Larger Lesion Size Research Articles

Clinical Factors Associated with Radionecrosis Following Stereotactic Radiosurgery in the Era of Modern Systemic Therapy

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) is commonly utilized in the treatment of brain metastases; however, radiation necrosis (RN) is a dose-limiting toxicity. Systemic therapy has greatly improved in recent years with the advent of immunotherapy and targeted therapy leading to increased overall survival. Here, we examined the impact of clinical factors on development of RN after SRS for brain metastasis in the era of modern systemic therapy. <h3>Materials/Methods</h3> We retrospectively reviewed patients treated with Linac-based SRS at a single institution from 2015-2020. Overall survival was calculated using the Kaplan-Meier method. Univariable (UVA) and multivariable (MVA) analysis was performed using Cox proportional hazards modeling. Covariates included age, sex, race, ethnicity, ECOG, primary cancer site, neurologic deficits at diagnosis, seizures, number/size of tumors, benign vs. malignant disease, prior systemic therapy, post-op vs. intact SRS, whole brain radiotherapy before or after SRS, edema at diagnosis, receipt and timing of immunotherapy/targeted therapy. Concurrent therapy was defined as within 30 days of SRS. <h3>Results</h3> 412 patients treated with SRS to 950 lesions were identified at a median follow-up of 8 months. Median age was 63 (interquartile range [IQR] 54-70) with 90% ECOG 0-1. At presentation, 53% had neurologic deficits and 7.6% had seizures. 82% were treated for malignant disease. 30% received post-op SRS. Prior to SRS, treatment included 1-9 lines of systemic therapy (58%), immunotherapy (24%), and WBRT (7.4%). SRS was given for 1-5 lesions in 91% of patients. Median tumor diameter was 2.0 cm (IQR 1.2-2.8). Median OS was 35 months (95% confidence interval [CI] 21-50); 1- and 2-year OS were 68% (95% CI 75-84) and 54% (95% CI 63-73). 17% developed radiographic RN with a median time to RN of 10 months (95% CI 9-13). Of 68 patients who developed RN, those with clinical symptoms (65%) were successfully treated with steroids (65%), laser interstitial thermal therapy (47%), bevacizumab (10%), and craniotomy (21%). On UVA, factors predictive of time to RN included post-op SRS (HR 1.84, 95% CI 1.12-3.00, p=0.015), number of treated lesions (HR 1.11, 95% CI 1.03-1.21, p=0.011), size of largest lesion (HR 1.46, 95% CI 1.17-1.81, p=0.001), malignant tumor (HR 4.17, 95% CI 1.49-11.11, p=0.006), prior systemic therapy (HR 1.7, 95% CI 1.1-2.86, p=0.046), and vasogenic edema at diagnosis (HR 1.97, 95% CI 1.19-3.26, p=0.008). On MVA, for every 1 cm increase in diameter of the largest lesion, the likelihood of developing RN was increased 1.45-fold (95% CI 1.12-1.88, p=0.005). Timing of systemic therapy did not impact RN rate. <h3>Conclusion</h3> Our data demonstrate that RN occurs in ∼17% of patients at a median of 10 months following SRS and can be successfully managed with medical and surgical therapies. The strongest predictor of RN was the size of the treated tumor. Our findings highlight the need for continued clinical surveillance as improved systemic therapy leads to increased long-term survival.

Frameless Fractionated Stereotactic Radiosurgery for Brain Metastases: An Institutional Series of 89 Cases

