Complete Responders Research Articles

Postradiotherapy Response Assessment Using 18F-FDG PET/CT in Salivary Gland Carcinoma-A Multicenter Study.

This multicenter study investigates the efficacy of 18F-FDG PET/CT in postradiotherapy (post-RT) response evaluation in salivary gland carcinoma (SGC). We retrospectively reviewed 115 SGC patients who underwent definitive or adjuvant RT followed by 18F-FDG PET/CT between 2004 and 2021. Most tumors were parotid gland malignancies (50%). The most common histological subtypes were adenoid cystic (29%) and mucoepidermoid carcinomas (18%). The median follow-up was 65 months. Post-RT anatomic images (CT/MRI) revealed complete response (CR) in 51 patients (44%). Among 53 patients with partial response or stable disease, only 17 (32%) patients experienced locoregional recurrence, with a 5-year locoregional control rate of 69%. Post-RT 18F-FDG PET/CT documented metabolic CR in 81 patients (70%). Metabolic complete responders had significantly higher 5-year locoregional control (90% vs 43%), distant metastasis-free survival (80% vs 48%), progression-free survival (76% vs 24%), and overall survival rates (89% vs 42%) compared with non-complete responders (all P < 0.001), as confirmed in both univariate and multivariate analyses. It identified additional viable tumors in 18 cases (16%) and facilitated salvage local therapies in 7 patients (6%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of post-RT 18F-FDG PET/CT were 63%, 91%, 70%, 88%, and 84%, respectively, in predicting locoregional recurrence. 18F-FDG PET/CT showed significantly higher sensitivity (88% vs 36%, P = 0.011) in tumors with pre-RT SUVmax ≥7.39 compared with those with SUVmax <7.39. Post-RT 18F-FDG PET/CT demonstrates high negative predictive value and specificity, with metabolic CR predicting excellent outcomes. Additionally, it exhibits higher sensitivity for high-SUVmax SGC, facilitating early detection of viable tumors.

Histological and photoacoustic evaluation of rectal cancer after neoadjuvant therapy using microvascular density.

As non-operative management of rectal cancer proliferates, re-staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co-registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD). Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation-specific-related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31-stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non-responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD. CD31 MVD and ERG nuclei density were strongly correlated (R2 = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm2; 95% CI 434-764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm2; 95% CI 64-306) and non-responders (117 nuclei/mm2; 95% CI 42-192). No significant difference was found between the partial responders and non-responders (P = 0.60). Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy.

Is an Electronic Nose Able to Predict Clinical Response following Neoadjuvant Treatment of Rectal Cancer? A Prospective Pilot Study.

Introduction: A watch-and-wait strategy for patients with rectal cancer who achieve a clinical complete response after neoadjuvant (chemo) radiotherapy is a valuable alternative to rectal resection. In this pilot study, we explored the use of an electronic nose to predict response to neoadjuvant therapy by analyzing breath-derived volatile organic compounds. Materials and Methods: A pilot study was performed between 2020 and 2022 on patients diagnosed with intermediate- or high-risk rectal cancer who were scheduled for neoadjuvant therapy. Breath samples were collected before and after (chemo) radiotherapy. A machine-learning model was developed to predict clinical response using curatively treated rectal cancer patients as controls. Results: For developing the machine-learning model, a total of 99 patients were included: 45 patients with rectal cancer and 54 controls. In the training set, the model successfully discriminated between patients with and without rectal cancer, with a sensitivity and specificity of 0.80 and 0.65, respectively, and an accuracy of 0.72. In the test set, the model predicted partial or (near) complete response with a sensitivity and specificity of 0.64 and 0.47, respectively, and an accuracy of 0.58. The AUC of the ROC curve was 0.63. Conclusions: The prediction model developed in this pilot study lacks the ability to accurately differentiate between partial and (near) complete responders with an electronic nose. Machine-learning studies demand a substantial number of patients and operate in a rapidly evolving field. Therefore, the prevalence of disease and duration of a study are crucial considerations for future research.

Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients.

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of Lachnospiraceae (FLach) as structural homologs of tumor-associated antigens, detect FLach-reactive CD8+ Tcells in complete responders before ICI therapy, and demonstrate that FLach peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides.

