Recurrent Carcinoma Research Articles

Development of a prediction model for recurrent parathyroid carcinoma lesions based on 3D-EnCT and ultrasound imaging features.

This study aimed to analyze the three-dimensional enhanced computed tomography (3D-EnCT) and ultrasound imaging features of recurrent parathyroid carcinoma lesions and develop a prediction model based on these features. The clinical data of 34 patients (48 cases) with recurrent parathyroid carcinoma who underwent surgical treatment at Beijing Chaoyang Hospital's Thyroid and Neck Surgery Department between January 2017 and April 2024 were retrospectively analyzed. A total of 103 suspicious lesions were identified through a combination of preoperative 3D-EnCT and ultrasound examinations. Patients admitted prior to 1 January 2023 were included in the training set, and those admitted after 1 January 2023 were included in the validation set. In the training set, lesions were categorized as positive or negative based on pathological analysis. Statistically significant imaging features were identified via intergroup comparisons. An imaging prediction model was developed based on the 3D-EnCT and ultrasound features, and the predictive performance of the model was evaluated via receiver operating characteristic curves in the validation set. Arterial- and venous-phase CT values, lesion boundaries, and blood flow signals were associated with pathological positivity. The 3D-EnCT prediction model based on these features achieved areas under the curve (AUCs) of 0.9 and 0.714 in the training and validation sets, respectively, whereas the ultrasound prediction model achieved AUCs of 0.601 and 0.621, respectively. The 3D-EnCT model demonstrated superior predictive performance. The 3D-EnCT prediction model demonstrated superior predictive performance for recurrent parathyroid carcinoma lesions.

Changes in the tumor microenvironment in recurrent head and neck squamous cell carcinoma and its implication on efficacy of immune checkpoint inhibitors.

Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included. Changes in intratumoral TIL (iTILs), stromal TIL (sTILs), and IPs were subjected to paired analysis between the initial and recurrent tumors. We investigated their relationship with the outcomes of ICIs. The density of iTIL and sTIL in the recurrent tumors was significantly lower compared to initial tumors. IP was significantly different; the proportion of desert IP was higher in recurrent tumors (83.8% vs. 35.1%, P < 0.001). Increased sTIL was a favorable indicator for overall response to ICIs and progression-free survival. Our findings suggest TILs decrease during recurrence compared with the initial tumor, resulting in a transition toward desert IP. Therefore, careful evaluation of TIL density in both initial and recurrent tumors is recommended when using ICIs in patients with R/M HNSCC.

Risk factors and nomogram predictive models for postsurgical progression/hyperprogression recurrence in hepatocellular carcinoma with macroscopic vascular invasion.

This study aimed to develop postsurgical progression/hyperprogression recurrence (type III-IV recurrence) prediction models for hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MaVI) and to guide treatment strategies in the accurate healthcare era. 393 HCC patients with MaVI from two central hospitals made up the entire study population. In developmental (290 patients) and validation (103 patients) cohorts, all patients were randomized into one or the other. Two prediction models for type III-IV recurrence were developed, based on the findings of univariate and multivariate analysis in the development cohort, and multidimensional verification was carried out in both cohorts. The postoperative recurrence rate of type III-IV in 393 HCC patients with MaVI was 70.9%. Young age, large tumor size (≥ 10cm), node number, incomplete tumor capsule, postoperative complications, and high Ki67 index were the independent risk factors for relapse of type III-IV. In the development cohort, two nomograms (pre- and postoperative) had the Area Under the ROC curve (AUC) of 0.827 and 0.891, respectively. The two nomograms performed well, according to multidimensional verification methods such as clinical impact curves, decision curve analysis (DCA), and calibration curves. The validation cohort saw similar encouraging results. Both nomograms could separate patients into two distinct prognosis subgroups with ideal cutoff values of 170.3 presurgery and 175.0 postsurgery (both P < 0.05). We constructed two novel and potentially clinically valuable models for predicting type III-IV recurrence. These two models can develop strategies for treating those suffering from HCC with MaVI owing to their strong prediction performance and availability.

