Fluorine-18 FDG PET/CT and New NIMS Grading System for Chemotherapy Response in Breast Cancer.

Background: Positron emission tomography with computed tomography (PET-CT) using fluorine 18-fluorodeoxyglucose (F-18 FDG) is increasingly used to stage patients with locally advanced breast cancer and for assessing treatment response after neoadjuvant chemotherapy (NACT). Aims and Objectives: The aim of the study was to assess the correlation between PET-CT parameters and pathologic response of breast primary after NACT in breast cancer patients and to devise a grading system called NIMS grading system for response assessment using PET quantitative parameters. Materials and Methods: 55 patients who underwent F-18 FDG PET-CT before starting the therapy and again after completion of therapy were identified and included in the study. The clinical data and the histopathologic findings were recorded. All the patients received chemotherapy followed by surgery with axillary lymph node dissection. The PET-CT results were interpreted both qualitatively by visual analysis and quantitatively by estimating maximum Standardized uptake values(SUVmax) and other parameters - SUVmean, SUL, SUVBSA, Metabolic tumor volume (MTV) and Total lesion glycolysis (TLG). Results: The sensitivity and specificity of F-18 FDG PET-CT to detect the residual disease after neoadjuvant chemotherapy was 75.6% & 92.8% respectively. Differences between complete response and residual disease were significant for ΔSUVmax(p=0.005), ΔSUVmean(p=0.006), ΔSUL (0.005) and ΔSUVBSA(0.004), while ΔMTV and ΔTLG were not significantly different between the two groups. The new NIMS grading system included scoring of ΔSUVmax, ΔSUVBSA, ΔTLG and ΔMTV on scale of 1 to 4 and correlated well with PERCIST criteria. Conclusion: F-18 FDG PET-CT had a good accuracy in the detection of residual disease after completion of NACT. Pre chemotherapy PET-CT is not adequate to predict the response of primary tumour to chemotherapy. However, changes in the values of various PET-CT parameters are a sensitive tool to assess the response to chemotherapy. The new grading system is easy to use and showed good correlation to PERCIST.

Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: a retrospective observational cohort study.

Background: The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT). Results: 198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2-10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85-4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21-0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03-0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13-0.72, p=0.007) were associated with decreased likelihood of response. Conclusion: No significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings.

Deciphering Tumor Response: The Role of Fluoro-18-d-Glucose Uptake in Evaluating Targeted Therapies with Tyrosine Kinase Inhibitors.

Background/Objectives: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented. Thus, our research aimed to explore the potential impact of various TKIs of GLUT-1 on the standard [18F]FDG-PET monitoring of tumor response in patients. Methods: To achieve this, we conducted an analysis on three patients who were undergoing treatment with different TKIs and harbored actionable alterations. Alongside the assessment of FDG data (including SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV)), we also examined the changes in tumor sizes through follow-up [18F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. Results: Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. Conclusions: These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [18F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy.

FGD-PET/CT three months after (chemo)radiotherapy for head and neck squamous cell carcinoma spares considerable number of patients from a salvage neck dissection.

PURPOSE: In the last decades FDG-PET/CT is increasingly used in combination with the standard diagnostic modalities (MRI + US-FNA) to identify residual neck disease (RND) after (chemo)radiotherapy for head-and-neck squamous cell carcinoma (HNSCC). The purpose of the current study is to identify the impact of increasing use of FDG-PET/CT on the accuracy of patient selection for salvage neck dissection (SND). MATERIALS AND METHODS: Between 2008 and 2022, 908 consecutive patients with node-positive HNSCC were treated with (chemo)radiotherapy in our institution. PRIMARY ENDPOINT: positive predictive value (PPV) of FDG-PET/CT for pathologic-confirmed RND (pRND) after SND, compared to the standard of care; MRI + US-FNA. Secondary endpoints: oncologic outcomes. RESULTS: Of the entire group, 130 patients (14 %) received SND. Of them only 53 patients (41 %) had pRND at the SND-specimens. The PPV of FDG-PET/CT for the detection of pRND was considerably better, compared to MRI + US-FNA; 89 % and 65 %, respectively. If FDG-PET/CT showed metabolic CR, these patients did not undergo SND. The NPV was 97.5 %, as only 2.5 % of these patients developed delayed regional failure. FDG-PET/CT considerably improved the accuracy of patient selection for SND, as significantly more patients treated in the second period, compared to first period of the study (n = 454 each) still had vital tumor at SND-specimen (53 % and 31 %, p = 0.008). Regional recurrence free-survival, DFS, OS and HNSCC-death were significantly worse in patients with pRND (p < 0.05) CONCLUSIONS: Incorporating FDG-PET/CT into the diagnostic pathway for the response evaluation after (chemo)radiotherapy significantly improved the accuracy of patient selection for SND and spared considerable number of patients (>20 %) from unnecessary SND. For patients with metabolic CR, SND can safely be omitted while for patients with no metabolic CR, SND is strongly advocated.

