Radiographic Recurrence Research Articles

Presenting characteristics and clinical outcomes of idiopathic versus neurofibromatosis type 2-associated spinal meningiomas: a retrospective institutional experience.

Spinal meningioma (SM) is a pathology with an estimated incidence of nearly 1000 diagnoses per year in the United States and presents in 20% of patients with neurofibromatosis type 2 (NF2). This multi-institutional retrospective cohort study aimed to assess clinical outcomes for patients with SM who underwent surgery between 1998 and 2020 with stratification by NF2 mutation status. Medical records were reviewed retrospectively to collect data on patient demographics, clinical presentation, tumor characteristics, treatment, and outcomes. Analyses were done to determine radiographic predictors of gross-total resection (GTR) and tumor recurrence, to assess radiographic characteristics of NF2-associated tumors, and to determine progression-free survival between groups. A total of 166 patients who received surgery for SM during the study period were included, of whom 133 were women (80%). Fifteen (9%) patients had a concurrent NF2 diagnosis. The mean age at surgery was 58 (SD 18) years. The mean presenting Karnofsky Performance Status score was 76 (SD 11), and the most common presenting symptoms were sensation changes (60%) and weakness (59%). Most tumors were in the thoracic spine (72%). GTR was achieved in 154 cases (93%). Eight patients with subtotal resection were treated with radiation therapy, and none received chemotherapy. Eighteen patients (11%) experienced radiographic recurrence of disease following surgery, with a mean time to recurrence of 4.2 years. NF2 patients were diagnosed at a significantly earlier mean age (33.3 [SD 15.4] years) compared with other patients. NF2 patients experienced progression at a significantly higher rate than other patients (40%), and in less time (mean 2.8 [SD 3.7] years). Radiographic characteristics, including tumor volume, T2 cord edema, dural tail sign, and calcification, were similar between NF2 and non-NF2 patients, between patients who underwent gross-total versus subtotal resection, and between patients who experienced tumor recurrence and those who did not. In this study of 166 surgically treated patients with SM, patients with NF2 presented earlier, experienced earlier progression, and experienced progression more frequently compared with those without NF2. Radiographic characteristics of tumors were relatively consistent between groups. While idiopathic SMs remain a relatively benign and highly manageable disease, considering tumor molecular characteristics and broader clinical history is paramount in providing efficacious and individualized patient care.

Glandular odontogenic cyst: A case series and literature review

AbstractAimThe glandular odontogenic cyst (GOC) is a rare odontogenic cyst with a potentially aggressive growth potential and high recurrence rate. An absence of pathognomonic clinical, radiographic and histopathological features means the glandular odontogenic cyst is rarely included in a differential diagnosis for a well‐defined radiolucent cyst or tumour of the jaw. There is an absence of clarity on the most effective method of treatment for GOCs to reduce recurrence risk.Materials and MethodsIn this case series, we documented the treatment of three male patients who were referred for further investigation of well‐defined, corticated radiolucent lesions. Two lesions were located in the body of the mandible and one in the anterior maxilla. All three patients were in their fifth decade of life. Two patients reported mild discomfort, while one patient was asymptomatic upon presentation.ResultsThe included cases were treated conservatively with enucleation and curettage under general anaesthesia. Histological examination confirmed a diagnosis of GOC in all cases. No clinical or radiographic recurrence has been observed.ConclusionThe clinical, radiographic and histological appearance of the GOC mimics other cysts and tumours of the jaw, most significantly central mucoepidermoid carcinoma. Long‐term follow‐up is recommended due to the potential for recurrence, which is influenced by lesion size, locularity and cortical plate integrity.

7856 In Pursuit of Solutions: Exploring Novel Therapeutic Strategies in the Treatment of a Rare, Aggressive Macroprolactinoma Post-Temozolomide: A Case Report

