Cases Of Progressive Disease Research Articles

Correlation between thyroid dysfunction and efficacy of immune checkpoint inhibitors in patients with advanced solid tumors

BackgroundImmune checkpoint inhibitors (ICIs) are currently the first line of tumor immunotherapy for the treatment of a wide range of tumors. However, the main side effect of immune checkpoint inhibitors is that they cause immune-related adverse events (irAEs) in patients. The relationship between the occurrence of immune side effects in patients and efficacy is controversial. The objective of this study was to confirm the relationship between patients who develop thyroid dysfunction after immune checkpoint inhibitors and efficacy.MethodsThis study was a retrospective real-world clinical study, and a total of 50 patients with advanced tumors treated with immune checkpoint inhibitors at Anqing People's Hospital from 2020.8 to 2022.5 were retrospectively collected. Among them, 30 patients with hypothyroidism and 20 patients with normal or hyperthyroidism occurred, and the treatment effects and prognostic differences between the two groups were compared.FindingAfter PD1 treatment in all patients, there were 10 cases of partial remission(PR), 18 cases of stable disease(SD) and 2 cases of progressive disease(PD) in patients who developed hypothyroidism, with a disease control rate(DCR) of 93.3% and objective remission rate(ORR) of 33.3%. There were 0 complete remission (CR) patient, 3 PR patients, 11 SD patients, 6 PD patients, 70.0% DCR and 15.0% ORR in patients who did not develop hypothyroidism. The DCR and ORR of patients who developed hypothyroidism were better than those of non-hypothyroid patients, and the difference was statistically significant (P < 0.05). Kaplan–Meier survival analysis showed that progression-free survival (PFS) reached 9.2 months (95% CI 7.726–10.779) in patients who developed hypothyroidism and did not hypothyroidism patients have a PFS of 7.3 months (95% CI 5.604–8.505), with a statistically significant difference (P = 0.0341 < 0.05). Further subgroup analysis revealed that among patients who developed hypothyroidism, PFS was 3.3 months (95% CI 0.630–5.440) in patients with cholangiocarcinoma, 6.89 months (95% CI 5.604–8.505) in patients with non-small cell lung cancer, > 12 months in patients with hepatocellular carcinoma, and 11.05 months (95% CI 9.308–12.792) in patients with esophageal cancer months and PFS for patients with gastric cancer was 9.74 months (95% CI 6.979–12.502).InterpretationWhen patients with advanced tumors were treated with immune checkpoint inhibitors, DCR and ORR were higher in patients who developed hypothyroidism, and patients had better PFS. The benefits were greater in patients with gastric, esophageal, and hepatocellular carcinomas.

NIMG-66. DEFINING PROGRESSIVE DISEASE: LOCALIZING VOXEL-AT-RISK ON MAGNETIC RESONANCE IMAGING USING DEEP LEARNING

Abstract Follow-up magnetic resonance imaging (MRI) of post-treatment glioblastoma (GBM) can be diagnostically challenging in differentiating progressive disease (PD) from coexisting treatment-related changes. The study aim was to train a machine learning model using multiple MRI timepoints from treated GBM patients with subsequent PD or at least six months of tumor-like, persistently stable disease (SD) to estimate PD risk. A retrospective, post-treatment GBM cohort (n=189) with 453 timepoints was identified with available MRI sequences (T1-weighted with and without contrast, T2-weighted, and fluid-attenuated inversion recovery). PD cases (n=154) showed new, enhancing PD followed by death within 3-6 months; timepoints included the MRI on the PD diagnosis date and the one directly prior. SD cases (n=35) exhibited stable, tumor-like enhancement over timepoints. Cases underwent voxel-wise annotation of PD versus SD. A multiclass, three-dimensional nnU-Net was trained to label voxels as PD, SD, or neither using timepoint sequences with five-fold cross-validation. Model performance was assessed using the ratio of predicted PD/SD voxels compared to each case’s actual PD or SD status. Classification accuracy of PD versus SD status, PD case-wise sensitivity and specificity, and a Receiver Operating Characteristic (ROC) analysis using the PD/SD ratio were presented. The five-fold model ensemble was evaluated on a holdout test set. Validation set performance showed 74.3% accuracy, 0.73 PD case-wise sensitivity, and 0.80 specificity. The holdout set exhibited 79.8% accuracy, 0.81 sensitivity, and 0.78 specificity for PD cases. The ROC analysis showed an area under the curve of 0.80 and 0.83 on the validation and holdout sets, respectively. The model showed high performance and classification accuracy in predicting which voxels were at risk of PD in post-treatment GBM cases. The model also differentiated between PD and SD regions. The model’s predicted PD/SD ratio may be clinically used to stratify patients’ PD risk.

Microwave ablation followed by cTACE in 5-cm HCC lesions: does a single-session approach affect liver function?

