Complete Response Group Research Articles

Follow-up strategy of radiofrequency ablation for papillary thyroid microcarcinoma: defining a response-to-ablation system.

To define a response-to-ablation system based on dynamic risk stratification proposed by the 2015 American Thyroid Association guidelines for predicting clinical outcomes and guiding follow-up strategies for patients with low-risk papillary thyroid microcarcinoma (PTMC) who underwent radiofrequency ablation (RFA). This retrospective study reviewed patients with low-risk PTMC who underwent RFA between 2014 and 2018. We classified patients into three groups based on their response to therapy at the 1-year follow-up: complete, indeterminate, and incomplete. The primary endpoints were local tumor progression (LTP) and disease-free survival (DFS). Among the 748 patients (mean age, 43.7 years ± 9.8; 586 women), 4.0% (30/748) had LTP during a median follow-up of 5 years. The response was complete in 80.2% (600/748) of the patients, indeterminate in 18.1% (135/748), and incomplete in 1.7% (13/748). The LTP rate in the final follow-up was 1% (6/600), 8.1% (11/135), and 100% (13/13), respectively. The risk of LTP was significantly different in the incomplete response group (HR, 1825.82; 95% CI: 458.27, 7274.36; p< 0.001) and indeterminate response group (HR, 8.12; 95% CI: 2.99, 22.09; p< 0.001) than in the complete response group. There were significant differences in DFS among groups (p< 0.001). The proportion of variation explained and C-index of the system was high (27.66% and 0.79, respectively). We defined a response-to-ablation system that provides a new paradigm for the management of patients with PTMC who underwent RFA. Our data confirm that the system can effectively predict the risk of LTP and guide ongoing follow-up recommendations. • The response-to-ablation system can classify patients with low-risk PTMC who underwent RFA into complete, indeterminate, or incomplete response categories. • Results suggest that, in this population, this system can identify three separate cohorts of patients who have significantly different clinical outcomes. • The response-to-ablation system will help better tailor the ongoing follow-up recommendations.

Trans-Arterial Chemoembolization for the Treatment of Hepatocellular Carcinoma: A Single Tertiary Care Institute Experience

Introduction: Trans-arterial chemoembolization (TACE) is a mainstay therapeutic option indicated in early-stage non- resectable hepatocellular carcinoma (HCC) and has been shown to be associated with survival improvements. This study aimed to evaluate the radiological and clinical response of those who underwent TACE. Aims &amp; Objectives: We aimed to evaluate the radiological and clinical response in patients who underwent Trans- arterial chemoembolization. Place and Duration of Study: This study was conducted in the Vascular Interventional Radiology Department, Dow Institute of Radiology, Dow University of Health Sciences, Ojha Campus Karachi for a period of 18 months between January 2021 and June 2022. Material &amp; Methods: HCC patients (n=181) who underwent TACE as their primary treatment at Dow Hospital Ojha Campus Karachi between January 1st, 2021, and June 30th, 2022 were included. Inclusion criteria followed the Barcelona Clinic Liver Cancer (BCLC) and Child-Pugh staging systems. Tumor response was evaluated using “modified Response Evaluation Criteria in Solid Tumors (mRECIST)”, and patients were categorized into complete response (CR) or partial response (PR) groups. The study compared background, clinico-laboratory, and radiological features between these groups, including HCC sizes and CT scan findings before and after TACE. The retrieved data was entered and analyzed using SPSS version.21. Results: Of the total 118 patients, 51.70% showed CR to the TACE, while PR was noted in 48.30%. Age, sex, viral hepatitis, and co-morbids showed no intergroup differences. However, Child-Pugh stage and BCLC were significantly associated with tumor response. Similarly, laboratory parameters revealed significant mean differences between the two groups (p&lt;0.001), except international normalized ratio and alanine transaminase. Those who had achieved CR had a mean number of tumor less than that of PR. Similarly, tumor size significantly decreased post-TACE (p&lt;0.0001). Moreover, arterial-phase enhancement and portal venous and delayed phases washout tumors before TACE were reported in 76.30%. Over half of the patients had no residual tumor tissue after TACE. Tumors with arterial-phase enhancement and portal venous and delayed phases washout were highly susceptible to TACE.Furthermore, Child-Pugh classA had a greater estimated mean survival than class B (p&lt;0.001). Conclusion: Over half of the patients showed complete response to the TACE. BCLC staging (B), Child-Pugh (stage A), and small tumors had a favourable effect on the radiological and clinical response in the early-stages of HCC. Tumors with an arterial-phase enhancement and portal venous and delayed phases washout were more susceptible to TACE.