Using three-dimensional model-based tumour volume change to predict the symptom improvement in patients with renal cell cancer.

In our recent study, we explored the efficacy of three-dimensional (3D) measurement of tumor volume in predicting the improvement of quality of life (QoL) in patients suffering from renal cell cancer (RCC), who were treated with axitinib and anti-PD-L1 antibodies. This study encompassed 18 RCC patients, including 10 men and 8 women, with an average age of 56.83 ± 9.94 years. By utilizing 3D Slicer software, we analyzed pre- and post-treatment CT scans to assess changes in tumor volume. Patients' QoL was evaluated through the FKSI-DRS questionnaire. Our findings revealed that 3D models for all patients were successfully created, and there was a moderate agreement between treatment response classifications based on RECIST 1.1 criteria and volumetric analysis (kappa = 0.556, p = 0.001). Notably, nine patients reported a clinically meaningful improvement in QoL following the treatment. Interestingly, the change in tumor volume as indicated by the 3D model showed a higher area under the curve in predicting QoL improvement compared to the change in diameter measured by CT, although this difference was not statistically significant (z = 0.593, p = 0.553). Furthermore, a multivariable analysis identified the change in tumor volume based on the 3D model as an independent predictor of QoL improvement (odds ratio = 1.073, 95% CI 1.002-1.149, p = 0.045).In conclusion, our study suggests that the change in tumor volume measured by a 3D model may be a more effective predictor of symptom improvement in RCC patients than traditional CT-based diameter measurements. This offers a novel approach for assessing treatment response and patient well-being, presenting a significant advancement in the field of RCC treatment.

Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial.

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.

Neoadjuvant treatment of pancreatic ductal adenocarcinoma: Whom, when and how.

Pancreatic ductal adenocarcinoma (PDAC), which is notorious for its aggressiveness and poor prognosis, remains an area of great unmet medical need, with a 5-year survival rate of 10% - the lowest of all solid tumours. At diagnosis, only 20% of patients have resectable pancreatic cancer (RPC) or borderline RPC (BRPC) disease, while 80% of patients have unresectable tumours that are locally advanced pancreatic cancer (LAPC) or have distant metastases. Nearly 60% of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy (CHT) because of postoperative complications and early cancer recurrence. An important paradigm shift to achieve better outcomes has been the sequence of therapy, with neoadjuvant CHT preceding surgery. Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers: RPC, BRPC, and LAPC. The main goal of neoadjuvant treatment (NAT) is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT, reducing tumour volume before surgery to improve the rate of margin-negative resection (R0 resection, a microscopic margin-negative resection), reducing the rate of positive lymph node occurrence at surgery, providing early treatment of occult micrometastatic disease, and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria. In this editorial, we summarize evidence concerning NAT of PDAC, providing insights into future practice and study design. Future research is needed to establish predictive biomarkers, measures of therapeutic response, and multidisciplinary strategies to improve patient-centered outcomes.

