Recurrent Carcinoma Research Articles

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

AbstractSitus 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 SIT were 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 15 year-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 125 min, from skin incision to cross-clamp. Liver extraction occurred 32 min after cold flush. The recipient was a 56 year-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.

Sirolimus-induced pulmonary toxicity without recurrence more than 8 years after everolimus replacement in a renal transplant patient with recurrent skin SCC: a case report

Abstract Background Interstitial Pneumonitis (IP) is one of the pulmonary complications associated with mammalian Target of Rapamycin-Inhibitors (mTOR-Is). Sirolimus and everolimus belong to mTOR-Is. According to studies, IP is caused by both. Case presentation This is a case report in a kidney transplant recipient. We want to present a case of IP after 50 months of sirolimus consumption. Sirolimus was discontinued, and cyclosporine was started. Thirty-seven months later, everolimus was prescribed as an alternative to cyclosporine due to the recurrence of skin Squamous Cell Carcinoma (SCC). Fortunately, no respiratory manifestations were seen after more than 8 years of everolimus consumption. Conclusions In conclusion, in cases with sirolimus-induced IP, discontinuation of sirolimus and replacement with everolimus are recommended after resolving clinical symptoms and pulmonary lesions.

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

Abstract Background 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 2 years. 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. Methods 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. Results The mean interval until local recurrence was 22 ± 27 months. 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 51–80 years (median, 56.5 years). 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 > 5 mm 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). Conclusions DLR, occurring more than 2 years 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 2 years 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.

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.

Exploring the FAP-Targeted Therapeutics for Adrenocortical Carcinoma: Choosing the Right Track.

Metastatic or recurrent adrenocortical carcinoma is a potentially lethal malignancy, presenting significant challenges in disease management owing to absence of effective systemic treatments. Significantly diminished survival rates necessitate rapid identification of specific molecules for the development of targeted therapeutics. Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts have been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. The effectiveness of various FAP inhibitors (FAPis) and FAP targeting peptide has been extensively documented in diverse clinical investigations. We have evaluated 3 molecules, that is, DOTA.SA.FAPi (SA.FAPi), FAPi46, and FAP2286, as potential theranostic probes for adrenocortical carcinoma.

Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors. Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed. The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980-2009 and 2010-2020 (P=0.995); however, the 1980-2009 group had significantly lower RFS rates (P=0.031). The 2010-2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group. Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Recurrent Patterns in Patients With Nasopharyngeal Caricinoma and Risks Leading to Inaccurate Delineation in Marginal Failure in the Era of Intensity-Modulated Radiotherapy.

To investigate the failure patterns of recurrent nasopharyngeal carcinoma (NPC), especially to identify the relationship between the recurrent-prone anatomic structures and the tumor regression sites after the introduction of chemotherapy (IC). A cohort of 1121 non-metastatic patients with NPC was retrospectively enrolled. The pretreatment and recurrent images of each patient were registered to the planning CT. Tumor regression sites after IC (Vicr) overlapped with recurrent tumor (rGTV) were evaluated for the delineation accuracy and dose sufficiency in marginal failure patients. A total of 126 (11.24%) experienced tumor recurrence. Re-evaluation of 12 patients with local marginal recurrence, their rGTV within Vicr predominantly located at choanae, sphenoidal sinus, and cavernous sinus. The regression sites did not receive the full 70 Gy but over half receiving with 60Gy. Analysis from marginal failure that exempts tumor regression sites from GTV or an insufficient prescription dose of less than 70 Gy may contribute to marginal failure.

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

A rare case of retroperitoneal recurrence as squamous cell carcinoma 10 years after nephroureterectomy

IntroductionLocal recurrence for upper tract urothelial carcinoma typically occurs within 2 years post‐surgery. We report a rare case of retroperitoneal recurrence as squamous cell carcinoma 10 years after nephroureterectomy.Case presentationA 67‐year‐old female was referred to our urology department for a left ureteral tumor. The surgical specimen of the laparoscopic left nephroureterectomy revealed urothelial carcinoma at the pT3 stage. Ten years post‐nephroureterectomy, magnetic resonance cholangiopancreatography revealed a mass lesion in the left retroperitoneum, a computed tomography‐guided biopsy revealed squamous cell carcinoma. Despite suspected distant metastases of other organ tumors, examinations such as digestive endoscopy and bronchoscopy did not reveal any tumor lesions. The patient was diagnosed with recurrent invasive urothelial carcinoma as a pathological feature of squamous cell carcinoma.ConclusionThe decision‐making process for treating malignant tumors, such as in cases with recurrence as squamous cell carcinoma, can be challenging.