Is Liver Resection Still Required for Patients Who Have Predictive Factors for Complete Pathologic Necrosis after Downstaging Treatments of Locally Advanced Hepatocellular Carcinoma?

BackgroundLiver resection can induce complete remission after tumor downstaging in patients with locally advanced hepatocellular carcinoma. However, additional benefits of liver resection have not been investigated in patients expected to have complete pathological necrosis (CPN) following HCC downstaging. MethodsBetween 2002 and 2019, 999 patients with locally advanced HCC underwent concurrent chemoradiotherapy (CCRT) (n=800) or transarterial radioembolization (TARE) (n=199). Among these patients, excluding those who underwent liver transplantation, 94 who underwent liver resection (OP group) and 867 who did not undergo surgical treatment (non-OP group) were included in this study. CPN predictive factors in the OP group were analyzed using logistic regression analysis. Long-term outcomes were compared between patients with CPN (op-CPN) and those with CPN predictive factors in the non-OP group (nop-CPNPF). ResultsOf the 94 patients in the OP group, 38 (40.4%) had CPN (CCRT, n=72; TARE, n=22). In the multivariate analysis, CPN predictive factors were complete radiologic response and tumor marker responders (odds ratio [OR] 18.468, p=0.006; OR 3.698, p=0.045). Among the non-OP group, 21 patients were in the nop-CPNPF group. There was no difference in DFS between the nop-CPNPF and op-CPN groups (40.0 ± 18.3 vs. 60.0 ± 14.0 months, p=0.838). The OS of the op-CPN group was not higher than that of the nop-CPNPF group (5-year OS: 39.4% vs. 33.3%, p=0.328). ConclusionsThe nop-CPNPF group showed long-term outcomes similar to those of the op-CPN group, suggesting that liver resection may not provide additional benefits for long-term outcomes in patients with CPN-PF after HCC downstaging.

Effect of add-on naldemedine treatment in patients with cancer and opioid-induced constipation insufficiently responding to magnesium oxide: a pooled, subgroup analysis of two randomized controlled trials.

To evaluate the additive effect of naldemedine tosylate (naldemedine) on opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment. We combined two randomized, double-blind, placebo-controlled, phase IIb and III trials of naldemedine and conducted a post hoc subgroup analysis. We evaluated the effect and safety of naldemedine in 116 patients who received naldemedine in addition to magnesium oxide (naldemedine group) and 117 patients who received placebo in addition to magnesium oxide (placebo group). Both groups included patients insufficiently responding to magnesium oxide for opioid-induced constipation. Effect was assessed using spontaneous bowel movement responder rate, complete spontaneous bowel movement responder rate, changes in spontaneous bowel movements and complete spontaneous bowel movements. Safety was also assessed. During the 2-week treatment period, the responder rates for spontaneous bowel movement and complete spontaneous bowel movement were 73.3 and 43.1% in naldemedine group, respectively, which were significantly higher (P<0.0001) than 41.9 and 14.5% in placebo group, respectively. Median time to first spontaneous bowel movement and first complete spontaneous bowel movement was significantly shorter (P<0.0001) in the naldemedine group (4.0 and 21.3h, respectively) than in the placebo group (27.7 and 211.7h, respectively). The incidence of adverse events and diarrhoea was significantly higher (P<0.05) in the naldemedine group than in the placebo group, while the incidence of serious adverse events and severe diarrhoea was not significantly different between the naldemedine and placebo groups. The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.

Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial.

