European Organization For Research And Treatment Of Cancer Criteria Research Articles

Outcome of Pneumocystis pneumonia in transplant and non-transplant HIV-negative immunocompromised patients.

Previous studies showed HIV-negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV-negative immunocompromised patients. In this retrospective cohort study at the University Health Network, we included all HIV-negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28-day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non-SOT patients. Of 160 non-HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21-87] years). PCP presentation in SOT recipients (n=14) was more severe than non-SOT patients (n=104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p=.037), shortness of breath (100% vs. 75/104 [74.3%], p=.037), median [range] O2 saturation (88% [75%, 99%] vs. 92%[70%, 99%], p=.040), and supplemental O2 requirement (12/14 [85.7%] vs. 59/104 [56.7%], p=.044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p=.176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p<.0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p=.0007) in SOT patients was different from non-SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non-SOT patients (aOR [CI95%]: 12.25 [3.08-48.62], p<.001). PCP presentation and outcomes in SOT recipients are more severe than in non-SOT patients. Further studies are required to explore the biological reasons for this difference.

Comparative analysis of different response criteria at early phase after PD-1 blockade in non-small lung cancer

PurposeTo compare different response criteria using computed tomography (CT) and positron emission tomography (PET) in measuring response and survival in the early phase after programmed death-1 (PD-1) blockade monotherapy in patients with advanced non-small cell lung cancer (NSCLC).MethodsA total of 54 patients with advanced NSCLC who had 2-deoxy-2-[fluorine-18]-fluoro-D-glucose PET or CT at baseline, and 4 and 9 weeks after PD-1 blockade, were registered. Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), the immune-modified RECIST (irRECIST), the PET Response Criteria in Solid Tumors (PERCIST), the immune-modified PERCIST (iPERCIST), and the European Organization for Research and Treatment of Cancer (EORTC) criteria for dichotomous groups, such as responders vs. non-responders and controlled vs. uncontrolled diseases. Cohen’s κ was used to evaluate the concordance among the different criteria.ResultsThe concordance between CT and PET response criteria was fair or slight for responders vs. non-responders, but the agreement between iPERCIST and irRECIST was moderate for controlled vs. uncontrolled diseases. The agreement between EORTC and PERCIST or iPERCIST in detecting responders was higher in the application of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than in the standardized uptake value corrected for lean body mass (SUL)peak. To distinguish controlled from uncontrolled disease, RECIST, irRECIST, and PET criteria (PERCIST, iPERCIST, and EORTC) defined by MTV or TLG were found to be significant predictors of progression-free survival. To distinguish responders from non-responders, iPERCIST by SULpeak or EORTC by TLG were identified as significant indicators. The EORTC criteria using TLG for the detection of responders or uncontrolled diseases had a significantly higher predictive value for response assessment.ConclusionsThe EORTC criteria based on TLG for the early detection of responders and uncontrolled disease were effective as a response assessment at 4 weeks after the PD-1 blockade. When SULpeak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect.

An analysis of prognostic factors in a cohort of low-grade gliomas and degree of consistency between RTOG and EORTC scores

Due to their rarity and heterogeneity and despite the introduction of molecular features in the current WHO classification, clinical criteria such as those from the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) are still being used to make treatment decisions in low-grade gliomas (LGG). Patients with diffuse low-grade glioma treated at our institution between 2002 and 2018 were analyzed, retrieving and assessing the degree of consistency between the EORTC and RTOG criteria, as well as the isocitrate dehydrogenase 1 and 2 (IDH) gene mutational status. Likewise, multivariate analyses were performed to ascertain the superiority of any of the factors over the others. One hundred and two patients were included. The degree of consistency between the RTOG and EORTC criteria was 71.6% (K = 0.426; p = 0.0001). Notably, 51.7% of those assigned to low risk by the EORTC were classified as high risk according to the RTOG classification. In multivariate analysis, only complete resection, age > 40 years, size and IDH mutation status were independently correlated with OS. When the RTOG and EORTC scores were entered into the model, only the EORTC model was independently associated with mortality. The degree of consistency between the EORT and RTOG criteria is low. Therefore, there is a need to integrate clinical-molecular scores to improve treatment decisions in LGG.