Treatment of recurrent tracheal adenoid cystic carcinoma with a covered airway stent loaded with Iodine-125 seeds: a 5-year follow-up case report

BackgroundThe treatment of recurrent tracheal adenoid cystic carcinoma (TACC), a rare pulmonary malignant tumor, typically involves bronchoscopic interventional therapy for patients ineligible for surgery or external radiotherapy. This report describes an innovative treatment approach for TACC, initially managed with interventional bronchoscopy and subsequently with a Y-shaped airway stent loaded with 125I seeds, following recurrence after 2 years.Case presentationA 50-year-old man presented with intermittent coughing for 2 months and was admitted to the hospital after the discovery of TACC a month earlier. Preoperative bronchial artery embolization was performed to reduce the risk of bleeding, followed by bronchoscopic tumor resection in January 2017 using an electric loop at the base, complemented by argon plasma coagulation (APC) and cryotherapy. Although short-term outcomes were favorable, the long-term prognosis remained suboptimal. Due to tumor recurrence, airway tumor resection and implantation of the 125I seed stent were performed under bronchoscope guidance in early 2019. The stent was removed 5 months later. The patient tolerated the procedure well and exhibited no signs of relapse or progression during the 5-year postoperative follow-up period. This case illustrates the successful application of a stent loaded with 125I seeds for treating unresectable TACC.ConclusionsTreatment of TACC with a covered airway stent loaded with 125I seeds may be a safe, effective, and scalable method.

Contrast-Enhanced Computed Tomography (CT) With Concordant Sonography as Sufficient Early Detection Tools for Recurrent and Persistent Cervical Metastases After (Chemo)radiotherapy (CRT).

Most challenging treatment needs are in recurrent or persisting head and neck squamous cell carcinoma (HNSCC) patients after (((chemo-)radiotherapy) (C)RT). This 10-year retrospective study included 100 patients, who initially received (C)RT followed by neck dissection (ND). The results of computed tomography (CT) and sonography were evaluated for residual/recurrent cervical lymph nodes and compared to the histopathology. On this basis we calculate the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). A total of 144 ND specimens were analyzed. The combination of CT and sonography (n = 103) reached values 97% sensitivity, 71% specificity, 98% NPV, 66% PPV, and 81% overall accuracy. For patients who received as primary treatment CRT the values for the combined imaging were: 100.0%, 73.5%, 100.0%, 66.7% and 82.7% respectively. Our study demonstrates that the combined use of CT and sonography reliably detects lymph node metastases, particularly in patients previously treated with CRT, even after a long time after treatment.

Prospective multicenter study of camrelizumab in real-world settings for asian patients with esophageal squamous cell carcinoma.

In this study, we aimed to evaluate the real-world efficacy and safety of camrelizumab and identify clinicolaboratory factors that predict treatment outcomes in patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) receiving camrelizumab. Herein, 174 patients with unresectable advanced, recurrent, or metastatic ESCC treated with camrelizumab monotherapy (n = 30), camrelizumab + chemotherapy (CT; n = 91), and camrelizumab + radiotherapy (RT; n = 53) between October 1, 2019 and October 1, 2022 were included. The median follow-up time was 20 months (range, 1-34 months). The median progression-free survival (PFS) and overall survival (OS) of the whole cohort were 8 months [95% confidence interval (CI), 6.5-9.5 months] and 14 months (95% CI, 11.2-16.8 months), respectively. After multivariate analysis, receiving > 4 cycles of camrelizumab was identified as an independent predictor of better PFS [hazard ratio (HR), 0.56; 95% CI, 0.38-0.827; P = 0.004] and OS (HR, 0.532; 95% CI, 0.341-0.83; P = 0.005). An intermediate-to-poor lung immune prognostic index (LIPI) was identified as an independent predictor of worse PFS (HR, 1.505; 95% CI, 1.032-2.196; P = 0.034) and OS (HR, 1.657; 95% CI, 1.094-2.51; P = 0.017). The disease control rate of patients in the camrelizumab monotherapy group, camrelizumab + CT group, and camrelizumab + RT group was 92.3% (95% CI, 74.9-99.1%), 90.6% (95% CI, 82.3-95.9%), and 96.1% (95% CI, 86.8-99.5%), respectively. The treatment-related adverse events (AEs) of grade 3 or higher were reported in 67 patients (38.5%). The most common treatment-related AEs were decreased neutrophil count (23.0%), decreased white blood cell count (19.5%), anemia (7.5%), and pneumonitis (4.6%). One patient (0.6%) died from a treatment-related AE of immune checkpoint inhibitor-induced myocarditis. Camrelizumab was safe and effective as both monotherapy and part of a combination therapy. Longer PFS and OS were associated with receiving > 4 cycles of camrelizumab and having a good LIPI. LIPI can be used as a prognostic biomarker for ESCC patients receiving camrelizumab + RT. ClinicalTrial.gov Identifier: CHICTR2000039499. Registered: 19th October 2020.

