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Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging Network (ACRIN) 6698 trial (ClinicalTrials.gov: NCT01042379). The challenge cohort was split into training (60%) and test (40%) sets, with teams blinded to test set pCR outcomes. Prediction performance was evaluated by area under the receiver operating characteristic curve (AUC) and compared with the benchmark established from the ACRIN 6698 primary analysis. Results Eight teams submitted final predictions. Entries from three teams had point estimators of AUC that were higher than the benchmark performance (AUC, 0.782 [95% CI: 0.670, 0.893], with AUCs of 0.803 [95% CI: 0.702, 0.904], 0.838 [95% CI: 0.748, 0.928], and 0.840 [95% CI: 0.748, 0.932]). A variety of approaches were used, ranging from extraction of individual features to deep learning and artificial intelligence methods, incorporating DCE and DWI alone or in combination. Conclusion The BMMR2 challenge identified several models with high predictive performance, which may further expand the value of multiparametric breast MRI as an early marker of treatment response. Clinical trial registration no. NCT01042379 Keywords: MRI, Breast, Tumor Response Supplemental material is available for this article. © RSNA, 2024.

Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval. Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000–2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response's relative risk (RR) alongside objective response rate (ORR) were meta-analyzed. Results: The median development time for breast cancer drugs was 7.8 years (95% CI 6.2–10.8). 26% of treatments were considered innovative ("first-in-indication") with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA's special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417–752) at 181 centers (IQR 142–223) across 19 countries (IQR 17–20). New drugs' HR were 0.78 for OS (95% CI 0.74–0.82) and 0.59 for PFS (95% CI 0.54–0.64) with a RR for tumor response of 1.61 (95% CI 1.46–1.76). Median improvements of OS were 2.8 months (IQR 1.8–5.8) and PFS were 4.4 months (IQR 2.2–7.1). In single-arm trials, the average ORR was 31% (95% CI 10–53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a 'high-value' ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097–17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840–86,062). Conclusions: Over the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods: A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results: A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions: With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration: This was a retrospective study and it did not interfere with treatment decisions. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) accounts for the 5–10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6–12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9–6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine Astragalus was commonly used to assist chemo-drug treatment in clinical cancer patients. However, whether Astragalus injection (AGI) reverses drug resistance remains unclear. Therefore, a meta-analysis is necessary to assess the effect of AGI on resistance reversement in cancer patients. Method: The studies presenting tumor response rates in cancer patients receiving chemo-drugs treatment in combination with AGI were systematically searched from six common scientific databases until February 2024. The relative risks (RRs) indicating the tumor response rate, 1-year survival rate, and quality of life improvement in clinical patients among two groups were calculated in metan package. The pooled RRs with 95% confidence intervals (CIs) were used to explore the effect of AGI on enhancing drug sensitivity in terms of tumor response, 1-year survival rate and quality of life improvement in cancer patients. Result: Fifty-one studies were included for meta-analysis following a thorough screening process that adhered to the inclusion and exclusion criteria. A total of 4613 patients were enrolled in all included trials. Results obtained indicated that AGI significantly enhanced the sensitivity of cancers to chemo-drugs with pooled RRs (95% CI) of 1.25 (1.18, 1.32), prolonged the 1-year survival rate of patients with pooled RRs (95% CI) of 1.34 (1.14, 1.57), improved the quality of life with pooled RRs (95% CI) of 1.61 (1.34, 1.93). Similarly, Astragalus's main component, astragaloside polysaccharides (APS), also enhances drug sensitivity in clinical cancer patients. Conclusion: Our findings demonstrated that AGI had the ability to resensitize cancers to chemo-drugs and improve the quality of life of cancer patients. Therefore, AGI could potentially be used as a drug resistance reversal for resistant cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Aim The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration This was a retrospective study and it did not interfere with treatment decisions.

Purpose To investigate Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) approximations of target lesion tumor burden by comparing categorical treatment response according to conventional RECIST versus actual tumor volume measurements of RECIST target lesions. Materials and Methods This is a retrospective cohort study of individuals with metastatic renal cell carcinoma enrolled in a clinical trial (from 2003 to 2017) and includes individuals who underwent baseline and at least one follow-up chest, abdominal, and pelvic CT study and with at least one target lesion. Target lesion volume was assessed by (a) Vmodel, a spherical model of conventional RECIST 1.1, which was extrapolated from RECIST diameter, and (b) Vactual, manually contoured volume. Volumetric responses were determined by the sum of target lesion volumes (Vmodel-sum TL and Vactual-sum TL, respectively). Categorical volumetric thresholds were extrapolated from RECIST. McNemar tests were used to compare categorical volume responses. Results Target lesions were assessed at baseline (638 participants), week 9 (593 participants), and week 17 (508 participants). Vmodel-sum TL classified more participants as having progressive disease (PD), compared with Vactual-sum TL at week 9 (52 vs 31 participants) and week 17 (57 vs 39 participants), with significant overall response discordance (P < .001). At week 9, 25 (48%) of 52 participants labeled with PD by Vmodel-sum TL were classified as having stable disease by Vactual-sum TL. Conclusion A model of RECIST 1.1 based on a single diameter measurement more frequently classified PD compared with response assessment by actual measured tumor volume. Keywords: Urinary, Kidney, Metastases, Oncology, Tumor Response, Volume Analysis, Outcomes Analysis ClinicalTrials.gov registration no. NCT01865747 © RSNA, 2023 Supplemental material is available for this article.

