Efficacy and safety of neoadjuvant PD-1 blockade with sintilimab in resectable squamous non-small cell lung cancer (sqNSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8531-8531 ◽  
Author(s):  
Ning Li ◽  
Jianming Ying ◽  
Xiuli Tao ◽  
Fan Zhang ◽  
Ziran Zhao ◽  
...  
Keyword(s):  
Neoadjuvant Treatment ◽  
Radical Resection ◽  
Pathologic Response ◽  
Efficacy And Safety ◽  
Viable Tumor ◽  
Standardized Uptake Values ◽  
Pet Ct ◽  
Treatment Naïve ◽  
Operation Results ◽  
Nsclc Patients

8531 Background: NSCLC patients who have potentially resectable disease often subsequently relapse after surgery. New therapy that prevents relapse after surgery is desperately needed. In this study, we tested the efficacy and safety of neoadjuvant sintilimab, an anti-PD-1 antibody, for patients with resectable sqNSCLC in China. Methods: All patients had treatment-naïve resectable sqNSCLC (stage IB-IIIA) that was confirmed by histopathology. Patients received two cycles of sintilimab (200 mg IV) on Day 1 and 22. Surgery was performed between Day 29-43. An enhanced PET/CT was obtained at baseline and seven days prior to surgery. Preliminary analysis of safety profile and efficacy was planned after at least 20 patients had received operation. Results: As of Jan. 28, 2019, 22 patients (20 males and 2 females) with sqNSCLC received two doses of sintilimab followed by radical resection. The median age was 61.5 yr (range, 48 to 70). Six (27.3%) and four (18.2%) patients experienced neoadjuvant treatment emergent adverse events (TEAEs) and neoadjuvant treatment-related AEs (TRAEs), respectively. Most of the TEAEs and TRAEs were grade 1 or 2. Three patients achieved radiological partial response: an ORR of 13.6% based on RECIST 1.1. Ten patients (45.5%) achieved a major pathologic response (MPR, ≤10% viable tumor cells), including four (18.2%) had complete pathologic response (no viable tumor cell). There was a direct correlation between pathological response and decrease in the standardized uptake values (SUV) in the primary tumor. Among nine patients with > 30% decrease of SUV, eight had MPR, compared with no MRP response in the 11 patients with ≤30% decrease of SUV. Conclusions: Neoadjuvant sintilimab for sqNSCLC patients was tolerable and the 45.5% MRP rate is encouraging. A decrease in SUV may be predictive of pathologic response after PD-1 therapy in sqNSCLC. Clinical trial information: ChiCTR-OIC-17013726.

740 CAMRELIZUMAB IN COMBINATION WITH PREOPERATIVE CHEMOTHERAPY FOR LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A SINGLE-ARM, OPEN-LABEL, PHASE II STUDY

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Yu Qi ◽  
Xiangrui Meng ◽  
Qingxia Fan
Keyword(s):  
Phase Ii ◽  
Preoperative Chemotherapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Reduction Rate ◽  
Complete Response ◽  
Pathologic Response ◽  
R0 Resection ◽  
Efficacy And Safety

Abstract   At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods 45 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3 M0) ESCC were enrolled from February 2020 to March 2021.The study was divided into two stages, stage1: we administered 1 cycle of Camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of Camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4 ~ 6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results At the cutoff date of Mar 9, 2021, 45 eligible pts were enrolled, neoadjuvant treatment was completed in 39 pts. Thus far 32 pts were resected, all patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 28 pts with 87.5% reduction rate. 19 pts (59.38%) reached major pathologic response, 9 pts (28.13%) reached pathologic complete response (no surgery related mortality). A total of 75.56% had AEs with 13.33% of grade ≥ 3 AEs. Date for median DFS and OS were not matured. Conclusion Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966.

scholarly journals Prognostic Relevance of a Complete Pathologic Response in Liver Transplantation for Hepatocellular Carcinoma

2019 ◽  
Vol 26 (13) ◽  
pp. 4556-4565 ◽  
Author(s):  
Michał Grąt ◽  
Marek Krawczyk ◽  
Jan Stypułkowski ◽  
Marcin Morawski ◽  
Maciej Krasnodębski ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Propensity Score ◽  
Neoadjuvant Treatment ◽  
Pathologic Response ◽  
Secondary Outcome ◽  
Complete Pathologic Response ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
Treatment Naïve

