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Purpose: Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. Methods: We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. Results: We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15 mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. Conclusion: In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management. [ABSTRACT FROM AUTHOR]

Simple Summary: Novel targeted agents in chronic lymphocytic leukemia (CLL) are employed with different strategies. The evolution of response assessment criteria of the clinical application of measurable residual disease (MRD) analysis and the novel genetic and non-genetic mechanisms of resistance according to the novel treatment strategies within clinical trials are reviewed. Our view on how this knowledge can be applied to the current and future real-life management of CLL patients is discussed. The recent evolution in chronic lymphocytic leukemia (CLL) targeted therapies led to a progressive change in the way clinicians manage the goals of treatment and evaluate the response to treatment in respect to the paradigm of the chemoimmunotherapy era. Continuous therapies with BTK inhibitors achieve prolonged and sustained control of the disease. On the other hand, venetoclax and anti-CD20 monoclonal antibodies or, more recently, ibrutinib plus venetoclax combinations, given for a fixed duration, achieve undetectable measurable residual disease (uMRD) in the vast majority of patients. On these grounds, a time-limited MRD-driven strategy, a previously unexplored scenario in CLL, is being attempted. On the other side of the spectrum, novel genetic and non-genetic mechanisms of resistance to targeted treatments are emerging. Here we review the response assessment criteria, the evolution and clinical application of MRD analysis and the mechanisms of resistance according to the novel treatment strategies within clinical trials. The extent to which this novel evidence will translate in the real-life management of CLL patients remains an open issue to be addressed. [ABSTRACT FROM AUTHOR]

Abstract The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed. Landmark analyses of progression‐free survival (PFS) and overall survival (OS) by end of treatment (EOT) and end of induction (EOI) response status according to RECIL 2017 and Lugano 2014 criteria, and prognostic value of response at EOT/EOI were also compared. Overall, 1333 patients were included from GOYA and 502 from GALLIUM. Complete response (CR) status according to RECIL 2017 criteria showed high concordance with complete metabolic response (CMR) status by Lugano 2014 criteria in both GOYA (92.5%) and GALLIUM (92.4%). EOT and EOI CR/CMR status by both criteria was highly prognostic for PFS in GOYA (RECIL 2017 [CR]: hazard ratio [HR], 0.35 [95% confidence interval [CI] 0.26–0.46]; Lugano 2014 [CMR]: HR, 0.35 [95% CI 0.26–0.48]; both p

Objectives The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC. Methods Data from JDM patients in the Rituximab in Myositis trial (n  = 48), PRINTO JDM trial (n  = 139), and consensus patient profiles (n  = 273) were included. Observed vs expected CSM contributions were compared using Sign test. Characteristics of MRC categories were compared by Wilcoxon tests with Bonferroni adjustment. Spearman correlation of changes in TIS and individual CSMs were examined. Agreement between physician-assessed change and MRC categories was evaluated by weighted Cohen's kappa. Results Of 457 JDM patients with IMACS CSMs and 380 with PRINTO CSMs, 9–13% had minimal, 19–23% had moderate and 41–50% had major improvement. The number of improved and absolute percentage change of CSMs increased by MRC improvement level. Patients with minimal improvement by MRC had a median of 0–1 CSM worsened, and those with moderate/major improvement had a median of zero worsening CSMs. Of patients improved by MRC, 94–95% had improvement in muscle strength and 93–95% had improvement in ≥ 1 patient-reported CSM. IMACS and PRINTO CSMs performed similarly. Physician-rated change and MRC improvement categories had moderate-to-substantial agreement (Kappa 0.5–0.7). Conclusion The ACR-EULAR MRC perform consistently across multiple studies, supporting its further use as an efficacy end point in JDM trials. [ABSTRACT FROM AUTHOR]

Objective The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. Methods Data from adult dermatomyositis/polymyositis patients in the rituximab (n  = 147), etanercept (n  = 14), and abatacept (n  = 19) trials, and consensus patient profiles (n  = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. Results Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. Conclusion The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.

The recent evolution in chronic lymphocytic leukemia (CLL) targeted therapies led to a progressive change in the way clinicians manage the goals of treatment and evaluate the response to treatment in respect to the paradigm of the chemoimmunotherapy era. Continuous therapies with BTK inhibitors achieve prolonged and sustained control of the disease. On the other hand, venetoclax and anti-CD20 monoclonal antibodies or, more recently, ibrutinib plus venetoclax combinations, given for a fixed duration, achieve undetectable measurable residual disease (uMRD) in the vast majority of patients. On these grounds, a time-limited MRD-driven strategy, a previously unexplored scenario in CLL, is being attempted. On the other side of the spectrum, novel genetic and non-genetic mechanisms of resistance to targeted treatments are emerging. Here we review the response assessment criteria, the evolution and clinical application of MRD analysis and the mechanisms of resistance according to the novel treatment strategies within clinical trials. The extent to which this novel evidence will translate in the real-life management of CLL patients remains an open issue to be addressed.

Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous, clonal myeloid neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and an increased risk of progression to acute myeloid leukemia. The diversity in disease severity, morphology, and genetic landscape challenges not only novel drug development but also therapeutic response assessment. The MDS International Working Group (IWG) response criteria were first published in the year 2000 focusing on measures of blast burden reduction and hematologic recovery. Despite revision of the IWG criteria in 2006, correlation between IWG-defined responses and patient-focused outcomes, including long-term benefits, remains limited and has potentially contributed to failures of several phase III clinical trials. Several IWG 2006 criteria also lacked clear definitions leading to problems in practical applications and interobserver and intraobserver consistency of response reporting. Although the 2018 revision addressed lower-risk MDS, the most recent update in 2023 redefined responses for higher-risk MDS and has set out to provide clear definitions to enhance consistency while focusing on clinically meaningful outcomes and patient-centered responses. In this review, we analyze the evolution of the MDS response criteria, limitations, and areas of improvement. [ABSTRACT FROM AUTHOR]

Serum and urine protein electrophoresis and immunofixation are the preferred techniques for monitoring monoclonal proteins and evaluating treatment response in multiple myeloma (MM) patients with measurable disease. However, urine studies are subjected to limitations that may lead to inaccuracies or prevent guidelines compliance. We retrospectively studied if the substitution of urine studies by measuring serum free light chains (sFLCs) results in a comparable disease monitoring, both in intact immunoglobulin (II) and light chain (LC) MM patients. In our cohort, equal or higher percentages of disease were identified by sFLCs at baseline and maximum response as compared to urine studies. Achieving very good partial response or better (≥VGPR) according to the response criteria proposed by the French group (evaluating sFLCs instead of urine) and the IMWG response criteria were associated to a 62% and 63% reduced risk of progression, respectively. A similar prognostic value for reaching ≥VGPR was also observed among LCMM patients when the French group and the IMWG response criteria were applied. Overall, these results support the replacement of urine studies by the sFLCs assay in IIMM. In LCMM, sFLCs could be used for monitoring and urine studies could be performed only to confirm complete remissions and progressions. [ABSTRACT FROM AUTHOR]

Serum and urine protein electrophoresis and immunofixation are the preferred techniques for monitoring monoclonal proteins and evaluating treatment response in multiple myeloma (MM) patients with measurable disease. However, urine studies are subjected to limitations that may lead to inaccuracies or prevent guidelines compliance. We retrospectively studied if the substitution of urine studies by measuring serum free light chains (sFLCs) results in a comparable disease monitoring, both in intact immunoglobulin (II) and light chain (LC) MM patients. In our cohort, equal or higher percentages of disease were identified by sFLCs at baseline and maximum response as compared to urine studies. Achieving very good partial response or better (≥VGPR) according to the response criteria proposed by the French group (evaluating sFLCs instead of urine) and the IMWG response criteria were associated to a 62% and 63% reduced risk of progression, respectively. A similar prognostic value for reaching ≥VGPR was also observed among LCMM patients when the French group and the IMWG response criteria were applied. Overall, these results support the replacement of urine studies by the sFLCs assay in IIMM. In LCMM, sFLCs could be used for monitoring and urine studies could be performed only to confirm complete remissions and progressions.

This study assessed the response to conventional transarterial chemoembolization (cTACE) in patients with liver metastases from rare tumor primaries using one-dimensional (1D) and three-dimensional (3D) quantitative response assessment methods, and investigate the relationship of lipiodol deposition in predicting response. This retrospective bicentric study included 16 patients with hepatic metastases from rare tumors treated with cTACE between 2002 and 2017. Multi-phasic MR imaging obtained before and after cTACE was used for assessment of response. Response evaluation criteria in solid tumors (RECIST) and modified-RECIST (mRECIST) were utilized for 1D response assessment, and volumetric RECIST (vRECIST) and enhancement-based quantitative European Association for Study of the Liver EASL (qEASL) were used for 3D response assessment. The same day post-cTACE CT scan was analyzed to quantify intratumoral lipiodol deposition (%). The mean and standard deviation (SD) of diameter of treated lesions per targeted area was 7.5 ± 5.4 cm, and the mean and SD of number of metastases in each targeted area was 4.2 ± 4.6. cTACE was technically successful in all patients, without major complications. While RECIST and vRECIST methods did not allocate patients with partial response, mRECIST and qEASL identified patients with partial response. Intratumoral lipiodol deposition significantly predicted treatment response according qEASL (R2 = 0.470, p < 0.01), while no association was shown between lipiodol deposition within treated tumor area and RECIST or mRECIST (p > 0.212). 3D quantitative volumetric response analysis can be used for stratification of response to cTACE in patients with hepatic metastases originating from rare primary tumors. Lipiodol deposition could potentially be used as an early surrogate to predict response to cTACE. [Display omitted] • cTACE was technically successful in all patients with liver metastases from rare tumor origins, without major complications. • Intratumoral lipiodol deposition on post-cTACE CT predicted treatment response according to qEASL (R2 = 0.470, p < 0.01) • There was no association between intratumoral lipiodol deposition and RECIST or mRECIST in patients (p > 0.212). [ABSTRACT FROM AUTHOR]

