Low Risk Of Distant Metastasis Research Articles

Contributions of Tissue Inhibitor of Metalloproteinase-1 Genotypes to the Risk of Metastasis in Gastric Cancer.

In gastric cancer (GCa) tissues, the mRNA and protein levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly elevated compared to adjacent non-cancerous tissues. Moreover, the abnormal up-regulation of TIMP-1 has been associated with a poor prognosis. However, the role of TIMP-1 genotypes in susceptibility to GCa has seldom been investigated. This study aimed to evaluate the influence of TIMP-1 genotypes on GCa susceptibility and their potential interactions with clinico-pathological factors, including age, sex, body mass index, smoking, alcohol consumption, Helicobacter pylori (H. pylori) infection, and metastasis status. TIMP-1 rs4898, rs6609533, and rs2070584 genotypes were analyzed in 161 patients with GCa and 483 non-cancer control subjects from a Taiwanese population using PCR-RFLP methodology and direct sequencing. The genotypic (p for trend=0.1987) and allelic (p=0.0733) frequencies of TIMP-1 rs4898 did not differ significantly between GCa cases and controls. Under the dominant model, combined CT+CC genotypes were not associated with GCa risk [odds ratio (OR)=0.74, 95% confidence interval (95%CI)=0.51-1.07, p=0.1272]. Similarly, no significant association was found for TIMP-1 rs6609533 or rs2070584 polymorphisms. Importantly, patients with GCa carrying the TIMP-1 rs4898 TT genotype exhibited a significantly enhanced risk of GCa when they had smoking (p=0.0140) and alcohol drinking habits (p=0.0011). Furthermore, the CC genotype of TIMP-1 rs4898 was linked to a lower risk of distant metastasis. The TIMP-1 rs4898 CC genotype may serve as a prognostic biomarker and could inform lifestyle modifications aimed at GCa prevention. Validation of TIMP-1 genotypic profile in diverse populations is warranted.

MammaPrint Genomic Assay Providing Prognostic Information in Early Breast Cancer: 10-Year Follow-Up From a Retrospective German Breast Cancer Registry Analysis

Introduction: Gene expression assays, such as the MammaPrint® (Agendia, Amsterdam, the Netherlands) 70-gene signature, are increasingly used by oncologists to understand breast cancer biology and improve treatment planning. This study assesses the utility of MammaPrint genomic risk in predicting treatment outcomes for women with breast cancer in a retrospective German cohort with a 10-year follow-up, treated based on clinicopathological features alone. Methods: The sample set of 117 tumours from the ‘Patients Tumour Bank of Hope’ (PATH) biobank with 10-year follow-up were classified using MammaPrint into high or low risk of distant metastasis. Patients were previously treated according to St. Gallen and Adjuvant! Online high- or low-risk criteria. Statistical analyses compared overall survival (OS) and treatment outcomes between clinical and genomic risk groups. Results: Among the 78 patients with clinically high-risk tumours, 50% (39) were reclassified as MammaPrint low risk. In total, 57.3% (67/117) patients with MammaPrint low-risk tumours demonstrated a significantly higher 10-year OS of 93.4%, irrespective of nodal status, compared to patients with MammaPrint high-risk tumours (71.2%; p=0.001). Chemotherapy improved OS in patients with MammaPrint high-risk tumours by 29.4%, but not for patients with MammaPrint low-risk tumours (p=0.016). Discussion: The findings confirm the prognostic utility of MammaPrint for identifying genomically low-risk patients who may safely omit chemotherapy while suggesting genomically high-risk cases may benefit from chemotherapy. By providing a more precise assessment of cancer risk than traditional clinicopathological methods alone, MammaPrint may help reduce unnecessary treatments and improve long-term quality of life for patients diagnosed with early-stage breast cancer.

