Radiological Recurrence Research Articles

Adjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitor, ribociclib, for localized hormone receptor-positive/HER2– breast cancer (LEADER)

Optimal timing and dosing of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor in early breast cancer is controversial. This prospective phase II clinical trial investigated tolerability and safety of two ribociclib dosing schedules. Patients with stage I–III hormone receptor-positive (HR+)/HER2– breast cancer on adjuvant endocrine therapy (ET) were randomized to two ribociclib dosing schedules: 400 mg continuous vs 600 mg intermittent, with initiation in early (prior ET < 2 years) vs delayed (prior ET ≥ 2 years) setting. Primary objective was to evaluate safety and tolerability of continuous vs intermittent schedule. Primary endpoint was proportion of patients who discontinued ribociclib before completion of all 12 cycles (measured at 12 months). Recurrence free survival (RFS) and circulating tumor DNA (ctDNA) detection were also evaluated. 81 patients were enrolled. Only six serious adverse events occurred, with no significant difference between treatment arms and no subject deaths. Twenty-five patients (31%) discontinued ribociclib before completion of 12 months, with no significant difference between treatment arms. Ribociclib discontinuation was higher in early vs delayed initiation (36% vs 21%). At median follow-up of 20 months, two patients in the intermittent arm (600 mg; Arm 2) experienced disease recurrence (2-year RFS 97%, 95%CI 88–99%), vs none in the continuous arm (400 mg; Arm 1) (2-year RFS 100%). ctDNA was only identified in the two subjects with recurrent disease at median of 7.5 months prior to radiological recurrence. Ribociclib is a safe and well-tolerated adjunct to adjuvant ET in early-stage breast cancer. Delayed initiation of ribociclib at 400 mg continuous dosing was feasible, better tolerated and associated with promising outcomes. ctDNA detection preceded clinical evidence of recurrence and may be considered as a surveillance tool in breast cancer.

Cerebral venous thrombosis as a rare complication of Sjögren's syndrome: case series and literature review.

As few cerebral venous thrombosis (CVT) patients with primary Sjögren's syndrome (pSS) have been reported, little is known about the characteristics of this rare complication. This study is aimed at describing the clinical features, treatment, and outcome of CVT combined with pSS. We reported five patients of CVT and pSS admitted to our hospital and searched the relevant case reports in PubMed for literature review. We reviewed a total of twelve patients with pSS and CVT. Among them, five patients were from our report in the present paper, and seven other patients were from the case reports searched in PubMed. In total twelve patients, eleven patients were female. The twelve patients had an average age of 43.7 ± 8.3years (age range, 26-57years). The symptoms of pSS included multiple caries (50%), dry mouth (41.7%), dry eyes (33.3%), arthritis symptoms (16.7%), and parotid gland swelling (8.3%). Headache was the most common neurological symptom in all patients. Four patients (33.3%) had no clinical symptoms associated with pSS. Anti-SSA antibodies were positive in all patients. Antiphospholipid antibodies (aPLs) were positive in 33.3% of patients. Unilateral transverse sinus (75.0%) was the most commonly involved venous sinus. All patients received anticoagulant therapy. Hydroxychloroquine was also administered to the patients. Seven patients were treated with glucocorticoids. All patients recovered completely with no clinical or radiological recurrence. pSS combined with CVT is a rare condition. Middle-aged women with pSS should be alert to the presence of CVT. It is of great importance to screen for autoimmune diseases during the clinical course of CVT, especially in patients with unilateral transverse sinus thrombosis. Effective treatment strategies require further study. Key Points • Patients combined with CVT are very rare. • Screening for autoimmune diseases in CVT patients is great important. • Patients may have good prognosis when effective treatment is administrated.

Radiologic Outcomes of Plantar Plate Repair through a Plantar Approach for the Dislocated Metatarsophalangeal Joint of the Lesser Toe.

