Low Risk Of Recurrence Research Articles

Novel Artificial Intelligence Combining Convolutional Neural Network and Support Vector Machine to Predict Colorectal Cancer Prognosis and Mutational Signatures From Hematoxylin and Eosin Images

Reducing recurrence following radical resection of colon cancer without overtreatment or undertreatment remains a challenge. Postoperative adjuvant chemotherapy (Adj) is currently administered based solely on pathologic TNM stage. However, prognosis can vary significantly among patients with the same disease stage. Therefore, novel classification systems in addition to the TNM are necessary to inform decision-making regarding postoperative treatment strategies, especially stage II and III disease, and minimize overtreatment and undertreatment with Adj. We developed a prognostic prediction system for colorectal cancer using a combined convolutional neural network and support vector machine approach to extract features from hematoxylin and eosin staining images. We combined the TNM and our artificial intelligence (AI)–based classification system into a modified TNM-AI classification system with high discriminative power for recurrence-free survival. Furthermore, the cancer cell population recognized by this system as low risk of recurrence exhibited the mutational signature SBS87 as a genetic phenotype. The novel AI-based classification system developed here is expected to play an important role in prognostic prediction and personalized treatment selection in oncology.

PET-CT-guided, symptom-based, patient-initiated surveillance versus clinical follow-up in head neck cancer patients (PETNECK2): study protocol for a multicentre feasibility study and non-inferiority, randomised, phase III trial

BackgroundApproximately 40% of treated head and neck cancer (HNC) patients develop recurrence. The risk of recurrence declines with time from treatment. Current guidelines recommend clinical follow-up every two months for the first two years after treatment, with reducing intensity over the next three years. However, evidence for the effectiveness of these regimes in detecting recurrence is lacking, with calls for more flexible, patient-centred follow-up strategies.MethodsPETNECK2 is a UK-based multi-centre programme examining a new paradigm of follow-up, using positron emission tomography-computed tomography (PET-CT)-guided, symptom-based, patient-initiated surveillance. This paradigm is being tested in a unblinded, non-inferiority, phase III, randomised controlled trial (RCT). Patients with HNC, one year after completing curative intent treatment, with no clinical symptoms or signs of loco-regional or distant metastasis will be randomised using a 1:1 allocation ratio to either regular scheduled follow-up, or to PET-CT guided, patient-initiated follow-up. Patients at a low risk of recurrence (negative PET-CT) will receive a face-to-face education session along with an Information and Support (I&S) resource package to monitor symptoms and be in control of initiating an urgent appointment when required. The primary outcome of the RCT is overall survival. The RCT also has an in-built pilot, a nested QuinteT Recruitment Intervention (QRI), and a nested mixed-methods study on patient experience and fear of cancer recurrence (FCR). An initial, single-arm feasibility study has been completed which determined the acceptability of the patient-initiated surveillance intervention, the completion rates of baseline questionnaires, and optimised the I&S resource prior to implementation in the RCT.DiscussionWe hypothesise that combining an additional 12-month post-treatment PET-CT scan and I&S resource will both identify patients with asymptomatic recurrence and identify those at low risk of future recurrence who will be empowered to monitor their symptoms and seek early clinical follow-up when recurrence is suspected. This change to a patient-centred model of care may have effects on both quality of life and fear of cancer recurrence.Trial registrationISRCTN: 13,709,798; 15-Oct-2021.

Shorter interval to surgery after self-expanding metallic stent may result in better oncologic outcomes in colon cancer obstruction

