Smaller Tumor Size Research Articles

Revisiting the Relationship Between Tumor Size and Risk in Well-Differentiated Thyroid Cancer.

Introduction: Large tumor size is associated with poorer outcomes in well-differentiated thyroid cancer, yet it remains unclear whether size >4 cm alone confers increased risk, independent of other markers of aggressive disease. The goal of this study was to assess the relationship between tumor size, other high-risk histopathological features, and survival in well-differentiated thyroid cancer and to evaluate the significance of 4 cm as a cutoff for management decisions. Methods: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2015) and categorized by tumor size (i.e., small [≤4 cm] or large [>4 cm]) and presence of high-risk histopathological features (e.g., extrathyroidal extension). First, propensity score matching was used to identify patients who were similar across all other observed characteristics except for small versus large tumor size, and a multivariable Cox proportional hazards model was used to estimate the relationship between tumor size and survival. Second, we assessed whether the presence of high-risk features demonstrates conditional effects on survival based on the presence of tumor size >4 cm using an interaction term. Finally, additional models assessed the relationship between incremental 1 cm increases in tumor size and survival. Analyses were repeated using a validation cohort from the Surveillance, Epidemiology, and End Results Program (2008-2013). Results: Of 193,133 patients in the primary cohort, 7.9% had tumors >4 cm, and 30% had at least one high-risk feature. After matching, tumor size >4 cm was independently associated with worse survival (HR 1.63, p < 0.001). However, tumor size >4 cm and one or more other high-risk features together yielded worse survival than either size >4 cm alone (MMD: 0.70, p < 0.001) or other high-risk features alone (MMD: 0.49, p < 0.001). When assessed in 1 cm increments, the largest increases in hazard of death occurred at 2 cm and 5 cm, not 4 cm. Results from the validation cohort were largely consistent with our primary findings. Conclusions: Concomitant high-risk features confer worse survival than large tumor size alone, and a 4 cm cutoff is not associated with the greatest increase in risk. These findings support a more nuanced approach to tumor size in the management of well-differentiated thyroid cancer.

Incidence and outcomes of Merkel cell carcinoma related to Merkel cell polyomavirus status in Iceland in 1981-2023

BackgroundImpact of Merkel cell polyomavirus (MCPyV) associated Merkel cell carcinoma (MCC) has not been assessed in the Icelandic population, nor in a whole population elsewhere. ObjectivesThe primary objective was to assess trends in the incidence of MCC in Iceland and the association with MCPyV. Secondary objectives aimed to analyze MCC outcomes. MethodsIn this retrospective cohort study, patients diagnosed with MCC between 1981 and 2021 were identified from the Icelandic Cancer Registry. Patients were separated into two groups based on MCPyV immunochemistry staining. Age-standardized incidence was calculated and Joinpoint analysis was used to assess incidence trends. A Cox proportional hazards model was used to assess survival differences between the two groups. ResultsOverall incidence of MCC increased from 0.015 to 0.26 per 100,000 persons, though the incidence of MCPyV positive cases recently decreased while negative cases increased. MCPyV negative tumors were associated with sun exposure (p<0.01), a history of keratinocyte carcinoma, smaller tumor size, and lower overall survival. LimitationsEven with population level data, comprehensively investigating associations with MCC is difficult due to its rarity. ConclusionMCPyV negative MCC tumors were associated with lower survival despite smaller tumor size. Thus, MCPyV status could be an important prognostic biomarker.

Criteria for predicting the development of recurrent peripheral nerve sheas tumors