A torn plantar plate (PP) is important pathologic anatomy related to a dislocated or subluxated metatarsophalangeal joint (MTPJ). Traditionally, a torn PP was treated with Weil osteotomy through a dorsal approach. However, because of the limited visualization of the dorsal approach, PP repair through a plantar approach has been proposed as a new technique. This study aimed to radiologically evaluate the outcome of PP repair through the plantar approach using an improved MTPJ overlap distance (MOD) on an anteroposterior view and the degree of subluxation on an oblique view. We also aimed to investigate the potential factors affecting the recurrence of MTPJ instability. In this study, we included 31 patients who had a subluxated or dislocated MTPJ of the second or third toe and underwent surgical PP repair. PP repair was performed via a plantar approach after shortening metatarsal (MT) osteotomy with a dorsal approach for longer MT bone. We assessed the severity of MTPJ subluxation by measuring the MOD and subluxation subtype on radiographs. Radiologic recurrence was defined as an increase in MOD or change from subluxation type A to subluxation type B. The relationship of recurrence with clinical and radiologic factors was evaluated by comparing the recurred group against the non-recurred group. Shortening MT osteotomy was performed in 26 of 31 cases (84%). Repeated measures analysis of variance comparing preoperation, pin removal, and the latest follow-up MOD values revealed the effectiveness of PP repair through the plantar approach (p < 0.001). The MOD did not significantly change after pin removal and the latest follow-up (p = 0.130), indicating that reduction was well maintained. None of the clinical and radiologic factors were significantly related to recurrence. However, 3 of 12 rheumatoid arthritis (RA) feet (25%) recurred and 3 of 5 recurred cases (60%) were RA feet. This result suggests that RA indicated a tendency for recurrence. PP repair through the plantar approach has the advantage of excellent visualization of a torn PP and direct repair. We, therefore, recommend using the plantar approach for PP repair of the MTPJ.

Ossifying fibroma and juvenile ossifying fibroma: A systematic review on clinical and radiological parameters, treatment modalities and recurrence

Ossifying fibroma (OF) is a rare benign fibro-osseous neoplasm developing mostly in maxillo-facial bones. OF is divided in cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF) and psammomatoid ossifying fibroma (PSOF). The aim of this systematic review was to synthetize the existing literature on OF, investigating the clinical and radiological parameters related to the different forms of the disease, and to compare the treatment modalities according to their associated recurrence rate. Three databases were searched in March 2024, with an update in September 2024. Eligibility criteria included studies reporting on patients with OF, surgical treatment and follow-up data. Of the 2016 studies identified, 22 were retained after eligibility assessment. A total of 492 patients were included. Most OF presented with painless swelling. COF affected 61.1% of women with a mean age of 29.5, JTOF presented in 55.7% of male children, and PSOF had no predilection for sex with a mean age of 19.5 years. Enucleation and curettage were associated with an elevated recurrence rate in JTOF (12/30) and PSOF (10/16). PSOF (6 cases) and JTOF (15 cases) showed no recurrence with radical surgery. Same recurrence rates in COF were seen for conservative and radical surgery. Although radical surgery seemed to avoid recurrence in JTOF and PSOF, conservative surgery such as enucleation and curettage with additional peripheral ostectomy should be considered primarily to lessen the morbidity induced by radical resection. Close clinical and radiological follow-up should be undertaken to diagnose early recurrence.

Ultrasound-guided renal artery balloon catheter occluded hybrid partial nephrectomy (UBo-HPN) with branch renal artery occlusion: a single arm trial

BackgroundOne key focus of partial nephrectomy is preserving renal function. Segmental renal artery occlusion with microdissection at the renal hilum confines ischemia, effectively reducing warm ischemic injury. Ultrasound-Guided Renal Artery Balloon Catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN) can achieve branch occlusion without the need for dissecting the renal hilum.ObjectiveTo investigate the feasibility and safety of UBo-HPN of branch renal artery occlusion in the treatment of localized renal tumors.Subject and methodsA prospective single-arm analysis involving 20 patients with renal localized tumors underwent robot assisted UBo-HPN with branch renal artery occlusion from August 2021 to July 2023, with an average follow-up of 12 months.ResultsAll patient was successfully operated on without conversion to conventional arterial clamping or radical nephrectomy. One case (5%) of minor complication occurred in the whole cohort, which was bruising around the puncture site. The mean total operative time was 95.8 min, with a mean operative time of 21.25 min for vascular intervention. The mean warm ischemia time was 20.35 min, and the median estimated blood loss was 50 ml. The median eGFR preservation percentage at postoperative 48 h, 30 days, and the latest follow-up were 87.52%, 91.47%, and 92.2%, respectively. After a median follow-up of 10.2 (2.3–19.2) months, no patients had radiological tumor recurrence or died from tumor-related causes.ConclusionsUBo-HPN with renal artery branch occlusion emerges as an efficient alternative to partial nephrectomy (PN), which achieved branch artery occlusion without dissecting the renal hilum. Long-term follow-up is expected for functional outcomes.

