Partial Response Group Research Articles

Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment

BackgroundThe introduction of the anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers and clinical response in these patients.MethodsThis single-center study included medical record data of patients with NSCLC treated with the PD-1 antibody as a first-line or subsequent line of treatment, either as monotherapy or in combination with chemotherapy. The patients were enrolled from 2020 to 2022. We dynamically evaluated multiple Th1 and Th2 cytokines in the blood serum and analyzed the phenotype of T cells from the peripheral blood to explore the correlation between cytokine levels, T cell phenotypes, and clinical response.ResultsA total of 88 patients with stage IIIA-IV NSCLC were enrolled, out of which 60 (68.18%) achieved a partial response (PR), 13 (14.77%) had stable disease (SD), and 15 (17.05%) experienced disease progression (PD). The disease control rate was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) in lymphocyte absolute counts after treatment in patients with PD. Higher levels of IFN-γ (P = 0.023, P < 0.05), TNF-α (P = 0.00098, P < 0.005), IL-4 (P = 0.0031, P < 0.005), IL-5 (P = 0.0015, P < 0.005), and IL-10 (P = 0.036, P < 0.05) were detected in the peripheral blood before treatment in the PR group compared to the PD group. Moreover, patients with high levels of IL-5, IL-13, IL-4, IL-6, IFN-γ, and TNF-α (> 10 ng/mL) had superior progression-free survival compared to those with low levels (< 10 ng/mL). Furthermore, PD-1 expression on CD8+ T cells was higher in patients who showed a PR than in those who did not show a response (SD + PD; P = 0.042, P < 0.05).ConclusionsThe findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated with disease progression. Serum cytokine levels may predict the effectiveness and survival rates of anti-PD-1 blockade therapy in patients with NSCLC. In addition, PD-1 expression on CD8+ T cells was positively associated with better clinical response. Our findings highlight the potential of peripheral blood biomarkers to predict the effectiveness of PD-1-targeted treatments in patients with NSCLC. Larger prospective studies are warranted to further clarify the value of these biomarkers.

Treatment Response Assessment in Multiple Myeloma: Histogram Analysis of Total Tumor Apparent Diffusion Coefficient based on Whole-body Diffusion-weighted MR Imaging.

The International Myeloma Working Group (IMWG) consensus criteria for response assessmentin multiple myeloma (MM) has methodological limitations. Whole-body diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) histogram analysis may be complementary to response assessment of MM. To explore the role of histogram analysis of the ADC based on the total tumor volume (ttADC) in response assessment in patients with newly diagnosed MM (NDMM). Retrospective. Thirty-six patients with NDMM. 3.0T/single-shot DWI echo planar imaging (EPI) sequence with an integrated slice-by-slice shimming (iShim) technique. Baseline (median: 1 day before treatment) and post-treatment (median: five cycles of therapy) whole-body DWI were analyzed. A region of interest (ROI) containing lesions on every section of baseline image was drawn to derive the per-patient total tumor data. Post-treatment image analysis was based on the same ROI as the corresponding baseline. Histogram metrics were extracted from both ROIs. Patients were categorized into the very good partial response or better (VGPR+) group and the less than VGPR group per the IMWG response criteria for response assessment. Progression-free survival (PFS) was also calculated. Mann-Whitney test and Fisher's exact or Chi-squared tests, Receiver operating characteristic (ROC) analysis and DeLong test, Kaplan-Meier analysis and Cox proportional hazards model. A two-tailed P-value <0.05 was considered statistically significant. Thirty patients were categorized into the VGPR+ group and six into the less than VGPR group. The ttADC histogram changes between post-treatment and baseline metrics (ΔttADC) revealed significant differences in all percentile values between the VGPR+ and less than VGPR groups. For distinguishing VGPR+, ΔttADC_5th percentile had the largest area under the curve (AUC) (0.950, 95% CI 0.821-0.995). Patients with lower ΔttADC_5th percentile values (cutoff point,188.193) showed significantly longer PFS (HR = 34.911, 95% CI 6.392-190.677). ttADC histogram may facilitate response assessment in patients with NDMM. 3 TECHNICAL EFFICACY: Stage 4.

