Metachronous Lesions Research Articles

Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps.

The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3years±6months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10mm. High-grade dysplasia or villous component, serrated polyps ≥10mm or with dysplasia or CRC. At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p<0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p<0.01) were independently associated with the development of advanced lesions at surveillance. Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes are associated with non-polypoid growth in ulcerative colitis-associated neoplasia.

Ulcerative colitis-associated neoplasia (UCAN) is characterised by multifocal tumourigenesis. A wide range of metachronous lesions have been reported to occur after endoscopic treatment of UCAN, which suggests the development of sporadic tumours in lesions treated as UCAN. Therefore, we aimed to evaluate differences of immunohistochemistry (IHC) in features and clinicopathological characteristics of intramucosal lesions in patients with ulcerative colitis (UC). We examined 35 intramucosal lesions resected for carcinoma or dysplasia by total colectomy from patients with UC and 71 sporadic adenomas (SAs) endoscopically resected from patients without UC. UC lesions were divided into the conventional UCAN group, defined as p53 mutant pattern andnormal expression of β-catenin, and the non-conventional UCAN group, defined as the rest. Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes were compared using IHC, and clinicopathological characteristics were investigated. Conventional and non-conventional UCAN lesions were located in the left colon and rectum. Relative to the SA lesions, UCAN lesions occurred in much younger patients and exhibited more frequent basal distribution of Ki-67 in tumour crypts. Conventional UCAN lesions tended to be non-polyploid and exhibited a higher frequency of normal AMACR expression than SA lesions. UC lesions were heterogeneous-only two of the eight patients with multiple lesions had lesions (both non-conventional UCAN lesions) exhibiting concordant IHC staining features. The basal pattern of Ki-67 distribution, normal expression of AMACR and a non-intestinal mucin phenotype were determined as characteristic features suggestive of UCAN. Non-polypoid growth was another a key feature of UCAN.

Optimal Surveillance of Metachronous Gastric Lesion after Endoscopic Resection of Early Gastric Cancer.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

Helicobacter pylori eradication following endoscopic resection might prevent metachronous gastric cancer: a systematic review and meta-analysis of studies from Japan and Korea.

A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia. PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups. Totally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98-2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43-1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44-0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found. The persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

Nd-YAG laser-assisted pulmonary metastasectomy: initial experience from a tertiary care cancer center in India.

Pulmonary metastasectomy is recommended for metastatic lung lesions when R0 resection is possible, the primary site is in controlled status, surgery is of low risk, and extrathoracic metastases are absent. We present the initial experiences of laser-assisted surgery (LAS) for pulmonary metastatic lesions from a tertiary care cancer center in India. All patients undergoing non-anatomical pulmonary metastasectomy between September 2022 and January 2023 for synchronous and metachronous lesions, operated on by a single consultant thoracic oncosurgeon in a tertiary care center of India, were identified from a prospective database. Ten patients with 124 metastatic lesions were included in the study. A hybrid approach (video-assisted thoracoscopic surgery (VATS) with mini-thoracotomy) was performed. Measurements of total lesion volume and lung parenchyma resected were taken from the final histopathological analysis of the intraoperative sample. LAS was performed for 102 lesions and stapled wedge resection for 22 lesions. Evidence of malignancy was noted in 88/102 (86.3%) of the lesions excised. Patients with LAS had advantages of parenchyma preservation, less postoperative morbidities, and shorter hospital stays. LAS of pulmonary metastatic lesions addresses more lesions in a single sitting; the bilateral lung lesions can be operated and has parenchyma preserving and good sealant properties. The online version contains supplementary material available at 10.1007/s12055-024-01723-8.

MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population

BackgroundEarly gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients.MethodsThis case–cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan–Meier and Cox proportional hazards model analyses.ResultsMIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03–5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07–8.95, p = 0.037).ConclusionsThis preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care.

Endoscopic submucosal dissection for lesions developing in the irradiated area of head and neck cancer.

Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions. Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single-center, retrospective study. Short- and long-term outcomes were evaluated. Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow-up of 40 (interquartile range, 29.5-61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3-year overall and disease-specific survivals were 81% (95% confidence interval, 64%-91%) and 94% (95% confidence interval, 79%-99%), respectively. Favorable local control and safety of endoscopic submucosal dissection were demonstrated.