Higher-risk myelodysplastic syndromes (HR-MDS) are clonal myeloid neoplasms that cause life-limiting complications from severe cytopenias and leukemic transformation. Efforts to better classify, prognosticate, and assess therapeutic responses in HR-MDS have resulted in publication of new clinical tools in the last several years. Given limited current treatment options and suboptimal outcomes, HR-MDS stands to benefit from the study of investigational agents.Higher-risk myelodysplastic syndromes (HR-MDS) are a heterogenous group of clonal myeloid-lineage malignancies often characterized by high-risk genetic lesions, increased blood transfusion needs, constitutional symptoms, elevated risk of progression to acute myeloid leukemia (AML), and therapeutic need for allogeneic bone marrow transplantation. Use of blast percentage and other morphologic features to define myelodysplastic neoplasm subtypes is rapidly shifting to incorporate genetics, resulting in a subset of former HR-MDS patients now being considered as AML in presence of leukemia-defining genetic alterations. A proliferation of prognostic tools has further focused use of genetic features to drive decision making in clinical management. Recently, criteria to assess response of HR-MDS to therapy were revised to incorporate more clinically meaningful endpoints and better match AML response criteria. Basic science investigations have resulted in improved understanding of the relationship between MDS genetic lesions, bone marrow stromal changes, germline predispositions, and disease phenotype. However, therapeutic advances have been more limited. There has been import of the IDH1 inhibitor ivosidenib, initially approved for AML; the Bcl-2 inhibitor venetoclax and liposomal daunorubicin/cytarabine (CPX-351) are under active investigation as well. Unfortunately, effective treatment of TP53-mutated disease remains elusive, though preliminary evidence suggests improved outcomes with oral decitabine/cedazuridine over parenteral hypomethylating agent monotherapy. Investigational agents with novel mechanisms of action may help expand the repertoire of treatment options for HR-MDS and trials continue to offer a hopeful therapeutic avenue for suitable patients., Competing Interests: Disclosure M.J.H. has no conflicts of interest. A.E.D. has received consulting fees from or served on advisory boards for Novartis, Geron, Keros, AbbVie, Apellis, Bristo-Myers Squibb, and Astellas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone agonists is the basis for drug treatment in patients with metastatic prostate cancer (PC). An accurate assessment of the response of the tumor and its metastases is of primary importance for making a clinical decision regarding the continuation of treatment, changing the line of drugs or the nature of therapy. The presented clinical case illustrates the possibilities of 99mTc-pyrophosphate skeletal scintigraphy for monitoring the response of PC bone metastases to ADT. The efficiency of hormone therapy with Triptorelin has been confirmed by positive changes in the visual and quantitative scintigraphic signs that manifest the metabolic activity of bone tissue in the area of a metastatic lesion. This was manifested by a marked decrease in the intensity of 99mTc-pyrophosphate accumulation in the foci of bone pathology, by a reduction in the number of visualized hot foci, and by a gradual normalization of the scintigraphic pattern. This variant of the metabolic response of bone metastases to ADT correlated with the positive changes in laboratory parameters, as well as with the signs of reversal of the tumor and its metastases, as evidenced by magnetic resonance imaging.

In many recurrent and/or metastatic cancers, the advent of immunotherapy opens up new scenarios of treatment response, with new phenomena, such as pseudoprogression and hyperprogression. Because of this, different immune-related response criteria have been developed, and new therapeutic strategies adopted, such as treatment beyond progression. Moreover, the role of progression-free survival as a surrogate has been questioned, and new surrogate endpoint hypotheses have arisen. A proper understanding of radiological imaging, an assessment of the biological events triggered by therapy, and the clinical evolution of the lesions and of the patient performance status are all factors that should be considered to guide the oncologist's treatment choice. The primary aim of this article is to discuss how all these concepts apply to recurrent/metastatic head and neck squamous cell carcinoma patients when treated with immunotherapy. [ABSTRACT FROM AUTHOR]

The use of immunotherapy has revolutionized the treatment regimen of certain cancer types, but response assessment has become a difficult task with conventional methods such as CT/MRT or FDG PET-CT and the classical response criteria such as RECIST or PERCIST which have been developed for chemotherapeutic treatment. Plenty of new tracers have been published to improve the assessment of treatment response and to stratify the patient population. We gathered the information on published tracers (in total, 106 individual SPECT/PET tracers were identified) and performed a descriptor-based analysis; in this way, we classify the tracers with regard to target choice, developability (probability to progress from preclinical stage into the clinic), translatability (probability to be widely applied in the 'real world'), and (assumed) diagnostic quality. In our analysis, we show that most tracers are targeting PD-L1, PD-1, CTLA-4, and CD8 receptors by using antibodies or their fragments. Another finding is that plenty of tracers possess only minor iterations regarding chelators and nuclides instead of approaching the problem in a new innovative way. Based on the data, we suggest an orthogonal approach by targeting intracellular targets with PET-activatable small molecules that are currently underrepresented. [ABSTRACT FROM AUTHOR]