Clinical Possibility of Caenorhabditis elegans as a Novel Evaluation Tool for Esophageal Cancer Patients Receiving Chemotherapy: A Prospective Study.

The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy's efficacy for esophageal cancer patients. We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated via the chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021, and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62-1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future.

Prognosis of post-neoadjuvant therapy patients who underwent immediate breast reconstruction: a SEER-based, propensity-matched study

ObjectiveThe application of immediate breast reconstruction (IBR) for post-neoadjuvant therapy (NAT) patients was controversial. The aim of this study was to investigate the long-term survival outcomes of IBR for these patients.MethodsData between January 2010 and November 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce the influence of confounding factors between the mastectomy alone group (MA) and the mastectomy with IBR group (IBR). The rates of 5 year breast cancer-specific survival (BCSS) were compared by Kaplan–Meier curves with log-rank test.ResultsThe IBR was associated with improved 5-year BCSS in the IBR group before PSM (88.5 vs. 79.1%, P < 0.001). The proportion of IBR increased from 21.5% in 2010 to 28.2% in 2017. After PSM, a total of 9,610 patients were enrolled for survival analysis (4,805 in each group). In the complete response (CR) group, the 5-year BCSS rates did not differ (93.4 vs. 95.6%, P = 0.16). In the non-CR group, the 5-year BCSS rate was higher in patients who received IBR (82.5% 79.4%, P = 0.034).ConclusionIn general, the application of IBR among post-NAT patients has steadily increased from 2010 to 2017. In the CR group, survival outcomes of post-NAT patients who received IBR were similar to those who received mastectomy alone. In the non-CR group, IBR was associated with potential survival benefits. More studies are expected to validate our findings.

Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy. We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response. Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group. Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.

Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study.

In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.

A new prognostic index associated with pathological complete response in rectal cancer

Purpose: Approximately half of rectal cancer cases are diagnosed at a locally advanced stage. It is important to identify biomarkers that can predict pathological complete response in patients undergoing surgery following neoadjuvant chemoradiotherapy.&#x0D; Materials and Methods: This retrospective study included 205 patients with locally advanced rectal cancer who underwent surgery and adjuvant chemotherapy following neoadjuvant chemoradiotherapy. Inflammatory biomarkers were assayed in the complete blood count before neoadjuvant therapy.&#x0D; Results: A pathological complete response was detected in 20.5% of the patients. The neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and pan-immune inflammation value were significantly lower in the pathological complete response (+) group than in the pathological complete response (-) group. The cut-off of the pan-immune inflammation value was ≤ 331.2, and this parameter had the best diagnostic performance of 90.4%.&#x0D; Conclusion: Neoadjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy remains the standard treatment approach for rectal cancer. Since pathological complete response improves oncological outcomes, it is important to identify biomarkers that can predict pathological complete response in rectal cancer

Camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC): A single-arm, phase II trial.

