Increased Risk Of Recurrence Research Articles

Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2.

Approximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor. The expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively. FOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (P=0.002, P<0.0001, and P<0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes (P<0.0001/P=0.002, P<0.0001/P<0.0001, and P<0.0001/P<0.0001, respectively). Immuno-morphometry revealed that 30-40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (P<0.0001), while MMP11 was expressed in normal colon epithelium at high levels. We conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence.

Colorectal cancer recurrence and its impact on survival after curative surgery: An analysis based on multistate models

AimTo investigate the usefulness of multistate models (MSM) for determining colorectal cancer (CRC) recurrence rate, to analyse the effect of different factors on tumour recurrence and death, and to assess the impact of recurrence for CRC prognosis. MethodsObservational follow-up study of incident CRC cases disease-free after curative resection in 2006–2013 (n = 994). Recurrence and mortality were analyzed with MSM, as well as covariate effects on transition probabilities. ResultsCumulative incidence of recurrence at 60 months was 13.7%. Five years after surgery, 70.3% of patients were alive and recurrence-free, and 8.4% were alive after recurrence.Recurrence has a negative impact on prognosis, with 5-year CRC-related mortality increasing from 3.8% for those who are recurrence-free 1-year after surgery to 33.6% for those with a recurrence.Advanced stage increases recurrence risk (HR = 1.53) and CRC-related mortality after recurrence (HR = 2.35). CRC-related death was associated with age in recurrence-free patients, and with comorbidity after recurrence.As expected, age≥75 years was a risk factor for non-CRC-related death with (HR = 7.76) or without recurrence (HR = 4.26), while its effect on recurrence risk was not demonstrated. ConclusionsMSM allows detailed analysis of recurrence and mortality in CRC. Recurrence has a negative impact on prognosis. Advanced stage was a determining factor for recurrence and CRC-death after recurrence.

Exercise and Nutrition Interventions for Prehabilitation in Hepato-Pancreato-Biliary Cancers: A Narrative Review.

Gastrointestinal (GI) cancers constitute over 25% of global cancer cases annually, with hepato-pancreato-biliary (HPB) cancers presenting particularly poor prognosis and challenging surgical treatments. While advancements in clinical care have improved post-operative outcomes over time, surgery for HPB cancers remains associated with high morbidity and mortality rates. Patients with HPB cancer are often older, diagnosed at later stages, and have a higher prevalence of co-morbid conditions, leading to reduced life expectancy, suboptimal post-operative recovery, and increased recurrence risk. Exercise and nutrition interventions have emerged as safe non-pharmacological strategies to enhance clinical outcomes among cancer survivors, but their potential in the pre-operative period for patients with HPB cancer remains underexplored. This narrative review evaluates existing evidence on exercise and nutritional interventions during pre-operative prehabilitation for HPB cancer populations, focusing on clinically relevant post-operative outcomes related to frailty and malnutrition. We conducted a literature search in PubMed and Google Scholar databases to identify studies utilizing a prehabilitation intervention in HPB cancer populations with exercise and nutritional components. The currently available evidence suggests that incorporating exercise and nutrition into prehabilitation programs offers a critical opportunity to enhance post-operative outcomes, mitigate the risk of comorbidities, and support overall survivorship among HPB cancer populations. This review underscores the need for further research to optimize the timing, duration, and components of pre-operative prehabilitation programs, emphasizing patient-centered, multidisciplinary approaches in this evolving field.

Management of cerebrospinal fluid pseudocysts in the laparoscopic age.