Feasibility of ctDNA in detecting minimal residual disease and predicting recurrence for colorectal cancer liver metastases.

Approximately 50% of patients diagnosed with colorectal cancer develop colorectal cancer liver metastases (CRLM). Although curative intent liver resection provides 5-year survival of 40-50%, up to 70% of patients develop recurrence of CRLM. Detection of minimal residual disease (MRD) is essential for timely, optimized treatment. This study evaluated the feasibility and utility of using circulating tumor DNA (ctDNA) to identify MRD and predict disease recurrence. Patients with CRLM that underwent liver resection and had known KRAS or PIK3CA mutations were retrospectively identified. Serial blood samples were collected every 3 months following surgery for disease surveillance. ctDNA was isolated from the samples and analyzed with digital PCR (dPCR). KRAS and PIK3CA mutations were identified by dPCR in 29 patients over 115 timepoints. In patients with detectable ctDNA at time of liver resection, 81% (13/16) developed disease recurrence, while 46% (6/13) of the patients with undetectable ctDNA recurred (p=0.064). Presence of ctDNA was detected in 27.6% (8/29) of the initial postoperative samples. Radiologic recurrence was later diagnosed in 100% (8/8) of these patients, while 52% (11/21) who had undetectable ctDNA postoperatively recurred (p=0.026). Detectable ctDNA postoperatively was associated with a shorter disease-free survival (DFS) of 9 months vs 13 months in patients who had undetectable ctDNA (HR 2.95, 95% CI 1.16-7.49; p=0.02). Liquid biopsy using dPCR can identify low levels of ctDNA, enabling early detection of disease recurrence. Additionally, the presence of ctDNA postoperatively was predictive of recurrence. This study corroborates current literature and provides rational for moving toward a clinical trial using ctDNA and dPCR to detect MRD after CRLM resection.

Detection of circulating tumor DNA by tumor-informed whole-genome sequencing enables prediction of recurrence in stage III colorectal cancer patients

IntroductionCirculating tumor (ctDNA) can be used to detect residual disease after cancer treatment. Detecting low-level ctDNA is challenging, due to the limited number of recoverable ctDNA fragments at any target loci. In response, we applied tumor-informed whole-genome sequencing (WGS), leveraging thousands of mutations for ctDNA detection. MethodsPerformance was evaluated in serial plasma samples (n = 1283) from 144 stage III colorectal cancer patients. Tumor/normal WGS was used to establish a patient-specific mutational fingerprint, which was searched for in 20x WGS plasma profiles. For reproducibility, paired aliquots of 172 plasma samples were analyzed in two independent laboratories. De novo variant calling was performed for serial plasma samples with a ctDNA level > 10 % (n = 17) to explore genomic evolution. ResultsWGS-based ctDNA detection was prognostic of recurrence: post-operation (Hazard ratio [HR] 6.75, 95 %CI 3.18–14.3, p < 0.001), post-adjuvant chemotherapy (HR 28.9, 95 %CI 10.1–82.8; p < 0.001), and during surveillance (HR 22.8, 95 %CI 13.7–37.9, p < 0.0001). The 3-year cumulative incidence of ctDNA detection in recurrence patients was 95 %. ctDNA was detected a median of 8.7 months before radiological recurrence. The independently analyzed plasma aliquots showed excellent agreement (Cohens Kappa=0.9, r = 0.99). Genomic characterization of serial plasma revealed significant evolution in mutations and copy number alterations, and the timing of mutational processes, such as 5-fluorouracil-induced mutations. ConclusionOur study supports the use of WGS for sensitive ctDNA detection and demonstrates that post-treatment ctDNA detection is highly prognostic of recurrence. Furthermore, plasma WGS can identify genomic differences distinguishing the primary tumor and relapsing metastasis, and monitor treatment-induced genomic changes.