Background: Overweight and especially obesity are associated with the risk of the development and progression of colorectal cancer. It can be assumed that there are multifaceted interactions between the tumor and adipose tissue during anti-tumor treatment. Cancer cells secrete exosomes, extracellular vesicles affecting the microenvironment of the tumor and promoting its progression or regression. The presence of transcription/translation/folding factors (heat shock proteins (HSPs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in exosomes secreted by irradiated cells and cells exposed to hyperthermia, indicates the cell adaptation to the thermal and radiation stress. Aim: To analyze the MMPs, TIMP1, and HSPs on CD9-positive (CD9+) exosomes, as well as on exosomes of adipocytic origin (FABP4+) in rectal cancer patients with overweight/obesity under thermoradiochemotherapy (TRCT) and their association with the immediate treatment efficacy. Methods: Since 2021, 20 patients (of those 8 men; median age 59.0 [52.0; 63.0] years, median body mass index 29.6 [28.5; 33.1] kg/m2) with morphologically verified rectal cancer (T3-4N0M0 and T3-4N1M0, differentiation grade G1–G3) have been participating in the study. They were treated with TRCT: external gamma therapy (2 Gy, 1 fraction/day, 5 days/week, total focal dose 54 Gy), chemotherapy with capecitabine (825 mg/m2 twice daily) combined with local hyperthermia (42–44 °C, 60 min, 3 times/week, 10 sessions). The TRCT efficacy was assessed by RECIST 1.1 and ESGAR criteria. Blood samples for exosomes were taken from the patients at baseline (point 1), in the middle of the treatment course (point 2), at 6 to 10 weeks after the end of TRCT (point 3), and at 6 months after point 1 (point 4). Small extracellular vesicles were isolated from plasma by ultrafiltration with double ultracentrifugation. The isolated exosomes were characterized by transmission electronic microscopy, flow cytometry and nanoparticle trajectory analysis (NTA). Results: TRCT resulted in complete tumor regression in 13/20 of the rectal cancer patients and partial regression or stabilization in 7/20. Four subpopulations of CD9+ and FABP4+ exosomes associated with the TRCT efficacy were identified (CD9+MMP2+, СD9+MMP2+9+TIMP1+, СD9+MMP2+9+TIMP1-, and FABP4+MMP2+9-TIMP1+). Compared to the CD9+ exosomes, the adipocytic vesicles had higher MMP2 expression (p = 0.026); however, the adipocyte vesicles subpopulation were virtually free of vesicles with combined MMP2 and MMP9 gelatinase expression. The HSPs expression by circulating exosomes at various TRCT steps was associated neither with direct treatment efficacy nor with the vesicle type. Conclusion: The expression of MMPs and TIMP1 on CD9+ and FABP4+ exosomes is associated with TRCT efficacy. In the future, vesicular markers could be used to build prognostic models, to identify patient groups with an unfavorable prognosis, and to personalize treatment and follow-up.

Purpose: Tumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients. Methods: Clinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and ΔTIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS). Results: Two hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02–4.05; p = 0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14–0.76; p = 0.009) and increased ΔTILs (OR 0.25, 95% CI 0.08–0.79; p = 0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS. Conclusions: This study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT. [ABSTRACT FROM AUTHOR]

Purpose: Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases. Materials and Methods: An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS). Results: Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0–52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3–8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively. Conclusion: IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves. [ABSTRACT FROM AUTHOR]

Background This prospective observational study evaluated the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC). A preplanned 2-year final analysis was performed to confirm survival and tumor behavior with nivolumab monotherapy. Patients and Methods The primary endpoint was overall survival (OS). The data regarding tumor size were prospectively collected and evaluated using the RECIST criteria. Exploratory analyses were performed for survival according to the tumor response and depth of response (DpR) in patients with measurable lesions who were receiving nivolumab monotherapy as third- or later-line therapy. Results In 487 patients, the median OS and progression-free survival (PFS) were 5.8 (95% CI 5.3-6.9) months and 1.8 (95% CI 1.7-2.0) months, respectively. The response rate (RR) was 14.5% in 282 patients with measurable lesions. In 234 patients treated with third- or later-line, the DpR was found to be associated with PFS and OS in the Spearman analysis (r  = 0.55 and 0.44, respectively) as well as using a discrete variable. When the DpR was divided into 5 groups (−20%≥DpR; −20%

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5x5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern. [ABSTRACT FROM AUTHOR]

Introduction: Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC‐A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. Methods: Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC‐A measurements in 2014–2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC‐A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. Results: Eighty patients were included. LCGM models identified two distinct trajectories of SCC‐A: low‐stable (40%; n = 32) and high‐decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23–10.53], p = 0.019), progression‐free survival (HR [95% CI]: 11.33 [3.19–40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high‐decline arm. Conclusion: PC patients' SCC‐A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC‐A might assist tumor monitoring after systemic therapies. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. Patients and Methods: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. Results: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1–2 or 3–4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). Conclusions: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen time points relative to baseline (∆FTV1 and ∆FTV2, respectively) were classified into high-standard or standard groups based on visual assessment of FTV under- and overestimation. Logistic regression models predicting pCR using single predictors (FTV0, ∆FTV1, and ∆FTV2) and multiple predictors (all three) were developed using bootstrap resampling with out-of-sample data evaluation with the area under the receiver operating characteristic curve (AUC) independently in each group. Results This study included 432 women (mean age, 49.0 years ± 10.6 [SD]). In the FTV0 model, the high-standard and standard groups showed similar AUCs (0.61 vs 0.62). The high-standard group had a higher estimated AUC compared with the standard group in the ∆FTV1 (0.74 vs 0.63), ∆FTV2 (0.79 vs 0.62), and multiple predictor models (0.85 vs 0.64), with a statistically significant difference for the latter two models (P = .03 and P = .01, respectively). Conclusion The findings in this study suggest that longitudinal variation in FTV estimation needs to be considered when using early FTV change as an MRI-based criterion for breast cancer treatment personalization. Keywords: Breast, Cancer, Dynamic Contrast-enhanced, MRI, Tumor Response ClinicalTrials.gov registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Ram in this issue.

Abstract Introduction Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted as the established treatment options for patients diagnosed with early-stage hepatocellular carcinoma (HCC) who are deemed unfit for surgical procedures. However, the effective implementation of these techniques is hindered by various challenges, primarily associated with the precise targeting of tumors within the liver. The utilization of thermal ablative methods is not recommended for hepatocellular carcinoma (HCC) that is located near intestinal loops, bile ducts, or in eccentric positions. The unmet need for non-thermal methods in the treatment of hepatocellular carcinoma (HCC) was addressed following the introduction of irreversible electroporation (IRE) as an innovative approach. Aim of the work To assess the efficacy, safety, and outcomes of IRE in the treatment of difficult-located HCC compared to transarterial chemoembolization (TACE). Methods This is a prospective study that included 24 patients with HCC who presented to the National Hepatology and Tropical Medicine Research Institute (NHTMRI) during the period from January 2017 to January 2020. Ten patients underwent IRE, while 14 patients underwent TACE. Results Sixteen patients (66.7%) were males; eight patients were females (33.3%). Their median age was 60.5 years (48–70 years). Seventeen patients (70.8%) were Child–Pugh class A, while seven patients (29.2%) were Child–Pugh class B. All the study population had a single focal lesion; the mean size of the focal lesions was 2.94 ± 0.59 cm. The most frequent difficult locations of HCC were segment V focal lesions adjacent to both the common bile duct and portal vein in eight patients (33.3%) followed by lesions adjacent to the inferior vena cava in five patients (20%) followed by the subcapsular lesions in three patients (12.5%) and lesions adjacent to the right kidney in two patients (8.3%). Complete response (CR) was higher in the IRE group (80%) compared to the TACE group (50%). Clinical decompensation occurred in six patients in the IRE group (60%) and eight patients in the TACE group (57.1%) (P value 1). Recurrence occurred in five patients (50%) treated with IRE and in seven patients (50%) treated with TACE (P value 1). Within the IRE group, two patients (20%) remained alive; on the other hand, within the TACE group six patients (42.9%) remained alive by the end of the study (P value 0.388). Conclusion Our data suggest that IRE is an effective procedure in the treatment of difficult-located HCC in terms of complete response, fewer sessions, and fewer side effects as compared to TACE.

