Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37–649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.

The Predictive Value of Tumor Volume, Inflammatory Biomarkers, and Their Dynamic Changes on Early Tumor Response for Elderly Patients With Esophageal Squamous Cell Carcinoma Underwent Radiotherapy

Background: To investigate the tumor volume, pre-treatment inflammatory biomarkers (pre-IBs), and their dynamic changes on early tumor response (ETR) in elderly patients (≥70 years) with esophageal squamous cell carcinoma (ESCC) underwent radiotherapy.Methods: The ETR was assessed according to RECIST 1.1 at 1 month after radiotherapy. The tumor volume ((gross tumor volume (GTV) at the initial treatment planning (GTVi), and GTV at shrinking irradiation field planning (GTVs)), IBs (neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and lymphocyte/monocyte (LMR)) which also included during treatment IBs (dur-IBs), and clinical variables were collected and analyzed from 197 patients received radiotherapy at our institution between 2015 and 2020. The tumor volume change rate (TVCR) and dynamic changes of IBs (delta-IBs) were defined as follows: TVCR=(1-GTVs/GTVi)×100%, delta-IBs=1-dur-IBs/pre-IBs. A nomogram based on logistic regression analysis were then established for predicting ETR.Results: GTVi and pre-LMR significantly decreased, pre-NLR, and pre-PLR significantly increased during radiotherapy or chemoradiotherapy (all P<0.001). Multivariate analysis indicated that TVCR [OR, 0.197; 95%CI, 0.093-0.414; P<0.001], pre-NLR [OR, 2.568; 95%CI, 1.031-6.394; P=0.043], and delta-NLR [OR, 2.831; 95%CI, 1.126-7.119; P=0.027] were statistically significant with ETR. And c-index of the nomogram established by combining all independent predictors for ETR was 0.769 [95%CI, 0.161–0.302].Conclusion: TVCR, Pre-NLR, and delta-NLR were significant with ETR in elderly patients with ESCC who underwent radiotherapy. And the developed nomogram with superior prediction ability for ETR could assist in patients counseling and guide to make individual treatments and follow-up strategies.

Role of positron emission tomography in predicting early tumor response to neoadjuvant chemotherapy for breast cancer

Background. Neoadjuvant chemotherapy (NACT) is an important stage in the treatment of patients with breast cancer. Positron emission tomography/computed tomography (PET/СT) with fluorodeoxyglucose labeled with 18F (18F-FDG) is widely used as an effective method of metabolic tumor imaging at the stages of treatment. The aim of this study was to evaluate the possibility of using PET/CT with 18F-FDG to determine the early tumor response to NACT.Materials and methods. The results of PET/CT with 18F-FDG in 27 patients with breast cancer were retrospectively analyzed. The study was performed before the start of NACT, after the 2nd cycle of chemotherapy and after completion of all courses, the maximum accumulation of 18F-FDG in the tumor tissue (SUVmax), as well as the dynamics of changes in SUVmax after NACT (SUV(%)) were assessed. According to the results of postoperative morphological examination, the patients were divided into two groups: with complete tumor regression (pCR) and with no complete tumor regression (non-pCR).Results. The results of the study showed that the SUV(%) between the primary and interim examination, as well as between the intermediate and preoperative PET/CT scans, was 66.6 ± 13.3 % and 31.6 ± 17.5 %, respectively. The dynamics of SUV(%) between the primary and intermediate scans in the pCR and non-pCR groups was 79.04 ± 4.1 % and 63.8 ± 13.1 %, respectively (p = 0.02). The SUVmax value in the pCR and non-pCR groups during the primary PET/CT scan was 8.5 ± 0.78 and 8.2 ± 0.78, respectively (p = 0.5), while the intermediate scan was 1.8 ± 0.35 and 3.0 ± 0.14 (p = 0.03). Based on the research results, an ROC analysis was carried out, which showed that the optimal value of SUV(%) is 73.55 %, which showed the highest sensitivity and specificity.Discussion. Given that the change in SUVmax between primary and intermediate PET/CT was more pronounced than between intermediate and preoperative scans, it can be assumed that metabolic changes in the background of NACT are observed already in the early stages of treatment and persist until the end of therapy, thus, the ineffectiveness of the chemotherapy regimen can be determined using an intermediate PET/CT scan and a timely change in the treatment plan.Conclusions. We consider 73.55 % to be the optimal value of SUV(%) for intermediate PET/CT scanning; for this indicator and above, it is expected to expect a complete morphological response of the tumor to NACT. We believe that PET/CT with 18F-FDG at an intermediate stage of observation during NACT is a valuable method for predicting early tumor response to therapy.