Peripheral nerve sheaths tumors (PNST) account for about 8 % of all nervous system cancers. The relapse rate ranges from 17.3 to 26.4 %, showing an upward trend. The causes and provoking factors for the development of relapses of PNST have not been fully studied. Purpose of the study: to establish criteria for predicting recurrence of PNST. Material and Methods. The study included 122 patients who were treated at the Department of Spine and Peripheral Nerve Surgery of A.I. Polenov Russian Research Neurosurgical Institute from 2009 to 2021. Among them, there were 87 (71.3 %) patients with primary PNST and 35 (28.7 %) patients with recurrent PNST. All patients underwent MRI and ENMG both before and after surgery. An immunohistochemical study of Ki67 and SO X10 markers was performed. Results. The majority of relapses occured within 1 year after surgery. In cases with radical removal of PNST, the risk of relapse was: 28.6 % for schwannomas 28.6 %, 37.1 % for neurofibromas and 34.3 % for MP NST 34.3 % (p≥0.05). The risk of developing relapse of PNST was 2.9 times higher in patients aged ≥49 years than in patients aged ≤48 years (p&lt;0.004). The larger the initial size of the tumor, the higher the risk of relapse in the late postoperative period. The risk of developing relapse of MP NST was 8.79 times higher in patients with tumor size of greater than 11.5 cm than in patients with smaller tumor size (p&lt;0.02). The of Ki67 level above 4.85 % in schwannomas and above 5.17 % in neurofibromas can predict relapse of PNST (p&lt;0.05). Loss of SO X10 protein expression was associated with an increase in histological anaplasia of the tumor, which causes a high risk of relapse and an unfavorable clinical course of the disease. Conclusion. Despite radical (total) resection of PNST, the risk of relapse remains high. The pathological type of tumor, its size, levels of SO X10 and Ki67 markers, patient’s age, degree of preoperative neurological deficit and extent of surgery are significant criteria for predicting the development of relapse of PNST.

Prognostic factors and impact of bone invasion in T1/2 size (

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered.

Immunohistochemical Expression of Caspase1 and Epidermal Growth Factor Receptor in Invasive Breast Carcinoma and Their Biological and Prognostic Associations.

Despite advances in breast carcinoma therapies, drug resistance mechanisms as anti-apoptosis and anti-pyroptosis limit the application of these therapies. This work assesses the immunohistochemical (IHC) expression of Caspase1 and EGFR in breast carcinoma and analyzes their clinicopathological associations as prognostic markers and potential therapeutic targets. Caspase1/EGFR expression patterns are utilized to specify breast carcinoma patients who may benefit from these therapies. After reviewing the hematoxylin and eosin-stained slides and the routine breast carcinoma IHC stains (estrogen receptors, progesterone receptors, HER2/NEU, Ki-67) by two pathologists and preparation of tissue microarray blocks, anti-Caspase-1 and EGFR IHC staining was performed using Horseradish Peroxidase (HRP) technique. Intensity and percentage-based scoring was applied dividing the 153 included breast carcinomas into Caspase1-negative and positive expression groups; and EGFR low and overexpression groups. Groups were statistically analyzed in relation to age, tumor size, histological and molecular subtype, grade, nodal status, metastasis/recurrence, TNM stage and Ki-67 proliferation index. Kaplan-Meier's analysis was used to compare disease-free survival (DFS) and overall survival (OS). Combined patterns based on Caspase1 and EGFR expression status were created to stratify patients into prognostic groups. Caspase1 was positive in 54.2% of breast carcinomas and its positivity was significantly associated with smaller tumor size, absence of metastasis/recurrence, luminal A and B molecular subtypes and longer OS (p<0.05). EGFR overexpression was detected in 32.7% of carcinomas and was significantly associated with larger tumor size, TNBLBC and a shorter OS (p<0.05). Caspase1-negative/EGFR-overexpression pattern comprised 14.4% of carcinomas and had the worst prognostic associations including larger tumor size, metastasis/recurrence, TNBLBC subtype and shortest OS (p=0.002, 0.002, 0.004 and ≤0.001 respectively). Conclusions: Combined Caspase1/EGFR IHC expression may provide a tool for selection of patients who benefit from combined EGFR-inhibitors with miR-155-5p down-regulators or photodynamic therapy via induction of apoptosis/pyroptosis in EGFR-overexpression carcinomas through enhanced Caspase1 signaling.