ABSTRACTBackground Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases.Methods Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink’s panels.Results A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72).Conclusions Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study.Trial registration ClinicalTrials.gov identifier: NCT04211090.

Introduction: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted as the established treatment options for patients diagnosed with early-stage hepatocellular carcinoma (HCC) who are deemed unfit for surgical procedures. However, the effective implementation of these techniques is hindered by various challenges, primarily associated with the precise targeting of tumors within the liver. The utilization of thermal ablative methods is not recommended for hepatocellular carcinoma (HCC) that is located near intestinal loops, bile ducts, or in eccentric positions. The unmet need for non-thermal methods in the treatment of hepatocellular carcinoma (HCC) was addressed following the introduction of irreversible electroporation (IRE) as an innovative approach. Aim of the work: To assess the efficacy, safety, and outcomes of IRE in the treatment of difficult-located HCC compared to transarterial chemoembolization (TACE). Methods: This is a prospective study that included 24 patients with HCC who presented to the National Hepatology and Tropical Medicine Research Institute (NHTMRI) during the period from January 2017 to January 2020. Ten patients underwent IRE, while 14 patients underwent TACE. Results: Sixteen patients (66.7%) were males; eight patients were females (33.3%). Their median age was 60.5 years (48–70 years). Seventeen patients (70.8%) were Child–Pugh class A, while seven patients (29.2%) were Child–Pugh class B. All the study population had a single focal lesion; the mean size of the focal lesions was 2.94 ± 0.59 cm. The most frequent difficult locations of HCC were segment V focal lesions adjacent to both the common bile duct and portal vein in eight patients (33.3%) followed by lesions adjacent to the inferior vena cava in five patients (20%) followed by the subcapsular lesions in three patients (12.5%) and lesions adjacent to the right kidney in two patients (8.3%). Complete response (CR) was higher in the IRE group (80%) compared to the TACE group (50%). Clinical decompensation occurred in six patients in the IRE group (60%) and eight patients in the TACE group (57.1%) (P value 1). Recurrence occurred in five patients (50%) treated with IRE and in seven patients (50%) treated with TACE (P value 1). Within the IRE group, two patients (20%) remained alive; on the other hand, within the TACE group six patients (42.9%) remained alive by the end of the study (P value 0.388). Conclusion: Our data suggest that IRE is an effective procedure in the treatment of difficult-located HCC in terms of complete response, fewer sessions, and fewer side effects as compared to TACE. [ABSTRACT FROM AUTHOR]

Early prediction of radiation response by imaging is a dynamic field of research and it can be obtained using a variety of noninvasive magnetic resonance imaging methods. Recently, intravoxel incoherent motion (IVIM) has gained interest in cancer imaging. IVIM carries both diffusion and perfusion information, making it a promising tool to assess tumor response. Here, we briefly introduced the basics of IVIM, reviewed existing studies of IVIM in various type of tumors during radiotherapy in order to show whether IVIM is a useful technique for an early assessment of radiation response. 31/40 studies reported an increase of IVIM parameters during radiotherapy compared to baseline. In 27 studies, this increase was higher in patients with good response to radiotherapy. Future directions including implementation of IVIM on MR-Linac and its limitation are discussed. Obtaining new radiologic biomarkers of radiotherapy response could open the way for a more personalized, biology-guided radiation therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). Materials and Methods: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. Results: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028–8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3–4 hematological toxicity between patients with sarcopenia and those without sarcopenia. Conclusions: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3–4 hematological toxicity. [ABSTRACT FROM AUTHOR]

Aim: A systematic review and meta-analysis were performed to evaluate the efficacy of treatments for previously treated advanced biliary tract cancer (BTC) patients. Materials & methods: Databases were searched for studies evaluating treatments for advanced (unresectable and/or metastatic) BTC patients who progressed on prior therapy. Pooled estimates of objective response rate (ORR), median overall survival (OS) and median progression-free survival (PFS) were calculated using random effects meta-analysis. Results: Across 31 studies evaluating chemotherapy or targeted treatment regimens in an unselected advanced BTC patient population, pooled ORR was 6.9%, median OS was 6.6 months and median PFS was 3.2 months. Conclusion: The efficacy of conventional treatments for previously treated advanced BTC patients is poor and could be improved by novel therapies. What is this article about? Most patients with biliary tract cancer are identified with advanced disease, and almost all go through a worsening of the disease after their first treatment. For patients who go on to receive their next treatment, current guidelines are unclear regarding the best treatment choice. Therefore, we examined the available medical literature and performed an analysis of multiple studies to calculate overall estimates of the clinical value of standard treatments for these patients. Our goal was to develop a benchmark against which to compare the clinical value of new treatments that are currently being assessed in clinical trials. What were the results? We identified 31 studies assessing standard treatments (involving chemotherapy or molecularly targeted treatments) in previously treated advanced biliary tract cancer patients. Across these studies, the objective tumor response rate was 6.9%, median overall survival was 6.6 months and median progression-free survival was 3.2 months. What do the results of the study mean? These results indicate that there is limited clinical value of standard treatments for patients with advanced biliary tract cancer whose disease worsened after first treatment. This medical need could potentially be met by new treatments, such as immunotherapies that restore the immune system's ability to attack cancer cells and thereby prolong patient survival. A synthesis of evidence from clinical studies indicates the need for more effective therapies for advanced biliary tract cancer patients whose disease progressed on prior therapy. #cholangiocarcinoma #bileductcancer [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we explored the use of bevacizumab as a treatment for NF2-related schwannomatosis, a condition characterized by the development of schwannomas on both vestibulocochlear nerves. This study revealed that the majority of patients experienced either improved or preserved hearing and effective control of the targeted vestibular schwannoma with bevacizumab. However, common adverse events included hypertension and fatigue, and severe adverse events led to treatment discontinuation in a quarter of the patients. Thus, while bevacizumab demonstrates positive effects on hearing, tumor control, and symptomatology in NF2-related schwannomatosis, careful consideration of potential side effects is crucial. (1) Background: NF2-related schwannomatosis, characterized by the development of bilateral vestibular schwannomas, often necessitates varied treatment approaches. Bevacizumab, though widely utilized, demonstrates variable effectiveness on hearing and tumor growth. At the same time, (serious) adverse events have been frequently reported. (2) Methods: A single center retrospective study was conducted, on NF2-related schwannomatosis patients treated with bevacizumab from 2013 to 2023, with the aim to assess treatment-related and clinical outcomes. Outcomes of interest comprised hearing, radiologic response, symptoms, and adverse events. (3) Results: Seventeen patients received 7.5 mg/kg bevacizumab for 7.1 months. Following treatment, 40% of the patients experienced hearing improvement, 53%, stable hearing, and 7%, hearing loss. Vestibular schwannoma regression occurred in 31%, and 69% remained stable. Further symptomatic improvement was reported by 41%, stable symptoms by 47%, and worsened symptoms by 12%. Treatment discontinuation due to adverse events was observed in 29% of cases. Hypertension (82%) and fatigue (29%) were most frequently reported, with no occurrences of grade 4/5 toxicities. (4) Conclusion: Supporting previous studies, bevacizumab demonstrated positive effects on hearing, tumor control, and symptoms in NF2-related schwannomatosis, albeit with common adverse events. Therefore, careful consideration of an appropriate management strategy is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC). Methods: We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed. Results: A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved. Conclusion: The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC. [ABSTRACT FROM AUTHOR]

