Radiological Response Criteria Research Articles

Malignant Pleural Mesothelioma: Staging and Radiological Response Criteria in Patients Treated with Immune Checkpoint Inhibitors.

Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.

Radiological response criteria in non-small cell lung cancer treated with immunotherapy: RECIST1.1 vs. iRECIST

article: Radiological response criteria in non-small cell lung cancer treated with immunotherapy: RECIST1.1 vs. iRECIST - Journal of Radiological Review 2022 December;9(4):171-6 - Minerva Medica - Journals

GCT-11. 24 Gy whole ventricular radiotherapy alone is sufficient for disease control in localised germinoma in CR after initial chemotherapy – final of the SIOP CNS GCT II study

SIOP CNS GCT II aimed to establish if 24 Gy Whole Ventricular Radiotherapy (WVRT) in localised germinoma is sufficient for tumour control. After central review of radiological response after ‘CarboPEI’ chemotherapy, patients in complete remission (CR) were consolidated with 24 Gy WVRT. Between 2/2012 and 7/2018, 194 patients from 8 European countries with histologically-confirmed fully-staged localised germinoma were registered, of whom 167 were protocol pts. CR after chemotherapy was achieved in 65 patients, Of the 102 patients not in CR after chemotherapy 91 had partial remission (PR), 8 stable disease (SD), 3 progressive disease (PD). All 65 patients in CR received 24 Gy WVRT alone; two of these relapsed, both locally, 7 and 12 months after diagnosis. Of the 102 non-CR patients after chemotherapy, 91 with PR and 8 with SD received 24 Gy WVRT and 16 Gy boost, of which five relapsed (four local, one distant) 2 -7 years from diagnosis. One additional patient who remained in CR died of infection in CR, 4 years after Dx. In three patients with PD all received 24 Gy ventricular irradiation with varying tumour boosts. 16-30 Gy, no relapses occurred. Median follow-up of the whole group was 4,2 years. 4- years event-free survival (EFS) for patients in CR treated with WVRT only (n=65) was 97% (standard error 2%). 4-years EFS for patients with non-CR ( WVRT 24 Gy and 16 Gy to 30 Gy tumour boost) (n=102) was 95% (standard error 2%). Localised germinoma in CR after chemotherapy had an excellent outcome with 24 Gy WVRT alone. 24 Gy WVRT is therefore considered the standard consolidation treatment in this group and should be used as the standard for further treatment studies in localised germinoma evaluating the recent international consensus on radiological response criteria ( Lancet Oncology accepted).

Comparison of radiologic response criteria as predictors for refractoriness and survival to transarterial chemoembolization among hepatocellular cancer: Outcomes from a Southeast Asian cohort

Objectives: Radiologic response helps select patients with hepatocellular carcinoma who may become refractory after repeated sessions of transarterial chemoembolization (TACE). The utility of the various criteria in assessing radiologic response and survival is, however, poorly defined. This study aimed to compare the modified response evaluation criteria in solid tumors and Choi criteria as well as identify other predictors of overall survival and refractory disease of HCC patients undergoing repetitive TACE. Material and Methods: The radiologic response, as well as clinical and laboratory characteristics of 39 patients treated with repetitive conventional TACE from January 2012 to January 2019, were analyzed in a retrospective cohort. Results: The median overall survival of patients was 23.2 months and overall mortality was 36%. Multivariate Cox regression analysis revealed that progressive disease (PD) using Choi criteria (HR = 5.47, CI 1.15–25.99, P = 0.033) and enhancement on follow-up CT (computed tomography) imaging (HR = 1.98, P = 0.034) were independent risk factors for poor survival as were Child-Pugh score (Hazard ratio = 3.47, P = 0.044), AST (HR = 7.6, P = 0.021), tumor size (HR = 5.47, P = 0.033), and neutrophil-lymphocyte ratio (HR = 1.25, P = 0.049). Multivariate analysis also showed that ALT (P = 0.005), enhancement (P = 0.003), Child-Pugh score (P = 0.010), and PD using Choi criteria (P = 0.022) were predictive of TACE refractoriness/failure. Conclusion: Predictors for poorer survival and TACE failure/refractory disease were identified. Radiologic response using the Choi criteria and persistent contrast enhancement on radiologic follow-up is ominous imaging signs on patient surveillance and should be included in a rational treatment strategy and the decision to switch therapy.