Synchronous multifocal osteosarcoma: Report of 4 cases and literature review

BackgroundMultifocal osteosarcoma (MFOS) is rare, accounting for approximately 1.5 % of osteosarcomas, and can be synchronous (lesions within six months) or metachronous (lesions after six months). The etiology and optimal treatment for MFOS remain controversial. This report presents four patients with synchronous MFOS and reviews the literature. Case presentationCase 1: A 24-year-old female with low back pain was found to have multiple lytic bone lesions with increased FDG uptake in the vertebral column and pelvic bones. Biopsy confirmed osteoblastoma-like osteosarcoma. After chemotherapy, she is alive after 5 months.Case 2: A 6-year-old girl with right knee pain had a distal femur mass and a calcified inguinal lesion. Biopsies revealed osteoblastic osteosarcoma with metastatic lymph node involvement. Following chemotherapy and surgeries, she experienced recurrence and required further surgery. She is alive after 21 months.Case 3: A 4-year-old boy with a walking disability had a sclerotic bone lesion in the distal femur and additional lesions in the pelvis and acetabulum. Biopsy confirmed osteoblastic osteosarcoma. Despite treatment, he developed metastases and died 7 months after diagnosis.Case 4: A 9-year-old girl with right knee swelling had a sclerotic lytic lesion in the distal femur and an acetabular lesion. Biopsies confirmed chondroblastic osteosarcoma. After chemotherapy and surgery, she experienced recurrence and underwent pelvic resection. She died 24 months after diagnosis. ConclusionSynchronous MFOS is a highly aggressive osteosarcoma variant with a poor prognosis. Aggressive, individualized treatment may improve outcomes, particularly in metachronous cases. Further research is needed to enhance understanding and management of this rare condition.

Long-term outcomes of endoscopic submucosal dissection for undifferentiated type early gastric cancer over 2 cm with R0 resection.

Endoscopic submucosal dissection (ESD) for over 2 cm in size undifferentiated type (UD type) early gastric cancer (EGC) confined to the mucosa is not only challenging, but also long-term outcomes are not well known. To evaluate the long-term outcomes of ESD done for UD type EGCs confined to the mucosa over 2 cm in size and compare the results with those where the lesions were less than 2 cm. 143 patients with UD type EGC confirmed on histology after ESD at a tertiary hospital were reviewed. Cases with synchronous and metachronous lesions and a case with emergency surgery after ESD were excluded. A total of 137 cases were enrolled. 79 cases who underwent R0 resection were divided into 2 cm or less (group A) and over 2 cm (group B) in size. Among 79 patients who underwent R0 resection, the number in group A and B were 51 and 28, respectively. The mean follow-up period (SD) was 79.71 ± 45.42 months. There was a local recurrence in group A (1/51, 2%) and group B (1/28, 3.6%) respectively. This patient in group A underwent surgery while the patient in group B underwent repeated ESD with no further recurrences in both patients. There was no regional lymph node metastasis, distant metastasis, and deaths in both groups. With R0 resection strategy for ESD on lesions over 2 cm, 20.4% (28/137) of patients were able to avoid surgery compared with expanded indication. If R0 resection is achieved by ESD, UD type EGCs over 2 cm also showed good and similar clinical outcomes as compared to lesions less than 2 cm when followed for over 5 years. With R0 resection strategy, several patients can avoid surgery.

Pagetic osteosarcoma: An analysis of the National Cancer Database.