The aim of the work described here was to explore the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and anti-angiogenesis therapies for unresectable hepatocellular carcinoma (HCC). Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non-responder groups were compared, and the correlations between CEUS parameters and progression-free survival (PFS) was evaluated. The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash-in rate ratio, wash-in perfusion index ratio and wash-out rate ratio differed significantly differed between the responder and non-responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000–0.307, p = 0.010). The median RT ratios of the responder and non-responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X-tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001). CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC. [ABSTRACT FROM AUTHOR]

Major strides have been made in the development of FLASH radiotherapy (FLASH RT) in the last ten years, but there are still many obstacles to overcome for transfer to the clinic to become a reality. Although preclinical and first-in-human clinical evidence suggests that ultra-high dose rates (UHDRs) induce a sparing effect in normal tissue without modifying the therapeutic effect on the tumor, successful clinical translation of FLASH-RT depends on a better understanding of the biological mechanisms underpinning the sparing effect. Suitable in vitro studies are required to fully understand the radiobiological mechanisms associated with UHDRs. From a technical point of view, it is also crucial to develop optimal technologies in terms of beam irradiation parameters for producing FLASH conditions. This review provides an overview of the research progress of FLASH RT and discusses the potential challenges to be faced before its clinical application. We critically summarize the preclinical evidence and in vitro studies on DNA damage following UHDR irradiation. We also highlight the ongoing developments of technologies for delivering FLASH-compliant beams, with a focus on laser-driven plasma accelerators suitable for performing basic radiobiological research on the UHDR effects. [ABSTRACT FROM AUTHOR]

Abstract Introduction Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC‐A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. Methods Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC‐A measurements in 2014–2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC‐A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. Results Eighty patients were included. LCGM models identified two distinct trajectories of SCC‐A: low‐stable (40%; n = 32) and high‐decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23–10.53], p = 0.019), progression‐free survival (HR [95% CI]: 11.33 [3.19–40.3], p

BackgroundKnowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies.ObjectiveTo investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells.MethodsWe conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random).ResultsForty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4–8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing 20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P

Abstract Background Studies have shown mixed results concerning the role of primary tumor volume (TV) and metastatic lymph node (NV) volume in response to the curative effect of definitive radiotherapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC). Objective We aimed to evaluate the impact of TV and NV on the efficacy of radical radiotherapy in LAHNSCC patients, with the goal of guiding individualized therapy. Patients and methods Patients with LAHNSCC who received radical radiation therapy and were reexamined within 6 months post-therapy from January 2012 to December 2021 were selected. The volumes of the primary tumors and metastatic lymph nodes were calculated by software and then were divided into a large TV group vs small TV group and a large NV group vs small NV group according to the relationship with the median. Additionally, patients who received concurrent chemoradiotherapy (CCRT) or not were divided into the CCRT group and the radiotherapy (RT) group. Patients with lymph node metastasis were divided into node concurrent chemotherapy (N-CCRT) group and a node metastatic chemotherapy (N-RT) group according to whether they received concurrent chemotherapy or not. The volume shrinkage rate (VSR), objective response rate (ORR), local control rate (LCR) and overall survival (OS) were recorded and analyzed. Results 96 patients were included in the primary tumor volume group, and 73 patients were included in the metastatic lymph node group. Receiver operating characteristic (ROC) curves were constructed for objective remission (OR) endpoints, and a volume threshold was defined for TV and NV patients. The threshold primary tumor volume was 32.45 cm3, and the threshold metastatic lymph node volume was 6.05 cm3.The primary TV shrinkage rates of the small TV and the large TV groups were basically the same, P = 0.801. Similarly, the ORR and LCR were not significantly different between the small TV group and the large TV group (P ORR = 0.118, P LCR = 0.315). Additionally, the TV shrinkage rate did not significantly differ between the CCRT group and the RT group, P = 0.133. Additionally, there was no significant difference in ORR or LCR in CCRT group (P ORR = 0.057, P LCR = 0.088). However, the metastatic lymph node volume shrinkage rate in the small NV group was significantly greater than that in the large NV group (P = 0.001). The ORR and LCR of the small NV subgroup were significantly greater than those of the large NV subgroup (P ORR = 0.002, P LCR = 0.037). Moreover, compared with that of the N-RT group, the NV shrinkage rate of the N-CCRT group was 84.10 ± s3.11%, and the shrinkage rate was 70.76 ± s5.77% (P = 0.047). For the ORR and LCR, the N-CCRT group and N-RT group were significantly different (P ORR = 0.030, P LCR = 0.037). The median OS of the whole group was 26 months. However, neither TV/NV nor concurrent chemotherapy seemed to influence OS. Conclusion Primary tumor volume is not a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Nevertheless, metastatic lymph nodes are a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Patients with smaller lymph nodes have better local control.