801. ROBOTIC ASSISTED LAPAROSCOPIC GIANT PARA-OESOPHAGEAL HERNIA REPAIR: 5-YEAR EXPERIENCE

Abstract Background Prior to laparoscopic era, giant paraesophageal hernia repair (GPEHR) was considered a relatively morbid operation requiring thoracotomy or laparotomy or both. GPEHR has been shown to be amenable to laparoscopic approach with low morbidity and mortality. We presented the outcome of over 200 cases of laparoscopic GPEHR (LGPEHR) with long-term follow- up over 20 years at DDW 2022. We have been performing robotic-assisted laparoscopic giant paraesophageal hernia repair (RAL-GPEHR) since 2018 and present our results. Methods We did a retrospective analysis of prospectively collected data of RAL- GPEHR using the DaVinci Xi between December 2018 and March 2024. All operating data are electronically recorded automatically by DaVinci Xi system for each surgeon/console user. Demographic data, clinical presentation, pre-operative assessment, and testing including haemoglobin (Hb), respiratory function {Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1)} as well as quality-of-life (QoL) with SF-36 questioners (including general health, physical, emotional, and social components), length of hospital stay (LOS), morbidity, mortality and follow up outcomes (Clinical, Hb, radiological, respiratory and QoL) were recorded. Results Twenty patients underwent RAL-GPEHR with 15(75%) having crural repair plus gastropexy and 5(25%) patients having additional Toupet fundoplication. Fourteen (70%) were females. Data is presented in Table 1. Presenting symptoms were dyspnoea, reflux, post-prandial pain, and dysphagia with 7(35%) anaemic. Eight (40%) were ASA III and 12(60%) ASA II. Thirteen (65%) were Type III-GPEH, 4(20%)-Type IV, one-Type II (5%) and 2(10%) recurrent GPEH. Blood loss was minimal with no intra-operative complications or conversions to open. One (5%) had post-operative chest infection. Symptoms improved in all post-operatively with improvement of Hb, FVC, FEV1 and QoL. Radiological recurrence occurred in one (5%) but remains asymptomatic. Conclusions This report represents our initial experience of a small number of patients undergoing RAL-GPEHR which has proved to be feasible and safe. A long-term follow- up with a large series of patients is required to compare long-term outcomes especially symptomatic recurrences and QoL.

Peptide Receptor Radionuclide Therapy in Advanced Refractory Meningiomas: Efficacy and Toxicity in a Long Follow-up.

Recurrence of meningiomas after surgery and radiotherapy deserves specific attention because of the lack of active third-line therapies. Somatostatin receptors are usually overexpressed on the cell membrane of meningiomas, and this has led the way to a radionuclide theranostic approach. Diagnoses with 68Ga-DOTA-octreotide and peptide receptor radionuclide therapy (PRRT) with 90Y/177Lu-DOTA-octreotide are currently possible options within experimental protocols or as compassionate use in small patient groups. Methods: From October 2009 to October 2021, 42 meningioma patients with radiologic recurrence after standard therapies were treated with 90Y-DOTATOC (dosage of 1.1 or 5.5 GBq) or with 177Lu-DOTATATE (dosage of 3.7 or 5.5 GBq) in a mean of 4 cycles. All patients showed intense uptake at diagnostic 68Ga-DOTATOC PET/CT or in an 111In-octreotide scan. Results: Of 42 patients treated, 5 patients received 90Y-DOTATOC with a cumulative activity of 11.1 GBq and 37 patients received 177Lu-DOTATATE with a cumulative activity of 22 GBq. The disease control rate was 57%. With a median follow-up of 63 mo, median progression-free survival was 16 mo, and median overall survival was 36 mo. Retreatment 177Lu-PRRT was performed in 6 patients with an administered median activity of 13 GBq in a mean of 5 cycles. With a 75.8-mo follow-up, median progression-free survival and overall survival were 6.5 and 17 mo, respectively. Only 1 patient discontinued the treatment because of grade 3 platelet toxicity. A rapidly transient grade 2 neutropenia was recorded in 1 retreated patient. Conclusion: PRRT in patients with advanced meningiomas overexpressing somatostatin receptor 2 was active and well tolerated, showing a 57% disease control rate. Furthermore, PRRT could represent a potential retreatment option. Further studies, also in combination with other treatments, are warranted.

Efficacy of Coil Embolization in Small, Anterior Circulation Aneurysms in Patients Less Than 40 Years Old.

Background: Ruptured and unruptured aneurysms are less common in younger individuals compared to older patients. Endovascular treatment has gained popularity over surgical options in the general population, but surgery remains the primary treatment for younger patients due to concerns about higher recurrence rates with endovascular procedures. Methods: This study compared the immediate and long-term outcomes of endovascular treatment in patients under 40 years with those aged 41-60. The study included 239 patients who underwent endovascular treatment for intracranial aneurysms, divided into two age groups: under 40 and 41-60 years. The rates of immediate radiologic outcomes, complications, and recurrence were assessed. Results: The results showed successful aneurysm obliteration rates of 70.1% in the younger group and 64.0% in the older group. The complication rates were 1.5% in the younger group and 3.5% in the older group, with the older group experiencing more procedure-related complications, though this difference was not statistically significant. Long-term follow-up revealed recurrence rates of 23.2% in the younger group and 18.2% in the older group, with no significant difference. Conclusions: The study suggests that endovascular treatment is as effective and safe for patients under 40 years. Therefore, it may be considered an acceptable first-line treatment for younger patients, aligning its use with that in older populations.

Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study.

The absence of postoperative circulating tumor DNA (ctDNA) identifies patients with resected colorectal cancer (CRC) with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. Our study presents the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. TRACC (tracking mutations in cell-free tumor DNA to predict relapse in early colorectal cancer) included patients with stage I to III resectable CRC. Prospective longitudinal plasma collection for ctDNA occurred pre- and postsurgery, post-ACT, every 3 months for year 1 and every 6 months in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2-year recurrence-free survival (RFS) by postoperative ctDNA detection (NCT04050345). Between December 2016 and August 2022, 1,203 were patients enrolled. Plasma samples (n = 997) from 214 patients were analyzed. One hundred forty-three patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; two (1.4%) stage I, 64 (44.8%) stage II, and 77 (53.8%) stage III. Median follow-up was 30.3 months (95% CI, 29.5-31.3). Two-year RFS was 91.1% in patients with ctDNA not detected postoperatively and 50.4% in those with ctDNA detected [HR, 6.5 (2.96-14.5); P < 0.0001]. Landmark negative predictive value (NPV) was 91.2% (95% CI, 83.9-95.9). Longitudinal sensitivity and specificity were 62.1% (95% CI, 42.2-79.3) and 85.9% (95% CI, 78.9-91.3), respectively. The median lead time from ctDNA detection to radiological recurrence was 7.3 months (IQR, 3.3-12.5; n = 9). Tissue-free MRD detection with longitudinal sampling predicts recurrence in patients with stage I to III CRC without the need for tissue sequencing. The UK TRACC Part C study is currently investigating the potential for ACT de-escalation in patients with undetectable postoperative ctDNA, given the high NPV indicating a low likelihood of residual disease.

Comparison of the Efficacy of Percutaneous Microwave Ablation Therapy versus Laparoscopic Partial Nephrectomy for Early-Stage Renal Tumors.

This study aimed to compare the efficacy of percutaneous microwave ablation therapy (MWAT) and laparoscopic partial nephrectomy (LPN) in early-stage renal cell carcinoma (RCC) classified as T1a; a retrospective analysis was conducted on patients treated between January 2017 and November 2023. Oncological outcomes, radiological recurrence, length of stay (LOS), and costs were evaluated. The study included 110 patients, with no significant differences between the two groups regarding residual tumors, local tumor progression, and disease-free survival rates (p > 0.05). The LPN group showed significantly lower pre/postoperative serum urea and creatinine and higher estimated glomerular filtration rate values, whereas the MWA group experienced significantly lower mean costs, complication rates, LOS in the hospital, and procedure durations (p ≤ 0.05). However, post-procedure residual tumors and local tumor progression rates did not differ significantly between the LPN and MWAT groups (p > 0.05). MWAT is as effective as LPN for T1a RCC lesions. In addition, MWAT has lower costs than LPN and is a cost-effective treatment method. Therefore, MWAT minimizes hospital stay and complications and since the oncological results are similar to LPN, it might be considered as the first choice of treatment in young patients.

Histologic Activity From Neoterminal Ileal Biopsies in Patients With Crohn's Disease in Endoscopic Remission is Associated With Postoperative Recurrence.

Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed. A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk. In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

Risk factors associated with radiological and clinical recurrences after laparoscopic repair of large hiatal hernia with TiO2Mesh™ reinforcement.

Laparoscopic repair of large para-esophageal hiatal hernias (LPHH) remains controversial. Several meta-analyses suggest hiatus reinforcement with mesh has better outcomes over cruroplasty in terms of less recurrence. The aim of this study was to evaluate the medium-term results of treating LPHH with a biosynthetic monofilament polypropylene mesh coated with titanium dioxide to enhance biocompatibility (TiO2Mesh™). A retrospective observational study, using data extracted from a prospectively collected database was performed at XXX from December 2014 to June 2023. Included participants were all patients who underwent laparoscopic repair of large (> 5cm) type III hiatal hernia in which a TiO2Mesh™ was used. The results of the study, including clinical and radiological recurrences as well as mesh-related morbidity, were analyzed. Sixty-seven patients were finally analyzed. Laparoscopic approach was attempted in all but conversion was needed in one patient because of bleeding in the lesser curvature. With a median follow-up of 41months (and 10 losses to follow-up), 22% of radiological recurrences and 19.3% of clinical recurrences were described. Regarding complications, one patient presented morbidity associated with the mesh (mesh erosion requiring endoscopic extraction). Recurrent hernia repair was an independent factor of clinical recurrence (OR 4.57 95% CI (1.28-16.31)). LPHH with TiO2Mesh™ is safe and feasible with a satisfactory medium-term recurrence and a low complication rate. Prospective randomized studies are needed to establish the standard repair of LPHH.

