Increased Risk Of Recurrence Research Articles

Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion.

Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain. The present systematic review, meta-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors. Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality. All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion. Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research. Risk ratio effect sizes (RR) and corresponding 95% Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of meta-analysis evidence with definition of current knowledge gaps and future research aims. In 38 050 female patients receiving adjuvant endocrine treatment, of whom 1805 had been exposed to TE, TE exposure of those on AI, did not increase all-cause mortality (RR 0.99 [95%CI 0.58, 1.69], I2=81%, P = 0.96; moderate GRADE certainty). However, such exposure may convey an increased risk of recurrence (RR 2.51 [95% CI 1.10, 5.72], I2=9%, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders. The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality, cannot be ruled out when TE is used during AI.

Life after benign paroxysmal positional vertigo: one-year analysis of recurrence, headaches, neck pain, falls, and functional vestibular symptoms.

Benign paroxysmal positional vertigo (BPPV) is a vestibular disorder causing recurrent episodes of vertigo. Despite symptom resolution at discharge, events such as relapses, migraines, neck pain, falls, and persistent postural-perceptual dizziness (PPPD) may occur. This study aims to estimate the incidence, timing, and risk factors for these symptoms. This multicenter, prospective, observational study recruited patients with a first episode of BPPV. Patients were treated with canalith repositioning maneuvers and discharged when no nystagmus was observed. Follow-up included in-person and telephone assessments over one year. The incidence and timing of symptoms were calculated, and risk factors were identified through regression models. 201 patients were recruited, and 124 met the inclusion criteria. 70.97% experienced events after discharge, though symptoms were not always severe enough to seek medical care. No useful risk factors were found for predicting BPPV recurrence. Low vitamin D levels increased recurrence risk but did not effectively discriminate patients. Women were more likely to develop headaches. Prior headaches, migraines, or neck pain were the strongest predictors of future occurrences of these conditions. Headaches or neck pain themselves triggered vestibular symptoms, often indistinguishable from BPPV. BPPV was associated with new-onset neck pain. The risk of falls increased with age. Anxiety triggered by BPPV predicted PPPD. Developing symptoms after discharge increased the likelihood of other events. Although BPPV is considered resolved when no nystagmus is observed during provocation tests, it should be understood as a condition accompanied by other symptoms that often persist after discharge in most patients.

Local Recurrence of Premalignant and Early Malignant Rectal Polyps Treated by TEM—A Single-Center Experience

Background: Transanal endoscopic microsurgery (TEM) is a minimally invasive approach for excising rectal polyps, particularly those with high-grade dysplasia (HGD) or early-stage rectal cancer (T1). This study aimed to evaluate the recurrence risk and its associated factors in patients treated with TEM for HGD and T1 rectal tumors. Methods: A retrospective review was conducted on 79 patients who underwent TEM for rectal lesions at Rabin Medical Center-Hasharon Hospital from 2005 to 2019. Data collected included demographics, tumor characteristics, and follow-up outcomes, with specific focus on tumor size, resection margins, mucin production, and distance from anal verge (AV). Separate and unified analyses were performed to assess the recurrence risk factors for both HGD and T1 patients. Results: Sixty-three patients were included in the final analysis. In the unified analysis, larger tumor size was significantly associated with increased recurrence risk (OR = 2.27, p = 0.028), and mucin production was a strong predictor of recurrence in the T1 group and combined analysis (p = 0.0012 and p = 0.014, respectively). Distance from AV demonstrated a borderline association with recurrence (p = 0.053). Conclusions: Larger tumor size and mucin production are significant predictors of recurrence in TEM-treated rectal polyps. Personalized follow-up and postoperative management are essential for patients with these risk factors to reduce the recurrence risk.

Dermatofibrosarcoma Protuberans: The Impact of the Surgical Incision Site in Relation to Tumor Recurrence.