Summary: Background: Uncertainty exists about how best to identify primary biliary cholangitis (PBC) patients who would benefit from second-line therapy. Existing, purely clinical, ursodeoxycholic acid (UDCA) response criteria accept degrees of liver biochemistry abnormality in responding patients, emerging data, however, suggest that any degree of ongoing abnormality may, in fact, be associated with an increased risk of adverse outcomes. This cohort study explores the link between response status, the biology of high-risk disease and its implications for clinical practice. Methods: Proteomics, exploring 19 markers previously identified as remaining elevated in PBC following UDCA therapy, were performed on 400 serum samples, from participants previously recruited to the UK-PBC Nested Cohort between 2014 and 2019. All participants had an established diagnosis of PBC and were taking therapeutic doses of UDCA for greater than 12 months. UDCA response status was assessed using Paris 1, Paris 2 and the POISE criteria, with additional analyses using normal liver blood tests stratified by bilirubin level. Statistical analysis using parametric t tests and 1-way ANOVA. Findings: Disease markers were statistically significantly higher in UDCA non-responders than in responders for all the UDCA response criteria, suggesting a meaningful link between biochemical disease status and disease mechanism. For each of the criteria, however, marker levels were also statistically significantly higher in responders with ongoing liver function test abnormality compared to those who had normalised their liver biochemistry. IL-4RA, IL-18-R1, CXCL11, 9 and 10, CD163 and ACE2 were consistently elevated across all responder groups with ongoing LFT abnormality. No statistically significant differences occurred between markers in normal LFT groups stratified by bilirubin level. Interpretation: This study provides evidence that any ongoing elevation in alkaline phosphatase levels in PBC after UDCA therapy is associated with some degree of ongoing disease activity. There was no difference in activity between patients with normal LFT when stratified by bilirubin. These findings suggest that if our goal is to completely control disease activity in PBC, then normalisation of alkaline phosphatase and bilirubin should be the treatment target. This would also simplify messaging around goals of therapy in PBC, benefiting both patients and clinicians. Funding: Funding by the UK Medical Research Council (Stratified Medicine Programme) and an independent research grant by Pfizer. The study funders played no role in the study design, data collection, data analyses, data interpretation or manuscript writing.

Determining the risk level of ground motions (GM) for structures is crucial for their damage control and resilience enhancement, while the assessment and measurement criteria of GM risk levels for structures isolated by double concave friction pendulum system (DCFPS) remain unclear. Through statistical analysis of the response distribution of DCFPS with various design parameters under 1013 GM records, this study determines an energy dissipation efficacy of 99 %, a floor velocity of 0.35 m/s, a floor velocity of 0.60 m/s, and the displacement capacity of DCFPS as the response criteria for assessing four performance states of efficacy, habitability, functionality, and safety, respectively. In addition, the value of GM intensity in PGA, PGV, PGD, and the equivalent velocity of seismic input energy (V E) for measuring the four GM risk levels corresponding to the four performance states are obtained. Furthermore, a classification of GMs based on earthquake magnitude and fault distance is proposed according to their risk to DCFPS. It is found that the intensity value of each GM risk level varies for different design parameters of DCFPS but fluctuate within a small range, however, great differences exist when using different intensity measures (IM) in classifying GM risk levels. Therefore, based on the correlation between IMs and DCFPS responses, the conservatism of PGA, PGV, PGD and V E in assessing the risk of GMs for DCFPS are evaluated. • Four performance states and corresponding response-based assessment criteria for FPS structures are proposed. • Effect of GM IMs on measuring GM risk levels is clarified. • A statistical analysis method for determining the relations between GM IMs and measures of structural response is proposed. • The value of IMs for measuring GM risk levels are proposed for DCFPS structures with various design parameters. • A classification of GMs using earthquake magnitude and fault distance is proposed based on their risk for DCFPS structures. [ABSTRACT FROM AUTHOR]

Summary: Standardizing response criteria for myelodysplastic syndromes (MDS), a clinically and biologically heterogeneous group of disorders, has been historically challenging. The International Working Group (IWG) response criteria, first proposed in 2000 and modified in 2006 and 2018, represent the best effort by a group of international experts to define a set of clinically meaningful end‐points in MDS. These criteria have been adopted in many MDS clinical trials, allowing for comparisons of response across trials. However, clinical experience has also revealed some limitations of these criteria, and most of the end‐points proposed by the IWG require further validation. In this review, we present a critical analysis of the current MDS response criteria from both a practical standpoint and based on currently available clinical trial data. Potential areas for improvement in the criteria are highlighted, which may be considered in future iterations of the response criteria. [ABSTRACT FROM AUTHOR]

Abstract The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher‐risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first‐line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P

The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years. [ABSTRACT FROM AUTHOR]

The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years.

Background: We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using 3 main classes and a total of 5 subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320., Methods: All patients with at least 1 available MRI before trial inclusion were included. 3D volume was evaluated on consecutive MRI until progression. 2D imaging response was centrally assessed by MRI modified Macdonald criteria. Clinical benefit was defined as neurological or functional status improvement or steroid decrease or discontinuation., Results: Sixteen patients with a median age of 58.5 years were included. Best 3DVGR classes were: 1, 2A, 3A, and 3B in 2 (16.7%), 4 (33.3%), 2 (16.7%), and 4 (33.3%) patients, respectively. All patients with progression-free survival longer than 6 months had best 3DVGR class 1 or 2. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3 (P = .061). All class 1 patients (2/2), 75% of class 2 patients (3/4), and only 10% of class 3 patients (1/10) had clinical benefit., Conclusions: Tumor 3DVGR classification may be helpful to identify early signals of treatment activity in meningioma clinical trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In many recurrent and/or metastatic cancers, the advent of immunotherapy opens up new scenarios of treatment response, with new phenomena, such as pseudoprogression and hyperprogression. Because of this, different immune-related response criteria have been developed, and new therapeutic strategies adopted, such as treatment beyond progression. Moreover, the role of progression-free survival as a surrogate has been questioned, and new surrogate endpoint hypotheses have arisen. A proper understanding of radiological imaging, an assessment of the biological events triggered by therapy, and the clinical evolution of the lesions and of the patient performance status are all factors that should be considered to guide the oncologist’s treatment choice. The primary aim of this article is to discuss how all these concepts apply to recurrent/metastatic head and neck squamous cell carcinoma patients when treated with immunotherapy.