e23503 Background: Pagetic osteosarcoma (Pagetic OS) is a rare cancer typically originating at bones affected by Paget disease. Pagetic OS may present as metachronous multifocal lesions primarily affecting the pelvis, proximal femur, and proximal humerus. There are currently no available sociodemographic descriptions of patients with Pagetic OS. Analyzing sociodemographic factors through the National Cancer Database may unveil important information about its epidemiology and guide future treatment. Methods: A retrospective cohort analysis utilizing the 2004–2020 National Cancer Database (NCDB) included patients with a histologically-confirmed diagnosis of Pagetic osteosarcoma (N = 128) using ICD-O-3 code 9184. Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charles/Deyo score) were analyzed by descriptive statistics. Incidence trends were interpreted in regression analysis. Results: In the NCDB, 128 patients were identified with a confirmed diagnosis of Pagetic osteosarcoma (Pagetic OS) between 2004 and 2020, with a steady incidence of diagnoses per year (R2 = 0.0). The average age of diagnosis was 68.9 years (SD = 13.4, range = 11-90 years). Men were more likely to be diagnosed than women (57% and 43%, respectively). Most patients were non-Hispanic White (71%), insured by Medicare (56%), and lived in a metropolitan area (85%). When compared individually, more patients were in the top median household income quartile (31%). The top two primary sites were the long bones of the lower limb including their associated joints (27%) and the pelvic bones excluding the sacrum, coccyx, and symphysis pubis (27%). Within the cohort, 31 patients received chemotherapy as primary treatment (24%) while 28 patients received primary radiation therapy (22%). Most patients (63%) did not undergo primary site surgery while 39 patients (31%) did receive surgery as primary treatment. The 90-day mortality included 15% of patients, who died 90 or fewer days after surgery was performed. The 2-year survival was 82% while the 5-year survival was 53% and the 10-year survival was significantly lower at approximately 11%. Most individuals (76%) had Charlson-Deyo comorbidity scores of 0. Conclusions: To the best of our knowledge, this NCDB analysis on Pagetic osteosarcoma (Pagetic OS) is the first of its kind on this specific subset of osteosarcoma. Previous research suggests the broader osteosarcoma occurs most frequently in adolescents. This data reveals that Pagetic OS is primarily diagnosed later in life (68.9 years), while still affecting a significantly wide age range (range = 11-90 years). Most patients were non-Hispanic White (71.1%), lived in a metropolitan area (85.2%), and belonged to the top median household income quartile (31.3%). Further research could unveil additional guidance on best practice in diagnosing and treating this cancer.

Serrated Polyps in Inflammatory Bowel Disease Indicate a Similar Risk of Metachronous Colorectal Neoplasia as in the General Population.

The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. 477 patients with serrated polyps were eligible (mean age 61years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps.

Treating Benign Ovarian Lesions in the Pediatric Population: A Single Institution's Retrospective Investigation of Laparoscopy Versus Open Repair.

Background: Benign ovarian lesions in the pediatric population have variable risk of recurrence or development of metachronous lesions, leading to variations in operative approach. Our study compares outcomes with differing surgical approaches to better elucidate risk of recurrent or metachronous lesions, time to development of these lesions, and hospital length of stay to determine if one operative approach has superior outcomes. Methods: We retrospectively examined data from Indiana University Health facilities from 2002 to 2020. Patients ≤18 years old who underwent surgical management of a benign ovarian lesion were included. Patients were categorized as undergoing oophorectomy versus ovarian sparing surgery (OSS), with open and laparoscopic approaches. Significance was defined as P < .05. Results: We identified 127 patients who underwent an open (n = 65) versus laparoscopic (n = 55) surgical approach. Patients undergoing open surgery had a greater mean size of lesion (P = .05) and longer length of stay (P < .01). Complication rates (P = .1), rates of developing a metachronous or recurrent lesion postoperatively (P = .47), and time to formation of additional lesions were similar between groups (P = .25). The incidence of identifying an additional lesion after surgery was 14.2% (n = 18) in the mean time of 29.5 ± 31.6 months [SEM 7.5]. Risk of developing a metachronous lesion was similar regardless of the operative approach. Surgery for recurrent ovarian lesions was rare and occurred in only 1 case. Conclusions: Laparoscopic surgery was performed for smaller lesions and was associated with a shorter length of hospital stay. Laparoscopic and OSS was found to have no increased risk of developing metachronous lesions nor increased reoperative risk compared with traditional open and oophorectomy techniques.

Abstract 4771: Assessment of Ki67 proliferation index in pre-malignant colonic adenomas: Implication for new biomarker testing to predict metachronous disease (The INCISE project)