PurposeMicrowave ablation (MWA) and conventional transarterial chemoembolization (cTACE) are locoregional treatments commonly performed in very early, early and intermediate stages of hepatocellular carcinoma (HCC). Despite combined locoregional approaches have shown encouraging results in obtaining complete tumor necrosis, their application in a single session is poorly described.Our aim was to evaluate the safety and efficacy of single-session MWA and cTACE treatment in 5-cm HCCs and its influence on liver function.Materials and methodsAll 5-cm HCCs treated by MWA and cTACE performed in a single-session in our Interventional Radiology unit between January 2020 and December 2022 were retrospectively recorded and analyzed. Patients with poor or missing pre- and post-treatment imaging were excluded. Technical success, clinical success, and complications rate were examined as primary endpoints. Pre- and post-treatment liver function laboratory parameters were also evaluated.ResultsA total of 15 lesions (mean lesion diameter, 5.0 ± 1.4 cm) in 15 patients (11 men; mean age, 67.1 ± 8.9 years) were retrospectively evaluated. Technical and clinical success were 100% and 73%, respectively. Four (27%) cases of partial response and no cases of progressive or stable disease were recorded. AST and ALT values have found to be significantly higher in post-treatment laboratory tests. No other significant differences between pre- and post-treatment laboratory values were registered. AST and ALT pre- and post-treatment higher differences (ΔAST and ΔALT) were significantly associated with a lower clinical success rate.ConclusionMWA and cTACE single-session approach is safe and effective for 5-cm HCCs, without significant liver function impairment. A post-treatment increase in AST and ALT values may be a predictor for clinical failure.

Bronchial artery chemoembolization in the treatment of refractory central lung cancer with atelectasis.

This study aims to explore the clinical application of bronchial artery chemoembolization (BACE) in managing refractory central lung cancer with atelectasis. The retrospective case series includes patients diagnosed with refractory central lung cancer and atelectasis who underwent BACE treatment at Yueyang Integrated Traditional Chinese and Western Medicine Hospital, affiliated with Shanghai University of Traditional Chinese Medicine, from January 2012 to December 2021. All 30 patients with lung cancer successfully underwent BACE procedures. Their ages ranged from 62 to 88 years, with an average age of 67.53. The treatment interval was 21 days, and the treatment cycle ranged from 2 to 12 times, averaging 4.13 times. During the BACE procedures, the Karnofsky Performance Status (KPS) score after 2 to 3 BACE cycles showed a significant improvement (82.0 ± 10.1 vs 68.3 ± 14.0, P < 0.001) than that of before BACE. Only nutritional support and symptomatic treatment were performed after BACE, and no major hemoptysis were observed. During follow-up, 23 cases resulted in mortality, while seven survived. The median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% CI: 4.6-9.4) and 10.0 (95% CI: 6.2-13.8) months, respectively, with 1-, 2-, and 3-year survival rates of 84.0%, 53.5%, and 11.3%, respectively. Eight cases exhibited bronchial recanalization and relief of atelectasis. According to the RECIST scale, there were 4 cases of complete response (CR), 16 cases of partial response (PR), 9 cases of stable disease (SD), and 1 case of progressive disease (PD). No serious adverse events were reported. BACE might be a safe intervention for refractory central lung cancer accompanied by atelectasis. The procedure exhibits satisfactory outcomes in tumor control, atelectasis relief, and enhancement of quality of life, warranting further investigation.

Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience

PurposeHepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment.Material and MethodsBetween 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm).ResultsIRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement.ConclusionThe current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.Graphical

Preliminary efficacy and safety of camrelizumab combined with cetuximab and chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): A phase II clinical trial.

