Node-negative Cancer Research Articles

Accuracy of an Artificial Intelligence System for Interval Breast Cancer Detection at Screening Mammography.

Background Artificial intelligence (AI) systems can be used to identify interval breast cancers, although the localizations are not always accurate. Purpose To evaluate AI localizations of interval cancers (ICs) on screening mammograms by IC category and histopathologic characteristics. Materials and Methods A screening mammography data set (median patient age, 57 years [IQR, 52-64 years]) that had been assessed by two human readers from January 2011 to December 2018 was retrospectively analyzed using a commercial AI system. The AI outputs were lesion locations (heatmaps) and the highest per-lesion risk score (range, 0-100) assigned to each case. AI heatmaps were considered false positive (FP) if they occurred on normal screening mammograms or on IC screening mammograms (ie, in patients subsequently diagnosed with IC) but outside the cancer boundary. A panel of consultant radiology experts classified ICs as normal or benign (true negative [TN]), uncertain (minimal signs of malignancy [MS]), or suspicious (false negative [FN]). Several specificity and sensitivity thresholds were applied. Mann-Whitney U tests, Kruskal-Wallis tests, and χ2 tests were used to compare groups. Results A total of 2052 screening mammograms (514 ICs and 1548 normal mammograms) were included. The median AI risk score was 50 (IQR, 32-82) for TN ICs, 76 (IQR, 41-90) for ICs with MS, and 89 (IQR, 81-95) for FN ICs (P = .005). Higher median AI scores were observed for invasive tumors (62 [IQR, 39-88]) than for noninvasive tumors (33 [IQR, 20-55]; P < .01) and for high-grade (grade 2-3) tumors (62 [IQR, 40-87]) than for low-grade (grade 0-1) tumors (45 [IQR, 26-81]; P = .02). At the 96% specificity threshold, the AI algorithm flagged 121 of 514 (23.5%) ICs and correctly localized the IC in 93 of 121 (76.9%) cases, with 48 FP heatmaps on the mammograms for ICs (rate, 0.093 per case) and 74 FP heatmaps on normal mammograms (rate, 0.048 per case). The AI algorithm correctly localized a lower proportion of TN ICs (54 of 427; 12.6%) than ICs with MS (35 of 76; 46%) and FN ICs (four of eight; 50% [95% CI: 13, 88]; P < .001). The AI algorithm localized a higher proportion of node-positive than node-negative cancers (P = .03). However, no evidence of a difference by cancer type (P = .09), grade (P = .27), or hormone receptor status (P = .12) was found. At 89.8% specificity and 79% sensitivity thresholds, AI detection increased to 181 (35.2%) and 256 (49.8%) of the 514 ICs, respectively, with FP heatmaps on 158 (10.2%) and 307 (19.8%) of the 1548 normal mammograms. Conclusion Use of a standalone AI system improved early cancer detection by correctly identifying some cancers missed by two human readers, with no differences based on histopathologic features except for node-positive cancers. © RSNA, 2024 Supplemental material is available for this article.

Abbreviated Breast MRI for Supplemental Screening in Patients With Dense Breasts: Comparison of Baseline Versus Subsequent-Round Examinations.

BACKGROUND. Abbreviated breast MRI (AB-MRI) achieves a higher cancer detection rate (CDR) than digital breast tomosynthesis when applied for baseline (i.e., first-round) supplemental screening of individuals with dense breasts. Limited literature has evaluated subsequent (i.e., sequential) AB-MRI screening rounds. OBJECTIVE. This study aimed to compare outcomes between baseline and subsequent rounds of screening AB-MRI in individuals with dense breasts who otherwise had an average risk for breast cancer. METHODS. This retrospective study included patients with dense breasts who otherwise had an average risk for breast cancer and underwent AB-MRI for supplemental screening between December 20, 2016, and May 10, 2023. The clinical interpretations and results of recommended biopsies for AB-MRI examinations were extracted from the EMR. Baseline and subsequent-round AB-MRI examinations were compared. RESULTS. The final sample included 2585 AB-MRI examinations (2007 baseline and 578 subsequent-round examinations) performed for supplemental screening of 2007 women (mean age, 57.1 years old) with dense breasts. Of 2007 baseline examinations, 1658 (82.6%) were assessed as BI-RADS category 1 or 2, 171 (8.5%) as BI-RADS category 3, and 178 (8.9%) as BI-RADS category 4 or 5. Of 578 subsequent-round examinations, 533 (92.2%) were assessed as BI-RADS category 1 or 2, 20 (3.5%) as BI-RADS category 3, and 25 (4.3%) as BI-RADS category 4 or 5 (p < .001). The abnormal interpretation rate (AIR) was 17.4% (349/2007) for baseline examinations versus 7.8% (45/578) for subsequent-round examinations (p < .001). For baseline examinations, PPV2 was 21.3% (38/178), PPV3 was 26.6% (38/143), and the CDR was 18.9 cancers per 1000 examinations (38/2007). For subsequent-round examinations, PPV2 was 28.0% (7/25) (p = .45), PPV3 was 29.2% (7/24) (p = .81), and the CDR was 12.1 cancers per 1000 examinations (7/578) (p = .37). All 45 cancers diagnosed by baseline or subsequent-round AB-MRI were stage 0 or 1. Seven cancers diagnosed by subsequent-round AB-MRI had a mean interval of 872 ± 373 (SD) days since prior AB-MRI and node-negative status at surgical axillary evaluation; six had an invasive component, all measuring 1.2 cm or less. CONCLUSION. Subsequent rounds of AB-MRI screening of individuals with dense breasts had lower AIR than baseline examinations while maintaining a high CDR. All cancers detected by subsequent-round examinations were early-stage node-negative cancers. CLINICAL IMPACT. The findings support sequential AB-MRI for supplemental screening in individuals with dense breasts. Further investigations are warranted to optimize the screening interval.