4048 Background: This study (NCT05476380) aimed to evaluate the safety and efficacy of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced ESCC, and to explore the potential risk factors of tumor immune microenvironment (TIM) which affect the efficiency of immunotherapy. Methods: Patients with resectable locally advanced thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 2) plus paclitaxel (175 mg/m2, day 1) and cisplatin (75 mg/m2, day 1) for three 21-day cycles before surgery. The primary endpoint was major pathological response (MPR), defined as ≤10% residual viable tumor cells in resected tissue. In order to screen out the potential biomarkers, the dissected lymph nodes were collected in the pathological complete response (pCR) and non-pCR groups. The infiltrated immune cells and the status of PD-L1 was evaluated by flowcytometry. Results: From February 20, 2021 to July 7, 2022, 38 patients were enrolled. 34 (89.5%) patients completed the full three-cycle treatment successfully. 34 patients underwent surgery and all received R0 resection. The MPR and pCR rates were 67.6% (23/34) and 17.6% (6/34), respectively. There were 2 (5.9%) patients having complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 32 (94.1%) patients had any-grade treatment-related adverse events, with the most common being leukocytopenia (73.5%). 18 (52.9%) patients had adverse events of grade 3 or worse. No treatment-related deaths occurred. Based on our findings, positive lymph nodes were one of the important reasons that the patients could not achieved pCR. TIM of the lymph nodes were then tested. Compared with MPR group, the infiltrated lymphocyte cells in the non-MPR group decreased from 93% to 52.4% (p = 0.02), the infiltrated CD8+ T cells also decreased from 11.8% to 5.9% (p = 0.02). However, the CD4+ T cells showed no significant difference between the MPR and non-MPR groups (46.2% vs 55%, p = 0.27). The expression of PD-L1 in the immune cells is one of the biomarkers for checkpoint inhibitors. In this trial, the expression of PD-L1 in the CD8+ T cells showed significant difference between the MPR and non-MPR groups (14.5% vs 6.7%, p = 0.02). Myeloid-derived suppressor cells (MDSCs) are a group of vastly heterogeneous immunosuppressive cells derived from immature myeloid progenitors that have been linked to poor patient prognosis and immunosuppression. We found more infiltrations of MDSCs in the non-MPR group compared with the MPR group (9.7% vs 4.7%, p = 0.04). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy shows promising efficacy and good safety in ESCC patients. Poor response to immunotherapy was related to lymph node metastasis in the TIM. Clinical trial information: NCT05476380 .

Do radioiodine-avid lymph nodes from differentiated thyroid cancer on the initial posttherapy scan need repeated 131I therapy?

Residual/recurrent lymph node metastase (LNM) is often found after differentiated thyroid cancer (DTC) surgery. This study aimed to investigate whether patients complicated with radioiodine-avid (131I+) lymph nodes from DTC on the initial posttherapy scan (PTS) need repeated 131I therapy. From June 2013 to August 2022, DTC patients with 131I+ lymph nodes on the initial PTS who received at least two cycles of 131I therapy were retrospectively enrolled. They were divided into a complete response (CR) group and an incomplete response (IR) group according to their response to the initial 131I therapy based on the 2015 American Thyroid Association (ATA) guidelines. A total of 170 DTC patients with 131I+ lymph nodes on the initial PTS were included; 42/170 (24.7%) patients were classified into the CR group and 128/170 (75.9%) were classified into the IR group according to their response to the initial 131I therapy. None of the 42 CR patients had disease progression at the subsequent follow-up, and 37/170 (21.8%) IR patients improved after repeated therapy. Univariate analysis showed that N stage (P=0.002), stimulated thyroglobulin (sTg) level before initial 131I therapy (P<0.001), LNM size (P<0.001), number of total residual/recurrent LNM (P=0.021), radioiodine-nonavid (131I-) LNM (P=0.002) and ultrasound features (P<0.001) were related to the initial treatment response. On multivariate analysis, sTg level (OR=1.186, P<0.001) and LNM size (OR=1.533, P=0.004) were independent risk factors for IR after initial 131I therapy. The optimal sTg level and LNM size cutoff value for predicting the treatment response after initial 131I therapy were 18.2 µg/l and 5mm. This study suggested that approximately one-quarter of patients with 131I+ lymph nodes on initial PTS, especially those with N0 or N1a stage, lower sTg level, smaller LNM size, ≤2 residual/recurrent LNMs, negative ultrasound features and no 131I- LNM, remain stable after one cycle of 131I therapy and do not need repeated therapy.