Abdominal CSF pseudocysts are an uncommon but challenging complication of ventriculoperitoneal shunts. Pseudocysts consist of a loculated intraperitoneal compartment that inadequately absorbs CSF and may be infected or sterile at diagnosis. The treatment goal is to clear infection if present, reduce inflammation, and reestablish long-term function in an absorptive (intraperitoneal) space. This aim of this paper was to study the efficacy of primary laparoscopic repositioning of the distal shunt catheter for treatment of sterile abdominal CSF pseudocysts. All patients treated for abdominal CSF pseudocysts at Dallas Children's Health from 1991 to 2021 were retrospectively reviewed. Patient history and pseudocyst characteristics were analyzed, with a primary outcome of pseudocyst recurrence at 1 year. Of 92 primary pseudocysts, 5 initial treatment strategies (groups) were used depending on culture status, clinical history, and surgeon preference: 1) shunt explant/external ventricular drain (EVD) placement (23/92), 2) distal tubing externalization (13/92), 3) laparoscopic repositioning (35/92), 4) open repositioning (4/92), and 5) other methods such as pseudocyst drainage or direct revision to another terminus (17/92). Seventy pseudocysts underwent shunt reimplantation in the peritoneal space. The 1-year peritoneal shunt survival for groups 1 and 2 combined was 90%, and 62% for group 3. In group 3, 1-year survival was better for those with normal systemic inflammatory markers (100%) than for those with high markers (47%) (p = 0.042). In a univariate Cox proportional hazards model, the risk of pseudocyst recurrence was increased if the most recent abdominal procedure was a nonshunt abdominal surgery (p = 0.012), and it approached statistical significance with male sex (p = 0.054) and elevated inflammatory markers (p = 0.056. Multivariate Cox analysis suggested increased recurrence risk with male sex (p = 0.05) and elevated inflammatory markers (p = 0.06), although the statistical significance threshold was not reached. The length of hospital stay was shorter for laparoscopic repositioning (6 days) than for explantation/EVD placement (21 days) (p < 0.0001). Ultimately, 62% of patients had a peritoneal terminus at the last follow-up, 33% (n = 30) had an extraperitoneal terminus (19 pleura, 8 right heart, and 3 gallbladder), and 5 patients were shunt free. Some sterile pseudocysts with normal systemic inflammatory markers can be effectively treated with laparoscopic repositioning, resulting in a significantly shorter hospitalization and modestly higher recurrence rate than shunt explantation.

Oncologic outcomes of robot-assisted laparoscopy versus conventional laparoscopy for the treatment of apparent early-stage endometrioid adenocarcinoma of the uterus

ObjectiveTo compare long-term oncologic outcomes in patients with clinically uterine-confined endometrioid endometrial cancer who underwent surgical staging with robot-assisted (RA) versus conventional laparoscopy. MethodsWe performed a retrospective chart review of patients with newly diagnosed, uterine-confined endometrioid endometrial cancer who were treated and had primary surgery at our institution between 1/1/2009–1/1/2018. Clinicopathologic, surgical, and survival data were collected. Appropriate statistical methods were applied. ResultsOf 1728 patients identified, 1389 (80.4%) underwent RA and 339 (19.6%) conventional laparoscopy. At diagnosis, median age was 60 years (range, 24–92) and median BMI was 30.2 kg/m2 (range, 15.1–71.5). In the RA group, patients had longer operative time (170 vs 152 min, P < .001), lower conversion rate to laparotomy (0.6% vs 4.7%, P < .001), and a higher proportion had a BMI > 40 kg/m2 (17.2% vs 11.5%, P = .01) and same-day discharge (19.2% vs 5.3%, P < .001). Overall, 93% (RA) and 90% (conventional) of patients underwent lymph node assessment (P = .1). Comparing the RA versus conventional groups, final surgical stage on pathology (P = .6), median follow-up (55.7 vs 52.9 months, P = .4), and rates of perioperative complications (9.9% vs 7.7%, P = .6), recurrence (9.5% vs 7.4%, P = .3), 5-year PFS (88.5% vs 91.0%, P = .3), and 5-year OS (92.5% vs 92.4%, P = .7) were not significantly different. No significant increase in risk of recurrence (HR = 1.2, 95% CI: 0.8–1.9, P = .3) or poorer OS outcomes (HR = 0.9, 95% CI: 0.6–1.4, P = .7) were observed in the RA group. ConclusionIn uterine-confined endometrioid endometrial cancers, surgical staging using RA laparoscopy was not associated with adverse survival outcomes compared to conventional laparoscopy.

Subcategorization of Perineural Invasion Stratifies Oral Cavity Squamous Cell Carcinoma Prognosis.