Comparison of PET-based criteria of evaluation of response to immunotherapy in patients with advanced melanoma.

e21536 Background: Immune checkpoint inhibitors (ICI), such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1), have evolved as a dominant strategy in the treatment of metastatic melanoma (MM) in the last decade. At least three PET-based criteria are available for the early assessment of response to immunotherapy: PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy (PECRIT), PET Response Evaluation Criteria for Immunotherapy (PERCIMT) and European Organization for Research and Treatment of Cancer (EORTC) criteria. The aim of this study was evaluation of the concordance of different PET-based criteria for the assessment of response to immunotherapy and to assess their capability of properly stratifying patients in terms of overall survival (OS) and progression free survival (PFS). Methods: We retrospectively enrolled patients with the following inclusion criteria: diagnosis of MM, treatment with ICI for MM and tumor assessment performed by at least two [18F]F-fluorodeoxyglucose (FDG) PET/CT scans (a baseline and ad interim scan). [18F]F-FDG PET/CT scans were analyzed according to PECRIT, PERCIMT and EORTC criteria. Agreement was assessed using Fleiss' kappa and Cohen’s kappa. Prognostic curves of PET/CT response according to different criteria were evaluated in terms of PFS and OS by Kaplan-Meier estimates and were compared by log-rank test. Results: From December 2021 to January 2022, 30 patients were enrolled. 18/30 patients received nivolumab, 8/30 pembrolizumab, 3/30 ipilimumab and 1/30 the combination of nivolumab and ipilimumab. According to PECRIT criteria, 6 patients achieved complete metabolic response (CMR), 7 partial metabolic response (PMR), 5 stable metabolic disease (SMD) and 12 (40%) progressive metabolic disease (PMD). By PERCIMT criteria, 6 patients had response classified as CMR, 9 PMR, 8 SMD and 7 (23.4%) PMD. Finally, by EORTC criteria there were 6 CMR, 10 PMR, 2 SMD and 12 (40%) PMD. In 9 cases out of 30, one criteria assessment differed from the other two and in one patient each criteria evaluation differed from the others (PMD by PECRIT, SMD by PERCIMT, PMR by EORTC). The percentage of patients concordantly evaluated by the three criteria was 68% (Fleiss’ kappa = 0.68). PECRIT and EORTC criteria showed the highest agreement (Cohen’s kappa 0.719), followed by PERCIMT and PERCRIT (Cohen’s kappa 0.69). PERCIMT and EORTC showed 64.4% of concordance. Furthermore, all three criteria were successful in stratifying patients in terms of OS and PFS (p-value &lt; 0.05). Conclusions: We observed substantial agreement among different PET evaluation criteria, with PECRIT and EORTC criteria showing the highest concordance. Analysis of a larger population is needed to prove the utility of PET response evaluation in early prognostic stratification.

Assessment of Treatment Response to Lenvatinib in Thyroid Cancer Monitored by F-18 FDG PET/CT Using PERCIST 1.0, Modified PERCIST and EORTC Criteria-Which One Is Most Suitable?

Simple SummaryIn patients with progressive metastatic radioiodine-refractory differentiated thyroid cancer, tyrosine kinase inhibitor (TKI) therapy with lenvatinib improves progression-free survival. Early identification of patients with therapeutic responses to the TKI therapy is clinically relevant due to common side effects and toxicity. The use of metabolic response criteria derived from F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can help to identify those patients who benefit from treatment. In our study, we evaluated different response criteria, namely, the Positron Emission Tomography Response Criteria In Solid Tumors (PERCIST) and European Organization for Research and Treatment of Cancer (EORTC) criteria, to find out which system might be more reliable and suitable in everyday clinical practice. The EORTC criteria could be applied to all patients, and the different PERCIST criteria, in 80% and 88%, respectively. Regarding their survival and treatment responses, patients with a progressive disease could be reliably identified by using all the criteria.Background: We aimed to compare the established metabolic response criteria PERCIST and EORTC for their applicability and predictive value in terms of clinical response assessment early after the initiation of lenvatinib therapy in patients with metastatic radioiodine-refractory (RAI) thyroid cancer (TC). Methods: In 25 patients treated with lenvatinib, baseline and 4-month follow-up F-18 FDG PET/CT images were analyzed using PERCIST 1.0, modified PERCIST (using SUVpeak or SUVmax) and EORTC criteria. Two groups were defined: disease control (DC) and progressive disease (PD), which were correlated with PFS and OS. Results: PERCIST, mPERCIST, PERCISTmax and EORTC could be applied in 80%, 80%, 88% and 100% of the patients based on the requirements of lesion assessment criteria, respectively. With PERCIST, mPERCIST, PERCISTmax and EORTC, the patients classified as DC and PD ranged from 65 to 68% and from 32 to 35%, respectively. Patients with DC exhibited a longer median PFS than patients with PD for EORTC (p < 0.014) and for PERCIST and mPERCIST (p = 0.037), respectively. Conclusion: EORTC and the different PERCIST criteria performed equally regarding the identification of patients with PD requiring treatment changes. However, the applicability of PERCIST 1.0 using SULpeak seems restricted due to the significant proportion of small tumor lesions.