Blindsight is a neuropsychological condition defined by residual visual function following destruction of primary visual cortex. This residual visual function is almost universally held to include capacities for voluntary discrimination in the total absence of awareness. So conceived, blindsight has had an enormous impact on the scientific study of consciousness. It is held to reveal a dramatic disconnect between performance and awareness and used to motivate diverse claims concerning the neural and cognitive basis of consciousness. Here I argue that this orthodox understanding of blindsight is fundamentally mistaken. Drawing on models from signal detection theory in conjunction with a wide range of behavioral and first-person evidence, I contend that blindsight is severely and qualitatively degraded but nonetheless conscious vision, unacknowledged due to conservative response biases. Psychophysical and functional arguments to the contrary are answered. A powerful positive case for the qualitatively degraded conscious vision hypothesis is then presented, detailing a set of distinctive predictions borne out by the data. Such data are further used to address the question of what it is like to have blindsight, as well as to explain the conservative and selectively unstable response criteria exhibited by blindsight subjects. On the view defended, blindsight does not reveal any dissociation between performance and awareness, nor does it speak to the neural or cognitive requirements for consciousness. A foundation stone of consciousness science requires radical reconsideration. [ABSTRACT FROM AUTHOR]

The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher‐risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first‐line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P < 0.001). Among 470 pts treated with hypomethylating agent (HMA) as first‐line therapy, the overall Response Rate, defined as HI or better was 39%. The median OS from time of best response was 21 mo, 8 mo, 14 mo, 12 mo, 13 mo, and 8 mo for CR, mCR, PR, HI, SD, and PD, respectively (P < 0.001). We validated those results in a separate cohort of 539 higher‐risk MDS pts treated at Moffitt Cancer Center who received first‐line HMA therapy, particularly addressing the value of mCR and mCR+HI. mCR alone without HI, SD, and PD outcomes were inferior to CR, PR, mCR+HI, and HI. In conclusion, CR by IWG 2006 response criteria can be used as a surrogate endpoint for OS in higher‐risk MDS pts. Any response associated with restoration of effective hematopoiesis is associated with better outcome. [ABSTRACT FROM AUTHOR]

Objectives: The ACR-EULAR Myositis Response Criteria (Total Improvement Score [TIS]) is a composite measure calculated using changes in myositis core set measures. It is unclear if achieving improvement per TIS reflects improvement in any symptoms of myositis patients. In this study, we examined the association between achieving TIS improvement and patient-centered outcome measures (PCOMs)., Methods: Adults with myositis were enrolled in a prospective study with baseline and 6-month visits. Six core set measures were collected at each visit along with the following PCOMs: Fatigue (visual analogue scale [VAS] and short form 36 [SF36]), pain (VAS, SF36), health-related quality of life (SF-36), physical function (PROMIS-physical function, SF36, sit-to-stand, timed up-and-go, and six-min walk) and physical activity (actigraphy). Mann-Whitney U was used to compare PCOMs between improvement groups. Spearman correlation and regression models were used for correlation and association between TIS and PCOMs, respectively., Results: Of 50 patients (six polymyositis, 24 dermatomyositis, 9 necrotizing myopathy, 11 anti-synthetase syndrome) enrolled (mean age: 52, 60% female), 21 patients satisfied the TIS improvement criteria at 6-months. PCOMs including fatigue, pain, quality of life, physical activity and physical function demonstrated significantly greater improvement in patients who had minimal TIS improvement compared with those with no improvement. Greater PCOM improvements were seen with moderate-major TIS improvement. TIS correlated moderately-strongly with most PCOMs., Conclusion: Achieving improvement criteria was accompanied by significant clinical improvements in fatigue, pain, health-related quality of life, physical function, and physical activity. These results support the use of TIS as a clinically meaningful metric of improvement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study aimed to establish a specified magnetic resonance imaging (MRI) signal and size criterion for assessing the response of desmoid-type fibromatosis (DF). This retrospective study included 129 patients with DF who received non-surgical therapy. All patients underwent pretreatment and 6-month-interval follow-up MRI for >3 years (6 follow-up visits). The correlation between signal grade and size was determined. Signal grade and size among three response groups (partial response [PR], stable disease [SD], progression disease [PD]) were compared. The specified signal and size criterion was established, used to assess tumour response at each follow-up, and compared with the reference. The Response Evaluation Criteria in Solid Tumours (RECIST)1.1 criterion at the end of the 3rd year was considered the reference. MRI signals were moderately correlated with size changes (r = −0.56 and −0.41 for T2 grade and contrast-enhanced T1 grade, respectively). Changes in T2 grade and size in the three response groups were significantly different (all p < 0.01). The signal and size criterion accurately predicted 95% of PR patients at 2nd follow-up and 81.2% of PD patients at the 3rd follow-up, while only 13.1% of PR and 56.3% of PD patients were predicted by RECIST1.1. However, the accuracy of the signal & size criterion for predicting SD was lower than that of RECIST1.1. MRI signal is useful in assessing the response of DF. Signal & size criterion can identify patients with PR and PD earlier than RECIST1.1. • MRI signal correlated moderately with size changes. • MRI signal and size criterion for assessing tumour response of DF was established. • Signal & size criterion can identify PR and PD patients at early follow-ups. [ABSTRACT FROM AUTHOR]