e18011 Background: Cetuximab and PD-1 inhibitors are widely used first-line therapy for R/M HNSCC and may provide potential synergy in R/M HNSCC. We conducted an open-label, single-arm, Simon's two-stage, phase II study of camrelizumab with cetuximab and cisplatin-based chemotherapy as first-line treatment in R/M HNSCC (NCT05673577). We report the results of stage 1 of this study. Methods: Eligible patients with R/M HNSCC not amenable to curative treatment were enrolled. Patients were treated with camrelizumab 200mg intravenously Q3W, cetuximab 400mg/m2 loading dose followed by 250mg/m2 weekly (21-day cycle), cisplatin 75mg/m2 Q3W, for up to 6 cycles, and nab-paclitaxel 125mg/m2 on d1, d8 (21-day cycle), for up to 6 cycles. Maintenance therapy with camrelizumab 200mg intravenously Q2W, cetuximab 500mg/m2 Q2W were given until intolerable toxicity or disease progression. Simon-minimax design was applied, if 9 of the 21 patients achieve PR or CR in the first stage, another 19 patients will be included. The primary endpoint is ORR. Secondary endpoints include PFS, OS, safety, etc, andmolecular biomarkers will be tested as exploratory endpoints. Results: A total of 21 patients were enrolled in the stage 1, with a median age of 65y (range 34-72y), M:F 19:2,ECOG (0:1) 1:20, and primary sites of oral cavity (n=6), oropharynx (n=3), hypopharynx (n=2), larynx (n=8), and unknown (n=2). By the cutoff date of Jan 10 2024, 20 patients were followed up (1 withdrew because of refusing and discontinuing treatment after SD). In total, 2 (9.5%) CR, 18 (85.7%) PR and 1 (4.8%) SD were observed as best response for an ORR of 95.2% and a DCR of 100%, meeting pre-planned criteria for trial continuation. Meanwhile, 18 patients achieved PR and 1 patient achieved SD after receiving the first two cycles of treatment (2 patients didn't complete accurate radiologic assessment of tumor response after 2 cycles of treatment and were confirmed PR after 4 cycles). Out of 21, 13 patients completed planned cycles of treatment and started maintenance therapy, 5 patients were still under planned cycles. The only one case of progressive disease occurred during the maintenance period. Grade 3 or above treatment-related adverse events were observed in 47.6% patients. One patient discontinued camrelizumab due to pneumonia, and one patient discontinued cetuximab due to grade 3 rash. Three patients reported fatal AEs, which was caused by tumor hemorrhage in the re-irradiated site, severe infectious pneumonia and choking due to swallowing, respectively. Conclusions: Camrelizumab combined with cetuximab and cisplatin-based chemotherapy induced a high ORR with prompt tumor shrinkage and was well tolerated in the scenario of first-line R/M HNSCC. These results meet protocol specifications for trial continuation. Final results will include long-term and stage 2 results. Clinical trial information: NCT05673577 .

Neoadjuvant immunochemotherapy and new radiomic predictor for resectable locally advanced oral squamous cell carcinoma.

6090 Background: The effectiveness of neoadjuvant immunochemotherapy (NAIC) in treating resectable locally advanced oral squamous cell carcinoma (LAOSCC) remains uncertain, with a notable lack of precise prognostic markers for NAIC outcomes. Methods: A single-arm prospective phase II trial was performed to assess the efficacy and safety of NAIC, consisting of 2 cycles of intravenous camrelizumab (200 mg), albumin paclitaxel (260 mg/m²), and cisplatin (75 mg/m²) administered every 3 weeks prior to radical surgery in LAOSCC patients. Adjuvant radiotherapy or chemoradiotherapy was determined by post-surgical pathology. Patients with previously untreated, stage III-IVB LAOSCC (the 8th edition of UICC/AJCC staging system), aged 18-75 years were enrolled. The primary endpoints were major pathological response (MPR, defined as ≤10% residual viable tumour (%RVT) cells) and safety, the second primary point was objective response rate (ORR) according to RECIST 1.1. To identify potential radiomic markers predictive of NAIC benefit, oscillating-gradient spin-echo (OGSE) magnetic resonance imaging sequences were obtained before and after NAIC. Results: From Feb 1, 2023 to Jan 1, 2024, 30 patients were enrolled, among which, 26 patients have received NAIC followed by surgery. The MPR rate was 65.4% (17/26), including a 34.6% (9/26) pathological complete response. Patients with PD-L1 (Combined Positive Score) ≥ 1 had higher MPR (80.0%, 16/20) than those with PD-L1 &lt; 1 (16.7%, 1/6). NAIC was well-tolerated, without adverse effects on subsequent surgery, only two patients experienced grade 3 or 4 adverse events during NAIC, including one with grade 4 neutropenia (3.8%), and one with grade 3 thrombocytopenia (3.8%). The ORR was 80.8% (21/26), with 15.4% (4/26) complete response, 65.4% (17/26) partial response, and with no cases of progressive disease observed. The mean cell diameters of the whole tumor were calculated based on the OGSE sequences, twenty patients completed the OGSE scaning pre- and post-NAIC treatment. Pearson correlation analyses found that small post-NAIC mean cell diameter significantly related with fewer %RVT ( p = 0.026), supporting its potential as new radiomic predictors of NAIC efficacy. Among patients with MPR, the cell diameters were significantly decreased after NAIC, with a mean cell diameter of 18.87 ± 2.49 μm and 14.77 ± 1.85 μm for pre- and post-NAIC tumor, respectively ( p = 0.001). Conclusions: Camrelizumab combined with albumin paclitaxel/cisplatin as NAIC for LAOSCC demonstrates promising MPR and well safety. Mean cell diameter of tumor, derived from OGSE sequences, emerges as a potential new radiomic marker for predicting NAIC efficacy. Ongoing follow-ups on long-term survival and the development of a bio-radiomic prediction model integrating pathological features with OGSE data are underway. Clinical trial information: ChiCTR2200066119.

Incidence, Correlates, and Prognostic Significance of Mixed Response in Advanced Non-small Cell Lung Cancer.

Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy. We analyzed patient-level data from ECOG-ACRIN E5508 (carboplatin-paclitaxel + bevacizumab induction followed by randomization to maintenance therapy regimens). For patients with at least 2 target lesions and available measurements after cycle 2, we characterized response as homogeneous response (HR, similar behavior of all lesions), MR (similar behavior but >30% difference in magnitude of best and least responding lesions), or true mixed response (TMR, best and least responding lesions showing different behavior: ≥10% growth versus ≥10% shrinkage). We compared category characteristics using Mann-Whitney U and Chi-square tests, and overall survival (OS) using log-rank test and Cox models. Among 965 evaluable patients, HR occurred in 609 patients (63%), MR in 208 (22%), and TMR in 148 (15%). Median OS was 13.6 months for HR, 12.0 months for MR, and 7.6 months for TMR (P < .001). Compared to HR, TMR had inferior OS among stable disease cases (HR 1.62; 95% CI, 1.23-2.12; P < .001) and a trend toward inferior OS among progressive disease cases (HR 1.39; 95% CI, 0.83-2.33; P = .2). In multivariate analysis, TMR was associated with worse OS (HR 1.48; 95% CI, 1.22-1.79; P < .001). True mixed response occurs in a substantial minority of lung cancer cases treated with chemotherapy and independently confers poor prognosis.

Transarterial Chemoembolization for Hepatic Metastasis of Solitary Fibrous Tumor

Background: Solitary fibrous tumors (SFT) are rare soft tissue tumors with a typically benign clinical course; however, up to 35% of SFT exhibit metastasis, resulting in a poor prognosis. The management of hepatic metastasis of SFT is yet to be established because of its rarity of cases. Objectives: Herein, we report the clinical results of 13 transarterial chemoembolization (TACE) sessions for hepatic metastasis in 5 patients with SFT. Patients and Methods: Patients with hepatic metastases from SFT who underwent TACE between May 2005 and April 2021 were retrospectively reviewed. Tumor response was evaluated using the modified response evaluation criteria in solid tumors (mRECIST). Results: Five patients (one male, mean age: 59.2 years) underwent 13 TACE sessions, resulting in four partial responses (PR, 30.8%), four stable disease cases (30.8%), and five progressive disease cases (38.5%). No severe complications occurred. Four of seven sessions (57.1%) of selective TACE showed partial response (PR). The mean progression-free survival (PFS) was 2.3 months (range: 0 - 8 months), and for sessions with PR, the mean PFS was 6.3 months (range: 3 - 8 months). The mean overall survival was 32.7 months (range: 18 - 44 months). Conclusion: This report suggests that TACE might be a potentially safe treatment option for hepatic metastasis of SFT, and it could offer a benefit in controlling local tumor growth in cases where selective TACE is applicable.

Novel use of alternate (Alt) response (Rp) criteria (Cr) for early prediction of outcomes in pancreatic (P) neuroendocrine tumors (NETs): Utilizing banked imaging data from the ECOG-ACRIN E2211 study.

4133 Background: The evaluation of treatment (Tx) Rp in NETs using CT/MRI scans can be difficult. Previous studies, including the E2211, have shown improved progression-free survival (PFS) but no significant difference in Rp as measured by RECIST 1.1 (R1.1) Cr. Thus, making it difficult to determine Tx effectiveness with short-term imaging, further complicated by differences in imaging protocols and inter-reader variability. Incorporating tumor density, using smaller threshold changes in tumor size, and novel quantitative features may be more sensitive and precise than R1.1 (e.g. CHOI in GIST) but they have not been studied for NETs. Methods: Banked CT images from the E2211 trial were repurposed to study novel Cr. Three radiologists provided a R1.1 assessment. Density and radiomic features were calculated from a 2D region of interest in the portal venous phase (as per CHOI Cr). Patients were classified as responders (PR), stable disease (SD), or progressive disease (PD) based on R1.1 and CHOI and compared with PFS to determine the best predictor. Radiomic features were analyzed using pyradiomics. Wilcoxon tests were used to compare scan quality by center type, agreement was measured using Cohen’s Kappa, and predictive value was quantified using the c-statistic and AUC for time-varying outcomes. Results: 67 patients had their scans repurposed for the study. Inter-reader agreement for overall imaging studies was fair, with only 5 of 9 PD cases noted by reviewer 1 being agreed upon by reviewer 2 (proportional agreement for PD = 0.56) and a Kappa of 0.6 (95% CI 0.41 – 0.79). The CHOI Cr showed improved prediction of PFS compared to R1.1 (12-month AUC 0.75 for CHOI vs 0.69 for R1.1, c-statistic 0.66 vs 0.64, p=0.22), and was able to predict improved PFS for PR versus SD at the first interval scan. This was not seen with R1.1 (table). Radiomics and texture analysis as a potential adjunct to CHOI is being studied and results will be presented. Conclusions: This study using repurposed banked imaging from an NCTN trial, found that there was significant variability in the interpretation of images, and that the R1.1 Cr had a poor correlation with Rp in PNETs. The CHOI Cr emerged as a better alternative as it may have a better correlation with PFS and the ability to predict outcomes at the point of first disease assessment. Importantly, CHOI Cr can be easily applied in clinical practice to inform treatment decisions. Further research is needed to confirm these findings and define the therapeutic importance. [Table: see text]

Efficiency and toxicity of nab-paclitaxel and camrelizumab in the second or above line treatment of advanced non-small cell lung cancer: a retrospective cohort study.