Recurrent Dermatofibrosarcoma Protuberans with Fibrosarcomatous Transformation: A Case Report

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma with a propensity for local recurrence but a low risk of distant metastasis. Fibrosarcomatous transformation (FS-DFSP) is a rare but aggressive variant associated with increased metastatic potential. Case presentation: We present the case of a 39-year-old male with recurrent DFSP involving the scalp, mandible, and humerus, complicated by fibrosarcomatous transformation and distant metastases to the lungs and bones. The patient underwent multiple excisions, radiation therapy, and systemic treatments including chemotherapy and imatinib, but ultimately experienced disease progression. Conclusion: This case highlights the challenges in managing recurrent DFSP with fibrosarcomatous transformation. The rarity of this entity necessitates a high index of suspicion for early diagnosis and aggressive multidisciplinary management to improve patient outcomes. Further research is needed to identify effective treatment strategies for this aggressive variant of DFSP.

Abstract PO1-02-05: An exploratory comparison of MINDACT and TAILORx genomic risk proportions and outcomes in patients with HR+/HER2-, node-negative early-stage breast cancer, stratified by clinical risk

Abstract Introduction: Genomic tests provide physicians with critical information to evaluate the risk of distant metastasis and inform treatment plans by identifying those patients who may safely avoid chemotherapy (CT). The 70-gene signature (MammaPrint, MP) through the MINDACT trial and the 21-gene signature (Oncotype DX, ODx) through the TAILORx trial are the only tests validated with level 1A evidence that can be used for CT de-escalation decisions. Differences in trial design have made direct comparison of results difficult. We provide a comparison of MammaPrint and ODx genomic risk distributions and associated survival in patients with HR+/HER2-, node-negative (N0) early-stage breast cancer (EBC), stratified by clinical risk. Methods: Data from the MINDACT 2021 publication in The Lancet Oncology and landmark TAILORx 2019 publication in The New England Journal of Medicine were reviewed, in addition to publicly available data submitted to the Dutch Health Technology Assessment (HTA) authorities regarding survival data in patients with clinical High Risk in TAILORx. In MINDACT, patients were randomized based on both clinical (as per MINDACT definition) and genomic risk (clinical high/MP low, randomized to treatment according to clinical risk [i.e. CT] vs treatment according to MammaPrint risk [i.e. no CT]), while in TAILORx randomization was based on genomic risk alone. In TAILORx, enrollment for the population in the RS 11–25 group was enriched by 73% to account for the larger than expected non-adherence to randomized treatment plan based on the ODx results, as described in the original publication. This enrichment was only done for the RS 11–25 group. In this analysis, this enrollment enrichment was removed by applying the same proportional 73% corrective factor to the RS 11–25 group. Outcome data are reported for Overall Survival (OS), the only comparable endpoint used in both trials. Results: This explorative comparison focuses on patients with HR+/HER2- and N0 EBC in MINDACT (n=4,225) and TAILORx (n=6,686, without population enrichment). Similar proportions of patients identified as candidates for CT de-escalation (MP Low Risk or ODx RS≤25) were observed in this population of MINDACT (75%) and TAILORx (80%) when removing the RS 11–25 population enrichment in TAILORx (Table). In clinical high risk patients, the proportion with genomic low risk of distant metastasis were also comparable between MINDACT (55%) and TAILORx (63%) (Table). In the original clinical high risk but MammaPrint Low Risk population treated without CT in MINDACT the reported 8-year OS was 93.9%. In TAILORx, the comparable population of patients (ie. clinical high risk, low genomic risk, not treated with CT) had a 9-year OS of 89.2% in the RS 0–10 group and 91.6% in the RS 11–25 group (Table). Conclusions: Accounting for differences in trial design and population, comparable proportions of patients with genomic low risk results were observed between MP and ODx, justifying similar rates of CT de-escalation. Patients with clinical high risk tumors who are MammaPrint Low Risk had an excellent survival at 8 years. Genomic risk distributions and associated OS in HR+HER2- N0 patients in MINDACT and TAILORx MP, MammaPrint; OS, Overall Survival; RS, Recurrence Score. Number of patients in the TAILORx RS 11 – 25 group are adjusted to remove the proportional enrichment in the trial. OS data presented per original MINDACT and TAILORx populations. Citation Format: Patrick Neven, Josephine Lopes-Cardozo, Fatima Cardoso, Laura Van ’t Veer. An exploratory comparison of MINDACT and TAILORx genomic risk proportions and outcomes in patients with HR+/HER2-, node-negative early-stage breast cancer, stratified by clinical risk [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 PO1-02-05.