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality. MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression. ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality. DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.

334. Impact of Overall Dexamethasone Exposure on Development of Invasive Pulmonary Aspergillosis in Hospitalized Patients with COVID-19

BackgroundAbbreviated courses of corticosteroids, such as dexamethasone, have demonstrated significant improvements in clinical outcomes among patients infected with COVID-19, although chronic corticosteroid use can predispose patients to opportunistic infections. The RECOVERY trial investigators showed reduced 28-day mortality among patients treated with 6 mg/day dexamethasone for up to 10 days, however in clinical practice the dosage and duration of dexamethasone therapy can vary widely based on severity of disease and provider discretion. Upon observing an anecdotal increase in the number of patients presenting with potential invasive aspergillosis during the third wave of COVID-19, we sought to evaluate the impact of overall dexamethasone exposure on the development of invasive pulmonary aspergillosis. MethodsPatients presenting to our institution from Dec. 2020 – Jan. 2021 with positive PCR for SARS-CoV-2 were screened for dexamethasone therapy. Assignment of high vs low dose dexamethasone groups were retrospectively made based on overall dexamethasone exposure. Low dose dexamethasone assignment was restricted to a total exposure of no more than 78 mg during a patient’s hospitalization. Adjudication of invasive pulmonary aspergillosis was made based on criteria that included host factors, radiologic findings, clinical factors, and mycological evidence.ResultsDexamethasone therapy was provided to 202 patients admitted to the hospital with COVID-19. Invasive pulmonary aspergillosis was determined to be probable in n=7 patients based on European Organization for Research and Treatment of Cancer (EORTC) criteria, and in n=13 patients based on expanded criteria. Patients in the low dose dexamethasone group were less likely to be diagnosed with probable IPA based on EORTC criteria (n=0, 0% on low dose vs. n=7, 11% on high dose) as well as expanded criteria (n=9, 5% on low dose vs. n=11, 17% on high dose), p< 0.001.ConclusionPatients hospitalized with COVID-19 receiving high-dose dexamethasone may be at a higher risk of opportunistic infections such as invasive pulmonary aspergillosis compared to patients who receive low-dose dexamethasone therapy. Further investigation is needed to obtain higher certainty of IPA diagnosis.Disclosures All Authors: No reported disclosures

Tumor response evaluation in patients with malignant melanoma undergoing immune checkpoint inhibitor therapy and prognosis prediction using 18F-FDG PET/CT: multicenter study for comparison of EORTC, PERCIST, and imPERCIST

ObjectiveIn 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 methodsMalignant 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.ResultsComplete 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).ConclusionsAll 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.

Efficacy and safety of JMT103 in patients with giant cell tumor of bone: A multicenter, single-arm, open-label, phase Ib/II study.

