on the incidence of recurrence after tri-modality therapy for esophageal adenocarcinomas.

Neoadjuvant chemoradiotherapy (nCRTx) reduces the incidence of recurrence, while anastomotic leakage has shown increase the risk of recurrence. The primary objective of this retrospective study was to investigate the incidence and pattern of recurrence and secondary median recurrence-free interval and post-recurrence survival in patients with and without anastomotic leakage after multimodal therapy for esophageal adenocarcinoma. Patients with recurrence after multimodal therapy between 2010 and 2018 were included. Six hundred and eighteen patients were included, 91 (14.7%) had leakage and 278 (45.0%) recurrence. Patients with leakage did not develop recurrence more often (48.4%) than those without (44.4%, [p = 0.484]). Recurrence-free interval for patients with (n = 44) and without leakage (n = 234) was 39 and 52 weeks, respectively (p = 0.049). Post-recurrence survival was 11 and 16 weeks, respectively (p = 0.702). Specified by recurrence site, post-recurrence survival for loco-regional recurrences was 27 versus 33 weeks (p = 0.387) for patients with and without leakage, for distant 9 versus 13 (p = 0.999), and for combined 11 versus 18 weeks (p = 0.492). No higher incidence of recurrent disease was observed in patients with anastomotic leakage, however it is associated with a shorter recurrence-free interval. This could have implications for surveillance, as early detection of recurrent disease could influence therapeutic options.

Detection of Circulating Tumor Cell-Related Markers in Gynecologic Cancer Using Microfluidic Devices: A Pilot Study.

The detection of circulating tumor cells (CTCs) is an emerging strategy for the early detection, prognostication, and identification of recurrent cancer. The clinical utility of CTC detection has been established, but few studies have employed this strategy for the detection of gynecologic cancers. Here, we present a novel, biochip-based microfluidic device for the detection of CTCs in gynecologic cancers. The study cohort included three patients with cervical cancer, eight with endometrial cancer, two with ovarian cancer, two with breast cancer, and one with vaginal small cell carcinoma. Four cancer type-specific molecular markers (PanCK, GATA3, HER2, and HE4), as well as CD13, were used for prognostication and recurrence detection, along with downstream genomic analysis. GATA3 and HER2 were markedly expressed in the patients with cervical cancer, and this expression was strongly correlated with the early detection of recurrent disease. All four molecular markers were expressed preoperatively in the patients with endometrial cancer, and the re-expression of different markers was observed at follow-up before recurrence was confirmed. CD13 was identified as an alternative prognostic marker for both cervical and endometrial cancer. Our pilot study indicated that the novel CTC detection system can be used for prognostication and early detection of disease recurrence, which needed further investigation.

Morphometric analyses in patients treated with subthreshold laser photocoagulation for central serous chorioretinopathy

Background and objectiveTo analyze changes in selected parameters in optical coherence tomography (OCT) after subthreshold laser coagulation (ST-LP) in patients with central serous chorioretinopathy (CSCR).Materials and methodsFifty-four eyes of 49 patients with CSCR were included in the study. Each patient underwent therapy with ST-LP with a frequency-doubled Neodym-YAG Laser and OCT imaging. In OCT the thickness of the central subfield, cube volume, average cube thickness, volume under the ETDRS grid, and average thickness under the ETDRS grid were collected.ResultsDecreases in total OCT volume and central retinal subfield thickness were statistically significant (p < 0.05). Possible correlations were observed between visual acuity at V3 (3 months after ST-LP) and Baseline and between central retinal subfield thickness at V1 (4 weeks after ST-LP) and visual acuity at BL.ConclusionA decrease in retinal thickness and retinal volume could be shown after ST-LP. Central retinal subfield thickness measured by OCT could be a more sensitive measure than mean retinal thickness or macular volume for early detection of disease recurrence occurring in some patients 3 months after ST-LP.