<h3>Purpose/Objective(s)</h3> Cobalt-60 stereotactic radiosurgery (SRS) conventionally involves frame-based immobilization and single-fraction treatment. However, certain anatomical and technical factors, including large lesion size, close proximity to critical structures, and prior radiation treatment, necessitate fractionated SRS, which requires mask-based immobilization. We present a large institutional experience with mask-based fractionated SRS for large, retreated, or critically-located brain metastases. <h3>Materials/Methods</h3> All patients treated with frameless fractionated SRS for brain metastases between March 2017 and August 2021 at a single institution were identified. Patient, tumor, and treatment variables were abstracted. The primary outcome was one-year local control (LC), which was analyzed with the Kaplan-Meier method. This study was approved by the institution's IRB. <h3>Results</h3> Seventy-four patients with a total of 89 brain metastases were treated. The median follow-up time was seven months. The median age at treatment was 64 years. Sixty-two percent of patients were female. The most common primary tumors were breast (24.7%), non-small cell lung (24.7%), small-cell lung (7.9%), renal cell (6.7%), and melanoma (6.7%). For the majority (62.9%) of tumors, the indication for fractionation was retreatment; other indications were large size (21.3%), critical location (12.4%), and medical comorbidity (3.4%). For all tumors, the mean maximal linear size was 35.5 mm; for tumors fractionated due to size, the mean size was 45.8 mm. The median total dose was 2,750 cGy (range: 1,620-3,000), and the median dose per fraction was 600 cGy (range: 405-900); the most common dose-fractionations were 3,000 cGy in 600 cGy per fraction (42.7% of patients) and 2500 cGy in 500 cGy per fraction (31.5% of patients). The mean target volume was 17.6 cc (range: 0.13-120.0), and the mean maximum dose was 4,980 cGy (range: 3,240-6,000). For 91% of treatments, the prescription isodose line was 50 to 59% (mean, 54%). Target coverage was 100% in all but one case, where it was 99%. For lesions near the brainstem, mean brainstem maximum point dose (MPD) was 9.78 Gy and mean brainstem mean dose was 3.56 Gy. For lesions near the optic pathway, mean optic nerve MPD was 14.39 Gy, mean optic nerve mean dose was 6.2 Gy, mean optic chiasm MPD was 11.7 Gy, and mean optic chiasm mean dose was 5.4 Gy. LC at 12 months was 91%. Nineteen percent of patients experienced acute grade 1-2 toxicity; one patient experienced acute grade 3 fatigue, and there was no other grade 3 or higher acute toxicities. Seventeen percent of patients had grade 1-2 radiation necrosis (RN); there were no cases of grade 3 or higher RN. <h3>Conclusion</h3> Cobalt-60 frameless fractionated SRS for brain metastases offers excellent local control. This treatment modality is technically feasible, offers excellent sparing of critical structures, and has minimal toxicity. Frameless fractionated SRS should be considered for large, retreated, or critically located metastases.

Head and neck mycetoma: Clinical findings, investigations, and predictors for recurrence of the disease in Sudan: A retrospective study.

IntroductionMycetoma is a unique neglected tropical disease which is found endemic in areas known as the “mycetoma belt”. Head and neck mycetoma is a rarity and it has many devastating impacts on patients and communities. In this study, we assessed clinical findings, investigations, and predictors for recurrence of head and neck mycetoma in Sudan.MethodologyA retrospective study was conducted at Mycetoma Research Center in Khartoum between January 1999 and December 2020 for all patients with head and neck mycetoma. Data were analyzed using R software version 4.0.2.ResultsWe included 107 patients with head and neck mycetoma. 65.4% were young adult males from mycetoma endemic areas in Sudan, and most of them were students (33.6%). Most of patients (64.4%) had actinomycetoma. Before presenting with head and neck mycetoma, majority (75.7%) had a long duration with mycetoma, and 30.8% had a history of trauma. The commonest invaded site was the parietal region (30.8%). The lesion started gradually in most of the patients (96.3%). 53.3% of the patients had large size lesions with no sweating, regional lymph nodes involvement, or distal vein involvement. CT scan was the most accurate diagnostic tool while 8.4% of patients were diagnosed by clinical examinations only. Laboratory investigations confirmed that 24/45 (44.4%) of actinomycetoma was caused by Streptomyces somaliensis while 13/28 (46.4%) of eumycetoma was caused by Madurella mycetomatis. All patients with recurrence of head and neck mycetoma underwent surgical excision of the lesion (n = 41/41 {100%}, p < 0.001).ConclusionIn head and neck mycetoma, the most common type was actinomycetes in Sudan. Majority had a long course of mycetoma and the commonest causative organism was Streptomyces somaliensis. The treatment outcome was poor and characterized by a low cure rate.

Factors associated with progression and mortality among patients undergoing stereotactic radiosurgery for intracranial metastasis: results from a national real-world registry.