The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma

BackgroundOwing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment.ResultsThe established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05).ConclusionsThe proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.

Regulation of ferroptosis-related genes in CD8+ NKT cells and classical monocytes may affect the immunotherapy response after combined treatment in triple negative breast cancer.

Drug resistance has led to the failure of immunotherapy in triple negative breast cancer patients. Here we aimed to explore the mechanisms of drug resistance in patients in order to enhance their response to immunotherapy. We downloaded publicly available single-cell RNA-sequencing data of peripheral blood mononuclear cells from patients after treatment to investigate the possible mechanisms of drug resistance. The publicly available TCGA transcriptomic data and somatic mutation data were used for further validation. In this study, a series of bioinformatics and machine learning methods were employed. We identified the vital roles of CD8+ NKT cells and classical monocytes in the immunotherapy response of triple-negative breast cancer patients. The proportion of these cell types was significantly increased in group partial response. We also found that downregulation of ferroptosis-related genes regulates the immune pathway. The analysis of scRNA data and TCGA transcriptomic data presented that DUSP1 may play a crucial role in immunotherapy resistance. Overall, the composition of the tumor microenvironment affects the immunotherapy response of patients, and DUSP1 may be a potential target for overcoming drug resistance.

Variability in Motor Threshold during Transcranial Magnetic Stimulation Treatment for Depression: Neurophysiological Implications.

The measurement of the motor threshold (MT) is an important element in determining stimulation intensity during Transcranial Magnetic Stimulation treatment (rTMS). The current recommendations propose its realization at least once a week. The variability in this motor threshold is an important factor to consider as it could translate certain neurophysiological specificities. We conducted a retrospective naturalistic study on data from 30 patients treated for treatment-resistant depression in an rTMS-specialized center. For each patient, weekly motor-evoked potential (MEP) was performed and several clinical elements were collected as part of our clinical interviews. Regarding response to treatment (Patient Health Questionnaire-9 (PHQ-9) before and after treatment), there was a mean difference of -8.88 (-21 to 0) in PHQ9 in the Theta Burst group, of -9.00 (-18 to -1) in the High-Frequency (10 Hz) group, and of -4.66 (-10 to +2) in the Low-Frequency (1 Hz) group. The mean improvement in depressive symptoms was 47% (p < 0.001, effect-size: 1.60). The motor threshold changed over the course of the treatment, with a minimum individual range of 1 point and a maximum of 19 points (total subset), and a greater concentration in the remission group (4 to 10) than in the other groups (3 to 10 in the response group, 1 to 8 in the partial response group, 3 to 19 in the stagnation group). We also note that the difference between MT at week 1 and week 6 was statistically significant only in the remission group, with a different evolutionary profile showing an upward trend in MT. Our findings suggest a potential predictive value of MT changes during treatment, particularly an increase in MT in patients who achieve remission and a distinct "break" in MT around the 4th week, which could predict nonresponse.

Efficacy of Autologous Stem Cell Transplantation for Myeloma Patients with Suboptimal Response: A Multicenter Retrospective Analysis

