Response Evaluation Criteria In Solid Tumors Criteria Research Articles

Analysis of the efficacy and safety of hepatic arterial infusion chemotherapy for unresectable hepatitis B-related intrahepatic cholangiocarcinoma

Objective: To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC). Methods: This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ2 test or Fisher's exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results: According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant(χ2=4.459,P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant(χ2=4.410,P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95%CI: 5.8 to 13.2 months) and 7.3 months (95%CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95%CI: 12.5 to 33.9 months) and 15.9 months (95%CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion: Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

A novel approach to evaluation of tumor response for advanced pulmonary adenocarcinoma using the intertumoral heterogeneity response score.

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3-10 measurable advanced lung adenocarcinoma lesions who underwent first-line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4-6weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression-free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Outcomes of Extramedullary Acute Myeloid Leukemia with Gemtuzumab Ozogamicin: Real-World Experience

Introduction: Extramedullary AML (EM AML) is characterized by the presence of leukemic cells in organs or tissues outside of the blood or bone marrow and remains a therapeutic challenge with dismal response rates to standard chemotherapy and short overall survival. Gemtuzumab Ozogamicin (GO) is an anti-CD33 antibody drug conjugate currently approved for single-agent therapy or in combination regimens for CD33+ relapsed/refractory (R/R) or newly diagnosed (ND) AML, respectively. Although GO is an active drug in AML, the optimal employment of this agent for treatment of EM AML at initial diagnosis, or at relapse, remains to be defined. Methods: A retrospective chart review on outcomes of GO in adults with EM AML at our institute from 2000 to 2023 was performed. Variables collected included age, sex, type of myeloid malignancy, and European LeukemiaNet (ELN) risk, bone marrow, peripheral blood and radiographic involvement, Response Evaluation Criteria in Solid Tumors (RECIST), prior lines of treatments, including stem cell transplant, next-generation sequencing (NGS), cytogenetics, mutational profile, and overall survival (OS). We screened patients with a diagnosis of EM AML who received GO at any point during their EM AML therapy. Patients with only CNS involvement as the extramedullary site were excluded. The aims of this study were to characterize responses and potential clinical benefit of EM AML to GO based regimens in the upfront and R/R settings. Results: 32 patients(pts) with EM AML received GO: 8 (25%) were ND and received GO-based induction regimen, while 22 (68.75%) received GO for R/R AML, and 2 (6.25%) patients received GO both at initial diagnosis and relapse. The median age of patient with ND EM AML was 66 years (y) (range: 28-84), and 60.5 (43-73) y in R/R EM AML. Twenty-four (75%) were men. One (12.5%) ND EM AML and 5 (10.1%) R/R EM AML had >1 extramedullary sites involved. The most frequent sites of EM-AML were skin (25%), lymph nodes (25%), soft tissues (25%), solid organs (25%), and visceral body cavity fluids (12.5%). Based on ELN 2022 risk group criteria, 17 patients were adverse, 8 with intermediate, and 3 with favorable risk. Next-Generation Sequencing (NGS) available for 21 patients identified mutations in TP53 (14.28%), FLT3 (19.04%), NPM1 (19.04%), KMT2A (19.04%), and ASXL1 (19.04%) as the most common mutations. Normal karyotype was noted in 6 (25%) R/R EM AML, while complex karyotype was present in 1 (12.5%) ND EM AML and 10 (41.67%) of R/R EM AML. While none of the ND pts had prior myeloid malignancy, R/R pts had prior AML (15), MDS (2), MDS-EB (1), CMML (1), therapy-related AML (1), myelofibrosis (1), and myeloid sarcoma (1). Concomitant bone marrow involvement at identification of EM AML was present in most ND cases (7/8, 88%) and R/R settings (16/23, 69.56%) (Table 1). Combination 7+3 plus GO was most frequently administered for ND EM AML (3/8) and R/R EM AML (8/24, 33%). Eleven patients had measurable radiologic findings prior to and following GO. Median OS was 10.91 months (m) (range: 0.2 to 27.1) for ND EM AML and 1.58 m (range: 0.7 to 7.5) for R/R EM-AML (Figure 1). 3 of 8 newly diagnosed EM-AML underwent allogeneic bone marrow transplant (AlloBMT) after GO based induction, followed by relapsed EM AML in 1 patient. Despite 50 percent of R/R EM AML pts undergoing prior AlloBMT, none had a durable disease-free response and received GO after relapse. Based on RECIST criteria, 7 of 11 (63.63%) pts achieved a response including 1 Complete Response (disappearance of all target lesions), 6 Partial Response (at least a 30% decrease in the sum of target lesions), and 2 Stable Disease (neither sufficient shrinkage nor increase). The 30-day mortality for ND and R/R were 12.5% and 8.33%, respectively. The 60-day mortality for ND and R/R were 25% and 50%, respectively. Conclusion: Our real-world single-institute experience in patients with EM AML suggests that GO combined with chemotherapy in the upfront setting results in promising outcomes with high overall response rates (CR 50%, PR 13%) by RECIST criteria, durable remissions, and prolonged overall survival in largely favorable and intermediate risk AML. However, despite high partial response rates (4% CR, 50% PR) following GO-based therapy in R/R EM AML, survival was less than 2 months likely due to the high proportion of patients in this cohort with poor risk disease. Further investigations and larger studies are warranted to establish the optimal use of GO in EM AML.

Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma Using Image-Guided Clip Placement.

Background The present study aims to evaluate the response of locally advanced breast carcinoma (LABC) to neoadjuvant chemotherapy (NACT) using image-guided clip placement based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Methods Thirty-four patients with LABC were included in the study. Consent for three-dimensional titanium clip placement (400/300/200 mm Liga clips) under local anesthesia with USG guidance was obtained. Serial sonographic/X-ray evaluations of tumor bed size were conducted before every cycle of NACT. All data were recorded in millimeters of concentric tumor regression/non-regression. Tumor regression in a concentric or Swiss cheese pattern and non-responders were evaluated. Assessment of the response to NACT was performed using RECIST criteria, dividing it into four categories. Tumor response was confirmed with computerized tomography (CT) conducted before and after the completion of NACT. Patients underwent surgical management, mostly modified radical mastectomy (MRM), as they had locally advanced breast carcinoma. Following MRM, the clips in the specimen guided the original site of the tumor for histopathological evaluation and response to chemotherapy. Results Tumor response was classified into four types: complete response (CR), partial response (PR), progressive disease (PD), and stable disease. RECIST 1.1 criteria were elaborated and defined. Data for all patients were entered into an Excel sheet (Microsoft Corporation, Redmond, Washington)to prepare a master chart, and the following observations were made and analyzed using SPSS software. The duration of chemotherapy for the study population ranged from 32 to 206 days, with a mean (±SD) of 111.82 (± 52.64) days and a median (IQR) of 81 (63, 158) days. The mean period between clip insertion and completion of NACT was 111.82 days. The baseline sum diameters and post-NACT diameters of the tumors were 70.50 (±13.60) mm before NACT and 17.75 (±17.20) mm after NACT. Hence, the mean size of the lump was statistically significantly lower after NACT, with a mean difference of 52.75 (p<0.05). The mean rate of reduction in tumor diameter was found to be 74.32% (±23.44%) based on RECIST 1.1 criteria. Pathological response was observed in all patients except for 8.8% of the patients. Clinical complete response was seen in 35.29% of patients, and partial response was observed in 52.92% of the patients based on RECIST 1.1 criteria. The study thus demonstrates the effectiveness of NACT in LABC, with a mean reduction in tumor diameter of 74.32%, assessed with the help of RECIST 1.1 criteria. Conclusion NACT for patients with LABC has shown a significant reduction in tumor size. NACT should be the initial mode of management for patients with LABC. RECIST 1.1 criteria are effective and can be used to assess tumor response to NACT. This has aided in the stratification of the response of NACT for further management through systemic therapy (adjuvant chemotherapy) after the surgical excision of the tumor.

Locally advanced thymoma; does neoadjuvant chemotherapy make a difference?

BackgroundRegardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the region. Surgical resection, via thymectomy, remains the mainstay treatment modality. In locally advanced and borderline resectable tumors, neoadjuvant chemotherapy (NACT) may be utilized to increase the chance of R0 resection, raising the question of its efficacy and safety.MethodsDemographic and clinical data from patients who presented to a tertiary cancer center between January 2015–October 2021 with a diagnosis of thymoma and underwent curative surgical resection was collected. Computed tomography scan was used to delineate clinical staging, tumor size and to detect post-therapeutic variations in tumor burden. The response evaluation criteria in solid tumors (RECIST) was used to classify the effect of NACT on tumor burden. The pathological response was determined by measuring the percentage of necrotic tissue.ResultsA total of 23 patients were diagnosed with thymoma. Most patients were male with a mean age 46 (± 15) years at diagnosis. The most common clinical stage was stage II with 5 patients (22%). A total of 12 patients had NACT as compared to 11 patients who had upfront surgery. The mean change in tumor volume was 165 cm3 (p = 0.079) and the change in and maximum diameter was 1.53 ± 1.49 cm (p < 0.01). The effect of NACT on tumor burden based on RECIST criteria was minimal as 8 patients had stable disease. Based on pathological findings, the average necrotic portion of the tumor was 39.5% (p = 0.152). The overall survival rate is 95.65%, mean survival was 115 months (4–125). Recurrence occurred in 5 patients. The NACT group had a higher risk for recurrence (4; 33.3%) with a mean survival of 43.8 months compared to 59.6 months in those who did not receive induction therapy.ConclusionsThe exact role of induction chemotherapy in locally advanced thymoma patients remains controversial. NACT effect after utilizing radiological and pathological assessment tools was not found to significantly improve oncological outcomes compared to upfront surgery in locally advanced disease, with minimal radiologic and pathologic effect. To further demonstrate the impact of induction chemotherapy, we recommend multicentric collaborative studies.