Radiomics Based on DCE-MRI for Predicting Response to Neoadjuvant Therapy in Breast Cancer

To compare the value of radiomics and diameter% based on pre- and early-treatment dynamic enhanced MR (DCE-MRI) of the breast in predicting response to neoadjuvant therapy (NAT) in breast cancer and to construct a tool for early noninvasive prediction of NAT outcomes. Retrospective analysis of clinical and imaging data of 142 patients with primary invasive breast cancer who underwent DCE-MRI before and after two cycles of NAT at our institution. Enroled patients were randomly assigned in a 7:3 ratio to the training group and the test group. Patients were divided into pathological complete response (pCR) and non-pathological complete response groups based on surgical pathology findings after NAT. The maximum diameter relative regression values (Diameter%) before and after treatment were calculated and the conventional imaging Diameter% model was constructed. Based on pre- and early-NAT DCE-MRI, the optimal features of pre-NAT, early-NAT, and delta radiomics were screened using redundancy analysis, least absolute shrinkage, and selection operator methods to construct the corresponding radiomics model and calculate the Radscores. Indicators that were statistically significant in the univariate analysis of clinical data were further screened by stepwise regression and combined with Radscores to construct the fusion model. All models were evaluated and compared. In the test set, the area under the curve (AUC) of the delta radiomics model (0.87) was higher than that of the pre-NAT, early-NAT radiomics models (0.57, 0.78) and the Diameter% model (0.83). The fusion model had the best efficacy in predicting pCR after NAT, with AUCs of 0.91 in the training and test sets. And its nomogram plot showed that Radscore of early-NAT radiomics had the greatest weight. In the test set, the fusion model and Delta radiomics model improved the efficacy of predicting pCR by 35.56% and 14.19%, respectively, compared to the Diameter% model (P=0 and .039). Clinical decision curves showed the highest overall clinical benefit for the fusion model. Radiomics, especially delta and early-NAT radiomics, may be potential biomarkers for early noninvasive prediction of NAT outcomes. And a fusion model constructed from meaningful clinicopathological indicators combined with radiomics can effectively predict NAT response.

Predictive Factors of Complete Response to Transarterial Chemoembolization in Intermediate Stage Hepatocellular Carcinoma beyond Up-To-7 Criteria.

To clarify the prognosis and identify predictors for obtaining a complete response (CR) by transarterial chemoembolization (TACE) in intermediate stage HCC beyond up-to-7 criteria. Of the 120 patients with intermediate stage HCC who were treated by TACE as the initial treatment from February 2007 to January 2016, 72 finally matched the following inclusion criteria: beyond up-to-7 criteria; Child-Pugh score under 7; and no combined therapy within 4 weeks after the initial TACE. The CR rate and overall survival (OS) were evaluated. Logistic regression analysis was performed to identify predictors of CR. The deterioration of liver function after TACE was also evaluated. The CR rate was 56.9%, and the overall median survival time (MST) was 37.7 months. The MST was 38.7 months in the CR group and 28.0 months in the non-CR group (p = 0.018). HCC within up-to-11 criteria was the only predictor of CR. The CR rate and MST were 70.7% and 37.7 months, respectively, in patients with HCC within up-to-11 criteria and 38.7% and 32.7 months, respectively, in the patients beyond up-to-11 criteria. Deterioration of the Child-Pugh score after the initial TACE and the 2nd TACE occurred in 24.2% and 12.0%, respectively, and deterioration of the modified albumin-bilirubin (mALBI) grade occurred in 17.6% and 7.4%, respectively. TACE can achieve high CR rates with prolonged overall survival for intermediate stage HCC beyond up-to-7 criteria. The predictor of CR was within up-to-11 criteria. Deterioration of liver function was not severe, but requires caution. Multidisciplinary approach as additional treatment after TACE is important.

