Early Prediction Of Therapeutic Response Research Articles

Clinical impact and potential utility of non-enhanced computed tomography performed immediately after transarterial chemoembolization for hepatocellular carcinoma.

Intratumoral lipiodol deposition following transarterial chemoembolization (TACE) is associated with the prognosis of hepatocellular carcinoma (HCC) patients. However, there is insufficient evidence regarding the actual clinical significance of the imaging tests conducted to evaluate the lipiodol uptake after TACE. This study evaluates the clinical impact and potential utility of performing immediate post-TACE non-enhanced computed tomography (NECT) on the treatment of HCC. This retrospective study at a tertiary referral center included patients undergoing their first session of conventional TACE for initial treatment of HCC from November 2021 to December 2022 with available immediate post-TACE NECT. Patients were categorized based on lipiodol uptake into Cohorts A (incomplete uptake with additional treatment before the first follow-up 1 month after TACE), B incomplete uptake without additional treatment before first follow-up), and C (complete uptake). Survival curves for the time to progression (TTP) were estimated using the Kaplan-Meier method and were compared by using the log-rank test. Out of 189 patients, 58 (29.6%) showed incomplete lipiodol uptake; 2 in Cohort A and 56 in Cohort B. Cohort C included 131 patients (69.3%). Cohort B had the highest rate of residual viable tumor (48.2%) 1 month after TACE, compared to the other cohorts (0% in Cohort A and 32.1% in Cohort C). The median TTP of Cohort B was 7.9 months [95% confidence interval (CI): 4.6-15.7 months], significantly shorter than the 15.4 months (95% CI: 10.9-20.9 months) for Cohort C (P=0.03). During follow-up, no progression occurred in Cohort A. Assessment of lipiodol uptake by performing immediate post-TACE NECT can stratify HCC patients and facilitate early prediction of therapeutic response. Identifying suboptimal lipiodol uptake immediately after TACE can aid future treatment adjustments and potentially improving oncologic outcomes.

Serial Changes of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab.

Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from HCC patients undergoing atezolizumab plus bevacizumab (Atezo+Bev), and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Changes in CTC numbers during Atezo+Bev reflected the tumor volume. Targeted RNA sequencing with next-generation sequencing (NGS) revealed that patients with elevated transforming growth factor (TGF)-β signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response. In addition, compared with changes in CTC counts, changes in TGF-β signaling molecule expression in CTCs accurately and promptly predicted treatment response. Overall, NGS analysis of CTC-derived RNA showed that changes in TGF-β signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-β molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev.

Short-length DNA fragments in plasma to predict clinical outcome in unresected glioblastoma patients.

2025 Background: Early prediction of therapeutic response is an important issue in glioblastoma patients. Cell-free DNA (cfDNA) concentration in plasma shown potential prognostic value. cfDNA release is influenced by non-tumor parameters. Short-length cfDNA (slDNA) may better reflect tumor evolution. The aim was to investigate plasmatic slDNA as prognostic marker in unresected glioblastoma patients. Methods: An ancillary study of a prospective trial was conducted (GLIOPLAK trial). Patients had newly diagnosed and histomolecular confirmed glioblastoma IDH wild-type (WHO 2021 classification). Patients with resected tumor were excluded. All patients underwent radiotherapy/temozolomide (RT/TMZ) schedule after biopsy. Plasmas were collected at three times during first-line treatment: before (pre-), after (post-) RT and at the time of disease progression/relapse. Cell-free DNA (cfDNA) was extracted from plasma using the QIAamp circulating nucleic acid kit (Qiagen). Short-length DNA (slDNA) fragments (equal or lower than 250 bp length) concentration was calculated based on AUC after automated electrophoresis using 4200 TapeStation System. Primary objective was to investigate the impact on survival of slDNA during RT/TMZ phase. Secondary objectives were to explore the association between tumor volume, corticosteroid exposition and slDNA. Results: Thirty-eight patients were included: median age was 63 [interquartile range 55-66], 84.2% (n=32) had Karnofsky index higher than 80% at baseline and median overall survival (OS) was 13.3 months [CI 95% 11.5; 15.5]. slDNA was detected in 69.4% at the pre-RT time (mean 722.3 pg/ml ±sd 1257.7) and in 83.3% at the post-RT-time (686.1 pg/ml ±1217.1). One third of the patients experienced a slDNA decrease between pre- and post-RT time. Presence of slDNA at the pre-RT time was associated with improved OS: median of 11.7 months [9.8-19.6] in the slDNA(+) group (n=25) versus 8.8months [5.5-NA] in the slDNA(-) group (n=11), HR 0.309 [0.133-0.716], log rank p=0.004. Decrease of slDNA concentration was also associated with better outcome compared to stability or increase of slDNA between pre- and post-RT: respectively median OS 14.1 vs 10.1 months, 0.424 [0.197-0.909], p=0.02. Corticosteroid exposition and dose were not correlated to slDNA concentration at pre-RT or slDNA variation (respectively correlation coefficient 0.081 and 0.047). At pre-RT, presence of slDNA was independent of tumor volume: mean 265.0 cm3 ±84.7 in slDNA(+) group vs 237.7 cm3 ±115.7 in slDNA(-) group, p=0.492. Total circulating cfDNA concentration did not influence OS in our cohort. Conclusions: slDNA during the RT/TMZ phase is an independent prognostic marker in unresected glioblastoma patients. The role of slDNA as a biomarker for adaptative treatment after RT as well as non-invasive molecular characterization tool can be explored in dedicated trial. Clinical trial information: NCT02617745 .