RECIP 1.0 Predicts Progression-Free Survival After [177Lu]Lu-PSMA Radiopharmaceutical Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Response Evaluation Criteria in Prostate-Specific Membrane Antigen Imaging (RECIP) 1.0 is an evidence-based framework to evaluate therapeutic efficacy in metastatic prostate cancer using prostate-specific membrane antigen (PSMA) PET/CT. This study aimed to evaluate the associations of interim PSMA PET/CT by RECIP 1.0 with short-term outcome after radiopharmaceutical treatment. Methods: This multicenter retrospective study included patients with metastatic castration-resistant prostate cancer who underwent [177Lu]Lu-PSMA radiopharmaceutical therapy at 3 academic centers and received PSMA PET/CT at baseline and at 12 wk. Pairs of PSMA PET/CT images were assessed by 5 readers for visual RECIP 1.0. The primary outcome was the association of RECIP with prostate-specific antigen progression-free survival (PSA-PFS) by Kaplan-Meier analysis. Results: In total, 124 of 287 screened patients met the inclusion criteria, with 0 (0%), 29 (23%), 54 (44%), and 41 (33%) of those 124 patients having complete response, partial response, stable disease, or progressive disease (PD) by visual RECIP 1.0, respectively. Patients with visual RECIP PD had a significantly shorter PSA-PFS than those with RECIP stable disease or with RECIP partial response (2.6 vs. 6.4 vs. 8.4 mo; P < 0.001). The median PSA-PFS among patients with RECIP PD versus those with non-RECIP PD was 2.6 versus 7.2 mo (hazard ratio, 13.0; 95% CI, 7.0-24.1; P < 0.001). Conclusion: PSMA PET/CT by RECIP 1.0 after 2 cycles of [177Lu]Lu-PSMA is prognostic for PSA-PFS. PSMA PET/CT by RECIP 1.0 may be used in earlier stages of prostate cancer to evaluate drug efficacy and to predict progression-free survival.

Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma.

OBJECTIVES: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). METHODS: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. CONCLUSION: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.

Intracranial response pattern, tolerability and biomarkers associated with brain metastases in non-small cell lung cancer treated by tislelizumab plus chemotherapy.

Background: Programmed cell death protein-1/programmed cell death protein-ligand 1 (PD-1/PD-L1) inhibitor and chemotherapy are the standard treatment for advanced non-small cell lung cancer (NSCLC) without sensitizing mutations. However, patients with untreated, symptomatic or recently-irradiated brain metastases (BMs) are mostly excluded from immunochemotherapy trials. This study aims to evaluate the intracranial response pattern, tolerability and biomarkers of tislelizumab plus chemotherapy in NSCLC with untreated, symptomatic or recently-irradiated BM. Methods: This multicenter, single-arm, phase 2 trial enrolled patients with treatment-naïve, brain-metastasized NSCLC. BM could be untreated or irradiated. Symptomatic or recently-irradiated BMs that were deemed clinically stable were allowed. Patients received tislelizumab (200 mg) plus pemetrexed (500 mg/m2) and carboplatin (AUC =5) on day 1 every 3 weeks for 4 cycles, followed by maintenance with tislelizumab plus pemetrexed. Primary endpoint was 1-year progression-free survival (PFS) rate. Secondary endpoints included intracranial efficacy and tolerability. PD-L1 expression, tumor mutational burden (TMB) and genomic alterations were evaluated as potential biomarkers. Results: A total of 36 patients were enrolled, 19.2% had prior brain radiotherapy, 8.3% had symptomatic BMs that required corticosteroids ≤10 mg/d or antiepileptics. Confirmed systemic and intracranial ORR (iORR) was 43.8% and 46.7%, respectively. One-year systematic PFS rate and One-year iPFS rate was 36.8% and 55.8%, respectively. About 41.7% patients had neurological adverse events, 90% patients had concordant intracranial-extracranial responses. No intracranial pseudoprogression or hyperprogression occurred. Patients with prior brain radiation trended towards higher systemic (83.3% vs. 34.6%) and iORR (75.0% vs. 42.3%). Similar intracranial efficacy was observed in tumors with different PD-L1 and TMB levels, while alterations in cytokine receptors pathway predicted higher iORR (P=0.081), prolonged systematic PFS [hazard ratio (HR) =0.16, P=0.021] and overall survival (OS) (HR =0.71, P=0.029). Conclusions: Untreated or irradiated BMs in NSCLC follows a conventional response and progression pattern under immunochemotherapy with altered cytokine receptors pathway being a potential biomarker for systemic and intracranial outcomes.

Is Ki-67 Really Useful as a Predictor for Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer?