Osteosarcoma of the mandible and its management: A rare case report

Osteosarcoma is a classical malignant bone-forming neoplasm, characterised by osteoid synthesis by malignant osteoblasts. Osteosarcomas have an aggressive clinical course with a high mortality rate, despite their relatively low risk of distant metastases. The jaw bone is the most common site of occurrence in the head and neck region. These neoplasms often show characteristic clinical behaviours, varied radiological appearances, and a wide-ranging histological growth pattern. Early diagnosis and radical surgery, followed by radiotherapy and chemotherapy if required, have been the treatment of choice. This case report emphasises the importance of early diagnosis of this tumour based on clinical features, radiographic examination, and confirmation by histopathology. Confirmation of the final diagnosis of osteosarcoma often requires a histopathological examination of the multiple biopsy specimens. Adjuvant chemotherapy followed by radical surgery resulted in an excellent prognosis in the present case. Considering the rarity of the neoplasm, its fast progression, and its aggressiveness, the present case report would contribute to a better understanding of osteosarcomas involving the jaw bone and the management of the tumour involving the central arch of the mandible with involvement of the adjacent soft tissue structures.

Evaluation of the efficacy of transarterial chemoembolization combined with microwave ablation followed by adjuvant therapy in patients with hepatocellular carcinoma.

This study aimed to explore the efficacy of transarterial chemoembolization (TACE) combined with microwave ablation (MWA) adjuvant to lenvatinib and anti-PD-1 antibodies for patients with hepatocellular carcinoma (HCC). A retrospective analysis of 67 patients with HCC treated at our hospital between October 2018 and May 2022 was conducted. All patients underwent a combination of TACE and MWA. Among them, 29 received postoperative treatment with molecular-targeted agents, like lenvatinib, along with anti-PD-1 antibodies such as sindilizumab, karelizumab, or tirilizumab. The remaining 38 patients did not receive postoperative systemic therapies, like targeted or immunotherapy. The survival and prognosis of all patients were analyzed. Nine patients in the observation group and 29 patients in the control group experienced recurrence, and the median progression-free survival 1 (PFS1) was not reached 'Not Applicable'(NA) and 17.05 months (P=0.035), respectively. Failure to combine adjuvant therapy was identified as an independent risk factor for tumor recurrence, and the observation group had a 0.245 times lower risk of recurrence compared to that in the control group (P=0.005). Multivariable Cox regression analysis confirmed that the maximum tumor size, and tumor number were risk factors for tumor recurrence. Patients with a large maximum tumor size had a 1.519 times higher risk of recurrence compared to those with a small maximum tumor size (P=0.006), and patients with a large number of tumors had a 5.978 times higher risk of recurrence compared to those with a small number of tumors (P=0.02). The median PFS2 of the two groups was 11.795 and 21.257 months, respectively, though not statistically significant (P=0.955). However, there was a disparity in the percentage of BCLC stages associated with recurrence between the two groups. In the observation group approximately 22.22% of patients progressed to stage C, while in the control group, this proportion was 34.48%. The observation group exhibited a lower risk of distant metastasis compared to the control group. Adjuvant treatment of HCC following TACE combined with MWA improved PFS and achieved better clinical outcomes compared to that with TACE combined with MWA alone.

Less Irradiation to Lymphocyte-Related Organs Reduced the Risk of G4 Lymphopenia in Esophageal Cancer: Re-Analysis of Prospective Trials.