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally invasive cutaneous sarcoma with a high propensity for recurrence, even following complete surgical excision. DFSP exhibits a low metastatic potential and is characterized by a distinctive honeycomb-like architecture composed of uniformly arranged spindle cells that frequently show CD34 immunostaining. Common surgical approaches include wide local excision (WLE), Mohs micrographic surgery (MMS), and, in severe cases, amputation.This literature review explores the impact of the surgical incision site on DFSP recurrence, placing particular emphasis on anatomically challenging regions, such as the head and neck, where achieving tumor-free margins is often difficult due to complex structures and limited tissue for resection. Our primary hypothesis is that DFSP cases arising in these intricate anatomical areas exhibit a higher recurrence risk compared to those on the trunk or extremities, where broader margins are more feasible. To investigate this hypothesis, data from a range of peer-reviewed studies and case reports were analyzed, including diverse patient populations from international sources, institutional case series, and large-scale database analyses, such as the Surveillance, Epidemiology, and End Results (SEER) Program. We evaluated recurrence rates, the adequacy of surgical margins, and anatomical influences across these studies while also focusing on histopathological findings like the presence of fibrosarcomatous (FS) variants, which are known to correlate with aggressive behavior and recurrence. We also reviewed emerging targeted therapies, particularly imatinib, as promising options for managing cases of unresectable or recurrent DFSP, thereby expanding therapeutic choices for clinicians when surgery alone proves inadequate.Our findings suggest a marked increase in recurrence risk for DFSP cases located in the head and neck region, attributed to limitations in achieving wide excision margins in these areas. This review underscores the importance of detailed preoperative planning, precise excision strategies, and individualized approaches based on tumor location to enhance surgical outcomes. Long-term surveillance remains crucial in DFSP management, particularly in high-risk locations, and continued research into targeted therapies offers hope for reducing recurrence rates and improving the quality of life for affected patients.

National trends in the prevalence and recurrence of anaphylaxis across all ages: The role of neighborhood deprivation and comorbidity (2002–2019)

BackgroundUnderstanding the trends of anaphylaxis and risk factors associated with its recurrence is essential for the effective management and prevention of this condition. ObjectiveThis study aimed to analyze the prevalence trends of anaphylaxis and identify risk factors for recurrence, with a focus on the influence of neighborhood deprivation and comorbidities, across all age groups. MethodsWe conducted a retrospective administrative cohort study on anaphylaxis utilizing the National Health Insurance-National Sample Cohort (NHIS-NSC) database in Korea (2002–2019). Anaphylaxis was defined with ICD-10 codes for the diagnosis combined with prescription codes. The Neighborhood Deprivation Index was used to identify the risk of recurrent anaphylaxis. Trends in the annual prevalence and recurrence of anaphylaxis were assessed through joinpoint regression and Cox proportional hazard models. ResultsOut of the 1,137,861 individuals studied, 37,012 (3.25%) cases of anaphylaxis were identified. Among these, 5783 individuals (15.6%) experienced a recurrence, half of them experiencing it within the first year after the initial episode. The highest incidence of anaphylaxis was observed in children and adolescents, followed by middle-aged adults. A rapid increase in anaphylaxis cases was observed from 2002 to 2006 (Annual Percentage Change [APC], 33.2), followed by a more gradual increase until 2013 (APC, 12.8), and a stable trend from 2013 to 2019 (APC, 0.61). Males and adult age groups exhibited an increased risk of recurrence. Living in an area with neighborhood deprivation and the presence of comorbid conditions were associated with increased recurrence risk. ConclusionsThe increasing prevalence of anaphylaxis and its association with certain risk factors calls for targeted intervention. Addressing neighborhood deprivation and comorbid conditions may aid in reducing the recurrence and overall burden of anaphylaxis.

Cost effectiveness analysis of BRAFV600E testing for low-risk papillary thyroid microcarcinomas.