Abstract 2420: Evaluating circulating tumor DNA (ctDNA) as a prognostic biomarker utilizing a tissue-free epigenomic assay in early-stage triple negative breast cancer (TNBC)

Abstract Background: ctDNA has shown promise as a prognostic biomarker in early-stage solid tumors. Current breast cancer clinical guidelines do not recommend routine screening for metastatic disease outside of clinical features suggestive of disease recurrence. The detection of ctDNA may be a useful biomarker for the management of early-stage cancer patients to identify patients who are at high risk of recurrence. Methods: Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery were included in this study. Blood samples were prospectively collected prior to, during, and after completion of neoadjuvant chemotherapy, post-surgery, and throughout pre-specified surveillance time points (every 6 months for 5 years). Plasma samples were analyzed using Guardant Reveal powered by Infinity, a tissue-free, multiomic assay that interrogates differentially methylated regions of DNA using an applied bioinformatics filter optimized to detect breast cancer DNA from non-cancerous cell-free DNA and estimate quantitative tumor fraction. Samples were sequenced and resulted blinded to the patients’ clinical data. Results: A total of 120 patients with evaluable plasma samples were included in this study. At baseline prior to chemotherapy, ctDNA was detected in 75% (54/72) of patients. Baseline ctDNA detection was higher in node-positive cancers (100%; 29/29) versus node-negative cancers (58%; 25/43; p&amp;lt;0.0001). ctDNA quantity was higher in node-positive cancers (p&amp;lt;0.0001), and in stage III versus stage II disease (p=0.0179). During surveillance follow-up, the sensitivity for detecting any distant metastatic recurrence was 71% (5/7). Among patients with samples drawn within one year of recurrence, the sensitivity for detecting distant recurrence was 83% (5/6) with a sample-level specificity of 98% (186/190) and a patient-level specificity of 94% (63/67). ctDNA detection prior to recurrence had a median lead time of 5.0 months (range, 4.6-5.6). Notably, the detection of ctDNA during follow-up was associated with worse recurrence-free (HR 23.3, 95% CI 2.70-201, p&amp;lt;0.0001) and distant-recurrence free survival (HR 29.3, 95% CI 1.86-461, p&amp;lt;0.0001). Conclusions: ctDNA is detected with a tissue-free MRD assay with high sensitivity and specificity for distant recurrence in early-stage TNBC. Furthermore, the presence of ctDNA during follow-up is a prognostic indicator. Additional prospective studies are needed to assess the clinical utility of ctDNA monitoring in early-stage TNBC. Citation Format: Foluso O. Ademuyiwa, Cynthia X. Ma, Katherine Weilbaecher, Rama Suresh, Lindsay Peterson, Ron Bose, Nusayba Bagegni, Caron E. Rigden, Ashley Frith, Katherine Clifton, Andrew Davis, Derek Dustin, Mingyang Cai. Evaluating circulating tumor DNA (ctDNA) as a prognostic biomarker utilizing a tissue-free epigenomic assay in early-stage triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2420.

Extensive lymphadenectomy may improve survival in node negative oesophageal cancer

Lymph node metastases are a major prognostic factor in survival of patients with oesophageal cancer. The number of lymph nodes removed during oesophagectomy has been previously proven to be associated with improved survival. The aim of this study was to examine the effect of lymph node harvest on survival specifically in pathologically node negative (pN0) patients with oesophageal cancer. Data were extracted from a prospectively populated single-surgeon database of oesophageal resections for cancer. All consecutive patients with pN0 were included. Patient-specific risk adjusted analysis of overall and disease-free survival was performed to identify the number of lymph nodes associated with improved survival. Inclusion criteria were met by 137 patients (49 squamous cell carcinoma and 88 adenocarcinoma). Adjusted for cancer stage, tumour (histological type, degree of differentiation, lympho-vascular invasion, neo-adjuvant therapy) and patient related factors (age, sex), increased lymph node number was associated with significant improvement in overall (P = 0.045) and disease free (P = 0.030) survival. Lymph node count ≥ 17 was associated with improved overall and disease-free survival. In this cohort of patients with pathologically node-negative oesophageal cancer, lymph node count of 17 or above was associated with significantly improved survival.

The effect of adjuvant chemotherapy on survival in node negative colorectal cancer with or without perineural invasion: a systematic review and meta-analysis.