This study aimed to explore the relationship between irradiation of lymphocyte-related organs at risk (LOARs) and lymphopenia during definitive concurrent chemoradiotherapy (dCCRT) for esophageal squamous cell carcinoma (ESCC). Cases of ESCC patients who received dCCRT from 2 prospective clinical trials were identified. To find its correlation with survival outcomes, grades of absolute lymphocyte counts (ALCs) nadir during radiotherapy were recorded following COX analysis. Associations of lymphocytes at nadir and dosimetric parameters including relative volumes of spleen and bone marrow receiving 0.5, 1, 2, 3, 5, 10, 20, 30, and 50Gy (V0.5, V1, V2, V3, V5, V10, V20, V30, and V50), and effective dose to circulating immune cells (EDIC) were examined by logistic risk regression analysis. The cutoffs of dosimetric parameters were determined by the receiver operating characteristic curve (ROC). A total of 556 patients were included. The incidences of grades 0, 1, 2, 3, and 4 (G4) lymphopenia during dCCRT were 0.2%, 0.5%, 9.7%, 59.7%, and 29.8%, respectively. Their median overall survival (OS) and progression-free survival (PFS) time were 50.2 and 24.3 months, respectively; the incidence of local recurrence and distant metastasis were 36.6% and 31.8%, respectively. Patients once suffering from G4 nadir during radiotherapy had unfavorable OS (HR, 1.28; P = .044) and a higher incidence of distant metastasis (HR, 1.52; P = .013). Furthermore, patients with EDIC ≤8.3Gy plus spleen V0.5 ≤11.1% and bone marrow V10 ≤33.2% were strongly associated with lower risk of G4 nadir (OR, 0.41; P = .004), better OS (HR, 0.71; P = .011) and lower risk of distant metastasis (HR, 0.56; P = .002). Smaller relative volumes of spleen V0.5 and bone marrow V10 plus lower EDIC were jointly prone to reduce the incidence of G4 nadir during definitive concurrent chemoradiotherapy. This modified therapeutic strategy could be a significant prognostic factor for survival outcomes in ESCC.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

538 Background: Adjuvant endocrine therapy (ET) is the standard of care for Estrogen Receptor (ER)-positive early-stage breast cancer. However, many patients suffer from adverse events associated with ET. The prognosis of patients with T1a/bN0 breast cancer with ER-positive and human epidermal growth factor 2 (HER2)-negative is excellent, and it is not clear whether adjuvant ET should be recommended. Here we evaluate the effect of adjuvant ET for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Methods: This study was a multicenter, retrospective cohort study that evaluated adjuvant ET for patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Patients who underwent surgery between 2008 and 2012 in 47 institutions of the Japan Clinical Oncology Group (JCOG) breast cancer group were eligible. We analyzed the cumulative incidence of distant metastasis as primary endpoint using the Gray test model and time to event endpoints (distant disease free survival and overall survival) using log-rank test between patients treated with and without adjuvant ET. We also used Gray test model for the analysis of the cumulative incidence of ipsilateral and contralateral breast cancer. Predictive factors were assessed using the Fine-Gray model and the Cox proportional hazards model. Results: The median follow-up period was 9.2 years. Of 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%] diseases), 3991 (83.9%) received adjuvant ET. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In the multivariate analysis, the independent risk factors of distant metastasis were no ET, mastectomy, high grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% (HR, 0.54; 95% CI, 0.38-0.77). Adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs 6.9%; sHR, 0.17; 95% CI 0.11-0.28, and 1.9% vs 5.2%; sHR, 0.33; 95% CI, 0.22-0.49). Conclusions: Adjuvant endocrine therapy significantly reduces distant metastases, however the absolute difference is small for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, it reduced ipsilateral and contralateral breast cancer as well. Shared decision making regarding the omission of adjuvant endocrine therapy is crucial, especially in patients with low risk of distant metastasis.