Different disease progression patterns based on RECIST and CA-125 criteria and the impact on prognosis in patients with ovarian cancer treated with PARP inhibitors.

e17536 Background: We aimed to assess the clinical features of disease progression (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 criteria, and analyse the impact on prognosis in ovarian cancer patients treated with poly (ADP-ribose) polymerase (PARP) inhibitors. Methods: All epithelial ovarian cancer patients included in this retrospective analysis were admitted to the Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University between January 2011 and July 2021. All enrolled patients were treated with PARP inhibitor monotherapy or combination therapy with antiangiogenic agents and regularly assessed with RECIST and CA-125 criteria until disease progression confirmed by RECIST criteria. Patients were divided to RECIST PD group and CA-125 PD group based on regular assessment: RECIST PD group comprised patients who were first confirmed with RECIST-assessed PD and did not achieve PD according to CA-125 criteria during the subsequent 28 days; CA-125 PD group comprised as follows: (i) patients who were first diagnosed with RECIST-assessed PD and defined as consistent if CA-125 PD occurred within the following 28 days; (ii) patients who had doubled CA-125 levels for the first time, confirmed after at least 1 week, and defined as consistent if subsequent RECIST progression occurred within 28 days of the initial doubling of CA-125; (iii) patients in whom the first occurrence of CA-125 was doubled and confirmed after at least 1 week, defined as priority PD of CA-125 provided there was no progression in RECIST assessment during the subsequent 28 days. Results: A total of 124 patients were included, with 64 (51.6%) in RECIST PD group and 60 (48.4%) in CA-125 PD group. Forty-three patients (34.7%) had disease progression consistent with RECIST and CA-125 criteria, 64 patients (51.6%) had priority PD with RECIST criteria, and 17 patients (13.7%) had priority PD with CA-125 criteria. The median interval between disease progression as determined by priority CA-125 criteria and subsequent RECIST criteria was 55 days (range 29–192 days). Patients in CA-125 PD group had a higher proportion of lymph node progression (40.0% vs. 17.2%, p = 0.005), multi-site disease progression (41.7% vs. 21.9%, p=0.018), and a worse prognosis with a median overall survival (OS) of 70.5 vs. 87.2 months (hazard ratio (HR)=2.01, p=0.015). In multivariate analysis, residual lesions after primary surgery (no vs. yes, HR=0.493, p=0.015), duration of PARP inhibitor treatment (≤ 6 vs. &gt; 6 months, HR=2.262, p=0.006), priority criteria for PD (RECIST vs. CA-125, HR=0.441, p=0.006), and BRCA1/2 mutation status (wild-type vs. mutation, HR=2.150, p=0.028) were significantly associated with OS. Conclusions: Priority disease progression based on CA-125 criteria in ovarian cancer patients treated with PARP inhibitors might suggest a poor prognosis.

Arterial chemotherapy in advanced hepatocellular carcinoma: An evolutionary trajectory exploration and pooled outcome analysis.