Abstract Approximately 40% of patients are found to have polyps at bowel screening colonoscopy, which are associated with a higher risk of developing future polyps or colorectal cancer. The British Society of Gastroenterology 2020 (BSG20) guidelines stratify patients into high/low risk of metachronous disease, using the size, dysplasia, and number of polyps found at index colonoscopy. This study aims to explore the prognostic significance of Ki67 proliferation percentages in adenomatous polyps, with metachronous disease. Tissue microarray (TMA) was constructed from 1201 index adenomatous polyps with representative cores of basal and luminal adenomatous epithelia. 67% patients were identified as high risk at index colonoscopy. The median time to detect metachronous polyps was 55 months (range 6-72 months) with 56% of patients developing metachronous polyps by the end of follow-up. TMA was stained for Ki67 using immunohistochemistry. Ki67 proliferation percentages in adenomatous epithelia was quantified using QuPath. Data was split into training (n=830) and test (n=371) datasets. The Ki67 proliferation cutpoint was made using Survmine R package using the training dataset. X2 test was used to study associations with clinicopathological criteria and Kaplan survival analysis was used to assess Ki67 association with metachronous lesions. Ki67 percentages were higher in lumina than in basal adenomatous epithelium (median Ki67 were 63% &amp; 48%; respectively). Total Ki67 percentages were computed by averaging luminal and basal values. Thresholds of 70%, 64% and 59% were employed to classify patients into low/high categories based on luminal, basal or total percentages; respectively. In the training cohort, high luminal, basal or total Ki67 were associated with metachronous lesions (p values 0.032, &amp;lt;0.001 and 0.006; respectively). Other associations were significant between luminal or total Ki67 and location of index polyps (p=0.017 &amp; p=0.044; respectively), histology (p=0.019) and advanced future lesion status (p=0.002 &amp; p&amp;lt;0.001; respectively). In multivariate cox regression analysis, high Ki67 was an independent prognostic factor for metachronous polyps (luminal Ki67 HR=1.28, CI: 1.052-1.560, p=0.014; basal Ki67 HR=1.639, CI: 1.313-2.046, p&amp;lt;0.001; total Ki67 HR=1.344, CI: 1.105-1.635, p=0.003) when adjusted to number of index polyps and BSG20 risk score. BSG20 risk score stratification of patients in terms of metachronous disease was improved when combined with luminal, basal or total Ki67 in the training datasets (all p&amp;lt;0.05). Prediction of metachronous disease by the combined groups was validated in the test cohort for luminal, basal and total Ki67 (all p&amp;lt;0.05). High Ki67 proliferation rates in adenomatous polyps are independently associated with the development of metachronous polyps and may help improve the BSG20 criteria. Citation Format: Gerard P. Lynch, Aula Ammar, Christopher Bigley, Mark Johnstone, Jakub Jawny, Hannah Morgan, Jennifer Hay, Noori Maka, Stephen McSorley, Joanne Edwards. Assessment of Ki67 proliferation index in pre-malignant colonic adenomas: Implication for new biomarker testing to predict metachronous disease (The INCISE project) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4771.

Stereotactic body radiotherapy as a viable treatment on extracranial oligometastases in melanoma patients: a retrospective multicentric study.

Stereotactic radiotherapy (SBRT) potentially has a role in the management of oligometastatic melanoma. However, literature with data specific to this management is very limited. The objectives of this study were to evaluate the time to local control (LC) of extra-cranial melanoma metastases after SBRT treatment and to help establish if SBRT is a useful therapy for oligometastatic melanoma. A retrospective study was conducted with data collected from two referral centers in France between 2007 and 2020. The oligometastatic status of patients was reported based on the latest recommendations with a maximum of three lesions prior to treatment. A total of 69 patients receiving SBRT for 88 oligometastatic melanoma metastases were included. The median follow-up time was 42.6 months. Most patients were treated for metachronous oligometastatic lesions. Occurrence of oligoprogression, oligorecurrence, and oligopersistence was reported in 42.0%, 39.1%, and 17.4% of cases, respectively. Treated lesions were mostly pulmonary (40.6%), followed by lymph node (34.8%) and hepatic sites (24.6%). Progression-free survival at 1, 2, and 3 years were 47.0% (35-59), 27.0% (16-39), and 25.0% (15.0-37.0), respectively. Time to LC rates at 1, 2, and 3 years were 94.2% (87.0-98.1), 90.3% (81.3-96.1), and 90.3% (81.3-96.1), respectively. Overall survival at 1, 2, and 3 years were 87% (76.0-93.0), 74.0% (76.0-93.0), and 61.0% (47.0-73.0), respectively. Only 17.4% of patients experienced acute, grade 1 or grade 2 toxicities with no reports of grade 3 or higher toxicities. SBRT demonstrated efficacy in managing melanoma patients with extracranial oligometastases and showed an overall low toxicity profile. Future randomized studies are needed to establish the role of SBRT in therapeutic approaches for patients with oligometastatic melanoma.

Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis.

Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

A208 ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR BARRETT’S NEOPLASIA: CLINICAL OUTCOMES AND MID-TERM FOLLOW-UP AT A CANADIAN TERTIARY REFERRAL CENTER

Abstract Background Endoscopic submucosal dissection (ESD) is an established technique for resecting early gastrointestinal neoplastic lesions. However, for Barrett’s neoplasia treatment, piecemeal EMR has been the standard approach, leaving the efficacy of ESD for Barrett’s neoplasia unclear. Aims To assess the outcomes of Barrett’s neoplasia treated with ESD at a tertiary center in Canada. Methods This is a single center, retrospective study. All patients aged over 18 who underwent ESD for Barrett’s neoplasia at St. Michael’s Hospital between December 2017 and August 2023 were included. Primary outcomes were En-bloc, R0, curative resection, and recurrence rates, while secondary outcomes focused on the adverse event rate. Results Of the 72 patients studied (mean age 67.7 years; 90% male), 31.9% (23/72) were SSBE and 68.1% (49/72) were LSBE. The mean±SD lesion size was 4.5±3.4 cm, with circumferential occupancy at 53.4±23.9 %. Paris classifications were as follows: 0-Is: 8 (11.1%), 0-IIa: 26 (36.1%), 0-IIb: 9 (12.5%), 0-IIc: 6 (8.3%), 0-IIa+IIc: 13 (18.6%), 0-IIa+Is: 10 (13.9%). The mean operation time stood at 144.4 (75.3) minutes. Adverse events comprised deep mural injury (4.1%) and delayed bleeding (2.8%). Pathology findings showed high-grade dysplasia in 6.9% and adenocarcinoma in 93.1%, further differentiated as: well-differentiated (55%), moderately differentiated (33%), and poorly differentiated (12%). The invasion depth was intramucosal in 76%, SM1 in 6%, and SM2-SM3 in 18%. Lympho-vascular invasion was present in 22%. En-bloc, R0, and curative resection rates were 96% (69/72), 82% (59/72), and 64% (46/72), respectively. Of the curative resection patients, 42 have completed follow-up EGD, with 11.9% (5/42) showing persistent dysplasia at first follow-up. These were treated by either EMR (4 cases) or ESD (1 case), leading to a 100% (42/42) complete remission of dysplasia (CRD) rate with median follow-up time of 127 (68-190) days. After achieving CRD, local recurrence was found in 2.4% (1/42) with a median follow-up time of 289 (136-524) days. This recurrence post-CRD was successfully treated with EMR, regaining CRD. Conclusions Our study showcases the Canadian experience of using ESD for Barrett’s neoplasia at a large single tertiary referral center. Given the challenging demarcation lines in Barrett’s neoplasia and the frequent presence of metachronous lesions, even with curative resection, 11.9% showed persistent lesions during the first follow-up. However, these lesions were treatable endoscopically, with 100% eventually achieving CRD. Although there was a 2.4% recurrence rate post-CRD, this too could be managed endoscopically. Overall, the mid-term outcomes of treating Barrett’s neoplasia with ESD are promising. Funding Agencies None

Combined Therapy of Chemotherapy and Radiofrequency Ablation for Pancreatic Cancer Patients With Metachronous Hepatic Metastatic Lesions After Radical Pancreatic Resection.

Hepatic metastasis frequently occurs in patients who have undergone radical pancreatic resection for pancreatic cancer. Besides chemotherapy, various local treatment approaches targeting hepatic lesions have been explored. However, research on radiofrequency ablation (RFA) as a localized therapy for hepatic metastasis is limited. Therefore, we conducted this retrospective study to provide clinical evidence. This is a single-center, retrospective, cohort study. After radical pancreaticoduodenectomy, 32 patients developed metachronous hepatic metastasis with fewer than 3 lesions, the largest of which was less than 3cm in diameter. These patients underwent combined treatment with chemotherapy and RFA. After 8 weeks of chemotherapy, patients received RFA for hepatic lesions. Additional chemotherapy was administered, and the patients' tumor status and survival were monitored. The primary endpoint of this study was overall survival (OS). Factors affecting OS were analyzed using the Cox risk model. Among the 32 patients, the mean OS was 28.4 months. Univariate and multivariate Cox regression analysis revealed that the time (in months) of liver metastasis (HR = 0.04, 95% CI: 0.01 to 0.19; P < 0.001), the number of liver metastases (HR = 7.08, 95% CI: 1.85 to 27.08, P = 0.004), and PD (progressive disease) response to the second round of chemotherapy (HR = 29.50, 95% CI: 1.46 to 597.27; P = 0.027) were independent predictors of poorer survival. Combined therapy with RFA and chemotherapy is safe in patients with hepatic metastasis after radical pancreaticoduodenectomy. Early recurrence (≤12months), three liver metastatic lesions, and a poor response to the second round of chemotherapy were associated with poor survival.