PD07-10 OUTCOMES OF PARTIAL NEPHRECTOMY FOR NON-METASTATIC cT2 RENAL TUMORS: RESULTS FROM A CANADIAN MULTI-INSTITUTIONAL COLLABORATIVE

You have accessJournal of UrologyCME1 Apr 2023PD07-10 OUTCOMES OF PARTIAL NEPHRECTOMY FOR NON-METASTATIC cT2 RENAL TUMORS: RESULTS FROM A CANADIAN MULTI-INSTITUTIONAL COLLABORATIVE Rahul Bansal, Raees Cassim, Ryan Sun, Ranjeeta Mallick, Antonio Finelli, Simon Tanguay, Darrel Drachenberg, Frederic Pouliot, Luke Lavallee, Alan So, Ricardo Rendon, Lori Wood, Anil Kapoor, Aly-Khan Lalani, Naveen Basappa, Lucas Dean, Bimal Bhindi, Georg Bjarnason, and Rodney Breau Rahul BansalRahul Bansal More articles by this author , Raees CassimRaees Cassim More articles by this author , Ryan SunRyan Sun More articles by this author , Ranjeeta MallickRanjeeta Mallick More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , Simon TanguaySimon Tanguay More articles by this author , Darrel DrachenbergDarrel Drachenberg More articles by this author , Frederic PouliotFrederic Pouliot More articles by this author , Luke LavalleeLuke Lavallee More articles by this author , Alan SoAlan So More articles by this author , Ricardo RendonRicardo Rendon More articles by this author , Lori WoodLori Wood More articles by this author , Anil KapoorAnil Kapoor More articles by this author , Aly-Khan LalaniAly-Khan Lalani More articles by this author , Naveen BasappaNaveen Basappa More articles by this author , Lucas DeanLucas Dean More articles by this author , Bimal BhindiBimal Bhindi More articles by this author , Georg BjarnasonGeorg Bjarnason More articles by this author , and Rodney BreauRodney Breau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003231.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of partial nephrectomy (PN) is not well defined for cT2 renal cell carcinoma (RCC) as compared to radical nephrectomy (RN). The aim of this study was to examine oncological outcomes of PN as compared to RN for non-metastatic cT2 RCC. METHODS: The Canadian Kidney Cancer information system was used to define patients who underwent surgery for non-metastatic cT2 RCC from January 2011 to October 2022. Patients with clear-cell, papillary, and chromophobe RCC were included. Other histology, multiple tumours, and hereditary RCC syndrome patients were excluded. Each PN patient was individually matched to RN up to 1:4 depending on availability of patients based on tumor size (+/-1cm), histology, grade (clear cell and papillary), and necrosis (clear cell). Matched patients were analyzed as clusters. RESULTS: A total of 1523 patients were identified, and 50 PN patients met study criteria who were then matched to 185 RN patients. Both groups had similar age, gender, smoking status, BMI, Charlson comorbidity index score, symptoms at presentation, baseline eGFR, hemoglobin and pathological characteristics. PN patients had smaller tumors (7.6 cm [IQR 23] vs 8.4 [IQR 2.4], p=0.0479), had higher likelihood of undergoing open surgery (72.9% vs 31.8%, p<0.0001) and less likely received adrenalectomy (2% vs 24.3%, p=0.0004). Positive surgical margin rates were similar in both groups (8.2% in PN vs 3.4% in RN, p=0.2296). Median follow up was not significantly different in either group (3.6 yrs [IQR 4.7] in PN vs 3.3 [4.7] yrs in RN, p=0.975). During the follow up period, PN patients had higher risk of local recurrence (HR 3.0, 95%CI 1.08-8.37) and lower risk of metastasis (HR 0.36, 95%CI 0.15-0.88), overall survival (HR 0.36, 95%CI 0.18-1.78) as compared to RN. Cancer specific recurrence was similar between both groups (HR 0.56 ,95%CI 0.18,1.78). PN patients preserved more GFR than RN patients (-14.4 [SD 17.9] vs -23.7[SD 15], p=0.0006). Complications rates were similar between PN and RN (18% vs 8.65%, p=0.0571). CONCLUSIONS: In this multi-institutional Canadian cohort of patients with non-metastatic cT2 RCC undergoing surgery, PN compared to RN was associated with higher local recurrence, lower risk of distant metastasis, and death from any cause with similar complications and better preservation of renal function. Despite individual patient matching, there is likely unadjusted selection bias resulting in superior cancer survival associated with PN. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e166 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rahul Bansal More articles by this author Raees Cassim More articles by this author Ryan Sun More articles by this author Ranjeeta Mallick More articles by this author Antonio Finelli More articles by this author Simon Tanguay More articles by this author Darrel Drachenberg More articles by this author Frederic Pouliot More articles by this author Luke Lavallee More articles by this author Alan So More articles by this author Ricardo Rendon More articles by this author Lori Wood More articles by this author Anil Kapoor More articles by this author Aly-Khan Lalani More articles by this author Naveen Basappa More articles by this author Lucas Dean More articles by this author Bimal Bhindi More articles by this author Georg Bjarnason More articles by this author Rodney Breau More articles by this author Expand All Advertisement PDF downloadLoading ...