Abstract Disclosure: N. Konindala: None. H. Darapu: None. K. Ruddiman: None. Introduction: Prolactinomas comprise 40-60% of all pituitary tumors. Most prolactinomas respond well to dopamine agonist treatment. About 10% of these tumors are aggressive prolactinomas (APRL). Although rare, APRLs pose a significant challenge in clinical practice as treatment beyond dopamine agonists, surgery and radiotherapy is limited. A fourth-line therapy called temozolomide may be needed. After temozolomide failure, treatment options are minimal, as there are no evidence-based therapies available for such aggressive pituitary tumors. The efficacy of novel treatment agents remains to be explored. Notably, our case is one of the few where investigational agents, including Pembrolizumab and Pazopanib have been used. We present a case report that contributes to the evolving understanding of potential therapeutic options and highlights the ongoing challenges in refractory prolactinoma management. Case Presentation: A 77-year-old male was diagnosed with a macroprolactinoma in 2001 and was started on cabergoline with a good therapeutic response. In 2011, there was hormonal and imaging evidence of progression, and the patient underwent transsphenoidal hypophysectomy with gross resection followed by gamma knife radiation. The patient was found to have a recurrence of his tumor five years later and underwent repeat transsphenoidal resection. He continued to show evidence of recurrence and was recommended for chemoradiation and adjunct temozolomide (TMZ). After 12 cycles of TMZ, a repeat MRI was done, which showed radiographic recurrence. The patient had a third transsphenoidal surgery done in August 2022, followed by the initiation of a PARP-1 inhibitor, Olaparib. The development of adverse effects complicated this, and treatment was transitioned to capecitabine and TMZ in Jan 2023. The patient had persistent tumor burden symptoms, and a VEGF inhibitor Avastin was initiated. His symptoms initially improved, but unfortunately, his prolactin levels rose from 895 mg/dL to 1,547mg/dL, indicating evidence of disease progression. Immunotherapy with pembrolizumab was started on 6/2023, and he was given three doses before a follow-up MRI showed continued progression of the disease. He was recommended to start pazopanib, a kinase inhibitor. Discussion: Aggressive Prolactinomas present a rare and intricate management challenge, necessitating a multidisciplinary approach. Despite standard therapies, achieving remission can be elusive. While Pembrolizumab showed promise in reported cases, our patient remained refractory. Literature indicates favorable responses to Pazopanib in a small number of refractory cases. A reassessment in a few months will evaluate our patient's response to Pazopanib. This case emphasizes the need for further research to refine refractory prolactinoma management and develop response indicators for investigational agents. Presentation: 6/3/2024

S1346 Timing of Index Ileocolic Resection is Associated With Radiographic Recurrence in Patients With Crohn’s Disease

S1346 Timing of Index Ileocolic Resection is Associated With Radiographic Recurrence in Patients With Crohn’s Disease

532. OPERATIVE TRENDS AND CLINICAL OUTCOMES OF OPEN, LAPAROSCOPIC AND ROBOTIC APPROACHES TO HIATAL AND PARAOESOPHAGEAL HERNIAS-A STUDY OF 1834 PATIENTS

Abstract Background Indications for repair of hiatal and paraesophageal hernia (HH/PEH) repair evolved significantly over the past two decades, impacted by the increasing application of minimally invasive surgical (MIS) approaches. This transition underscores the importance of evaluating the operative trends and clinical outcomes associated with open (open), laparoscopic (lap), and robotic surgeries especially in cases of giant hernias (over 50% intrathoracic stomach). Understanding these dynamics is crucial, especially as MIS becomes increasingly prevalent in managing complex cases, including giant hernias. The aim of this study is to assess critical outcomes achieved during the evolution from open to lap to robotic HH/PEH repair in a high volume center. Methods This is a retrospective review of 1834 patients undergoing open (958), lap (390), and robot (486), consecutive HH/PEH repairs prospectively entered into an IRB approved database from 2000 to 2023 at a high-volume center. Patient demographics, operative techniques, and top three most common presenting symptoms were studied overtime. Impact of operative technique, hernia type and size, operative outcomes including length of stay (LOS), radiographic recurrence (esophagram at 3 and 12 months), revisional surgery, on post-operative symptom resolution was evaluated. Results Annual volume increased overtime, with 418 repairs (78% robotic) in the last two years. Average hernia size decreased over the study period. The majority of patients (99.1%) presented with symptoms (Fig 1) and robotic repair had significantly better symptomatic resolution than open surgery (p<0.05). This advantage persists with symptoms in giant hernias (p<.001) LOS decreased over the study period (Fig 1). Overall radiographic recurrence (8.6%) and reoperative rate (2.4%) did not differ among operative techniques, however robotic repair had higher radiographic recurrence rate in case of giant hernia (18%, p<.001). Conclusion The operative volume of HH/PEH repair has increased overtime associated with the increased application along with advancements in MIS and robotic operative techniques. Surgical interventions markedly ameliorate HH/PEH symptoms, with greater improvement observed in large hernia cases. Significant improvement in LOS and at least equivalent clinical results favors MIS, particularly robotic surgery. Although the incidence of anatomic recurrent hernia and reoperation is relatively low continued assessment of especially robotic operations to decrease this incidence further is warranted.

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.

Adjuvant imatinib in high-risk resected gastrointestinal stromal tumors: Merely delaying the inevitable?

Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.

Minimally Invasive Method for Treatment of Syndromic Congenital Vertical Talus Deformity in Children.