Neoadjuvant chemotherapy (NACT) is routinely offered to operable locally advanced breast cancer (LABC) patients desirous of breast conservation surgery and inoperable LABC patients. Pathological complete response (pCR) following chemotherapy is recognized as a surrogate for survival outcomes in high grade tumour subtypes. Many biological and tumor characters have been shown to predict pCR. The current study was performed with the aim of investigating the ability of Ki-67 in predicting pCR with NACT in breast cancer patients. A total of 105 patients with locally advanced breast cancer who completed NACT followed by surgery were included in this study from January 2020 till December 2022. Patients with advanced metastatic breast carcinoma, who did not give consent for NACT, who did not complete NACT and who did not undergo surgery were excluded. All patients were assessed for Ki-67 score on core-needle biopsy samples and response rate was assessed clinically and by histopathological examination of resected specimen. Quantitative variables were compared using unpaired t-test or Mann-Whitney 'U' test and for categorical variables Chi-square or Fisher's exact test were used. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive potential of Ki-67 expression levels in predicting pCR. To identify the predictive factors associated with pCR, univariate analysis was performed. The P value < 0.05 was considered as statistically significant. Mean age was 51.57 ± 10.8 years. 51 patients achieved clinical complete response (cCR) and 33 achieved pCR after NACT. Mean Ki-67 index in overall study population, in pCR group and no pCR group was 46.44 ± 22.92%, 51.60 ± 22.3% and 44.06 ± 22.7%, respectively. On univariate analysis, ER negativity, PR negativity and Her 2neu positivity were found predictive of pCR. On subgroup analysis, TNBC and Her 2neu positive sub groups were associated with higher cCR and pCR rate. We found no significant association between Ki-67 and pCR. This result may be confounded by the fact that a significant duration of the study was in the COVID-19 pandemic. Validation of this data is required in a large prospective study.

Associations of concomitant medications with immune-related adverse events and survival in advanced cancers treated with immune checkpoint inhibitors: a comprehensive pan-cancer analysis.

BACKGROUND: While concomitant medications can affect the efficacy of immune checkpoint inhibitors (ICIs), few studies have assessed associations of concomitant medications with the occurrence and profile of immune-related adverse events (irAEs). METHODS: This study assessed associations of concomitant medication (antibiotics/proton pump inhibitors (PPIs)/corticosteroids)-based risk model termed the "drug score" with survival and the occurrence and profile of irAEs in 851 patients with advanced cancer treated with ICIs (with or without other agents). The study also assessed the survival impact of the occurrence of irAEs, using a landmark analysis to minimize immortal time bias. Multivariable Cox proportional hazard analyses were conducted for progression-free survival (PFS) and overall survival (OS). RESULTS: The drug score classified patients into three risk groups, with significantly different PFS and OS. Notably, the score's predictive capability was better in patients treated with ICIs only than in those treated with ICIs plus other agents. The landmark analysis showed that patients who developed irAEs had significantly longer PFS and OS than those without irAEs. Generally, concomitant medications were negatively associated with the occurrence of irAEs, especially endocrine irAEs, whereas PPI use was positively associated with gastrointestinal irAEs, as an exception. CONCLUSIONS: Using a large pan-cancer cohort, the prognostic ability of the drug score was validated, as well as that of the occurrence of irAEs. The negative association between concomitant medications and irAE occurrence could be an indirect measure of the detrimental effect on the immune system induced by one or more concomitant drugs.

Optimal cut-off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy.

BACKGROUND: We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). METHODS: According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan-Meier curves and log-rank tests. RESULTS: Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. CONCLUSIONS: With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

Papel de la imagen de movimiento incoherente intravóxel (IVIM) en la evaluación de la respuesta del carcinoma hepatocelular después de la quimioembolización transarterial (TACE): un estudio prospectivo / Role of intravoxel incoherent motion (IVIM) imaging in response assessment of hepatocellular carcinoma after transarterial chemoembolization (TACE): a prospective study