To evaluate whether subcategorization of perineural invasion (PNI) improves the prognostic resolution of the American Joint Committee on Cancer, Eighth Edition (AJCC8) staging system in oral cavity squamous cell carcinoma (OCSCC). OCSCC tumor specimens from patients seen at a tertiary care institution who underwent primary surgical resection between January 2019 and June 2021 were sorted into four PNI categories: negative, intratumoral, peripheral, and extratumoral. The prognostic effect of these PNI categories were assessed through Kaplan-Meier, Cox regression, and log-rank testing using recurrence-free survival (RFS) and overall survival (OS) as primary and secondary outcomes respectively. A total of 158 patients were examined. The median follow-up time was 21 months. PNI subcategorization further stratified RFS (p = 0.007) and OS (p = 0.002). Extratumoral PNI was associated with a 4.5-fold increase in recurrence risk (adjusted hazards ratio [aHR]: 4.53; 95% confidence interval [CI]: 1.1-18.66) and worse OS when compared with PNI negative disease (aHR: 5.71; 95% CI: 1.0-32.67). Peripheral PNI was associated with worse OS (aHR: 5.7; 95% CI: 1.35-24.08) but not worse RFS (p = 0.18) when compared with PNI negative disease. Interestingly, intratumoral PNI was not associated with significant differences in RFS (p = 0.087) or OS (p = 0.22) when compared with PNI negative disease. Subcategorization of OCSCC tumors into extratumoral, peripheral, and intratumoral PNI stratifies RFS and OS when compared with patients with PNI negative disease in an incremental fashion. This pilot study suggests that there may be added benefit in subcategorization of PNI in the prognostic evaluation of OCSCC. 4 Laryngoscope, 134:1656-1662, 2024.

Endometriosis with colonic and rectal involvement: surgical approach and outcomes in 142 patients.

Endometriosis involving the colon and/or rectum (CRE) is operatively managed using various methods. We aimed to determine if a more limited excision is associated with 30-day complications, symptom improvement, and/or recurrence. This is a retrospective review of consecutive cases of patients who underwent surgical management of CRE between 2010 and 2018. Primary outcomes were the associations between risk factors and symptom improvement, 30-day complications, and time to recurrence. Multivariable logistic regression assessed the independent risk factors. Of 2681 endometriosis cases, 142 [5.3%of total, mean age 35.4 (31.0; 39.0) years, 73.9% stage IV] underwent CRE excision (superficial partial = 66.9%,segmental = 27.5%,full thickness = 1.41%). Minor complications (14.8%) were associated with blood loss [150 (112; 288) vs. 100 (50.0; 200) mls, p = 0.046], Sigmoid involvement [45.5% vs. 12.2%, HR 5.89 (1.4; 22.5), p = 0.01], stoma formation[52.6% vs. 8.9%, HR 10.9 (3.65; 34.1), p < 0.001], and segmental resection [38.5% vs. 5.8%, HR 9.75 (3.54; 30.4), p < 0.001]. Superficial, partial-thickness resections were associated with decreased risk [(4.2% vs. 36.2%), HR 0.08 (0.02; 0.24), p < 0.001]. Factors associated with major complications (8.5%) were blood loss [250 (100; 400) vs. 100 (50.0; 200) mls, p = 0.03], open surgery [31.6% vs. 4.9%, HR 8.74 (2.36; 32.9), p = 0.001], stomaformation [42% vs. 3.3%, HR 20.3 (5.41; 90.0), p < 0.001], and segmental colectomy [28.2% vs. 0.9%, HR 34.6 (6.25; 876), p < 0.001]. Partial-thickness resection was associated with decreased risk ([.05% vs. 23.4%, HR 8.74 (2.36; 32.9), p < 0.001]. 19.1% experienced recurrence. Open surgery [5.2% vs. 21.3%, HR 0.14 (0.02; 1.05), p = 0.027] and superficial partial thickness excision [23.4% vs. 10.6%, HR 2.86 (1.08; 7.59), p = 0.027] were associated. Segmental resection was associated with decreasedrecurrence risk [7.6% vs. 23.5%, HR 0.27 (0.08; 0.91), p = 0.024]. Limiting resection to partial-thickness or full-thickness disc excision compared to bowel resection may improve complications but increase recurrence risk.