Autologous stem cell transplantation (ASCT) is the standard of care for myeloma patients when partial response (PR) or better is achieved after induction therapy. However, its clinical significance in patients with suboptimal response (SR), including stable disease (SD) and progressive disease (PD) before ASCT, has not been established. Additionally, functional high-risk (FHR), including RS and early PD within 12 months, was a poor prognostic factor up to now. This study aimed to evaluate the efficacy of ASCT in myeloma patients having SR in novel agent era. This multicenter, retrospective study was conducted using the Transplant Registry Unified Management Program (TRUMP) database of the Japanese Society of Transplantation and Cellular Therapy (JSTCT) and included 3898 patients with transplant-eligible patients with newly diagnosed multiple myeloma who underwent ASCT between 2007 and 2020 and were followed up until 2021. The SR rate was 4.7% including 1.7% of PD. In survival time analysis for overall cases, The significant difference of PFS between the VGPR and PR groups were observed while there was no significant difference of OS between the VGPR and PR groups. Additionally, there was no significant difference of OS and PFS between the PR and SD groups. Therefore, we focused on the PR, SD, and PD groups as the purpose of this retrospective study was to investigate the clinical significance of ASCT in patients with SR compared with those with PR. The median age of the patients was 60 years (range, 30-77 years). In total, 1605 (97.4%), 561 (38.2%), and 512 (34.9%) patients received bortezomib, immunomodulatory drug (IMiD), and both bortezomib and IMiD, respectively. A total of 558 (38.0%) patients received reinduction therapy. There were 229 (37.7 %) patients with high-risk cytogenetic risk (HRCA). In a median follow-up period of 31.7 months, a significant difference was observed in 30-month overall survival (OS) rates between the PR, SD, and PD groups (86.3%, 78.5%, and 39.4%, respectively; p <0.001). In a comparison between the PR and SD groups, the OS in the SD group was significantly shorter than that in the PR among the patients with HRCA (p <0.001) and in the patients treated with reinduction therapy (p = 0.013). Concerning the PD group, the 30-month OS and PFS rates in the PD group were 39.4% and 17.9%. Finally, early PD within 12 months after ASCT predicted short OS, whereas OS without early PD even in the PD group was similar to that in the SD and PR groups. In conclusion, the OS in the SR was not always short, but the SR in the HRCA and the reinduction therapy groups predicted to short OS so that alternative therapeutic options to ASCT are needed. OS in the PD group was significantly short, but ASCT improved clinical outcome when early PD was not occurred even in the PD group.

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.

Relationship between Plasma IP-10/CXCL10 Levels and the Initial Therapeutic Response in Patients Treated with Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma

Introduction: Atezolizumab plus bevacizumab combination therapy (AB) was the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). IFN-γ-induced protein 10 (IP-10/CXCL10) is a chemokine to inhibit HCC proliferation by promoting the migration of cytotoxic T cells. We focused on the relationship between plasma IP-10/CXCL10 levels and the initial therapeutic response in patients receiving AB therapy. Methods: Forty-six patients receiving AB therapy were enrolled. Plasma IP-10/CXCL10 levels were measured at baseline, 3–7 days, 3 weeks, 6 weeks, and 8–12 weeks after the start of AB therapy. The initial therapeutic response was evaluated at 8–12 weeks. Results: The baseline IP-10/CXCL10 levels of partial response (PR) group was higher than that of stable disease (SD) or progressive disease (PD) group. Patients with the baseline IP-10/CXCL10 of 84 pg/mL or higher were likely to present PR than patients below (71 vs. 35%, p = 0.031), but prediction of PD using the baseline IP-10/CXCL10 levels was difficult. In contrast, IP-10/CXCL10 ratio of the PR group was lower than that of the SD/PD group at 3, 6, and 8–12 weeks. Patients with the 3, 6, and 8–12 weeks IP-10/CXCL10 ratio of 1.3, 0.4, and 0.4 or lower were likely to present PR than patients with ≥1.3, 0.4, and 0.4 (88, 35, 35 vs. 30, 3.8, 0%, p < 0.001, 0.011, 0.002). In other hand, the 3, 6, and 8–12 weeks IP-10/CXCL10 ratio for PD group was higher than that for non-PD group. Patients with the 3, 6, and 8–12 weeks IP-10/CXCL10 ratio of 1.3, 1.7, and 1.9 or higher were likely to present PD than patients below (85, 62, 57 vs. 32, 23, 14%, p = 0.002, 0.034, 0.009). Conclusion: High baseline IP-10/CXCL10 levels may be associated with better outcome, and high IP-10/CXCL10 ratio after 3–12 weeks may be associated with worse outcome in u-HCC patients receiving AB therapy.