Introducción: La evaluación de la respuesta del carcinoma hepatocelular (CHC) se basa actualmente en el realce en la fase arterial, que no tiene en cuenta los cambios microestructurales en el tumor después de la quimioembolización transarterial (TACE). Objetivo: Este estudio prospectivo se llevó a cabo para evaluar la viabilidad y la eficacia de la imagen de movimiento incoherente intravóxel (IVIM) en la evaluación de la respuesta de CHC después de TACE. A 39 pacientes cirróticos con 48 CHC se les realizó una resonancia magnética (RM) 1 semana antes y 6 semanas después de la TACE. Se midieron parámetros IVIM como Dlenta (difusión verdadera), Drápida (seudodifusión), la fracción de perfusión y el ADC antes y después de la TACE. Los valores antes y después de la TACE en las lesiones LR-TR no viables y viables según la clasificación LI-RADS de categorías de respuesta al tratamiento se compararon mediante pruebas t emparejadas. Se realizó un análisis de la curva ROC para calcular la sensibilidad y la especificidad y proponer valores de corte.Resultado: Las lesiones no viables mostraron un aumento significativo de la Dlenta (1,208±0,581 frente a 1,560±0,494, valor de p=–0,0207) y de ADC (1,37±0,53 frente a 1,65±0,4287, valor de p=–0,016) después de la TACE. También se observó una disminución significativa de los valores de Drápida (33,7±10,4 frente a 23,75±12,13, valor de p=0,0005) y f (19,92±10,54 frente a 12,9±10,41, valor de p=0,012) después de la TACE en las lesiones no viables en comparación con las viables. El cambio en la difusión verdadera tuvo el mayor AUC (0,741) entre los parámetros IVIM, con un aumento superior a 0,075 entre los valores previos y posteriores a la TACE, con una sensibilidad y especificidad del 81,8 y el 60%, respectivamente, para la respuesta completa. Conclusión: La IVIM es factible para evaluar la respuesta en el CHC después de la TACE. La difusión verdadera es más sensible y específica que la difusión aparente para...(AU)

Introduction: Response evaluation of hepatocellular carcinoma (HCC) currently is based on arterial phase enhancement which doesn’t take into microstructural changes in the tumor after trans-arterial chemoembolization (TACE). Aim: This prospective study was conducted to assess the feasibility and efficacy of intravoxel incoherent motion imaging (IVIM) in response evaluation of HCC after TACE. 39 cirrhotic patients with 48 HCC underwent MR imaging 1 week within and 6weeks after TACE. IVIM parameters like Dslow (true diffusion), Dfast (pseudodiffusion), perfusion fraction and ADC were measured prior to and postTACE. The pre and postTACE values in LR-TR (LIRADS-treatment response) nonviable and viable lesions were compared using paired t-tests. ROC curve analysis was done to calculate sensitivity and specificity and propose cut-off values. Result: Non-viable lesions showed a significant increase in Dslow (1.208±0.581 vs. 1.560±0.494, p-value –0.0207) and ADC (1.37±0.53 vs. 1.65±0.4287, p-value 0.016) after TACE. There was also significant decrease in Dfast (33.7±10.4 vs. 23.75±12.13, p-value 0.0005) and f (19.92±10.54 vs. 12.9±10.41, p-value 0.012) values after TACE in non-viable lesions compared to viable lesions. The change in true diffusion had the highest AUC (0.741) among IVIM parameters with greater than 0.075 increase between preTACE and postTACE values having a sensitivity and specificity of 81.8% and 60% respectively for complete response. Conclusion: IVIM imaging is feasible to assess the response in HCC after TACE. True diffusion is more sensitive and specific than apparent diffusion in evaluating the response.(AU)

Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis.

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).

Role of intravoxel incoherent motion (IVIM) imaging in response assessment of hepatocellular carcinoma after transarterial chemoembolization (TACE) - A prospective study.

INTRODUCTION: Response evaluation of hepatocellular carcinoma (HCC) currently is based on arterial phase enhancement which doesn't take into microstructural changes in the tumor after trans-arterial chemoembolization (TACE). AIM: This prospective study was conducted to assess the feasibility and efficacy of intravascular incoherent motion imaging (IVIM) in response evaluation of HCC after TACE. 39 cirrhotic patients with 48 HCC underwent MR imaging 1 week within and 6weeks after TACE. IVIM parameters like Dslow (true diffusion), Dfast (pseudodiffusion), perfusion fraction and ADC were measured prior to and postTACE. The pre and post TACE values in LR-TR (LIRADS - treatment response) nonviable and viable lesions were compared using paired t-tests. ROC curve analysis was done to calculate sensitivity and specificity and propose cut-off values. RESULT: Non-viable lesions showed a significant increase in Dslow (1.208 ± 0.581 vs 1.560 ± 0.494, P-value -.0207) and ADC (1.37 ± 0.53 vs 1.65 ± 0.4287, P value .016) after TACE. There was also significant decrease in Dfast (33.7 ± 10.4 vs 23.75 ± 12.13, P value .0005) and f (19.92 ± 10.54 vs 12.9 ± 10.41, P value .012) values after TACE in non-viable lesions compared to viable lesions. The change in true diffusion had the highest AUC (0.741) among IVIM parameters with greater than 0.075 increase between preTACE and postTACE values having a sensitivity and specificity of 81.8% and 60% respectively for complete response. CONCLUSION: IVIM imaging is feasible to assess the response in HCC after TACE. True diffusion is more sensitive and specific than apparent diffusion in evaluating the response.