Clinical Characteristics and Outcomes of Neonatal Hepatoblastoma: A Single Center Study

ObjectiveHepatoblastoma (HB) diagnosed within one month following birth qualifies for a diagnosis of neonatal HB, whose prognosis is reportedly controversial, and its treatment is challenging. This study discussed the diagnosis, treatment, and outcomes of neonatal HB at a single center so as to enhance its overall management in the future. MethodsThe clinical information of babies diagnosed with neonatal HB at our center from August 2009 to September 2023 were retrospectively analyzed for demographics, clinical features, therapy, and outcomes. The outcomes were estimated by the Kaplan–Meier analysis method. ResultsThe study comprised 79 patients aged less than one year old, among which 14 had neonatal HB whereas 65 were non-neonatal HB patients. No differences were found between groups regarding gender, birth weight, delivery details, parental age, clinical signs, or treatment strategies. Neonatal HB patients were more likely to have PRETEXT I-II, smaller tumor size, congenital diseases, and lower risk tumor grade (p < 0.05). Additionally, the AFP levels of all neonatal HB patients were greater than 10,000 ng/ml (p = 0.009) and they had higher levels of ferritin (p = 0.003) and hemoglobin (p = 0.021), but lower levels of serum total proteins (p = 0.001). The three-year survival rate (100% vs 90.8%) and three-year event-free survival rate (100% vs 86.2%) in the neonatal HB group were higher than the non-neonatal HB group. ConclusionNeonatal HB patients have unique clinical features and can achieve an excellent prognosis following combined treatment with surgery and chemotherapy. Tumor resection, when carefully performed, was safe even in babies younger than one months old. Further and long-term studies are needed from a larger neonatal HB population. Level of EvidenceLevel III.

The feasibility of visualizing and quantifying muscle changes in postoperative oral cancer patients using Quantitative Muscle Ultrasound (QMUS)

PurposeQuantitative muscle ultrasound (QMUS) is a patient friendly tool for examining orofacial muscles. Resection of tissue can have an effect on the architecture and function of these muscles. The aim of this study is to investigate the feasibility of visualizing and quantifying muscle changes in postoperative oral cancer patients and to relate the findings to tumor and patient characteristics.MethodsAdult patients with a resected first primary pT1 or T2 oral squamous cell carcinoma, at least one year post operatively, where included. Ultrasound data were collected of the geniohyoid muscle, digastric muscles, masseter muscle, transverse muscle and genioglossus muscle. Ultrasound images were labeled as clearly visible, questionable or unclear. Of the clear muscles, echogenicity and muscle thickness were measured.Results37 patients were included. The masseter muscle was clearly visible in all ultrasound images, both intrinsic tongue muscles had the lowest visibility (45.9%). There was a significant correlation between visibility and tumor localization for the genioglossus (p = 0.029). Age correlated with the visibility of the genioglossus muscle, BMI with the genioglossus and transverse muscles. Echogenicity and muscle thickness of the clearly identified muscles did not differ from normative values.ConclusionQMUS of orofacial muscles is feasible in postoperative oral cancer patients with relatively small tumor sizes. Tongue resections negatively affected the visibility of the two intrinsic tongue muscles. These preliminary results for particular muscles indicate that the use of ultrasound might be promising in oral cancer patients to help determine targeted goals in post-operative rehabilitation.

HGG-35. SIGNIFICANT RESPONSE TO LAROTRECTINIB AS FIRST LINE THERAPY IN INFANT WITH INFANT-TYPE HEMISPHERIC GLIOMA

Abstract BACKGROUND Infant-type hemispheric gliomas represent a recent WHO classification of high grade pediatric brain tumors that are often characterized by NTRK, ROS1, MET or ALK fusions. Novel agents may target their driver mutations but are not yet considered front line therapy. METHODS Patient data was reviewed retrospectively through chart review. RESULTS A 7 day old male infant who presented with vomiting, shaking and a full fontanelle was found to have a 8.7 x 7.2 x 9.3 cm solid and cystic mass with internal hemorrhage in the right parietal and occipital lobes associated with significant mass effect and midline shift. He underwent VP shunt placement and tumor biopsy, but later developed seizures and declining mental status. Cyst decompression was used as stabilizing measure. Due to his very small size and tenuous clinical status full tumor resection was not feasible at that time. Pathology revealed an infant-type hemispheric glioma with ETV6-NTRK3 fusion. Although cytogenetic testing for NTRK alterations was negative, the fusion was confirmed by NGS. Given his age and the risks for electrolyte imbalances and cytopenias in a patient with recent hemorrhage, we elected to treat with Larotrectinib instead of traditional cytotoxic chemotherapy. He had notable disease response within 8 weeks and remains on drug 18 months later with continued response. His tumor now measures 2 x 1.5 x 1.6 cm. He has had one grade 3 toxicity with neutropenia, which was likely impacted by viral bone marrow suppression. He is currently meeting most developmental milestones but does have orthotics and sees speech therapy. CONCLUSIONS Targeted agents may represent a viable front line therapy to decrease tumor mass and temporize very young patients until they can undergo definitive resection and therapy. Future clinical trials will need to compare efficacy to current standards of care.