INNV-16. SPINAL POST-TREATMENT SURVEILLANCE IN MEDULLOBLASTOMA – A SYSTEMATIC REVIEW OF THE LITERATURE AND CLINICAL TRIALS

Abstract BACKGROUND Monitoring for dissemination in medulloblastoma involves spinal MRIs (sMRIs) and lumbar punctures (LPs). The frequency and duration of these studies vary depending on risk of dissemination; general practice varies between and within institutions. Our goal is to review the current practice in post-treatment monitoring via examination of published data, clinical trial standards, and expert practice. METHODS We reviewed the available literature and accessible clinical trial protocols. Using PRISMA guidelines, we conducted searches of Ovid MEDLINE, Embase, and PubMed to identify studies which detailed relapse rates and patterns, and recommended practice for patients with medulloblastoma aged 3-21 years. Eligible studies from 1990 to present were included. RESULTS Thirteen multi-institutional clinical trials from North America and Europe were analyzed for frequency of post-therapy surveillance with LPs/sMRIs. Several studies (n=8) recommend LPs/sMRIs every 3-6 months in standard risk and every 3 months in high risk disease for two years when initially completing therapy, and then often diverge in frequency after 2 years. Some studies (n=5) did not include post-treatment recommendations. Cumulative data on relapse from available clinical trial reports and single institution studies (n=673 relapses) demonstrated local failure rate of 18.4%, distant failure of 49.1%, and combined distant and local failure of 32.5%. Spine-only relapses were reported to occur in approximately 13-20%, with one small study reporting spine-only relapse rate of 37.5%. DISCUSSION Patterns of recurrence in medulloblastoma have shifted over time as therapeutic approaches have evolved, including more spinal-only recurrences. Standardized guidance regarding surveillance could have significant impact on clinical detection and streamline management to minimize unnecessary examinations. Early detection of recurrent disease could optimize treatment options for providers and families, whether focusing on curative approaches or quality of life.

ODP446 Where's the Nodule?: Atypical Presentation of an Occult Metastatic Papillary Thryoid Carcinoma

Abstract Papillary thyroid Carcinoma (PTC) with apparent distant metastasis but lacking a primary thyroid cancer on pre-operative ultrasonographic examination, is referred by some as occult PTC. In most cases, primary carcinomas are identified after careful pathologic examination of the specimen but in some rare cases the primary tumors were not detected. Hereby, we describe the rare case of a patient with metastatic PTC without initial visualization on imaging of primary tumor location along with inconsistent pathology results between fine needle aspiration (FNA) biopsy and gross specimen pathology results. A 60-year-old female with past medical history of Diabetes Mellitus type 2 and Hypothyroidism presenting for follow-up visit after being found with neck nodules on head and neck CT scan. Thyroid and neck Ultrasound (US) were performed finding three right irregularly shaped hypoechoic lymph nodes (LN's) measuring &amp;gt; 1 cm, concerning for metastatic disease, but no thyroid nodules were noted. Patient denies family history of thyroid cancer, and no head and neck radiation exposure. Physical examination did not reveal goiter or palpable nodules. Laboratory results: TSH: 2.95 and Total T4: 9.32, both within normal range. Cervical LN's FNA biopsy was performed, yielding results consistent with PTC tall cell variant. Chest CT scan showed suspicious lesions for pulmonary micrometastasis. Total thyroidectomy was performed and gross pathology findings showed an infiltrating, follicular variant PTC with multifocal tiny primary tumors of the thyroid, with lesions measuring up to 0.2 cm, dimension which explains why nodules could not be identified on imaging studies. LN's FNA biopsy results and thyroid pathology did not correlate. Thyroid gross pathology was clearly PTC with follicular variant, infiltrating a small area away from greatest dimension tumor, with cells with apparent dedifferentiation to tall cell cytologic features. Due to high risk of recurrence, radioactive iodine therapy was recommended as adjunctive therapy for metastatic disease and eradication of residual neck disease to be started with levels of TSH&amp;gt;30 mU/ml. Postopertative Thyroglobulin level (Tg) was adequate &amp;lt; 0. 01 ng/ml but unreliable based on above normal range antithyroglobulin antibody &amp;gt; 1000 IU/ml, which increases risk of recurrence. Whole body scan also done showing bilateral lung metastasis and small neck metastatic disease. Repeated postoperative thyroid US also demonstrated a suspicious cystic lymph node in right central neck for which FNA with saline washout of aspirate for Tg measurement was ordered. Metastatic thyroid carcinoma without primary tumor after extensive thyroid sampling is a rare but existent phenomenon that can be encountered in daily practice. Genotyping or immunostaining mestastatic lesions could help direct the Pathologist to the source of the metastasis. Patients with a higher risk of recurrence are monitored more aggressively as it is believed that early detection of recurrent disease offers the best opportunity for effective treatment. Presentation: No date and time listed