e16125 Background: Hepatic artery infusion chemotherapy (HAIC) is widely used for the treatment of advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, there have been inconsistent conclusions on the effectiveness of HAIC in previous studies, and the analysis landscape regarding relevant articles and clinical trials is lacking on this topic. We conducted a bibliometric analysis to explore the development of HAIC, and a pooled analysis using individual patient data to evaluate the outcomes of HAIC in advanced HCC. Methods: The Web of Science Core Collection was searched from its earliest records until October 2022, to identify studies associated with HAIC for advanced HCC. Relevant documents were collected and analyzed using R bibliometrix. During the same period, two international clinical trial registered platforms, ClinicalTrials.gov and ChiCTR.org, were searched for oxaliplatin-based HAIC utilization in HCC. A total of 845 patients treated with HAIC or its combination therapy from 17 pre-registered studies were analyzed to assess the overall survival (OS), progression-free survival (PFS), objective response rate (ORR per Response Evaluation Criteria in Solid Tumors (RECIST)), disease control rate (DCR per RECIST), and adverse events (AEs). Results: We identified 539 studies and derived the evolutionary trajectory of HAIC from the perspective of scientometry. Contributions of publications were presented at the country, institution, and author levels. Conversion therapy, Folfox, oxaliplatin and immunotherapy became new research foci. A total of 88 registered trials were identified and a comprehensive landscape of these trials was provided. Further interactive exploration of the trials was accessible through a HAICshiny application (https://sysucc.shinyapps.io/clinical-trial-of-HAIC-FO/). The OS was 13.7 months (95% confidence interval (CI) 12.2-15.3), and the corresponding times were 13.2, 13.8, 12.8, and 13.7 months in the cisplatin, oxaliplatin, HAIC monotherapy, and concomitant therapy subgroups, respectively. The corresponding PFS was 7.0 months (95% CI 6.5-7.8) in the whole cohort and 5.2, 7.7, 7.6, and 6.8 months in the subgroup cohorts. According to RECIST criteria, ORR and DCR reached 0.34 and 0.80, respectively. Comparable survival and tumor response were observed between the HAIC and its combination therapy groups. The incidence of AEs was identified, and most of them were manageable. Conclusions: This study illustrates the evolutionary trajectory of HAIC from the perspective of scientometry. The efficacy outcomes of HAIC in the treatment of advanced HCC were verified with manageable safety profiles. Further trials regarding HAIC implementation are emerging, and more effort is required to improve the quality of trials.

Real-life use of trametinib after immunotherapy failure in BRAF wild-type advanced melanoma.

BRAF V600 wild-type advanced melanomas quickly reach a therapeutic dead-end, after immunotherapy failure. Even if preclinical studies have suggested sensitivity to MEK inhibitors such as trametinib in NRAS, NF1 or GNA mutated melanoma, therapeutic options are limited for these patients. We present a retrospective monocentric study of 22 patients with advanced melanoma treated by trametinib after immunotherapy resistance. Melanomas harboured NRAS (20), NF1 (1) or GNA 11 (1) mutations. For most of them (18), anti-PD1 was associated with trametinib. A disease-control was reported in 36% of patients (8/22), with six stable diseases and two partial responses according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Median progression-free survival was 2 months (1-14) and median overall survival was 6.5 months (2-24). In patients with progressive disease (14/22), dissociated radiologic responses and clinical benefits such as pain reduction were seen in five patients. High blood level of lactate dehydrogenase (LDH) seemed associated with trametinib failure, without significance ( P = 0.06). Adverse events (grade 1-3) occurred in 91% of patients during the first weeks of treatment, mainly papulo-pustular rashes (77%), leg oedemas (36%), asthenia (18%) and diarrhoea (14%). This real-life study showed that trametinib may benefit some metastatic melanoma that progressed after chemotherapy and immune checkpoint inhibitors. Objective disease control (partial response or stable disease) using RECIST criteria was observed in 36% of patients. Because of frequent side-effects which can alter the quality of life and the short response duration, this off-label option has to be discussed with the patient. Studies with combination therapy with trametinib to improve relapse-free survival and lower side-effects are ongoing.

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

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

The Role of a Neoadjuvant RET Inhibitor in Medullary Thyroid Cancer

The Role of a Neoadjuvant <i>RET</i> Inhibitor in Medullary Thyroid Cancer

Peptide Receptor Radionuclide Therapy in Patients With Advanced Progressive Medullary Thyroid Cancer: Efficacy, Safety, and Survival Predictors.

