BACKGROUND: There is growing interest in the development and application of standardized imaging criteria (SIC), to minimize variability and improve the reproducibility of image interpretation in head and neck squamous cell carcinoma (HNSCC).
METHODS: \"Squamous cell carcinoma\" AND \"standardized interpretation criteria\" OR \"radiographic response assessment\" were searched using PubMed and Google Scholar for articles published between 2009 and 2024, returning 56 publications. After abstract review, 18 were selected for further evaluation, and 6 different SICs (i.e., PERCIST, Porceddu, Hopkins, NI-RADS, modified Deauville, and Cuneo) were included in this review. Each SIC is evaluated in the context of 8 desired traits of a standardized reporting system.
RESULTS: Two SICs have societal endorsements (i.e., PERCIST, NI-RADS); four can be used in the evaluation of locoregional and systemic disease (i.e., PERCIST, Hopkins, NI-RADS, Cuneo), and four have specific categories for equivocal imaging results (i.e., Porceddu, NI-RADS, modified Deauville, and Cuneo). All demonstrated areas for future improvement in the context of the 8 desired traits.
CONCLUSIONS: Multiple SICs have been developed for and demonstrated value in HNSCC post-treatment imaging; however, these systems remain underutilized. Selecting an SIC with features that best match the needs of one\'s practice is expected to maximize the likelihood of successful implementation.

BACKGROUND: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.
METHODS: Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs).
RESULTS: A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities.
CONCLUSIONS: In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).

Immunotherapy using immune checkpoint inhibitors (ICIs) is a breakthrough in oncology development and has been applied to multiple solid tumors. However, unlike traditional cancer treatment approaches, immune checkpoint inhibitors (ICIs) initiate indirect cytotoxicity by generating inflammation, which causes enlargement of the lesion in some cases. Therefore, rather than declaring progressive disease (PD) immediately, confirmation upon follow-up radiological evaluation after four-eight weeks is suggested according to immune-related Response Evaluation Criteria in Solid Tumors (ir-RECIST). Given the difficulty for clinicians to immediately distinguish pseudoprogression from true disease progression, we need novel tools to assist in this field. Radiomics, an innovative data analysis technique that quantifies tumor characteristics through high-throughput extraction of quantitative features from images, can enable the detection of additional information from early imaging. This review will summarize the recent advances in radiomics concerning immunotherapy. Notably, we will discuss the potential of applying radiomics to differentiate pseudoprogression from PD to avoid condition exacerbation during confirmatory periods. We also review the applications of radiomics in hyperprogression, immune-related biomarkers, efficacy, and immune-related adverse events (irAEs). We found that radiomics has shown promising results in precision cancer immunotherapy with early detection in noninvasive ways.

OBJECTIVE: Activity estimates should be accurately evaluated in phase 2 clinical trials to ensure appropriate decisions about proceeding to phase 3 trials. RECIST v1.1. progression-free survival (PFS) is a common endpoint in oncology; however, it can be influenced by assessment criteria and trial design. We assessed the value of central adjudication of investigator-assessed PFS times of participants in a double-blind, randomised phase 2 trial evaluating regorafenib versus placebo in advanced gastro-oesophageal cancer (AGITG INTEGRATE) to inform plans for central review in future trials.
METHODS: We calculated the proportion of participants with a disagreement between the site investigator assessment and blinded independent central review and in whom central review resulted in a change, then evaluated the effect of central review on study conclusions by comparing hazard ratios (HRs) for PFS based on site review versus central review. Post-progression unblinding was assessed with similar methods. Simulation studies explored the effect of differential and non-differential measurement error on treatment effect estimation and study power.
RESULTS: Disagreements between site assessments versus central review occurred in 8/147 (5.4%) participants, 5 resulting in amended date of progression (3.4%). PFS HRs (sites vs central review progression dates) were similar (0.39 vs 0.40). RECIST progression occurred in 82/86 (95%) of cases where post-progression unblinding was requested by the site investigator.
CONCLUSIONS: Blinded independent central review was feasible and supported the reliability of site assessments, trial results, and conclusions. Modelling showed that when treatment effects were large and outcome assessments blinded, central review was unlikely to affect conclusions.

Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to evaluate efficacy after molecular targeted therapies in hepatocellular carcinoma (HCC) patients is still controversial. A systemic review was performed to compare the objective response rate (ORR) and disease control rate (DCR) and a meta-analysis was conducted to compare the correlation between objective response and overall survival (OS).
Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach.
EMBASE, PubMed, Web of Science and Cochrane Library were searched through 31 December 2021.
We included studies assessing the efficacy of molecular targeted therapy for HCC according to both RECIST 1.1 and mRECIST.
Two investigators extracted data independently. The consistency between RECIST 1.1 vs mRECIST is measured by the k coefficient. HRs with corresponding 95% CIs were used for meta-analysis.
23 studies comprising 2574 patients were included in systematic review. The ORR according to mRECIST is higher than RECIST1.1 (15.9% vs 7.8%, p<0.001). The DCR is similar (68.4% vs 67.2%, p=0.5). The agreement of tumour response is moderate for objective response (k=0.499) and perfect for progressive disease (k=0.901), calculated from 8 studies including 372 patients. OS was significantly longer in response group than non-response group according to mRECIST (HR 0.56, 95% CI 0.41 to 0.78, p=0.0004) calculated from 7 studies including 566 patients, however, the RECIST1.1 could not distinguish the OS well (HR 0.68, 95% CI 0.44 to 1.05, p=0.08). Subgroup analusis by type of treatment was conducted.
mRECIST may be more accurate than RECIST 1.1 in assessing ORR after molecular targeted therapies in HCC patients and can better assess the prognosis. However, the performance of both criteria in assessing disease progression is identical.
CRD42020200895.
Ethics approval is not required in this meta-analysis.