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma: comparison of long-term outcome between radiotherapy and chemotherapy

To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and to compare the treatment outcome between postoperative radiotherapy (RT) and chemotherapy in a retrospective analysis nearly 20y. A retrospective cohort study of 56 patients with orbital NRSTS were reviewed, 34 of whom received postoperative RT, and 22 received postoperative chemotherapy. The clinicopathological features, local recurrence, metastases, and survival data were recorded. Survival analysis was performed using the Kaplan-Meier method. During follow-up (111.8mo, ranged 8-233mo) for 56 patients, 19 patients of them developed local recurrence, and 7 patients developed distant metastases. Fifteen patients died during follow-up period. Overall survival rates considering the whole study group was 78.57% at 5y, and 72.16% at 10y after the initial diagnosis. Compared with chemotherapy, RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy, 0.263, 95% confidence interval (CI), 0.095-0.728, P=0.0015]; with lower risk of distant metastasis (hazard ratio for RT vs chemotherapy, 0.073, 95%CI, 0.015-0.364, P=0.0014); and with lower risk of death from disease (hazard ratio for RT vs chemotherapy, 0.066, 95%CI, 0.022-0.200, P<0.0001). The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group. In patients with orbital NRSTS, postoperative RT provides better control of local recurrence, distant metastasis, and death from disease than chemotherapy. RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Abstract GS5-10: Utility of the 70-gene MammaPrint test for prediction of extended endocrine therapy benefit in patients with early-stage breast cancer in the IDEAL Trial