532 - A Multicenter, Multicohort, Open-Label, Single Arm per Cohort, Phase II Study to Assess the Efficacy and Safety of Tabelecleucel in Patients with EBV-Associated Diseases Using an Adaptive Two-Stage Study Design

Background Epstein-Barr virus infection is associated with a variety of life-threatening malignant and non-malignant diseases. In immunocompromised individuals where T-cell function is impaired, loss of immune control of Epstein-Barr virus (EBV) can lead to proliferation of EBV-transformed B cells and result in immunodeficiency-associated lymphoproliferative diseases (IA-LPD). EBV-driven IA-LPDs are a heterogenous group of diseases with variable clinical and pathologic features, including primary immunodeficiency-associated LPD (EBV+ PID-LPD), acquired immunodeficiency-associated LPD (EBV+ AID-LPD), and post-transplant lymphoproliferative disorder (EBV+ PTLD). In addition, EBV-infection of mesenchymal cells can cause sarcomas, including leiomyosarcoma (EBV+ sarcoma). In rare instances, EBV viremia (ie, persistent EBV infection) can lead to non-malignant yet life-threatening complications such as chronic active EBV (CAEBV) or hemophagocytic lymphohistiocytosis (HLH). During the transition from primary EBV infection to latent state, only a subset of viral genes is expressed. The resulting latency proteins are a target of CD8+ T cells, making EBV+ malignancies good candidates for treatment with EBV-targeted cytotoxic lymphocytes. Tabelecleucel (tab-cel) is an off-the-shelf, partially human leukocyte antigen (HLA)-matched, allogeneic EBV-specific T-cell immunotherapy generated from screened EBV+ donors. Tabelecleucel is characterized by both HLA genotype and HLA restriction, the HLA allele(s) through which tab-cel exerts cytotoxic activity. Tab-cel is selected for each patient from an inventory based on the HLA restriction(s) and partial HLA matching. Initial safety and efficacy data support that tab-cel was well tolerated and showed clinical activity in patients with each of the EBV-associated diseases being proposed in study 205 [Nikiforow S et al. ESMO 2020; Kurlander LS et al. Ann Oncol 2018; Prockop S et al. JCI 2020]. These data encourage investigation to further evaluate the safety and efficacy of tab-cel in these populations. Study design and objectives This is a multicenter, multicohort, open-label, single-arm per cohort, phase II study to assess the efficacy and safety of tab-cel in patients with EBV-associated diseases (ATA129-EBV-205). The primary objective of the study is to assess the clinical benefit of tab-cel as measured by objective response rate. This study will also evaluate clinically relevant disease-specific outcomes and will characterize the safety profile of tab-cel in these patient populations. This study will enroll patients who are relapsed/refractory or newly diagnosed and ineligible for first-line therapy in the following cohorts: EBV+ AID-LPD, EBV+ PID-LPD, EBV+ sarcoma, including LMS, CAEBV/HLH and EBV+ PTLD with central nervous system [CNS]-involvement. In addition, a cohort of patients with previously untreated EBV+ PTLD where first-line therapy is not appropriate is planned to start enrollment in 2021. A Phase III study of tab-cel for solid organ or allogeneic hematopoietic cell transplant patients with EBV+ PTLD after failure of rituximab or rituximab plus chemotherapy (NCT03394365) is ongoing. Patients in each cohort will receive tab-cel in 35-day cycles. During each cycle, patients will receive intravenous tab-cel at a dose of 2 × 106 cells/kg on days 1, 8, and 15, followed by an observation period through day 35 (Figure 1). An adaptive two-stage design will be used for each cohort in this study, and for each, a maximum of eight patients will be enrolled in stage 1. The decision to move to stage 2 enrollment for any given cohort will be based on an analysis of the first eight evaluable patients in the cohort using investigator's assessment (per defined radiologic, clinical, and/or laboratory response criteria). If at least two among the first eight evaluable patients in stage 1 are responders W(ie, complete response or partial response), additional patients may be enrolled in stage 2 of that cohort. The number of patients enrolled in stage 2 will depend on the number of observed responders in stage 1 (Table 1). This design will allow for minimization of the expected number of patients required to evaluate the efficacy of tab-cel in each disease cohort independently. Figure 1. Study design schema Download : Download high-res image (589KB) Download : Download full-size image Disclosures Prockop: Jasper Pharmaceuticals: Research Funding; Mesoblast: Consultancy, Research Funding; Atara Biotherapeutics: Research Funding; Memorial Sloan Kettering: Patents & Royalties: IP related to the development of third party viral specific T cells with all of my interests assigned to MSK. Dinavahi: Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Navarro: Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Guzman-Becerra: Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Sun: Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Gamelin: Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company.

