scholarly journals Predicting tumor response and outcome of second-look surgery with 18F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer

Author(s):  
Nicolas Aide ◽  
Pauline Fauchille ◽  
Elodie Coquan ◽  
Gwenael Ferron ◽  
Pierre Combe ◽  
...  

Abstract Background This ancillary study aimed to evaluate 18F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of 18F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery. Materials and methods Central review was performed by two readers blinded to the received treatment and to the patients’ outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease). Also analyzed was the percentage change in metabolic active tumor volume (MATV) and total lesion glycolysis (TLG). Results Twenty-four patients were included in this ancillary study: 10 received chemotherapy + placebo and 14 chemotherapy + nintedanib. PERCIST and EORTC criteria showed similar discriminative power in predicting PSF and OS. Variation in MATV/TLG did not predict PFS or OS, and no optimal threshold could be found for MATV/TLG for predicting survival. Complete cytoreductive surgery (no residual disease versus residual disease < 0.25 cm/0.25–2.5 cm/> 2.5 cm) was more frequent in responders versus non-responders (P = 0.002 for PERCIST and P = 0.02 for EORTC criteria). No correlation was observed between the variation of PET data and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET, but a statistically significant correlation was observed between ΔSULpeak and ΔCA-125 between baseline sample and that performed after the second cycle. Conclusion 18F-FDG PET using EORTC or PERCIST criteria appeared to be a useful tool in ovarian cancer trials to analyze early tumor response, and predict second-look surgery outcome and survival. An advantage of PERCIST is the correlation of ΔSULpeak and ΔCA-125, PET response preceding tumor markers response by 1 month. Neither MATV nor TLG was useful in predicting survival. Trial registration NCT01583322 ARCAGY/ GINECO GROUP GINECO-OV119, 24 April 2012

Author(s):  
Christos Sachpekidis ◽  
Annette Kopp-Schneider ◽  
Leyun Pan ◽  
Dimitrios Papamichail ◽  
Uwe Haberkorn ◽  
...  

Abstract Purpose In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [18F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment. Methods Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [18F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients’ response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Patients were further grouped into two groups: those demonstrating metabolic benefit (MB), including patients with SMD, PMR, and CMR, and those demonstrating no MB (no-MB), including patients with PMD. Moreover, patterns of [18F]FDG uptake suggestive of radiologic immune-related adverse events (irAEs) were documented. Progression-free survival (PFS) was measured from the date of interim PET/CT until disease progression or death from any cause. Results Median follow-up from interim PET/CT was 24.2 months (19.3–41.7 months). According to the EORTC criteria, 14 patients showed MB (1 CMR, 6 PMR, and 7 SMD), while 11 patients showed no-MB (PMD). Respectively, the application of the PERCIMT criteria revealed that 19 patients had MB (1 CMR, 6 PMR, and 12 SMD), and 6 of them had no-MB (PMD). With regard to PFS, no significant difference was observed between patients with MB and no-MB on interim PET/CT according to the EORTC criteria (p = 0.088). In contrary, according to the PERCIMT criteria, patients demonstrating MB had a significantly longer PFS than those showing no-MB (p = 0.045). The emergence of radiologic irAEs (n = 11 patients) was not associated with a significant survival benefit. Regarding the sub-cohort undergoing also a third PET/CT, 14/17 patients (82%) showed concordant responses and 3/17 (18%) had a mismatch of response assessment between interim and late PET/CT. Conclusion PET/CT-based response of metastatic melanoma to PD-1 blockade after application of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results.


Author(s):  
Kazuhiro Kitajima ◽  
Tadashi Watabe ◽  
Masatoyo Nakajo ◽  
Mana Ishibashi ◽  
Hiromitsu Daisaki ◽  
...  

Abstract Objective In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers. Materials and methods Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen’s κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival. Results Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively). Conclusions All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.


1997 ◽  
Vol 115 (5) ◽  
pp. 1542-1547
Author(s):  
Eddie Fernando Candido Murta ◽  
Jurandyr Moreira de Andrade ◽  
Maurício Mesquita Sabino de Freitas ◽  
Sérgio Bighetti

OBJECTIVE:This study was conducted on patients with ovarian cancer in order to evaluate survival. DESIGN: A retrospective study of 119 cases of ovarian cancer from January 1977 to December 1992 with observation until 1993. LOCATION: Department of Gynecology and Obstetrics, Ribeirão Preto School of Medicine, São Paulo University. PARTICIPANTS: Of the 119 cases, 70 (58.8%) presented epithelial carcinomas and 21 (17.6%) tumors of the sexual girdle/stroma. DATA SOURCE: The data were obtained from the medical records of the patients. MEASUREMENT: Statistical analysis of survival time was based on the nonparametric Mann-Whitney test with the level of significance set at P < 0.05. RESULTS: The patients with a negative second look had a mean survival of 79.4 ± 48.5 months versus 24.2 ± 15.1 months for patients with a positive second look (P < 0.02). CONCLUSIONS: It is concluded that patients with a negative second look present a better prognosis compared to those with residual disease.