Concomitant Eruptive Squamous Atypia and Bullous Drug Eruption Associated with Pembrolizumab

This study involves the case of a rare eruptive squamous atypia (ESA) reaction and concurrent bullous eruption following pembrolizumab treatment for recurrent neck squamous cell carcinoma. This report aims to raise awareness to possible concurrent skin reactions related to PD-1 inhibitor treatment that has otherwise only been reported twice in melanoma patients.

Response to Bridging Therapy as a Prognostic Indicator of Post-Transplantation Hepatocellular Carcinoma Recurrence and Survival: A Systematic Review

Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC) in cirrhotic livers. Neoadjuvant bridging treatment in patients qualifying and listed for LT is advised but is still debatable owing to the low level of evidence. The aim of this study was to perform a systematic review to assess the prognostic value of bridging therapy, in terms of radiological and histopathological examination outcomes, for survival after LT. The systematic review was performed according to the PRISMA 2020 guidelines. The MEDLINE and Web of Science databases were searched. In total, five studies were included. An evaluation with the ROBINS-I resulted in studies classified as the following: moderate risk of bias (n = 1) and serious risk of bias (n = 4). The results of the analysis indicated that favorable LT outcomes were most common with complete response or partial radiological response. Poor radiological response or progressive disease during bridging treatment was generally associated with worse overall LT survival. There were not enough data to support the use of this approach to achieve a complete pathologic response. Radiological, pathological, histological, cellular, and molecular tumor features should be included in future LT qualification models.

Value of high frame rate contrast-enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma.

To investigate the value of vascular morphology on high frame rate contrast-enhanced ultrasound (H-CEUS) and CEUS Li-RADS in predicting microvascular invasion (MVI), Ki-67 expression and recurrence of hepatocellular carcinoma (HCC). This retrospective study enrolled 78 patients with single HCC diagnosed by postoperative pathology between January 1, 2021, and June 30, 2022. All patients underwent ultrasound and H-CEUS examination before operation. H-CEUS image features and CEUS Li-RADS were compared in different MVI status and Ki-67 level. Multiple logistic regression analysis was performed to select independent variables for MVI. Differences in recurrence among different H-CEUS image features, MVI status and Ki-67 level were further analyzed. Tumor shape, vascular morphology, LR-M category, necrosis and AFP level were different between the MVI-positive group and MVI-negative group (p < 0.05). Vascular morphology and LR-M category were independent risk factors related to MVI (p < 0.05). Vascular morphology was also different between the high Ki-67 expression group and low Ki-67 expression group (p < 0.05). Vascular morphology, MVI status and Ki-67 expression were different between the recurrence group and no recurrence group (p < 0.05). The vascular morphology of HCC on H-CEUS can indicate the risk of MVI status, Ki-67 expression and recurrence, which provides a feasible imaging technique for predicting the prognosis before operation. H-CEUS shows the different vascular morphology of HCC in arterial phase and indicates the risk of MVI, Ki-67 expression and recurrence, which provides a feasible imaging technique for clinician to judge the risk of MVI pre-operation and adopt appropriate treatment. H-CEUS can clearly show different vascular morphology of HCC in arterial phase. Vascular morphology on H-CEUS is associated with MVI status, Ki-67 expression and HCC recurrence. Preoperative MVI and Ki-67 expression prediction could help surgeons choose a more appropriate treatment plan.