IntroductionColon cancer obstruction is one of the most serious conditions in colorectal surgery. However, the use of self-expanding metallic stent (SEMS) has made it possible to avoid emergency surgery and stoma creation, therefore enabling minimally invasive surgery and one-stage operation. In this study, we aimed to investigate whether there is an optimal interval from SEMS to surgery for the best long-term oncologic outcomes. MethodsObstructive colon cancer patients treated with SEMS insertion and received surgery were included in the study. Patient data were retrospectively reviewed in prospectively collected data. Using the ROC curve, the optimal interval to surgery after SEMS insertion was 10 days; the patients were divided into the early surgery group (≤10 days, ES) and the late surgery group (>10 days, LS). Factors contributing to the 5-year disease-free survival (DFS) and overall survival (OS) were analyzed. Results83 patients were included in this study. Eight patients (9.6 %) had SEMS insertion failure, with 3 perforations and 5 failed expansions. There were no differences between the ES group and the LS group in terms of pathologic characteristics, incidence of stoma creation, and adjuvant chemotherapy. Twenty-six patients (31.3 %) had recurrences; local (Arnarson et al., 2023) [6], peritoneal seeding (Lee et al., 2013) [8], liver (Ho et al., 2017) [11], lung [7], bone (van Hooft et al., 2020) [2], and abdominal wall metastasis (Chen and Sheen-Chen, 2000) [1]. The 5-year DFS rate was significantly better in the ES group than the LS group (74.3 % vs. 55.01 %; p = 0.0394). The 5-year OS was slightly better in the ES group than the LS group (76.11 % vs. 58.75 %; p = 0.0901). In univariable analysis, the ES group showed a lower risk of recurrence than the LS group (OR: 0.447 [0.204–0.984], p = 0.0455), but this was not reproduced in the multivariable analysis. ConclusionThis study has shown that the long-term oncologic outcomes were better in patients who received surgery after SEMS within 10 days. Hence, we propose with caution that elective surgery might be suggested to take place within 10 days from SEMS insertion for better oncologic outcomes.

Epilepsy surgery for children with epileptic spasms: A systematic review and meta-analysis with focus on predictors and outcomes.

To conduct a systematic review of the literature regarding rates and predictors of favorable seizure outcome after resective surgery for epileptic spasms (ES) in pediatric patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed. We searched PubMed, EMBASE, and Cochrane CENTRAL for articles published on the prevalence or incidence of epileptic spasm since 1985. Abstract, full-text review, and data extraction were conducted by two independent reviewers. Meta-analysis was performed to assess overall seizure freedom rate. Subject-level analysis was performed on a subset of studies to identify prognostic indicators. A total of 21 retrospective studies (n = 531) were included. Meta-analysis of all studies demonstrated a pooled seizure freedom rate of 68.8%. Subject-level analysis on 18 studies (n = 360) demonstrated a significant association between duration of spasms and recurrence of spasms after surgery, with an estimated increased risk of 7% per additional year of spasms prior to operation. Patients who underwent resective surgery that was not a hemispherectomy (i.e., lobectomy, lesionectomy, etc.) had an increased recurrence risk of 57% compared to patients who had undergone hemispherectomy. Resective surgery results in seizure freedom for the majority of pediatric patients with epileptic spasms. Patients who undergo hemispherectomy have lower risk of recurrence than patients who undergo other types of surgical resection. Increased duration of spasms prior to surgery is associated with increased recurrence risk after surgery. PLAIN LANGUAGE SUMMARY: Children with epileptic spasms (ES) that do not respond to medications may benefit from surgical treatment. Our study reviewed existing research to understand how effective surgery is in treating ES in children and what factors predict better outcomes. Researchers followed strict guidelines to search for and analyze studies published since 1985, finding 21 studies with a total of 531 patients. They found that, on average, nearly 70% of children became seizure-free after surgery. Further individual analysis of 360 patients showed that longer duration of spasms before surgery increased the risk of spasms returning by 7% per year. Additionally, children who had less extensive surgeries, such as removal of only a specific part of the brain, had a 57% higher risk of seizure recurrence compared to those who had a hemispherectomy, which removed or disconnected half of the brain. Overall, the study concludes that surgery can often stop seizures, especially when more extensive surgery is performed and when the surgery is done sooner rather than later.

Surgical outcomes of hidradenitis suppurativa: evaluating factors influencing recurrence and complications after 284 complete excisions

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory disorder associated with tunnel formation and scarring. Surgical excision is a potential curative therapy for HS. Objectives To characterize the surgical outcomes of patients with HS undergoing complete excision and to identify the risk factors associated with postoperative recurrence. Methods This retrospective 16-year cohort study enrolled patients 20 years or older who underwent complete excision for HS lesions at the National Taiwan University Hospital. We assessed the rates of postsurgical recurrence and complications, and estimated the odds ratio (ORs) with 95% confidence intervals (CIs) of their association with potential risk factors using generalized estimating equations. Results In total, 136 patients with HS and the 284 corresponding complete excisions were identified. Recurrence developed in 88 (31.0%) operations, while complications occurred in 102 (35.9%). Common types of complications included wound dehiscence, hypertrophic scars, and surgical site infection. Clinical factors associated with a lower risk of recurrence were male sex (aOR, 0.48; 95% CI, 0.23–0.98), operation at atypical locations (aOR, 0.28; 95% CI, 0.08–0.99), and wound repair by split-thickness skin graft (aOR, 0.31; 95% CI, 0.12–0.77). Wound dehiscence was associated with an increased risk of recurrence (aOR, 2.55; 95% CI, 1.21–5.42). No independent factors were identified as being associated with composite postoperative complications. Conclusions Complete excision alone is effective in curing HS in Asians. Recurrence developed in about one-third of the complete excisions performed for HS. Sex, operative locations, methods of wound repair, and wound dehiscence were major determinants for recurrence.