Congenital Vertical Talus (CVT) is a rare form of rigid flatfoot commonly seen in patients with underlying neurologic syndromes. This study aims to evaluate the long-term effectiveness of the minimally invasive method for correcting CVT deformity in a large cohort of syndromic patients. A single author recorded preoperative, 2-week postoperative, 1-year postoperative, and most recent radiographic measurements and complications for 25 patients treated with the minimally invasive method from 2006 to 2021. Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires were administered for 12 patients after January 1, 2015, when the institution began collecting PROMIS in all orthopaedic patients. Average follow-up was 55 months (13-111); 18 patients had minimum 24-month follow-up. Forty feet in 25 patients were analyzed. The average preoperative lateral talar axis-first metatarsal base angle (TAMBA) was 68.7 ± 21.3 vs 12.1 ± 8.9 after initial surgical intervention (P < .0001). There was a statistically significant increase in the lateral TAMBA between the initial postoperative and final follow-up visits (13.0 vs 21.6, P = .02). Radiographic recurrence of talonavicular deformity was noted in 12 feet (30.9%); 7 (15.55%) required corrective surgery. Larger preoperative lateral TAMBA was predictive of recurrence. Notably, patients with arthrogryposis experienced higher radiographic recurrence than other syndromic patients (45.0% vs 14.3%, P = .0384). PROMIS scores were within population norms. The study suggests that less than one-third of syndromic CVT patients experienced a radiographic recurrence of talonavicular deformity, with 15% requiring further surgical intervention at an average of 55 months following the initial procedure. A higher incidence of radiographic recurrence occurred in patients with distal arthrogryposis. These findings, along with the satisfactory patient-reported outcomes, suggest that the minimally invasive technique is an effective treatment method for syndromic CVT, underscoring the necessity for clinicians to provide detailed prognoses and consider more intensive follow-up for those at higher risk.

FIVE-YEAR FOLLOW-UP OF THIRD-GENERATION PERCUTANEOUS CHEVRON AND AKIN OSTEOTOMIES (PECA) FOR HALLUX VALGUS

BackgroundRecent large studies of third-generation minimally invasive hallux valgus surgery (MIS) have demonstrated significant improvement in clinical and radiological outcomes. It remains unknown whether these clinical and radiological outcomes are maintained in the medium to long-term. The aim of this study was to investigate the five-year clinical and radiological outcomes following third-generation MIS hallux valgus surgery.MethodsA retrospective observational single surgeon case series of consecutive patients undergoing primary isolated third-generation percutaneous Chevron and Akin osteotomies (PECA) for hallux valgus with a minimum 60 month clinical and radiographic follow up. Primary outcome was radiographic assessment of the hallux valgus angle (HVA) and intermetatarsal angle (IMA) pre-operatively, 6 months and ≥60 months following PECA. Secondary outcomes included the Manchester-Oxford Foot Questionnaire, patient satisfaction, Euroqol-5D Visual Analogue Scale and Visual Analogue Scale for Pain.ResultsBetween 2012 and 2014, 126 consecutive feet underwent isolated third-generation PECA. The mean follow up was 68.8±7.3 (range 60–88) months. There was a significant improvement in radiographic deformity correction; IMA improved from 13.0±3.0 to 6.0±2.6, (p &lt; 0.001) and HVA improved from 27.5±7.6 to 7.8±5.1. There was a statistically significant but not clinically relevant increase of 1.2±2.6° in the HVA between 6 month and ≥60 month radiographs. There was an increase in IMA of 0.1±1.6º between 6 month and ≥60 month radiographs which was not statistically or clinically significant. MOXFQ Index score at ≥follow up was 10.1±17.0. The radiographic recurrence rate was 2.6% at final follow up. The screw removal rate was 4.0%.ConclusionRadiological deformity correction following third-generation PECA is maintained at a mean follow up of 68.8 months with a radiographic recurrence rate of 2.6%. Clinical PROMs and patient satisfaction levels are high and comparable to other third-generation studies with shorter duration of follow up.

Impact of circulating tumor DNA (ctDNA) surveillance on clinical care for patients with stage I-III breast cancer: Findings from a multi-institutional study.