QOL-50. THE ROLE OF TUMOR SIZE IN COGNITIVE FUNCTIONING AMONG SURVIVORS TREATED FOR MEDULLOBLASTOMA

Abstract BACKGROUND Medical and treatment variables, including presence of post-operative cerebellar mutism syndrome (CMS), shunt placement, craniospinal radiation, and total radiotherapy (RT) dose, have been evaluated as potential risk factors for adverse cognitive effects among pediatric patients diagnosed and treated for medulloblastoma. Larger brain tumor size is associated with increased risk of medical complications, but cognitive risk of larger tumor size remains unknown. METHODS Cognitive scores were examined for 40 participants diagnosed and treated for medulloblastoma. The age-appropriate Wechsler Intelligence Scale was administered at the start of RT and up to 10 years post-RT (M=4.96, SD=3.78). A total of 162 evaluations were examined across participants. Linear mixed models examined change in Wechsler Index scores over time since RT based on tumor size, which was dichotomized at the median diameter (small ≤4.6cm versus large &amp;gt;4.6cm), covarying for maternal education, total RT dose, and presence of CMS. RESULTS Patients (72.5% male) were diagnosed with medulloblastoma and began RT at a mean age of 8.89 years. Groups did not differ on demographic or medical variables with the exception of presence/absence of CMS, with a higher proportion of patients diagnosed with CMS having large-size tumors (40%) versus small-size tumors (5%). Tumor size did not predict change in IQ, working memory, or processing speed performance over time since RT after accounting for covariates. CMS was associated with significant decline in processing speed (p&amp;lt;.001) and IQ over time (p&amp;lt;.05); RT dose was associated with significant working memory and IQ decline (both p&amp;lt;.05); and maternal education was associated with decline in processing speed, working memory, and IQ (all p&amp;lt;.05). CONCLUSIONS While tumor size may be associated with treatment intensity and other medical risk factors, CMS and RT dose significantly increase cognitive risk, independent of tumor size. Lower socioeconomic status also increases cognitive risk post-RT, which may illuminate pathways for prevention and intervention efforts.

Surgical management of ovarian masses in children and adolescents: experience of an academic institution in France.

Surgical management of ovarian masses in girls still challenging. The aim of the study is to report an 8-year experience in managing children with ovarian masses, and to demonstrate the advantages and the limitations of laparoscopy for such lesions. Data of girls aged less than 18years operated because of an ovarian mass between January 2015 and February 2023 were retrospectively reviewed. Patients were divided into two groups: group A including children operated by laparoscopy, and Group B of patients who underwent open surgery. Eighty-eight children were enrolled. Laparoscopy was performed in 56 patients (63.6%). Group A patients had smaller tumor size (53.6±38.5 vs. 122.2±75.4mm, P<0.0001), shorter operative time (50.4±20.3 vs. 71.5±36.5min, P = 0.004), reduced length of hospital stay (1.4±1.1 vs. 3±2.3days, P<0.0001), and absence of postoperative complications. Only 3 cases (5.7%) of recurrence were seen exclusively within patients followed for benign tumors during a mean follow-up period of 4.6±3years. Laparoscopy should be done in benign ovarian lesions or/and if a torsion is seen. For tumors at high risk of malignancy, laparoscopy can be performed to establish a clear macroscopic diagnosis, for staging of the disease, and resection of small tumors. Conversion to open surgery is indicated in case of doubt.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer

BackgroundTo determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC).MethodsWe reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors.ResultsEGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861–0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042–0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type.ConclusionNon-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.

Current landscape of primary small bowel leiomyosarcoma: cases report and a decade of insights

The incidence of leiomyosarcoma (LMS) is about 4–5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (&amp;lt; 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.