Early improvements in signs and symptoms predict clinical response to baricitinib in patients with moderate-to-severe atopic dermatitis.

Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87-100%; NPV 68-100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92-100%; NPV 80-100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.

PD-0154 Early prediction of therapeutic response by regular functional MRI during the treatment of NPC

PD-0154 Early prediction of therapeutic response by regular functional MRI during the treatment of NPC

GlucoCEST MRI for the Evaluation Response to Chemotherapeutic and Metabolic Treatments in a Murine Triple-Negative Breast Cancer: A Comparison with[18F]F-FDG-PET.

Triple-negative breast cancer (TNBC) patients have usually poor outcome after chemotherapy and early prediction of therapeutic response would be helpful. [18F]F-FDG-PET/CT acquisitions are often carried out to monitor variation in metabolic activity associated with response to the therapy, despite moderate accuracy and radiation exposure limit its application. The glucoCEST technique relies on the use of unlabelled D-glucose to assess glucose uptake with conventional MRI scanners and is currently under active investigations at clinical level. This work aims at validating the potential of MRI-glucoCEST in monitoring the therapeutic responses in a TNBC tumor murine model. Breast tumor (4T1)-bearing mice were treated with doxorubicin or dichloroacetate for 1week. PET/CT with [18F]F-FDG and MRI-glucoCEST were performed at baseline and after 3 cycles of treatment. Metabolic changes measured with [18F]F-FDG-PET and glucoCEST were compared and evaluated with changes in tumor volumes. Doxorubicin-treated mice showed a significant decrease in tumor growth when compared to the control group. GlucoCEST imaging provided metabolic response after three cycles of treatment. Conversely, no variations were detected in [18F]F-FDG uptake. Dichloroacetate-treated mice did not show any decrease either in tumor volume or in tumor metabolic activity as assessed by both glucoCEST and [18F]F-FDG-PET. Metabolic changes during doxorubicin treatment can be predicted by glucoCEST imaging that appears more sensitive than [18F]F-FDG-PET in reporting on therapeutic response. These findings support the view that glucoCEST may be a sensitive technique for monitoring metabolic response, but future studies are needed to explore the accuracy of this approach in other tumor types and treatments.

Serum miR-222-3p as a Double-Edged Sword in Predicting Efficacy and Trastuzumab-Induced Cardiotoxicity for HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Target Therapy.

Background: We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer patients receiving neoadjuvant therapy (NAT).Methods: A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events.Results: The miR-222-3p low group was more likely to achieve pCR [odds ratio (OR) = 0.258, P = 0.043]. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230, Pinteraction = 0.025). The miR-222-3p low group was correlated with superior DFS (P = 0.029) and OS (P = 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity (P < 0.05) and anemia (P = 0.013).Conclusions: Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT.

MRI features and texture analysis for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy and tumor recurrence of locally advanced rectal cancer.

This study aimed to evaluate the efficiency of imaging features and texture analysis (TA) based on baseline rectal MRI for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) and tumor recurrence in patients with locally advanced rectal cancer (LARC). Consecutive patients with LARC who underwent rectal MRI between January 2014 and December 2015 and surgical resection after completing nCRT were retrospectively enrolled. Imaging features were analyzed, and TA parameters were extracted from the tumor volume of interest (VOI) from baseline rectal MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal TA parameter cutoff values to stratify the patients. Logistic and Cox regression analyses were performed to assess the efficacy of each imaging feature and texture parameter in predicting tumor response and disease-free survival. In total, 78 consecutive patients were enrolled. In the logistic regression, good treatment response was associated with lower tumor location (OR = 13.284, p = 0.012), low Conv_Min (OR = 0.300, p = 0.013) and high Conv_Std (OR = 3.174, p = 0.016), Shape_Sphericity (OR = 3.170, p = 0.015), and Shape_Compacity (OR = 2.779, p = 0.032). In the Cox regression, a greater risk of tumor recurrence was related to higher cT stage (HR = 5.374, p = 0.044), pelvic side wall lymph node positivity (HR = 2.721, p = 0.013), and gray-level run length matrix_long-run low gray-level emphasis (HR = 2.268, p = 0.046). Imaging features and TA based on baseline rectal MRI could be valuable for predicting the treatment response to nCRT for rectal cancer and tumor recurrence. • Imaging features and texture parameters of T2-weighted MR images of rectal cancer can help to predict treatment response and the risk for tumor recurrence. • Tumor location as well as conventional and shape indices of texture features can help to predict treatment response for rectal cancer. • Clinical T stage, positive pelvic side wall lymph nodes, and the high-order texture parameter, GLRLM_LRLGE, can help to predict tumor recurrence for rectal cancer.