1986 ◽  
Vol 4 (6) ◽  
pp. 965-971 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
S Chiara ◽  
M R Sertoli ◽  
M G Daga ◽  
...  

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.


2005 ◽  
Vol 15 (1) ◽  
pp. 19-25 ◽  
Author(s):  
J. Rahaman ◽  
P. Dottino ◽  
T. S. Jennings ◽  
J. Holland ◽  
C. J. Cohen

In a single-institution retrospective cohort study, 230 patients were treated for stage III primary ovarian cancer and 175 became eligible for second-look operations by virtue of a complete clinical response after primary surgical cytoreduction and platinum-based combination chemotherapy. Of these, 109 underwent a second-look operation. Optimal primary cytoreduction was defined as residual disease ≤1 cm. Median follow-up was 68.3 months. Five-year survival for all the 230 stage III ovarian cancers was 43.4%. Among all eligible patients (n = 175), there was no survival difference (P = 0.67) in those having second look (57.3%, 5-year survival) versus no second look (48.7%). In those patients with optimal primary cytoreduction (n = 118), there was no survival advantage to second look (69% versus 61%, P = 0.7). However, in those with suboptimal primary cytoreduction (n = 47), 5-year survival was 36% in those having second look versus only 13% in those refusing second look (P < 0.05). Multivariate analysis identified second-look surgery as the only significant independent prognostic variable affecting survival (RR = 0.321, P < 0.04). Patients with suboptimal debulking at primary surgery for stage III ovarian cancer appear to achieve a survival benefit from second-look surgical procedures, presumably from the early identification and treatment of residual disease.


2020 ◽  
Vol 21 (15) ◽  
pp. 5406 ◽  
Author(s):  
Bastien Jamet ◽  
Elena Zamagni ◽  
Cristina Nanni ◽  
Clément Bailly ◽  
Thomas Carlier ◽  
...  

Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10−5 and 10−6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17539-e17539
Author(s):  
Kari Kubalanza ◽  
Teresa Kim ◽  
Mingyan Zhang ◽  
Joshua Garrett Cohen ◽  
Sanaz Memarzadeh ◽  
...  

e17539 Background: Neoadjuvant chemotherapy (NACT) with interval debulking surgery is considered for patients with advanced-stage ovarian carcinoma (OC) who are not ideal candidates for primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally resected. Moreover, response to NACT may be a suitable surrogate end point for long-term clinical outcome in ovarian cancer. The aim of the present study is to evaluate the utility of a three-tier Chemotherapy Response Score (CRS) and validate whether residual disease or evidence of regression following NACT may provide prognostic information in ovarian cancer. Methods: We conducted a retrospective single-institution study of patients who received NACT with carboplatin and paclitaxel for FIGO stage III/IV ovarian cancer. Response to NACT was graded as no or minimal tumor response (CRS1); appreciable tumor response amid readily identifiable viable tumor (CRS2); or complete/near-complete response with no residual tumor or minimal scattered tumor foci (CRS3) as described previously (Böhm S, et al. J Clin Oncol 33:2457-2463). Multivariate progression free survival (PFS) and overall survival (OS) analyses were performed accounting for age, FIGO stage and BRCA status. Results: Of the 86 patients accrued to date, median age was 65 years, 62% had stage IV disease and 16% had a somatic/germline BRCA mutation. CRS scores 1, 2 and 3 were found in 26 (30%), 43 (50%) and 17 (20%) of cases, respectively, and were associated with PFS (log rank p = 0.002). A high CRS score predicted improved PFS and OS (CRS 2/3 vs 1; median PFS 17.3 vs. 11.8 mo, adjusted hazard ratio (HR), 0.33; 95%CI 0.17-0.62; p < 0.001; median OS 47.9 vs. 38.3 mo, adjusted HR 0.36, 95%CI 0.15-0.88, p = 0.026). Similarly, when comparing CRS 3 with 1/2, the high score predicted improved outcome for PFS but not OS (median PFS 17.3 vs. 14.7 mo, adjusted HR, 0.42; 95%CI 0.19-0.95; p = 0.037; median OS 48.6 vs. 46.5 mo, adjusted HR 0.43, 95%CI 0.14-1.35, p = 0.149). Conclusions: In this study, we validate a simple three-tier chemotherapy response scoring system for assessing histopathologic response of OC to NACT. Residual disease and evidence of complete/near complete regression following NACT provides prognostic information in OC. CRS may serve as a potential surrogate marker for long-term outcome and be a useful alternative intermediate end point in future clinical trials.


1996 ◽  
Vol 14 (2) ◽  
pp. 343-350 ◽  
Author(s):  
E Pujade-Lauraine ◽  
J P Guastalla ◽  
N Colombo ◽  
P Devillier ◽  
E François ◽  
...  

PURPOSE The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.


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