Background: Neoadjuvant chemoradiotherapy has emerged as the established treatment for locally advanced rectal cancer. Nevertheless, there remains a debate regarding the necessity of adjuvant chemotherapy for patients with locally advanced rectal cancer who exhibit a favorable tumor response (ypT0-2N0) after neoadjuvant chemoradiotherapy and surgery. Thus, the objective of this study is to investigate the impact of adjuvant chemotherapy on the oncological prognosis of rectal cancer patients who have a good response to neoadjuvant chemoradiotherapy. Materials and methods: The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles were searched in the Web of Science, PubMed, and Cochrane Library databases. The primary outcomes assessed were 5-year overall survival, disease-free survival, cancer-specific survival, recurrence-free survival, local recurrence, and distant metastasis. The data was summarized using a random effects model. Results: A meta-analysis was conducted using 18 retrospective studies published between 2009 and 2023. The studies included 9 from China and 5 from Korea, involving a total of 6566 patients with ypT0-2N0 rectal cancer after neoadjuvant chemoradiotherapy. The pooled data revealed that adjuvant chemotherapy significantly improved 5-year overall survival (OR=1.75, 95% CI: 1.15-2.65, P=0.008), recurrence-free survival (OR=1.73, 95% CI: 1.20-2.48, P=0.003), and reduced distant metastasis (OR=0.68, 95% CI: 0.51-0.92, P=0.011). However, adjuvant chemotherapy did not have a significant effect on disease-free survival, cancer-specific survival, and local recurrence in ypT0-2N0 rectal cancer. Subgroup analysis indicated that adjuvant chemotherapy was beneficial in improving overall survival for ypT1-2N0 rectal cancer (OR=1.89, 95% CI: 1.13-3.19, P=0.003). Conclusion: The findings of themeta-analysis suggest that adjuvant chemotherapy may provide benefits in terms of oncological outcomes for rectal cancer patients with ypT0-2N0 after neoadjuvant chemoradiotherapy and radical surgery. However, further prospective clinical studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Studies have shown mixed results concerning the role of primary tumor volume (TV) and metastatic lymph node (NV) volume in response to the curative effect of definitive radiotherapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC). Objective: We aimed to evaluate the impact of TV and NV on the efficacy of radical radiotherapy in LAHNSCC patients, with the goal of guiding individualized therapy. Patients and methods: Patients with LAHNSCC who received radical radiation therapy and were reexamined within 6 months post-therapy from January 2012 to December 2021 were selected. The volumes of the primary tumors and metastatic lymph nodes were calculated by software and then were divided into a large TV group vs small TV group and a large NV group vs small NV group according to the relationship with the median. Additionally, patients who received concurrent chemoradiotherapy (CCRT) or not were divided into the CCRT group and the radiotherapy (RT) group. Patients with lymph node metastasis were divided into node concurrent chemotherapy (N-CCRT) group and a node metastatic chemotherapy (N-RT) group according to whether they received concurrent chemotherapy or not. The volume shrinkage rate (VSR), objective response rate (ORR), local control rate (LCR) and overall survival (OS) were recorded and analyzed. Results: 96 patients were included in the primary tumor volume group, and 73 patients were included in the metastatic lymph node group. Receiver operating characteristic (ROC) curves were constructed for objective remission (OR) endpoints, and a volume threshold was defined for TV and NV patients. The threshold primary tumor volume was 32.45 cm3, and the threshold metastatic lymph node volume was 6.05 cm3.The primary TV shrinkage rates of the small TV and the large TV groups were basically the same, P = 0.801. Similarly, the ORR and LCR were not significantly different between the small TV group and the large TV group (PORR = 0.118, PLCR = 0.315). Additionally, the TV shrinkage rate did not significantly differ between the CCRT group and the RT group, P = 0.133. Additionally, there was no significant difference in ORR or LCR in CCRT group (PORR = 0.057, PLCR = 0.088). However, the metastatic lymph node volume shrinkage rate in the small NV group was significantly greater than that in the large NV group (P = 0.001). The ORR and LCR of the small NV subgroup were significantly greater than those of the large NV subgroup (PORR = 0.002, PLCR = 0.037). Moreover, compared with that of the N-RT group, the NV shrinkage rate of the N-CCRT group was 84.10 ± s3.11%, and the shrinkage rate was 70.76 ± s5.77% (P = 0.047). For the ORR and LCR, the N-CCRT group and N-RT group were significantly different (PORR = 0.030, PLCR = 0.037). The median OS of the whole group was 26 months. However, neither TV/NV nor concurrent chemotherapy seemed to influence OS. Conclusion: Primary tumor volume is not a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Nevertheless, metastatic lymph nodes are a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Patients with smaller lymph nodes have better local control. [ABSTRACT FROM AUTHOR]

Objective To evaluate the relationship between plasma heat shock protein 90α (HSP90α) levels and treatment response after four weeks and long-term prognosis after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Methods The clinical data of HCC patients who underwent TACE in the Department of Interventional Radiology, Cancer Hospital of Chinese Academy of Medical Sciences from August 2017 to December 2018 were retrospectively collected. Chi-square tests were used to analyze the relationship between plasma HSP90α level and clinicopathological features before TACE treatment. Univariate and multivariate logistic regression analysis was used to analyze the influencing factors of TACE treatment response. Univariate and multivariate Cox regression analysis was used to analyze the influencing factors of progression-free survival (PFS) after TACE treatment. Results The expression level of plasma HSP90α in 96 patients before TACE treatment was (99.70 ± 66.61) ng/ml. Compared with the low HSP90α group ( n=66), the high HSP90α group ( n=30) had larger tumors, higher alpha-fetoprotein enrichment, more positive vascular invasions, and more advanced Barcelona Clinic Liver Cancer (BCLC) stages (all P<0.05). After four weeks of TACE treatment, 41 patients in the response group and 55 patients in the non-response group were evaluated. The difference of HSP90α expression levels between the response group and the non-response group before and after TACE treatment was (-32.20±22.79) ng/ml and (7.20±51.94) ng/ml, respectively, and the difference was statistically significant ( P<0.001). Multivariate logistic regression analysis showed that Child-Pugh classification ( OR=0.186, P=0.046), vascular invasion ( OR=0.132, P=0.025), and the percentage reduction of plasma HSP90α after TACE treatment (percentage reduction 25%-50%: OR=5.061, P=0.013; percentage reduction >50%: OR= 86.831, P<0.001) were independent influencing factors for the response to TACE treatment in HCC. The median PFS of the 96 patients was 8.7 months. Multivariate Cox regression analysis showed that BCLC stage (stage B: HR=2.804, P=0.008; stage C: HR=4.628, P<0.001) and the percentage reduction of plasma HSP90α after TACE treatment (percentage reduction 25%-50%: HR=0.569, P=0.051; percentage reduction >50%: HR=0.198, P<0.001) were independent influence factors for the PFS in these HCC patients after TACE treatment. [ABSTRACT FROM AUTHOR]