It was aimed at assessing the benefits of adjuvant chemotherapy (ACT) for patients with node-negative colorectal cancer (CRC) either with or without perineural invasion (PNI). We systematically searched PubMed, Cochrane Library, Embase, and Web of Science from database inception through October 1, 2023. Survival outcomes were analyzed using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Heterogeneity for the descriptive meta-analyses was quantified using the I2 statistic. Ten studies included in this review. ACT improved overall survival (OS) (HR 0.52, 95% CI 0.40-0.69) and disease-free survival (DFS) (HR 0.53, 95% CI 0.35-0.82) in PNI + patients but did not affect DFS (HR 1.13, 95% CI 0.72-1.77) in PNI- patients. A disease-specific survival (DSS) benefit with chemotherapy was observed in PNI + (HR 0.76, 95% CI 0.58-0.99) and PNI- patients (HR 0.76, 95% CI 0.57-1.00). And PNI decreased DFS (HR 1.94, 95% CI 1.52-2.47) and OS (HR 1.75, 95% CI 0.96-3.17) in node-negative CRC. In conclusion, chemotherapy appears most beneficial for survival outcomes in node-negative patients with PNI, but may also confer some advantage in those without PNI. Identifier INPLASY2021120103.

Development of a Screening Nomogram for Regional Lymph Node Metastasis Development in Muscle Invasive Bladder Cancer after Multiagent Systemic Therapy

A reliable method of identifying clinically node negative bladder cancer patients at greater risk of developing lymph node metastasis and may require intensified therapy is needed. The purpose of this study was to create a nomogram to quantify the risk for regional lymphatic involvement in non-metastatic muscle invasive bladder cancer. Usingthe National Cancer Database, patients with clinical T2-4N0M0 urothelial carcinoma of the bladder between the years of 2004 - 2020 were selected. All patients completed multiagent chemotherapy followed by surgery for pathologic nodal staging to determine presence or absence of nodal disease. No neoadjuvant radiation therapy was allowed and patients with history of prior malignancies were excluded. Following a 70:30 training to testing data split, baseline variables were assessed using univariate logistic regression. Variables were selected for inclusion in the multivariate logistic regression model using a combination of previously reported findings in the literature and/or if found to have a p-value < 0.05 on univariate analysis. A nomogram was constructed using this final model with assessment using calibration plots and the area under the receiver operating characteristics curve (AUC), respectively. An empiric cut point was chosen at 95% sensitivity to identify patients at "high" and "low" risk for pathologic nodal disease with overall assessment in both cohorts using chi-square. A total of 6194patients were identified for study with a median age of 65 years (IQR = 58 - 71 years). Most patients were male (68.0%) with T2 disease (81.2%). The final multivariate model included age at time of diagnosis (OR = 0.99; 95% CI = 0.99 - 1.00; p = 0.172), time from diagnosis to initiation of chemotherapy (OR = 1.00; 95% CI = 1.00 - 1.01; p = 0.005), papillary histology (OR = 0.85; 95% CI = 0.72 - 1.01; p = 0.068), and clinical T stage (Table 1). Model calibration demonstrated excellent goodness-of-fit with good discrimination (AUC = 0.644). Within the training data, high risk patients were seen to have a twofold increase in pathologic nodal disease (N = 835/3924, 21.2%) when compared to those identified as low risk (N = 38/347, 9.9%) (p < 0.001). Validation within the testing data set demonstrated similar results with pathologic node rates of 22.8% and 7.8% for high- and low-risk patients, respectively (AUC = 0.645, p < 0.001). This study demonstrates a clinically applicable risk stratification tool for identifying patients at risk for developing lymphadenopathy in T2-4 bladder cancer and may help guide future research in selecting patients eligible for escalation of therapy. Future studies should aim to externally validate this tool within prospective cohorts, and seek to determine if this nomogram may provide further prognostic utility.

Neural Invasion is an Independent Prognostic Factor in Young and Lymph Node Negative Gastric Cancer Patients Underwent Curative Gastrectomy

Background The prognostic significance of neural invasion (NI) in gastric cancer (GC) has not been established. This study is to investigate the characteristic and prognostic value of NI in GC. Methods 592 patients who had undergone gastrectomy for GC were retrospectively analyzed. NI was defined when cancer cells infiltrated into the perineurium or neural fascicles by hematoxylin and eosin staining of surgical specimens. NI and the other clinical factors were analyzed. Results NI was detected in 270 of the 592 patients. NI was associated with tumor size, site, depth of invasion, lymph node metastasis, TNM stage, D dissection, tumor differentiation, Lauren classification, and blood vessel invasion. NI was associated with the overall survival. Multivariate analysis indicated that NI was not an independent prognostic factor for total patients, while NI independently predicted prognosis for age < 60 and lymph node metastasis negative patients by subgroup analysis. Concomitant existence of NI with tumor size ≥3cm, TNM stage III, or diffused Lauren classification independently predicted prognosis. Conclusions The frequency of NI is high in GC patients and increases with disease progression. NI is related to poor survival in GC patients who underwent curative gastrectomy and provides independent prognostic value for young and lymph node metastasis negative patients.