549 Background: Tumor-informed ctDNA-based detection of minimal residual disease (MRD) in the adjuvant setting for patients (pts) with early breast cancer (EBC) is strongly associated with recurrence. However, the clinical impact of early ctDNA detection and potential therapeutic intervention remains unclear. In this multi-institution retrospective analysis, we investigated whether ctDNA detection in the adjuvant setting impacted the care of pts with EBC. Methods: This multisite (4 geographically distinct regions in the US) study included ptswith stage I-III EBC who had adjuvant MRD testing between 11/2020 - 01/2024. A personalized, tumor-informed 16-plex PCR assay (Signatera) was used for plasma ctDNA detection. All tests were ordered in the real-world clinical setting. Data were obtained by retrospective review of electronic medical records. Results: As of 01/2024, 464 EBC pts had tumor-informed ctDNA testing to monitor MRD. Of these, 58 pts (13%) were ctDNA+ at ≥1 timepoint post-surgery: 7 (12%) with stage I EBC, 25 (43%) stage II, 26 (45%) with stage III. Tumor subtypes included HR+/HER2- (38; 65%), HR-/HER2- (17; 30%), and HER2+ (3; 5%). Of the ctDNA+ group, most pts (47; 81%) had testing at &gt;1 timepoint (median 3; range 1-20 timepoints). Overall, 28 (48%) had ctDNA+ at all timepoints, 11 (19%) were persistently ctDNA+ after initial ≥1 negative result (ctDNA-), and 19 (33%) cleared ctDNA after initial ≥1 ctDNA+ result. Adjuvant ctDNA+ results impacted the care plan in 53/58 (91%) pts. 45/58 (78%) had restaging imaging within 1 year of a ctDNA+ result, and 25/45 (56%) had radiographic evidence of recurrence at that time: 23 distant and 2 local recurrences. 10/25 (40%) of these recurrences were in pts with HR-/HER2- EBC. Of 20 pts that were ctDNA+ despite no radiographic evidence of recurrence (MRD+ corresponding to molecular recurrence), 17/20 (85%) had HR+/HER2- EBC. At least 5/20 (25%) had increased imaging surveillance after ctDNA+ results, and at least 14/20 (70%) had repeat ctDNA testing. In 9/20 (45%) pts with molecular recurrence, providers changed therapy based on the ctDNA+ result, including enrollment into a clinical trial. 5/9 (56%) of these pts had a subsequent ctDNA clearance, 4 (80%) of whom remained without radiologic evidence of disease (median follow-up 12.53 (range 6.08-21.6) months from time of ctDNA+). 3/9 pts had persistent ctDNA+ despite change in therapy and all 3/3 (100%) of these pts had a radiographic recurrence. Conclusions: In this multi-institutional study, ctDNA detection impacted clinical care in most pts. A subset of pts had a change in systemic therapy with subsequent ctDNA clearance which was associated with better prognosis compared to those without ctDNA clearance. Further validation of these findings in additional datasets and clinical trial(s) are needed to inform incorporation of ctDNA testing into routine care.

Detection of molecular residual disease in stage II and III melanoma utilizing circulating tumor DNA.

e21564 Background: Overall survival for patients with melanoma has significantly improved with advancements in immunotherapy, especially with immune checkpoint inhibitors and BRAF/MEK inhibitors becoming standard of care for advanced melanoma. However, the decision to proceed with adjuvant therapy should be considered against the risk of adverse side effects, particularly in early-stage melanoma patients. Accurate biomarkers are needed to risk stratify patients, determine who will most likely benefit from adjuvant therapy, and identify when the ideal time is to initiate treatment. This study evaluates the prognostic value of personalized, tumor-informed circulating tumor DNA (ctDNA) testing in patients with stage II and III melanoma. Methods: In this real-world study, plasma samples (n =429) were analyzed from 90 stage IIA-IIID cutaneous melanoma patients treated at Rush University Medical Center between 03/30/2021 and 01/30/2024. A clinically-validated, personalized, tumor-informed 16-plex PCR assay (SignateraTM, Natera, Inc.) was used for detection and quantification of ctDNA in plasma samples. Results: Personalized, tumor-informed ctDNA assays were created using tissue samples from either initial biopsy or surgical excision specimen. Assay design was successful for 100% (90/90) of patients with sufficient tissue; test requests for 4 patients could not proceed due to insufficient tissue. ctDNA was detectable in 28% (25/90) of patients at one or more time points. There was a higher ctDNA-positivity rate in stage III patients (20/50, 40%) compared to stage II patients (5/40, 13%). Of the 25 patients with identifiable ctDNA during surveillance, 13 tested positive on the initial test (2 stage II and 11 stage III). Eighteen of the 25 ctDNA-positive patients received immunotherapy; eight patients achieved sustained ctDNA clearance, 2 had transient clearance, 2 have remained positive on ctDNA testing, and 6 continue to receive adjuvant IO and follow-up ctDNA testing. Clinical or radiographic recurrence occurred in 11/90 patients, 10 of whom tested positive for ctDNA. Conclusions: Personalized, tumor-informed ctDNA offers an adjunct to conventional monitoring for melanoma patients to detect molecular residual disease and was found to be prognostic in our patient cohort. Prospective studies are needed to evaluate the role of ctDNA in clinical decision making for surveillance imaging intervals and appropriate initiation, intensification, or discontinuation of adjuvant therapy.

Correlation of circulating tumor DNA and recurrence in patients with metastatic colorectal cancer with no evidence of disease: An open-label, prospective, phase II study.