Fighting breast tumors mandates finding different agents devoid of chemotherapy side effects. Repurposing existing drugs, such as statins, presents a promising avenue for the development of novel cancer therapeutics. Based on the different effects of statin members, this study aims to evaluate the effect of two of the most promising lipophilic statins, Simvastatin and Pitavastatin, and their combination with a conventional chemotherapeutic regimen of doxorubicin and cyclophosphamide on breast cancer cells. MDA-MB-231 and MCF7 cell lines were used to analyze the effects of Pitavastatin and simvastatin in combination with doxorubicin/cyclophosphamide. Cell viability and cell cycle were analyzed and certain apoptosis-related genes such as Bax, Bcl2, and caspase-3, besides cyclin D1 were analyzed using qPCR. The viability of breast cancer cells decreased significantly after treatment with a doxorubicin/cyclophosphamide combination in the presence of Pitavastatin or simvastatin compared with dual doxorubicin/cyclophosphamide with a higher effect in MDA-MB-231 cells than MCF7. In MDA-MB-231, The triple combination of Pitavastatin or simvastatin with doxorubicin/cyclophosphamide resulted in an increase in the expression levels of apoptotic markers than treatment with doxorubicin/cyclophosphamide combination (Bax (p-value = 0.09& 0.02, respectively), Bax/Bcl2 ratio (p-value = 0.0002& <0.0001, respectively)). However, the increase in caspase3 wasn't significant (p-value = 0.45& 0.09, respectively). Moreover, the expression of cyclin D1 decreased (p-value = 0.0002& <0.0001, respectively) and the cell cycle was arrested in the G1 phase. Combination of Pitavastatin or simvastatin with doxorubicin/ cyclophosphamide may induce apoptosis in breast cancer cells via upregulation of the Bax/Bcl2 pathway, potentially providing a promising new therapeutic strategy for breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Vessels encapsulating tumor clusters (VETC) is a novel vascular pattern structurally and functionally distinct from microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study aims to explore the prognostic value of VETC in patients receiving hepatic arterial infusion chemotherapy (HAIC) for unresectable HCC. Methods: From January 2016 to December 2017, 145 patients receiving HAIC as the initial treatment for unresectable HCC were enrolled and stratified into two groups according to their VETC status. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were evaluated. Results: The patients were divided into two groups: VETC+ (n = 31, 21.8%) and VETC− (n = 114, 78.2%). The patients in the VETC+ group had worse ORR and DCR than those in the VETC− group (RECIST: ORR: 25.8% vs. 47.4%, P = 0.031; DCR: 56.1% vs. 76.3%, P = 0.007; mRECIST: ORR: 41.0% vs. 52.6%, P = 0.008; DCR: 56.1% vs. 76.3%, P = 0.007). Patients with VETC+ had significantly shorter OS and PFS than those with VETC− (median OS: 10.2 vs. 21.6 months, P < 0.001; median PFS: 3.3 vs. 7.2 months, P < 0.001). Multivariate analysis revealed VETC status as an independent prognostic factor for OS (HR: 2.40; 95% CI: 1.46–3.94; P = 0.001) and PFS (HR: 1.97; 95% CI: 1.20–3.22; P = 0.007). Conclusion: VETC status correlates remarkably well with the tumor response and long-term survival in patients undergoing HAIC. It may be a promising efficacy predictor and help identify patients who will benefit from HAIC. [ABSTRACT FROM AUTHOR]

The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes. [ABSTRACT FROM AUTHOR]

Rishabh Lohray,1 Kritin K Verma,2 Leo L Wang,3 Dylan Haynes,3 Daniel J Lewis3 1Baylor College of Medicine, Houston, TX, USA; 2Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, USA; 3Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Daniel J Lewis, Penn Dermatology Oncology Center, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Suite 1-330S, Philadelphia, PA, 19104, USA, Tel +1 215-360-0909, Fax +1 215-662-4132, Email Daniel.Lewis@pennmedicine.upenn.eduIntroduction: Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings.Areas Covered: Real-world studies on avelumab for MCC from North and South America, Europe, and Asia have been presented in this review. Most studies are on patients over age 70 and have a male-predominant sex ratio. Overall response rates range from 29.1% to 72.1%, (disease control rate: 60.0– 72.7%; complete response rate: 15.8%– 37.2%; partial rate: 18.2– 42.1%; stable disease: 7.1– 30.9%; progressive disease: 7.1– 40.0%) and median progression free survival ranges from 8.1 to 24.1 months depending on the population studied. Immunosuppressed patients appear to benefit from avelumab as well, with response rates equivalent to the general population. Patients receiving avelumab as a first-line agent tend to have better outcomes than those using it as a second-line therapy. Fatigue, infusion-related reactions, and dyspnea were some of the most common adverse events identified in real-world studies. Autoimmune hepatitis and thyroiditis were also observed.Conclusion: The use of avelumab as a safe and effective treatment option for advanced MCC is supported by real-world data, although additional study is required to assess long-term efficacy and safety outcomes.Keywords: Merkel cell carcinoma, avelumab, real-world studies, immune-checkpoint inhibitors, tumor response, adverse events

PURPOSETo compare tumor perfusion on cone-beam computed tomography (CBCT) after hepatic artery infusion port implantation with the tumor response to hepatic arterial infusion chemotherapy (HAIC) in patients with hepatocellular carcinoma (HCC).METHODSThis retrospective study was conducted in patients with advanced HCC treated with HAIC from 2015 to 2020. We performed CBCT with contrast injection via a port on the day following implantation. We classified tumor perfusion on CBCT into three groups: hyperperfusion, isoperfusion, and hypoperfusion. We also evaluated tumor response to HAIC on follow-up images using RECIST 1.1 and compared it with tumor perfusion on CBCT.RESULTSThis study included 206 tumors in 193 patients (mean: 60.5 years) with HCC. There were 100 hyperperfusion tumors (48.5%), 92 isoperfusion tumors (44.7%), and 14 hypoperfusion tumors (6.8%). The tumor response to HAIC included 10 tumors with a complete response (CR) (4.9%), 66 tumors with a partial response (32%), 60 tumors with stable disease (29.1%), and 70 tumors with progressive disease (34%). Hyperperfusion tumors had a 65% objective response rate (ORR) and a 92% disease control rate (DCR). Isoperfusion tumors had a 12% ORR and a 46.8% DCR, while hypoperfusion tumors had a 0% ORR and a 7.1% DCR. A CR was shown only in hyperperfusion tumors. The ORR and DCR of the three groups were different, with statistical significance (P < 0.001).CONCLUSIONHyperperfusion tumors on CBCT showed a better tumor response to HAIC, with a 65% ORR in patients with HCC. Tumor perfusion on CBCT after implantation of the hepatic arterial infusion port was associated with the tumor response to HAIC.