A machine learning-based approach to predict energy layer for each field in spot-scanning proton arc therapy for lung cancer: A feasibility study.

Determining the optimal energy layer (EL) for each field, under considering both dose constraints and delivery efficiency, is crucial to promoting the development of proton arc therapy (PAT) technology. This study aimed to explore the feasibility and potential clinical benefits of utilizing machine learning (ML) technique to automatically select EL for each field in PAT plans of lung cancer. Proton Bragg peak position (BPP) was employed to characterize EL. The ground truth BPPs for each field were determined using the modified ELO-SPAT framework. Features in geometric, water-equivalent thicknesses (WET) and beamlet were defined and extracted. By analyzing the relationship between the extracted features and ground truth, a polynomial regression model with L2-norm regularization (Ridge regression) was constructed and trained. The performance of the regression model was reported as an error between the predictions and the ground truth. Besides, the predictions were used to make PAT plans (PAT_PRED). These plans were compared with those using the ground truth BPPs (PAT_TRUTH) and the mid-WET of the target volumes (PAT_MID) in terms of relative biological effectiveness-weighted dose (RWD) distributions. One hundred ten patients with lung cancer, a total of 7920 samples, were enrolled retrospectively, with 5940 cases randomly selected as the training set and the remaining 1980 cases as the testing set. Nine patients (648 samples) were collected additionally to evaluate the regression model in terms of plan quality and robustness. With regard to the prediction errors, the root mean squared errors and mean absolute errors between the ML-predicted and ground truth BPPs for the testing set were 9.165 and 6.572mm, respectively, indicating differences of approximately two to three ELs. As for plan quality, the PAT_TRUTH and PAT_PRED plans performed similarly in terms of plan robustness, target coverage and organs at risk (OARs) protection, with differences smaller than 0.5Gy(RBE). This trend was also observed for dose conformity and uniformity. The PAT_MID plans produced the lowest robustness index and lowest doses to OARs, along with the highest heterogeneity index, indicating better protection for OARs, improved plan robustness, but compromised dose homogeneity. Additionally, for relatively small tumor sizes, the PAT_MID plan demonstrated a notably poor dose conformity index. Within this cohort under investigation, our study demonstrated the feasibility of using ML technique to predict ELs for each field, offering a fast (within 2 s) and memory-efficient reduced way to select ELs for PAT plan.

A comparative analysis of surgically excised hereditary and sporadic pheochromocytomas: Insights from a single-center experience.

Pheochromocytoma is a tumor that usually originating from adrenal medullary chromaffin cells and producing one or more catecholamines, can manifest as hereditary or sporadic. While the majority pheochromocytomas are sporadic, hereditary forms are often associated with genetic syndromes such as von Hippel-Lindau, multiple endocrine neoplasia type 2, and neurofibromatosis type 1. This study aims to analyze data from our series of surgically excited pheochromocytoma patients and compare the characteristics between hereditary and sporadic cases. We retrospectively evaluated 33 diagnosed pheochromocytoma patients, documenting clinical features, surgical complications, and tumor characteristics in both hereditary and sporadic cases. Among the patients, 21% (7 individuals) had hereditary pheochromocytoma, while 79% (26 individuals) had sporadic cases. During diagnosis, hereditary pheochromocytoma patients exhibited a significantly lower mean age compared to the sporadic group (26.4 ± 9.9 years vs. 50.4 ± 14.0 years; p < 0.001). The maximum tumor size was also lower in hereditary cases compared to sporadic cases (p = 0.004). Adrenal tumor localization analysis showed that 63.6% were right-sided, 24.2% were left-sided, and 12.1% were bilateral. Laboratory analysis revealed significantly higher urinary norepinephrine levels in hereditary pheochromocytoma patients (p = 0.021). Our findings suggest that hereditary pheochromocytoma cases are characterized by a younger age at diagnosis, smaller tumor size, and a higher prevalence of multiple bilateral adrenal adenomas. We recommend genetic testing for all pheochromocytoma patients, particularly those with early-onset disease and bilateral adrenal tumors.