Prognostic value of baseline MRI features in patients treated with thermal ablation for hepatocellular carcinoma

PurposeTo investigate prognostic value of baseline MRI features for time-to-recurrence (TTR) and local recurrence in patients with early hepatocellular carcinoma (HCC). MethodBaseline and follow-up images of 88 patients treated with thermal ablation followed by adjuvant sorafenib or matching placebo due to HCC within the phase II prospective randomized trial (SORAMIC) were included. Baseline MRI images were evaluated in terms of atypical enhancement (lack of wash-in or wash-out), lesion diameter, tumor capsule, peritumoral enhancement on arterial phase, intratumoral fat, irregular margin, satellite lesions, and peritumoral hypointensity on hepatobiliary phase. Prognostic value of these features for TTR and local recurrence were assessed with univariable and multivariable Cox proportional hazard models. ResultsRecurrence at any location was diagnosed during follow-up in 30 patients, and the median TTR was 16.4 (95% CI, 15 – NA) months. The presence of more than one lesion (p = 0.028) and peritumoral hypointensity on hepatobiliary phase images (p = 0.012) at baseline were significantly associated with shorter TTR in univariable analysis. AFP > 15 mg/dL (p = 0.084), and history of cirrhosis (p = 0.099) were marginally non-significant. Peritumoral hypointensity on hepatobiliary phase images was the only significant risk factor for recurrence in multivariable analysis (p = 0.003).Local recurrence (adjacent to thermal scar) was diagnosed in eleven (8.3%) out of 132 lesions that underwent thermal ablation. The only significant risk factor for local recurrence was a lesion diameter larger than 3 cm (22.2% vs. 4.5%, p = 0.007). ConclusionsPeritumoral hypointensity on hepatobiliary phase can serve as imaging biomarker to identify increased recurrence risk in patients undergoing thermal ablation for early-stage HCC.

Trazodone-Induced Priapism and Increased Recurrence Risk With Antipsychotics

Trazodone-Induced Priapism and Increased Recurrence Risk With Antipsychotics

GWAS-identified telomere length associated genetic variants predict risk of recurrence of HPV-positive oropharyngeal cancer after definitive radiotherapy.

Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP). A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations. Of the 16TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3-11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5-4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival. Not applicable.

Transcriptional intra-tumour heterogeneity predicted by deep learning in routine breast histopathology slides provides independent prognostic information

BackgroundIntra-tumour heterogeneity (ITH) causes diagnostic challenges and increases the risk for disease recurrence. Quantification of ITH is challenging and has not been demonstrated in large studies. It has previously been shown that deep learning can enable spatially resolved prediction of molecular phenotypes from digital histopathology whole slide images (WSIs). Here we propose a novel method (Deep-ITH) to predict and measure ITH, and we evaluate its prognostic performance in breast cancer. MethodsDeep convolutional neural networks were used to spatially predict gene-expression (PAM50 set) from WSIs. For each predicted transcript, 12 measures of heterogeneity were extracted in the training data set (N = 931). A prognostic score to dichotomise patients into Deep-ITH low- and high-risk groups was established using an elastic-net regularised Cox proportional hazards model (recurrence-free survival). Prognostic performance was evaluated in two independent data sets: SöS-BC-1 (N = 1358) and SCAN-B-Lund (N = 1262). ResultsWe observed an increase in risk of recurrence in the high-risk group with hazard ratio (HR) 2.11 (95%CI:1.22–3.60; p = 0.007) using nested cross-validation. Subgroup analyses confirmed the prognostic performance in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, grade 3, and large tumour subgroups. The prognostic value was confirmed in the independent SöS-BC-1 cohort (HR=1.84; 95%CI:1.03–3.3; p = 3.99 ×10−2). In the other external cohort, significant HR was observed in the subgroup of histological grade 2 patients, as well as in the subgroup of patients with small tumours (<20 mm). ConclusionWe developed a novel method for an automated, scalable, and cost-efficient measure of ITH from WSIs that provides independent prognostic value for breast cancer. SignificanceTranscriptional ITH predicted by deep learning models enables prediction of patient survival from routine histopathology WSIs in breast cancer.

Meningioma Grading beyond Histopathology: Relevance of Epigenetic and Genetic Features to Predict Clinical Outcome.