BackgroundNeuroblastoma is an embryonic tumour of the sympathetic nervous system, metastatic in half of the patients at diagnosis, with a high preponderance of osteomedullary disease, making accurate evaluation of metastatic sites and response to therapy challenging. Metaiodobenzylguanidine (mIBG), taken into cells via the norepinephrine transporter, provides a sensitive and specific method of assessing tumour in both soft tissue and bone sites. The goal of this report was to develop consensus guidelines for the use of mIBG scans in staging, response assessment and surveillance in neuroblastoma.MethodsThe International Neuroblastoma Risk Group (INRG) Task Force, including a multidisciplinary group in paediatric oncology of North and South America, Europe, Oceania and Asia, formed a subcommittee on metastatic disease evaluation, including expert nuclear medicine physicians and oncologists, who developed these guidelines based on their experience and the medical literature, with approval by the larger INRG Task Force.ResultsGuidelines for patient preparation, radiotracer administration, techniques of scanning including timing, energy, specific views, and use of single photon emission computed tomography are included. Optimal timing of scans in relation to therapy and for surveillance is reviewed. Validated semi-quantitative scoring methods in current use are reviewed, with recommendations for use in prognosis and response evaluation.ConclusionsMetaiodobenzylguanidine scans are the most sensitive and specific method of staging and response evaluation in neuroblastoma, particularly when used with a semi-quantitative scoring method. Use of the optimal techniques for mIBG in staging and response, including a semi-quantitative score, is essential for evaluation of the efficacy of new therapy.

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Rationale and Objectives: The purpose of the study was to investigate interobserver and intersequence variability in measuring hepatocellular carcinoma on magnetic resonance imaging (MRI).Methods and Materials: Twenty treatment-naïve lesions on Gadoxetic Acid enhanced MRI scans from 20 patients were retrospectively measured by six reviewers with different levels of experience, twice, six weeks apart, on eight different MRI sequences, in randomized order. The sequences include arterial, hepatobiliary, transitional, portal venous, T2, and diffusion weighted images. The single longest diameter (SLD) and longest diameter perpendicular to the longest overall diameter were measured on axial images and products of diameters calculated in accordance to response evaluation criteria in solid tumors v1.1 and World Health Organization response criteria respectively. Lesion-wise intraclass correlation coefficients were used to estimate measurement agreement.Results: All intraclass correlation coefficients were greater than 0.95. No substantive differences between SLD and products of diameters metrics. Means (∼2.8 mm, SLD) and standard deviations (∼2 mm, SLD) were similar across sequences and observers. Similarly, pairwise comparison between observers grouped by experience showed statistically significant differences, but the effect size was minor (∼2 mm). Arterial and HPB-weighted images had similar mean dimensions (2.76 cm) while the smallest mean was in the transitional phase (2.62 cm). A lesion was not measured on 140 occasions (7%), mostly in ADC.Conclusion: There is high interobserver and intersequence reliability despite small differences between observers based on experience level. Our results suggest that accurate measurements can be made on arterial phase despite the possibility of indistinct margins. Lesions, however, are more likely to be missed on diffusion-related sequences. [ABSTRACT FROM AUTHOR]

Purpose: Defining robust criteria for drug activity in preclinical studies allows for fewer animals per treatment group, and potentially allows for inclusion of additional cancer models that more accurately represent genetic diversity and, potentially, allows for tumor sensitivity biomarker identification.Methods: Using a single-mouse design, 32 pediatric xenograft tumor models representing diverse pediatric cancer types [Ewing sarcoma (9), brain (4), rhabdomyosarcoma (10), Wilms tumor (4), and non-CNS rhabdoid tumors (5)] were evaluated for response to a single administration of pegylated-SN38 (PLX038A), a controlled-release PEGylated formulation of SN-38. Endpoints measured were percent tumor regression, and event-free survival (EFS). The correlation between response to PLX038A was compared to that for ten models treated with irinotecan (2.5 mg/kg × 5 days × 2 cycles), using a traditional design (10 mice/group). Correlations between tumor sensitivity, genetic mutations and gene expression were sought. Models showing no disease at week 20 were categorized as 'extreme responders' to PLX038A, whereas those with EFS less than 5 weeks were categorized as 'resistant'.Results: The activity of PLX038A was evaluable in 31/32 models. PLX038A induced > 50% volume regressions in 25 models (78%). Initial tumor volume regression correlated only modestly with EFS (r2 = 0.238), but sensitivity to PLX038A was better correlated with response to irinotecan when one tumor hypersensitive to PLX038A was omitted (r2 = 0.6844). Mutations in 53BP1 were observed in three of six sensitive tumor models compared to none in resistant models (n = 6).Conclusions: This study demonstrates the feasibility of using a single-mouse design for assessing the antitumor activity of an agent, while encompassing greater genetic diversity representative of childhood cancers. PLX038A was highly active in most xenograft models, and tumor sensitivity to PLX038A was correlated with sensitivity to irinotecan, validating the single-mouse design in identifying agents with the same mechanism of action. Biomarkers that correlated with model sensitivity included wild-type TP53, or mutant TP53 but with a mutation in 53BP1, thus a defect in DNA damage response. These results support the value of the single-mouse experimental design. [ABSTRACT FROM AUTHOR]