RAF1 Expression is Correlated with HAF, a Parameter of Liver Computed Tomographic Perfusion, and may Predict the Early Therapeutic Response to Sorafenib in Advanced Hepatocellular Carcinoma Patients.

ObjectivesMonitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.MethodsA total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.ResultsAccording to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.ConclusionRAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

Diffusion-Related MRI Parameters for Assessing Early Treatment Response of Liver Metastases to Cytotoxic Therapy in Colorectal Cancer

The objective of our study was to evaluate early therapeutic response after cytotoxic chemotherapy in patients with liver metastasis from colorectal cancer (CRC) using intravoxel incoherent motion (IVIM) DWI and dynamic contrast-enhanced MRI (DCE-MRI). Nineteen patients with liver metastasis from CRC underwent DCE-MRI and IVIM DWI at baseline and after the first cycle of chemotherapy. IVIM DWI parameters including the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) and DCE-MRI perfusion parameters including the volume transfer constant (K(trans)), reverse volume transfer constant (Kep), extravascular extracellular volume fraction (Ve), and initial area under the concentration curve in 60 seconds (iAUC) were calculated. The response evaluation was based on Response Evaluation Criteria in Solid Tumors version 1.1. There were eight responding and 11 nonresponding patients. ADC (baseline value vs value after first cycle of chemotherapy [mean ± SD]: 1191.9 ± 232.2 vs 1263.5 ± 266.4 × 10(-3) mm(2)/s; p = 0.012), D (1085.9 ± 232.9 vs 1173.5 ± 248.9 × 10(-3) mm(2)/s; p = 0.012), and f (173.7% ± 39.8% vs 133.5% ± 28.3%; p = 0.017) showed a significant change after the first cycle of chemotherapy in the response group, whereas ADC and D showed no significant change in the nonresponse group. In addition, DCE-MRI perfusion parameters showed no significant changes. A correlation was found between each of perfusion-related IVIM parameters and the DCE-MRI parameters before chemotherapy (r = 1.33, p > 0.05). Diffusion-related MRI parameters are useful for the early prediction of therapeutic response after cytotoxic chemotherapy for liver metastasis from CRC.

Functional diffusion map of malignant brain tumors: A surrogate imaging biomarker for early prediction of therapeutic response and patient survival

PurposeTo evaluate the ability of functional diffusion mapping “fDM” to predict early treatment response and survival in patients with primary malignant brain tumors. Patients and methodsForty-six brain tumor patients were examined by diffusion MRI before and 3 weeks after initiation of chemo- and/or radiotherapy. Images were co-registered to pretherapy scans, and tumor volumes with significant changes in apparent diffusion coefficient values were spatially displayed as functional diffusion maps. The predictive values of percentage of change in whole-tumor volume, mean ADC and fDM parameters for treatment response were evaluated by their correlation with the standard clinico-radiologic response criteria and overall survival of the two response groups was determined. ResultsOf the analyzed 46 brain tumors, 21 tumors were responding and 25 were stable/non-responding. At 3 weeks after initiation of therapy, the percentage of tumor volume with significant increase in diffusion (VR; red voxels) was the strongest predictor of treatment response than the changes in whole-tumor volume and mean ADC values determined at the same time point as compared to their pretherapy values. VR threshold of 14.5% at 3 weeks had sensitivity, specificity, positive and negative predictive values of 100% for all differentiating responding from stable/non-responding tumors. Overall survival in stable/non-responding group was shorter than in the responding group (8.7 versus 35.6 months; ∗∗P<0.001). ConclusionThe use of fDM provided an early and direct surrogate marker for predicting treatment response and patient survival in patients with malignant brain tumor.

FDG-PET und FDG-PET / CT: Möglicher Stellenwert im Rahmen der Strahlentherapie des Rektumkarzinoms

This paper aims to analyze the role of FDG-PET and FDG-PET / CT in the course of multimodal therapy of rectal cancer (tumor staging, radiotherapy planning and prognosis). The role of FDG-PET or FDG-PET / CT in the staging of rectal cancer has not fully elucidated yet. However, as FDG-PET can distinguish between scars and tumor tissue it is superior to CT or MRI in detecting local recurrence. For radiotherapy planning FDG-PET / CT can localize the tumor extension thus offering important additional information. This may result in sparing of the rectal sphincter. Still, the primary target volume encloses mesorectal tissues and other local lymphatics, thus the value of additional PET / CT information remains limited. First studies revealed a correlation between metabolic response to radiochemotherapy and oncological results. An early prediction of therapeutic response during the course of neoadjuvant radiochemotherapy would be extremely helpful to stratify the patients.

17 Early prediction of therapeutic response by non-invasive imaging

17 Early prediction of therapeutic response by non-invasive imaging