Endoscopic endonasal resection of Rathke cleft cysts: a single-institution analysis of 148 consecutive patients.

The traditional treatment of sellar Rathke cleft cysts (RCCs) generally involves transsellar drainage; however, suprasellar RCCs present unique challenges to appropriate management and technical complexity. Reports on overall outcomes for the endoscopic endonasal approach (EEA) for this pathology are limited. The EEA for RCCs allows three surgical techniques: marsupialization, fenestration, and fenestration with cyst wall resection. The authors performed a retrospective review of consecutive patients with RCCs that had been treated via an EEA at a single institution between January 2004 and May 2021. Marsupialization entailed the removal of cyst contents while maintaining a drainage pathway into the sphenoid sinus. Fenestration involved the removal of cyst contents, followed by separation from the sphenoid sinus, often with a free mucosal graft or vascularized nasoseptal flap. Cyst wall resection, either partial or complete, was added to select cases. A total of 148 patients underwent an EEA for RCC. Marsupialization or fenestration was performed in 88 cases (59.5%) and cyst wall resection in 60 (40.5%). Cysts were classified as having a purely sellar origin (43.2%), sellar origin with suprasellar extension (37.8%), and purely suprasellar origin (18.9%). Radiological recurrence was demonstrated in 22 cases (14.9%) at an average 39.7 months' follow-up (median 45 months, range 0.5-99 months), including 13 symptomatic cases (8.8%). Cases with cyst wall resection had no significantly different rate of recurrence (11.7% vs 15.9%, p = 0.48) or postoperative permanent anterior pituitary dysfunction (21.6% vs 12.5%, p = 0.29) compared to those of fenestrated and marsupialized cases. There was no significant difference in postoperative permanent posterior pituitary dysfunction based on technique, although such dysfunction tended to worsen with cyst wall resection (13.6% vs 4.0%, p = 0.09). Based on cyst location, purely suprasellar cysts were more likely to have a radiological recurrence (28.6%) than sellar cysts with suprasellar extension (12.5%) and purely sellar cysts (9.4%; p = 0.008). Most notably, of the 28 purely suprasellar cysts, selective cyst wall resection significantly improved the long-term (10-year) recurrence risk compared to fenestration alone (17.4% vs 80.0%, p = 0.0005) without any significant added risk of endocrinopathy. Endoscopic endonasal marsupialization or fenestration of sellar RCCs may be the ideal treatment strategy, whereas purely suprasellar cysts benefit from partial cyst wall resection to prevent recurrence. Selective cyst wall resection reduced long-term recurrence rates without significantly increasing rates of hypopituitarism.

Analysis of ctDNA assay as a strategy for watchful waiting in locally advanced esophageal cancer.

e16126 Background: Standard treatment for locally advanced esophagogastric (EG) cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. The treatment goal is curative in order to control the tumor in the thorax, prevent regional recurrence, and to help prevent or delay metastatic progression. Despite achieving pathologic complete response (pCR) after surgery, patients with supposed local control may have recurrence up to a third of the time. Circulating tumor DNA (ctDNA) is an evolving tool in the field of oncology used as an informative biomarker. We provide longitudinal, real world observation of ctDNA minimal residual disease (MRD) to predict pCR and risk of recurrence. Methods: 22 participants with newly diagnosed locoregional EG cancer were enrolled under single institution approved protocol [IRB#1864127-7]. CtDNA-based MRD levels were obtained by Natera SignateraTM bespoke mPCR-NGS assay. Additionally, Natera Altera TM was used as a non-invasive biopsy to provide the comprehensive tumor-specific genomic profile. We evaluated thirteen participants who underwent definitive surgery and those who did not. Non-invasive plasma samples were surveilled at various timepoints which included the time of diagnosis, during neoadjuvant CRT, after definitive surgery. The primary outcome is a comparison of assay recurrence (AR) to disease recurrence (DR) defined as radiologic or clinical disease recurrence in participants with locoregional disease. Exploratory endpoints examine the profile of tumor. Results: Baseline levels were detected (n = 22) at new diagnoses. Longitudinal results demonstrated ctDNA clearance in eight participants while undergoing neoadjuvant chemoradiaton. Residual ctDNA were found in five participants for which two had clinical disease recurrence. Esophagectomy was done in three participants achieving pCR. Post procedural ctDNA were detected in one participant. Conclusions: The clearance of ctDNA favors less clinical disease recurrence in this study. This may indicate that ctDNA clearance confers lower risk of relapase. However, a larger cohort prospective study will be needed to validate the application of ctDNA as an early biomarker. The future application of ctDNA can be used to identify patients who may benefit from a watchful waiting adjuvant strategy instead of proceeding with invasive esophagectomy.