Given the good prognosis of low-risk papillary thyroid microcarcinomas (lrPTMCs), accurate risk stratification is valuable to optimize management: active surveillance (AS) vs. hemithyroidectomy (HT). BRAFV600E positive lrPTMC is associated with increased recurrence risk; hence, AS was suggested for mutation-negative lrPTMC. This study aims to evaluate the cost-effectiveness of BRAFV600E testing for lrPTMC. Decision tree cost-effectiveness analytic model. We performed a cost-effectiveness analysis of the management strategies for lrPTMCs: AS, HT, and BRAFV600E genetic testing (GT), in which treatment pathways were determined by BRAFV600E status. Data on probabilities and complications were derived from current literature. One- and two-way sensitivity analyses were conducted to ascertain model robustness. Our model found GT as the cost-effective strategy, providing an additional 0.35 QALYs and an additional cost of $902 with an Incremental Cost-effectiveness ratio of $2542 compared to AS. In contrast, surgical intervention showed a lower utility with an increased cost of $381, positioning GT as the preferred strategy. Sensitivity analysis identified age at diagnosis as the most influential factor for cost-effectiveness between AS and GT; younger patients exhibited a lower ICER, indicating greater cost savings per QALY, till up to age 48years, where AS becomes favorable. GT consistently outperformed QALY gains across varying incidences of BRAFV600E positivity tumors. In conclusion, this study demonstrates the economic and clinical advantages of incorporating BRAFV600E genetic testing in the management of lrPTMCs. Our model supports further real-life studies of BRAFV600E testing for lrPTMCs.

Prognostic impact of targetable driver alterations in resected early-stage lung cancer.

Apart from ALK fusions and the common EGFR mutations, targetable molecular alterations are irrelevant for adjuvant treatment decision making in early-stage non-small cell lung cancer (NSCLC). This retrospective analysis aimed to investigate if there is a difference in recurrence-free survival in stage I-III NSCLC harboring druggable molecular alterations compared to subtypes without targetable molecular alterations. All consecutive patients who underwent surgery with curative intent for NSCLC (stage I-III) with targetable mutations between January 2015 and December 2020 at three Austrian institutions were identified and compared with tumors without targetable molecular alterations. Tumors with the EGFR-mutated subtype were excluded due to already existing results from prospective trials. One hundred and sixty subjects had tumors with molecular alterations and 355 subjects served as control cohort. There was a higher prevalence of female sex (P<0.001) and never-smokers (P=0.01) among patients with tumors harboring oncogenic driver mutations. The three most common alterations were the KRAS G12C mutation (n=92), ALK fusions (n=21), and the BRAF V600E mutation (n=15). The 1-, 3- and 5-year cumulative incidence of recurrence estimates were 16%, 38% and 46% in patients without molecular alterations and 16%, 38% and 48% in patients with the KRAS G12C mutation and 12%, 33% and 55% in patients with other molecular alterations, respectively (P=0.89). Univariable predictors of an increased recurrence risk were higher tumor stage (P<0.001), receipt of neoadjuvant treatment (P<0.001) and receipt of adjuvant treatment (P=0.03). The lack of association between molecular alteration status and recurrence risk prevailed after multivariable adjustment for tumor stage and perioperative treatment (P=0.82 for KRAS G12C mutation and P=0.43 for any other molecular alteration). NSCLC patients with resected tumors that harbor molecular alterations have the same recurrence risk as patients with tumors without molecular alterations if treated with surgery plus chemotherapy when indicated.

Is tamoxifen good enough for the Asian population in ER+ HER2- post-menopausal women with early breast cancer? A nationwide population-based cohort study.

Numerous clinical trials have compared the efficacy of endocrine therapy in post-menopausal breast cancer patients. This study aims to explore whether there is a difference in recurrence rates between this population using tamoxifen and aromatase inhibitors (AIs) by analyzing real-world data. This retrospective cohort study utilized the National Health Insurance (NHI) claims data and the Taiwan Cancer Registry (TCR). We identified 6,050 patients aged over 55 diagnosed with ER-positive, HER2-negative early breast cancer between 2012 and 2016 (4,451 on AIs alone and 1,599 on tamoxifen alone). Recurrence in both groups was assessed until the end of 2020. Hazards were measured based on age of diagnosis, cancer stage, adjuvant chemotherapy, radiation therapy, type of endocrine therapy used, and adherence. Recurrence‑free survival between the AIs and tamoxifen groups was evaluated using the Kaplan-Meier model. The average age was 65.1 years, with a median follow-up time of 5.7 years and a median duration of endocrine therapy of 4.5 years. The recurrence rate was 2.2%. Using tamoxifen as endocrine therapy reduces the risk of recurrence compared to AIs (adjusted HR: 0.32, p < 0.0001). There was no statistical difference between the two drugs in stage 1 breast cancer. However, in stage 2, the risk of breast cancer recurrence decreased to 0.15 times with the use of tamoxifen compared to AIs (p = 0.0002). Stage 2 cancer, histological grade 3, and non-adherence increased recurrence risk in post-menopausal breast cancer patients. Based on real-world data analysis, in ER-positive, HER2-negative post-menopausal women with early breast cancer in Taiwan, the use of tamoxifen compared to AIs is associated with a lower risk of recurrence. Improved adherence to medication can break the cycle of recurrence and improve health outcomes.