Meningiomas are common tumors of the central nervous system. The grading system established by the World Health Organization (WHO) has recently included pTERT mutations and CDKN2A/B homozygous deletions as criteria for grade 3, owing to their association with increased recurrence risk. However, these alterations identify only a portion of meningiomas that are devoid of histopathological malignancy and are prone to recurrence. Over the last few years, the integration of epigenetic, genetic, transcriptomic, and proteomic profiling has led to the identification of three main groups of meningiomas with distinct clinical outcomes and peculiar genetic features. Meningiomas in the first group have the best prognosis, are distinguished by the lack of NF2 alterations and chromosomal instability, and may be responsive to cytotoxic drugs. Meningiomas in the second group have an intermediate prognosis and are characterized by NF2 alterations, mild chromosomal instability, and enrichment in immune cells. Meningiomas in the third group had the worst prognosis, displayed NF2 alterations coupled with high chromosomal instability, and were resistant to cytotoxic treatment. Classification into these three groups predicts the recurrence risk of meningiomas more accurately than WHO grading and could be applicable in routine practice, owing to the possibility of distinguishing the different groups by specific immunostaining.

Video-EEG-monitoring to guide antiseizure medication withdrawal

BackgroundDiscontinuing anti-seizure medication (ASM) should be considered in persons with epilepsy with long-term seizure freedom. Clinicians should also pursue ASM withdrawal in persons with one-time seizures without increased recurrence risk and those with suspected non-epileptic events. However, ASM withdrawal is associated with the risk of recurring seizures. Monitored ASM withdrawal in an epilepsy monitoring unit (EMU) could help better evaluate the risk of seizure recurrence. Here, we investigate the practice of EMU-guided ASM withdrawal, assess its indications, and aim to determine positive and negative predictors for successful withdrawal.MethodsWe screened the medical records of all patients admitted to our EMU between November 1, 2019, and October 31, 2021, and included patients of at least 18 years admitted with the aim of permanent ASM withdrawal. We defined four groups of withdrawal indications: (1) long-term seizure freedom; (2) suspected non-epileptic events; (3) history of epileptic seizures but not fulfilling diagnostic criteria of epilepsy; and (4) seizure-freedom after epilepsy surgery. Successful withdrawal was defined according to the following criteria: no recoding of (sub)clinical seizure activity during VEM (groups 1, 2, and 3), patients did not meet the International League Against Epilepsy (ILAE) definition of epilepsy (groups 2 and 3) [14], and patients were discharged without ongoing ASM treatment (all groups). We also evaluated the prediction model by Lamberink et al. (LPM) for the risk of seizure recurrence in groups 1 and 3.Results55/651 (8.6%) patients fulfilled the inclusion criteria. Withdrawal indications were distributed as follows; group 1: 2/55 (3.6%); group 2: 44/55 (80%); group 3: 9/55 (16,4%); group 4: 0/55. Overall, ASM withdrawal was successful in 90.9%. The sensitivity of the LPM for a 2-year 50% relapse risk threshold was 75%, the specificity 33.3%; for a 5-year relapse risk respectively 12.5% and 33.3%, suggesting that the model is not suitable for risk assessment in patients with one-time seizures or acute-symptomatic seizures, who constituted most of the evaluated patients.ConclusionsOur study suggests that EMU-guided ASM withdrawal could be a helpful tool to support clinical decision-making and improve patient safety. Prospective, randomized trials should further evaluate this method in the future.

Diagnostic accuracy of apparent diffusion coefficient (ADC) in differentiating low- and high-grade gliomas, taking histopathology as the gold standard