La valoración de la respuesta a la terapia es una de las indicaciones más complejas de los estudios de imagen. Valorar la respuesta a la terapia de un paciente incluido en un ensayo clínico usualmente está sujeto a unos criterios de respuesta estandarizados para ese contexto. Sin embargo, en la práctica clínica habitual se realizan muchos estudios en los que la pregunta clínica es si el tratamiento que recibe el paciente está siendo o no efectivo. Responder a esta pregunta representa uno de los mayores retos de los especialistas en imagen, especialmente con la introducción de nuevas modalidades de tratamiento, cuyos efectos directos sobre el tejido tumoral son inicialmente poco conocidos. Tenemos un papel esencial en la introducción de nuevas terapias, valorando sus efectos y sus beneficios en las diferentes situaciones clínicas. El conocimiento de estos efectos ha llevado a desarrollar nuevos criterios de respuesta que, a pesar de ser aplicables únicamente en ensayos clínicos, nos ofrecen información de cómo interpretar los hallazgos en la práctica clínica. Therapy response assessment is one of the most challenging indications of imaging studies. In clinical trial patients is usually measured with standardized response criteria. However, in the clinical practice, many studies are carried out in which the clinical question is whether or not the treatment is being effective. Answering this question is one of the greatest challenges for diagnostic imaging physicians, especially when a new treatment modality is being introduced, whose effects on tumoral lesions are firstly poorly understood. We have an essential role in the introduction of new therapies, assessing their effects and benefits. The knowledge of these effects has led to the development of many response criteria that, despite being applicable only in clinical trials, offer us information on how to interpret the findings in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Many methods used to assess the effectiveness of immune checkpoint (programmed death-ligand 1 or cytotoxic T-lymphocyte-associated protein 4) inhibitors for non-small cell lung cancer (NSCLC) are insufficient, as the therapeutic benefit of these agents is often underestimated. Consequently, immune-related evaluation criteria have been developed to better reflect their efficacy. The aim of this consensus was to obtain the opinion of lung cancer experts on the adequacy of immune-response criteria for evaluating the efficacy of these treatments. Methods: Through two rounds of a modified Delphi consensus, 18 Spanish lung cancer experts participated in a 15-item questionnaire regarding the use of immunotherapies for NSCLC and the assessment criteria used to evaluate their effectiveness. Results: Consensus was achieved on 80% of the items in the questionnaire. The panelists agreed that although the Response Evaluation Criteria in Solid Tumors (RECIST) are standard for the evaluation of solid tumors, immune-related response criteria would be useful for measuring the efficacy of immunotherapy. In addition, they considered that an overall survival (OS) rate at 2–5 years is the most useful end point for assessing the benefit of immunotherapy, as clinical benefit may extend beyond the RECIST criteria-defined progression of disease. Conclusions: Although immune-related response criteria have been developed to better evaluate the efficacy of immunotherapy, their use has not been validated and is restricted to investigational applications. However, they may prove to be a useful tool for measuring the efficacy of immunotherapy agents in NSCLC, especially the OS rate at 2–5 years. [ABSTRACT FROM AUTHOR]

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.

The lack of standardized criteria for measuring therapeutic response has been a major obstacle to the development of therapeutic trials in chronic graft-versus-host disease (cGvHD). Nevertheless, recent advances have been made in understanding of the biology and pathophysiology of cGvHD, as well as establishing more precise criteria for the diagnosis and classification of disease manifestations. The momentum has shifted, and currently there is a long list of new potential treatment targets being identified for cGvHD. Consequently, new drugs are being implemented for its prophylaxis and treatment. It is crucial to continue that trend and develop better systems to test new drugs in clinical practice that would eventually translate toward seeking regulatory review and approval. We provide a historical perspective and current challenges in conducting cGvHD clinical trials.