Salvage peptide receptor radionuclide therapy in patients with progressive neuroendocrine tumors: a systematic review and meta-analysis.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment option in patients with metastatic neuroendocrine tumors (NETs). Recently, salvage PRRT has been introduced for progressing NET patients. This systematic review and meta-analysis evaluated the therapeutic efficacy, survival, and toxicity of salvage PRRT in patients with progressive NETs. A systematic (PubMed, Embase, Cochrane, and Scopus) were performed. To determine therapeutic efficacy, objective response rate (ORR), and disease control rate (DCR) were identified using radiologic response criteria. To determine survival, progression-free survival (PFS), and overall survival (OS) were verified. To determine toxicity, information was collected on serious (grades 3 or 4) hematologic and renal adverse events. Nine articles featuring 426 patients were included in this study. Salvage PRRT achieved pooled proportions of ORR in 17.1% [95% confidence interval (CI) 11.6-23.5] and DCR in 76.9% (95% CI 72.3-81.0) of patients. Salvage PRRT demonstrated pooled estimates of PFS of 14.1 months (95% CI 12.2-15.9) and OS of 26.8 months (95% CI 18.8-34.9). Pooled proportions of hematologic and renal toxicities were 10.8% (95% CI 5.9-16.8) and 0.7% (95% CI 0.2-1.8), respectively. A subgroup direct comparison study with initial PRRT revealed that salvage PRRT showed significantly lower therapeutic efficacy (ORR and DCR, all P < 0.001) and shorter PFS (P = 0.03) despite similar hematologic toxicity (P = 0.25) and renal toxicity (P = 0.45). Salvage PRRT is effective in patients with progressive NETs, and toxicity appeared to be similar to initial PRRT which could be a feasible treatment option.

GCT-76. 24Gy WHOLE VENTRICULAR RADIOTHERAPY ALONE IS SUFFICIENT FOR DISEASE CONTROL IN LOCALISED GERMINOMA IN CR AFTER INITIAL CHEMOTHERAPY – EARLY RESULTS OF THE SIOP CNS GCT II STUDY

SIOP CNS GCT II aimed to establish if 24Gy Whole Ventricular Radiotherapy (WVRT) in localised germinoma is sufficient for tumour control. After central review of radiological response after ‘CarboPEI’ chemotherapy, patients in complete remission (CR) were consolidated with 24Gy WVRT. Between 2/2012 and 7/2018, 182 patients from 8 European countries with histologically-confirmed fully-staged localised germinoma were registered. 70 patients were in CR after chemotherapy, 98 in partial remission (PR), seven had stable disease, two progressive disease, and in five no response data were documented. Of the 70 patients in CR, 58 received 24Gy WVRT alone; two of these relapsed, one local and one disseminated, two and six years after diagnosis. Of the 98 patients in PR after chemotherapy, 86 received 24Gy WVRT and 16Gy boost, of which five relapsed (three local, two distant) 12–24 months from diagnosis. Twelve patients in each of the CR/PR groups received non-protocol or undocumented radiotherapy fields/doses. Median follow-up was 3.7 years. Event-free survival (EFS) for patients in CR and with WVRT only (n=58) was 98% at 4 years. 4-years EFS of patients with PR and WVRT 24Gy and 16Gy tumor boost (n=86) was 95%. Localised germinoma in CR after chemotherapy had an excellent outcome with 24Gy WVRT alone; 24GY WVRT can therefore be considered standard consolidation treatment in this group. International consensus on radiological response criteria is of utmost importance to avoid over- and undertreatment of such patients and to pave the way for further treatment reduction in this group of patients.