Gliomas are known to be one of the most grievous malignant central nervous system (CNS) tumors and have a high mortality rate with a low survival rate severe disability and increase risk of recurrence. Aim of his study is to determine the diagnostic accuracy of apparent diffusion coefficient (ADC) in differentiating low-grade and high-grade gliomas, taking histopathology as the gold standard. It is a Cross-sectional validation study conducted at the Armed Forces Institute of Radiology and Imaging, (AFIRI) Rawalpindi, Pakistan from 28th February 2022 to 27th August 2022. Materials and methods: A total of 215 patients with focal brain lesions of age 25-65 years of either gender were included. Patients with a cardiac pacemaker, breastfeeding females, de-myelinating lesions and malignant infiltrates, and renal failure were excluded. Then diffusion-weighted magnetic resonance imaging was performed on each patient by using a 1.5 Tesla MR system. The area of greatest diffusion restriction (lowest ADC) within the solid tumor component was identified while avoiding areas of peritumoral edema. Results of ADC were interpreted by a consultant radiologist (at least 5 years of post-fellowship experience) for high or low-grade glioma. After this, each patient has undergone a biopsy in the concerned ward, and histopathology results were compared with ADC findings. Results: Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of apparent diffusion coefficient (ADC) in differentiating low- and high-grade gliomas, taking histopathology as the gold standard was 93.65%, 87.64%, 91.47%, 90.70% and 91.16% respectively. Conclusion: This study concluded that apparent diffusion coefficient (ADC) is the non-invasive modality of choice with high diagnostic accuracy in differentiating low- and high-grade gliomas.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world

BackgroundThe risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. MethodsWe used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50–99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. ResultsAmong 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%–5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. ConclusionsIn patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.

Abstract P2-03-01: Sarcopenia on baseline imaging is associated with toxicity-related discontinuation of endocrine therapy in women with early-stage hormone-positive breast cancer

Abstract Background Adjuvant endocrine therapy (ET) is standard of care in women with hormone receptor-positive (HR+) breast cancer (BC) with the goal to reduce recurrence. However, early discontinuation of ET occurs in 30-40% of women, largely attributable to toxicity, and leads to increased recurrence risk. There is considerable overlap in risk factors that predict toxicity from ET and chemotherapy, including age, co-morbidities, and geriatric conditions. Baseline low skeletal muscle area (SMA) on chest computed tomography (CT) is a surrogate marker for sarcopenia and predicts for significant toxicity and intolerance to chemotherapy in women with BC. No study has assessed the association of sarcopenia with toxicity-related discontinuation of ET in women with early-stage HR+ BC. Methods This single center retrospective cohort study included consecutive women with Stage 0-II HR+ BC who received ET and adjuvant radiotherapy (RT) from 01/2011-12/2017. Inclusion required a minimum of 5-year clinical follow-up after diagnosis. We used a validated deep learning pipeline to quantify SMA (cm2) at the tenth thoracic (T10) vertebral body on existing RT planning CT. The skeletal muscle index (SMI [cm2/m2] = SMA/(patient height (m))2) was calculated to adjust for patient height. Sarcopenia was defined as SMI&amp;lt; 32.3 cm2/m2, based on a previously validated independent cohort of young healthy women. The primary endpoint was toxicity-related discontinuation of ET less than 60 months after initiation of ET. Secondary endpoints included any NCI CTCAE v5.0 Grade 3-5 toxicity from ET and ipsilateral breast tumor recurrence. We assessed associations between ET discontinuation and SMI (continuous), as well as thoracic sarcopenia (dichotomous), using logistic regression adjusting for baseline characteristics. We used cox proportional hazards regression to assess disease-free survival (DFS), defined as ipsilateral breast tumor recurrence, locoregional recurrence, or distant metastasis adjusting for baseline and treatment characteristics. Results A total of 265 women (median age 67 years) met inclusion criteria. The majority of women had a comorbidity index of 0-1 (89%) and were Caucasian (89%). The median follow-up was 82 months, 5-year overall survival was 96% and 5-year DFS was 94%. Diagnoses included DCIS (12%), IDC (76%), or ILC (12%); most were T1 (69%) or T2 (18%) and N0 (85%), ER-positive (100%), PR-positive (85%), or HER2-negative (9%). Most common ET type was anastrozole (63%), letrozole (16%), and tamoxifen (17%). SMI (continuous) was not associated with older age, Charlson Comorbidity Index (CCI), race, or tumor stage. A total of 64 (24%) women experienced toxicity-related early discontinuation of ET. On multivariate analysis (MVA), lower SMI was associated with increased toxicity-related early discontinuation of ET (Odds Ratio [OR] 0.89 per 1 cm2/m2 SMI, p=0.001) independent of age, CCI, ET type, or receipt of adjuvant chemotherapy. Lower SMI was associated with higher risk of grade 3-5 toxicity from ET (OR 0.89 per 1 unit SMI, p=0.001) independent of age, CCI, ET type, or receipt of adjuvant chemotherapy. On MVA, sarcopenia was associated with higher risk of toxicity-related early discontinuation of ET (OR 2.43, p=0.019). DFS was associated with toxicity-related early discontinuation of ET (HR 8.06, p=0.005), grade 3 histology (HR 1.42, p=0.042), and multifocal disease (HR 2.55, p=0.040), but not age, histology, stage, or lymphovascular invasion (p&amp;gt;.05 for all). Conclusion Low baseline thoracic skeletal muscle is associated with toxicity-related early ET discontinuation in women with early-stage HR+ BC. Further studies should attempt to generalize this association to all HR+ BC who are candidates for ET. High-risk patients may be candidates for aggressive symptom management or alternative adjuvant therapies. Citation Format: Anurag Saraf, Ismail Tahir, Bonnie Hu, Anna-Sophia Dietrich, Paul Erik Tonnesen, Greg Sharp, Gayle Tillman, Florian Fintelmann, Rachel Jimenez. Sarcopenia on baseline imaging is associated with toxicity-related discontinuation of endocrine therapy in women with early-stage hormone-positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-01.