Impact of tumor size on overall survival and cancer-specific survival of early-onset colon and rectal cancer: a retrospective cohort study

PurposeThis study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer.MethodsEarly-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan–Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer.ResultsSeventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan–Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm.ConclusionPatients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.

WDR61 ablation triggers R-loop accumulation and suppresses breast cancer progression.

Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R-loop, and loss of WDR61 leads to R-loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R-loop and counteracts endogenous DNA damage in tumor cells.

A clinicopathological-imaging nomogram for the prediction of pathological complete response in breast cancer cases administered neoadjuvant therapy

ObjectiveTo construct a user-friendly nomogram with MRI and clinicopathological parameters for the prediction of pathological complete response (pCR) after neoadjuvant therapy (NAT) in patients with breast cancer (BC). MethodsWe retrospectively enrolled consecutive female patients pathologically confirmed with breast cancer who received NAT followed by surgery between January 2018 and December 2022 as the development cohort. Additionally, we prospectively collected eligible candidates between January 2023 and December 2023 as an external validation group at our institution. Pretreatment MRI features and clinicopathological variables were collected, and the pre- and post-treatment background parenchymal enhancement (BPE) and the changes in BPE on two MRIs were compared between patients who achieved pCR and those who did not. Multivariable logistic regression analysis was used to identify independent variables associated with pCR in the development cohort. These independent variables were combined into a predictive nomogram for which performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, decision curve analysis, and external validation. ResultsIn the development cohort, there were a total of 276 female patients with a mean age of 48.3 ± 8.7 years, while in the validation cohort, there were 87 female patients with a mean age of 49.0 ± 9.5 years. Independent prognostic factors of pCR included small tumor size, HER2(+), high Ki-67 index,high signal enhancement ratio (SER), low minimum value of apparent diffusion coefficient (ADCmin), and significantly decreased BPE after NAT(change of BPE). The nomogram, which incorporates the above parameters, demonstrated excellent predictive performance in both the development and external validation cohorts, with AUC values of 0.900 and 0.850, respectively. Additionally, the nomogram showed excellent calibration capacities, as indicated by Hosmer-Lemeshow test p values of 0.508 and 0.423 in the two cohorts. Furthermore, the nomogram provided greater net benefits compared to the default simple schemes in both cohorts. ConclusionA nomogram constructed using tumor size, HER2 status, Ki-67 index, SER, ADCmin, and changes in pre- and post-NAT BPE demonstrated strong predictive performance, calibration ability, and greater net benefits for predicting pCR in patients with BC after NAT. This suggests that the user-friendly nomogram could be a valuable imaging biomarker for identifying suitable candidates for NAT.