A Multicenter, Multicohort, Open-Label, Single-Arm per Cohort, Phase II Study to Assess the Efficacy and Safety of Tabelecleucel in Patients with EBV-Associated Diseases Using an Adaptive Two-Stage Study Design

Background Epstein-Barr virus infection is associated with a variety of life-threatening malignant and non-malignant diseases. In immunocompromised individuals where T-cell function is impaired, loss of immune control of Epstein-Barr virus (EBV) can lead to proliferation of EBV-transformed B cells and result in immunodeficiency-associated lymphoproliferative diseases (IA-LPD). EBV-driven IA-LPDs are a heterogenous group of diseases with variable clinical and pathologic features, including primary immunodeficiency-associated LPD (EBV+ PID-LPD), acquired immunodeficiency-associated LPD (EBV+ AID-LPD), and post-transplant lymphoproliferative disorder (EBV+ PTLD). In addition, EBV-infection of mesenchymal cells can cause sarcomas, including leiomyosarcoma (EBV+ sarcoma). In rare instances, EBV viremia (ie, persistent EBV infection) can lead to non-malignant yet life-threatening complications such as chronic active EBV (CAEBV) or hemophagocytic lymphohistiocytosis (HLH). During the transition from primary EBV infection to latent state, only a subset of viral genes is expressed. The resulting latency proteins are a target of CD8+ T cells, making EBV+ malignancies good candidates for treatment with EBV-targeted cytotoxic lymphocytes. Tabelecleucel (tab-cel) is an off-the-shelf, partially human leukocyte antigen (HLA)-matched, allogeneic EBV-specific T-cell immunotherapy generated from screened EBV+ donors. Tabelecleucel is characterized by both HLA genotype and HLA restriction, the HLA allele(s) through which tab-cel exerts cytotoxic activity. Tab-cel is selected for each patient from an inventory based on the HLA restriction(s) and partial HLA matching. Initial safety and efficacy data support that tab-cel was well tolerated and showed clinical activity in patients with each of the EBV-associated diseases being proposed in study 205 [Nikiforow S et al. ESMO 2020; Kurlander LS et al. Ann Oncol 2018; Prockop S et al.JCI 2020]. These data encourage investigation to further evaluate the safety and efficacy of tab-cel in these populations. Study design and objectives This is a multicenter, multicohort, open-label, single-arm per cohort, phase II study to assess the efficacy and safety of tab-cel in patients with EBV-associated diseases (ATA129-EBV-205). The primary objective of the study is to assess the clinical benefit of tab-cel as measured by objective response rate. This study will also evaluate clinically relevant disease-specific outcomes and will characterize the safety profile of tab-cel in these patient populations. This study will enroll patients who are relapsed/refractory or newly diagnosed and ineligible for first-line therapy in the following cohorts: EBV+ AID-LPD, EBV+ PID-LPD, EBV+ sarcoma, including LMS, CAEBV/HLH and EBV+ PTLD with central nervous system [CNS]-involvement. In addition, a cohort of patients with previously untreated EBV+ PTLD where first-line therapy is not appropriate is planned to start enrollment in 2021. A Phase III study of tab-cel for solid organ or allogeneic hematopoietic cell transplant patients with EBV+ PTLD after failure of rituximab or rituximab plus chemotherapy (NCT03394365) is ongoing. Patients in each cohort will receive tab-cel in 35-day cycles. During each cycle, patients will receive intravenous tab-cel at a dose of 2 × 106 cells/kg on days 1, 8, and 15, followed by an observation period through day 35 (Figure 1). An adaptive two-stage design will be used for each cohort in this study, and for each, a maximum of eight patients will be enrolled in stage 1. The decision to move to stage 2 enrollment for any given cohort will be based on an analysis of the first eight evaluable patients in the cohort using investigator's assessment (per defined radiologic, clinical, and/or laboratory response criteria). If at least two among the first eight evaluable patients in stage 1 are responders W(ie, complete response or partial response), additional patients may be enrolled in stage 2 of that cohort. The number of patients enrolled in stage 2 will depend on the number of observed responders in stage 1 (Table 1). This design will allow for minimization of the expected number of patients required to evaluate the efficacy of tab-cel in each disease cohort independently. Figure 1. Study design schema Disclosures Prockop: Jasper Pharmaceuticals: Research Funding; Mesoblast: Consultancy, Research Funding; Atara Biotherapeutics: Research Funding; Memorial Sloan Kettering: Patents &amp; Royalties: IP related to the development of third party viral specific T cells with all of my interests assigned to MSK. Dinavahi:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Navarro:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Guzman-Becerra:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Sun:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Gamelin:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company.

Radiological tumor response and histopathological correlation of hepatocellular carcinoma treated with stereotactic body radiation therapy as a bridge to liver transplantation.