11526 Background: JMT103 is a novel, fully humanized IgG4 monoclonal antibody targeting RANKL, inhibiting osteoclastogenesis and osteoclast-mediated bone resorption. A multicenter, single-arm, open-label, phase Ib/II study was conducted to evaluate the efficacy and safety of JMT103 in patients (pts) with Giant cell tumor of bone (GCTB). Methods: Eligible pts (ECOG: 0-2) were adults with pathologically confirmed unresectable GCTB or their planned surgery is associated with severe morbidity. Pts with active dental or jaw condition requiring oral surgery, other anti-tumor therapies, anti-RANKL antibody or concurrent use of bisphosphonates were excluded. 2 mg/kg JMT103 was administrated subcutaneously every 4 weeks with a loading dose on days 8 and day 15 of the first 4 week of therapy. The primary endpoint was tumor response, defined as elimination of at least 90% giant cells or objective response of the target lesion assessed by radiologic imaging as per Modified Inverse Choi density/size (ICDS) or the Modified European Organization for Research and Treatment of Cancer (EORTC) criteria within 12 weeks. Secondary endpoints included safety profile, change of pain score using Brief Pain Inventory-Short Form, and suppression of bone-resorption biomarkers. Results: 38 pts (14 males) were enrolled between June 3 and December 24, 2020. The median age was 31 years (range 18-57). Lesions sites included lower extremities (39.5%), upper extremities (31.6%), spine (21.1%) and pelvis (13.2%). Among 32 pts with at least 1 efficacy evaluation within 12 weeks, 26 (81.3%, 95% CI: 63.6-92.8) had a tumor response by at least one response criteria. All 7 pts who underwent histological assessments had a tumor response. 25 of 32 pts assessed by radiology had a tumor response. As per ICDS criteria, 23 of 32 (71.9%) had a response; as per EORTC criteria, 15 of 17 (88.2%) had a response. 21 of 26 (80.8%) pts who complained of pain at baseline experienced reduced pain during the treatment. The median reductions in bone-resorption biomarkers were 71.8% (IQR 67.7-82.4) for uNTx/Cr (p &lt; 0.001) and 81.4% (IQR 68.3-84.7) for sCTx (p &lt; 0.001) at day 8. Of all 38 pts who were included in safety analyses, treatment-related adverse events (TRAEs) occurred in 14 pts. The most common TRAEs were hypophosphatemia (18.4%), hypocalcemia (7.9%) and blood bilirubin increased (7.9%). 1 patient (2.6%) was reported a grade 3 AE but it was not related to the treatment; other AEs were grade 1–2. Conclusions: JMT103 demonstrated encouraging anti-tumor efficacy and manageable safety profile in pts with unresectable GCTB or at high risk of severe morbidity after surgery. Clinical trial information: NCT04255576.

First-in-Humans Study of the SSTR Antagonist 177Lu-DOTA-LM3 for Peptide Receptor Radionuclide Therapy in Patients with Metastatic Neuroendocrine Neoplasms: Dosimetry, Safety, and Efficacy.

The objective of this study was to assess the safety, dosimetry, and efficacy of the 177Lu-labeled somatostatin receptor (SSTR) antagonist DOTA-p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (177Lu-DOTA-LM3) in patients with metastatic neuroendocrine neoplasms (NENs). Methods: Fifty-one patients (aged 27-76 y; mean, 51.6 ± 13.9 y) with metastatic NENs underwent peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-LM3 between August 2017 and December 2019. The median administered activity per cycle was 6.1 ± 0.88 GBq (range, 2.8-7.4 GBq). 68Ga-NODAGA-LM3 PET/CT was used for patient selection and follow-up after 177Lu-DOTA-LM3 PRRT. Morphologic and molecular responses were evaluated in accordance with RECIST 1.1 and the criteria of the European Organisation for Research and Treatment of Cancer (EORTC). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dosimetry was performed on 11 patients and compared with the SSTR agonist 177Lu-DOTATOC in 247 patients undergoing PRRT on the same dosimetry protocol. Results: Higher uptake and a longer effective half-life were found for 177Lu-DOTA-LM3 than for the agonist 177Lu-DOTATOC in the whole body and in the kidneys, spleen, and metastases, resulting in higher mean absorbed organ and tumor doses. All patients tolerated therapy without any serious acute adverse effects. Mild nausea without vomiting was observed in 5 (9.8%) patients; no other symptoms were reported. The most severe delayed adverse event was Common Terminology Criteria (CTC)-3 thrombocytopenia in 3 (5.9%) patients. Neither CTC-4 thrombocytopenia nor CTC-3-4 anemia or leukopenia was observed after treatment. No significant decline in renal function was observed, nor was hepatotoxicity. According to RECIST 1.1, disease control could be reached in 40 patients (disease control rate, 85.1%) of the 47 patients monitored after 177Lu-DOTA-LM3 PRRT, with a partial response in 17 (36.2%) and stable disease in 23 (48.9%), whereas 7 patients (14.9%) had progressive disease, and by EORTC criteria, there was complete remission in 2 patients (4.3%), partial remission in 21 (44.7%), stable disease in 18 (38.3%), and progressive disease in 6 (12.8%). Conclusion: The antagonist PRRT with 177Lu-DOTA-LM3 could be administered without severe adverse effects and was well tolerated by most patients, with thrombocytopenia occurring in only a few. No other severe adverse effects were observed; in particular, there was no nephrotoxicity. The SSTR antagonist 177Lu-DOTA-LM3 appears to be promising for PRRT, provides a favorable biodistribution and higher tumor radiation doses than SSTR agonists, and was effective in treating advanced metastatic NENs, especially in patients with low or no SSTR agonist binding, even achieving complete remission in some patients.