Primary results (median follow-up, 10.7 months) from the pivotal EPCORE® NHL-1 study in relapsed or refractory (R/R) large B-cell lymphoma (LBCL) demonstrated deep, durable responses with epcoritamab, a CD3xCD20 bispecific antibody, when used as monotherapy. We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival (PFS) and overall survival (OS) rates were 27.8% and 44.6%, respectively. An estimated 64.2% of complete responders remained in CR at 24 months. Estimated 24-month PFS and OS rates among complete responders were 65.1% and 78.2%, respectively. Of 119 minimal residual disease (MRD)-evaluable patients, 45.4% had MRD negativity, which correlated with longer PFS and OS. CR rates were generally consistent across predefined subgroups: 36% prior chimeric antigen receptor (CAR) T-cell therapy, 32% primary refractory disease, and 37% International Prognostic Index ≥3. The most common treatment-emergent adverse events were cytokine release syndrome (51.0%), pyrexia (24.8%), fatigue (24.2%), and neutropenia (23.6%). These results underscore the long-term benefit of epcoritamab for treating R/R LBCL with deep responses across subgroups, including patients with hard-to-treat disease and expected poor prognosis (ClinicalTrials.gov Registration: NCT03625037).

Abstract B053: SUMOylation and TIGIT inhibition: a novel immunotherapy combination for pancreatic cancer

Abstract Introduction: Immune checkpoint inhibitors have shown promise in many other solid tumors but have been disappointing in pancreatic ductal adenocarcinoma (PDAC). Preclinical work demonstrates that the immune checkpoint receptor TIGIT plays a key role in PDAC immune evasion and may be a better therapeutic target than the PD1 or CTLA4 axes. Post-translational small-ubiquitin-like modification (SUMOylation) regulates the activity of numerous proteins involved in cell proliferation. Our laboratory has shown that inhibition of SUMOylation with small molecule TAK-981 favorably modulates the PDAC immune microenvironment and specifically increases the expression of TIGIT binding partners CD226 on immune cells and CD155 on tumor cells. We hypothesized that inhibition of SUMOylation with small molecule TAK-981 would synergize with anti-TIGIT antibody therapy to induce anti-tumor immunity. Methods:All studies utilized a murine PDAC organoid line (KPC46) derived from a liver metastasis in a genetically engineered mouse model (KPC). KPC46 consistently metastasizes to the liver when implanted orthotopically into the tail of the pancreas in immunocompetent mice. Following tumor implantation, mice were surveilled by ultrasound until tumors reached 5-7 mm in diameter, then randomized to one of two treatment groups: TAK-981 + anti-TIGIT or vehicle control (n=10/group). Monotherapies were not included, as each drug alone did not produce significant responses in prior studies using this model. The treatment cohort received 15 mg/kg of TAK-981 and 100 micrograms of anti-TIGIT antibody via intraperitoneal injection every 48 hours starting 14 and 15 days, respectively, post-implantation, for a total of 4 weeks. Complete responders were defined as absence of disease after 2 months of observation. Complete responders and age-matched controls (n=3/group) were rechallenged with subcutaneous tumor injection and monitored for tumor development. Results:Survival of PDAC mice was significantly prolonged in the combination group when compared to the control group (median survival 81 vs 42 days, P&amp;lt;0.05). A total of 4 mice (40%) were deemed complete responders after 2 months of monitoring. The re-challenge experiment produced tumors in all three control mice but none of the treated mice by 4 weeks after implantation. Conclusion:In this study, we explored the combination of two promising immunotherapy agents for PDAC which demonstrated significant additive effects generating durable and complete responses. We were able to confirm the presence of protective immunity. These results are rarely seen in PDAC experiments. Further experiments to better understand and optimize these effects are underway. These drugs are currently in clinical trials for solid tumors and could feasibly be studied in the near future in PDAC. Citation Format: Jorge R de la Torre Medina, Utsav Joshi, Jaynath Shankara Narayanan, Herve Tiriac, Yuan Chen, Rebekah White. SUMOylation and TIGIT inhibition: a novel immunotherapy combination for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B053.

Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma

AbstractEngineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day –28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients’ immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy.