Bilateral Wilms tumor: 10-year experience from a single center in China.

Nephron sparing surgery (NSS) had become the main surgical treatment for bilateral nephroblastoma. But it remained a challenge for surgeons to balance the dilemma between complete tumor resection to reduce tumor recurrence and renal parenchyma preservation to reduce end-stage renal disease (ESRD). In this study, we summarized our clinical experience for bilateral Wilms tumors managed in our center and evaluated the influence of different surgical approaches on prognosis. The clinical data of patients with bilateral Wilms tumor in our hospital from January 2010 to December 2020 were retrospectively analyzed, and the clinical symptoms, surgical approaches and prognosis of the disease were summarized. We reviewed medical records of 16 patients, including 13 (81.3%) girls and 3 (18.7%) boys. The mean age of the patients was 17.88±11.65 months (range, 6-42 months). Five patients presented with hypertension and two presented with hemihypertrophy. Fifteen cases had synchronous tumors, while only one patient had metachronous bilateral lesions. Thirteen patients received neoadjuvant chemotherapy and only 8 kidneys (30.8%) responded to chemotherapy. Two patients gave up surgery, and the other fourteen patients underwent radical resection, of which 2 patients only underwent unilateral radical nephrectomy (RN); 7 and 5 patients underwent single-stage and two-stage operation for bilateral lesions, respectively. In all surgical patients, RN was performed on 5 kidneys, and NSS was performed on 21 kidneys. The positive margins after NSS were found in 6 kidneys (35.3%). After a median follow-up period of 26.3 months, local tumor recurrence and renal insufficiency occurred in two and one patients. The 5-year overall and event-free survival rates were 78.1% and 58.6%, respectively. In univariable analysis, the survival rate in the initial chemotherapy group (92.3%) was significantly higher than that in the initial surgery group (33.3%) (P=0.048), whereas positive margin and staged operation (P>0.05) appeared not significantly associated with overall survival. The proportion of tumor reduction after preoperative chemotherapy is relatively low for bilateral Wilms tumor, but preoperative chemotherapy could improve overall survival. NSS is recommended for bilateral Wilms tumor, and the customized procedure can be selected according to the location and anatomical features of tumor.

P1065 Endoscopic Submucosal Dissection for High-Risk Colorectal Colitis-Associated Neoplasia in Inflammatory Bowel Disease: a Real-World Multicenter Study

Abstract Background Inflammatory bowel disease (IBD) patients have a 2-3-fold increased risk of developing colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN), including non-polypoid lesions and large non-pedunculated colon polyps, are often not amenable to conventional resection techniques. Aim of this study was to evaluate effectiveness and safety of endoscopic submucosal dissection (ESD) of HR-CANs. Methods In this real-world, multicenter, retrospective study, we included consecutive IBD patients referred to nine Tertiary Italian Endoscopy Centers (January 2014 - April 2023) to undergo an ESD or a hybrid-ESD (hESD), for HR-CANs. The primary outcome was rate of en bloc, R0 resection and adverse events (AEs). The secondary outcome was rate of local recurrence, metachronous lesions, and post-dissection surgery. Results 96 HR-CANs (89.6% non-polypoid, 79.2% left-side colon, 34.8 mm ± 16.2 mm, 15.6% invasive pit-pattern) in 91 patients with colonic IBD (58.2% male, 60.8 ± 12.2 years, 83.4% ulcerative colitis, disease duration of 183 ± 104 months, 14.3% endoscopic activity) were included. ESD and hESD were performed in 82.3% and 17.7% of cases. The final histopathological diagnoses were serrated sessile lesions in 14.6%, low-grade dysplasia in 32.3%, high-grade dysplasia in 38.5%, adenocarcinoma in 14.6%. Overall, en bloc and R0 resection were achieved in 95.9% and 85.4% of cases. AEs occurred in 12.5% of cases, all managed endoscopically and conservatively. After a mean follow-up of 23.4 months, local recurrence and metachronous lesions occurred each in 3.1% (n=3) of cases. Post-dissection surgery was required in 11.5% (n=11) of cases (7 for histopathology, 2 for recurrences, 2 for refractory IBD). At univariate analysis the left site was identified as a predictor of higher rate of en bloc resection (OR 0.07; 0.007-0.77; p=0.02), while the female sex as a predictor of lower rate of AEs (OR 0.17; 0.03-0.81; p=0.02). Further, the invasive pit pattern was associated with higher rate of post-dissection surgery (OR 6.25; 1.6-24.3; p=0.008). Conclusion Our findings showed that ESD of HR-CANs, when performed in Tertiary Endoscopy Centers, was effective and safe in patients with colonic IBD. However, further prospective studies including a long-term follow-up are still required to highlight the impact of ESD for IBD patients’ dysplasia-free survival.