Quantitative Prediction of Posttransplant Hepatocellular Carcinoma Prognosis Using ADV Score: Validation with Korea-Nationwide Transplantation Registry Database

ObjectiveThe aim of this study is to validate the prognostic impact of ADV score (α-fetoprotein [AFP]–des-γ-carboxyprothrombin [DCP]–tumor volume [TV] score) for predicting prognosis of hepatocellular carcinoma (HCC) following liver transplantation (LT). BackgroundADV score has been reported as a prognostic surrogate biomarker of HCC following LT and hepatectomy. MethodsThe study patients were 1599 LT recipients selected from the Korean Organ Transplantation Registry database. ResultsDeceased-donor and living-donor LTs were performed in 143 and 1456 cases, respectively. Weak correlation was present among AFP, DCP, and TV. The viable HCC group showed ADV score-dependent disease-free survival (DFS) and overall patient survival (OS) rates from 1log to 10log (p<0.001). Prognosis of complete pathological response group was comparable to that of ADV score <1log (p≥0.099). ADV score cutoff of 5log (ADV-5log) for DFS and OS was obtained through receiver operating characteristic curve analysis with area under the curve ≥0.705. Both ADV-5log and Milan criteria were independent risk factors for DFS and OS, and their prognostic impacts were comparable to each other. Combination of these two factors resulted in further prognostic stratification, showing hazard ratios for DFS and OS as 2.98 and 2.26 respectively for one risk factor and 7.92 and 8.19 respectively for two risk factors (p<0.001). ABO-incompatible recipients with ADV score ≥8log or two risk factors showed higher recurrence rates. ConclusionsThis validation study revealed that ADV score is a reliable surrogate biomarker for posttransplant HCC prognosis, which can be used for selecting LT candidates and guiding risk-based posttransplant follow-up surveillance.

Chemical Exchange Saturation Transfer MRI: Capability for Predicting Therapeutic Effect of Chemoradiotherapy on Non-Small Cell Lung Cancer Patients.

Amide proton transfer (APT) weighted chemical exchange saturation transfer CEST (APTw/CEST) magnetic resonance imaging (MRI) has been suggested as having the potential for assessing the therapeutic effect of brain tumors or rectal cancer. Moreover, diffusion-weighted imaging (DWI) and positron emission tomography fused with computed tomography by means of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET/CT) have been suggested as useful in same setting. To compare the capability of APTw/CEST imaging, DWI, and FDG-PET/CT for predicting therapeutic effect of chemoradiotherapy (CRT) on stage III non-small cell lung cancer (NSCLC) patients. Prospective. Eighty-four consecutive patients with Stage III NSCLC, 45 men (age range, 62-75 years; mean age, 71 years) and 39 women (age range, 57-75 years; mean age, 70 years). All patients were then divided into two groups (Response Evaluation Criteria in Solid Tumors [RECIST] responders, consisting of the complete response and partial response groups, and RECIST non-responders, consisting of the stable disease and progressive disease groups). 3 T, echo planar imaging or fast advanced spin-echo (FASE) sequences for DWI and 2D half Fourier FASE sequences with magnetization transfer pulses for CEST imaging. Magnetization transfer ratio asymmetry (MTRasym ) at 3.5 ppm, apparent diffusion coefficient (ADC), and maximum standard uptake value (SUVmax, ) on PET/CT were assessed by means of region of interest (ROI) measurements at primary tumor. Kaplan-Meier method followed by log-rank test and Cox proportional hazards regression analysis with multivariate analysis. A P value <0.05 was considered statistically significant. Progression-free survival (PFS) and overall survival (OS) had significant difference between two groups. MTRasym at 3.5 ppm (hazard ratio [HR] = 0.70) and SUVmax (HR = 1.41) were identified as significant predictors for PFS. Tumor staging (HR = 0.57) was also significant predictors for OS. APTw/CEST imaging showed potential performance as DWI and FDG-PET/CT for predicting the therapeutic effect of CRT on stage III NSCLC patients. 2 TECHNICAL EFFICACY: Stage 1.

AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation

(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.

Abstract P1-13-05: Extracellular vesicles-transported lncRNA BCDR1 promotes tumor cell proliferation and therapy resistance via upregulating G1/S-phase transition in breast cancer

Abstract Background Extracellular vesicles (EVs), secreted by tumor cells for intercellular communication, play an important role in breast cancer progression. Previous studies have proved that lncRNA could use EVs to transmit signals and affect the progression and treatment of breast cancer. In addition, a previous study has found that, in HER2 therapy-resistant tumors, CDK4/6 activity and cell cycle progression genes were involved and might serve as treatment targets. However, recent clinical trials were not supportive of the use of CDK4/6 inhibitors in HER2 enriched internal subtypes of breast cancer. In this study, we aim to explore the role of EVs-transported long noncoding RNA BCDR1 in the promotion of cell cycle progression in HER2-positive breast cancer, exploring a new potential target in combination with CDK4/6 inhibitor and anti-HER2 treatment. Methods Samples were collected from patients with HER2 overexpression receiving neoadjuvant therapy. RNA-seq was performed to identify differentially expressed RNAs between pathological complete response (pCR) and non-pCR group. In addition, serum extracellular vesicles were collected and determined through RNA-seq. The drug response and proliferation rate of tumor cells were measured in breast cancer cells (HCC-1954, BT-474 and MCF-7). Quantitative RT-PCR (qRT-PCR) was used to detect the expression levels of BCDR1 and its potential target genes. RNA-seq and GSEA analysis was carried out to determine the target pathways regulated by BCDR1. DNA fiber assay, mass spectrometry, and flow cytometry were used to understand the underlying mechanism of BCDR1. Results Core needle biopsy tissues from HER2-positive breast cancer patients with any ER status were collected before NAC. Among genes differentially overexpressed, BCDR1 was found to be downregulated in pCR group compared with non-pCR group. BCDR1 was also elevated in plasma EVs in the non-pCR group. In addition, overexpression of BCDR1 in breast cancer cells promoted cell proliferation and HER2 treatment resistance. Through pathway analysis, we found BCDR1 could facilitate G1/S-phase transition. Flow cytometry confirmed these findings. We also noticed that proteins that regulate DNA licensing including minichromosome maintenance proteins (MCMs) were enriched in BCDR1 overexpression cells. Through DNA fiber assay, we confirmed that BCDR1 could promote DNA replication initiation. Interestingly, under CDK4/6 inhibitor treatment, BCDR1 was induced, unrevealing an internal treatment-resistant mechanism in these tumor cells. Through EVs RT-qPCR, we found BCDR1 could transport from high expression cells to low, with the same biological function. We also explored antisense oligonucleotide (ASO) use in the inhibition of BCDR1 biological function and transportation. Conclusion BCDR1 promotes cell proliferation and therapy resistance via upregulating DNA licensing in breast cancer. BCDR1 could transported through EVs with same biological function. This study also suggests that BCDR1 could serve as a biomarker and therapeutic target in breast cancer. Citation Format: Qi Zhang, Bingqiu Xiu, Yayun Chi, Jiong Wu. Extracellular vesicles-transported lncRNA BCDR1 promotes tumor cell proliferation and therapy resistance via upregulating G1/S-phase transition in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-05.

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma.

Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein-protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 (OLFM4) and the Nanog homeobox (NANOG) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.