Paclitaxel-based chemotherapy represented by nanoparticle albumin-bound paclitaxel (nab-ptx) combined with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has become the standard model for the 1st treatment of advanced non-small cell lung cancer (NSCLC) with negative driver genes (such as EGFR, ALK, etc.), indicating that nab-ptx and PD-1/PD-L1 inhibitors are synergistic. Considering PD-1/PD-L1 inhibitors alone or chemotherapy single has limited efficiency in the 2nd line or above of NSCLC, so it is of great significance to explore the combination of PD-1/PD-L1 inhibitors and nab-ptx to further improve the therapeutic efficiency in such field. We retrospectively collected the date of these advanced NSCLC patients who accept the combination treatment of PD-1/PD-L1 inhibitor and nab-ptx in the 2nd or above line. We further analysed baseline clinical characteristics, therapeutic efficacy, treatment-related adverse events (AEs) and followed up survival. The main parameters of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. A total of 53 patients were enrolled in this study. The preliminary results indicated that the ORR of the combination of camrelizumab and nab-ptx was about 36% in the 2nd or above line of NSCLC, with 19 cases of partial response (PR), 16 of stable disease (SD), and 18 cases of progressive disease (PD); the mean PFS and OS were 5 months and 10 months, respectively. Further subgroup analysis demonstrated that the expression of PD-L1 level and the decrease of regulatory T cell (Treg) correlated with the efficiency. the main adverse reactions were neuropathy, bone marrow suppression, fatigue, and hypothyroidism, most of which were mild and tolerable, indicating such regimen was higher efficiency and lower cytotoxicity for NSCLC. The combination of nab-ptx and camrelizumab shows promising efficiency and lower toxicities for advanced NSCLC in the 2nd or above line treatment. The mechanism of action may be related to depleting Treg ratio; such a regimen may have the potential to become an effective treatment approach for NSCLC. However, due to the limitation of sample size, the real value of this regimen needs to be further confirmed in the future.

Comparative outcome of cisplatin-capecitabine regimen with oxaliplatincapecitabine regimen in advanced gastric carcinoma: a quasi-experimental study

Chemotherapy is the primary therapeutic choice for advanced gastric cancer. The goal of this study was to assess the effectiveness and toxicity of the cisplatin-capecitabine regimen versus the oxaliplatin-capecitabine regimen in treating advanced gastric cancer. Between February 2021 and March 2022, this quasi-experimental study was conducted on 64 advanced gastric cancer patients. Purposive sampling was used to include those who met the inclusion criteria and distributed them evenly between the two arms. Arm A got an injection of cisplatin (80 mg/m2 on day 1) with oral capecitabine (1000 mg/m2 b.i.d. on days 1–14), whereas arm B received an injection of oxaliplatin (130 mg/m2 on day 1) plus oral capecitabine (1000 mg/m2 b.i.d. on days 1–14), every 3 weeks for 6 cycles. A final check-up was done at 12 weeks after the treatment. In arm A, 18 (56.2%) patients exhibited partial response compared to 15 (46.9%) in arm B. Stable diseases were also reported in both arms (18.8% in arm A and 21.9% in arm B). There were 8 (25.0%) cases of progressive disease in arm A and 10 (31.2%) cases in Arm B. The median progression-free survival in arms A (5.6 months) was almost similar to arm B (5.9 months). The most prevalent toxicities in both arms were vomiting, diarrhea, anemia, neutropenia, oral mucositis, paresthesia, handfoot syndrome, and renal toxicity. There were no statistically significant variations in outcomes between the two arms. In conclusion, the cisplatincapecitabine regimen is as effective as the oxaliplatin-capecitabine regimen in advanced gastric cancer. BSMMU J 2022; 15(3): 180-185

Efficacy of combined organ-sparing management of invasive upper urinary tract urothelial carcinoma.