Stereotactic radiosurgery (SRS) has been increasingly employed in recent years to treat intracranial metastatic lesions. However, there is still a need for optimization of treatment paradigms to provide better local control and prevent progressive intracranial disease. In the current study, the authors utilized a national collaborative registry to investigate the outcomes of patients with intracranial metastatic disease who underwent SRS and to determine factors associated with lesion treatment response, overall progression, and mortality. The NeuroPoint Alliance SRS registry was queried for all patients with intracranial metastatic lesions undergoing single- or multifraction SRS at participating institutions between 2016 and 2020. The main outcomes of interest included lesion response (lesion-level analysis), progression using Response Assessment for Neuro-Oncology criteria, and mortality (patient-level analysis). Kaplan-Meier analysis was used to report time to progression and overall survival, and multivariable Cox proportional hazards analysis was used to investigate factors associated with lesion response, progression, and mortality. A total of 501 patients (1447 intracranial metastatic lesions) who underwent SRS and had available follow-up were included in the current analyses. The most common primary tumor was lung cancer (49.5%, n = 248), followed by breast (15.4%, n = 77) and melanoma (12.2%, n = 61). Most patients had a single lesion (44.9%, n = 225), 29.3% (n = 147) had 2 or 3 lesions, and 25.7% (n = 129) had > 3 lesions. The mean sum of baseline measurements of the lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) was 35.54 mm (SD 25.94). At follow-up, 671 lesions (46.4%) had a complete response, 631 (43.6%) had a partial response (≥ 30% decrease in longest diameter) or were stable (< 30% decrease but < 20% increase), and 145 (10%) showed progression (> 20% increase in longest diameter). On multivariable Cox proportional hazards analysis, melanoma-associated lesions (HR 0.48, 95% CI 0.34-0.67; p < 0.001) and larger lesion size (HR 0.94, 95% CI 0.93-0.96; p < 0.001) showed lower odds of lesion regression, while a higher biologically effective dose was associated with higher odds (HR 1.001, 95% CI 1.0001-1.00023; p < 0.001). A total of 237 patients (47.3%) had overall progression (local failure or intracranial progressive disease), with a median time to progression of 10.03 months after the index SRS. Factors found to be associated with increased hazards of progression included male sex (HR 1.48, 95% CI 1.108-1.99; p = 0.008), while administration of immunotherapy (before or after SRS) was found to be associated with lower hazards of overall progression (HR 0.62, 95% CI 0.460-0.85; p = 0.003). A total of 121 patients (23.95%) died during the follow-up period, with a median survival of 19.4 months from the time of initial SRS. A higher recursive partitioning analysis score (HR 21.3485, 95% CI 1.53202-3.6285; p < 0.001) was found to be associated with higher hazards of mortality, while single-fraction treatment compared with hypofractionated treatment (HR 0.082, 95% CI 0.011-0.61; p = 0.015), administration of immunotherapy (HR 0.385, 95% CI 0.233-0.64; p < 0.001), and presence of single compared with > 3 lesions (HR 0.427, 95% CI 0.187-0.98; p = 0.044) were found to be associated with lower risk of mortality. The comparability of results between this study and those of previously published clinical trials affirms the value of multicenter databases with real-world data collected without predetermined research purpose.

Distribution Pattern Analysis of Cortical Brain Infarcts on Diffusion-Weighted Magnetic Resonance Imaging: A Hypothesis-Generating Approach to the Burden of Silent Embolic Stroke.

Background In patients with covert cerebrovascular disease or proximal source of embolism, embolic silent brain infarction may precede major stroke events. Therefore, characterization of particularly cortical silent brain infarction is essential for identifying affected patients and commencing adequate secondary prevention. This study aimed to investigate differences in the distribution pattern of cortical ischemic stroke lesions to assess potential predilection sites of cortical silent brain infarction. Methods and Results We prospectively included all consecutive patients with stroke presenting from January 1 to December 31, 2018. Diffusion-weighted imaging lesions were used to generate voxel-based lesion maps and assigned to atlas-based cortical regions of interest in middle cerebral artery territories. Each region-of-interest lesion frequency was related to the respective region-of-interest volume to identify frequently affected and underrepresented cerebral cortex areas. Diffusion-weighted imaging data for voxel-based lesion maps were available in 334 out of 633 patients. Primary analysis revealed that small- (<0.24 cc) and medium-sized (0.24-2640 cc) lesions distributed predominantly along regions associated with sensorimotor or language function. Detailed analysis within middle cerebral artery territories showed an approximated frequency of missed cortical stroke lesions of up to 67% in the right and 69% in the left hemisphere. In particular, the frontal, temporal, and occipital cortices were underrepresented. Larger lesion size and areas associated with higher cortical function led to hospital admission. Conclusions Cortical brain infarcts in hospitalized patients are not dispersed equally but are predominantly located in brain structures associated with motor control and sensory and language function. Matching underrepresented cerebral cortex regions to symptoms not yet associated with stroke warrants further exploration.