Pediatric Rhabdomyosarcomas: Three-Dimensional Radiological Assessments after Induction Chemotherapy Predict Survival Better than One-Dimensional and Two-Dimensional Measurements

Radiological response to neoadjuvant chemotherapy is currently used to assess the efficacy of treatment in pediatric patients with rhabdomyosarcoma (RMS), but the association between early tumor response on imaging and survival is still controversial. The aim of this study was to investigate the prognostic value of assessing radiological response after induction therapy in pediatric RMS, comparing four different methods. This retrospective, two-center study was conducted on 66 non-metastatic RMS patients. Two radiologists measured tumor size on pre- and post-treatment magnetic resonance (MR) or computed tomography (CT) images using four methods: considering maximal diameter with the 1D-RECIST (Response Evaluation Criteria in Solid Tumors); multiplying the two maximal diameters with the 2D-WHO (World Health Organization); multiplying the three maximal diameters with the 3D-EpSSG (European pediatric Soft tissue sarcoma Study Group); obtaining a software-assisted volume assessment with the 3D-Osirix. Each patient was classified as a responder or non-responder based on the proposed thresholds for each method. Tumor response was compared with survival using Kaplan–Meier plots, the log-rank test, and Cox’s regression. Agreement between methods and observers (weighted-κ) was also calculated. The 5-year event-free survival (5yr-EFS) calculated with the Kaplan–Meier plots was significantly longer for responders than for non-responders with all the methods, but the 3D assessments differentiated between the two groups better than the 1D-RECIST or 2D-WHO (p1D-RECIST = 0.018, p2D-WHO = 0.007, p3D-EpSSG and p3D-Osirix < 0.0001). Comparing the 5yr-EFS of responders and non-responders also produced adjusted hazard ratios of 3.57 (p = 0.0158) for the 1D-RECIST, 5.05 for the 2D-WHO (p = 0.0042), 14.40 for the 3D-EpSSG (p < 0.0001) and 11.60 for the 3D-Osirix (p < 0.0001), indicating that the volumetric measurements were significantly more strongly associated with EFS. Inter-method agreement was excellent between the 3D-EpSSG and the 3D-Osirix (κ = 0.98), and moderate for the other comparisons (0.5 < κ < 0.8). The 1D-RECIST and the 2D-WHO tended to underestimate response to treatment. Inter-observer agreement was excellent with all methods (κ > 0.8) except for the 2D-WHO (κ = 0.7). In conclusion, early tumor response was confirmed as a significant prognostic factor in RMS, and the 3D-EpSSG and 3D-Osirix methods predicted response to treatment better than the 1D-RECIST or 2D-WHO measurements.

Correction to: Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial

The article Effect of early tumor response on the health-related quality of life among patients.

Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial

Background This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial. Methods HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively. Results Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and − 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were − 0.0019 and − 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358–0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291–0.841). Conclusions Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): Final results of the phase II AVETUX trial (AIO-KRK-0216).