Fertility sparing therapy in women with lymph node negative cervical cancer >2cm – oncologic and fertility outcomes of neoadjuvant chemotherapy followed by radical vaginal trachelectomy

ObjectiveSimple or radical trachelectomy are accepted fertility sparing therapies for patients diagnosed with cervical cancer ≤2 cm. In patients with larger tumors a fertility sparing concept is considered experimental. The...

Indocyanine green guided sentinel lymph node biopsy may have a high sensitivity for early (T1/T2) colon cancer: A prospective study in Indian patients.

Indocyanine green (ICG) dye guided near infrared fluorescence (NIR) imaging is a promising tool for mapping lymphatics. The aim of this study was to evaluate the role of ICG guided SLN biopsy in Indian colon cancer patients. Forty-eight patients of clinically staged T1-T3 node negative colon cancer underwent laparoscopic/open resection. Patients received colonoscopic peritumoral submucosal ICG injections for laparoscopic (n= 32) and subserosal injections for open resections (n= 16) followed by the detection of SLN using NIR camera. SLNs underwent conventional hematoxylin and eosin (H & E) staging with additional serial sectioning and immunohistochemistry for pancytokeratin antibody (ultra-staging). Detection rate and upstaging rate were the primary end points. Forty-eight patients were recruited. An average of 2.08 ± 1.27 SLNs were identified in 45 patients at a mean time of 8.2 ± 3.68 minutes with a detection rate of 93.75%. Mean age and mean BMI were 59.7 ± 12.54 years and 24.8 ± 4.09 kg/m2 , respectively. Eighteen patients had node positive disease, and SLN was false negative in four of these patients resulting in a sensitivity of 77.77% with a trend towards higher sensitivity for T1-T2 tumours (90% vs. 62.5%, p= 0.068). Upstaging rate was 10%. Negative predictive value (NPV) and accuracy of the procedure were 87.09% and 91.11%, respectively. ICG guided SLN biopsy can identify metastatic lymph nodes in colon cancer patients that can be missed on H & E staging with relatively higher sensitivity for early (T1/T2) tumours.

Surgical templates for inguinal lymph node dissection in cN0 penile cancer: A comparative study.

Modified and superficial inguinal lymph node dissection (MILD and SILD) are the 2 widely used templates for surgical staging of clinically node negative (cN0) penile cancer (PeCa); however, no previous reports have compared their outcomes. We compared these 2 surgical templates for oncological outcomes and complications. We retrospectively reviewed records of cN0 PeCa patients who underwent MILD/SILD at our cancer care center from January 2013 to December 2019. Patients who developed a penile recurrence during follow up were excluded from analysis of oncological outcomes. The 2 groups (MILD and SILD) were compared for baseline clinico-pathological characteristics. The primary outcome was the groin recurrence free survival (gRFS). Secondary outcomes included the false negative rate (FNR) and disease free survival (DFS) for both templates and also the post-operative wound related complication. Of the 146 patients with intermediate and high risk N0 PeCa, 74 (50.7%) and 72 (49.3%) underwent MILD and SILD respectively. The 2 groups were comparable with regards to the distribution of T stage, tumor grade and the proportion of intermediate and high-risk patients. At a median follow up of 34 months (47 for SILD and 23 for MILD), a total of 5 groin recurrences were encountered; all of them occurred in the MILD group. The gRFS and DFS for the MILD group was 93.2% and 91.8% respectively; while that for the SILD group was 100% and 94.4% respectively. Too few events had occurred to determine any statistically significant difference. The FNR for MILD and SILD was 26.3% and 0% respectively. The overall complication rate was significantly higher in the SILD group (46% vs 20.3%, p=0.001), especially for Clavien Dindo 3A complications. MILD can fail to pick up micro-metastatic disease in a small proportion of cN0 PeCa patients, while SILD provides better oncological clearance with no groin recurrences. This oncological superiority comes at the cost of a higher incidence of wound-related complications.

Node-negative colon cancer: histological, molecular, and stromal features predicting disease recurrence

BackgroundWithin the group of node-negative colon cancer patients, presumed to have a good prognosis, a significant percentage of patients develops cancer-recurrence. Current high-risk features prove inadequate to select these particular high-risk patients. In the process of tailor-made care and shared decision-making the need to identify these patients grows. In this study we investigate the value of adding molecular markers and the tumour-stroma ratio (TSR) to conventional histological tumour staging methods to improve the selection of high risk patients.MethodsWe retrospectively analysed 201 patients diagnosed with TNM-stage I-II colon cancer and treated by complete oncological resection between November 1st 2002 and December 31st 2012 at the Jeroen Bosch Hospital. Conventional histological tumour staging, BRAF mutations, KRAS mutations, MSI status and TSR were determined. Differences between groups based on TSR and mutation status, in disease free survival were analysed using Cox-Regression analyses.ResultsPoorly differentiated histology (p = 0.002), high-TSR (p = 0.033), BRAF-mutation (p = 0.008) and MSI (p = 0.011) were identified as significant risk factors for cancer recurrence. The risk of recurrence increased in the presence of both a BRAF-mutation and high-TSR compared to the absence of both factors or presence of only one factor (HR = 3.66 BRAF-mt/TSR-low (p = 0.006), HR 2.82 BRAF-wt/TSR-high (p = 0.015), HR = 4.39 BRAF-mt/TSR-high (p = 0.023)). This was also seen in tumours with MSI and high-TSR (HR = 2.46 MSS/TSR-high (p = 0.041), HR = 3.31 MSI/TSR-high (p = 0.045).ConclusionJudging by the higher HR for the combination of the prognostic factors TSR and BRAF compared to the HRs of these prognostic factors individually, the prognostication for disease free survival can be improved by determining both TSR and BRAF instead of BRAF alone, as is done in current daily practise. In this study MSI also shows additional value to TSR in the prognostication of disease free survival. Adopting TSR into daily diagnostics will be of additional value next to currently used molecular markers in risk stratification of patients with node negative colon cancer and is therefore advised.