The Impact of Lenvatinib on Tumor Blood Vessel Shrinkage of Hepatocellular Carcinoma during Treatment: An Imaging-Based Analysis

Introduction: When lenvatinib is administered to people with hepatocellular carcinoma (HCC), tumor blood flow is reduced due to the inhibition of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR). Few studies have examined the decrease in tumor blood flow with respect to changes in tumor blood vessels (TBVs) in clinical practice. We investigated the mechanism of tumor blood flow control by investigating changes in the diameter of relatively large TBVs in large-sized lesions with high blood flow. Methods: From January 2011 to October 2021, patients receiving lenvatinib for unresectable intrahepatic HCC at Toranomon Hospital, Tokyo, Japan, were considered for inclusion. We investigated the TBV diameter in the arterial phase of dynamic computed tomography before treatment and its change over time (2–12 weeks after lenvatinib initiation). The relationship between changes in TBV diameter and prognosis was also examined. Results: Of 114 patients treated with lenvatinib for HCC, 26 patients who had intrahepatic lesions with a tumor diameter of 30 mm or more enrolled in the study. The median tumor and TBV diameters before treatment were 58 mm and 2.55 mm, respectively. Twenty-five patients (96%) had a shrinkage in TBV diameter 2–12 weeks after lenvatinib administration. The maximum TBV diameter shrinkage of 20% or more was observed in 19 patients (73%), and progression-free survival was prolonged in these patients compared to the group with less than 20% TBV diameter shrinkage (p = 0.039). Discussion/Conclusion: Due to the antiangiogenic effect of lenvatinib, a shrinkage in the TBV diameter of HCC was observed. The shrinkage of TBV may be regarded as a process of normalization of TBVs. The shrinkage of TBVs in imaging analysis may be associated with improved prognosis; however, additional studies are still required.

Transplantation for Nonresectable Colorectal Liver Metastases: Long-Term Follow-Up of the First Prospective Pilot Study.

To determine whether liver transplantation (LT) can provide long-term overall survival (OS) in selected patients with nonresectable liver-only colorectal liver metastases (nrCRLM). In 2005 the first prospective pilot study on LT for nrCRLM was initiated in Norway. We here report long-term data from this study. Main inclusion criteria were nrCRLM, excised primary tumors, and 6 weeks of chemotherapy. Carcinoembryonic antigen >80µg/L, progressive disease on chemotherapy, size of largest lesion >5.5cm, and <2 years from primary tumor resection to LT were previously found to be associated with survival. The sum of these factors constitutes the Oslo Score. From 2006 to 2012, 23 patients underwent LT in the study. In February 2022, the actual 5-year and 10-year OS after LT were 43.5% and 26.1%, respectively. All patients alive were observed for more than 10 years (range: 133-168 months). Four patients were alive without signs of cancer and with no evidence for disease of median of 102 months (53-133 months). A fifth patient died of noncancer cause after 164 months with no evidence for disease for 31 months. For patients with Oslo Score of 0 or 1, the 5-year and 10-year actual OS was 75% and 50%, respectively (n=6). For patients with Oslo Score of 2, the 5-year and 10- year actual OS 50% was 33% (n=6). All patients with Oslo score 3 or 4 were deceased 86 months post-LT (n=9). LT for nrCRLM can provide long term survival and perhaps cure for selected patients. The OS is excellent compared to oncological treatment options and in line with results from studies on resectable CRLM.

Comparison of two pathological processing methods for large endoscopic submucosal dissection (ESD) specimens

AimsAccurate histopathological evaluation of the endoscopic submucosal dissection (ESD) specimens is essential for clinicians to guide further triage and management. This study aimed to report a novel processing technique for...

Bone Lesions Detected on Breast MRI: Clinical Outcomes and Features Associated with Metastatic Breast Cancer.

To determine prevalence and frequency of malignancy among bone lesions detected on breast MRI and to identify clinical and imaging features associated with bone metastases from breast cancer (BC), as bone lesions are suboptimally evaluated on breast imaging protocols and can present a diagnostic challenge. This IRB-approved retrospective review of breast MRIs performed from June 2009 to June 2018 identified patients with bone lesions. Demographic, clinical, and MRI features were reviewed. Clinical outcome of bone lesions was determined based on pathology and/or additional diagnostic imaging. All benign lesions had ≥ 2 years of imaging follow-up. Statistics were computed with Fisher's exact and Wilcoxon rank sum tests. Among all patients with breast MRI, 1.2% (340/29 461) had bone lesions. Of these, 224 were confirmed benign or metastatic BC by pathology or imaging follow-up, with 70.1% (157/224) be- nign and 29.9% (67/224) metastatic. Bone metastases were associated with BC history (P < 0.001), with metastases occurring in 58.2% (53/91) of patients with current BC, 17.9% (14/78) patients with prior BC, and 0.0% (0/55) without BC. Bone metastases were associated with invasive and ad- vanced stage BC and, on MRI, with location in sternum, ribs, or clavicles, larger size, multiplicity, andT1 hypointensity (all P < 0.01 in tests of overall association). Of clinically confirmed breast MRI-detected bone lesions, 30% were bone metastases; all were detected in patients with current or prior BC. Metastases were associated with advanced stage, invasive carcinoma, larger lesion size, multiplicity, low T1 signal, and non-spine location.