3549 Background: Patients with metastatic colorectal cancer (mCRC) can achieve no evidence of disease (NED) after curative treatment. However, how to precisely guide the treatment after NED remained to be explored. Minimal residual disease (MRD) detection using circulating tumor DNA (ctDNA) analysis has shown to help identify patients’ risk of relapse in early-stage CRC. Thus we aimed to explore the feasibility of ctDNA by a tumor-informed personalized approach to predict recurrence and guide chemotherapy in mCRC with NED. Methods: We enrolled mCRC patients who achieved NED after local curative treatment from June 2022 to December 2023. Surgical or puncture tissues were collected. Blood samples were collected prior to curative treatment, at 1 month after curative treatment, and subsequently every 2–3 months until disease progression or completion of a 2-year follow-up period. Tumor-derived variants were identified by whole-exon sequencing of the tissue samples. Up to 50 highly ranked variants were selected for the personalized panel design, which was used to assess the MRD status of blood samples. Patients with negative MRD post curative treatment were followed, while those with positive MRD were subjected to investigator-determined adjuvant chemotherapy (ACT). Results: A total of 106 mCRC patients with NED after curative treatment were enrolled. The ctDNA was detected in 62 patients (92.5%, 62/67) pre curative treatment and in 55 patients (51.9%, 55/106) post curative treatment. At a median follow-up period of 252 days, 42 patients experienced recurrence and 33 patients (78.6%) had positive ctDNA post curative treatment. Patients with positive ctDNA post curative treatment demonstrated an inferior recurrence-free survival (RFS) than those with negative ctDNA (HR: 4.58, 95% CI: 2.18–9.64; P&lt;0.001), which was not observed by CEA (HR: 1.87, 95% CI: 0.84–4.15; P=0.12). In patients with negative ctDNA after curative treatment, there was no difference in RFS between those treated with ACT or not (HR: 2.51, 95% CI: 0.48–13.04; P=0.25). During the dynamic longitudinal monitoring of ctDNA, the median RFS was 5.6 months, 15.5 months, 10.2 months and unreached in patients with persistently positive ctDNA, converted negative ctDNA, converted positive ctDNA, and persistently negative ctDNA, respectively (log-rank P for trend &lt;0.001). All recurrent patients had at least one positive ctDNA detection before imaging confirmed recurrence, and the median lead time interval of ctDNA positivity to radiographic recurrence was 112 days (range, 3–441 days). Conclusions: Our results demonstrated that patients with ctDNA negative post curative treatment had superior RFS compared with those with positive ctDNA. Post curative treatment and dynamic ctDNA had the potential to guide ACT in mCRC patients with NED. The follow-up is still on-going. Clinical trial information: NCT05635630 .

Abstract PO3-13-09: Personalized ctDNA testing for detection of molecular residual disease in patients with localized HR+ breast cancer: temporal dynamics and impact on clinical outcomes

Abstract Background: Molecular residual disease (MRD) describes detectable circulating tumor DNA (ctDNA) after definitive surgery and is an expanding field in breast oncology. Multiple studies have demonstrated detectable MRD to be poorly prognostic, and clinical trials are now underway assessing the efficacy of therapeutic interception. However, most retrospective studies did not obtain baseline imaging at the time of MRD detection, such that the proportion of patients with detectable ctDNA and concurrent radiographically evident recurrent disease is not known. Furthermore, the role of serial ctDNA testing in the adjuvant setting remains unclear. Meanwhile, tumor-informed assays such as the SignateraTM platform are now covered by Medicare. To address these outstanding clinical questions, we aimed to determine the temporal dynamics of MRD detection in HR+/HER2- breast cancer, association with radiographic recurrence, and impact on clinical outcomes. Methods: Patients with HR+/HER2- breast cancer who underwent MRD testing either as part of a clinical trial or via an expanded access program were reviewed for MRD positivity and assessed alongside clinically annotated data. All patients completed surgical resection prior to MRD testing. Whole exome sequencing of primary tumor tissue and personalized ctDNA primers were designed for multiplex PCR targeting up to 16 single nucleotide variants for MRD testing via the SignateraTM platform. Clinical data was determined through focused chart review. Results: Among 185 patients with HR+/HER2- breast cancer who underwent MRD testing, 37 patients (20%) did not complete testing due to factors including tumor tissue not meeting pathology parameters, insufficient quantity of primary tissue, or tumor/normal discordance. 14 patients (8%) had detectable ctDNA (1, 5, and 8 patients had stage I, II, and III breast cancer, respectively). Among the 6 patients who did not have stage III disease, 3 had other high-risk features (Oncotype 40; grade 3 disease x2). Overall, 71% (n=10) of the +MRD population tested positive at the first test, while 29% (n=4) tested positive only on serial sampling. Median time from surgery to positive test was 3.5 years (range: 1 month – 10.2 years). Twelve patients (86%) were on adjuvant endocrine therapy at the time of detectable MRD. Among the 14 +MRD patients, 9 underwent staging scans shortly after positive MRD testing, and among these patients, 3 (33%) had radiographic evidence of asymptomatic metastatic recurrence (2 bone-only; 1 visceral); two of these pts had 1 MRD test, while the other had a negative test followed by a positive test 11 months later. The other 3 patients with radiographic recurrences had scans prompted only by clinical symptoms &amp;gt;6 months after +MRD. Among the 4 patients with serial data after first +MRD testing, none experienced subsequent ctDNA clearance. Serial testing occurred over a median of 11.5 months (range 1.1-21.7 months). With median follow up of 8.6 months, 43% (n=6) of patients with +MRD had distant disease recurrence. Conclusions: Personalized tumor-informed ctDNA testing identified patients with high risk of recurrence, including patients without classic high-risk clinical, pathologic, or genomic features, suggesting a complementary role of MRD testing for risk assessment. Serial monitoring was necessary to identify MRD in more than a quarter of patients. Furthermore, one-third of patients with +MRD disease had asymptomatic metastatic recurrence, highlighting the importance of staging scans in studies and clinical trials assessing therapeutic interception in the adjuvant setting. Citation Format: Arielle Medford, Elyssa Denault, Zanta Ephrem, Douglas Micalizzi, Yael Bar, Rachel Abelman, Amy Comander, Justine Knape, Minetta Liu, Angel Rodriguez, Steven Isakoff, Beverly Moy, Laura Spring, Aditya Bardia. Personalized ctDNA testing for detection of molecular residual disease in patients with localized HR+ breast cancer: temporal dynamics and impact on clinical outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-09.