Abstract Background A complete pathologic response (CPR) after neoadjuvant treatment is reported to be associated with an exceptionally low risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic role of CPR in liver transplantation for HCC. Methods This retrospective cohort study was based on 222 HCC transplant recipients. Incidence of recurrence and survival at 5 years were the primary and secondary outcome measures, respectively. Competing risk analyses were applied to evaluate recurrence incidence and its predictors. Propensity score matching was performed to compare the outcomes for patients after neoadjuvant treatment with and without CPR. Results Neoadjuvant treatment was performed for 127 patients, 32 of whom achieved CPR (25.2%). Comparison of baseline characteristics showed that the patients with CPR were at lowest baseline recurrence risk, followed by treatment-naïve patients and patients without CPR. Adjusted for potential confounders, CPR did not have any significant effects on tumor recurrence. No significant net reclassification improvement was noted after addition of CPR to existing criteria. Neoadjuvant treatment without CPR was associated with increased risk of recurrence in subgroups within the Milan criteria (p = 0.016), with alpha-fetoprotein concentration (AFP) model not exceeding 2 points (p = 0.021) and within the Warsaw criteria (p = 0.007) compared with treatment-naïve patients who were at risk similar to those with CPR. The 5-year incidences of recurrence in propensity score-matched patients with and without CPR were respectively 14.0% and 15.9% (p = 0.661), with corresponding survival rates of 73.2% and 67.4%, respectively (p = 0.329). Conclusions The findings showed that CPR is not independently associated with long-term outcomes after liver transplantation for HCC.

scholarly journals Combining PD-L1 Expression and Standardized Uptake Values in FDG-PET/CT Can Predict Prognosis in Patients With Resectable Non–Small-Cell Lung Cancer

2021 ◽  
Vol 28 ◽  
pp. 107327482110383
Author(s):  
Tomoyuki Miyazawa ◽  
Kanji Otsubo ◽  
Hiroki Sakai ◽  
Hiroyuki Kimura ◽  
Motohiro Chosokabe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Small Cell Lung Cancer ◽  
Fdg Pet ◽  
Small Cell ◽  
Small Cell Lung ◽  
Standardized Uptake Values ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Nsclc Patients

Background This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non–small-cell lung cancer (NSCLC). Methods We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. Results PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUVmax (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUVmax were significantly negative prognostic factors in univariate analysis for overall survival (OS) ( P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) ( P = 0.0012 and P < 0.0001). Kaplan–Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUVmax < 3, intermediate in patients with positive PD-L1 expression and SUVmax < 3 and those with negative PD-L1 expression and SUVmax ≥ 3, and poor in patients with positive PD-L1 expression and SUVmax ≥ 3. Conclusion Combining PD-L1 expression and preoperative FDG-PET/CT SUVmax in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.

486 UTILITY OF 18F-FDG/PET FOR PREDICTING HISTOPATHOLOGICAL RESPONSE TO NEOADJUVANT INDUCTION CHEMOTHERAPY AND CHEMORADIOTHERAPY FOR ESOPHAGEAL AND JUNCTIONAL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Flávio Sabino ◽  
Marco Guimarães-Filho ◽  
Michel Carneiro ◽  
Luciana Ribeiro ◽  
Daniel Fernandes ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Fdg Pet ◽  
Metabolic Response ◽  
Neoadjuvant Treatment ◽  
Pathologic Response ◽  
Response Evaluation ◽  
Histopathological Response ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract   Neoadjuvant treatment followed by esophagectomy is the standard therapy for patients with resectable esophageal cancer. Data have demonstrated that patients with pathologic complete response (pCR) have better survival. Several studies have been exploring whether 18F-FDG/PET performed during neoadjuvant treatment can predict a pCR, but the results are conflicting. The aim of this study was to assess the role of 18F-FDG PET/CT for predicting the histopathological response to neoadjuvant induction chemotherapy (IC) and chemoradiotherapy (CR). Methods Patients with proven squamous cell or adenocarcinoma of the esophagus or GEJ were enrolled in this prospective study. Patients received two cycles of IC with carboplatin and paclitaxel followed by concurrent CR and then esophagectomy. Metabolic response was evaluated according to PERSIST criteria by 18F-FDG PET/CT performed at baseline, at day 14 of chemotherapy and four to eight weeks after the completion of CR. Tumoral pretreatment, induction and posttreatment FDG-standardized uptake value normalized to lean body mass SULmean and percentage change were assessed. These parameters were correlated with the pathologic response using the Mandard tumor regression grade (TRG) scale. Results Thirty patients finished the IC plus CR and 16 had esophagectomy. The median age was 57 years, 75% were male and 56% had adenocarcinoma. The mean of SULmean prior to treatment, after one cycle of IC and after CR were respectively 6.12, 4.67 and 1.52. After one cycle of IC, one patient had metabolic progression, eight remained stable and seven had partial metabolic response. All metabolic responders had good histopathological response (Mandard 1 or 2). After CR, five patients had complete metabolic response (CMR). However, three of them had poor histopathological response (Mandard &gt;2). Conclusion Our initial results suggests that the early PERSIST-based metabolic response evaluation appears useful to predict a good histopathological response. Thus, an interim 18FFDG PET/CT may help to identify good responders during the neoadjuvant treatment. However, the late metabolic response evaluation after CR had a poor pathologic correlation. In this way, a CMR after CR should not be assumed to be synonymous of complete pathologic response.