Abstract PO3-22-07: Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment

Abstract Background: Neoadjuvant chemotherapy (NACT) is increasingly used for axillary downstaging in clinically node-positive breast cancer patients, and a considerable proportion achieves axillary pathological complete response (ax-pCR). After NACT, axillary staging can be done by targeted axillary dissection (TAD). In case of metastases at TAD, axillary lymph node dissection (ALND) is offered regardless of metastases size. This contrasts primary surgery, where small sentinel node metastases (ypN0(i) and ypN1mi) and ≤2 positive sentinel nodes do not confer ALND, although a proportion of patients with small metastases have additional metastatic lymph nodes (LNs) in the axilla. So far, the residual metastatic burden in the axilla when TAD LNs are positive after NACT is unknown. If subgroups of patients with low residual metastatic burden in the axilla (non-TAD LNs) could be identified, these subgroups may be offered de-escalated axillary treatment. Therefore, we investigated the risk of residual metastatic burden in the axilla when the TAD LNs harbored metastases. Methods: We retrospectively retrieved DBCG data on patients staged by TAD after NACT in Denmark between 1.1.2016-31.8.2021. We registered: age, breast biopsy date, type of surgery, type of axillary surgery, count of LNs, sentinel nodes, and marked lymph nodes with and without metastases, including metastasis size, breast tumor histology and receptor subtype, breast tumor size at diagnosis and in the surgical specimen, malignancy grade and type of neoadjuvant treatment. We excluded patients with inflammatory breast cancer, &amp;lt; 4/&amp;gt;8 cycles of NACT, or a non-standard NACT regimen. The primary outcome was risk factors for having high ( &amp;gt;3), low (1-3), or no residual metastatic burden in the axilla when the TAD LNs harbored metastases. We modeled risk factors for both high and low residual metastatic burden in the axilla using multivariable logistic regression and constructed risk models based on the regression coefficients. Results: We identified 1626 patients receiving NACT and TAD in the inclusion period. After excluding ineligible patients and patients who achieved ax-pCR with no subsequent ALND (46%), the study included 383 patients with positive LNs at TAD for further analysis: thereof 188, 127, and 68 with 0, 1-3 and &amp;gt;3 positive non-TAD LNs, respectively. In the adjusted logistic regression analysis, we found that breast pCR (OR= 0.06, 95% CI &amp;lt; .01-0.41, p &amp;lt; .001) and a low proportion of positive TAD LNs (0-66% vs &amp;gt;66%) (OR=0.32, 95% CI 0.17-0.58, p = &amp;lt; .001) were associated with low risk of high residual metastatic burden in the axilla. Patients with one or both low-risk factors present had an 8% (14 of 176 patients) risk of high residual metastatic burden in the axilla. The predictive value of the model for having &amp;lt; 3 non-TAD LN metastases was 92%. When analyzing the 315 patients with ≤3 positive non-TAD LNs, the adjusted logistic regression analysis of 1-3 vs 0 positive non-TAD LNs showed that ypN0(i) in the TAD LN (OR=0.14, 95% CI 0.04-0.53, p = 0.002), small tumor size at diagnosis (20-49 mm vs ≥ 50 mm) (OR = 0.29, 95% CI 0.14-0.60, p = 0.002), breast pCR (OR= 0.38, 95% CI 0.15-0.98, p = 0.04) and low proportion of positive TAD LNs (33-66% vs &amp;gt;66%) (OR= 0.46, 95% CI 0.27-0.77, p = 0.01) were associated with no residual metastases in the axilla. Using these risk factors, 19% (11/58) of the patients in the lowest risk quartile had further metastatic spread to the axilla. Conclusion: Based on an extensive breast cancer registry, we find that breast pCR, low proportion of positive TAD LNs, small metastases, and small tumor size are associated with low risk of residual metastatic LNs in the axilla when the TAD LNs are positive after NACT. With these risk factors, we propose two models to identify patients with low non-TAD residual metastatic burden and patients with a high likelihood of no further metastases. The models can guide breast surgeons in de-escalating axillary treatment in these groups. Citation Format: Frederikke Munck, Maj-Britt Jensen, Ilse Vejborg, Maria Gerlach, Maja Maraldo, Niels Kroman, Tove Tvedskov. Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment [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 PO3-22-07.

Abstract PO3-13-12: ER-positive/HER2-negative breast cancer in Adolescent &amp; Young Adult (AYA) age group has a specific biological feature and worse outcome compared to other generations