Low tristetraprolin expression activates phenotypic plasticity and primes transition to lethal prostate cancer in mice.

Phenotypic plasticity is a hallmark of cancer and increasingly realized as a mechanism of resistance to androgen receptor (AR)-targeted therapy. Now that many prostate cancer (PCa) patients are treated upfront with AR-targeted agents, it's critical to identify actionable mechanisms that drive phenotypic plasticity, to prevent the emergence of resistance. We showed that loss of tristetraprolin (TTP, gene ZFP36) increased NF-κB activation, and was associated with higher rates of aggressive disease and early recurrence in primary PCa. We also examined the clinical and biological impact of ZFP36 loss with co-loss of PTEN, a known driver of PCa. Analysis of multiple independent primary PCa cohorts demonstrated that PTEN and ZFP36 co-loss was associated with increased recurrence risk. Engineering prostate-specific Zfp36 deletion in vivo, induced prostatic intraepithelial neoplasia, and, with Pten co-deletion, resulted in rapid progression to castration-resistant adenocarcinoma. Zfp36 loss altered the cell state driven by Pten loss, demonstrated by enrichment of EMT, inflammation, TNFα/NF-κB, IL6-JAK/STAT3 gene sets. Additionally, our work revealed that ZFP36 loss also induced enrichment of multiple gene sets involved in mononuclear cell migration, chemotaxis, and proliferation. Use of the NF-κB inhibitor, dimethylaminoparthenolide (DMAPT) induced marked therapeutic responses in tumors with PTEN and ZFP36 co-loss and reversed castration resistance.

Association of BRAF V600E allele frequency with clinicopathologic outcomes in papillary thyroid cancer.

BRAF V600E mutation is the most common genetic driver of papillary thyroid cancer (PTC), where it is found with various allele frequency (AF), reflecting the proportion of cells carrying the mutant and wild-type gene alleles. To determine whether BRAF V600E AF can improve prognostication and inform initial surgical management of PTC. Retrospective cohort study (2016-2019). UCLA health. Consecutive patients with Bethesda V/VI nodules and isolated BRAF V600E mutation who underwent surgery with histopathology showing PTC. Blinded ThyroSeq v3 molecular analysis after completion of initial management and follow-up. Aggressive histopathology and cancer persistence/recurrence. Of 73 patients, the median BRAF V600E AF was 25.5% (IQR, 16.7-34.3%). Higher median AF was seen in patients classified as American Thyroid Association (ATA) high-risk (37%) vs. intermediate-risk (25.3%, p<0.01) and low-risk (24.7%, p<0.01), largely attributed to higher AF in patients with gross extrathyroidal extension (ETE) (40.1% vs. 25.2% without gross ETE, p=0.02). No differences in AF were observed on the basis of lymph node positivity or presence of aggressive variants of PTC. A higher BRAF V600E AF was also found in patients with tumors ≥2cm vs. <2cm (median 32.0% vs. 24.4%, p<0.01). Over 4.1 years of follow-up, disease persistence/recurrence was found in 7 patients (9.4%) and was associated with higher median AF than those without recurrence (35.3% vs. 25.2%, p=0.02). Higher AF was associated with poorer recurrence-free survival (AF≥35%, HR 7.40, CI 1.4-38.1). Higher AF was associated with gross ETE and increased recurrence risk. This may inform initial management in patients with PTC harboring an isolated BRAF V600E mutation.