Abstract Background: The IDEAL trial showed no significant benefit of 5 years extended endocrine therapy (EET) using letrozole in postmenopausal patients with hormone receptor positive (HR+) breast cancer (BC) versus 2.5 years. Genomic classifiers may assist with treatment decisions by predicting EET benefit. The 70-gene MammaPrint (MP) test classifies tumors as having a higher or lower risk of distant metastasis in HR+ early-stage BC. A MP lower risk result can be further classified as either Ultra-Low risk or Low risk of distant metastasis. In the NSABP B42 trial, MP predicted a statistically significant absolute benefit from EET in patients with a MP Low Risk result. Here, we aimed to determine the utility of MP in identifying a subgroup of patients enrolled in the IDEAL trial for which 5 years of EET is beneficial compared to 2.5 years. Methods: A total of 869 patients had available primary tumor tissue for testing. MP results were available for 545/869 patients, of which 515 did not have an event at 2.5 year after randomization and were used for our analyses. The MP result for each patient was calculated by Agendia while blinded to patient clinical outcomes. The primary endpoint was distant recurrence (DR). Secondary endpoints were recurrence free interval (RFI) and breast cancer free interval (BCFI) as defined by STEEP criteria. Patients were classified as higher risk (score -1.000 - 0) or lower risk (score 0.001 - 1.000). Lower risk tumors were further classified as either MP Ultra-Low (score &amp;gt; 0.355) or MP Low Risk (score ≥ 0.001, ≤ 0.355). Likelihood ratio test based on stratified Cox proportional hazards (PH) model were used to evaluate treatment by risk group interaction. Differences in endpoints between treatment groups were assessed by stratified log-rank tests. Hazard ratios (HR) and 95% Confidence Intervals (CI) were computed based on the stratified Cox PH model. Results: The clinical characteristics of the 515 IDEAL samples with a MP result were comparable to the whole IDEAL cohort (n=1820). Within the 2.5 year EET group, 50.6% (n=134) were MP higher risk and 49.4% (n=131) MP lower risk, of which 14.5% (n=19/131) were MP Ultra-Low. Within the 5 year EET group, 50.0% (n=125) were MP higher risk and 50.0% (n=125) MP lower risk, of which 11.2% (n=14/125) were MP Ultra-Low. Among patients with MP lower risk tumors, 5 years vs. 2.5 years of EET resulted in a significant absolute benefit of 9.8% for DR (HR=0.42, [95% CI 0.174-0.996]), 9.8% for RFI (HR=0.43, [95% CI 0.198-0.934]), and 8.8% (HR=0.53, [95% CI 0.264-1.055]) for BCFI, whereas patients with MP higher risk tumors did not derive significant benefit (Table 1). Within the MP lower risk group, 5 year vs 2.5 year EET benefit was more pronounced in MP Low tumors, which exhibited a significant benefit of 10.1% for DR (HR=0.32, [95% CI 0.116-0.866]), 11.7% for RFI (HR=0.35, [95% CI 0.147-0.824]), and 9.7% for BCFI (HR=0.48, [95% CI 0.225-1.015]); MP Ultra Low tumors did not derive significant benefit. Treatment-by-risk group interaction was statistically significant for RFI. Conclusion: A significant EET benefit was observed for MammaPrint lower risk tumors but not for MP higher risk tumors. MammaPrint Low tumors exhibited the largest absolute benefit of 5 years of EET compared to 2.5 years. Consistent with the findings in the NSABP B42 trial, the results from this second randomized trial provide clinically meaningful implications in patient selection for extended endocrine therapy. Table 1. IDEAL: 10-year outcome analysis comparing 5 years vs. 2.5 years of EET using letrozole stratified by MP risk. **MammaPrint Lower Risk &amp; Higher Risk (n=515) and *** MammaPrint Low Risk &amp; High Risk (n=482) Citation Format: Gerrit-Jan Liefers, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Cornelis J.H. van de Velde, Miranda Kleijn, Christa Dreezen, Andrea Menicucci, Laura van’t Veer, William Audeh. Utility of the 70-gene MammaPrint test for prediction of extended endocrine therapy benefit in patients with early-stage breast cancer in the IDEAL Trial [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 GS5-10.

Outcomes of partial nephrectomy for non-metastatic cT2 renal tumors: Results from a Canadian multi-institutional collaborative.

690 Background: The role of partial nephrectomy (PN) is not well defined for cT2 renal cell carcinoma (RCC) as compared to radical nephrectomy (RN). The aim of this study was to examine oncological outcomes of PN as compared to RN for non-metastatic cT2 RCC. Methods: The Canadian Kidney Cancer information system was used to define patients who underwent surgery for non-metastatic cT2 RCC from January 2011 to October 2022. Patients with clear-cell, papillary, and chromophobe RCC were included. Other histology, multiple tumours, and hereditary RCC syndrome patients were excluded. Each PN patient was individually matched to RN up to 1:4 depending on availability of patients based on tumor size (+/- 1cm), histology, grade (clear cell and papillary), and necrosis (clear cell). Matched patients were analyzed as clusters. Results: A total of 1523 patients were identified, and 50 PN patients met study criteria who were then matched to 185 RN patients. Both groups had similar age, gender, smoking status, BMI, Charlson comorbidity index score, symptoms at presentation, baseline eGFR, hemoglobin and pathological characteristics. PN patients had smaller tumors (7.6 cm [IQR 2] vs 8.4 [IQR 2.4], p=0.05), had higher likelihood of undergoing open surgery (72.9% vs 31.8%, p&lt;0.0001) and less likely received adrenalectomy (2% vs 24.3%, p=0.0004). Positive surgical margin rates were similar in both groups (8.2% in PN vs 3.4% in RN, p=0.2). Median follow up was not significantly different in either group (3.6 yrs [IQR 4.7] in PN vs 3.3 [4.7] yrs in RN, p=0.9). During the follow up period, PN patients had higher risk of local recurrence (HR 3.0, 95%CI 1.08-8.37), lower risk of distant metastasis (HR 0.36, 95%CI 0.15-0.88), better cancer specific survival (HR 0.56, 95%CI 0.18-1.78) and overall survival (HR 0.36, 95%CI 0.11-1.19) and as compared to RN. At 6 months and beyond after surgery, PN patients had less decline in eGFR than RN patients (-16.6 [SD 21.1] vs -24.4[SD 16.2], p=0.0002). Complications rates between PN and RN were (18% vs 9%, p=0.057). Conclusions: In this multi-institutional Canadian cohort of patients with non-metastatic cT2 RCC undergoing surgery, PN compared to RN was associated with slightly higher risk of peri-operative complications, better preservation of renal function, and higher risk of local recurrence. The lower risk of distant metastasis and death was likely from residual confounding unaccounted for in the individual patient match. [Table: see text]