The Value of Dynamic Contrast-Enhanced MRI in Predicting the Response of Idiopathic Granulomatous Mastitis to Steroid Therapy and Comparison of Clinical and Radiological Outcomes

Background: The aim of this study was to investigate the value of pre-treatment dynamic contrast-enhanced MRI (DCE-MRI) findings in predicting clinical and radiological response to treatment in patients with idiopathic granulomatous mastitis (IGM) receiving steroid therapy and to compare clinical and DCE-MRI results after treatment. Methods: Pre- and post-treatment MRI examinations of 86 patients (with a mean age of 33.8 years; range, 20–57 years) diagnosed with IGM between January 2014 and September 2022 were retrospectively evaluated. Lesion characteristics and longest diameter, number of involved quadrants, retroareolar involvement, and presence of fistula or lymphadenopathy were noted. Patients were categorized into clinical complete response (CCR), clinical non-response (CNR) groups based on clinical response and into radiological complete response (RCR) and radiological non-response (RNR) groups based on radiological response. Results: The analyses revealed no relationship between the lesion type (abscess, NME, abscess, and NME), presence of lymphadenopathy or fistula, number of involved quadrants, retroareolar involvement, and treatment response on pre-treatment MRI (p&gt;0.05). The longest lesion diameter was smaller in the CCR group than in the CNR group (p = 0.02). After treatment, 40.7% (35/86) of the patients achieved RCR + CCR, while 16.3% (14/86) achieved RNR + CNR. On the other hand, 43% (37/86) of the patients achieved CCR + RNR. Conclusion: CCR is more common in patients with smaller lesions. Other pre-treatment MRI findings were not correlated with radiological or clinical response. A significant proportion of patients with CCR had residual lesions radiologically.

Quantitative analysis of superb microvascular imaging for monitoring tumor response to chemoradiotherapy in locally advanced cervical cancer.

As an ultrasound (US) image processing method, superb microvascular imaging (SMI) extracts and visualizes flow signals from vessels through advanced clutter suppression technology. We investigated the feasibility of SMI in monitoring treatment response in patients with locally advanced cervical cancer (LACC) undergoing chemoradiotherapy (CRT). Forty-nine patients underwent CRT and received SMI examination at 3 time points: before therapy (baseline), 3 weeks during, and 1 month after CRT. The maximum tumor diameter (Dmax), vascularity index (VI), and their percentage changes (ΔDmax and ΔVI) were calculated. ΔDmax was compared with MRI results as the reference standard. Based on the MRI findings, 44 were classified as complete response (CR) group and 5 as partial response (PR) group. The Dmax and ΔDmax showed decrease in CR and PR groups at 3 weeks during CRT (P< 0.05), but no significant difference between the two groups (P > 0.05). Compared to the baseline, significant decrease in VI and ΔVI were observed at during and after treatment in the two groups (P< 0.05). Moreover, there were significant differences in VI and ΔVI at 3 weeks during CRT between the CR and PR groups (P< 0.05). ΔVI at 3 weeks during CRT showed a better predictive performance for responder prognosis than VI (AUC = 0.964, AUC = 0.950, respectively, P = 0.001), with a cut-off value of 41.6% yielding 100% sensitivity and 86.4% specificity. The SMI parameters (VI and ΔVI) have potential for monitoring treatment response in LACC.

Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients.

We aimed to identify the differently expressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant systemic therapy with trastuzumab in HER2-positive breast cancer patients. This study was retrospectively analyzed from consecutively collected patient data. We recruited 64 women with breast cancer and categorized them into 3 groups: complete response (CR), partial response (PR), and drug resistance (DR). The final number of patients in the study was 20. RNA from 20 core needle biopsy paraffin-embedded tissues and 4 cultured cell lines (SKBR3 and BT474 breast cancer parent cells and cultured resistant cells) was extracted, reverse transcribed, and subjected to GeneChip array analysis. The obtained data were analyzed using Gene Ontology, Kyoto Gene and Genome Encyclopedia, Database for Annotation, Visualization and Integrated Discovery. In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines were identified. Among these, 3,224 were upregulated and 3,432 were downregulated. Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment in HER2-type breast cancer, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in the CR group. This multigene assay-based study provides insights into breast cancer signaling and possible predictions of therapeutic response to targeted therapies such as trastuzumab.