Ethanol sclerotherapy in pediatric rectal prolapse: efficacy, complications, and influencing factors

IntroductionRectal prolapse is prevalent in children and the elderly, impacting quality of life significantly. Traditional surgical interventions carry risks, especially in pediatric patients. Ethanol sclerotherapy offers a less invasive alternative, inducing fibrosis and thickening of the rectal wall. Despite its potential benefits, procedural complications are possible, emphasizing the need for careful patient selection and procedural expertise. This study aims to evaluate the safety and efficacy of sclerotherapy in treating rectal prolapse in a tertiary referral center in southern Iran.MethodsPatient records from Nemazee Hospital covering January 2014 to December 2023 were retrospectively analyzed. Pediatric patients undergoing ethanol sclerotherapy for rectal prolapse were included. Data on demographics, presentation, procedures, and outcomes were collected. Ethical approval was obtained, and specific inclusion/exclusion criteria were applied. Statistical analyses were conducted using SPSS version 26.ResultsOne hundred thirty patients were evaluated, with a mean age of 10.74 ± 5.320 years. Most patients experienced constipation (56.9%). 74.2% responded well to sclerotherapy, with 12.9% needing a second injection. Complications were minimal, with bleeding being the most common (4.6%). Recurrence occurred in 18.6% of cases. Male patients showed a higher total complication rate (P = 0.010). Diarrhea-dominant patients had no recurrences post-sclerotherapy. Age significantly influenced treatment response and recurrence (P = 0.017, P = 0.035).ConclusionMale predominance contradicted global pediatric rectal prolapse ratios, possibly influenced by cultural factors. Sclerotherapy remains effective, though response rates vary. Older age correlated with lower response rates and higher recurrence. Constipation-dominant prolapse was associated with increased recurrence risk. Male patients had a higher complication rate, highlighting the need for tailored management strategies.

Predictive and Prognostic Value of Inflammatory and Nutritional Indexes in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy.

Background and Objectives: Neoadjuvant chemotherapy (NAC) improves survival by increasing pathologic complete response (pCR). Blood-based indexes have been studied in breast cancer for predicting pCR and prognosis, but the results are conflicting. We aimed to assess the impact of inflammatory and nutritional indexes on pCR and survival. Materials and Methods: We retrospectively analyzed 304 patients. Pre-NAC laboratory data were used to calculate their neutrophil-to-lymphocyte ratios (NLR), pan-immune inflammation values (PIV), lactate dehydrogenase-albumin ratios (LAR), and prognostic nutritional indexes. The optimal cut-off values were determined through an analysis of the receiver operating characteristic curve. Survival analyses were performed using the Kaplan-Meier method. Multivariate regression analyses were performed to reveal the factors predicting pCR. Univariate and multivariate survival analyses were conducted to identify prognostic factors predicting survival. Results: The median follow-up was 38.5 months. pCR was achieved in 41.4% of the patients. In the univariate analyses, the NLR (p = 0.032) and PIV (p = 0.002) were indexes associated with pCR. In the multivariate analysis, the PIV (p = 0.008) was the only index significantly correlated with pCR. According to the multivariate Cox regression analyses, clinical stage 3 (p = 0.032), a pathologic response other than pCR (p = 0.021), and a high LAR (≥4.72) (p = 0.002) were correlated with increased recurrence risk. The univariate Cox regression analyses revealed that failure to achieve pCR (p = 0.037) and the presence of a high LAR (p = 0.044) were significant predictors of overall survival. However, the multivariate analyses failed to identify any significant predictors of death. Conclusions: We found that the PIV was more effective than the other indexes in predicting pCR. To our knowledge, this study is the first to determine an association between the LAR and disease-free survival in patients with breast cancer receiving NAC. We concluded that a high LAR was a poor prognostic factor, especially in patients without a pCR. Therefore, close postoperative monitoring and the intensification of adjuvant treatment should be considered for these patients. However, further studies are needed to confirm our findings.

Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. This retrospective cohort study included women aged 18years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

Left Atrial Low-Voltage Extent Predicts the Recurrence of Supraventricular Arrhythmias.