Abstract Background To develop and validate radiomics models for prediction of tumor response to neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC) using both pre-NAT and post-NAT multiparameter magnetic resonance imaging (mpMRI). Methods In this multicenter study, a total of 563 patients were included from two independent centers. 453 patients from center 1 were split into training and testing cohorts, the remaining 110 from center 2 served as an external validation cohort. Pre-NAT and post-NAT mpMRI was collected for feature extraction. The radiomics models were constructed using machine learning from a training cohort. The accuracy of the models was verified in a testing cohort and an independent external validation cohort. Model performance was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. Results The model constructed with pre-NAT mpMRI had favorable accuracy for prediction of non-response to NAT in the training cohort (AUC = 0.84), testing cohort (AUC = 0.81), and external validation cohort (AUC = 0.79). The model constructed with both pre-NAT and post-NAT mpMRI had powerful diagnostic value for pathologic complete response in the training cohort (AUC = 0.86), testing cohort (AUC = 0.87), and external validation cohort (AUC = 0.87). Conclusions Models constructed with multiphase and multiparameter MRI were able to predict tumor response to NAT with high accuracy and robustness, which may assist in individualized management of LARC.

The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4–18.5) and 4 months (CI = 95%, 2.09–5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC.

Meng-Chao Luo,1,2,&ast; Jia-Yi Wu,1,3,&ast; Jun-Yi Wu,1,3 Zhong-Tai Lin,1,2 Yi-Nan Li,3 Zhen-Xin Zeng,3 Shao-Ming Wei,1,2 Mao-Lin Yan1,3 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of General Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88217130, Fax +86 591-87557768, Email yanmaolin74@163.com Shao-Ming Wei, Department of General Surgery, Fujian Provincial Hospital, Jinrong South Road 516, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88618707, Fax +86 591-88618900, Email 67468424@qq.comPurpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy.Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration > 50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS).Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991– 45.950, p< 0.001; high-DCP group: OR: 17.853; 95% CI: 4.478– 71.179, p< 0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p< 0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p< 0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p< 0.001).Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of > 50% predicts better treatment outcomes in uHCC patients.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, des-gamma-carboxyprothrombin, combination therapy, tumor response

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT “number of involved organs” by metastasis and smoking pack years were independently associated with PD (p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort.

Background: Gut bacteria-derived short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) are considered to have beneficial metabolic, anti-inflammatory as well as anti-carcinogenic effects. Previous preclinical studies indicated bidirectional interactions between gut bacteria and the chemotherapeutic capecitabine or its metabolite 5-FU. This study investigated the effect of three cycles of capecitabine on fecal SCFA and BCFA levels and their associations with tumor response, nutritional status, physical performance, chemotherapy-induced toxicity, systemic inflammation and bacterial abundances in patients with colorectal cancer (CRC). Methods: Forty-four patients with metastatic or unresectable CRC, scheduled for treatment with capecitabine (± bevacizumab), were prospectively enrolled. Patients collected a fecal sample and completed a questionnaire before (T1), during (T2) and after (T3) three cycles of capecitabine. Tumor response (CT/MRI scans), nutritional status (MUST score), physical performance (Karnofsky Performance Score) and chemotherapy-induced toxicity (CTCAE) were recorded. Additional data on clinical characteristics, treatment regimen, medical history and blood inflammatory parameters were collected. Fecal SCFA and BCFA concentrations were determined by gas chromatography–mass spectrometry (GC–MS). Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. Results: Fecal levels of the SCFA valerate and caproate decreased significantly during three cycles of capecitabine. Furthermore, baseline levels of the BCFA iso-butyrate were associated with tumor response. Nutritional status, physical performance and chemotherapy-induced toxicity were not significantly associated with SCFA or BCFA. Baseline SCFA correlated positively with blood neutrophil counts. At all time points, we identified associations between SCFA and BCFA and the relative abundance of bacterial taxa on family level. Conclusions: The present study provided first indications for a potential role of SCFA and BCFA during capecitabine treatment as well as implications for further research. Trial registration: The current study was registered in the Dutch Trial Register (NTR6957) on 17/01/2018 and can be consulted via the International Clinical Trial Registry Platform (ICTRP). [ABSTRACT FROM AUTHOR]

Background: To develop and validate radiomics models for prediction of tumor response to neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC) using both pre-NAT and post-NAT multiparameter magnetic resonance imaging (mpMRI). Methods: In this multicenter study, a total of 563 patients were included from two independent centers. 453 patients from center 1 were split into training and testing cohorts, the remaining 110 from center 2 served as an external validation cohort. Pre-NAT and post-NAT mpMRI was collected for feature extraction. The radiomics models were constructed using machine learning from a training cohort. The accuracy of the models was verified in a testing cohort and an independent external validation cohort. Model performance was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. Results: The model constructed with pre-NAT mpMRI had favorable accuracy for prediction of non-response to NAT in the training cohort (AUC = 0.84), testing cohort (AUC = 0.81), and external validation cohort (AUC = 0.79). The model constructed with both pre-NAT and post-NAT mpMRI had powerful diagnostic value for pathologic complete response in the training cohort (AUC = 0.86), testing cohort (AUC = 0.87), and external validation cohort (AUC = 0.87). Conclusions: Models constructed with multiphase and multiparameter MRI were able to predict tumor response to NAT with high accuracy and robustness, which may assist in individualized management of LARC. [ABSTRACT FROM AUTHOR]

Background: To date, no specific studies have reported the use of dynamic serum tumor markers (STMs) as prognostic factors in patients with advanced non-small-cell lung cancer (NSCLC) who receive first-line immunotherapy. Therefore, it is unclear whether STMs can be used as a prognostic factor for first-line immunotherapy in advanced NSCLC. Objectives: To elucidate the role of STMs in monitoring immunotherapy response in advanced NSCLC. Patients were treated with first-line programmed cell death-1/programmed cell death ligand-1 inhibitors at four Chinese centers. Design: This was a multicenter retrospective study. Methods: Blood samples were collected at baseline and after 6–8 weeks of treatment. Computed tomography scans were used to evaluate treatment efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Post-treatment drops in STMs [Serum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125)] were decreased ⩾20% (Group C) over baseline was used as cutoff level for defining a marker response. If STMs were increased by ⩾20% after treatment, the therapeutic effect was limited (Group A). Patients with STM changes between a 20% increase or decrease were enrolled in Group B. In univariate and multivariate stepwise Cox regression analyses, STMs and RECIST responses were analyzed for their impact on progression-free survival (PFS) and overall survival (OS). Results: The analysis included 716 patients. By multivariate analysis, CEA, NSE, CYFRA21-1, CA19-9, and CA125 (Group A versus Group B and Group A versus Group C) were associated with significant differences in PFS. Similar results were observed in the OS analysis. Similar results were observed in the adenocarcinoma subgroup analyses. In squamous cell carcinoma subgroup analyses, there was no statistical difference in PFS (p = 0.147) or OS (p = 0.068) between Group A and Group B for CA125. Conclusion: The increase and decrease in serum levels of STMs might be reliable prognostic factors for immunotherapy efficacy in NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: For Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), measuring up to two target lesions per organ is an arbitrary criterion. Objectives: We sought to compare response assessment using RECIST1.1 and modified RECIST1.1 (mRECIST1.1, measuring the single largest lesion per organ) in advanced non-small cell lung cancer (aNSCLC) patients undergoing anti-PD-1/PD-L1 monotherapy. Methods: Concordance of radiologic response categorization between RECIST1.1 and mRECIST1.1 was compared using the Kappa statistics. C-index was calculated to evaluate prognostic accuracy of radiologic response by the two criteria. The Kaplan–Meier method and Cox regression analysis were conducted for progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients who had at least two target lesions in any organ per the RECIST1.1 were eligible for comparison analysis. Tumor response showed excellent concordance when measured using the RECIST1.1 and mRECIST1.1 (Kappa = 0.961). C-index by these two criteria was similar for PFS (0.784 versus 0.785) and OS (0.649 versus 0.652). Responders had significantly longer PFS and OS versus non-responders (p < 0.05), whichever criterion adopted. Radiologic response remained a significant predictor of PFS and OS in multivariate analysis (p < 0.05). Conclusion: The mRECIST1.1 was comparable to RECIST1.1 in response assessment among aNSCLC patients who received single-agent PD-1/PD-L1 inhibitor. The mRECIST1.1, with reduced number of lesions to be measured, may be sufficient and more convenient to assess antitumor activity in clinical practice. [ABSTRACT FROM AUTHOR]