Nomogram for predicting early recurrence of hepatocellular carcinoma with narrow resection margin.

Narrow resection margin hepatocellular carcinoma (NRM-HCC) has a high incidence of early recurrence. Our study was designed to identify prognostic factors in patients with NRM-HCC, establish and validate a nomogram model to predict early recurrence of NRM-HCC patients. We retrospectively analyzed data from 2957 NRM-HCC patients who underwent radical hepatectomy at three medical centers between December 2009 and January 2015. Patients were randomly assigned to a training cohort (n = 2069) and a validation cohort (n = 888). Using univariate and multivariate COX regression to determine early relapse factors in NRM-HCC patients, and used these factors to construct a nomogram. The accuracy of the prediction was evaluated using the C-index, receiver operating characteristic (ROC) and calibration curve. Decision curve analysis (DCA) assessed the predictive value of the models. Finally, the recurrence-free survival of different risks was analyzed using Kaplan-Meier (K-M) method. The nomogram of NRM model contains alpha-fetoprotein (AFP), alkaline phosphatase (ALP), tumor size, tumor number, microvascular invasion (MVI), tumor capsular, and satellite nodules. The model shows good discrimination with C-indexes of 0.71 (95% CI: 0.69-0.72) and 0.72 (95% CI: 0.70-0.75) in the train cohort and test cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different early recurrence. The web-based tools are convenient for clinical practice. NRM model demonstrated favorable performance in predicting early recurrence in NRM-HCC patients. This novel model will be helpful to guide postoperative follow-up and adjuvant therapy.

Safety and Effectiveness of Percutaneous Ethanol Injection as a Treatment for Locally Recurrent Papillary Thyroid Carcinoma

Background: Reoperation for recurrent papillary thyroid cancer (PTC) is associated with a high risk of complications and limited success in achieving sustained remission. Percutaneous ethanol injection (PEI) presents a potential non-surgical alternative for managing locally recurrent PTC. Objectives: This study aimed to evaluate the safety and effectiveness of PEI in treating recurrent PTC. Methods: From October 2017 to September 2021, PEI was administered to 39 recurrent lesions (23 lateral and 16 central) in 17 patients with PTC. The median follow-up duration was 21.4 months (range, 4.1 - 37.9), with ethanol injections delivered every 3 months under ultrasound (US) guidance as needed. Results: Most patients tolerated the treatment well, experiencing only mild local pain, though one patient reported Horner syndrome following the procedure. In terms of treatment frequency, 31 lesions required 3 or fewer injections, while the remaining lesions required more. The mean initial volume of the lesions decreased from 0.12 mm³ (range: 0.06 - 0.34 mm³) to 0.03 mm³ (range: 0.0 - 0.14 mm³), representing an average reduction of 72.6% (range: 20.0 - 100.0%). Of the 39 lymph nodes treated in 17 patients, 21 lymph nodes (54%) were completely resolved. Seven lymph nodes remain under ongoing ethanol treatment, while 11 lymph nodes in 4 patients were addressed with alternative treatments, including surgery. Conclusions: Percutaneous ethanol injection appears to be a safe and effective treatment option for managing locally recurrent thyroid carcinomas in select patients. However, further comparative, prospective, long-term studies are needed to evaluate PEI’s impact on patient survival and recurrence rates.

Effect of performance status on the therapeutic effect of nivolumab in recurrent or metastatic squamous cell carcinoma of the head and neck.