Presentation, imaging, patterns of care, growth, and outcome in sporadic and von Hippel-Lindau-associated central nervous system hemangioblastomas.

Hemangioblastoma is a relatively rare neoplasm occurring mostly in the cerebellum that may arise sporadically or in the context of von Hippel-Lindau (VHL) syndrome. Presentation, imaging, natural history, surgical patterns of care, and outcomes are incompletely defined for this uncommon lesion. We reviewed our large institutional series to help clarify these issues. Retrospective analysis of consecutive, neurosurgically managed CNS hemangioblastomas at Mayo Clinic, 1988-2018. Two hundred and eighty five hemangioblastomas were treated in 184 unique patients (115 sporadic, 69 VHL). Compared to sporadic patients, VHL patients were younger (36.7 vs 51.7years; p < 0.0001), were treated while asymptomatic more commonly (47.3 vs 4.2%; p < 0.0001), had smaller lesions (6.6 vs 13.9mL; p < 0.0001), and harbored lesions with associated cysts less frequently (51.0 vs 75.0%; p = 0.0002). Macrocystic tumor architecture was associated with larger lesion size and greater symptom severity. Solid lesions later formed cysts at a median 130months. Growth in both total volume and solid component accelerated after cyst formation (10.6 and 6.0 times median rate prior to cyst emergence). VHL patients died at a younger age (47.9 vs 74.5, p = 0.0017) and were more likely to die of direct disease sequelae. Though treatment-free survival time was significantly longer in sporadic cases, a substantial fraction (> 40%) developed tumor recurrence/progression requiring additional treatment. Hemangioblastoma presentation varies with etiology and clinical course is more complicated in VHL cases. Nodular lesions often develop cysts over time which is associated with accelerated tumor growth. Sporadic cases have a previously unappreciated but substantial risk of late recurrence/progression requiring treatment.

18F-FDG PET/CT and contrast-enhanced CT in the diagnosis of Castleman disease.

Castleman disease (CD) is a rare group of lymphoproliferative disorders, which is easily confused with lymphoma or other solid tumors. Hence, this study aimed to investigate the diagnostic role of 18F-FDG PET/CT and contrast-enhanced CT (CECT) in patients with CD. Clinicopathological characteristics, and 18F-FDG PET/CT and CECT findings and parameters were retrospectively reviewed in 32 patients with CD. These 32 patients (12 males, 20 females; median age, 41years) consisted of 17 unicentric CD (UCD) patients and 15 multicentric CD (MCD) patients. Compared with MCD, UCD had a higher prevalence in female (82.4% vs. 40.0%) and hyaline vascular subtype (94.1% vs. 40.0%) (P < 0.05). FDG uptake was avid in all cases, including moderate uptake in 7 cases and intense uptake in 25 cases. The median SUVmax, SUVmean, MLV, and TLG of all cases were 4.4 (range, 1.4-23.6), 2.7 (range, 1.1-15.2), 26.6 (range, 4.8-393.0), and 78.8 (range, 9.4-1545.6), respectively. The lesions of 29 cases showed homogeneous enhancement, and marked enhancement was observed in 27 cases. 18F-FDG PET/CT corrected 6.3% CECT diagnoses, while CECT corrected 37.5% PET/CT diagnosis. The accuracy of combined PET/CT and CECT was superior to PET/CT or CECT alone (78.1%, 31.3%, and 62.5%). Besides, higher SUVmax and SUVmean were found in male subjects, MCD, and plasma cell subtype (P < 0.05), while higher MLV and TLG were observed in larger lesion size and volume (P < 0.05). Castleman disease most commonly appears as marked and homogeneous enhancement meanwhile with moderate or intense FDG uptake. 18F-FDG PET/CT combined with CECT was the effectively diagnostic modality for CD. The glucose metabolism of CD was associated with gender, clinical classification, histopathological classification, and lesion size and volume.