Paraesophageal hernia recurrence following repair: making the case for reoperative surgery in a propensity-matched cohort.

Paraesophageal hernia repairs (PEHRs) have high rates of radiographic recurrence, with some patients requiring repeat operation. This study characterizes patients who underwent PEHR to identify the factors associated with postoperative symptom improvement and radiographic recurrence. We furthermore use propensity score matching to compare patients undergoing initial and reoperative PEHR to identify the factors predictive of recurrence or need for reoperation. After IRB approval, patients who underwent PEHR at a tertiary care center between January 2018 and December 2022 were identified. Patient characteristics, preoperative imaging, operative findings, and postoperative outcomes were recorded. A computational generalization of inverse propensity score weight was then used to construct populations of initial and redo PEHR patients with similar covariate distributions. A total of 244 patients underwent PEHR (78.7% female, mean age 65.4 ± 12.3years). Most repairs were performed with crural closure (81.4%) and fundoplication (71.7%) with 14.2% utilizing mesh. Postoperatively, 76.5% of patients had subjective symptom improvement and of 157 patients with postoperative imaging, 52.9% had evidence of radiographic recurrence at a mean follow-up of 10.4 ± 13.6months. Only 4.9% of patients required a redo operation. Hernia type, crural closure, fundoplication, and mesh usage were not predictors of radiographic recurrence or symptom improvement (P > 0.05). Propensity weight score analysis of 50 redo PEHRs compared to a matched cohort of 194 initial operations revealed lower rates of postoperative symptom improvement (P < 0.05) but no differences in need for revision, complication rates, ED visits, or readmissions. Most PEHR patients have symptomatic improvement with minimal complications and reoperations despite frequent radiographic recurrence. Hernia type, crural closure, fundoplication, and mesh usage were not significantly associated with recurrence or symptom improvement. Compared to initial PEHR, reoperative PEHRs had lower rates of symptom improvement but similar rates of recurrence, complications, and need for reoperation.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1cm vs. 1.2cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

INTERCEPT Program of circulating tumor DNA (ctDNA) testing for minimal residual disease (MRD) in colorectal cancer (CRC): Results from a prospective clinical cohort.