[18F]-florbetaben PET/CT Imaging in the Alzheimer’s Disease Mouse Model APPswe/PS1dE9

2018 ◽  
Vol 16 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. Stenzel ◽  
C. Rühlmann ◽  
T. Lindner ◽  
S. Polei ◽  
S. Teipel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
New Drugs ◽  
Imaging Data ◽  
Wild Type ◽  
Preclinical Research ◽  
Standardized Uptake Values ◽  
Pet Ct

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [<sup>18</sup>F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [<sup>18</sup>F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [<sup>18</sup>F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [<sup>18</sup>F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [<sup>18</sup>F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [<sup>18</sup>F]-florbetaben in the APPswe/PS1dE9 mouse model.

scholarly journals Differential and staging diagnosis for NSCLC patients With [68Ga] Ga-DOTA-FAPI-04 and 2-[18F]FDG PET/CT

2021 ◽  
Vol 96-97 ◽  
pp. S46-S47
Author(s):  
Xin Zhou ◽  
Xiaoxia Xu ◽  
Shuailiang Wang ◽  
Hua Zhu ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Nsclc Patients

scholarly journals Implications of Standardized Uptake Values of Oral Squamous Cell Carcinoma in PET-CT on Prognosis, Tumor Characteristics and Mitochondrial DNA Heteroplasmy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2273
Author(s):  
Lukas Latzko ◽  
Bernd Schöpf ◽  
Hansi Weissensteiner ◽  
Federica Fazzini ◽  
Liane Fendt ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Mitochondrial Dna ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Rates ◽  
Tumor Characteristics ◽  
Dna Mutations ◽  
Standardized Uptake Values ◽  
Pet Ct

Under aerobic conditions, some cancers switch to glycolysis to cover their energy requirements. Taking advantage of this process, functional imaging techniques such as PET-CT can be used to detect and assess tumorous tissues. The aim of this study was to investigate standardized uptake values and mitochondrial DNA mutations in oral squamous cell carcinoma. A cohort of 57 patients underwent 18[F]FDG-PET-CT and standardized uptake values were collected. In 15 patients, data on mitochondrial DNA mutations of the tumor were available. Kaplan–Meier curves were calculated, and correlation analyses as well as univariate Cox proportional hazard models were performed. Using ROC analysis to determine a statistical threshold for SUVmax in PET investigations, a cut-off value was determined at 9.765 MB/mL. Survival analysis for SUVmax in these groups showed a Hazard Ratio of 4 (95% CI 1.7–9) in the high SUVmax group with 5-year survival rates of 23.5% (p = 0.00042). For SUVmax and clinicopathological tumor features, significant correlations were found. A tendency towards higher mtDNA heteroplasmy levels in high SUVmax groups could be observed. We were able to confirm the prognostic value of SUVmax in OSCC, showing higher survival rates at lower SUVmax levels. Correlations between SUVmax and distinct tumor characteristics were highly significant, providing evidence that SUVmax may act as a reliable diagnostic parameter. Correlation analysis of mtDNA mutations suggests an influence on metabolic activity in OSCC.

Sign in / Sign up

Export Citation Format

Share Document