P55 Real-world clinical and patient-reported outcomes of talimogene laherparepvec (T-VEC) treatment for melanoma in transit and nodal metastases at a UK centre

Abstract Talimogene laherparepvec (T-VEC) is a National Institute for Health and Care Excellence-approved oncolytic viral intralesional immunotherapy licensed for unresectable stage III(B)–IV(M1a) melanoma. It is a genetically modified herpes simplex virus that selectively replicates in tumour cells, leading to local and systemic antitumour immune responses, improving overall survival. The randomized phase III OPTiM trial reported a complete response in 28.2% of patients (Andtbacka RH, Collichio F, Harrington KJ et al. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec vs. granulocyte-macrophage colony-stimulating factor in unresectable stage III–IV melanoma. J Immunother Cancer 2019; 7:145). We report a retrospective review of clinical and patient-reported outcomes of a dermatology-led T-VEC service at a regional UK melanoma centre between January 2019 and January 2023. Treatment involves a loading dose and then two-weekly nurse-delivered intralesional injections. Patient demographics, clinical characteristics, toxicities, treatment responses and patient satisfaction were recorded. Sixteen patients (11 women and five men) were treated; the average patient age was 73 years (range 42–87). Seven patients had stage IIIB disease, six stage IIIC and three stage IVM1a. Eight had received prior nonsurgical treatments (adjuvant therapy, electrochemotherapy, diphencyprone). The number of lesions treated per visit ranged from 1 to 24 (median 5) over a median of six visits (range 2–24). Four patients (25%) had a complete response (CR), with median time to CR being 8 weeks; all have maintained the response (range 6–45 months). Eight (50%) showed partial response (PR), with three continuing treatment. Nine patients overall had progressive disease (five in the PR group and four who were nonresponders). In total, five patients died. Patients experienced mainly flu-like symptoms (44%), pyrexia (31%), fatigue (19%), muscle pain (19%), nausea (19%), headache (19%), diarrhoea (6%), joint pain (6%), local swelling (19%), lymphadenopathy (6%) and mild pain (25%). No grade 3 or 4 toxicity occurred. A patient satisfaction questionnaire was returned by seven of eight patients who completed treatment. All said they received adequate information to make treatment decisions. Eighty-six per cent rated the service excellent. Our results show comparable efficacy and side-effects to published clinical trials and demonstrate that T-VEC is a well-tolerated and safe treatment option, delaying or potentially avoiding need for more toxic systemic agents. We highlight that dermatologists and nurse specialists are well placed to deliver T-VEC in patients with melanoma.

Dynamics of level of the tumor-associated marker SCCA in neoadjuvant superselective intra-arterial chemotherapy in patients with cervical squamous cell carcinoma

Background. Evaluation of a tumor-associated marker SCCA (squamous cell carcinoma antigen) level is used in cervical squamous cell carcinoma (CC) to predict the course of the tumor process, monitor the effectiveness of chemo- and chemoradiotherapy, and for preclinical detection of recurrence in follow-up of patients after the completion of primary treatment. However, publications devoted to the study of the possibility of using SCCA level as an additional criterion for the effectiveness of neoadjuvant intra-arterial chemotherapy (IACT) are still rare.Aim. Study of the tumor marker SCCA level in patients with locally advanced squamous CC during neoadjuvant IACT as an additional factor in assessing its effectiveness.Materials and methods. 53 patients with locally advanced squamous CC IB—IVB stages (T1b-3bN0-1M0-1) were included to the study. The mean age of patients was 45.6 years (25-64 years). All patients underwent superselective neoadjuvant IACT with cisplatine (in combination with intravenous administration of docetaxel or paclitaxel). Serum SCCA levels in CC patients were assessed before the first and after the second course of neoadjuvant IACT compared to the clinical effect of treatment after two courses (RECIST 1.1 criteria).Results. SCCA level after 2 courses decreased in all patients with initially increased its level, while the proportion of SCCA-positive cases decreased from 71.7 to 26.4 %. When baseline SCCA values were normal, a complete response was achieved more often than with initially elevated levels (26.7 % vs 15.8 %), while distribution by tumor stages was similar in both subgroups. It has been established that if, after 2 courses of neoadjuvant IACT, SCCA levels exceeds 2.1 ng/ml and/or (for patients with initially increased SCCA value) it decreased by less than 60 % from the baseline, probability to achieve complete response after realization of effect of 2 courses of IACT was extremely small. Strong correlation (R = 0.829) between initial level of SCCA and degree of its decrease after 2 courses of IACT was discovered in the group of patients with complete response after the second course of IACT. It was getting lower in partial response group (R = 0.778) and stabilization group (R = 0.750).Conclusion. Dynamics of SCCA level after 2 courses of IACT in squamous CC patients can be used as additional criterion of the degree of treatment effectiveness.