Incidence of low volume metastases after retrospective ultrastaging of patients with early stage, node negative cervical cancer and receipt of post-operative adjuvant therapy.

e17506 Background: Nodal positivity directs receipt of adjuvant post-operative therapy in early stage cervical cancer; the significance of low-volume metastases (LVM) is unclear. We hypothesized patients with early stage cervical cancer with high risk factors on pathology and negative nodes would have a higher incidence of LVM on retrospective ultrastaging. Methods: This retrospective cohort study collected clinicopathologic data via chart review on early stage cervical cancer patients treated at our institution from January 2011 - June 2021. The study was approved by the IRB. Inclusion criteria included patients &gt;18 years old who underwent a radical hysterectomy/trachelectomy with pathology-proven negative nodes who went on to be recommended for post-operative adjuvant therapy, due to factors defined under Sedlis or Peters criteria. Patients were excluded for rare histology or prior pelvic radiation. Resected nodes were ultrastaged, performed by 4 re-cuts at 20 microns on each lymph node staging, stained with H&amp;E and one level with CK AE1/AE3 to identify presence of any LVM. Analysis was performed via descriptive statistics with Microsoft Excel. Results: 199 patients were treated with radical hysterectomy between 2011-2021; 20 met study criteria. The average age at diagnosis was 51 years: 65% Caucasian, 25% Black, 10% Latino. 75% had Squamous cell carcinoma, 85% (n=17) of the cohort were a 2009 FIGO pathologic Stage 1B. 35% of the cohort underwent a minimally invasive hysterectomy. Tumor size varied: 25% (n=5) of tumors were less than 2 cm, 35% (n=7) of tumors measured greater than or equal to 2 cm, 30% (n=6) measured greater than or equal to 3 cm, and 10% (n=2) measured greater than or equal to 4 cm. Lymphovascular space invasion was noted in 75% (n=15) of samples. Superficial stromal invasion was noted in 5% (n=1), deep stromal invasion was noted in 65% (n=13). 5% (n=1) of patients had parametrial invasion, and 5% (n=1) had positive margins. A full bilateral pelvic lymphadenectomy was performed on every patient, with 245 nodal blocks ultrastaged. 80% (n=16) received adjuvant therapy: 3 chemoradiation, 13 radiation, 4 declined. LVM was identified in 5% (n=1) patients; a macrometastases was identified as missed in the initial pathologic evaluation of another. 10% (n=2) patients developed recurrence, one at the pelvic brim and one distant (lung). The patient with the newly identified LVM received adjuvant radiation, and developed recurrence at the pelvic brim. Conclusions: The results of this small study suggest traditional “high risk” factors in surgically managed cervical cancer is associated with positive ultrastaged nodes in 5% of cases. This finding suggests that utilization of sentinel node identification with associated ultrastaging will accurately identify patients who will benefit from adjuvant therapy.

The role of adjuvant chemotherapy (CT) for early stage resectable node negative small cell lung cancer with size of ≤ 2 cm post-surgical resection: A SEER plus based statistical analysis.

e20643 Background: Small cell lung cancer (SCLC) is a poorly differentiated neuroendocrine tumor accounting for 15% of all lung cancers. Surgical resection followed by adjuvant platinum-etoposide is recommended for patients with limited-stage SCLC (T1 N0M0). In this study, we sought to evaluate the survival benefit of adjuvant chemotherapy for patients with ≤2 cm size SCLC following surgical resection. Methods: We utilized Surveillance, Epidemiology and End Results (SEER) plus 18 registries to identify adult patients (≥18 years) diagnosed with small cell cancer of the lung with tumor size of ≤ 2 cm from 2010 to 2018. The study population comprised of patients who underwent surgical resection followed by adjuvant chemotherapy and patients who received surgical resection alone. Kaplan-Meier and long rank tests were used to compare overall survival between the two groups. Multivariate survival analysis was done using the Cox proportional hazards regression model. Results: 419 patients were identified, with 203 (48%) receiving adjuvant CT while 216 (52%) not receiving adjuvant CT. The population who received adjuvant chemotherapy was younger than those who did not (Median years: 67 years vs 71 years, p &lt; 0.001). The 5-year overall survival rate was significantly higher for those receiving adjuvant CT (49% vs 40.9%, P value &lt; 0.001). On multivariate analysis after adjusting for age, gender, race, and origin, adjuvant chemotherapy was associated with better overall survival (HR:0.67; 95% CI 0.54 - 0.88, p = 0.003). Conclusions: Our study demonstrates that adjuvant CT should be used for early-stage small cell lung cancer irrespective of tumor size following surgical resection.