Abstract C104: Dual primary pancreas cancers – Related or independent lesions?

Abstract Background: Not infrequently, an apparent second pancreas ductal adenocarcinoma (PDAC) is identified either synchronously or metachronously. To date, it remains unclear whether these individual PDACs represent intrapancreatic metastases or a new primary PDAC. Here, we sought to understand the clinicogenomic features of this patient population to provide insights on the underlying biology and management implications. Methods: Memorial Sloan Kettering Cancer Center (MSK) institutional databases were searched for patients with two PDAC diagnoses and at least one pancreatic resection or patients who had undergone completion/total pancreatectomy and then manually curated. Detailed demographic and clinical information were abstracted from the medical record. Metachronous patients excluded if previous surgical margin positive for invasive or pre-invasive carcinoma. All patients were either consented to MSK IMPACT for somatic and germline sequencing (N=16), were approved for de-identified genomic analyses by IRB (N=3), or were excluded from genomic analysis (N=2). KRAS wild-type (WT) tumors were interrogated for targetable fusions with Archer FusionPlex solid tumor panel. Results: N=21 patients (pts) identified, N=6 synchronous, N=15 metachronous. Mean age at diagnosis of first PDAC (PDAC1): 67.1y (51.2–79.1y). PDAC risk factors: 52% (10/19) smoking history, 15% (2/13) with first degree relative with PDAC, 85% (11/13) with first degree relative with any malignancy, and 40% (8/20) with history of premalignant pancreas lesion. N=2 pts with pathogenic germline mutation in ATM. By morphology, 80% (4/5) of synchronous and 65% (11/17) of asynchronous lesions indistinguishable. Two lesions, both metachronous, demonstrated divergent histology while remaining cases demonstrated focal differences. Genomically, 40% (10/25) samples with mKRAS G12V, G12R (16%), G12D (12%), Q61H (8%), G12C (4%); 20% KRAS WT. Of available paired tumor samples, 71% (5/7) with identical KRAS alleles and additional driver mutations. N= 1 pt with different KRAS alleles also had divergent TP53 alleles and CDKN2A/B loss occur in metachronous lesions 14 m apart. N=1 pt with KRAS WT tumor had an actionable fusion involving FGFR2. For metachronous lesions, median interval PDAC1 to PDAC2: 5.1 y (1.1 – 15.2 y). At median follow-up of 7.2 y (0.2 – 15.4 y) from PDAC1, 90% (19/21) have undergone completion/total pancreatectomy and N=16 (76%) alive with 5-year survival rate of 93% (14/15). Conclusions: The clinical, pathologic, and genomic data strongly suggest that two PDAC, independent of disease interval, most often represent the same phylogenetic entity. KRAS allele variant adjudication was the single most important discriminator and was in concordance with other driver oncogenes. Pathogenic germline variants were rare and limited to gATM; notably no gBRCA/PALB2. Acknowledging the highly selected nature of this cohort, solitary intrapancreatic metastases demonstrate a more favorable biology and these patients may benefit from personalized management approaches beyond traditional paradigms. Citation Format: Joshua D. Schoenfeld, Hulya Sahan-Ozkan, Nadeem Bilani, Michael I. D'Angelica, William R. Jarnagin, Jeffrey Drebin, Diane Reidy-Lagunes, Alice C. Wei, Sree B. Chalasani, Anna M. Varghese, Fiyinfolu Balogun, Wungki Park, Kenneth H. Yu, Olca Basturk, Eileen M. O'Reilly. Dual primary pancreas cancers – Related or independent lesions? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C104.