Outcomes of bioabsorbable fixation in the treatment of osteochondral lesions of the knee in adolescent patients

BackgroundBioabsorbable fixation in managing osteochondral lesions is increasing in popularity. The purpose was to report on outcomes using bioabsorbable fixation nails for osteochondral lesions of the knee in a pediatric and adolescent population. MethodsA retrospective review of pediatric patients undergoing surgery with bioabsorbable fixation for knee osteochondral lesions was performed. Demographic, clinical, and surgical data was collected including symptom duration, lesion location, size, use of bone grafting, and number of implants. Return to activities was documented. Patients recommended revision surgery were compared to those who were not. Results47 patients with median age 13.9 years and 25.5% female were included with median clinical follow-up of 47.3 weeks. 87.2% of patients were cleared for full activities. Four male patients (8.5%) were recommended revision surgery, of whom three underwent surgery including removal of loose bioabsorbable fixation. Demographic data did not differ between the group with successful versus failed primary surgery (p > 0.05). Symptom duration was more acute (<1 month) in the four recommended revision surgery (75% versus 9.3%, p = 0.008). The group recommended revision also had larger lesion size (median 5.4 cm2 versus 2 cm2, p = 0.04). Distal femoral physeal status, lesion location, necessity for bone grafting, and number of implants did not differ between groups. ConclusionsAdolescents had a high return to activity following bioabsorbable fixation for knee osteochondral lesions with 87.2% cleared for full return. In the 8.5% of patients who were deemed to have failed primary fixation, symptoms were more likely to be acute in nature with larger lesion sizes.

Seborrheic Keratosis With Malignant Transformation (Invasive or Noninvasive Squamous Cell Carcinoma Arising in Seborrheic Keratosis): A Clinicopathologic and Immunohistochemical Study of 11 Cases.

Seborrheic keratosis is a common benign neoplasm composed of basaloid keratinocytes. However, little is known about the malignant transformation of the tumor. Eleven cases of seborrheic keratosis with malignant transformation were analyzed. The 11 patients included 5 male patients and 6 female patients with a median age of 75 years at diagnosis (68-90 years). The tumors arose at various sites from the scalp (n = 3) to the lower leg (n = 2). The median tumor size was 12 (10-32) and 40 (20-75) mm in 7 noninvasive and 4 invasive cases, respectively. One patient exhibited in-transit skin metastasis. Histopathology of the malignant components resembled porocarcinoma or inverted follicular keratosis. Bowenoid and pagetoid spreading was frequently observed. The malignant components expressed cytokeratin 5/6 (100%) and GATA3 (73%), but not cytokeratin 7 (0%), cytokeratin 19 (9%), BerEP4 (0%), c-kit (0%), and NUT (0%). No significant immunoreactivity of YAP1 was observed in any of the cases. Mutant-type immunostaining of p53 and PTEN was observed in 91% and 82% of the cases, respectively. An increase in p16 expression was seen in 6 (86%) of the 7 cases with noninvasive carcinoma, although a loss of p16 immunoexpression was seen in the invasive carcinoma component in 3 (75%) of the 4 cases. This study demonstrated that seborrheic keratosis can undergo malignant transformation, particularly in large-sized lesions in elderly patients. Malignant components mimic porocarcinoma or inverted follicular keratosis. Malignant transformation induced by TP53 and PTEN mutations and tumor invasion by CDKN2A inactivating mutations are suggested in this study.

Risk factors and consequences of conversion in minimally invasive distal pancreatectomy.

Background:Although recent studies have reported potential benefits of laparoscopic approach in distal pancreatectomy, reports of conversion during minimally invasive distal pancreatectomy (MIDP) were limited.Methods:This was a retrospective study using data from Sir Run Run Shaw Hospital around May 2013 to December 2018. Outcomes of patients who had conversions during MIDP were compared with patients with successful MIDP and with patients undergoing open distal pancreatectomy (ODP).Results:Two-hundred and eighty-three cases were included in this study: 225 (79.5%) had MIDP, 30 (10.6%) had conversions and 28 (9.9%) had outpatient department. The risk factors for conversion included large lesion size (heart rates [HR]: 5.632, 95% confidencevinterval [CI]: 1.036–1.450, P = 0.018) and pancreatic cancer (HR: 6.957, 95% CI: 1.359–8.022, P = 0.009). Compared with MIDP, those who required conversion were associated with longer operations (P = 0.003), higher blood loss (P < 0.001) and more severe of the complications (P < 0.001). However, no statistically significant differences were found between the conversion group and ODP.Conclusions:Large lesion size and pancreatic cancer were reported to be independent risk factors for conversion during MIDP. As for post-operative outcomes, the outcomes of successfully MIDP were better than those for conversion. However, conversion did not lead to worsening outcomes when compared with ODP.