The study aimed to evaluate the objective response level to neoadjuvant platinum-based chemotherapy and tumour complexity reduction in patients with invasive upper tract urothelial cancer (UTUC), and to estimate the functional and oncological outcomes of the combined organ-sparing approach compared to radical nephroureterectomy. This prospective, non-randomised cohort study was conducted by the National Cancer Institute of Ukraine. Patients with invasive UTUC were enrolled between October 2016 and January 2021. Patients were allocated to one of two cohorts depending on the estimated glomerular filtration rate (eGFR) of the affected kidney. In cases where eGFR was preserved, neoadjuvant chemotherapy with an organ-sparing approach was used; all other cases proceeded directly to radical nephroureterectomy. A total of 64 patients (32 in each cohort) with invasive UTUC were enrolled. Both groups were comparable in terms of age, sex, T stage, maximal tumour size, eGFR, Eastern Cooperation Oncology Group (ECOG) performance status, body mass Index (BMI), and haemoglobin level. After four cycles of chemotherapy, there were no cases of progressive disease, stable disease [16 (50%), partial response; 12 (38%); and complete response, 4 (12%)]. The average maximal tumour size decreased by 2.3 cm. Prior to surgical treatment, total GFR according to scintigraphy did not statistically differ in both groups (р = 0.13). However, 3 months after surgery patients who underwent the organ-sparing approach had a better total eGFR (р = 0.0039), which was probably owing to the preserved kidney function (18.9 +5.1 mL/min). Better 2-year recurrence-free survival was also observed in the organ-sparing management group (85% vs 72%, log-rank test; p = 0.03). Neoadjuvant systemic therapy reduces the surgical complexity of invasive UTUC without influencing the safety profile. The gemcitabine/cisplatin regimen leads to high regression rates among invasive UTUC, which could result in an organ-sparing approach in selected cases. Kidney function preservation remains a key parameter that can increase the possibility of effective systemic treatment.

Cisplatin-Capecitabine vs Oxaliplatin-Capecitabine: Comparison of Outcomes in Advanced Gastric Carcinoma Patients

Introduction: Chemotherapy is the primary therapeutic choice for advanced gastric cancer. Different types of medicine combinations are can be used for chemotherapy treatment, but oxaliplatin is one of the more common ones, used to treat metastasized cancer. But recently, cisplatin has shown similar outcome, while costing less for the patients and the hospital. The goal of this study was to assess the effectiveness of cisplatin-capecitabine versus oxaliplatin-capecitabine in treating advanced gastric cancer by measuring disease response and toxicity levels. Methods: This Quasi-Experimental study was conducted at the Department of Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. The study duration was 1 year, from February 2021 to March 2022. During this period, a total of 64 cases of advanced gastric cancer were divided in two equal groups, Arm A who had received cisplatin capecitabine, and Arm B who received oxaliplatin capecitabine. Result: In Arm A, 18 (56.3%) patients exhibited partial response (PR), whereas 15 (46.9%) patients in Arm B showed PR. Stable diseases (SD) were also reported in both arms (18.8% in arm A and 21.9% in arm B). There were 8 (25.0%) cases of progressive disease (PD) in Arm A and 10 (31.3%) cases in Arm B. The most prevalent toxicities in both arms were vomiting, diarrhea, anemia, neutropenia, oral mucositis, paresthesia, hand-foot syndrome, and renal toxicity. There were no statistically significant variations in outcomes between the two arms (p-value &gt; 0.05). Conclusion: In advanced gastric cancer, the Cisplatin-Capecitabine regimen is equally effective as Oxaliplatin-Capecitabine, and there was no significant difference between the presenting toxic effects. As the Cisplatin-Capecitabine regimen is less costly than the combination of Oxaliplatin-Capecitabine, and shows similar outcomes in terms of response and toxicity, it is a valid alternative choice of medicine for patients who are unable to afford an .........

Analysis of Immune Pharmacodynamic and Baseline Biomarkers in Patients with Relapsed or Refractory Follicular Lymphoma Treated with Mosunetuzumab in Combination with Lenalidomide