Progressive metastatic medullary thyroid carcinoma (MTC) is often characterized by rapid disease progression and poor prognosis, with only few therapeutic options available. Peptide receptor radionuclide therapy (PRRT) has demonstrated remarkable success in the management of gastroenteropancreatic neuroendocrine tumors and has also been suggested to treat MTC. However, evidence on its effectiveness and long-term outcome for this indication is still limited. The objective of this study was to assess the safety and efficacy of PRRT in patients with advanced, progressive MTC and to determine survival. Potential predictors of survival were also evaluated. From September 2003 to June 2019, 28 patients (15 men and 13 women; mean age, 49 ± 14 years) with progressive, somatostatin receptor-positive advanced MTC received PRRT with 177Lu- or 90Y-labeled somatostatin analogs at Zentralklinik Bad Berka, Germany. Toxicity was graded according to Common Terminology Criteria for Adverse Events version 5.0. Treatment response was evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1, as well as molecular imaging criteria (European Organisation for Research and Treatment of Cancer). Kaplan-Meier analysis was used to calculate progression-free survival (PFS) and overall survival (OS), defined from the start of PRRT. Univariate and multivariate Cox regression analyses were performed to identify parameters associated with PFS and OS. Seventy-seven cycles of PRRT were administered (mean cumulative administered activity, 16.0 ± 7.8 GBq). No acute or long-term grade 3/4 toxicity was recorded with a follow-up of 3 to 140 months, except for 1 patient (4%) who suffered from grade 3 anemia (possibly related to disease progression). According to the RECIST criteria, the disease control rate after 3 to 4 months of PRRT was 56% (partial remission, 12%; stable disease, 44%). The disease control rate (72%) was higher by molecular response evaluation. Median OS and PFS were 63.7 and 10.1 months, respectively. The annual OS rates were 84% at 1 year, 65% at 3 years, 57% at 5 years, and 18% at 10 years. The annual PFS rates were 42% at 1 year, 21% at 2 years, and 13% at 5 years. Patients with bone metastases had poorer OS and PFS than those without metastases (median OS, 58.7 vs 92.3 months [P = 0.035; hazard ratio, 2.7; 95% confidence interval, 0.92-7.84]; median PFS, 8.5 vs 12.8 months [P = 0.592; hazard ratio, 1.2; 95% confidence interval, 0.56-2.76]). Peptide receptor radionuclide therapy was well tolerated and effective in patients with advanced, aggressive MTC. Bone metastasis was an independent adverse prognostic factor for OS.

Personalized dendritic cell vaccination in cancer therapy: An evidence-based research study.

Although chemotherapy is considered to be the golden standard, it does not come without a price. Toxicities and resistance are frequently limiting its effectiveness. Immunotherapy has emerged as a safer therapeutic alternative but still has a long way until it has proven to be of equal efficacy. A type of immunotherapy is dendritic cell (DC) vaccination. We have developed a novel platform for the generation of autologous DCs that have been activated against peptides that are personalized for each patient individually. The aim of the study was to clinically evaluate this platform. Our platform and our algorithm for the determination of the immunogenic peptides has been tested. DC generation was verified both morphologically and by CD80/86 expression. Peptide antigenicity was determined using a number of T-cell epitope prediction algorithms. Response to therapy was evaluated using response evaluation criteria in solid tumors (RECIST) criteria by the doctors involved. Immune status was also evaluated before and after DC vaccination and correlated with circulated tumor cell count. It was found that DC vaccine increased immune activation while correlated with decreased circulating tumor cell counts. Clinical evaluation by the determination of immune markers may be a superior tool than using RECIST criteria. Dendritic cell therapies could prove to be a valuable tool in cancer treatment.

Nanotheranostic Strategies for Cancer Immunotherapy.

Despite advancements in cancer immunotherapy, heterogeneity in tumor response impose barriers to successful treatments and accurate prognosis. Effective therapy and early outcome detection are critical as toxicity profiles following immunotherapies can severely affect patients' quality of life. Existing imaging techniques, including positron emission tomography, computed tomography, magnetic resonance imaging, or multiplexed imaging, are often used in clinics yet suffer from limitations in the early assessment of immune response. Conventional strategies to validate immune response mainly rely on the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified iRECIST for immuno-oncology drug trials. However, accurate monitoring of immunotherapy efficacy is challenging since the response does not always follow conventional RECIST criteria due to delayed and variable kinetics in immunotherapy responses. Engineered nanomaterials for immunotherapy applications have significantly contributed to overcoming these challenges by improving drug delivery and dynamic imaging techniques. This review summarizes challenges in recent immune-modulation approaches and traditional imaging tools, followed by emerging developments in three-in-one nanoimmunotheranostic systems co-opting nanotechnology, immunotherapy, and imaging. In addition, a comprehensive overview of imaging modalities in recent cancer immunotherapy research and a brief outlook on how nanotheranostic platforms can potentially advance to clinical translations for the field of immuno-oncology is presented.

A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology.