Circulating tumor DNA (ctDNA) to predict response to neoadjuvant chemotherapy (NAC) and prognosis in patients (pts) with early breast cancer (BC).

e12642 Background: pCR to NAC is an important predictor of clinical recurrence. Up to 16% of patients with pCR may experience disease recurrence, 45% of patients with RD do not. Longitudinal ctDNA testing offers a minimally invasive approach for monitoring treatment response EBC patients receiving NAC. We evaluated whether ctDNA status and dynamics can predict the tumor response to NAC and the risk of recurrence in patients with EBC. Methods: We conducted an observational, retrospective, single-center study to investigate whether ctDNA can predict tumor response to NAC and prognosis in BC patients. 74 pts received standard of care NAC;g 4 patients were treated in the adjuvant setting. Blood samples were collected at diagnosis from 44 pts (baseline) and longitudinally during treatment from 34 patients. Tumor response and progression outcomes were reported. A clinically validated, tumor-informed ctDNA assay (Signatera). ctDNA status and dynamics were correlated with pathologic and radiologic outcomes. Results: 29 TNBC pts were ctDNA+ at baseline, 6 were ctDNA- Of the 29 pts, early ctDNA clearance by week 6 of NAC was observed in 10 pts, weeks 7-16 in 9 pts, clearance post-surgery in 1, 3 pts remained ctDNA+ after surgery, serial ctDNA testing is underway for the remaining 6 pts. All TNBC patients who had radiological complete response (CR) had early clearance of ctDNA . All pts with persistent ctDNA positivity levels after completion of NAC had radiological partial response (PR). Of the 9 TNBC pts with undetectable baseline ctDNA, 33% achieved CR on MRI and 43% achieved pathologic CR. Of the 19 TNBC pts with ctDNA clearance in response to NAC, 89% (17/19) remained ctDNA- and with no evidence of disease (NED) (length of follow up). 1 pt initially cleared their ctDNA on NAC, turned ctDNA+ 4 weeks prior to radiological recurrence. 1 pt with ctDNA clearance on NAC remained ctDNA post-surgery but experienced recurrence. All (n=3) TNBC pts with persistent ctDNA-positivity levels after curative treatment (NAC and surgery) had disease recurrence. The remaining 6 pts ctDNA are ongoing NAC. Of the 6 pts with undetectable baseline ctDNA, 6/6 continued to be ctDNA- regardless of their disease status. At diagnosis, 8/9 ER+ ps were ctDNA+. 3/8 (38%) ER+ pts with positive baseline ctDNA had early clearance of ctDNA after NAC. All 3 had residual disease on pathology. 2/8 (25%) remained ctDNA+ after surgery and neither achieved radiologic CR or pCR. The remaining 3 pts are ongoing NAC. Conclusions: In early TNBC, ctDNA monitoring can be used to predict tumor response to NAC and tailor therapeutic regimens. ctDNA persistence can predict early recurrence and helps identify patients in which treatment escalation or enrollment on clinical trials is necessary. In ER positive breast cancer, and despite the small number of patients, ctDNA clearance does not predict response to NAC.