27 Background: Minimal residual disease, defined by ctDNA+ in the absence of macroscopic of disease, represents a new and clinically poorly defined subset of patients (pts). While observational cohorts have been reported on the prognosis of MRD, there is little information on the impact of returning and acting on ctDNA results on the subsequent ability to detect radiographic disease. Here we provide real-world evidence form a large prospective cohort where ctDNA testing was routinely performed and returned to pts and providers, providing opportunities to understand the prognostic performance of ctDNA in practice, including the rate of false negatives defined as radiographic recurrence without detectable ctDNA. Methods: The INTERCEPT program enrolled pts undergoing curative intent surgery for stages II-IV CRC at MD Anderson Cancer Center. A tumor-informed MRD assay (Signatera) was drawn post-operatively and every 3 months as per established reimbursement guidelines. Pts enrolled between Jan-Dec 2022 were included with follow up through Aug, 2023. Post-op timepoint was defined as any test within 6.5 months of surgery to include adjuvant therapy. A false negative result was defined as a negative test but with radiographic detection of recurrence within the subsequent 4 months. Results: A total of 1,140 pts were included, with 44.7% female and 39% with advanced disease. At least one ctDNA+ result was obtained in 338 patients (29.6%). When limited to pts with a post-operative/post-adjuvant timepoint (n= 520) and a median follow up of 10.4m, the 12m DFS was 94.2% for ctDNA-, and 54.3% for pts with at least 1 ctDNA+ test (median DFS of 14.9m); HR 17.67 (95% CI: 10.08 – 30.99), p&lt;0.0001. When segregated by stage, ctDNA remained the most important predictor of outcomes [Table], such that pts with stage IV ctDNA- had better prognosis than pts with stage II ctDNA+ (38.9% vs 87.7% 12mDFS, p=.002). For 15 pts, we detected a false negative ctDNA, representing a rate of 1.3% (15/1140) corresponding to a negative predictive value (NPV) of 98.1%. Conclusions: In this first prospective real-world ctDNA program, MRD testing had a high NPV (98.1%) with very few false negative cases. The prognostic importance of ctDNA was confirmed and exceeded the risk prediction of stage alone, underlying and supporting the importance of introducing the test in practice and the need to investigate interventional studies, as are ongoing in the INTERCEPT program (crcmrd.org). [Table: see text]

Prognostic value of circulating tumor DNA following local therapy in colorectal cancer with liver metastases.

26 Background: Local therapies have the potential to cure a portion of patients with colorectal cancer with liver-only metastatic disease (CRLM). Peri-operative chemotherapy has not been shown to improve overall survival when added to local therapy in CRLM. Circulating-tumor DNA (ct-DNA) may have potential to help guide management decisions following local therapy. Methods: We conducted a retrospective analysis of health records of CRLM patients who had tumor-informed ct-DNA (Signatera) measurement following curative-intent local therapy prior to August 30th, 2023. Disease-free survival (DFS) was defined as the time from ct-DNA test until radiographic evidence of disease. Descriptive characteristics of the cohort, ct-DNA results and their impact on adjuvant therapy decisions were recorded. Survival analysis was carried out using R software v4.3.1 with survival and survminer packages. The Kaplan–Meier method was used to estimate the survival distribution. Log-rank test was used for comparison. A multivariable Cox proportional hazards model was used to assess prognostic factors associated with DFS ( coxph). Results: 27 patients with CRLM underwent local therapy followed by ct-DNA collection. The median age was 61 years, 67% were male, and 85% were White. Molecular characteristics: KRAS 31%, NRAS/BRAF 0%, microsatellite instability 4%. The median time from initial diagnosis to treatment of liver disease was 21.0 months. 63% of patients received less than 6 months of systemic therapy prior to local therapy. ct-DNA was checked prior to definitive therapy in 12 cases and was positive in 5 cases (detection rate of 42%). Liver-directed therapy involved: resection (n=15), ablation (6), radiation (2) or a combination (4). The median follow-up time from liver-directed therapy was 13.2 months. Post-local therapy chemotherapy was initiated prior to recurrence in 59% of cases. ct-DNA results contributed to immediate post-management decisions in 15% of cases. There were 14 radiographic recurrences (11 to liver only, 3 to other sites). Positive ct-DNA on initial testing following local therapy was associated with poorer DFS in univariate analysis and was the only prognostic factor identified on multivariable analysis. Conclusions: ct-DNA positivity following local therapy for CRLM is associated with earlier recurrence. Baseline testing before local therapy may be important for interpretation of testing results post-local therapy, given frequent missed disease detection. Additional clinical trial data is needed to explore ct-DNA-guided treatment decisions in CRLM. [Table: see text]

NIMG-35. RADIO-PATHOMIC MAPS OF TUMOR PROBABILITY IDENTIFY GLIOBLASTOMA INVASION BEYOND 5-ALA GUIDED RESECTION MARGINS THAT EVENTUALLY EXHIBIT TUMOR RECURRENCE