Response evaluation after immunotherapy in NSCLC: Early response assessment using FDG PET/CT.

The present study aimed to evaluate the role of early F-18 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) in non-small cell lung cancer patients undergoing immune checkpoint inhibitor (ICI) treatment.Twenty-four non-small cell lung cancer patients who received nivolumab or pembrolizumab and underwent FDG PET/CT as an interim analysis after 2 or 3 cycles of ICI treatment were retrospectively enrolled. Tumor response was assessed using the PET Response Criteria in Solid Tumors 1.0 (PERCIST) and the European Organization for Research and Treatment of Cancer (EORTC) criteria after 2 or 3 cycles of ICI treatment (SCAN-1) and after an additional 2 cycles of ICI treatment (SCAN-2). The best overall response was determined by FDG PET/CT or chest CT at ≥ 3 months after therapy initiation, and the clinical benefit was investigated. progression-free survival was investigated, and its correlation with clinicopathologic and metabolic parameters was examined using a Cox multivariate proportional hazards model.In the interim analysis, 4 patients achieved a complete metabolic response (CMR), 1 patient exhibited a partial metabolic response (PMR), and 14 patients had Progressive metabolic disease (PMD) according to the PERCIST and EORTC criteria. Four patients showed stable metabolic disease (SMD) according to the PERCIST criteria, and 2 patients showed different responses (i.e., PMR) according to the EORTC criteria. Patients with a CMR or PMR at SCAN-1 had a clinical benefit. Among the 4 patients with SMD at SCAN-1, only 1 experienced a clinical benefit regardless of the percent change in the peak standardized uptake value. Two patients with discordant response assessments between the PERCIST and EORTC criteria showed conflicting clinical benefits. Among the 14 patients with PMD, none experienced any clinical benefit. Only metabolic parameters were significant factors for predicting progression in the multivariate analysis (peak standardized uptake value and metabolic tumor volume, HRs of 1.18 and 1.00, respectively).Based on early F-18 FDG PET/CT after ICI treatment, metabolic parameters could predict post-treatment progression. Responses after ICI treatment were correctly assessed in patients with a CMR, a PMR, and PMD, but patients with SMD required a meticulous follow-up because of varying clinical benefits.

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

PurposeIn 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.MethodsTwenty-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.ResultsMedian 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.ConclusionPET/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.

Agreement Between the European Organization for Research and Treatment of Cancer and Positron Emission Tomography Response Criteria in Solid Tumors in Evaluating Treatment Response in Solid Malignant Tumors.

IntroductionFluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is used for non-invasive staging and restaging of solid malignant tumors. PET-CT based criteria have been developed to evaluate the response to targeted therapy. These include the European Organization for Research and Treatment of Cancer (EORTC) and the PET Response Criteria in Solid Tumors (PERCIST). The aim of this study was to determine the agreement between EORTC and PERCIST criteria for treatment response evaluation in patients with solid malignant tumors.Materials and methodsThis was a retrospective study conducted from February 2017 till July 2017. Electronic medical records of patients diagnosed with solid malignant tumors were searched. Experienced radiologists evaluated the PET-CT images based on EORTC and PERCIST criteria. The Kappa (κ) test was used for evaluation of agreement between treatment response according to EORTC and PERCIST criteria.ResultsOut of 54 patients, 41 (75.9%) were male and 13 (24.1%) were female with a mean age of 57.09 ± 10.65 years. According to EORTC criteria, complete metabolic response (CMR) was seen in five (9.3%) of patients, partial metabolic response (PMR) was seen in 36 (66.7%) of patients, progressive metabolic disease (PMD) was seen in nine (16.7%) of patients and stable metabolic disease (SMD) was seen in four (7.4%) of patients. According to PERCIST criteria, CMR was seen in five (9.3%) of patients, PMR was seen in 33 (61.1%) of patients, PMD was seen in nine (16.7%) of patients and SMD was seen in seven (13.0%) of patients. EORTC and PERCIST agreed on 43 (79.6%) of the patients with κ-coefficient of 0.62 indicating good agreement (p-value of <0.001).ConclusionEORTC and PERCIST criteria have a good agreement in evaluating treatment response in solid malignant tumors. Therefore, adoption of EORTC or PERCIST in PET-CT reporting can standardize the evaluation of oncological treatment results.