Systemic chemotherapy is the primary treatment strategy for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). Therapeutic strategies are changing considerably with the introduction of molecular-targeted and immune checkpoint inhibitor (ICI) therapies in addition to conventional cytotoxic therapy. The CheckMate-141 and KEYNOTE-048 trials have enabled the use of ICIs as first-line treatment to improve the overall prognosis of RM-SCCHN. However, background factors affecting treatment responses, including performance status (PS), remain poorly defined. Therefore, we investigated the effect of PS in patients treated with nivolumab. We retrospectively reviewed the treatment outcomes and backgrounds of 31 patients with RM-SCCHN who received nivolumab monotherapy between April 2017 and March 2023. The patient background was male/female = 29/2, median age was 68years (range 39-85), PS0/1/2 = 14/15/2, and oral/oropharynx/hypopharynx/larynx = 2/12/12/5. Median overall survival was 8.0months (95% confidence interval [CI]: 4.3-30.6months), median progression-free survival was 3.0months (95% CI 1.7-9.1months), and objective response rate was 22.6% (95% CI 11.1-40.1%). Immune-related adverse events of grade 3 or higher were observed in three patients (9.7%). Eight (29.6%) of the 27 patients (excluding four patients who maintained complete response for over 2 years) were successfully transferred to post-treatment. In the multivariate analysis, Eastern Cooperative Oncology Group (ECOG) PS (Hazard Ratio: 9.87, 95% CI 1.79-54.56) was associated with poor survival. The efficacy of nivolumab is reduced in patients with poor PS.

A Young Girl with Recurrent Fallopian Tube Carcinoma (FTC): An Interesting Case Report

Primary fallopian tube carcinoma (FTC) is a rare disease which frequently occurs among post-menopausal women. It is often grouped under the epithelial ovarian cancer umbrella. The treatment of choice is surgery and chemotherapy. Our patient was a young teenage girl with recurrent FTC who responded well to surgery and chemotherapy. We discuss on the epidemiology, risk factors, principles of management and prognosis of FTC.

ASO Visual Abstract: Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

ASO Visual Abstract: Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

Matching the opposites: liver transplantation from a situs viscerum inversus totalis donor.

Situs viscerum inversus totalis (SIT) is a rare congenital anomaly. Deceased donors with this condition are often declined because of the technical issues in both the organ's procurement and its transplant. Only eight cases of deceased donor organs with SITwere reported to be used for liver transplantation (LT). We herein present a case of LT using a graft from an SIT donor: a modified retroversus piggyback technique was used. A 15year-old female was referred to our institution as a potential donor. An SIT condition was discovered during standard donor evaluation together with the presence of a complex triple arterial pedicle. Procurement operative time was 125min, from skin incision to cross-clamp. Liver extraction occurred 32min after cold flush. The recipient was a 56year-old male affected by recurrent hepatocellular carcinoma (HCC) on hepatitis C related liver cirrhosis. Position and orientation trials of the graft were made and it was decided to implant it with the retroversus technique. Direct duct-to-duct biliary reconstruction was achieved. The postoperative course was uneventful. To our knowledge, this is the first implant with retroversus technique combined to direct biliary reconstruction and the first repetition of that technique. Cases like this highlight how technical complexity can be overcome leading to successful management of difficult scenarios in a safe manner.

The epidemiological and histopathological factors for delayed local recurrence in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy in oral cancer. Approximately 26% of OSCC cases recur after initial curative treatment, with over 80% of these recurrences occurring within the first 2years. Delayed local recurrence (DLR) occurring beyond the 2-year period in cases of OSCC is infrequent. The aim of this study is to investigate the histopathological characteristics associated with DLR. This study included 197 patients diagnosed with OSCC who underwent primary surgery from 2006 to 2022. Epidemiological features, such as age and gender, and histopathological features, including primary tumor sites, TNM staging, histopathological grading, depth of invasion, the presence of lymphovascular or perineural invasion, and the utilization of radiation therapy (RT) and neck dissection (ND) were analyzed. The mean interval until local recurrence was 22 ± 27months. There were 10 cases of DLR (20.83%) among 51 patients with local recurrence. The epidemiological and histopathological analysis of these cases is as follows: 10 patients (3 males and 7 females) aged 51-80years (median, 56.5years). Primary tumor sites were tongue (n = 3), maxillary gingiva (n = 1), mandibular gingiva (n = 3), retromolar trigone (n = 1), and buccal mucosa (n = 2). Tumor size was advanced (T3/T4) in 5 cases, while a smaller size (T1/T2) was observed in 5 cases. No lymph node metastasis was 80.0%. Histopathological grading was well differentiated in 9 cases and moderately differentiated in 1 case, with no cases of poorly differentiated tumors. Depth of invasion > 5mm was 70.0% of the cases (n = 7). Lymphovascular invasion and perineural invasion were not present. Three patients received RT, and 8 patients underwent ND. There were 2 patients who consumed alcohol, and 2 patients who smoked tobacco. The results showed that histological differentiation had a significant relationship with the interval (p = 0.031). DLR, occurring more than 2years after the initial tumor resection surgery, is infrequent. Histological differentiation is associated with tumor recurrence intervals. Patients with a higher histological grading require more precise follow-up observation during the initial 2years after surgery.