Re-Evaluating the Omission of Radiation Therapy in Low-Risk Patients With Early-Stage Breast Cancer

Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.

Mohs Micrographic Surgery for Cutaneous Squamous Cell Carcinoma.

The first-line treatment of the localized form of cutaneous squamous cell carcinoma (cSCC) remains surgical excision. Either conventional excision (CE) with margins or Mohs micrographic surgery (MMS) may be preferred, depending on the risk factors of cSCC, the characteristics of the tumor, and the available technical facilities. This article presents a systematic review of the current literature spanning from 1974 to 2023, comparing outcomes of cSCC treated with MMS versus cSCC treated with conventional excision. Out of the 6821 records identified through the database search, a total of 156 studies were screened, of which 10 were included in the review. The majority of the included studies showed that treatment of cSCC with MMS consistently exhibits a significantly lower risk of recurrence compared to treatment with CE. In addition, MMS is emerging as the preferred technique for the resection of cSCC located in aesthetically or functionally challenging anatomical areas. The studies generally demonstrate that MMS is a safer and more effective treatment of cSCC than CE. Nevertheless, outcomes such as recurrence rates and cost-effectiveness should be assessed more precisely, in order to allow for a more tailored approach in determining the appropriate indication for the use of MMS.

The safety and efficacy of myomectomy in the treatment of recurrent uterine fibroids after HIFU.

To evaluate the safety and efficacy of myomectomy for recurrent uterine fibroids (UFs) after high-intensity focused ultrasound (HIFU) ablation. This was a retrospective study. Patients who underwent abdominal myomectomy (AM) and laparoscopic myomectomy (LM) from January 2018 to December 2021 at the Three Gorges Hospital of Chongqing University were included. Among them, 73 had undergone prior HIFU ablation (Group 1), while 120 had not undergone HIFU (Group 2). Outcome measures included operating time, estimated blood loss (EBL), blood transfusion, postoperative activity times (PAT), duration of hospital stay (DOHS), and complications. The operating time was 90.0 min (70.5, 115.0) for Group 1 and 110.0 min (81.5, 130.0) for Group 2 (P < 0.05). During all AM pathways, there were no significant differences observed between the two groups in EBL, blood transfusion, PAT, DOHS, and complications; however, operating time was shorter in Group 1. The operating time, EBL, blood transfusion, PAT, DOHS, and complications were similar in both groups during LM pathway. During the follow-up 40 (range: 24-53) months, the rate of relief, recurrence, and reintervention in Groups 1 and 2 was 78.1% versus 74.1%, 14.6% versus 16.4%, and 3.7% versus 2.6%, respectively (P > 0.05). Myomectomy is a safe and effective surgical method for treating recurrent UFs after HIFU. Myomectomy for treating recurrent UFs resulted in a shorter operative and hospital stay, reduced blood loss, faster postoperative recovery, and fewer complications, better symptom relief rates, and lower risk of recurrence or reintervention. These findings indicate that previous HIFU ablation does not worsen the outcomes of the subsequent myomectomy.

An incidentally found mass on the remnant stomach after a Roux-en-Y gastric bypass

BackgroundIncidentally found masses are a widely discussed area of medicine, and there are conflicting opinions as to how to deal with these findings, particularly in the stomach—which has limited documentation in the literature. Here we present a middle-aged female who was found to have an incidentally found mass on her remnant stomach 10 years after a Roux-en-Y gastric bypass (RYGB) surgery.Case presentationWe present the case of a 66-year-old female who is 10 years post-op from a RYGB. After a bout of self-resolving diarrheal illness prompted a computed tomography (CT) scan in the emergency department, she was diagnosed with a 9-cm mass on her remnant stomach that after resection was found to be a gastrointestinal stromal tumor (GIST) with the PDGRRA p.D842V gene mutation.ConclusionThe National Comprehensive Cancer Network (NCCN) outlines guidelines for the workup of abdominal masses. While endoscopic ultrasound is a common step in diagnosis of gastric masses, for a patient who has had a RYGB, access to the remnant stomach, which is no longer a part of the alimentary tract, is not possible. Thus, this patient’s mass was surgically resected. Given the low risk of recurrence, her future care consists of follow-up with medical oncology in accordance with the NCCN guidelines.

Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant (Pinteraction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; Pinteraction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.

The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a low Risk of Recurrence in Acromegaly.

a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype. To study whether the GH response to OGTT predicts the risk of recurrence after initial surgical cure. Retrospective, observational study. Two tertiary care centers. We investigated 254 patients with acromegaly who were cured by surgery. All patients underwent OGTT at diagnosis before pituitary surgery. A peak-to-basal GH ratio ≥ 120% within 90 minutes was used to distinguish paradoxical (GH-Par) from non-paradoxical acromegalic patients (GH-NPar). Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence. A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in three patients of the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with the risk of recurrence (HR 0.18, 95% CI, 0.05-0.63; P = 0.007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI, 1.01-2.47; P = 0.04). our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.

PSMD14 is a novel prognostic marker and therapeutic target in osteosarcoma

BackgroundOsteosarcoma is a bone tumor that is characterized by high malignancy and a high mortality rate, and that originates from primitive osteoblastic mesenchymal cells and is most common in rapidly growing long bones. PSMD14, also known as RPN11 or POH1, is a member of the JAMM isopeptidase family, which is able to remove the substrate protein ubiquitination label, thereby regulating the stability and function of the substrate protein. In this study, we explored the expression and potential biological significance of the PSMD14 deubiquitinating enzyme in osteosarcoma.MethodsImmunohistochemical methods were used to detect the expression of PSMD14 in biopsies of 91 osteosarcoma patients, and the specimens were classified into high and low PSMD14 expression groups. The correlation between PSMD14 expression and clinical indicators and prognosis was compared.SiRNA was used to downregulate PSMD14 in two osteosarcoma cell lines (HOS and SJSA-1), and the effects of downregulation of PSMD14 on the viability, proliferation, and invasion ability of osteosarcoma cells were analyzed.ResultsWe identified significant differences in recurrence, metastasis, and survival time of the osteosarcoma patients on the basis of PSMD14 expression. High expression of PSMD14 in osteosarcoma patients was associated with a low survival rate and high risk of metastasis and recurrence. Down-regulation of PSMD14 inhibited the viability, proliferation, and invasiveness of osteosarcoma cell lines.ConclusionsPSMD14 may be a new prognostic marker and therapeutic target for osteosarcoma.

Topical and Intralesional Immunotherapy for the Management of Basal Cell Carcinoma.

Basal Cell Carcinoma (BCC) is the most common type of cancer among the white population. Individuals with fair skin have an average lifetime risk of around 30% for developing BCC, and there is a noticeable upward trend in its incidence rate. The principal treatment objectives for BCC involve achieving the total excision of the tumor while maximizing the preservation of function and cosmesis. Surgery is considered the treatment of choice for BCC for two main reasons: it allows for the highest cure rates and facilitates histological control of resection margins. However, in the subgroup of patients with low-risk recurrence or medical contraindications for surgery, new non-surgical treatment alternatives can provide an excellent oncological and cosmetic outcome. An evident and justified instance of these local therapies occurred during the COVID-19 pandemic, a period when surgical interventions carried out in hospital settings were not a viable option.

Operative Repair of Hamstring Injuries From the Jackling Position in Rugby.