FP1.8 - Optimizing Rectal Cancer Treatment: Comprehensive response to Neoadjuvant therapy

Abstract Aims This study aimed to assess the outcomes and feasibility of a watch-and-wait strategy in patients with rectal cancer showing a complete response to neoadjuvant chemoradiotherapy (CRT). The primary objectives included evaluating the oncological results, disease-free interval, and survival rates in patients who underwent the watch-and-wait approach after a complete clinical response. Methods The study involved a retrospective analysis of last 10 years of rectal cancer patients enrolled in a complete responder surveillance program in an acute general hospital. Cohort characteristics, including age, performance status, tumor histology, distance from the anal verge, and treatment modalities, were documented. Results The median age was 74 (57-90), and the median performance status was 1, with the age at diagnosis being 69. All cohort members had a histologically confirmed rectal adenocarcinoma. The median tumor-to-anal-verge distance was 5 cm (1-10 cm). Neoadjuvant chemotherapy was administered to 55% of patients. All patients underwent long-course radiotherapy, and 35% received papillon contact brachytherapy. Total neoadjuvant therapy was received by 10%. The median follow-up involved approximately 9 colonoscopies. During follow-up, 25% of patients experienced recurrence, with a median disease-free interval of 3.5 years. Conclusion The findings of this study, in addition to ongoing prospective clinical trials and insights from databases such as EURECCA and OnCore, indicate that a watch-and-wait approach can be safe and effective for selected rectal cancer patients who have achieved a complete response to neoadjuvant CRT. This study highlights the significance of additional research to identify appropriate patients for this approach and to refine its implementation in rectal cancer management.

754. PATHOLOGICAL RESPONSE PREDICTS EFFICACY OF ADJUVANT FLOT CHEMOTHERAPY IN GASTROESOPHAGEAL CANCER: AN INTERNATIONAL COHORT STUDY

Abstract Background Perioperative FLOT-based chemotherapy is the current standard of care for all patients with locally-advanced gastroesophageal cancer. However, many patients are unable to complete all planned adjuvant FLOT cycles due to treatment related toxicity and diminished performance status after radical surgery. Within this context, it is unclear whether adjuvant FLOT will improve oncological outcomes for patients with cancers that either don’t respond or respond exceptionally well to neoadjuvant FLOT. To facilitate clinical decision-making, we examined whether pathological response to neoadjuvant FLOT can guide its adjuvant use. Methods Prospectively collected data from 43 centres across 12 countries was analysed. Patients with non-metastatic gastroesophageal adenocarcinoma who received neoadjuvant FLOT followed by radical surgery between 2017-2022 were included. Pathological response was assessed using validated tumour regression grading (TRG) systems. All TRG were trichotomized into minimal responders (MR=worse TRG category), complete responders (CR=pathological complete response), and partial responders (PR=all TRG categories between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT within these cohorts were compared using Kaplan Meier and Cox regression analysis. These findings were validated using propensity score matched analysis. Results 1887 patients (MR n=459, CR n=221, PR n=1207) were evaluated. The median follow-up was 25.5 months. In the MR group, there was no DFS (HR=1.03, 95%CI 0.78-1.36) or adjusted-OS (HR=0.96, 95%CI 0.70-1.30) difference between those who did (n=272) and did not (n=187) receive adjuvant FLOT. In the CR group, there was no DFS (HR=0.88, 95%CI 0.41-1.85) or OS (HR=0.69, 95%CI 0.31-1.54) difference between those who did (n=136) and did not (n=85) receive adjuvant FLOT. In the PR group (adjuvant FLOT n=847, no adjuvant FLOT n=360), adjuvant FLOT conferred a significant DFS (HR=0.68, 95%CI 0.55-0.86) and OS (HR=0.55, 95%CI 0.44-0.69) benefit. Conclusions Pathological response to neoadjuvant FLOT predicts therapeutic efficacy to adjuvant FLOT. Only partial responders benefit from adjuvant treatment. Our findings challenge the current doctrine that perioperative FLOT should be applied to all patients regardless of pathological tumour response.

Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP‐Ribose)‐Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study

The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients. Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS). From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS. This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

Stereotactic Ablative Radiation Therapy for Oligometastatic Ovarian Cancer Lymph Node Disease: The MITO-RT3/RAD Phase II Trial

PurposeMITO-RT3/RAD (NCT04593381) is a prospective multicenter Phase II trial designed to assess the effectiveness and safety of stereotactic body radiotherapy (SBRT) in patients diagnosed with oligometastatic ovarian cancer (oligo-MPR-OC). In this report, we provide the results of the trial in the setting of lymph node disease. MethodsThe primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival (PFS), overall survival (OS), treatment-free interval (TFI), and toxicity rates. Sample size was based on a previous study reporting an average 70.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 70.0% to 85.0%, with an α error of 0.05 (one-side) and a β error of 0.1. ResultsThe study met its primary endpoint of a statistically significant improvement of CR. 135 patients with 249 lesions were enrolled across fifteen Institutions from May 2019 to November 2023. CR were observed in 194 lesions (77.9%), PR in 40 (16.1%), SD in 14 (5.6%), and Progressive Disease (PD) in one lesion (0.4%). The ORR was 94%, with an overall clinical benefit rate of 99.6%. CR lesions exhibited a significantly higher LC rate than partial or not responding lesions (12-month LC: 92.7% vs. 63.1%, p<0.001). The 12-months actuarial rates for PFS and for OS were 36.6% (CR 38.3% vs not-CR 18.8%; p: 0.022) and 97.2% (CR 97.8% vs not-CR 93.8%; p: 0.067), respectively. The 12-months actuarial rate for Treatment Free Interval was 52.7% (CR 58.4% vs not-CR 24.4%; p: 0.004). CR was substantially associated with higher PFS (p: 0.036) and TFI (p: 0.006) rates at the univariate analysis. Twenty-three patients (17.0%) experienced mild acute toxicity. Late toxicity was reported in 9 patients (6.7%), mostly Grade 1. ConclusionsThis trial confirms the efficacy of ablative SBRT, with minimal toxicity observed. SBRT offered a high CR rate, promising long-term outcomes and systemic-therapy-free survival rate for complete responders.

ABCL-191 Extended Follow-Up Beyond 2.5 Years Demonstrates Long-Term Efficacy in Complete Responders Following Epcoritamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

ABCL-191 Extended Follow-Up Beyond 2.5 Years Demonstrates Long-Term Efficacy in Complete Responders Following Epcoritamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

Extended Follow-Up Beyond 2 .5 Years Demonstrates Long-Term Efficacy in Complete Responders Following Epcoritamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

Extended Follow-Up Beyond 2 .5 Years Demonstrates Long-Term Efficacy in Complete Responders Following Epcoritamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

15O]H2O PET/MRI for Assessment of Complete Response to Neoadjuvant or Induction Chemotherapy in Patients with Muscle-Invasive Bladder Cancer: A Pilot Study.

Background: Accurate assessment of therapy response to chemotherapy could possibly offer a bladder-sparing approach in selected patients with localized muscle-invasive bladder cancer (MIBC). The aim of this study was to evaluate whether [15O]H2O PET/MRI can be used for assessment of complete local pathological response to preoperative chemotherapy in patients with MIBC. Methods: This prospective pilot study included 13 patients with MIBC treated with neoadjuvant or induction chemotherapy and subsequent radical cystectomy. Patients underwent a [15O]H2O PET/MRI scan before chemotherapy and another scan after chemotherapy before radical cystectomy. Volumes of interest were delineated on T2-weighted MRI and transferred to parametric images for dynamic analysis. Tumor blood flow (TBF) was estimated by [15O]H2O PET. Changes in TBF were compared with histopathology. The Wilcoxon matched-pairs signed-ranks test was used for comparing pre- and post-chemotherapy measurements. Results: Mean TBF decreased by 49%. Mean TBF in complete responders (ypT0N0/ypTis) was not significantly different from non-complete responders (≥ypT1) (p = 0.52). Conclusions: Despite a measurable decrease in TBF after chemotherapy treatment, we were not able to estimate a TBF threshold for identifying complete responders to chemotherapy for MIBC patients. Further studies are needed to elucidate the potential of [15O]H2O PET/MRI in assessing therapy response in MIBC.

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Identifying Complete Responders Following Chemotherapy-only Neoadjuvant Treatment for Rectal Cancer: Role of MRI.

Identifying Complete Responders Following Chemotherapy-only Neoadjuvant Treatment for Rectal Cancer: Role of MRI.

RECIST 1.1, mRECIST, and Choi criteria for evaluating treatment response and survival outcomes in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab.