Abstract 686: Subsequent invasive breast cancer risk after DCIS treatment in multinational PRECISION consortium cohorts comprising 48,576 patients

Abstract Background: Although DCIS is a precursor of invasive breast cancer (IBC), most DCIS lesions never will progress. As we cannot distinguish reliably progressive from harmless DCIS yet, almost all women with DCIS are treated extensively with surgery and often adjuvant radiotherapy or endocrine treatment, implying overtreatment of many thousands of women with harmless DCIS. PRECISION aims to reduce such overtreatment by identifying factors associated with subsequent ipsilateral IBC. Many factors have been implicated in subsequent DCIS and IBC risk, but most studies relied on small series with limited prognostic power. To overcome this, we conducted pooled analyses of four large cohorts with DCIS from three different countries. Methods: Cohorts were pooled with data of 48,804 women with DCIS: a population-based cohort (NL, n=18,996), prospective, a population-based, screening cohort (Sloane, UK, n=8,462), a single center cohort (MDACC, USA, n=2,363), and a representative DCIS patient series from the National Cancer Database Special Study (USA, n=18,983). Patients with missing data on treatment and follow-up or follow-up shorter than six months were excluded from analyses. Risk of a subsequent ipsilateral invasive breast cancer (iIBC) was assessed in three DCIS lesion size groups (&amp;lt;20mm, 20-50mm and ≥50mm) and in patients who had clear surgical margins (&amp;lt;2mm) after final breast conserving surgery (BCS) versus patients who did not. Cox proportional hazards models were used to assess differences in risk of IBC, with a focus on DCIS size and margin status. Results: In final analyses, 48,576 patients, diagnosed between 1999 and 2017, were included. Median follow-up was 7.6 years (range 0.5-21.1). In multivariable analyses, patients with smaller size of DCIS (&amp;lt;20mm) had a decreased risk of iIBC compared with women with larger lesion size (HR 0.81; 95% CI 0.68-0.97). In 33,091 BCS treated patients, patients with clear surgical margins had a decreased risk of iIBC (HR 0.68; 95% CI 0.52-0.90). Conclusion: In our quest to reduce overtreatment for women with DCIS, we have identified free surgical margins and smaller lesion size as independent factors reducing the risk of subsequent ipsilateral invasive breast cancer, irrespective of the treatment received. Knowledge of these, and additional, factors could aid in selecting patients suitable for less invasive management strategies such as active surveillance or omitting radiotherapy. This work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043); Web site: https://cancergrandchallenges.org/teams/precision Citation Format: Renee S. Schmitz, Alexandra W. van den Belt-Dusebout, Karen Clements, Yi Ren, Chiara Cresta, Jasmine Timbres, Yat-Hee Liu, Danalyn Byng, Thomas Lynch, Brian Menegaz, Deborah Collyar, Terry Hyslop, Michael Schaapveld, Elinor Sawyer, Shelley E. Hwang, Alastair Thompson, Marc D. Ryser, Jelle Wesseling, Esther H. Lips, Marjanka K. Schmidt, Grand Challenge PRECISION Consortium. Subsequent invasive breast cancer risk after DCIS treatment in multinational PRECISION consortium cohorts comprising 48,576 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 686.

Executive functions and psychosocial impairment in children following arterial ischemic stroke

ABSTRACT This study examined the executive function (EF) of children with a history of arterial ischemic stroke (AIS) and preserved intellectual abilities, with reference to age at stroke onset, lesion characteristics, language, and motor functioning. In addition, the associations between EF and emotional and behavioral functioning were investigated. A batteryof standardized neuropsychological tests was administered to children withprevious AIS aged 7–12 in order to assess EF, including inhibition, working memory, cognitive flexibility, and attention. Parents rated questionnaires regarding real-life emotional and behavioral functioning. Finally, clinical and neuroradiological data were also gathered. Thirty patients were enrolled. Eight children fall in the lower end of the normative range or below in more than half of the EF measures, with working memory, inhibition and cognitive flexibility equally impaired, and attention relatively better preserved. Larger lesion size and language deficits were significantly associated with higher EF impairment. Emotional and behavioral functioning was lower in children with weaker EF. Children with a history of AIS, even those with preserved intellectual functioning, have a high risk of showing poor EF, mostly regardless of clinical features or functional impairment. EF difficulties are in turn associated with emotional and behavioral problems. Therefore, a standardized evaluation of EF in this population is mandatory as part of the follow-up, in order to ensure an early intervention and prevent related difficulties.