Abstract 4136539: Management of Malignant SVC Syndrome and Acute SVC Thrombosis with Complex Endovascular Intervention

Superior vena cava (SVC) syndrome occurs when there is SVC occlusion or obstruction. SVC obstruction can cause an increase in venous return pressure up to 40 mm Hg, producing edema of the face, neck and chest wall. Blood flow can be diverted to the right atrium through collateral venous networks in cases of gradual SVC compression. The most common cause of SVC syndrome is malignancy, as seen in 70% of cases. Traditionally, treatment is with radiation therapy but advances have now allowed for an endovascular approach. We present a case of malignant SVC syndrome with a complex percutaneous treatment approach that provided palliation with near immediate symptom improvement. A 64 year-old-female with history of cerebrovascular accident on Eliquis, right upper lobe squamous cell carcinoma of the lung in remission, and a mediastinal nodule under surveillance presented with facial and bilateral upper extremity edema. CT revealed bilateral pulmonary embolism and a large SVC thrombus causing impaired venous return. Invasive angiogram confirmed a 95% thrombotic tubular stenosis for which she underwent aspiration thrombectomy with alpha VAC F-18, then angioplasty with an Armada (Abbott) 10 x 40 mm compliant balloon and stenting with the Express (Boston Scientific) 10 x 37 mm stent. There was 0% residual stenosis and immediate clinical improvement. Oncological workup confirmed the right mediastinal mass to be a recurrence of squamous cell carcinoma. SVC syndrome occurred due to mediastinal mass compression and a near occlusive SVC thrombus. Aspiration thrombectomy was effective in treating the SVC thrombosis and was performed alongside pulmonary embolism thrombectomy. The Armada balloon is intended for lesion dilation in the peripheral arteries, but was safely used here for venous dilation. The Express stent is intended for palliation of malignant biliary neoplasms but has versatility and was utilized here for malignant neoplasm surrounding the SVC. Peripheral endovascular stenting is an advantageous treatment option for malignant SVC syndrome given the challenges due to recurrence from mass effect. This provides additional support to maintain vessel patency and is a safe palliation option for improvement in quality of life.

PATH-45. TREATMENT OF FGFR1 – ALTERED WHO GRADE 1 GLIONEURONAL TUMORS WITH FGFR INHIBITOR ERDAFITINIB

Abstract INTRODUCTION Low-grade mitogen-activated protein kinase (MAPK) pathway-altered glioneuronal tumors carry distinct molecular alterations, which may represent therapeutic opportunities to avoid or delay toxic treatments like radiation. Erdafitinib is a pan-FGFR tyrosine kinase inhibitor, regulatorily approved in recurrent urothelial carcinoma, and is under clinical investigation for recurrent FGFR-altered gliomas (NCT05859334). METHODS We report two patients with FGFR1-altered rosette-forming glioneuronal tumors (RGNT) treated with erdafitinib. RESULTS Patient 1 is a 32-year-old woman who presented with obstructive hydrocephalus and a non-enhancing pineal tumor. She underwent a subtotal resection, with histopathology initially consistent with a low grade dysembryoplastic neuroepithelial tumor. She was under observant management for 7 years, and developed worsening symptoms with slow non-enhancing growth, although stable per RANO low grade criteria. The initial tissue was sent for next-generation sequencing (NGS) and DNA methylation profiling, revealing an FGFR1 pathogenic variant with DNA methylation profiling matching with RGNT. Patient began Erdafitinib 8 mg daily, and had stable disease per RANO at 6 months. She developed CTCAE grade 1 toxicities of subretinal fluid, fatigue, dry skin, and paronychia. Patient 2 is a 34-year-old man diagnosed 1 year prior with a tectal tumor, who underwent biopsy due to non-measurable/ non-enhancing progression. Histopathology was consistent with RGNT. NGS revealed FGFR1 mutation, PIK3CA mutation, and NF1 pathogenic variant, described in the literature as characteristic of RGNT. There was insufficient tissue for DNA methylation profiling. Patient started erdafitinib 8 mg daily and remains clinically stable for 1 month. He developed asymptomatic hyperphosphatemia (CTCAE grade 1). Both patients have tolerated treatment without interruptions or dose reductions. CONCLUSION Erdafitinib is a well-tolerated and potentially efficacious treatment of FGFR1- altered RGNT, and may avoid the need for radiation. Diagnosis of MAPK- altered low-grade glioneuronal tumors, specifically RGNT, is increasingly reliant on molecular data, and can significantly impact treatment options.