ADAMTS13 Biomarkers in Management of Immune Thrombotic Thrombocytopenic Purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare but potentially fatal blood disorder resulting from acquired deficiency of plasma ADAMTS13, a metalloprotease that cleaves endothelium-derived ultralarge von Willebrand factor. Standard of care for iTTP including therapeutic plasma exchange, caplacizumab, and immunosuppressives, known as triple therapy, has led to a significant reduction in the disease-related mortality rate. The first International Society of Thrombosis and Haemostasis TTP guideline stresses the importance of having plasma ADAMTS13 activity testing in the algorithm for diagnosis and management of iTTP. However, the predictive role of assessing plasma ADAMTS13 activity and inhibitors or other ADAMTS13-related parameters in patients with acute iTTP and during remission has not been systematically evaluated. To review and assess the predictive values of testing plasma ADAMTS13 activity, antigen, and inhibitors or anti-ADAMTS13 immunoglobulin G at various stages of disease in outcomes of iTTP. Peer-reviewed publications and personal experience. We conclude that assessing ADAMTS13 biomarkers is not only essential for establishing the initial diagnosis, but also crucial for risk stratification and the early detection of disease recurrence. This may guide therapeutic interventions during acute episodes and for long-term follow-up of iTTP patients.

Ultra-sensitive monitoring of leukemia patients using superRCA mutation detection assays

Rare tumor-specific mutations in patient samples serve as excellent markers to monitor the course of malignant disease and responses to therapy in clinical routine, and improved assay techniques are needed for broad adoption. We describe herein a highly sensitive and selective molecule amplification technology - superRCA assays - for rapid and highly specific detection of DNA sequence variants present at very low frequencies in DNA samples. Using a standard flow cytometer we demonstrate precise, ultra-sensitive detection of single-nucleotide mutant sequences from malignant cells against up to a 100,000-fold excess of DNA from normal cells in either bone marrow or peripheral blood, to follow the course of patients treated for acute myeloid leukemia (AML). We also demonstrate that sequence variants located in a high-GC region may be sensitively detected, and we illustrate the potential of the technology for early detection of disease recurrence as a basis for prompt change of therapy.

Abstract 530: UMAP- Personalized lung cancer monitoring platform

Abstract Lung cancer is the leading cause of cancer death, accounting for 1.6 million deaths per year. The prognosis for newly diagnosed cases is overall poor and strongly influenced by clinical stage at time of diagnosis, with dismal survival rates for cases diagnosed at a late stage. However, molecular profiling at diagnosis and advances in precision medicine has vastly improved the clinical management of lung cancer patients. An efficient evaluation of treatment response and early detection of recurrent disease can further improve survival rates. However, response evaluation during treatment is still limited to either radiological evaluation at fixed intervals or the risk-associated trans-thoracic biopsies that cannot be performed frequently. Therefore, there is an imperative need to identify minimally invasive, personalised biomarkers that can longitudinally monitor treatment response as well as early detect and map emerging resistance mechanisms leading to relapse. Employing liquid biopsy platforms to analyse tumor biomarkers in circulating nucleic acids, especially circulating tumor DNA (ctDNA), is a promising approach for longitudinal disease monitoring as it is less invasive and quantitative. Here we present the Umeå Molecular Adaptive Platform (UMAP) aimed for developing personalised tumor biomarkers for disease monitoring of individual lung cancer patients following curative treatment. The UMAP employs matched diagnostic tumor tissue and plasma samples from Swedish lung cancer patients (retrieved from Uppsala-Umeå Comprehensive Cancer Consortium, Sweden) and entails mutational profiling of tumor tissue, specifically identifying disease-associated large structural variants (SVs) and single nucleotide variants (SNVs) by long read sequencing using Oxford Nanopore Technology (ONT) and Illumina TST170 target enrichment sequencing, respectively. Individualized SVs and SNVs biomarker assays are then developed for droplet digital PCR (ddPCR) -based analysis and quantification in ctDNA isolated from corresponding plasma samples. This tailored, patient-specific panel can then be used to longitudinally monitor disease evolution and treatment response during the entire therapy regimen using blood-based sampling. The UMAP workflow has been optimised by mutational profiling of 3 lung cancer cell lines (H1299, H1975 and H2228) and fresh frozen tumor tissues from 12 lung cancer patients using ONT and Illumina TST170 panel followed by development of robust, highly sensitive ddPCR assays for targeting candidate SNVs and SVs with minimal hands-on time and with detection limit as low as 0.001%. Impact of this tailored approach on improving survival can be evaluated by implementing UMAP in a prospective clinical trial with patients with advanced lung cancer disease. Citation Format: Zahra Haider, Linda Köhn, Nicholas Karlowatz, Mikael B. Johansson, Jonas A. Nilsson. UMAP- Personalized lung cancer monitoring platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 530.

Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma.

High-level amplification of MDM2 and other genes in the 12q13–15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasive distinction between these liposarcomas and other retroperitoneal tumors in differential diagnosis, and might be useful for the early detection of disease recurrence. In this study, we performed shallow whole genome sequencing of cell-free DNA extracted from 10 plasma samples from 3 patients with DDLPS and 1 patient with WDLPS. In addition, we studied 31 plasma samples from 11 patients with other types of soft tissue tumors. We detected MDM2 amplification in cell-free DNA of 2 of 3 patients with DDLPS. By applying a genome-wide approach to the analysis of cell-free DNA, we also detected amplification of other genes that are known to be recurrently affected in DDLPS. Based on the analysis of one patient with DDLPS with longitudinal plasma samples available, we show that tracking MDM2 amplification in cell-free DNA may be potentially useful for evaluation of response to treatment. The patient with WDLPS and patients with other soft tissue tumors in differential diagnosis were negative for the MDM2 amplification in cell-free DNA. In summary, we demonstrate the feasibility of detecting amplification of MDM2 and other DDLPS-associated genes in plasma cell-free DNA using technology that is already routinely applied for other clinical indications. Our results may have clinical implications for improved diagnosis and surveillance of patients with retroperitoneal tumors.

Recurrent Neovascular Age-Related Macular Degeneration after Discontinuation of Vascular Endothelial Growth Factor Inhibitors Managed in a Treat-and-Extend Regimen

To investigate the recurrence rate of active macular neovascularization in patients with neovascular age-related macular degeneration (nAMD) previously followed up in a treat-and-extend (TE) regimen in which treatment had been stopped because of disease stability. Prospective cohort study. One hundred five patients with nAMD previously followed up in a TE regimen treated with aflibercept injections. All patients with a dry macula on 3 consecutive visits 12 weeks apart were eligible to participate in the study. Patients were examined at baseline and then monitored for disease recurrence 4, 6, 8, 10, and 12 months after the last injection. The proportion of patients with recurrent disease within 12 months after the last injection. Change in best-corrected visual acuity (BCVA) at the time of recurrence and after resumed therapy. Evidence of recurrent nAMD was seen in 54 of 102 patients (52.9%) after 12 months of follow-up. The mean time to recurrence after the last injection was 6.7 ± 2.2 months. The BCVA decreased from 71.7 ± 10.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 68.1 ± 11.1 ETDRS letters at the recurrence (P= 0.12). After treatment resumed, BCVA increased to 71.4 ± 10.0 ETDRS letters (P= not significant compared with baseline). Patients with a pigment epithelial detachment (PED) at baseline showed a 74% (14/19) recurrence rate compared with 48% (40/83) in patients without a PED (P < 0.05). Only 22 of 54 patients (40.7%) with recurrent disease showed symptoms of visual loss or metamorphopsia. Recurrent nAMD is common in previously stable patients for whom anti-VEGF injections have been suspended. It is difficult to predict which patients will experience a recurrence, and most of these patients do not show symptoms in the early stages of reactivation. Long-term follow-up is important, and early detection of recurrent disease can improve the chances for maintained visual function.

Radiological Surveillance Post-Curative Colorectal Cancer Resection: Is There a Need for a Targeted Protocol?

BackgroundThe frequency of radiological surveillance after curative colorectal cancer resection has long been a controversial issue with the need to balance potential harm from ionizing radiation and the financial burden of intense surveillance against advantages of early detection of recurrent disease. NICE guidelines issued in 2018 suggested having two surveillance computed tomography (CT) scans within three years of surgery without specifying the timing or the interval.AimTo examine whether an evidence-based flexible approach based on individual patients’ risk factors can add value to surveillance protocols. Reaching a targeted protocol that can maximize early detection of metastasis without consumption of resources and most important without compromising patient safety.MethodologyA retrospective study involving five years of data of patients who underwent curative colorectal cancer resections. Data extracted after patients completed their three-year surveillance CT scans, CT reports retrieved together with post-operative histology reports, and a detailed database was constructed.ResultsOf 179 patients included, 66 developed recurrence (7 local and 59 distant). Recurrence increased from 23.5% in T1 to 66% in T4 (P=0.0001). The median time to recurrence 23 months in T4 disease compared to 36, 42 and 43 months for stages T1, T2 and T3, respectively (P=0.0001). A similar incremental increase in recurrence noted from 22% in the N0 stage to 73.5% in the N2 stage (P=0.0001); the median time to recurrence of 14 months in N2 patients compared to 45 and 33 months for stages N0 and N1, respectively (P=0.0001). Recurrence correlated well with positive extramural vascular invasion (EMVI) status, (71.7% versus 19.3% P=0.0001) being detected significantly earlier in EMVI positive group at 17 versus 45 months (P=0.0001).ConclusionFlexible protocol for radiological surveillance after curative resection of colorectal cancer, based on known pathological prognostic factors, is likely to be more effective in maximizing resource utilization as well as improving patient outcomes.