The incidence of left atrial (LA) supraventricular arrhythmias is increasing. Even after LA ablation, recurrence of these tachycardias is common. MRI studies show that LA cardiomyopathy is a significant risk factor for recurrence and correlates with low voltage areas detected via 3D electroanatomic mapping (EAM). There are limited data on the impact of low voltage extent detected by EAM on recurrence-free survival. Voltage thresholds defining low voltage vary across different studies. This study aims to investigate the impact of the extent of low voltage areas in the LA on recurrence-free survival and to assess whether defining low voltage areas using thresholds of 0.5, 0.4, or 0.3 mV offers better predictive performance. Patients with atrial arrhythmia who underwent LA EAM at Ulm University Heart Center between September 2018 and September 2022 were included from the ATRIUM registry. ROC analysis determined the voltage threshold for predicting recurrence-free survival. Kaplan-Meier and logistic regression models adjusted for patient variables were used to analyze recurrence-free survival. Of 1089 screened patients, 108 met the inclusion criteria. ROC analysis indicated that a 0.4 mV threshold for low voltage provided the best predictive performance. Logistic regression showed a 1.039-fold increase in recurrence risk per percent increase in LA low voltage area (odds ratio = 1.039, 95% CI 1.014-1.064). Low voltage extent in EAM correlates with 1-year recurrence rate after ablation of left atrial supraventricular arrhythmias. The threshold of 0.4 mV is the most suitable for predicting recurrences of those examined.

Discerning the impact of ctDNA detection on patient decision-making in early-stage breast cancer

The impact of knowledge of circulating tumor DNA (ctDNA) status on patient decisions in high-risk triple-negative breast cancer (TNBC) weighing benefit and toxicity is unknown. Here, 286 women with a history of non-metastatic breast cancer who had received chemotherapy completed a survey mimicking scenarios of residual TNBC after chemotherapy and unknown, negative, or positive ctDNA status to determine the shift in the decision to receive adjuvant therapy. Participants were then presented scenarios mimicking possible post-neoadjuvant therapies and rated acceptability. A general linear model with repeated measures determined contributions of risk reduction and toxicity. When the hypothetical risk of recurrence mimicked ctDNA negativity, significantly less participants were accepting of adjuvant capecitabine versus no therapy. When presented with ctDNA positivity and increased recurrence risk, the degree of benefit impacted acceptability more than the toxicity profile. As genomic technology advances and ctDNA assays become commercially available, it is imperative to understand the impact on patient decision-making.

Alterations of striatal phosphodiesterase 10 A and their association with recurrence rate in bipolar I disorder

Phosphodiesterase 10 A (PDE10A), a pivotal element of the second messenger signaling downstream of the dopamine receptor stimulation, is conceived to be crucially involved in the mood instability of bipolar I disorder (BD-I) as a primary causal factor or in response to dysregulated dopaminergic tone. We aimed to determine whether striatal PDE10A availability is altered in patients with BD-I and assessed its relationship with the clinical characteristics of BD-I. This case-control study used positron emission tomography (PET) with 2-(2-(3-(4-(2-[18F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659), a radioligand that binds to PDE10A, to examine the alterations of the striatal PDE10A availability in the living brains of individuals with BD-I and their association with the clinical characteristics of BD-I. [18F]MNI-659 PET data were acquired from 25 patients with BD-I and 27 age- and sex-matched healthy controls. Patients with BD-I had significantly lower PDE10A availability than controls in the executive (F = 8.86; P = 0.005) and sensorimotor (F = 6.13; P = 0.017) subregions of the striatum. Lower PDE10A availability in the executive subregion was significantly associated with a higher frequency of mood episodes in patients with BD-I (r = –0.546; P = 0.007). This study provides the first evidence of altered PDE10A availability in patients with BD-I. Lower PDE10A availability in the executive subregion of the striatum is associated with an increased recurrence risk, suggesting that PDE10A may prevent BD-I relapse. Further studies are required to elucidate the role of PDE10A in BD-I pathophysiology and explore its potential as a treatment target.

Treatment outcomes in patients with papillary thyroid cancer undergoing radiofrequency ablation of metastatic lymph nodes.