Concordance between RTOG and EORTC prognostic criteria in low-grade gliomas.

Aim: European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) criteria are used to choose treatment in low-grade gliomas. However, no data exist on their concordance. Methods: Low-grade glioma patients treated at our institution from 1998 to 2015 and assessable for both RTOG and EORTC criteria were included to analyze their concordance. Surgery extension, postsurgical treatments, molecular characteristics (IDH mutation, MGMT methylation and 1p/19q codeletion) were recorded. Results: We included 99 patients. The concordance was low (50.5%; K=0.127; p =0.021) but for two subgroups: EORTC high-risk patients were also RTOG high-risk patients (concordance: 97.5%) and RTOG low-risk patients were also EORTC low-risk patients (concordance: 90.9%). Conclusion: The concordance between RTOG and EORTC criteria is low. Thus, clinical trials adopting different risk criteria are not comparable.

Evaluation of response in patients of metastatic castration resistant prostate cancer undergoing systemic radiotherapy with lutetium177-prostate-specific membrane antigen: A comparison between response evaluation criteria in solid tumors, positron-emission tomography response criteria in solid tumors, European organization for research and treatment of cancer, and MDA criteria assessed by gallium 68-prostate-specific membrane antigen positron-emission tomography-computed tomography.

Introduction:We evaluated various morphological and molecular response criteria in metastatic castration-resistant prostate cancer (PCa) patient undergoing peptide receptor radioligand therapy (PRLT) with Lutetium177-prostate-specific membrane antigen (PSMA) by using Gallium 68-PSMA positron-emission tomography-computed tomography (Ga68-PSMA PET-CT).Methods:A total of 46 pre- and 8–12 weeks’ post-PRLT Ga68-PSMA PET-CT studies were reanalyzed (23 comparisons). Prostate-specific antigen drop of ≥50% and ≥25% increase was considered as partial response (PR) and progressive disease (PD), respectively, for biochemical response (BR) while change in-between was considered as stable disease (SD). Response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and MD Anderson (MDA) criteria for morphological response while PET response criteria in solid tumors 1.0 (PERCIST 1.0) and European organization for research and treatment of cancer (EORTC) criteria for molecular response were used. Kappa coefficient was derived to see the level of agreement.Results:The proportion of PD, PR, and SD by BR and RECIST criteria was 9 (39.13%), 3 (13.04%), and 11 (47.83%) and 5 (21.74%), 2 (8.70%), and 16 (69.57%), respectively. The proportion of PD, PR, and SD was same by PERCIST and EORTC criteria and which were 8 (34.78%), 5 (21.74%), and 10 (43.48%). The proportion of PD, PR, and SD by MDA criteria was 1 (4.35%), 1 (4.35%), and 21 (91.30%), respectively. Poor agreement between BR and both morphological criteria while a statistically significant agreement with both molecular criteria seen.Conclusion:We concluded that molecular criteria performed better than morphological criteria in response assessment by Ga68-PSMA PET-CT in metastatic castration resistant PCa patients undergoing PRLT.

18F-FDG PET/CT in therapy response and in predicting responders or non-responders in malignant pleural mesothelioma patients, by using semi-quantitative mRECIST and EORTC criteria.