P-166 Local recurrence after endoscopic submucosal dissection of early gastric cancer

Endoscopic submucosal dissection (ESD) is considered the treatment of choice for early gastric cancer (EGC) with a negligible risk of lymph node metastasis. However, locally recurrent lesions on artificial ulcer scars are difficult to manage. Therefore, predicting the risk of local recurrence after ESD is important to manage and prevent the event. This study aimed to elucidate risk factors associated with local recurrence after ESD of EGC. Between November 2008 and February 2016, consecutive patients (n=641; mean age, 69.3±9.5 years; men, 77.2%) with EGC who underwent ESD at a single tertiary referral hospital were retrospectively analyzed to evaluate the incidence and factors associated with local recurrence. Local recurrence was defined as the development of neoplastic lesions at or adjacent to the site of the post-ESD scar. En bloc and complete resection rates were 97.8% and 93.6%, respectively. The local recurrence rate after ESD was 3.1%. The mean follow-up period after ESD was 50.7±32.5 months. One case of gastric cancer-related death (0.15%) was noted, wherein the patient had refused additive surgical resection after ESD for EGC with lymphatic and deep submucosal invasion. Lesion size ≥15 mm, incomplete histologic resection, undifferentiated adenocarcinoma, scar, and absence of erythema of the surface were associated with a higher risk of local recurrence. Predicting local recurrence during regular endoscopic surveillance after ESD is important, especially in patients with a larger lesion size (≥15 mm), incomplete histologic resection, surface changes of scars, and no erythema of the surface.

Identifying factors that may influence the classification performance of radiomics models using contrast-enhanced mammography (CEM) images

BackgroundRadiomics plays an important role in the field of oncology. Few studies have focused on the identification of factors that may influence the classification performance of radiomics models. The goal of this study was to use contrast-enhanced mammography (CEM) images to identify factors that may potentially influence the performance of radiomics models in diagnosing breast lesions.MethodsA total of 157 women with 161 breast lesions were included. Least absolute shrinkage and selection operator (LASSO) regression and the random forest (RF) algorithm were employed to construct radiomics models. The classification result for each lesion was obtained by using 100 rounds of five-fold cross-validation. The image features interpreted by the radiologists were used in the exploratory factor analyses. Univariate and multivariate analyses were performed to determine the association between the image features and misclassification. Additional exploratory analyses were performed to examine the findings.ResultsAmong the lesions misclassified by both LASSO and RF ≥ 20% of the iterations in the cross-validation and those misclassified by both algorithms ≤5% of the iterations, univariate analysis showed that larger lesion size and the presence of rim artifacts and/or ripple artifacts were associated with more misclassifications among benign lesions, and smaller lesion size was associated with more misclassifications among malignant lesions (all p < 0.050). Multivariate analysis showed that smaller lesion size (odds ratio [OR] = 0.699, p = 0.002) and the presence of air trapping artifacts (OR = 35.568, p = 0.025) were factors that may lead to misclassification among malignant lesions. Additional exploratory analyses showed that benign lesions with rim artifacts and small malignant lesions (< 20 mm) with air trapping artifacts were misclassified by approximately 50% more in rate compared with benign and malignant lesions without these factors.ConclusionsLesion size and artifacts in CEM images may affect the diagnostic performance of radiomics models. The classification results for lesions presenting with certain factors may be less reliable.

Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1\u03b1 in mice after spinal cord injury

Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of microglia repopulation after SCI remain unknown. Here, we used single-cell RNA sequencing to portray the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. B cells and migDCs, located in the meninges under physiological conditions, are involved in immune surveillance. Microglia quickly reduced, and peripheral myeloid cells infiltrated three days-post-injury (dpi). At 14 dpi, microglia repopulated, myeloid cells were reduced, and lymphocytes infiltrated. Importantly, genetic lineage tracing of nestin+ and Cx3cr1+ cells in vivo showed that the repopulation of microglia was derived from residual microglia after SCI. We found that residual microglia regress to a developmental growth state in the early stages after SCI. Hif1α promotes microglial proliferation. Conditional ablation of Hif1α in microglia causes larger lesion sizes, fewer axon fibers, and impaired functional recovery in the late stages after SCI. Our results mapped the immune heterogeneity in SCI and raised the possibility that targeting Hif1α may help in axon regeneration and functional recovery after SCI.

The clinical features and long-term surgical outcomes of different types of abdominal wall endometriosis.

To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.