Analytical and clinical validation of a personalized, tumor-informed circulating tumor DNA assay for minimal residual disease detection.

e14545 Background: The detection of minimal residual disease (MRD) through circulating tumor DNA (ctDNA) analysis provides an advanced molecular method for early identification of surgical patients at high risk of recurrence. In this study, we present the development of mClear, a personalized, tumor-informed next-generation sequencing (NGS) assay for MRD detection. Furthermore, we report the analytical and clinical validation processes conducted to evaluate the performance of the MRD assay. Methods: mClear is designed to assess MRD in patients with solid tumors. Whole exome sequencing (WES) was performed on tumor tissues and matched peripheral blood samples to detect somatic variants comprehensively. Personalized MRD assays were carefully designed by selecting up to 40 prioritized variants, including single nucleotide variants (SNVs), small insertions and deletions (InDels), and fusions while ensuring coverage of 21 additional key driver genes. For analytical validation, we utilized a pan-cancer MRD ctDNA quality control product (LDT-999, LDT Bioscience), characterized by known variant allele frequency (VAF) gradients of 0%, 0.005%, 0.05%, and 0.5%, confirmed through droplet digital PCR (ddPCR). We conducted 18 replicate tests at VAF gradients of 0.5% and 0.05%, 23 replicates at the 0.005% VAF gradient, and 16 replicates at the 0% VAF gradient. For clinical validation, preoperative and postoperative blood samples from a cohort of 264 pan-cancer patients were analyzed. ctDNA collected for MRD detection underwent ultra-deep next-generation sequencing (100,000× average depth of coverage). The library preparation process commenced with an input of 30ng DNA. Results: At VAF gradients of 0.5% and 0.05%, the assay achieved an excellent sensitivity of 100%, and at VAF gradients of 0.005% and 0%, it demonstrated a sensitivity of 95.7% and a specificity of 100%. Preoperative ctDNA was detected in 86.7% (72/83) of the pan-cancer patients with 71.4% (5/7), 90.9% (10/11), 85.5% (47/55), and 100.0% (10/10) in pathological stage (pStage)I, pStage II, pStage III, and pStage IV, respectively. In the pan-cancer cohort, the positive rate of longitudinal MRD was 35.7% (75/210) with 17.8% (21/118), 50.0% (13/26), 55.1% (27/49), and 82.4% (14/17) in pStage I, II, III, and IV, respectively. In four patients who relapsed, MRD detection during surveillance preceded radiological recurrence by a lead time of 1-8 months. Conclusions: Our personalized MRD assay demonstrated excellent analytical sensitivity and specificity with a limit of detection (LoD) of 0.005% VAF at the sample level. Furthermore, it displayed high clinical sensitivity for the detection of ctDNA in the pan-cancer cohort, highlighting its potential for monitoring of recurrence.

USE OF MESH REPAIR IN HIATAL HERNIAS: OUR EXPERIENCE

Abstract Aim The use of meshes, their composition and fixation as reinforcement in hiatal hernia (HH) is currently controversial. The aim of this study is to evaluate the safety of the use of mesh in hiatoplasty, as well as to compare the medium-term results between absorbable and non-absorbable prosthesis. Methods Prospective study of a series of cases of patients with hiatal hernia operated on in our center between July 2010 and December 2023. In all cases, reinforcement hiatoplasty with prosthesis. Intra-surgical and post-operative complications were recorded. Clinical and radiological recurrence was evaluated. Results A total of 84 patients were operated on, in 12 cases (14.3%) a APTC mesh was placed, in 38 (45.2%) a cPTFE mesh and 34 (40.5%) a P4HB mesh. The percentage of overall clinical recurrence that we found occurred in 6 patients (7.1%). Radiological recurrence occurred in 9 patients (10.7%), of which 4 (10.5%) were treated with cPTFE mesh and another 4 (11.8%) with P4HB mesh, and 1 (8.3%) with APTC mesh. No statistically significant differences. 2 (16.7%) in the APTC group had some complication, 11 (28.9%) in the cPTFE group and 7 (20.6%) in the P4HB group. Conclusions No cases of serious intra- or posto-perative complications have been reported. The main medium-term complication was dysphagia with no differences between groups. There are no statistically significant differences in clinical or radiological recurrence between patients treated with different prosthetic materials.

Thiazides for kidney stone recurrence prevention.

Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation. The clinical routine to prescribe thiazides for kidney stone prevention has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of recurrence. Yet, adverse events such as new onset diabetes mellitus and gout were more common in patients receiving hydrochlorothiazide compared to placebo. As demonstrated by a novel meta-analysis presented in this review encompassing all randomized placebo-controlled trials with thiazide monotherapy, current trial evidence does not indicate that thiazide monotherapy is significantly better than placebo in preventing kidney stone recurrence. Given the limited efficacy and possible adverse effects, we advocate for a restrictive use of thiazides for kidney stone recurrence prevention. Clearly, there remains a high unmet medical need for effective, targeted therapies to prevent recurrence of kidney stones.