To evaluate the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in therapy response assessment according modified response evaluating criteria of solid tumors (mRECIST) and the predictive role of volume-based semi-quantitative parameters in patients with malignant pleural mesothelioma (MPM). Furthermore modified RECIST criteria for MPM mRECIST and the European Organization for Research and Treatment of Cancer (EORTC) criteria were compared and the predictive role of 18F-FDG PET/CT in the post-therapy outcome. Thirty five selected patients with MPM underwent 18F-FDG PET/CT scan at baseline (1) and after therapy (2). Semi-quantitative 18F-FDG PET/CT parameters were collected for each scan and also differences (Δ) ΔSUVmax, ΔSUVav, ΔMTV, ΔTLG, response index (RI)max% and RIav% were evaluated. Radiologic response to therapy was assessed by using the mRECIST and EORTC. The correlation between response to therapy assessed by EORTC and mRECIST criteria was moderate (K=0.418; 95%CI:0099-0736). According to mRECIST, statistical differences between responders and non-responders were significant in the analysis of semi-quantitative parameters. According mRECIST criteria, all parameters defined a good area under the curve (AUC) but the better AUC resulted for ΔMTV (cut-off≤11.3, sensitivity=91.3%, specificity=91.7%) and ΔTLG (cut-off≤59.1, sensitivity=82.6%, specificity=100%). Kaplan-Meier curves between responders and non-responders did not show statistically significant differences. The semi-quantitative analysis of 18F-FDG PET/CT has an important role in MPM therapy response assessment and has a predictive role in distinguishing responders and non-responders.

Integration of stereotactic radiotherapy in the treatment of metastatic colorectal cancer patients: a real practice study with long-term outcome and prognostic factors.

BackgroundThere are very few clinical or prognostic studies on the role of SRT (Stereotactic Radiation Therapy) in the continuum of care of metastatic colorectal cancer (mCRC) patients.Patients and methodsPatients affected by oligo-mCRC were treated with SRT before or after front-line standard treatments. SRT was delivered according to a risk-adapted protocol. Total body CT (Computed Tomography) scan was done before therapy and every three months thereafter. The radiologic responses to therapy were evaluated by RECIST (Response Evaluation Criteria In Solid Tumors). FDG-PET (FluoroDeoxyGlucose - Positron Emission Tomography) was done before and after SRT; metabolic responses were evaluated by using the EORTC (European Organization for Research and Treatment of Cancer) criteria. The Kaplan-Meier product limit method was applied to graph Overall Survival (OS) and Progression-Free Survival (PFS).ResultsForty-seven patients were included. Twenty-one patients had disease limited to lungs, 9 to lung and liver, 7 only to liver, 10 to multiple sites. The median prescription SRT dose was 60 Gy per organ in 3 fractions (median biological effective dose of 180 Gy). The reduction of delta SUVmax (maximum Standardized Uptake Value) correlated with the local control (p<0.001) and two-years survival (p=0.003). At univariate analysis, localization of primary tumor, site of metastases, KRAS (Kirsten RAt Sarcoma) oncogene mutational status, response to first-line chemotherapy, response to SRT and number of treated lesions predicted both PFS and OS.DiscussionThis real practice experience suggests that further studies are needed to analyze the promising role of SRT in the multidisciplinary management of mCRC.

Evaluation of RECIST, PERCIST, EORTC, and MDA Criteria for Assessing Treatment Response with Ga68-PSMA PET-CT in Metastatic Prostate Cancer Patient with Biochemical Progression: a Comparative Study.

The aim of the study was to compare response evaluation criteria in solid tumours 1.1 (RECIST 1.1), positron emission tomography response criteria in solid tumours (PERCIST), European organisation for research and treatment of cancer (EORTC), and MD Anderson (MDA) criteria for response assessment by Gallium 68-prostate-specific membrane antigen positron emission tomography-computed tomography (Ga68-PSMA PET-CT) in metastatic adenocarcinoma prostate cancer (mPCa) patients with biochemical progression. Eighty-eight mPCa patients with pre and post treatment Ga68-PSMA PET-CT were included. A ≥ 25% increase and ≥ 2ng/ml above the nadir if prostate specific antigen (PSA) drop or ≥ 2ng/ml above the baseline if PSA does not drop was considered as biochemical progression. RECIST 1.1 and MDA criteria for morphology and PERCIST and EORTC criteria for molecular response were investigated. Percentages of progressive disease (PD), partial response (PR), and stable disease (SD) were calculated. Chi-square test was used for statistical significance. Proportion of PD, SD, and PR by RECIST 1.1 and MDA criteria were 44 (50.57%), 39 (44.83%), 4 (4.6%), and 33 (39.76%), 48 (57.83%), 2 (2.41%) respectively. Proportion of PD, SD, and PR by PERCIST and EORTC criteria were 71 (80.68%), 11 (12.50%), 6 (6.82%), and 74 (84.09%), 8 (9.09%), 6 (6.82%) respectively. Chi-square test showed statistically significant (P < 0.05) higher proportion of progression detected by both molecular criteria as compare to both morphological criteria. We concluded that for Ga68-PSMA PET-CT response evaluation, molecular criteria performed better than morphological criteria in mPCa patient with PSA progression.