Abstract Background: Adolescents &amp; Young Adults (AYA) is commonly defined as patients younger than 40 years old. Breast cancer patients in AYA has been reported to have poor outcome compared to other generation, however, the clinicopathological and biological features of AYA breast cancer remains controversial partly because many previous studies did not consider the difference in subtypes by age. We aim to clarify the features of AYA compared with the other age group in ER-positive/HER2-negative breast cancer, assuming the effects of age-related hormonal status. Material and Methods: Each analyzed cohort were divided into four age groups; AYA (15-39yo), perimenopausal (40-55yo), menopausal (55-65yo), and old (65+yo). Clinicopathological and biological features were analyzed using gene set variation analysis and the xCell algorithm using mRNA expression profiles of large independent public databases (METABRIC; n = 1,903, GSE96058; n = 3,273). Results: We found that both clinical and pathological T-category of AJCC staging were larger in AYA and Old compared from the other groups. Pathological N-category as well as pathological Stage were higher in AYA. Nottingham histological grade 3 was significantly higher in the AYA compared with the other older groups. Among the subtypes, AYA breast cancer was significantly associated with higher rate of triple-negative breast cancer compared to the others, as expected. Considering the whole cohort, ER and PgR positivity trended to be lower, but HER2-positivity trended to be higher in AYA. Within the ER-positive/HER2-negative subtype, PgR positivity was higher in the AYA and Perimenopausal groups compared to others. AYA had poorer disease-specific survival than other groups (p = 0.010 and p = 0.002, respectively), as well as overall survival, especially compared to perimenopausal group. The survival difference was more pronounced in ER-positive/HER2-negative breast cancer patients. In biological analysis in ER-positive/HER2-negative subtype, we found that estrogen response late signaling level decreased as the age group gets older. AYA breast cancer had significant enrichment in cell proliferation-related gene sets (G2M checkpoint, E2F targets, and MYC target v1), other pro-cancerous gene sets (MTORC1, unfolded protein response, and PI3K/ACT/MTOR signaling), consistently in two cohorts (all p ≦ 0.028), when compared to the other age groups. Interestingly, the features were observed even in the small tumor size (T1/T2) subgroup. Furthermore, AYA breast cancer showed significantly high BRCAness (all p≦0.002) and DNA repair (all p≦0.023) compared to other age groups. The infiltration fraction of several immune cells: CD8+ T cells, M1 macrophages, regulatory T cells, helper type 2 T cells, were significantly higher, and M2 macrophages were significantly lower in AYA, consistently in two cohorts. Conclusion: ER-positive/HER2-negative breast cancer in AYA was highly proliferative with high immune cell infiltrations compared to other generations. This may be related to the difference in outcomes in each age group. Considering these unique features may enable us to fine tune treatment strategies for AYA. Citation Format: Masanori Oshi, Akimitsu Yamada, Mahato Sasamoto, Kei Kawashima, Yoshie Fujiwara, Shoko Adachi, Shinya Yamamoto, Kazutaka Narui, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. ER-positive/HER2-negative breast cancer in Adolescent &amp; Young Adult (AYA) age group has a specific biological feature and worse outcome compared to other generations [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 PO3-13-12.

Abstract PO4-23-04: Is breast-conserving surgery an optional local therapy for non-inflammatory skin involvement (T4b) breast cancer? A Propensity Score Matching and Inverse Probability Weighting Analysis of SEER Database Results

Abstract Introduction: Although breast-conserving surgery (BCS) usage has been widespread in breast cancer treatment, it is still controversial about its application in non-inflammatory skin involvement (T4b) breast cancer. We designed this study to compare the prognosis for BCS versus mastectomy in this population. Methods: This retrospective cohort study included patients from the SEER database diagnosed with tumor stage T4b breast cancer from 1998 to 2019. To create prognostic factors, balance between BCS+RT and Mastectomy+RT groups, we calculated propensity scores for each patient. The calculation was based on the advance assessment for factors affecting prognosis, with the use of univariable and multivariable Cox proportional hazards models. Based on it, two propensity score-based matchings were conducted, including propensity score matching (PSM) and inverse probability weighting (IPTW). After adjustment, we performed Kaplan-Meier curves and multivariable Cox proportional hazards models to estimate BCSS and OS. Results: Of 4,680 patients who met the criterion, 588 received BCS+RT, and 4092 received Mastectomy+RT. In the propensity score matching (PSM) cohort, BCS+RT was found to improve breast cancer cause-specific survival (HR, 0.67; 95% CI, 0.53 to 0.85; p=0.001) and overall survival (HR, 0.72; 95% CI, 0.59 to 0.88; p=0.001). Similar results in the analysis of the IPTW-matched cohort confirm this result (BCSS: HR, 0.672; OS: HR, 0.722). Subgroup analysis revealed that those less than 70 years old, grade I+II, 3cm or smaller tumor size, hormone receptor-positive, or received chemotherapy treatment were more likely to benefit from BCS+RT (all p&amp;lt; 0.05). Conclusions: Locally treatment with BCS usage presented a significantly better survival than with mastectomy for non-inflammatory skin involvement (T4b) breast cancer patients. This finding provided evidence of selection in the local treatment of these patients. Citation Format: Jingyi Lin, Shiping Luo, Jie Zhang, Chuangui Song. Is breast-conserving surgery an optional local therapy for non-inflammatory skin involvement (T4b) breast cancer? A Propensity Score Matching and Inverse Probability Weighting Analysis of SEER Database Results [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 PO4-23-04.