Stereotactic body radiotherapy (SBRT) is a precise and conformal treatment modality used in the management of metastatic spine tumors. Multiple studies have demonstrated its safety and efficacy for pain and tumor control. However, no uniform quantitative imaging methodology exists to evaluate response to treatment in these patients. This study presents radiographic local control rates post-SBRT, systematically compares measurements acquired according to WHO and Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and explores the relationship to patient outcome. The authors performed a retrospective review of prospectively obtained data from a cohort of 59 consecutive patients (81 metastatic isocenters) treated with SBRT and followed with serial MRI scans. Measurements were performed by a neuroradiologist blinded to the patients' clinical course. Local control status was determined according to both WHO and RECIST measurements, and agreement between the measuring methodologies was calculated and reported. Eighty-one isocenters (111 vertebral bodies) were treated with SBRT. The mean treatment dose was 13.96 Gy and the median follow-up duration was 10.8 months, during which 408 MRI scans were evaluated with both WHO and RECIST criteria for each scan point. Imaging demonstrated a mean unidimensional size decrease of 0.2 cm (p = 0.14) and a mean area size decrease of 0.99 cm2 (p = 0.03). Although 88% of the case classifications were concordant and the agreement was significant, WHO criteria were found to be more sensitive to tumor size change. The local control rates according to WHO and RECIST were 95% and 98%, respectively. Although WHO volumetric measurements are admittedly superior for tumor size measurement, RECIST is simpler, reproducible, and for the first time is shown here to be comparable to WHO criteria. Thus, the application of RECIST methodology appears to be a suitable standard for evaluating post-SBRT treatment response. Moreover, using comprehensive and consistent measuring approaches, this study substantiates the efficacy of SBRT in the treatment of spine metastases.

Assessing Treatment Response after Lung SABR: An Evaluation of the Predictive Value of RECIST Criteria

<h3>Purpose/Objective(s)</h3> Response Evaluation Criteria In Solid Tumors (RECIST) – version 1.1 is a commonly used framework to assess treatment response. However, response assessment after lung stereotactic ablative radiotherapy (SABR) can be difficult due to radiation-induced lung changes. The goal of this study was to assess how frequently lung lesions treated with SABR triggered RECIST criteria for recurrence and to correlate RECIST findings with actual treatment outcomes. <h3>Materials/Methods</h3> We reviewed patients who were treated with lung SABR between 2010-2015. Prescribed dose was 54-60 Gy in 3-8 fractions. Both primary lung and metastatic lesions were included. All lesion measurements were based on maximum diameter on CT axial slices. After treatment, progressive disease (PD) by RECIST was based on strict RECIST criteria and defined as: 1) increase of ≥ 20% compared to post-treatment minimum and 2) ≥ 5 mm absolute increase. The final assessment of recurrence was based on subsequent changes in lesions size after PD by RECIST and, when available, PET scan and/or pathology. When assessing subsequent changes in lesion size, stability (≤ 20% change) in size for at least one year or a decrease (> 20%) in size indicated no recurrence, while subsequent growth (> 20%) indicated recurrence. The assessment of lesion response by the treating radiation oncologist (RO) in the clinical record was also recorded when available. <h3>Results</h3> A total of 85 patients, with 88 lesions, met inclusion criteria. 75 of these lesions were lung primaries, the remainder were metastases. Median patient age was 79 years (IQR: 73-85) and mean lesion size was 2.1 ± 0.9 cm. Median follow-up was 52 months (IQR: 33-68). 66% (58/88) of treated lesions met criteria for PD by RECIST. However, on final assessment only 10% (9/88) were found to have recurrence. The positive predictive value (PPV) of RECIST criteria was 0.16. In the subset of patients with primary lung tumors only, 64% (48/75) were classified as PD by RECIST, but only 12% (9/75) were categorized as recurrence on final assessment. PPV was 0.19. The predictive value of RECIST was lower when PD by RECIST was triggered ≤ 12 vs. > 12 months post-treatment (PPV 0.08 vs. PPV 0.21). Median time to PD by RECIST was 19 months (IQR: 12-27) for those with recurrence vs. 15 months (IQR: 8-24) for those without recurrence on final assessment (p=0.13). Assessment by treating RO was only available for 57% (50/88) of cases, but concordance with final study assessment was 0.85, translating to an overall predictive accuracy of 94% (47/50). <h3>Conclusion</h3> Using strict RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, on further follow-up only a minority of these patients were felt to have recurrence, leading to a poor PPV for RECIST criteria in this setting. Further work is needed to develop validated criteria for designation of recurrence after lung SABR.

Real-life multi-center retrospective analysis on nivolumab in difficult-to-treat patients with advanced hepatocellular carcinoma.

BACKGROUNDHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The landscape of the systemic treatment for advanced HCC is changing quickly, and recently, the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab regimen. Nivolumab monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of care. This is a particular population of interest.AIMTo evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other treatment.METHODSWe conducted a retrospective, multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary hospitals. All patients had had prior chemotherapy or were intolerant or ineligible for treatments. All study subjects received nivolumab 3 mg/kg in monotherapy, administered once every two weeks intravenously. Treatment continued until disease progression, severe adverse events or death. Data were retrieved from patients’ medical records. The outcome parameters such as radiological response according to response evaluation criteria in solid tumors (RECIST) criteria, the biological response through the evolution of the alpha-fetoprotein (AFP) level, and clinical response considering both the Child–Pugh (CP) score and the World Health Organization (WHO) performance status (PS) were reported. A safety profile was also reported. Statistical analysis was performed using the SPSS Statistics 27 statistical software package.RESULTSThe radiological overall response rate (defined as complete or partial response according to the immune RECIST and modified RECIST criteria) to nivolumab monotherapy was 24.1%. The biological overall response rate (defined as a decrease of ≥ 25% in AFP blood level) was 20.7%. Radiological and biological responses were significantly associated both with each other (P < 0.001) and with overall survival (P < 0.005 for radiological response and P < 0.001 for biological response). Overall survival was 14.5 mo (+/- 2.1), and progression-free survival was 10.9 mo (+/- 2.3). After 4 mo of treatment, 78.3% of patients remained clinically stable or even showed improvement in WHO PS. Grade 3 adverse events occurred in 17.2% of patients, none had grade 4 adverse events, and no patients ceased nivolumab due to adverse events.CONCLUSIONNivolumab monotherapy is a good treatment choice in frail patients with HCC who are ineligible for the standard of care or other validated systemic treatments.

Clinical Outcomes of Drug-Eluting Bead Transarterial Chemoembolization Loaded with Raltitrexed for the Treatment of Unresectable or Recurrent Hepatocellular Carcinoma.

Objectives Although raltitrexed shows therapeutic effects in many types of malignant tumors, the therapeutic effects and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) loaded with raltitrexed for the treatment of hepatocellular carcinoma (HCC) are rare. This study aimed to investigate the safety and efficacy of DEB-TACE with raltitrexed-loaded CalliSpheres beads (CB) in patients with unresectable or recurrent HCC. Methods Between May 2018 and October 2021, 41 patients with unresectable or recurrent HCC treated by DEB-TACE loaded with raltitrexed were retrospectively enrolled. The primary end points were overall survival and progression-free survival. The response evaluation criteria in solid tumors (RECIST) criteria and modified RECIST criteria (mRECIST) were used to assess the tumor response after the DEB-TACE procedure. Results A total of 79 DEB-TACE procedures were successfully performed, and the technical success rate was 100%. The overall response rate and disease control rate assessed by mRECIST criteria were 76.9% and 88.5%, 62.5% and 70.8%, and 35.3% and 47.1%, respectively, at 1, 3, and 6 months postprocedure. The mean progression-free survival and overall survival were 21.6 ± 3.6 and 43.7 ± 5.8 months, respectively. The 6-, 24-, and 36-month overall survival rates were 86.8%, 62.7%, and 57.1%, respectively. Minor complications were observed in 21 patients (51.2%), with no treatment-related mortality or severe adverse events. The most common treatment-related complications were abdominal pain (48.8%) and nausea (29.3%). Conclusion DEB-TACE with raltitrexed-loaded CB suggests a feasible, safe, and efficacious palliative regimen in unresectable or recurrent HCC patients.

Bone-specific response according to MDA criteria predicts immunotherapy efficacy among advanced non-small cell lung cancer (NSCLC) patients

PurposeThe presence of bone metastasis at baseline has been associated with dismal prognosis under immunotherapy in advanced non-small cell lung cancer (NSCLC). Response Evaluation Criteria in Solid Tumors (RECIST) criteria may be limited for bone-specific response evaluation. Whether their assessment through MD Anderson (MDA) criteria predict immunotherapy efficacy is unknown.Materials and methodsWe conducted a single-center retrospective study to assess the use of MDA criteria in evaluating bone metastasis in NSCLC treated with immunotherapy. Radiological imaging were reviewed to classify bone lesions as osteolytic, osteoblastic, or mixed. Bone response to treatment data was classified according to MDA criteria.Results222 patients received single-agent immunotherapy. The presence of bone metastasis increased the risk of death both in the univariate (HR: 1.46, 95% CI, 1.05–2.03, p = 0.024) and in the multivariate model (HR: 1.61, 95% CI, 1.10–2.36, p = 0.015). According to MDA criteria, 57.3% of patients had progressive disease as best response, 29.5% stable disease, 11.4% partial response and 1.6% complete response. Bone-specific objective response was associated with a significantly increased median overall survival (11.3 vs. 3.1 months, p = 0.027) and longer median progression-free survival (6 vs. 2.1 months, p = 0.056). The median time to bone failure (TBF) was 2.4 months (IQR, 1.67–3.0). In 25.7% of cases, TBF was shorter than progression-free survival according to RECIST 1.1 criteria. TBF was positively correlated with overall survival (HR = 0.73, p = 0.00019).ConclusionsMDA criteria represent a reliable tool in assessing bone-specific response, offering a more accurate evaluation with the aim to earlier predict survival outcomes or treatment failure compared to RECIST criteria for advanced NSCLC patients receiving immunotherapy.