Phase 1b Study of the Immunocytokine Simlukafusp alfa (FAP-IL2v), in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma.

This phase 1b trial evaluated FAP-IL2v, a novel immune-cytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC). Patients received FAP-IL2v either on a continuous weekly (QW) schedule, or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules. The primary objectives were to evaluate the safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity for the combination of FAP-IL2v with cetuximab. Exploratory objectives included pharmacodynamic analyses. A total of 58 patients were enrolled, 19 patients into the dose-escalation, and 39 patients into the expansion part. The MTD of FAP-IL2v was defined as 10 mg (QW/Q2W) in combination with cetuximab (500 mg/m2, Q2W), which was further tested in the expansion part. The most common FAP-IL2v-related adverse events with a grade 3 or 4 severity were hypophosphatemia (19%), lymphopenia (16%), and infusion-related reaction (14%). The pharmacokinetics of FAP-IL2v in combination with cetuximab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded intratumoral NK and CD8 T cells. Four patients achieved a partial response, the objective response rate was 7% (95% CI: 3.2, 14.7). The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).].

Deep learning radiomics based on contrast enhanced MRI for preoperatively predicting early recurrence in hepatocellular carcinoma after curative resection

PurposeTo explore the role of deep learning (DL) and radiomics-based integrated approach based on contrast enhanced magnetic resonance imaging (CEMRI) for predicting early recurrence (ER) in hepatocellular carcinoma (HCC) patients after curative resection.MethodsTotal 165 HCC patients (ER, n = 96 vs. non-early recurrence (NER), n = 69) were retrospectively collected and divided into a training cohort (n = 132) and a validation cohort (n = 33). From pretreatment CEMR images, a total of 3111 radiomics features were extracted, and radiomics models were constructed using five machine learning classifiers (logistic regression, support vector machine, k-nearest neighbor, extreme gradient Boosting, and multilayer perceptron). DL models were established via three variations of ResNet architecture. The clinical-radiological (CR), radiomics combined with clinical-radiological (RCR), and deep learning combined with RCR (DLRCR) models were constructed. Model discrimination, calibration, and clinical utilities were evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis, respectively. The best-performing model was compared with the widely used staging systems and preoperative prognostic indexes.ResultsThe RCR model (area under the curve (AUC): 0.841 and 0.811) and the optimal radiomics model (AUC: 0.839 and 0.804) achieved better performance than the CR model (AUC: 0.662 and 0.752) in the training and validation cohorts, respectively. The optimal DL model (AUC: 0.870 and 0.826) outperformed the radiomics model in the both cohorts. The DL, radiomics, and CR predictors (aspartate aminotransferase (AST) and tumor diameter) were combined to construct the DLRCR model. The DLRCR model presented the best performance over any model, yielding an AUC, an accuracy, a sensitivity, a specificity of 0.917, 0.886, 0.889, and 0.882 in the training cohort and of 0.844, 0.818, 0.800, and 0.846 in the validation cohort, respectively. The DLRCR model achieved better clinical utility compared to the clinical staging systems and prognostic indexes.ConclusionBoth radiomics and DL models derived from CEMRI can predict HCC recurrence, and DL and radiomics-based integrated approach can provide a more effective tool for the precise prediction of ER for HCC patients undergoing resection.