To assess the imaging findings of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) as a bridging therapy prior to liver transplantation (LT), with histopathological correlation at liver explant. Our institutional review board approved this retrospective study. The study subjects included 25 HCC lesions in 23 patients (20 males; median age, 60 years; range 41-68 years) who underwent LT after SBRT for HCC as a bridge to LT in a single tertiary referral institution over a 12-year period. Target HCC lesions were assessed for imaging biomarkers on contrast-enhanced CT or MRI including change in HCC diameter and assessment of percentage necrosis. The radiologic response at pre-LT imaging was compared to explant pathology. There was a positive correlation between the tumor size (Spearman's ρ = 0.86; p < 0.001) and percentage necrosis (p < 0.001) on Pre-LT imaging and those on pathology. Partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST 1.1 were seen in 8 (32%), 15 (60%), and 2 (8%) lesions on pre-LT imaging, respectively. Of the 15 lesions with radiologic SD, 5/15 (33%) showed necrosis of more than 50% on post-SBRT imaging, while 9/15 (60%) showed necrosis of more than 50% at explant pathologic analysis, showing a tendency to underestimate the degree of tumor necrosis compared to pathology. RECIST 1.1 radiologic response criteria may underestimate the response to treatment with SBRT, and radiologic estimation of percent tumor necrosis was more closely correlated with pathologic percent tumor necrosis.

Progressive Desmoid Tumor: Radiomics Compared With Conventional Response Criteria for Predicting Progression During Systemic Therapy-A Multicenter Study by the French Sarcoma Group.

OBJECTIVE. The response of desmoid tumors (DTs) to chemotherapy is evaluated with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in daily practice and clinical trials. MRI shows early change in heterogeneity in responding tumors due to a decrease in cellular area and an increase in fibronecrotic content before dimensional response. Heterogeneity can be quantified with radiomics. Our aim was to develop radiomics-based response criteria and to compare their performances with clinical and radiologic response criteria. MATERIALS AND METHODS. Forty-two patients (median age, 38.2 years) were included in this retrospective multicenter study because they presented with progressive DT and had an MRI examination at baseline, which we refer to as "MRI-0," and an early MRI evaluation performed after the first chemotherapy cycle (mean time after first chemotherapy cycle, 3 months [SD, 28 days]), which we refer to as "MRI-1." After signal intensity normalization, voxel size standardization, discretization, and segmentation of DT volume on fat-suppressed contrast-enhanced T1-weighted imaging, 90 baseline and delta 3D radiomics features were extracted. Using cross-validation and least absolute shrinkage and selection operator-penalized Cox regression, a radiomics score was generated. The performances of models based on the radiomics score, modified Response Evaluation Criteria in Solid Tumors, European Association for the Study of the Liver criteria, Cheson criteria, Choi criteria, and revised Choi criteria from MRI-0 to MRI-1 to predict progression-free survival (PFS, as defined by RECIST 1.1) were assessed with the concordance index. The results were adjusted for performance status, tumor volume, prior chemotherapy, current chemotherapy, and β-catenin mutation. RESULTS. There were 10 cases of progression. The radiomics score included four variables. A high score indicated a poor prognosis. The radiomics score independently correlated with PFS (adjusted hazard ratio = 5.60, p = 0.003), and none of the usual response criteria independently correlated with PFS. The prognostic model based on the radiomics score had the highest concordance index (0.84; 95% CI, 0.71-0.96). CONCLUSION. Quantifying early changes in heterogeneity through a dedicated radiomics score could improve response evaluation for patients with DT undergoing chemotherapy.

Efficacy and Safety of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

The aim of this study was to evaluate the efficacy and safety of Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients. The median age of patients was 66.5 years (range, 30-88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects. Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.

Impact of obesity, structural severity and their combination on the efficacy of viscosupplementation in patients with knee osteoarthritis

BackgroundObesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough to formally refute VS in such patients in whom surgery is sometimes contraindicated?ObjectivesTo compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined.MethodsPost-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.− 2), OARSI radiological grade (1–2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons (obese versus non-obese, OARSI 1–2 versus 3, and both combined) in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test.ResultsOne-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups (all p < 0.01). At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients (4.9 ± 4.1 versus 7.1 ± 4.9; p = 0.008) and in patients OARSI 1–2 versus 3 (4.8 ± 4.3 versus 6.4 ± 4.5; p = 0.009). However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score.ConclusionThese results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS.