Exploring phenotypes of deep vein thrombosis in relation to clinical outcomes beyond recurrence

BackgroundDeep vein thrombosis (DVT) is a multifactorial disease with several outcomes, but current classifications solely stratify it based on recurrence risk. ObjectivesWe aimed to identify DVT phenotypes and assess their relation to recurrent venous thromboembolism (VTE), postthrombotic syndrome, arterial events, and cancer. Patients/MethodsHierarchical clustering was performed on a DVT cohort with a follow-up of up to 5 years using 23 baseline characteristics. Phenotypes were summarized by discriminative characteristics. Hazard ratios (HRs) were calculated using Cox regression; the recurrence risk was adjusted for the anticoagulant therapy duration. The study was carried out in accordance with the Declaration of Helsinki and approved by the medical ethics committee. ResultsIn total, 825 patients were clustered into 4 phenotypes: 1. women using estrogen therapy (n = 112); 2. patients with a cardiovascular risk profile (n = 268); 3. patients with previous VTE (n = 128); and 4. patients without discriminant characteristics (n = 317). Overall, the risks of recurrence, postthrombotic syndrome, arterial events, and cancer were low in phenotype 1 (reference), intermediate in phenotype 4 (HR: 4.6, 1.2, 2.2, 1.8), and high in phenotypes 2 (HR: 6.1, 1.6, 4.5, 2.9) and 3 (HR: 5.7, 2.5, 2.3, 3.7). ConclusionsThis study identified 4 distinct phenotypes among patients with DVT that are not only associated with the increasing recurrence risk but also with outcomes beyond recurrence. Our results thereby highlight the limitations of current risk stratifications that stratify based on the predictors of the recurrence risk only. Overall, risks were lowest in women using estrogen therapy and highest in patients with a cardiovascular risk profile. These findings might inform a more personalized approach to clinical management.

Abstract WMP77: High Early Recurrence In Symptomatic Intracranial Atherosclerosis Treated Medically In The Real World Compared To Clinical Trials

Background: While optimizing medical treatment contributed to the low recurrence risk seen in SAMMPRIS medical arm, other factors such as delayed enrollment may have contributed to this low event rate. In this study, we aim to determine the 30-day recurrence risk in a real-world setting in patients with symptomatic intracranial atherosclerosis. Methods: We used a stroke registry of a comprehensive stroke center to identify hospitalized patients with acute ischemic stroke in the setting of symptomatic intracranial atherosclerosis of the ICA, M1, vertebral, or basilar with 50-99% luminal narrowing. We excluded patients with a clear indication for anticoagulation and those who received endovascular treatment. The outcome was recurrent stroke attributed to the affected artery within 30-days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. Results: Among 131 symptomatic 50-99% intracranial stenosis hospitalizations over 3 years, 66 patients met the inclusion criteria. The mean age was 71.9 years and 51.5% were men; 75.8% were treated with best medical management (dual antiplatelet therapy/high intensity stain therapy). Over 30-day follow-up, 21.2 % had recurrent stroke, 57.1% (8/14) occurred within first 7 days. The recurrence risk was similar to another real world ICAD cohort, and higher than that seen in SAMMPRIS (Figure). While maximal medical treatment was the only factor associated with a lower rate of recurrence (OR 0.32 95% CI 0.09-1.12, p = 0.075), the recurrence rate in patients treated with maximal medical therapy (16.0%, 95% CI 8.1-29.3%) and those SAMMPRIS eligible (17.6%, 95% CI 7.9-34.9%) remained elevated. Conclusions: In patients with symptomatic ICAS, the real-world recurrence is higher than that seen in clinical trials, despite optimally using the same medical treatment strategies. This may suggest that the low risk of recurrence achieved in clinical trials may not apply to real world practice.