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.

Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer.

Efficacy and toxicities of anlotinib (ANL) show large inter-patient variation, which may partly be explained by differences in ANL exposure. Exposure-response/toxicities relationship have not been investigated for ANL. Therefore, the aim of the present study was to explore the association between the trough plasma concentration (Ctrough) of ANL and treatment outcomes in Chinese patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who started third-line or further ANL alone therapy between January 2021 and October 2022. This study examined the ANL Ctrough and clinical response evaluation at day 43 after initiation of ANL treatment. We evaluated the association between the ANL Ctrough and clinical efficacy and toxicities. Additionally, this study defined patients with complete response (CR), partial response (PR) and stable disease (SD) as responder. The receiver-operating characteristic (ROC) curve combined with Youden index was identify the potential threshold value of ANL Ctrough for the responder. 52 patients were evaluated for analyses. The median ANL Ctrough was 11.45ng/ml (range, 3.69-26.36 ng/ml). The ANL Ctrough values in the PR group (n=6, 15.51 ng/ml (range, 8.19-17.37 ng/ml)) was significantly higher than in the PD group (n=8, 7.44 ng/ml (range, 5.41-14.69 ng/ml), p=0.001). The area under the ROC curve (AUCROC) was 0.76 (95% confidence interval (CI), 0.58-0.93; p=0.022) and threshold value of ANL Ctrough predicting responder was 10.29 ng/ml (sensitivity 65.9% and specificity 87.5%, the best Youden index was 0.53). The disease control rate (DCR) was 84.6%, and DCR was significantly higher in the high-exposure group (≥10.29ng/ml) than low-exposure group (<10.29ng/ml) (96.67% vs 68.18%, p=0.005). Although there was no significant difference in ANL Ctrough between grade ≥ 3 and grade ≤2 toxicities, the incidence of any grade hand-foot syndrome (70.0% vs 36.36%, p=0.016) and thyroid-stimulating hormone elevation (53.33% vs 22.73%, p =0.026) was significantly higher in the high-exposure group compared with the low-exposure group. Considering these results, we propose that maintaining ANL Ctrough ≥ 10.29ng/ml was important for achieving the response in advanced NSCLC patients treated with ANL.

Cerebrospinal fluid exosomal microRNAs as biomarkers for diagnosing or monitoring the progression of non-small cell lung cancer with leptomeningeal metastases

ABSTRACT Non-small-cell lung cancer (NSCLC) has a terrible consequence called leptomeningeal metastases (LM). It is crucial to look for novel biomarkers because none of the known biomarkers could effectively reflect the oncogenesis, progression and therapeutic responses of LM. Exosomal miRNAs from plasma have a critical function in lung cancer, according to growing data. However, unique biomarkers of cerebrospinal fluid (CSF) are more representative for patients with LM, which have not been reported. Here, we explore the possibility of using CSF-derived exosomal microRNAs as potential biomarkers for NSCLC-LM. Nine NSCLC-LM patients who received regular intrathecal chemotherapy with permetexed were divided into a partial response (PR) group and a progressive disease (PD) group. CSF samples were taken from all patients before and after intrathecal treatment and five non-cancerous controls. Using the size exclusion chromatography (SEC) method, the exosome microRNAs were isolated and profiled. Between LM patients and controls, 56 differentially expressed genes (DEGs) were found, of which three highly elevated diagnostic biomarkers (hsa-miR-183-5p, hsa-miR-96-5p and hsa-miR-182-5p) were ruled out. The two most significant DEGs between the untreated PR group and the PD group were determined to be upregulated hsa-miR-509-3p and downregulated hsa-miR-449a, and they may serve as potential indicators of intrathecal anti-pemetrexed treatment. Hsa-miR-1-3p increased gradually with the intrathecal chemotherapy in the PR group, which might offer a new approach to screen optimal patients and estimate the efficacy. This study revealed specific CSF exosomal miRNAs profile and dynamic changes of patients with NSCLC-LM for the first time and identified several potential exosomal miRNA biomarkers in diagnosis, drug resistance and prognosis.

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.

Efficacy and Safety of Lenvatinib After Progression on First-line Atezolizumab Plus Bevacizumab Treatment in Advanced Hepatocellular Carcinoma Patients.