Comparison of Magnetic Resonance Imaging With Positron Emission Tomography/Computed Tomography in the Evaluation of Response to Neoadjuvant Therapy of Breast Cancer

IntroductionThe present study aims to determine the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography–computed tomography (PET-CT) in predicting a pathological response of molecular subtypes of breast cancer to neoadjuvant chemotherapy (NAC). Materials and methodsWe retrospectively analyzed patients with breast cancer who were operated after NAC between January 2018 and May 2020. Radiological responses were evaluated as per the Response Evaluation Criteria in Solid Tumors (RECIST) and changes in contrast enhancement patterns on MRI and the classification of PET Response Criteria in Solid Tumors (PERCIST) on PET-CT. The presence of a pathological response was evaluated based on the Sataloff classification. The agreement between the radiological response determined through imaging modalities before and after the NAC and the postoperative pathological complete response (pCR) was evaluated and compared statistically. Among the patients diagnosed with breast cancer between the ages of 18 and 80 y, those with N (+) at the time of diagnosis, those with T2 and advanced tumors, and those who were planned for breast conserving surgery were included in our study. Male patients, patients with distant metastases at the time of diagnosis, and patients with other system malignancies were excluded. ResultsThe study included 88 patients who had undergone surgery for breast cancer after NAC between January 2018 and May 2020. The study was conducted retrospectively in a single center. The tumor diameters and standard uptake values significantly decreased after NAC (P < 0.001). Estrogen receptor (ER) and progesterone receptor (PR) positivity were negatively associated with pCR (P = 0.03 and P = 0.03, respectively), whereas there was a significant positive association between HER-2 positivity and pCR (P = 0.004). There was a moderate agreement between the RECIST criteria used with MRI and pCR (k: 0.46). Moreover, a good agreement between PET-CT-PERCIST and pCR was detected (k: 0.61). In predicting pCR after NAC, MRI showed a selectivity of 80.7%, a sensitivity of 65.2%, a positive predictive value (PPV) of 75%, and a negative predictive value (NPV) of 72.4%. The corresponding rates for PET-CT were 75.7%, 100%, 57.9%, and 100%. ConclusionsWhen evaluating pCR after NAC, MRI was found to be more sensitive in patients with ER-positive cancer cell nuclei with weak to medium staining intensity and a loss of E-cadherin expression, whereas PET-CT was found to be more sensitive in patients with HER-2 overexpression, Luminal B, or Ki-67 proliferation >14% (P = 0.01).

Molecular Subtypes As Emerging Predictors of Clinicopathological Response to Neoadjuvant Chemotherapy (NACT) in Locally Advanced Breast Cancer (LABC): A Single-Centre Experience in Western India.

Introduction: Locally advanced breast cancer (LABC) is a subset of breast cancer characterized by the most advanced breast tumours in the absence of distant metastasis. Treatment of LABC has evolved from a single modality treatment to multimodality management. Neoadjuvant chemotherapy (NACT) is increasingly being used to treat patients with LABC. This study assessed tumour response after NACT using clinical changes, Response Evaluation Criteria in Solid Tumors (RECIST) criteria and pathological report.Methodology: This study was a prospective as well as retrospective observational study carried out in the department of general surgery, Dr. Sampurnanand Medical College, Jodhpur. All the patients admitted with stage III (IIIA, IIIB, IIIC) were included in the study after obtaining approval from the institutional ethical committee. Clinical response was assessed by RECIST criteria (clinical complete response (cCR), clinical partial response (cPR), clinical progressive disease (cPD), and clinical stable disease (cSD)) and pathological response by histopathological report (pCR). Response of various molecular subtypes was noted.Results: Among 31 patients included in the study, cCR observed in 22.58% cases, cPR observed in 61.29% cases while cPD and cSD seen in 3.22% and 12.90% cases, respectively. Pathological complete response (pCR) observed in 19.35% cases. Favourable response seen with human epidermal growth factor receptor 2 (HER2) overexpression (cCR = 50%, pCR = 37.50%) followed by triple negative (cCR = 25%, pCR = 25%) molecular subtypes.Conclusions: It can be concluded that molecular subtype determination helps in deciding treatment protocol in patients with LABC with HER2 overexpression and triple-negative breast cancers having a better clinicopathological response to NACT than luminal subtypes. NACT results in downstaging of tumours, thus, help in achieving surgically clear margins and elimination of micrometastases which decreases the recurrence rates and morbidity/mortality of patients.