Obesity is a well-known risk factor for the development of renal cell carcinoma (RCC), one of the most frequent malignant urogenital tumors. The development of immunotherapy (IO)-based combinations for the treatment of metastatic RCC (mRCC) has led to a marked improvement of patients' outcomes and quality of life. The ARON-1 study (NCT05287464) was designed to globally analyze real-world treatment outcomes of mRCC patients receiving first-line immune-based combinations. In this sub-analysis, we investigated the role of body mass index (BMI) in patients treated by immuno-oncology combinations stratified by clinico-pathological features. According to our results, the prognostic significance and the association of BMI with treatment outcome may vary across clinico-pathological mRCC subgroups. Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immunooncology agents (IO + IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as firstline therapy for metastatic renal cell carcinoma (mRCC). Patients and Methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. Results: A total of 675 patients were included; BMI was > 25 kg/m 2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI > 25 kg/m 2 versus those with BMI =25 kg/m 2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio > 4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P = .044). In the BMI =25 kg/m 2 subgroup, significant differences were found between patients with NLR > 4 versus =4 (62% vs. 82%, P = .002) and patients treated by IO + IO versus IO + TKIs combinations (64% vs. 83%, P = .002). Conclusion: Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups. [ABSTRACT FROM AUTHOR]

The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4–18.5) and 4 months (CI = 95%, 2.09–5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC. [ABSTRACT FROM AUTHOR]

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain belowthe luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment. [ABSTRACT FROM AUTHOR]

To establish a prediction model for the efficacy of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC), using pretreatment magnetic resonance imaging (MRI) multisequence image features and clinical parameters. Patients with clinicopathologically confirmed LARC were included (training and validation datasets, n = 100 and 27, respectively). Clinical data of patients were collected retrospectively. We analyzed MRI multisequence imaging features. The tumor regression grading (TRG) system proposed by Mandard et al was adopted. Grade 1-2 of TRG was a good response group, and grade 3-5 of TRG was a poor response group. In this study, a clinical model, a single sequence imaging model, and a comprehensive model combined with clinical imaging were constructed, respectively. The area under the subject operating characteristic curve (AUC) was used to evaluate the predictive efficacy of clinical, imaging, and comprehensive models. The decision curve analysis method evaluated the clinical benefit of several models, and the nomogram of efficacy prediction was constructed. The AUC value of the comprehensive prediction model is 0.99 in the training data set and 0.94 in the test data set, which is significantly higher than other models. Radiomic Nomo charts were developed using Rad scores obtained from the integrated image omics model, circumferential resection margin(CRM), DoTD, and carcinoembryonic antigen(CEA). Nomo charts showed good resolution. The calibrating and discriminating ability of the synthetic prediction model is better than that of the single clinical model and the single sequence clinical image omics fusion model. Nomograph, based on pretreatment MRI characteristics and clinical risk factors, has the potential to be used as a noninvasive tool to predict outcomes in patients with LARC after nCRT. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. The first-line treatment for GC is a combination of platinum and fluoropyrimidine-based therapy. Based on the positive results of RAINBOW and REGARD trials, ramucirumab either alone or in combination with paclitaxel has proved to be a safe and active option for second-line treatment in GC patients. Material and methods: Advanced GC patients who received a 28-day cycles of ramucirumab and paclitaxel until disease progression or unacceptable toxicity were evaluated. Eligible patients had ECOG PS ≤ 1 and adequate organ function. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method and Cox proportional-hazards regression models were used for survival analyses. Results: In our single institution experience, we included a total of 67 patients. A median OS of 8 months and a median PFS of 4 months, were recorded. In patients experiencing an initial partial response (PR), we observed a significant association between tumor response and survival outcomes (OS and PFS). The OS and PFS were 15 and 11 months in patients who experienced PR compared to 8 and 4 months in patients without PR (p = 0.02; p = 0.04). Conclusion: Treatment with ramucirumab plus paclitaxel yielded the highest overall response rate reported to date for patients with previously treated advanced GC. In our experience, the initial tumor response is associated with a greater survival benefit which could be further improved by the identification of biomarkers predicting response. [ABSTRACT FROM AUTHOR]

Drug discovery and approval in oncology is mediated by the use of imaging to evaluate drug efficacy in clinical trials. Imaging is performed while patients receive therapy to evaluate their response to treatment. Response criteria, specifically Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), are standardized and can be used at different time points to classify response into the categories of complete response, partial response, stable disease, or disease progression. At the trial level, categorical responses for all patients are summated into image-based trial endpoints. These outcome measures, including objective response rate (ORR) and progression-free survival (PFS), are characteristics that can be derived from imaging and can be used as surrogates for overall survival (OS). Similar to OS, ORR and PFS describe the efficacy of a drug. U.S. Food and Drug Administration (FDA) regulatory approval requires therapies to demonstrate direct evidence of clinical benefit, such as improved OS. However, multiple programs have been created to expedite drug approval for life-threatening illnesses, including advanced cancer. ORR and PFS have been accepted by the FDA as adequate predictors of OS on which to base drug approval decisions, thus substantially shortening the time and cost of drug development (1). Use of imaging surrogate markers for drug approval has become increasingly common, accounting for more than 90% of approvals through the Accelerated Approval Program and allowing for use of many therapies which have altered the course of cancer. Keywords: Oncology, Tumor Response  RSNA, 2021.