Background: Mosunetuzumab (M) is a bispecific monoclonal antibody targeting CD20 and CD3 that redirects T cells to eliminate B cells and has shown efficacy in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL; Budde et al. Lancet Oncol 2022). Lenalidomide (Len) is clinically active in FL, and its immunomodulatory activity offers potential synergistic efficacy when combined with M. Here, we present preliminary data from a Phase Ib/II trial (NCT04246086), which aimed to characterize pharmacodynamic biomarkers and investigate baseline (BL) features of early progressive disease (PD), in pts with R/R FL treated with M+Len. Methods: Eligible pts had Grade 1-3a R/R FL and received ≥1 prior systemic anti-cancer therapy. Pts received ≤12 cycles of M+Len (Cycle [C] 1: 21 days; C2-12: 28 days). In C1, step-up doses of intravenous M were given on C1 Day (D) 1 (1mg) and C1D8 (2mg), with the target dose (30mg) given on C1D15 and then on D1 of C2‒12. Len (20mg) was administered orally on D2‒22 (n=10) and on D1-21 of C2-12 for the remaining 19 pts. Activation of immune cells during M+Len treatment was assessed in longitudinal collections of peripheral blood by flow cytometry, and plasma IL-6 levels were evaluated by enzyme-linked immunosorbent assay. CD20 expression was assessed by immunohistochemistry in BL and PD biopsies. CD20 loss was defined as ≤5% CD20+PAX5+ cells. Mutation profiling was performed by next-generation sequencing (NGS). A modified version of the AVENIO circulating tumor (ct)DNA analysis workflow and pipeline (Roche; for research use only) was used for NGS, based on the previously described CAPP-Seq technology (Kurtz et al. J Clin Oncol 2018). Results: A transient reduction in circulating T-cell counts (likely due to margination) and increase in percentage (%) of T cells expressing the activation marker CD69 were observed after M monotherapy in C1, and these kinetics were maintained in subsequent cycles, particularly in the CD4 T-cell population. Maturation of T cells, measured as % of T cells expressing human leukocyte antigen DR, increased after C2, following the addition of Len, and was sustained throughout M+Len treatment. The % of circulating programmed cell death protein 1 (PD-1)+ CD4 T cells increased after the first cycle of M, implying a rapid activation of T cells by M, and progressively decreased after C2. A decrease in % of PD1+ CD4 T cells suggested that sustained PD-1 expression, often a sign of T cell exhaustion, does not occur during M+Len treatment. Natural killer (NK) cells showed transient activation following M infusion (assessed as margination and % of CD69+ NK cells), and a sustained increase in functional markers, like granzyme B, during treatment with M+Len. IL-6 secretion was often enhanced after the first M infusion in C1. However, increased IL-6 levels were not observed after M+Len co-administration in subsequent cycles. As of April 25, 2022, 29 pts had been enrolled and were evaluable for efficacy. Best objective response rate was 89.7%, with complete metabolic response (CMR) observed in 21 pts (72.4%). Five cases of early PD (≤6 cycles of treatment) were observed. BL CD20 expression was heterogeneous (n=25 BL biopsies), and one CD20-negative pt experienced early PD. Two pts with early PD showed CD20 loss at progression. ctDNA analysis was performed in a subgroup of 5 pts with PD vs 5 with CMR for signal seeking. A trend towards higher median ctDNA levels at BL, measured as mutant molecules per mL, was observed in pts with early PD (400.1) vs CMR (58.6). Moreover, a higher median number of somatic variants was found in plasma (145.0) vs tissue (120.0) at BL, with a lower median concordance of plasma variants in tissue in pts with early PD (n=4; 43.8%) compared with those achieving CMR (n=5; 94.1%), suggesting higher tumor heterogeneity in early PD. Conclusions: In pts with R/R FL, our preliminary data suggest that M+Len activates the immune system. Increased % of T and NK cells expressing maturation and functional markers were observed during M+Len treatment. In contrast, addition of Len to M did not enhance IL-6 secretion, a cytokine known to be related with cytokine release syndrome, which is consistent with the manageable safety profile previously reported for this combination. Future investigations with a larger sample size are needed to further assess the prognostic value of CD20 expression in response to the M+Len combination and the prognostic value of ctDNA measurement at BL.

Clinical characteristics and prognosis of patients with newly-diagnosed multiple myeloma with t(11;14)

Objective: To explore the clinical characteristics and prognosis of multiple myeloma (MM) patients with t(11;14). Methods: The clinical data of patients newly diagnosed with MM with t(11;14), which confirmed by fluorescence in situ hybridization (FISH), from January 1, 2016 to May 31, 2021 in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine was retrospectively collected. A total of 45 patients were included. Bortezomib based induction therapy were given to 88.9% (40/45) patients, while 11.1% (5/45) received Imids-based therapy. Fourteen patients underwent the autologous hematopoietic stem cell transplantation (AHSCT). The clinical characteristics, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and risk factors affecting survival were analyzed. Results: The average age of patients were (58.8±9.6) years, and 62.2%(28/45)were male. A relatively high incidence of bone lesion 82.2%(37/45)was observed. After 4 cycles induction therapy, the ORR was 66.7% (30/45), and ≥very good partial response (VGPR) was 31.3% (14/45). The rate of ≥VGPR increased to 92.9% (13/14) after AHSCT. The follow-up time [M(Q1,Q3)] was 27(20,42)months. The PFS was 34 (95%CI: 23-45) months, the median OS was 44 (95%CI:33-51) months. Median PFS were 48 (only 3 cases of progressive disease, CI not available) months and 24 (95%CI:13-35) months in the transplantation group and non-transplant group respectively (P=0.115). Median OS were 60 (only 1 case of death, CI not available) months and 48 (95%CI:22-74) months in the transplantation group and non-transplantation group, respectively (P=0.238). Cox regression analysis indicated that the number of plasma cell ≥50% in bone marrow and CD20 expression on myeloma cells were the risk factors for PFS[OR=3.272,95%CI:1.167-9.170,P=0.024;OR=3.480,95%CI:1.082-11.234,P=0.036]. No significant effective factor on OS was found. Conclusions: For multiple myeloma patient with t(11;14), the response rate with novel agents induction therapy is not high, but autologous stem cell transplantation can deepen remission. The high burden of bone marrow plasma cells and the expression of CD20 may be associated with the poor prognosis.