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.

Although objective response rate and disease control rate are commonly used as primary endpoints of lung cancer trials, it remains unclear whether objective response rate and disease control rate correctly reflect the overall survival in a non-small cell lung cancer phase II trial evaluating a non-first-line chemotherapy. Objective response rate might be easily affected by chance because the small number of patients in each trial achieved complete or partial response in the phase II non-first-line setting. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (UMIN000040412). Four databases were searched for eligible trials. A Spearman\'s rank correlation with hazard ratio of overall survival was calculated each for odds ratio of objective response rate, difference of objective response rate (%), odds ratio of disease control rate, and difference of disease control rate (%). Of 74 eligible trials, 73 reported objective response rate and 68 reported disease control rates. Nine (12%) trials included patients with driver mutation status. Thirteen (18%) and two (3%) RCTs specifically included adenocarcinoma/non-squamous and squamous subtype of non-small cell lung cancer, respectively. The Eastern Cooperative Oncology Group performance status 0-2 (N=41, 55%) and the performance status 0-1 (N=25, 34%) were frequently used performance status criteria. The median number of patients in the two arms was 116 (interquartile range, 82-159). The correlation between trial-level odds ratio of objective response rate and hazard ratio of overall survival was weak (r=-0.29, 95% CI: -0.49 to -0.05, P=0.014). An exploratory subgroup analysis suggested that fewer responders were associated with poorer correlation. Odds ratio of disease control survival (r=-0.53, 95% CI: -0.68 to -0.32, P<0.001) had moderate rank correlations with hazard ratio of overall survival. Instead of objective response rate, disease control rate should be used as the primary endpoint in a randomized phase II trial evaluating non-first-line chemotherapy for non-small cell lung cancer.

BACKGROUND: The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib.
METHODS: We described a 55-year-old man with good performance status (PS).
METHODS: He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018.
METHODS: He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib.
RESULTS: It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable.
CONCLUSIONS: This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.

OBJECTIVE: There is increasing adoption of Liver Imaging Reporting and Data System (LI-RADS) treatment response (LR-TR) criteria. However, there is still a relative lack of evidence evaluating the performance of these criteria. We performed this study to assess the diagnostic accuracy of LI-RADS LR-TR criteria.
METHODS: A thorough search of PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials for studies reporting diagnostic accuracy of LI-RADS LR-TR criteria was conducted through 30 June 2020. The meta-analytic summary of sensitivity, specificity, and diagnostic odds ratio of LI-RADS LR-TR criteria was computed using explant histopathology as the reference standard. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.
RESULTS: Four studies were found eligible for meta-analysis. The total number of LR-TR observations was 462 (240 patients, 82.5% males). Different locoregional therapies (LRTs), including bland embolization, chemoembolization, radiofrequency ablation, and microwave ablation, had been used. The mean time interval between LRT and liver transplantation ranged from 181 to 219 days. There was a moderate to good inter-reader agreement for LR-TR criteria. The pooled sensitivity and specificity of LR-TR criteria for viable disease were 62% (95% CI, 49-74%; I2 = 69%) and 87% (95% CI, 76-93%; I2 = 57%), respectively. The pooled diagnostic odds ratio and area under the curve were 9.83 (95% CI, 5.34-18.08; I2 = 19%) and 0.80.
CONCLUSIONS: LI-RADS LR-TR criteria have acceptable diagnostic performance for the diagnosis of viable tumor after LRT. Well-designed prospective studies evaluating criteria of equivocal lesions and effect of different LRTs should be performed.
CONCLUSIONS: • The pooled sensitivity and specificity of LI-RADS LR-TR criteria for the diagnosis of viable tumor were 62% and 87%, respectively. • The pooled diagnostic odds ratio and area under the curve were 9.83 and 0.80. • LR-TR criteria had a moderate to good inter-reader agreement.

Optimal Phase-II design to evaluate new therapies in refractory/relapsed Ewing sarcomas (ES) remains imperfectly defined.
Recurrent/refractory ES phase-I/II trials analysis to improve trials design.
Comprehensive review of therapeutic trials registered on five databases (who.int/trialsearch, clinicaltrials.gov, clinicaltrialsregister.eu, e-cancer.fr, and umin.ac.jp) and/or published in PubMed/ASCO/ESMO websites, between 2005 and 2018, using the criterion: (Ewing sarcoma OR bone sarcoma OR sarcoma) AND (Phase-I or Phase-II).
The 146 trials identified (77 phase-I/II, 67 phase-II, and 2 phase-II/III) tested targeted (34%), chemo- (23%), immune therapies (19%), or combined therapies (24%). Twenty-three trials were ES specific and 48 had a specific ES stratum. Usually multicentric (88%), few trials were international (30%). Inclusion criteria cover the recurrent ES age range for only 12% of trials and allowed only accrual of measurable diseases (RECIST criteria). Single-arm design was the most frequent (88%) testing mainly single drugs (61%), only 5% were randomized. Primary efficacy outcome was response rate (RR=CR+PR; Complete+Partial response) (n = 116/146; 79%), rarely progression-free or overall survival (16% PFS and 3% OS). H0 and H1 hypotheses were variable (3%-25% and 20%-50%, respectively). The 62 published trials enrolled 827 ES patients. RR was poor (10%; 15 CR=1.7%, 68 PR=8.3%). Stable disease was the best response for 186 patients (25%). Median PFS/OS was of 1.9 (range 1.3-14.7) and 7.6 months (5-30), respectively. Eleven (18%) published trials were considered positive, with median RR/PFS/OS of 15% (7%-30%), 4.5 (1.3-10), and 16.6 months (6.9-30), respectively.
This review supports the need to develop the international randomized phase-II trials across all age ranges with PFS as primary endpoint.