Diagnostic utility of (18)f-fluciclovine positron emission tomography (FACBC) in biochemically recurrent (BCR) prostate cancer (PCa) based on prior primary treatment modality for localized disease and the impact of FACBC findings on treatment selection.

34 Background: Management of BCR PCa requires accurate assessment of location and extent of recurrent disease. FACBC has been shown to be a sensitive modality for detection and localization of recurrent disease but treatment guidelines are based on the findings of conventional (conv) imaging, including computed tomography, magnetic resonance imaging, or bone scintigraphy, and little is known about how prior treatment impacts FACBC findings and concordance with conv scans. Methods: This single-center retrospective study included 137 patients (pts) who had FACBC for BCR at the University of Wisconsin-Madison from 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts were classified by type of primary treatment for localized PCa, either radical prostatectomy (RP) or radiation therapy (RT). Findings of conv scans performed within 4 weeks prior or any time after FACBC were collected. Results: 105 pts had RP and 32 pts had RT as their primary PCa treatment. Gleason score and PSA at diagnosis were similar between groups. Median PSA at time of FACBC was higher in the RT compared to RP group (3.3 vs 0.7 ng/dL) and median time from initial diagnosis to FACBC was longer (70 vs 55 months). Frequency of (+) FACBC findings was higher in the RT group (66% vs 47%); only 3% of pts in the RT group had a (-) FACBC compared to 29% in the RP group. The rate of (+) lesions in the prostate/prostate bed was higher in the RT group (41% vs 22%), while the rate of (+) lesions in pelvic nodes and distant sites was similar between groups. Of 69 pts who also had conv imaging, 61% had concordant conv imaging findings. In the RT group, conv and FACBC findings were similar in 47% of pts and not similar in 28%. In the RP group, conv and FACBC findings were similar in 26% of pts and not similar in 17%. Management after FACBC is listed in table. Median time from FACBC to first (+) conv scans was 6 (range: 0-18) and 5 (range: 0-17) months for RT and RP groups, respectively. Conclusions: In this large retrospective cohort, pts treated with initial RT had a longer median time from diagnosis to FACBC and higher median PSA at the time of FACBC compared to the RP group. RT patients had a higher rate of (+) FACBC findings but were more likely to continue on observation. The median time from FACBC to first (+) conv scan was 5-6 months, supporting the role of FACBC in earlier detection of recurrent disease in both groups of patients. Further analysis of concordance between FACBC and conv imaging is in process. [Table: see text]

Initial Stage of Cutaneous Primary Melanoma Plays a Key Role in the Pattern and Timing of Disease Recurrence

Given recent developments in the treatment of metastatic melanoma, early detection of disease recurrence is crucial. The aim of this single-centre retrospective cohort study was to investigate the impact of the initial stage of primary melanoma on the pattern and timing of disease recurrence and post-recurrence survival. Patients diagnosed with cutaneous melanoma with initial stage IA–IIID, between January 1996 and December 2018 and who developed disease recurrence until May 2019 were included (n = 784). Earlier stage at diagnosis was associated with a higher proportion of locoregional and a lower proportion of distant metastasis (p = 0.01). The median time to first metastasis decreased with the more advanced stages at initial diagnosis: 3.32 years (interquartile range (IQR) 1.72–6.14 years) for stage I, 1.85 years (IQR 0.99–3.78 years) for stage II and 1.19 years (IQR 0.70–2.42 years) for stage III disease (p < 0.001). These findings add evidence that American Joint Committee on Cancer stages at initial diagnosis of melanoma play a key role in the pattern and timing of disease recurrence and may be helpful to improve surveillance strategies in the follow-up of patients with melanoma.

TRIM study protocol - a prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma

BackgroundThe incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only.MethodsThe TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/− whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group.DiscussionThis is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM.ResultsThe first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden.Trial registrationClinicalTrials.gov, NCT 03116412. Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412