Quantitative evaluation of liver metastases density on computed tomography: A new tool to evaluate early response to bevacizumab-containing chemotherapy

BackgroundResponse Evaluation Criteria in Solid Tumors (RECIST) are used to assess tumour shrinkage after cytotoxic chemotherapy, but may be inadequate for efficacy evaluation of anti-angiogenic therapies. AimsThis study aimed to identify novel radiologic tumour response criteria based on early changes in tumour size and density, observed on computed tomography (CT), in patients with colorectal liver metastases (CRLM) treated with bevacizumab-containing chemotherapy. MethodsCT of 71 and 68 CRLM patients treated with bevacizumab and non-bevacizumab-based regimens, respectively, were retrospectively reviewed. Tumour size, tumour density, and tumour-to-liver density (TTLD) ratio were determined at baseline and at first restaging. We tested their correlation with progression-free (PFS) and overall survival (OS) using the log-rank test. ResultsIn the bevacizumab group, neither RECIST response nor tumour density variation was correlated with PFS or OS. In contrast, PFS and OS were significantly longer in patients with tumour size reduction ≥15% (RECIST−15%) and/or decrease in TTLD ratio not exceeding −10% (TTLD−10%) than in patients who did not reach any of those criteria, in univariate and multivariate analysis. Only size-response criteria predicted clinical outcome in the non-bevacizumab group. ConclusionsThis study highlights new quantitative CT criteria that may early predict the efficacy of bevacizumab in CRLM patients.

Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases

BackgroundTo evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. MethodsThe participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). ResultsThe rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). ConclusionsUnder BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.

Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304

BackgroundSoft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS.MethodsWe compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities.ResultsSeventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival.ConclusionIn the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS.Trial registrationUMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Clinical Value of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Evaluation after Primary Treatment of Advanced Epithelial Ovarian Cancer

AimsTo prospectively evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the definition of the treatment response after primary treatment of advanced epithelial ovarian cancer (EOC). Materials and methodsForty-nine patients with advanced EOC had an 18F-FDG PET/CT scan before and after primary treatment. The treatment response was defined with the currently used radiological and serological Response Criteria in Solid Tumors (RECIST1.1/GCIC) criteria and the modified PET Response Criteria in Solid Tumors (PERCIST). The concordance of the two methods was analysed. If the patient had a complete response to primary treatment by conventional criteria, the end of treatment 18F-FDG PET/CT scan (etPET/CT) was not opened until retrospectively at the time of disease progression. The ability of etPET/CT to predict the time to disease recurrence was analysed. The recurrence patterns were observed with an 18F-FDG PET/CT at the first relapse. ResultsThe agreement of the RECIST1.1/GCIC and modified PERCIST criteria in defining the primary treatment response in the whole patient cohort was good (weighted kappa coefficient = 0.78). Of the complete responders (n = 28), 34% had metabolically active lesions present in the etPET/CT, most typically in the lymph nodes. The same anatomical sites tended to activate at disease relapse, but were seldom the only site of relapse. In patients with widespread intra-abdominal carsinosis at diagnosis, the definition of metabolic response was challenging due to problems in distinguishing the physiological FDG accumulation in the bowel loops from the residual tumour in the same area. The presence of metabolically active lesions in the etPET/CT did not predict earlier disease relapse in the complete responders. ConclusionsIn the present study, etPET/CT revealed metabolically active lesions in complete responders after EOC primary therapy, but they were insignificant for the patient's prognosis. The current study does not favour routine use of 18F-FDG PET/CT after EOC primary treatment for complete responders.

Radiologic Pseudoprogression during Anti–PD-1 Therapy for Advanced Non–Small Cell Lung Cancer