Abstract Current standard of care for glioblastoma includes surgery followed by chemotherapy and radiation, with extent of resection strongly correlated with survival. There is a need to improve the detection of tumor invasion beyond traditional imaging methods, as the full extent of tumor is known to be underestimated. Fluorescence-guided surgery with 5-Aminolevulinic acid (5-ALA) allows surgeons to visualize tumor cells beyond what is seen within traditional MR imaging margins. In this study, we compared tumor probability maps (TPMs) that detect tumor outside of contrast enhancement (CE) to the 5-ALA-guided resection cavity in glioblastoma patients. 3 pathologically confirmed glioblastoma patients that followed standard of care and underwent 5-ALA surgery were included. Patient 1 was a 56-year-old male with radiographic recurrence at 26 days, patient 2 was a 61-year-old male with radiographic recurrence at 130 days, and patient 3 was a 72-year-old male with cystic recurrence at 84 days, all post 5-ALA surgery. A previously published algorithm, using T1, T1C, FLAIR, and ADC as input and autopsy tissue as ground truth, was used to generate TPMs. Pre-surgical TPMs were qualitatively compared to pre-surgical CE, post-5-ALA surgical resection cavities, and radiographic recurrence seen as CE. In patients 1 and 2, TPMs identified areas suspicious of tumor that was not resected and later exhibited radiographic recurrence. Patient 3 had cystic recurrence only identified on post-resection T1C. In all patients, the extent of 5-ALA resection was greater than CE volume, but smaller than TPM identified tumor. These findings suggest that there was residual tumor that was unidentified via 5-ALA and traditional imaging but was identified by the TPMs. Future studies could utilize these maps in conjunction with 5-ALA to maximize surgical resections and prolong overall survival.

NIMG-24. RECURRENT OLIGODENDROGLIOMA DEMONSTRATES EARLY INCREASE IN CEREBRAL BLOOD FLOW AND NORMALIZATION IN RESPONSE TO TREATMENT

Abstract Oligodendrogliomas, molecularly defined by the presence of both IDH mutation and 1p/19q codeletion, are more treatment responsive than other gliomas, and due to short capillary segments, demonstrate elevated CBF regardless of grade or contrast enhancement. Arterial Spin Labeling (ASL) allows noninvasive perfusion imaging assessment of cerebral blood flow (CBF) without contrast administration. Changes in CBF are recognized in association with malignant transformation of gliomas however in the setting of treatment, CBF has only been studied to assist in differentiating radiation treatment effect from progressive glioma. This single center retrospective study was undertaken to evaluate if CBF, measured by ASL, might normalize following treatment of recurrent oligodendrogliomas. Clinical database query identified 151 patients with molecularly confirmed oligodendroglioma, 34 of which had available ASL imaging. Expert reader review of all available MRI sequences, blinded to treatment timeline, were performed by two independent radiologists at a PACS station. There were 6 radiographic recurrences identified and in 5/6 CBF was the first radiographic change. Contrast enhancement did not develop for 1.5-12 months after change in CBF for 4/5 recurrences. ASL imaging before and after non-surgical therapy for recurrent disease was available for 4 patients. Two patients were treated with lomustine, one with bevacizumab and one with proton re-radiation. By the second MRI following treatment initiation, all patients had normalization of CBF. At the first post treatment MRI, 3/4 of patients demonstrated normalization of CBF while only 2/4 demonstrated normalization of dynamic susceptibility contrast-derived cerebral blood volume. During the subsequent 6 months, FLAIR hyperintensities remained stable in all patients. This work supports further study if normalization of ASL-derived CBF may be an early radiographic biomarker for response to treatment, especially in non or minimally enhancing recurrent gliomas.

NCOG-28. RECURRENCE OF PLEOMORPHIC XANTHOASTROCYTOMA PRESENTING WITH DIFFUSE LEPTOMENINGEAL SPREAD

Abstract Pleomorphic xanthoastrocytomas (PXAs) are rare primary brain tumors that mainly affect children and young adults. We report a case of recurrent PXA in an adult and review the literature. To our knowledge, this is the first adult report highlighting clinical, CSF, and imaging findings of recurrent PXA with leptomeningeal spread. A 60-year-old woman presented with a 2-month history of fluctuating mental status, aphasia, low-back pain, progressive paraparesis, and urinary retention. She was previously diagnosed with a left temporal PXA 17 years prior and underwent gross total resection with no evidence of tumor recurrence for the next several years. Approximately 10 months prior to her current presentation, she was found to have radiographic recurrence of the left temporal PXA. She underwent gross total resection, with final pathology revealing anaplastic transformation, WHO grade 3, BRAF V600E mutation positive. She next underwent photon radiotherapy, and chemotherapy with temozolomide. She had good clinical and radiographic response to treatment for 8 months prior to developing her current symptomatology. MRI of the brain and spine showed local recurrence with new diffuse contrast enhancement of the spinal cord and nerve roots. Cerebrospinal fluid (CSF) analysis showed a total nucleated cell count of 10/mcL, protein &amp;gt;1250 mg/dL, glucose &amp;lt; 20 mg/dL, and xanthochromia. CSF cytology was positive for malignant cells consistent with PXA. Although PXA is often associated with a favorable prognosis, recurrence with anaplastic transformation can be associated with dissemination throughout the nervous system and worse outcomes. Despite the rarity of such cases, clinicians should remain vigilant, especially when anaplastic transformation occurs. Early detection of leptomeningeal involvement through thorough CSF analysis and appropriate imaging can facilitate prompt intervention and potentially improve patient outcomes.