P285 Does the presence of detrusor muscle in the initial transurethral resection affect the efficacy of immediate second transurethral resection in improving recurrence and progression in T1 high-grade non-muscle invasive bladder carcinoma?

P285 Does the presence of detrusor muscle in the initial transurethral resection affect the efficacy of immediate second transurethral resection in improving recurrence and progression in T1 high-grade non-muscle invasive bladder carcinoma?

Criteria for Re-Irradiation.

The treatment options for patients with progressive malignant tumors despite primary radiotherapy are often limited. In selected cases, re-irradiation can be offered. This article concerns the selection criteria and results of re-irradiation for certain types of cancer. This review is based on pertinent publications retrieved by a selective search in PubMed, with particular attention to glioblastoma, head and neck tumors, and prostatic carcinoma. The published studies of re-irradiation are few in number and often of limited methodological quality. For glioblastoma, a randomized controlled trial (RCT) found that adding re-irradiation to treatment with bevacizumab yielded no significant improvement in either median progression-free survival or median overall survival (hazard ratio [HR] 0.73; p = 0.05 and HR 0.98; p = 0.46, respectively). Re-irradiation is a treatment option for locoregional recurrences of head and neck tumors after primary radiotherapy, but it carries a risk of serious side effects. For unresectable recurrences of nasopharyngeal carcinoma, an RCT has shown that hyperfractionated re-irradiation is more effective than normofractionated re-irradiation (overall survival: HR 0.54, p = 0.014). For locally recurrent prostatic carcinoma after radiotherapy, re-irradiation can yield good oncologic outcomes with an acceptable level of urogenital and gastrointestinal side effects (5-year recurrence-free survival: stereotactic body radiation therapy (SBRT), 58%; high dose rate (HDR) brachytherapy, 77%; versus salvage prostatectomy, 72%). RCTs on this topic are lacking. Re-irradiation is a treatment option for selected cancer patients. As the available scientific evidence is limited, multidisciplinary collaboration and participatory decision-making are particularly important.

Clinical and molecular determinants of response to maintenance olaparib for primary and recurrent epithelial ovarian carcinoma

Clinical and molecular determinants of response to maintenance olaparib for primary and recurrent epithelial ovarian carcinoma

The impact of the cancer genome atlas status among patients with recurrent endometrioid endometrial carcinoma treated with secondary cytoreductive surgery

The impact of the cancer genome atlas status among patients with recurrent endometrioid endometrial carcinoma treated with secondary cytoreductive surgery

The efficacy and safety of cadonilimab after first anti-PD-1 failure in the treatment of recurrent endometrial and cervical carcinoma: A retrospective, real-world study

The efficacy and safety of cadonilimab after first anti-PD-1 failure in the treatment of recurrent endometrial and cervical carcinoma: A retrospective, real-world study

Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study.

Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors. Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high. The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control. Here, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors. NCT04510129.

Prognostic factors for hepatocellular carcinoma recurrence after liver transplantation or resection – single-center experience.

Prognostic factors for hepatocellular carcinoma recurrence after liver transplantation or resection – single-center experience.

ZNF143-mediated upregulation of MEX3C promotes hepatocellular carcinoma progression

BackgroundMicrovascular invasion is strongly associated with aggressive tumor behavior and recurrence in hepatocellular carcinoma (HCC) patients. Zinc finger protein 143(ZNF143) is a transcription factor involved in a wide variety of physiological and developmental processes. This study primarily focuses on the exact biological role and mechanism of ZNF143 in HCC migration and invasion. MethodsThe expression and prognosis of ZNF143 in HCC patients were analyzed. The levels of ZNF143, mex-3 RNA binding family member C (MEX3C) were quantified by western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration ability was detected by wound- healing assay. Matrigel transwell assay was conducted to evaluate the invasion of HCC cells. The differential expression genes of ZNF143 overexpression and knockdown were screened by mRNA profiling analysis. Dual luciferase assay was performed to determine the promoter activity of MEX3C. The enrichment of ZNF143 at MEX3C promoter was determined by chromatin immunoprecipitation (ChIP). ResultsZNF143 is overexpressed in HCC tissues and that its overexpression is correlated with poorer prognosis, especially in HCC patients with higher tumor grades and microvascular invasion. Gain- and loss-of function experiments showed that ZNF143 promotes migration and invasion in HCC cells. mRNA profiling showed that ZNF143 significantly upregulates MEX3C. ZNF143 was positively correlated with MEX3C expression in HCC tissue. ZNF143 activates MEX3C transcription by directly binding to its promoter. MEX3C knockdown inhibited migration and invasion induced by ZNF143 overexpression in HCC cells. ConclusionZNF143 promotes HCC cell migration and invasion by binding to MEX3C promoter and activating its expression.