Anti-programmed cell death protein 1 (PD-1) therapy can lead to unconventional tumor responses, including radiologic pseudoprogression. Here we havedetermined the real-world incidence of radiologic pseudoprogression in advanced NSCLC and compared radiologic response criteria for assessment of disease response. The electronic medical records of all patients with NSCLC who were receiving anti-PD-1 therapy at our institution over a 3-year period were retrospectively reviewed, and patients with clinically suspected radiologic pseudoprogression were identified. Patients without available follow-up imaging or clinical data were excluded. Imaging examinations were then analyzed to determine whether progression was confirmed on subsequent reimaging. Assessments of tumor response by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (RECIST 1.1), the unidimensional immune-related response criteria (iRRC), and the iRECIST criteria for all patients were performed and compared. A total of 228 consecutive patients began receiving anti-PD-1 therapy over a 3-year period. Of the 166 of these patients who were evaluable, most (80%) received nivolumab. Fifteen patients (9%) were clinically suspected of having radiologic pseudoprogression on account of tumor enlargement and/or development of new lesions on computed tomography images during the first 4 to 6 weeks of therapy, and they continued receiving anti-PD-1 therapy. Three of these patients (2%) demonstrated evidence of radiologic pseudoprogression at first reimaging. The iRRC and immune RECIST criteria were more accurate in classifying radiologic pseudoprogression as nonprogression; none of the three cases were deemed progression by the iRRC or immune RECIST, whereas all three cases were determined to be progression according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Radiologic pseudoprogression is a clinical challenge but an uncommon occurrence in patients with NSCLC who are receiving anti-PD-1 therapy.

Cancer Immunotherapy Trials Underutilize Immune Response Monitoring.

Immune-related radiological and biomarker monitoring in cancer immunotherapy trials permits interrogation of efficacy and reasons for therapeutic failure. We report the results from a cross-sectional analysis of response monitoring in 685 T-cell checkpoint-targeted cancer immunotherapy trials in solid malignancies, as registered on the U.S. National Institutes of Health trial registry by October 2016. Immune-related radiological response criteria were registered for only 25% of clinical trials. Only 38% of trials registered an exploratory immunological biomarker, and registration of immunological biomarkers has decreased over the last 15 years. We suggest that increasing the utilization of immune-related response monitoring across cancer immunotherapy trials will improve analysis of outcomes and facilitate translational efforts to extend the benefit of immunotherapy to a greater proportion of patients with cancer.

Hepatocellular Carcinoma: Diagnosis, Treatment Algorithms, and Imaging Appearance after Transarterial Chemoembolization.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, with incidence increasing worldwide. Unfortunately, the overall prognosis for patients with HCC is poor and many patients present with advanced stages of disease that preclude curative therapies. Diagnostic and interventional radiologists play a key role in the management of patients with HCC. Diagnostic radiologists can use contrast-enhanced computed tomography (CT), magnetic resonance imaging, and ultrasound to diagnose and stage HCC, without the need for pathologic confirmation, by following established criteria. Once staged, the interventional radiologist can treat the appropriate patients with percutaneous ablation, transarterial chemoembolization, or radioembolization. Follow-up imaging after these liver-directed therapies for HCC can be characterized according to various radiologic response criteria; although, enhancement-based criteria, such as European Association for the Study of the Liver and modified Response Evaluation Criteria in Solid Tumors, are more reflective of treatment effect in HCC. Newer imaging technologies like volumetric analysis, dual-energy CT, cone beam CT and perfusion CT may provide additional benefits for patients with HCC.

Clinical Impact of Preoperative Chemotherapy on Microscopic Cancer Spread Surrounding Colorectal Liver Metastases.

A potentially favorable effect of chemotherapy on the incidence of micrometastases has been reported in patients with colorectal liver metastases (CLMs); however, the actual influence of chemotherapy on the distribution of micrometastases and surgical curability remains unclear. The clinical impact of preoperative chemotherapy on the incidence and distribution of micrometastases was assessed in 191 patients with 357 CLM nodules. Potential radiologic measures for predicting the extent of microscopic cancer spread and surgical curability were then sought among the size-based and non-size-based radiologic response criteria. Multivariate analysis estimated a reduced incidence of micrometastases in patients receiving preoperative chemotherapy (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26-0.76, p=0.003). Furthermore, the addition of biologic agents to the preoperative chemotherapy regimen was correlated with a reduced incidence of microscopic cancer spread beyond a width of 1mm from the margin of the main tumor (OR 0.28, 95% CI 0.11-0.74, p=0.010 for bevacizumab; and OR 0.29, 95% CI 0.09-0.99, p=0.048 for anti-epidermal growth factor receptor antibody). Receiver operating characteristic analyses revealed that the computed tomography (CT) morphologic response showed a moderate predictive power for the distribution of micrometastases, with an area under the curve of 0.687, while size-based response criteria were not reliable for estimating the extent of microscopic cancer spread. Notwithstanding the potential selection of patients after preoperative chemotherapy, the incidence and distribution of micrometastases may be reduced by preoperative chemotherapy. CT morphologic response may be a reliable predictor of both the degree of microscopic cancer spread and the curability of surgery.