96 Background: Single agent PD-1/L1 inhibition is efficacious in MCRC patients (pts) with high microsatellite instability (MSI-H). For the vast majority of MCRC pts with MS stable (MSS) phenotype the role of immunotherapy remains undetermined. Methods: The single arm phase II AVETUX trial combined mFOLFOX6 and cetuximab with avelumab (10mg/kg day 1 from cycle 2 onwards) in RAS/BRAF wildtype (local lab) MCRC pts. Primary endpoint was 12 month progression-free survival rate. Secondary endpoints included overall response rate (ORR), tolerability, overall survival and translational research evaluating tissue including PD-L1 expression (tumour/immune cells) and serial ctDNA. Efficacy analyses were done by intention to treat (ITT). Results: Overall 43 pts were enrolled. Median age was 61 (range 29-82), 14 pts (33%) were female and 39 (91%) left sided. 30 pts (70%) had liver mets and 17 (40%) liver mets only. 2 pts were MSI-H, one MSI-low and 40 MSS. Besides immediate and otherwise unexplained fever in 4 pts treatment was well tolerated and avelumab was not associated with unexpected adverse events to standard FOLFOX/cetuximab. Central tissue review found 4 pts to be ineligible due to low frequent KRAS or BRAF mutation (15-31%). Thus, ITT included 39 pts. The ORR was 79.5%, including 6 complete (CR) and 25 partial responses (PR). Further 5 stable diseases were noted, thus disease control rate was 92.3%; 2 pts had progression and 1 was not evaluable. Early tumor shrinkage (ETS) rate (≥20% after 8 weeks) was 79.5% (1 CR, 27 PR and 3 SD with ≥20% - < 30%). In MSI-H pts 1 PR and 1 SD and in the 3 low RAS mut pts 2 PR were noted. Panel sequencing was feasible with 153 mutations detected, showing an immediate ctDNA drop within 4 weeks of treatment, mirroring the high rate of early tumor response. Notably, the 4 pts with fever had a high T cell infiltration in the tumor. Final data including the primary endpoint and translational data will be presented at the meeting. Conclusions: The AVETUX regimen was feasible producing a high rate of responses in MSS pts mainly occurring within the first 8 weeks. The noted ORR/ETS of 79.5% warrants further evaluation in a randomized trial. Clinical trial information: NCT03174405.

Pretreatment heterogeneous enhancement pattern of hepatocellular carcinoma can be new predictor for early response to lenvatinib

Background: The aims of this study were to identify useful predictors of early tumor response to lenvatinib, and to evaluate the utility of estimation of tumor differentiation from pretreatment image analysis. Methods: We evaluated 37 consecutive patients with unresectable hepatocellular carcinoma (HCC) diagnosed by dynamic computed tomography (CT) who received lenvatinib. Pretreatment arterial- and portal-phase dynamic CT images were classified into three enhancement patterns: Type-2 is a homogeneous enhancement pattern with increased arterial blood flow; Type-3 is a heterogeneous enhancement pattern with a septum-like structure; and Type-4 is a heterogeneous enhancement pattern with irregularly shaped ring structures. Generally, macroscopic classification of the nodular type of SNEG and CMN types strongly relates to the Type-3 enhancement pattern, and histologically, the Type-1 enhancement pattern represents well-differentiated HCC, while the Type-2 and -3 patterns represent moderately-differentiated HCC; the Type-4 enhancement pattern is a significantly specific feature for predicting poorly-differentiated HCC. Treatment response was evaluated using mRECIST at 8–12 weeks after initiation of lenvatinib. Results: In early treatment response evaluation, 6 of 37 patients (16%) achieved a complete response (CR), 22 (59%) experienced a partial response (PR), 6 (16%) had stable disease (SD), and 3 (8%) had progressive disease (PD); therefore, 28 of 37 patients (76%) experienced an objective response (OR). By dynamic CT enhancement pattern using mRECIST, the objective response rate (ORR) was significantly elevated along with increasing heterogeneity of enhancement pattern from Type-2 (54%) to Type-4 pattern (89%; P=0.046). Multivariate logistic regression analysis revealed that a pretreatment dynamic CT heterogeneous enhancement pattern (Type-3 and -4) (hazard ratio, 6.12; P=0.040) is a useful predictor of early OR. Conclusion: Lenvatinib provided a good early treatment response in patients with unresectable HCC. Estimation of tumor differentiation using image analysis was also useful for predicting early tumor response.