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

BACKGROUND: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. METHODS: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. RESULTS: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. CONCLUSIONS: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.

Induction chemotherapy followed by response evaluation and esophagectomy for advanced esophageal cancer.

INTRODUCTION: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival. MATERIAL AND METHODS: Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by (18F-FDG PET)/CT. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival (OS) was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. RESULTS: 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8-33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02-3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02-2.10) was associated with worse survival (p = 0.04). CONCLUSION: In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %.

Assessing Radiological Response to Immunotherapy in Lung Cancer: An Evolving Arena.

In the past decade, immune checkpoint inhibitors (ICIs) have entered the treatment landscape of non-small-cell lung cancer, signalling a paradigm shift within the field characterized by significant survival benefits for patients with advanced and metastatic disease, and especially those with non-targetable genetic oncogenic driver mutations. However, the shift towards immune-based treatments has created new challenges in oncology. Atypical immunotherapy response patterns, including pseudo-progression and hyperprogressive disease, as well as immune-related adverse events have generated the need for new methods to predict patient response to treatment. Hence, new versions of the traditional Response Evaluation Criteria for Solid Tumors (RECIST) have emerged to help characterise with better accuracy radiological findings concerning patient response classification to immunotherapy. This review discusses response evaluation criteria relevant to unique radiological findings observed in patients treated with immunotherapy for non-small-cell lung cancer.

Delta-radiomics features for predicting the major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

OBJECTIVES: To investigate if delta-radiomics features have the potential to predict the major pathological response (MPR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) patients. METHODS: Two hundred six stage IIA-IIIB NSCLC patients from three institutions (Database1 = 164; Database2 = 21; Database3 = 21) who received neoadjuvant chemoimmunotherapy and surgery were included. Patients in Database1 were randomly assigned to the training dataset and test dataset, with a ratio of 0.7:0.3. Patients in Database2 and Database3 were used as two independent external validation datasets. Contrast-enhanced CT scans were obtained at baseline and before surgery. The delta-radiomics features were defined as the relative net change of radiomics features between baseline and preoperative. The delta-radiomics model and pre-treatment radiomics model were established. The performance of Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) for predicting MPR was also evaluated. RESULTS: Half of the patients (106/206, 51.5%) showed MPR after neoadjuvant chemoimmunotherapy. For predicting MPR, the delta-radiomics model achieved a satisfying area under the curves (AUCs) values of 0.768, 0.732, 0.833, and 0.716 in the training, test, and two external validation databases, respectively, which showed a superior predictive performance than the pre-treatment radiomics model (0.644, 0.616, 0.475, and 0.608). Compared with iRECIST criteria (0.624, 0.572, 0.650, and 0.466), a mixed model that combines delta-radiomics features and iRECIST had higher AUC values for MPR prediction of 0.777, 0.761, 0.850, and 0.670 in four sets. CONCLUSION: The delta-radiomics model demonstrated superior diagnostic performance compared to pre-treatment radiomics model and iRECIST criteria in predicting MPR preoperatively in neoadjuvant chemoimmunotherapy for stage II-III NSCLC. CLINICAL RELEVANCE STATEMENT: Delta-radiomics features based on the relative net change of radiomics features between baseline and preoperative CT scans serve a vital support tool in accurately identifying responses to neoadjuvant chemoimmunotherapy, which can help physicians make more appropriate treatment decisions. KEY POINTS: • The performances of pre-treatment radiomics model and iRECIST model in predicting major pathological response of neoadjuvant chemoimmunotherapy were unsatisfactory. • The delta-radiomics features based on relative net change of radiomics features between baseline and preoperative CT scans may be used as a noninvasive biomarker for predicting major pathological response of neoadjuvant chemoimmunotherapy. • Combining delta-radiomics features and iRECIST can further improve the predictive performance of responses to neoadjuvant chemoimmunotherapy.