Circumferential Resection Margin is Associated With Distant Metastasis After Rectal Cancer Surgery: A Nation-wide Population-based Study Cohort.

To evaluate circumferential resection margin (CRM) as a risk factor for distant metastasis (DM) in rectal cancer. The treatment of rectal cancer has evolved over the last decades. Surgical radicality is considered the most important factor in preventing recurrences including local and distant. CRM ≤1.0 mm is considered to increase recurrence risk. This study explores the risk of DM in relation to exact CRM. All patients treated with abdominal resection surgery for rectal cancer between 2005 and 2013 in Sweden were eligible for inclusion in this retrospective study. Primary endpoint was DM. Twelve thousand one hundred forty-six cases were identified. Eight thousand five hundred ninety-three cases were analyzed after exclusion. Seven hundred seventeen (8.6%) patients had CRM ≤1.0mm and 7577 (91.4%) patients had CRM >1.0 mm. DM recurrence rate at 5 years was 42.1% (95% CI 32.5-50.3), 31.5% (95% CI 27.3-35.5), 25.8% (95% Confidence Interval (CI) 16.2-34.4), and 19.5% (95% CI 18.5-19.5) when CRM was 0.0 mm, 0.1 to 1.0 mm, 1.1 to 1.9 mm, and CRM ≥2mm, respectively. Multivariable analysis revealed higher DM risk in CRM 0.0-1.0 mm versus >1.0 mm (hazard ratio 1.30, 95% CI 1.05-1.60; P = 0.015). No significant difference in DM risk in CRM 1.1-1.9 mm versus ≥2.0 mm (hazard ratio 0.66, 95% CI 0.34-1.28; P = 0.224) could be detected. The risk of DM decreases with increasing CRM. Moreover, CRM ≤1.0 mm is a significant risk factor for DM. Thus, CRM is a dominant factor when discussing risk of DM after rectal cancer surgery.

Technical note: Noninvasive monitoring of normal tissue radiation damage using spectral quantitative ultrasound spectroscopy.

While radiation therapy (RT) is a critical component of breast cancer therapy and is known to decrease overall local recurrence rates, recent studies have shown that normal tissue radiation damage may increase recurrence risk. Fibrosis is a well-known consequence of RT, but the specific sequence of molecular and mechanical changes induced by RT remains poorly understood. To improve cancer therapy outcomes, there is a need to understand the role of the irradiated tissue microenvironment in tumor recurrence. This study seeks to evaluate the use of spectral quantitative ultrasound (spectral QUS) for real time determination of the normal tissue characteristic radiation response and to correlate these results to molecular features in irradiated tissues. Murine mammary fat pads (MFPs) were irradiated to 20Gy, and spectral QUS was used to analyze tissue physical properties pre-irradiation as well as at 1, 5, and 10 days post-irradiation. Tissues were processed for scanning electron microscopy imaging as well as histological and immunohistochemical staining to evaluate morphology and structure. Tissue morphological and structural changes were observed non-invasively following radiation using mid-band fit (MBF), spectral slope (SS), and spectral intercept (SI) measurements obtained from spectral QUS. Statistically significant shifts in MBF and SI indicate structural tissue changes in real time, which matched histological observations. Radiation damage was indicated by increased adipose tissue density and extracellular matrix (ECM) deposition. Our findings demonstrate the potential of using spectral QUS to noninvasively evaluate normal tissue changes resulting from radiation damage. This supports further pre-clinical studies to determine how the tissue microenvironment and physical properties change in response to therapy, which may be important for improving treatment strategies.