Abstract 3387: ctDNA dynamics in early stage node negative lung cancers

Abstract Introduction: Patients with early-stage lung cancers have a high risk of relapse and death even after curative surgery. Detection of circulating tumour DNA (ctDNA) in plasma perioperatively is associated with shorter recurrence free survival (RFS). ctDNA-Lung-Detect is an investigator-initiated prospective study of ctDNA detection and association with RFS in patients with early stage non-small cell lung cancer (NSCLC). Methods: Patients with clinically staged T&amp;lt;4cm N0 NSCLC planned for surgical resection at the Princess Margaret/University Health Network underwent ctDNA assessment before and after surgery (~1 month and 1 year). ctDNA minimal residual disease (MRD) was detected using the highly sensitive and specific tumor-informed Residual Disease and Recurrence (RaDaR®, Inivata, Cambridge, UK) assay, which can track up to 48 tumor-specific variants in plasma. Results: Since August 2021, 64 eligible patients were enrolled (Table 1). One had isolated metastasis from a remote non-lung primary and subsequently excluded; another had their preoperative sample missed but was included. Preoperative ctDNA was detected in 15/62 (23.8%) patients and 1/63 (1.6%) post-operatively at the 1-month landmark timepoint (occult N2 disease found at surgery). All but one (93.3%) had ctDNA clearance with surgical resection. Two patients have recurred radiographically and in plasma at 1 year post-operatively, 1/15 with preoperative ctDNA detected (6.7%) and 1/47 without preoperative ctDNA detected (2.1%). Patients with higher T stage, tumor size, squamous histology, and without actionable driver alterations were more likely to have ctDNA detected at any timepoint. Conclusions: In patients with early stage NSCLC (small node negative tumors), 24% have detectable ctDNA pre-operatively. Surgical resection led to ctDNA clearance in 93% of cases. Our results support ongoing testing beyond the initial MRD landmark. Assessment of the impact on RFS post resection is ongoing. Citation Format: Jamie Feng, Tom Waddell, Kazuhiro Yasufuku, Andrew Pierre, Shaf Keshavjee, Jonathan Yeung, Marcelo Cypel, Laura Donahoe, Elliot Wakeam, Marc de Perrot, Jennifer Law, Alexandra Salvarrey, Lisa W. Le, Jennifer Lister, Michael Cabanero, Ming Tsao, Christodoulos Pipinikas, Karen Howarth, Natasha Leighl. ctDNA dynamics in early stage node negative lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3387.

MP46-02 LYMPHOVASCULAR INVASION IN NON-METASTATIC MUSCLE INVASIVE BLADDER CANCER IS ASSOCIATED WITH CHARACTERISTIC GENETIC MUTATIONS

You have accessJournal of UrologyCME1 Apr 2023MP46-02 LYMPHOVASCULAR INVASION IN NON-METASTATIC MUSCLE INVASIVE BLADDER CANCER IS ASSOCIATED WITH CHARACTERISTIC GENETIC MUTATIONS Mohammed Al-Toubat, Ahmed El-Shafie, Allison H. Feibus, Seyedbehzad Jazayeri, Naser Mubarak, Khalid Mohammed, and Mark Bandyk K. C. Balaji Mohammed Al-ToubatMohammed Al-Toubat More articles by this author , Ahmed El-ShafieAhmed El-Shafie More articles by this author , Allison H. FeibusAllison H. Feibus More articles by this author , Seyedbehzad JazayeriSeyedbehzad Jazayeri More articles by this author , Naser MubarakNaser Mubarak More articles by this author , Khalid MohammedKhalid Mohammed More articles by this author , and Mark Bandyk K. C. BalajiMark Bandyk K. C. Balaji More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003292.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymphovascular invasion (LVI) in invasive bladder cancer is strongly associated with metastatic disease. We aim to identify the genes that could be the potential drivers of LVI in non-metastatic lymph node negative muscle invasive bladder cancer (M0N0MIBC). METHODS: We queried the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry. Key genes were identified in respect to LVI status in 316 patients with M0N0MIBC. The relationships among LVI-associated genomic subtypes, clinicopathological features and patient outcomes were explored. All patients had imaging and pathologic evaluation to ensure M0 and N0 status. We included frequency rates of > 5% and p/q values <0.05 were considered statistically significant to maintain >95% true positive detection rate. SPSS V24 was used for analyses. RESULTS: A total of 316 patients were included in our study cohort, all of which had M0N0MIBC disease. Overall, 112 (35.4%) patients had LVI-positive and 204 (64.6%) patients were LVI-negative. Male patients constituted the majority of the cohort [230 (72.8%)]. 248 men (78.5%) in the cohort were Caucasian. Median age was 70 years (65-75 IQR). At the time of the analysis, 312 (98%) patients had not received any systemic treatment. LVI was associated with a higher T stage and more aggressive grade (p=0.02). We identified alterations in 56 genes. Patients with LVI had significantly higher mutation alterations rate in 7 genes (p<0.001) - CDKN2A, CDKN2ADT, CDKN2B, MTAP, HMCN1, DMRTA1, KMT2D. There was downregulation of 3 genes - RB1, SOX4 and CDKAL1 among those with LVI (Figure 1). Patients with LVI had a shorter overall survival (p<0.001) and a shorter 5 year progression-free survival (p<0.001) (Figure 2). CONCLUSIONS: Imbalance between genetic expression of extracellular matrix components (HMCN1) and cell-cycle regulators (CDK family) could initiate LVI in association with disease progression in patients with N0M0MIBC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e630 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammed Al-Toubat More articles by this author Ahmed El-Shafie More articles by this author Allison H. Feibus More articles by this author Seyedbehzad Jazayeri More articles by this author Naser Mubarak More articles by this author Khalid Mohammed More articles by this author Mark Bandyk K. C. Balaji More articles by this author Expand All Advertisement PDF downloadLoading ...