This study aimed to assess the clinical impact of lenvatinib after disease progression on atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC). A total of 14 patients who received lenvatinib after failure of atezolizumab plus bevacizumab and all patients were classified as having a Barcelona Clinic Liver Cancer stage C. Six patients had macrovascular invasion, and a liver occupation rate of >50% was reported in seven patients. The Kaplan-Meier method was performed to analyze the cumulative survival, while log-rank test was used to detect the differences. The dose of lenvatinib was determined based on body weight. The participants' responses to lenvatinib treatment were as follows: 21.4% achieved partial response (PR), while 35.7% had a stable disease, with a disease control rate of 57.1%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 months and 8.3 months, respectively; the median PFS and OS were 6.7 months and 10.5 months in the PR group. No significant difference was observed in the median PFS and OS between patients with and without macrovascular invasion or liver occupation rate of >50%. Most of the adverse events (AEs) were categorized as grade 1-2; all patients tolerated the AEs, and no drug-related mortality was reported. Additionally, half of the population underwent subsequent therapy after progression on lenvatinib treatment. Lenvatinib is effective and can be safely used as second-line systemic therapy after progression on atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice.

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.

Baseline differences in metabolic profiles of patients with lung squamous cell carcinoma responding or not responding to treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel)

Background: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a preparation widely used in chemotherapy for cancers. However, only some patients benefit from this treatment. Therefore, identifying which patients will respond to nab-paclitaxel therapy is crucial. Methods: A cohort of 32 patients with lung squamous cell carcinoma (LUSC) treated with nab-paclitaxel were enrolled in this study. Plasma samples were collected before chemotherapy and used to perform metabolomic and lipidomic analyses. Tumor response to two cycles of chemotherapy was evaluated. Metabolites differentially present among populations were screened and analyzed. Results: According to the RECIST criteria, one-third of patients had a significant response to nab-paclitaxel, whereas one-fifth showed no discernible benefit. According to the criteria of variable importance in projection &gt;1 and fold change &gt;2, we identified 61, 81 and 54 differential metabolites between the progressive disease (PD) vs partial response (PR), PD vs stable disease (SD), and SD vs PR groups, respectively. Moreover, we used three variation in logistic regression models and ROC diagnostic curves to identify optimal metabolites for stratifying patients with differing chemotherapeutic responses. The PD vs SD, SD vs PR, and PD vs PR groups were well separated on the basis of cis-9,10-epoxystearic acid/octapentaenoic acid (AUC 0.9330), salicyluric acid/DG (18:1/20:5/0:0) (AUC 1.0000) and D-glyceric acid/9,12-octadecadienoic acid (AUC 1.0000), respectively. Conclusion: The baseline metabolic profiles significantly differed between responder and non-responder patients with LUSC treated with nab-paclitaxel. These differential metabolites have the potential to predict the outcomes of patients with LUSC before chemotherapy.

DLCO and Spirometry in non-small cell lung cancer patients receiving EGFR-TKI in Indonesia

Abstract Introduction EGFR-TKI is the treatment of choice in non-small cell lung cancer (NSCLC) with EGFR mutation in exon 19 or 21. The influence of EGFR-TKI therapy on lung function is still unrecognizable in NSCLC patients. Objectives This prospective study aims to examine the influence of EGFR-TKI therapy on lung function of lung adenocarcinoma patients with a single mutation in EGFR exon 19 or 21 at Persahabatan National Respiratory Center Hospital Jakarta, Indonesia. The pulmonary function test (PFT), including spirometry and diffusing capacity (DLCO), was performed before and after three months of EGFR-TKI therapy. After three months, the patients were divided into groups based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and the change of PFT was compared before and after therapy. Results Among twenty lung cancer patients enrolled, we found increase of predicted mean FVC value from 60.6% to 68.25% (p=0.03), mean predicted FEV1 value from 59.7% to 67.05% (p=0.036), mean DLCO from 11.55 ml/minute/mmHg to 13.72 ml/min/mmHg (p=0.004), and predicted DLCO from 53.4% to 63.85% (p=0.03). The increase of mean predicted DLCO was greatest in the partial response group, which was 16.43% (p=0.056). Conclusion This study found that the majority of NSCLC patients with single EGFR exon 19 or 21 mutation had significantly improved lung function after EGFR-TKI therapy. Lung function test might become a beneficial tool to evaluate the effectiveness of EGFR-TKI in NSCLC patients, especially in clinical setting where computerized tomography (CT) scan is not available.