Rationale and Objectives: Analyze the impact of implementing a structured reporting system for primary brain tumors, the Brain Tumor Reporting and Data System, on attitudes toward radiology reports at a single institution.Materials and Methods: Following Institutional Review Board approval, an initial 22 question, 5 point (1-worst to 5-best), survey was sent to faculty members, house staff members, and nonphysician providers at our institution who participate in the direct care of brain tumor patients. Results were used to develop a structured reporting strategy for brain tumors which was implemented across an entire neuroradiology section in a staged approach. Nine months following structured reporting implementation, a follow-up 27 question survey was sent to the same group of providers. Keyword search of radiology reports was used to assess usage of Brain Tumor Reporting and Data System over time.Results: Fifty-three brain tumor care providers responded to the initial survey and 38 to the follow-up survey. After implementing BT-RADS, respondents reported improved attitudes across multiple areas including: report consistency (4.3 vs. 3.4; p < 0.001), report ambiguity (4.2 vs. 3.2, p < 0.001), radiologist/physician communication (4.5 vs. 3.8; p < 0.001), facilitation of patient management (4.2 vs. 3.6; p = 0.003), and confidence in reports (4.3 vs. 3.5; p < 0.001). Providers were more satisfied with the BT-RADS structured reporting system (4.3 vs. 3.7; p = 0.04). Use of the reporting template progressively increased with 81% of brain tumor reports dictated using the new template by 9 months.Conclusion: Implementing a structured template for brain tumor imaging improves perception of radiology reports among radiologists and referring providers involved in the care of brain tumor patients. [ABSTRACT FROM AUTHOR]

According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described. [ABSTRACT FROM AUTHOR]

Abstract Aim We seek to characterize how faster tumour shrinkage rate (k) can lead to paradoxically shorter Response Evaluation Criteria in Solid Tumors (RECIST) time to progression ('TTP20' – tumour size exceeding its minimum by 5 mm and 20%) [1] and, therefore, progression-free survival (PFS). Specifically, we investigate under what conditions this paradoxical behaviour occurs, what fraction of patients satisfy these conditions, whether this phenomenon can invert population-level PFS hazard ratio, and consistency of an alternative time-to-event benefit metric with k. Methods We use a mathematical model treating tumour burden as decreasing drug-sensitive and increasing drug-resistant cell subpopulations. We fit this model to data from several clinical trials with different indications [2]. We simulated a more effective treatment and recorded whether patients' TTP20 increased or decreased. We performed a study-level analysis to compare the relationship of speed and depth of response with TTP20 for both the administered 'control' and simulated 'more effective' drug. We propose and test an alternative benefit metric: the model-projected time that tumour size reaches 120% of baseline (TTB120). Results Depending on indication, 3–27% of patients are estimated to have a paradoxically inverse relationship between k and TTP20. Simulated head-to-head studies show that TTP20-based PFS can favour the less effective drug. In contrast, TTB120 always favours the more effective drug. Conclusion We demonstrate the paradoxical behaviour of RECIST TTP20 – as an exemplar of percent-change-from-nadir based cancer progression criterion – both in theory and in observed patient data at the individual and trial level. We propose an alternative tumour size–based criterion (TTB120) that is directionally consistent with tumour shrinkage rate. Highlights • A Response Evaluation Criteria in Solid Tumors (RECIST) time to progression (TTP) criterion is tumour size exceeding 120% of its minimum. • A simple mathematical model well describes tumour response and relapse in treated patients. • Increasing tumour shrinkage rate in this model often leads to paradoxically shorter TTP. • This effect is large and frequent enough to invert population-level TTP-based outcomes. • We propose an alternative time to event metric that is consistent with shrinkage rate. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

The gut is the largest organ that helps with the immune function. Gut health, especially in young pigs has a significant benefit to health and performance. In an attempt to maintain and enhance intestinal health in pigs and improve productivity in the absence of in-feed antibiotics, researchers have evaluated a wide range of feed additives. Some of these additives such as zinc oxide, copper sulphate, egg yolk antibodies, mannan-oligosaccharides and spray dried porcine plasma and their effectiveness are discussed in this review. One approach to evaluate the effectiveness of these additives in vivo is to use an appropriate disease challenge model. Over the years, researchers have used a number of challenge models which include the use of specific strains of enterotoxigenic Escherichia coli, bacteria lipopolysaccharide challenge, oral challenge with Salmonella enteric serotype Typhimurium, sanitation challenge, and Lawsonia intercellularis challenge. These challenge models together with the criteria used to evaluate the responses of the animals to them are also discussed in this review.

We evaluated tumor response at Computed Tomography (CT) according to three radiologic criteria: RECIST 1.1, CHOI and tumor volume in 34 patients with metastatic adrenocortical carcinoma (ACC) submitted to standard chemotherapy. These three criteria agreed in defining partial response, stable or progressive disease in 24 patients (70.5%). Partial response (PR) was observed in 29.4%, 29.4% and 41.2% of patients according to RECIST 1.1, CHOI and tumor volume, respectively. It was associated with a favorable prognosis, regardless of the criterion adopted. The concordance of all the 3 criteria in defining the disease response identified 8 patients (23.5%) which displayed a very good prognosis: median progression free survival (PFS) and overall survival (OS) 14.9 and 37.7 months, respectively. Seven patients (20.6%) with PR assessed by one or two criteria, however, still had a better prognosis than non-responding patients, both in terms of PFS: median 12.3 versus 9.9 months and OS: 21 versus 12.2, respectively. In conclusions, the CT assessment of disease response of ACC patients to chemotherapy with 3 different criteria is feasible and allows the identification of a patient subset with a more favorable outcome. PR with at least one criterion can be useful to early identify patients that deserve continuing the therapy.