The jackling position within rugby has not been previously described as a mechanism for proximal hamstring injuries. Acute surgical repair of proximal hamstring avulsion injuries sustained from the jackling contact position enables a return to a previous level of sporting activity with low risk of recurrence. Case series; Level of evidence, 4. This study included 54 professional rugby players (mean age, 26 ± 4.8 years) who underwent acute primary surgical repair of complete, proximal hamstring avulsion injuries. The mean follow-up time was 17 months (range, 12-24 months). Mean isometric hamstring strength and function testing was performed at 3 months and 1 year after repair. Of the 54 players, 51 (94.4%) returned to their preinjury level of sporting activity. The mean time from surgical repair to full sporting activity was 7 months (range, 4-12 months). No patients had recurrence of the primary injury. At 1 year postoperatively, patients had significantly restored mean isometric hamstring muscle strength when compared with the uninjured leg at 0° (98.4% ± 2.8%), 15° (95.9% ± 2.9%), and 45° (92.9% ± 4.1%); improved Lower Extremity Functional Score (78.0 ± 2.0); and improved Marx activity rating score (14.3 ± 1.5) (P < .001 for all). Acute surgical repair of proximal hamstring avulsion injuries caused by the contact jackling position produced a high return to preinjury level of sporting activity, increased muscle strength, and improved functional outcome scores, with a low risk of recurrence at short-term follow-up.

Nuevas perspectivas en el tratamiento del cáncer de tiroides de bajo riesgo. Experiencia con la lobectomía tiroidea en una cohorte de 114 pacientes

Background: The treatment of low-risk differentiated thyroid cancer (DTC) is still a matter of debate. Over the past few decades, there has been a shift towards a more personalized approach, tailored to the individual risks of each patient and tumor. The current practice guidelines recommend lobectomy in selected patients, with low risk of recurrence. Objective: To describe the results of thyroid lobectomy in a cohort of patients with DTC with low risk of recurrence. Material and methods: We conducted a descriptive and observational study. The medical records of patients with DTC who underwent thyroid lobectomy between January 2015 and April 2023 were retrospectively reviewed. Results: A total of 114 patients were operated on; mean age was 44 ± 12 years and 90 (79%) were women. The median tumor size was 9.4 mm (IQR 25-75% 7-13 mm), and 103 nodules (90%) were solid on ultrasound. Only 2 patients with vascular invasion involving &gt; 4 vessels required completion thyroidectomy. There were no major complications and only one patient developed temporary recurrent laryngeal palsy. There were no locoregional or distant recurrences during mean follow-up of 33.4 months. Conclusion: Thyroid lobectomy for low-risk DTC had low morbidity and no recurrences in the series presented. The rigorous selection of patients and the interaction of a multidisciplinary team are considered essential for the successful implementation of this therapeutic approach.

A phase 2 study to determine the pathological (path) response to neoadjuvant nivolumab (nivo) and relatlimab (rela) in stage I to III resectable Merkel cell carcinoma (Neo-MCC).

TPS9613 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cancer of the skin with viral and sun related aetiologies, and an overall mortality rate twice that observed in cutaneous melanoma (33% vs 15%). The 5-year disease specific survival is 60% to 87% for those presenting with local disease, 39% to 62% for nodal disease and 11% to 20% for metastatic disease (1). Neoadjuvant therapy (NAT) is a powerful treatment platform to rapidly assess drug activity in resectable cancers. In melanoma, using International Neoadjuvant Melanoma Consortium (INMC) path response criteria (2), a major path response to immunotherapy (≤10% viable tumor) correlates with low risk of recurrence in resectable stage III disease (Menzies et al., 2021), and improved survival and EFS when immunotherapy is given neoadjuvantly as compared to adjuvant (adj) treatment (Patel et al., 2022). In a study of NAT anti-PD1 monotherapy with nivolumab, in patients (pts) with resectable IIA-IV MCC (N=36), 47.2% of pts achieved a complete path response (pCR) (Topalian et al., 2020). Other benefits of NAT include early insight into response, feedback to pts regarding their individual response and prognosis, ability to tailor subsequent management, and collection of translational specimens to explore mechanisms of response and resistance. The Neo-MCC trial will examine whether combination PD-1 blockade plus lymphocyte-activation 3 (LAG3) checkpoint inhibition will achieve a high rate of path response with manageable toxicity in pts with resectable stage I-III MCC. Methods: Pts with histologically confirmed resectable clinical stage I (≥ 10 mm), II or III Merkel cell carcinoma, are eligible (N=20). All pts undergo complete resection (RES) at wk 6 following NAT with 2 doses of nivo (480 mg, IV) plus rela (160 mg, IV) at wk 0 and 4. Standard of care sentinel lymph node biopsy will be completed as indicated. Pts with non-path response (&gt;50% viable tumor) or partial path response (&gt;10% - ≤50% viable tumor) at RES will receive adj radiotherapy (RT) to all disease sites, including the draining lymph node basin. Pts with pCR (0% viable tumor) or near-pCR response (≤10% viable tumor) will receive no further adj treatment. Pts with involved RES path margins will be considered for adj RT, following multidisciplinary team consultation to determine the role of further surgery. CT, and FDG PET/CT will be performed at baseline (BL), prior to RES to measure NAT response, and 6-monthly over a 10-year follow-up period. Tumor and fecal samples are collected at BL, RES, and recurrence. Blood samples are collected at BL, wk 4, RES, and recurrence. The primary endpoint is the rate of pCR at RES after NAT using INMC response criteria. Secondary endpoints include RFS, OS, safety/tolerability, surgical outcomes, QOL, and biomarker analyses. 1. Mistry, et al., 2022. 2. Tetzlaff et al., 2018. Clinical trial information: NCT06151236 .

Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA): NRG-GI008.

TPS3641 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines vserial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate v delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox v FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Current accrual (as of 02-02-2024) is 240/1,912. NCT05174169. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .

Inguinal lymphangioma in an adult patient mimicking an irreducible inguinal hernia: A case report

IntroductionLymphangiomas are rare benign vascular malformations of the lymphatic system. They are usually located in the head, neck, and axilla and are typically present during the first two years of life. A few cases of inguinal lymphangioma have been reported in adults. Case presentationWe report a 35-year-old male who presented with left groin swelling for a one-year duration associated with on and off pain. On examination, he had soft, irreducible left inguinal swelling with positive cough impulse and no tenderness on palpation. Ultrasound (US) and magnetic resonance imaging (MRI) were done for him, showing a well-defined lobulated cystic lesion located between subcutaneous and deep fascia measuring around 6.5 × 4.2 × 8.1 cm with multiple internal septations. The lesion shows Low signal intensity in the T1 weighted image and high signal intensity in the T2 weighted image. 97 % alcohol was injected under US guidance and aspirated after 30 min. The swelling significantly decreased in size clinically and radiologically during the follow-up. Clinical discussionLymphangioma rarely occurs in the inguinal region, presenting a diagnostic challenge as it mimics various inguinal conditions. Differential diagnoses include inguinal hernia, hydrocele of the cord, lymphadenopathy, or hematoma. Imaging is used to determine the size, invasion, relation to surrounding structures, and extension to the abdominal cavity. MRI is the diagnostic modality of choice in non-emergency settings. Complete surgical excision is the gold standard for the management with the lowest risk of recurrence. Alternative non-surgical treatment options have been used successfully in poor surgical candidates. Different sclerosing agents have been used with low complications and rates of recurrence. Ethanol is a widely available sclerosing agent, and it was used with no recurrence or side effects during the follow-up period. ConclusionSurgeons should have a high index of suspicion when investigating any inguinal mass, considering such a rare presentation as part of the differential. Sclerotherapy is an effective treatment for lymphangioma and should be considered as an alternative modality in non-surgical candidates.

Harnessing cell-free orphan non-coding RNAs as a predictive measure of long-term survival in neoadjuvant breast cancer therapy.