Contrast-enhanced computed tomography radiomics in predicting primary site response to neoadjuvant chemotherapy in high-risk neuroblastoma.

To explore the clinical value of contrast-enhanced computed tomography (CECT) radiomics in predicting primary site response to neoadjuvant chemotherapy in high-risk neuroblastoma. Seventy patients were retrospectively included and separated into very good partial response (VGPR) group and non-VGPR group according to the changes in primary tumor volume. The clinical features with statistical difference between the two groups were used to construct the clinical models using a logistic regression (LR) algorithm. The radiomics models based on different radiomics features selected by Kruskal-Wallis (KW) test and recursive feature elimination (RFE) were established using support vector machine (SVM) and LR algorithms. The radiomics score (Radscore) and clinical features were integrated into the combined models. Leave-one-out cross-validation (LOOCV) was used to validate the predictive performance of models in the entire dataset. The optimal clinical model achieved an area under the curve (AUC) of 0.767 [95% confidence interval (CI): 0.638, 0.896] and an accuracy of 0.771 after LOOCV. The AUCs of the best KW + SVM, KW + LR, RFE + SVM, and RFE + LR radiomics models were 0.816, 0.826, 0.853, and 0.850, respectively, and the corresponding AUCs after LOOCV were 0.780, 0.785, 0.755, and 0.772, respectively. The AUC and accuracy after LOOCV of the optimal combined model was 0.804 (95% CI: 0.694, 0.915) and 0.814, respectively. The Delong test showed a statistical difference in predictive performance between the optimal clinical and combined models after LOOCV (Z = 2.003, P = 0.045). The decision curve analysis showed that the combined model performs better than the clinical model. The CECT radiomics models have a favorable predictive performance in predicting VGPR of high-risk neuroblastoma to neoadjuvant chemotherapy. When integrating radiomics features and clinical features, the predictive performance of the combined models can be further improved.

Tumor thickness in mesothelioma predicts differential response to neoadjuvant therapy and survival

ObjectiveNeoadjuvant systemic therapy in resectable malignant pleural mesothelioma remains controversial and demonstrates variable responses. We sought to evaluate tumor thickness as a predictor of response to neoadjuvant therapy and as a prognostic marker for overall survival. MethodsData from patients who underwent neoadjuvant therapy followed by cytoreductive surgery from 2002 to 2019 were reviewed. Baseline and postneoadjuvant therapy tumor thickness were measured on computed tomography. Radiological tumor response was categorized as progressive disease (≥20% increase), partial response (≥30% decrease), or stable disease (in between). Tumor response outcomes were modeled using logistic regression and multinomial regression models. Overall survival was evaluated based on tumor thickness and tumor response. ResultsOf the 143 patients reviewed, 36 (25%) had progressive disease, 54 (38%) had stable disease, and 56 (39%) had partial response. The baseline tumor thickness of the progressive disease group (36 mm) was lower than in both stable disease and partial response groups (both 63 mm; P < .001). Both logistic regression and multinomial regression analyses demonstrated that thicker baseline tumor thickness was associated with decreased probability of progressive disease and increased probability of partial response. In a multivariable Cox model, thicker postneoadjuvant therapy tumor thickness was associated with worse overall survival (hazard ratio, 1.01, 95% confidence interval, 1.00-1.01, P = .008). The same trend was observed for thicker baseline tumor thickness (hazard ratio, 1.02, 95% confidence interval, 1.01-1.04, P = .008), and the risk was decreased in tumors with partial response (hazard ratio, 0.98, 95% confidence interval, 0.96-0.100, P = .014). ConclusionsWe present the first study demonstrating the relationship between baseline tumor thickness and differential radiographic response to neoadjuvant therapy and survival. Further studies are needed to validate tumor thickness as both a prognostic and predictive biomarker.