Lymph node metastases in papillary thyroid cancer (PTC) increases recurrence risk and negatively impact survival. Traditional treatments like re-operation and radioactive iodine (RAI) have downsides. Radiofrequency ablation (RFA) is an emerging non-surgical therapeutic option, but there is seldom data on its efficacy and safety specifically for metastatic lymph nodes. We aimed to evaluate clinical outcomes of RFA applied to cervical lymph nodes in patients with PTC metastasis in North American population. This was a single-institution retrospective analysis of 68 PTC patients with lymph nodes who underwent percutaneous RFA from January 2020 to December 2022. Volume reduction ratio (VRR), changes in thyroglobulin (Tg) levels, lymph node regrowth rate, and complications were assessed. Treatment response and outcomes were analyzed. Median lymph node maximum diameter was 12.9 mm and median volume was 0.27 mL at baseline. After RFA, median VRR was 79.5% [interquartile range (IQR), 50-89.7%]. Post-RFA, Tg to an average of 0.2 ng/mL (IQR, 0-0.6 ng/mL). In the 19 patients (27.9%) with undetectable Tg after RFA, median VRR was 86% (IQR, 73-94%). Quantitative Tg decrease strongly correlated with VRR percentage (r=0.82, P<0.001). Lymph node regrowth was seen in 5 patients (7.4%) over median 18 months follow-up. Only one patient experienced transient thermal injury associated with Horner's syndrome and symptoms resolved within 1 month. In patients with PTC and metastatic cervical lymph nodes, RFA provided marked volume reduction and meaningful biochemical response without major complications. Excellent radiographic control was achieved in most patients. RFA demonstrates early promise as an emerging non-surgical therapeutic option for PTC patients with metastatic lymph nodes.

Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma

Background and aimInflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma (HCC). However, the tumor-protective functions of growth differentiation factors (GDFs) in HCC are yet to be clarified. In this study, we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform in vitro and in vivo experiments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC. MethodsThe gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues. A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression. Loss-of-function experiments were also performed in vitro and in vivo to investigate the role of GDF7 in HCC. ResultsThe mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in paratumors (P < 0.001). Kaplan–Meier analysis showed that decreased GDF7 expression in HCC was associated with worse overall survival (5-year rate: 61.8% vs. 27.5%, P < 0.001) and increased recurrence risk (P < 0.001). Multivariate Cox regression analysis demonstrated that low GDF7 expression, the presence of microvascular invasion, and elevated alpha-fetoprotein (AFP) levels were independent risk factors for tumor recurrence and poor survival. Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model. GDF7 knockdown promoted migration and invasion via epithelial–mesenchymal transition. Meanwhile, a negative correlation between JunB proto-oncogene (JUNB) and GDF7 was observed in HCC tissues. Modulating JUNB levels altered GDF7 protein expression. ConclusionGDF7 is a potential biomarker for predicting superior outcomes in patients with HCC. GDF7 amplification is a potential therapeutic option for HCC.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

413. LYMPH NODE MAJOR PATHOLOGIC RESPONSE IS A POTENTIAL PROGNOSTIC FACTOR AFTER NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Esophageal cancer ranks tenth in incidence and is the sixth most common cause of cancer-related deaths. Neoadjuvant chemoradiotherapy before and after surgery has been shown to improve ESCC patients' survival compared with surgery alone. However, the outcomes of nCRT are heterogeneous, and clinical or pathological methods that can predict nCRT responses have been extensively studied. There are currently no standard grading methods that assess the treatment response in lymph nodes after nCRT. We aimed to assess the clinicopathological relevance and determine the prognostic significance of lymph node major pathologic response (MPR) after nCRT in ESCC patients. Methods Patients who received nCRT for ESCC followed by surgery were retrospectively reviewed and classified into different lymph node stage (LNS) according to their pathological regression: LNS0 (no tumor cells in lymph node before nCRT); LNS1 (residual tumor cells in lymph node after nCRT≤50%; major pathologic response); LNS2 (residual tumor cells in lymph node after nCRT&amp;gt;50%; not major pathologic response). Results In total, 187patients, comprising 91,49 and 47 patients with LNS stage of 0(no tumor cells in lymph node before nCRT),1(major pathologic response), or 2(not major pathologic response), respectively, were included. The result showed that the higher LNS stage was strongly associated with decreased overall survival (P&amp;lt;0.001) and disease-free survival (P&amp;lt;0.001), and increased recurrence risks (P=0.002). The cox regression showed MPR was significantly an independent prognostic factor of OS and DFS. Among 96 patients with clinically positive LNs,54patients (56.3%) showed discordance between the PT and LN pathological regression grades. Conclusions Residual tumor cells in lymph node after nCRT≤50% could be defined as lymph node major complete response. The Lymph node MPR can be an independent prognostic indicator of ESCC patients who received nCRT plus curative surgery.