585 Background: Pathologic complete response (pCR) is a valuable metric for predicting survival following neoadjuvant therapy (NAT) in breast cancer; however, blood-based biomarkers may refine the prediction of treatment outcomes and inform follow-up treatment decisions. Orphan non-coding RNAs (oncRNAs) are a novel category of small RNAs that are present in tumors and largely absent in healthy tissue. Here, we explore the feasibility of a tumor-naive oncRNA-based liquid biopsy assay for predicting distant recurrence-free survival (DRFS) in breast cancer patients using a standard blood draw. Methods: Our cohort included 538 high-risk breast cancer patients from the multicenter I-SPY2 trial having serum available after NAT and before surgery (timepoint T3). Of the 538 patients (mean age: 48.8 ± 10.3), 191 (36%) achieved pCR. We isolated small RNA from 0.8 mL of patient serum and sequenced it at an average depth of 50 million 100-bp single-end reads. We used our catalog of tumor-derived oncRNAs, discovered in The Cancer Genome Atlas, to develop an AI model for predicting tumor burden based on tumor size. Our AI model was trained on oncRNA profiles from an independent cohort of 719 serum samples collected at diagnosis from individuals with cancer. We assessed tumor burden by oncRNA in the I-SPY2 cohort at T3 and associated this measure with DRFS using robust cutpoints established for each of the two pCR groups: high- ( n=70) and low-burden ( n=468) cutpoints were verified through cross-validation and almost all folds converged on a single value, which we used in our analysis. Results: The continuous oncRNA-derived tumor burden at T3 had a hazards ratio (HR) of 2.4 (95% CI: 1.1–5.1) for predicting DRFS. This measure remained significant in multivariate Cox models that included pCR (HR = 2.7 [1.3–5.6]) or residual cancer burden (RCB II/III versus 0/I; HR = 3.4 [1.6–7.1]). Patients with pCR had a 3-year DRFS of 94%; patients with pCR having low ( n=180) versus high ( n=11) oncRNA burden resulted in 95% and 73% 3-year DRFS, respectively (HR = 7.4 [2.3–24]). Those without pCR had a 3-year DRFS of 78% and stratification by oncRNA burden resulted in 85% and 71% 3-year DRFS for the low ( n=288) and high ( n=59) burden groups, respectively (HR=2.4 [1.5–3.9]). Importantly, we saw no restricted mean survival time difference (RMST) at 3 years between those with and without pCR among the high oncRNA burden group (0.1-month difference, p=0.97). Conclusions: We demonstrate the utility of a tumor-naive, oncRNA-derived tumor burden AI model as a predictive measure of treatment outcome and as a prognostic biomarker that can be used in addition to pCR to further stratify patients as low or high risk of recurrence. Integration of our oncRNA assay with existing biomarkers and clinicopathologic variables, has the potential to add value for predicting outcomes and prioritizing patients that would benefit from additional care.

Guideline concordance of recurrence risk assessment for early breast cancer in a county-level setting in China.

e23263 Background: Guideline-centric risk-based decision-making is crucial for the treatment of HR+HER2- and HER2+ early breast cancer (eBC). However, the consistency of recurrence risk assessment (RA) between real-life clinical practice and guidelines in China has not been thoroughly investigated. As part of the interim analysis of CHASE001 (NCT05544123), we explored the guideline concordance of RA for HR+HER2- and HER2+ eBC in a county-level setting in China. Methods: Cohorts of HR+HER2- and HER2+ eBC patients (pts) from a county-level observational study (CHASE001) were included in this analysis. Clinical recurrence risk were collected for each patient. Descriptive statistics reported the proportion of pts classified into each risk level under real-life assessment by healthcare professionals (HCPs) (H-low/intermediate/high) and guideline-consistent assessment (G-low/intermediate/high). To investigate the factors associated with lower consistency, univariate (UVA) and multivariate logistic regression analysis (MVA) were performed. Results: 1254 HR+HER2- and 841 HER2+ eBC pts from 26 county-level hospitals were included in this analysis. A comparison between recurrence risk under HCPs assessment (HA) and guideline-consistent assessment (GA) revealed divergence. In HR+HER2- cohort, the proportions of pts classified as low, intermediate (int), and high clinical risk for recurrence under HA/GA were 27.2%/2.0%, 48.0%/57.4%, 24.8%/40.6%, respectively. Notably, 36.8% of pts classified as G-int were categorized as H-low, while 47.5% G-high pts were classified as H-int/low. On UVA and MVA, pT1 stage, histological grade 1 and Ki67 &lt; 20% were associated with G-int/H-low; whereas lymphovascular invasion and pN1 were associated with G-high/H-lower. Among 562 G-int/high premenopausal pts, 280 (49.8%) achieved ovarian function suppression (OFS) and the OFS rates were 46.1% in G-int and 55.3% in G-high pts. In HER2+ cohort, the proportions of pts classified as low, int and high risk under HA/GA were 17.2%/0%, 48.2%/51.2% and 34.6%/48.8%. In pts with pN0, 17.2% were classified as H-low and 12% as H-high. In pts with positive lymph nodes (LN+), 11% were classified as H-low and 31% as H-int. Dual anti-HER2 target therapy was administered in 72% of pts with LN+. In both cohorts, HCPs who were medical oncologists had higher consistency with guideline for high-risk evaluation compared to surgical oncologists, whereas surgical oncologists showed higher consistency for int-risk evaluation compared to medical oncologists. Conclusions: This analysis highlights differences in clinical practice between county-level HCPs and guideline recommendations, revealing a significant underestimation of breast cancer recurrence risk. Further efforts should be made to enhance guideline adherence and promote guideline-centric clinical risk-based decision-making at county-level hospitals. Clinical trial information: NCT05544123 .