FDG PET/CT for prognostic stratification of patients with metastatic breast cancer treated with first line systemic therapy: Comparison of EORTC criteria and PERCIST.

AimEvaluate response and predict prognosis of patients with newly diagnosed metastatic breast cancer treated with first line systemic therapy using European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in solid Tumours (PERCIST).MethodsFrom December 2006 to August 2013, 57 women with newly diagnosed metastatic breast cancer were retrospectively evaluated. FDG-PET/CT was performed within one month before treatment and repeated after at least 3 cycles of treatment. Metabolic response evaluation was evaluated by two readers according to both EORTC criteria and PERCIST, classifying the patients into 4 response groups: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD).ResultsWith EORTC criteria, 22 patients had CMR, 17 PMR, 6 SMD and 12 PMD. With PERCIST, 20 patients had CMR, 15 PMR, 10 SMD and 12 PMD. There was agreement between EORTC and PERCIST in 84% of the patients. By log-rank analysis, metabolic response evaluated with both EORTC criteria and PERCIST was able to predict overall survival (p = 0.028 and 0.002 respectively). CMR patient group had longer median OS than patients in the combined PMR+SMD+PMD group (60 vs 26 months both with EORTC and PERCIST; p = 0.009 and 0.006 respectively). By multivariate analysis, CMR either with EORTC or PERCIST remained an independent predictor of survival.ConclusionMetabolic response evaluation with EORTC criteria and PERCIST gave similar prognostic stratification for metastatic breast cancer treated with a first line of systemic therapy.

Regorafenib in antiangiogenic-naive, chemotherapy-refractory advanced colorectal cancer: A phase IIb trial.

782 Background: The oral multikinase inhibitor regorafenib improves overall survival in advanced colorectal cancer (CRC). The aim of this study was to investigate the safety and efficacy of regorafenib in antiangiogenic-naïve patients with chemotherapy-refractory CRC. Methods: In this single-center, single-arm, phase 2b study, patients received regorafenib 160 mg/day for 3 weeks on/1 week off. Tumor response assessed by RECIST 1.1 and tumor metabolic response by [18F] fluorodeoxyglucose positron emission tomography (PET/CT) according to the European Organization for Research and Treatment of Cancer (EORTC) criteria were evaluated at week 8 (W8). PFS rate was defined as the percentage of evaluable patients alive without progression at W8. Safety was assessed until the cut-off date (May 2, 2017). Results: Overall, 59 patients (59.3% male; median age 58.0 yrs) received regorafenib (median dose 148.8 mg/day). The W8 PFS rate was 46.6% (95% CI 33.3% - 60.1%) and median PFS and OS were 3.6 and 7.5 months, respectively. Overall disease control rate (DCR) was 50.8% by RECIST and 62.7% by EORTC criteria (Table). Most common regorafenib-related grade ≥3 AEs were hypertension (35.6%), hand-foot skin reaction (HFSR) (25.4%) and hypophosphatemia (22.0%). One patient discontinued treatment due to drug-related HFSR. Conclusions: The W8 PFS rate and overall DCR support the anti-tumor activity of regorafenib in antiangiogenic-naïve, chemotherapy-refractory advanced CRC. Compared with the previous phase 3 CORRECT and CONCUR trials, the median PFS suggests a better outcome in this population. These data provide the basis for further investigation of regorafenib’s role in earlier treatment lines in metastatic CRC and on the use of PET/CT in tumor response assessment. Clinical trial information: NCT02465502. [Table: see text]