Adverse impact of tumor deposits in lymph node negative rectal cancer — a national cohort study

PurposeThis study aimed to investigate the prognostic effect of tumor deposits (TDs) in lymph node negative rectal cancer.MethodsPatients who had undergone surgery for rectal cancer with curative intention between 2011 and 2014 were extracted from the Swedish Colorectal Cancer Registry. Patients with positive lymph nodes, undisclosed TD status, stage IV disease, non-radical resections, or any outcome (local recurrence (LR), distant metastasis (DM) or mortality) within 90 days after surgery were excluded. TDs status was based on histopathological reports. Cox-regression analyses were used to examine the prognostic impact of TDs on LR, DM, and overall survival (OS) in lymph node–negative rectal cancer.ResultsA total of 5455 patients were assessed for inclusion of which 2667 patients were analyzed, with TDs present in 158 patients. TD-positive patients had a lower 5-year DM-free survival (72.8%, p < 0.0001) and 5-year overall survival (75.9%, p = 0.016), but not 5-year LR-free survival (97.6%) compared to TD-negative patients (90.2%, 83.1% and 95.6%, respectively). In multivariable regression analysis, TDs increased the risk of DM [HR 4.06, 95% CI 2.72–6.06, p < 0.001] and reduced the OS [HR 1.83, 95% CI 1.35–2.48, p < 0.001]. For LR, only univariable regression analysis was performed which showed no increased risk of LR [HR 1.88, 95% CI 0.86–4.11, p = 0.11].ConclusionTDs are a negative predictor of DM and OS in lymph node–negative rectal cancer and could be taken into consideration when planning adjuvant treatment.

10-Year efficacy and co-morbidity outcomes of a phase III randomised trial of conventional vs. hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CHHiP; CRUK/06/016).

304 Background: Five-year results from the CHHiP trial indicated that moderate hypofractionation of 60 Gray (Gy)/20 fractions (f) was non-inferior to 74Gy/37f (Lancet Oncology, 2016). Reporting of long-term efficacy and side effects is essential in a patient population that remain at risk of recurrence years after treatment. Here we report specific co-morbidity data collected at 10 years and an update of efficacy. Methods: Between October 2002 and June 2011, 3216 men with node negative T1b-T3a localised prostate cancer with risk of seminal vesical involvement ≤30% were randomised (1:1:1 ratio) to 74Gy/37f (control), 60Gy/20f or 57Gy/19f. Patients received 3-6 months of androgen deprivation prior to radiotherapy. The primary endpoint was time to biochemical failure (Phoenix consensus guidelines) or clinical failure (BCF). The non-inferiority design specified a critical hazard ratio (HR) of 1.208 for each hypofractionated schedule compared to control. Data on specific radiotherapy related co-morbidities were collected at 10-year follow-up and are presented as frequency and percentages. Analysis was by intention-to-treat; HRs quoted are unadjusted. Results: With a median follow up of 12.1 years, 10-year BCF-free rates (95% CI) were 74Gy: 76.0% (73.1%, 78.6%); 60Gy: 79.8% (77.1%, 82.3%) and 57Gy: 73.4% (70.5%, 76.1%). For 60Gy/20f, non-inferiority was confirmed: HR60=0.84 (90% CI 0.72, 0.97) with borderline significance for superiority (HR=0.84 (95% CI 0.70, 1.00). As in the primary analysis, for 57Gy/19f, non-inferiority could not be declared: HR57=1.13 (90% CI 0.98, 1.30). 10-year overall survival (95% CI) was 78.5% (75.9%, 81.0%), 82.9% (80.4%, 85.0%) and 79.9% (77.3%, 82.2%) in the 74Gy, 60Gy and 57Gy groups. Bone fractures were reported in 2% (15/700), 2% (19/771) and 3% (22/719) of patients in the 74Gy, 60Gy and 57Gy groups respectively at 10 years. The most common intervention reported was a sigmoidoscopy with 12% (79/681), 8% (60/739) and 9% (65/702) in the 74Gy, 60Gy and 57Gy groups respectively. Of those patients who underwent a sigmoidoscopy it was due to symptoms for 81% (63/78) 81% (48/59) and 85% (55/65) of patients in the 74Gy, 60Gy and 57Gy group respectively. Frequencies of all other pre-specified co-morbidities or related interventions (ureteric obstruction, bowel strictures, trans-urethral resection of prostate, urethrotomy, urethral dilatation or long term catheterisation or treatment of proctopathy with steroid, sucralfate, formalin, laser coagulation or rectal diversion) were &lt;1% in all groups. Conclusions: With a median follow-up of 12 years, oncological outcomes following 60Gy/20f continue to be non-inferior to those with 74Gy/37f. Late co-morbidities were very low across all treatment groups. These data support the long-term safety of moderate hypofractionation. Clinical trial information: 97182923 .