We aimed to compare the early responder rates, defined as complete or partial responders, using response evaluation criteria in solid tumors (RECIST) 1.1, modified RECIST (mRECIST), and Choi criteria in advanced HCC patients treated with atezolizumab-bevacizumab (atezo-bev), and to correlate them with progression-free survival (PFS) and overall survival (OS). This retrospective study included advanced HCC patients treated with ≥ 3 cycles of atezo-bev. Two reviewers assessed responses using RECIST 1.1, mRECIST, and Choi criteria at 1st follow-up imaging. Kaplan-Meier curves with log-rank tests evaluated and compared PFS and OS. Cox proportional hazard models identified survival outcome predictors. Kappa statistics assessed inter-reader agreement. We evaluated 77 patients (65 men; mean age, 62.8 ± 12.3 years). Choi's criteria revealed the highest early responders rate (53.2%), exceeding mRECIST (32.5-33.8%) and RECIST 1.1 (24.7-26.0%), with an excellent agreement in all criteria (κ, 0.85-0.95). Across criteria, a consistent number of patients progressed (23-26) and was associated with significantly poor OS (ps ≤ 0.049). Responders by any criteria showed longer PFS (ps ≤ 0.009), and 1-year OS (ps ≤ 0.01). Choi criteria linked to significantly better OS without landmark (p = 0.003), with 1-year OS rates at 76.9% for responders vs 38.1% for non-responders. Cox analysis identified responders by Choi criteria as a significant OS predictor. Choi criteria identified more early responders than RECIST 1.1 and mRECIST, significantly correlating with improved OS. Choi criteria could be considered as a formal response assessment criterion for the emerging atezo-bev systemic treatment. For atezo-bev treatment of advanced HCC, more comprehensive response criteria, such as Choi criteria, could be effective in identifying early responders and predicting survival outcomes along with RECIST 1.1 and mRECIST. Choi criteria identified a higher rate of early responders compared to mRECIST and RECIST1.1 following atezo-bev treatment. Responders by all criteria had longer PFS and 1-year OS, and only those by Choi criteria experienced longer OS without landmark time. Choi criteria, with RECIST 1.1 and mRECIST, is an effective response assessment tool for atezo-bev treatment.

Monitoring of neoadjuvant chemotherapy through time domain diffuse optics: breast tissue composition changes and collagen discriminative potential.

The purpose of this clinical study is to test a broad spectral range (635-1060 nm) time-domain diffuse optical spectroscopy in monitoring the response of breast cancer patients to neoadjuvant chemotherapy (NAC). The broadband operation allows us to fully analyze tissue composition in terms of hemoglobin, water, lipids and collagen concentration, which has never been systematically studied until now during the course of therapy. Patients are subjected to multiple breast optical imaging sessions, each one performed at different stages of NAC, both on tumor-bearing and contralateral healthy breasts. We correlate the optical results with conventional imaging techniques and pathological response. Preliminary outcomes on 10 patients' data show an average significant reduction in the concentrations of oxy-hemoglobin (-53%, p = 0.0020), collagen (-36%, p = 0.0039) and water (-15%, p = 0.0195), and increase in lipids (+39%, p = 0.0137) from baseline to the end of therapy in the tumor-bearing breast of patients who responded to therapy at least partially. With respect to scattering, the scattering amplitude, a, increases slightly (+15%, p = 0.0039) by the end of the therapy compared to the baseline, while the scattering slope, b, shows no significant change (+4%, p = 0.9219). Some change in the constituents' concentrations was also noticed in the contralateral healthy breast, even though it was significant only for oxy-hemoglobin concentration. We observed that collagen seems to be the only component distinguishing between complete and partial responders by the end of 2-3 weeks from the baseline. In the complete responder group, collagen significantly decreased after 2-3 weeks with respect to baseline (p = 0.0423). While the partial responder group also showed a decrease, it did not reach statistical significance (p = 0.1012). This suggests that collagen could serve as a potential biomarker to measure NAC effectiveness early during treatment. Even though obtained on a small group of patients, these initial results are consistent with those of standard medical modalities and highlight the sensitivity of the technique to changes that occur in breast composition during NAC.