Clinical application of radiotherapy in patients with oligometastatic ovarian cancer: a sharp tool to prolong the interval of systemic treatment

BackgroundWith the advances of radiation technology, treatment of oligometastatic disease, with limited metastatic burden, have more chances to achieve long-term local control. Here we aim to evaluate the efficacy and safety of radiotherapy (RT) in oligometastatic ovarian cancer patients.MethodsA retrospective analysis collecting 142 patients (189 lesions) with oligometastatic ovarian cancer were included in the study. All pateints received radiotherapy and the curative effect and response rate were evaluated by diagnostic imaging after 1–3 months of radiotherapy with RECIST. Endpoints were the rate of complete response (CR), chemotherapy-free interval (CFI), local control (LC) rate and overall survival (OS) rate. Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG). Logistic and Cox regression were used for the uni- and multivariate analysis of factors influencing survival outcomes.ResultsFrom 2013.1.1 to 2020.12.30, a total of 142 ovarian cancer patients (189 oligometastasis lesions) were included in the analysis. Prescribed doses to an average GTV of 3.10 cm were 1.8–8 Gy/fraction, median BED (28–115, a/b = 10 Gy), 5–28 fractions. For 179 evaluable lesions, the cases of CR, partial response (PR), stable disease (SD) and progressive disease (PD) after radiotherapy were 22,39,38 and 80 respectively. The disease control rate (DCR): CR + PR + SD was 55.31%, and the objective response rate (ORR): CR + PR was 34.08%. No patient developed grade 3 or higher side effect. The median CFI was 14 months (1–99 months), and the LC rate was 69.7%, 54.3% and 40.9% in 1 year, 2 years and 5 years respectively. GTV < 3 cm before treatment, platinum sensitivity, time from the last treatment ≥ 6 months, single lesion and BED(a/b = 10 Gy) ≥ 60 are the factors of good LC (p < 0.05). The total OS of 1 year, 2 years and 5 years were 67.1%, 52.6% and 30.3%, respectively. Single lesion (HR 0.598, 95%CI 0.405–0.884), DCR (HR 0.640, 95% CI 0.448–0.918) and ORR(HR 0.466, 95% CI 0.308–0.707) were the significant factors influencing 5-year OS.ConclusionFor patients with oligometastatic ovarian cancer, radiotherapy has high LC, long chemotherapy-free interval, and survival benefits. Subgroup analysis shows that patients with single lesion and good local treatment results have higher overall survival rate, suggesting that active treatment is also beneficial for oligometastatic ovarian cancer patients.

P-030: Regular monitoring with whole body low-dose CT for osteolysis in multiple myeloma reveals more cases of progressive bone disease than imaging performed by clinical indication

P-030: Regular monitoring with whole body low-dose CT for osteolysis in multiple myeloma reveals more cases of progressive bone disease than imaging performed by clinical indication

Evaluation of 11 C-choline positron emission tomography/computed tomography for determining treatment response in castration-resistant prostate cancer patients.

The utility of 11 C-choline positron emission tomography/computed tomography for determining treatment response as compared with prostate-specific antigen response and prognosis prediction in castration-resistant prostate cancer patients was investigated. Eighty-four 11 C-choline-positron emission tomography/computed tomography scans before/after treatments with abiraterone (n = 12 patients), enzalutamide (n = 3), docetaxel (n = 9), cabazitaxel (n = 5), radiation therapy alone (n = 3), radiation therapy, enzalutamide, and/or abiraterone (n = 5), radium-223 (n = 4), and radiofrequency ablation (n = 1) in 42 castration-resistant prostate cancer patients were retrospectively examined. Prostate-specific antigen values were determined before and after treatment. Using the Kaplan-Meier method, the correlation of Positron Emission Tomography Response Criteria In Solid Tumors with prostate-specific antigen response and prognostic impact was evaluated. Pretreatment 11 C-choline-positron emission tomography/computed tomography findings identified local, lymph node, bone, and visceral metastasis in 12, 12, 29, and five patients, respectively. Following treatments, complete metabolic response was noted in one, partial metabolic response in eight, stable metabolic disease in 13, and progressive metabolic disease in 20. Mean prostate-specific antigen change for complete metabolic response, partial metabolic response, stable metabolic disease and progressive metabolic disease was -48.9%, -55.0% (range -92.4% to -19.1%), -4.2% (-33.2% to 35.1%), and 142.7% (30.7% to 373.8%), respectively, significantly greater in the progressive metabolic disease cases (P < 0.01). Positron Emission Tomography Response Criteria In Solid Tumors was well correlated with prostate-specific antigen change. Patients with no progression (complete metabolic response/partial metabolic response/stable metabolic disease) showed significantly longer cancer-specific survival than progressive metabolic disease (P < 0.005). Using pretreatment 11 C-choline-positron emission tomography/computed tomography results to divide into three groups; (a) local and/or lymph node metastasis without bone metastasis (n = 10), (b) <6 bone metastasis sites (n = 16), (c) ≥6 bone metastasis sites and/or visceral metastasis (n = 16), cancer-specific survival showed significant stratification (P < 0.001). 11 C-choline-positron emission tomography/computed tomography may reflect castration-resistant prostate cancer metastatic lesion activity for treatment response and prognosis evaluations.

Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study.

Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.