Predictive factors for nodal recurrence in differentiated thyroid cancers

IntroductionDifferentiated thyroid carcinoma usually has a good prognosis. Primary treatment is surgery, followed by radioactive iodine ablation based on risk stratification. The incidence of local and distant recurrence is 30%. Recurrence can be managed surgically or with multiple cycles of radioactive iodine ablation. There are multiple risk factors for structural disease recurrence proposed by the American Thyroid Association. In this study, we attempted to study the risk factors of structural recurrence in differentiated carcinoma thyroid and the pattern of recurrence in patients with node negative thyroid cancer who underwent total thyroidectomy. MethodologyThis study selected a retrospective cohort of 1498 patients with differentiated thyroid cancer: out of these, 137 patients who presented after thyroidectomy with cervical nodal recurrence from January 2017 to December 2020 were included. The risk factors for central and lateral lymph node metastasis were analysed by univariate and multivariate analyses, including age, gender, T-stage, extrathyroidal extension, multifocality and high-risk variants. In addition, the presence of TERT/BRAF mutations was studied as a risk factor for central and lateral nodal recurrence. ResultsOut of 1498 patients, 137 who fit the inclusion criteria were analysed. Majority were female (73%); mean age was 43.1 years. Lateral compartment neck nodal recurrence was more common (84%), while isolated central compartment nodal recurrence occurred only in 16%. Most recurrences were seen in the first 1 year (23.3%) or after 10 years post-total thyroidectomy (35.7%). On univariate variate analysis, multifocality, extrathyroidal extension and high-risk variants stage were significant factors for nodal recurrence. However, on multivariate analysis for lateral compartment recurrence, multifocality, extrathyroidal extension and age were found to be significant. On multivariate analysis, multifocality, extrathyroidal extension and presence of high-risk variants were significant predictors of central compartment nodal metastasis. ROC curve analysis showed AUC for ETE (AUC-0.795), multifocality (AUC-0.860), presence of high-risk variants (AUC-0.727) and T-stage (AUC-0.771) as sensitive predictive factors for central compartment. 69 percent patients with very early recurrences (<6 month) had TERT/BRAF V600 E mutations. ConclusionIn our study, we have noted extrathyroidal extension and multifocality as significant risk factors for nodal recurrence. BRAF and TERT mutations are associated with aggressive clinical course and early recurrences. There is limited role of prophylactic central compartment node dissection.

Breast Cancer Screening in Women With Dense Breasts: Current Status and Future Directions for Appropriate Risk Stratification and Imaging Utilization.

Breast density continues to be a prevailing topic in the field of breast imaging, with continued complexities contributing to overall confusion and controversy among patients and the medical community. In this article, we explore the current status of breast cancer screening in women with dense breasts including breast density legislation. Risk-based approaches to supplemental screening may be more financially cost-effective. While all advanced imaging modalities detect additional primarily invasive, node-negative cancers, the degree to which this occurs can vary by density category. Future directions include expanding the use of density-inclusive risk models with appropriate risk stratification and imaging utilization. Further research is needed, however, to better understand how to optimize population-based screening programs with knowledge of patients' individualized risk, including breast density assessment, to improve the benefit-to-harm ratio of breast cancer screening.

Selection Factors for Treatment and Stratification of Rare Abdominal or Pelvic Tumors with Peritoneal Metastases.

To maximize the results of treatments for peritoneal metastases for rare abdominal or pelvic tumors, selection of patients with a possibility for long-term success is necessary. Because these malignancies are rare, data from which these selection factors can be extracted do not exist. In order to facilitate knowledgeable patient selection for treatment, the well established clinical and histopathologic features of the common malignancies treated for peritoneal metastases were reviewed. The potential application of selection factors for common diagnoses was explored in an attempt to provide selection factors for rare tumors. The histopathologic grade, the lymph node status, the Ki-67 proliferation index, prior surgical score (PSS), preoperative radiologic imaging, preoperative laparoscopic assessment, response to neoadjuvant chemotherapy, peritoneal cancer index (PCI), and completeness of cytoreduction score were all included in this search for relevant selection factors for a rare disease. To facilitate the use of selection factors from common peritoneal metastases diagnoses, these diseases were divided into four groups. Placement of the rare cause of peritoneal metastases into one of these four groups will allow knowledgeable selection for treatment. Rare diseases with a natural history resembling low-grade appendiceal neoplasms are in group 1, diseases resembling lymph node negative colorectal cancer are in group 2, diseases resembling lymph node positive colorectal peritoneal metastases in group 3, and diseases resembling gastric cancer in group 4.