Efficacy of preoperative therapy in patients with high and low risk of distant metastasis in non-small cell lung cancer

Background. To select the optimal treatment for non-small cell lung cancer (NSCLC), it is important to predict the risk of distant metastasis and the effectiveness of therapy. The effect of neoadjuvant chemotherapy (NAC) on distant metastasis remains poorly understood. In this study we evaluated the feasibility of predicting the risk of distant metastasis and effectiveness of various treatment options for pre- and intraoperative therapy in NSCLC patients with high and low risk of distant metastasis, divided based on the assessment of morphological changes in the epithelium of small bronchi located near the primary tumor.Material and Methods. The study included 171 patients with NSCLC (T1-4N0-3M0). Various premalignant lesions: isolated basal cell hyperplasia (BCH+SM-D-), basal cell hyperplasia with squamous cell metaplasia (BCH+SM+D-) and squamous cell metaplasia with dysplasia (BCH-SM+D+) were identified in the bronchial epithelium of small bronchi taken at a distance of 3–5 cm from the tumor. Preliminary studies have shown that the detection of BCH+SM-D- or BCH-SM+D-in small bronchi are the markers of high risk of NSCLC distant metastasis, and the detection of BCH+SM+D- and BCH-SM-D- are the markers of low risk of NSCLC distant metastasis. 52.6 % of patients (90/171) received 2–3 courses of neoadjuvant chemotherapy (NAC), 41.1 % (37/90) of patients underwent intraoperative radiation therapy (IORT) at a single dose of 10–15 Gy and 47.4 % (81/171) of patients received platinum-based adjuvant chemotherapy (AC).Results. Both treatment options (NAC+IORT+ and NAC+IORT–) effectively reduced the incidence of distant metastases in the high-risk group patients during the first 2 years of follow-up compared with the high-risk group patients who did not received therapy. In the low-risk group patients, distant metastases rarely occurred, regardless of the treatment option. Adjuvant chemotherapy was found to have no influence on the frequency of distant metastases. Metastasis-free and overall survival rates were better in the low-risk group patients or in patients who received the NAC+IORT+ regimen.Conclusion. Combination of NAC and IORT resulted in the increase in metastasis-free and overall survival rates.

MicroRNA-126 expression in the peripheral white blood cells of patients with breast and ovarian cancer is a potential biomarker for the early prediction of cancer risk in the carriers of methylated BRCA1.

Constitutive breast cancer type 1 gene (BRCA1) promoter methylation is associated with increased cancer risk, but its role in cancer-free (CF) female carriers is incompletely understood. MicroRNA (miR) is modulated during early tumorigenesis. The present study assessed the modulation of miR-126 expression in the peripheral white blood cells (WBC) of patients with breast cancer (BC) and ovarian cancer (OC) as a biomarker of cancer risk in BRCA1 methylation carriers. A total of 1,114 female subjects [502 patients with BC, 187 patients with OC and 425 CF volunteers] were involved. Screening for BRCA1 promoter methylation in WBC was performed using the methylation–specific polymerase chain reaction (PCR) assay, BRCA1 mRNA was analyzed using a reverse transcription-quantitative PCR assay and miR-126 expression was analyzed using a stem-loop RT-qPCR assay. WBC BRCA1 promoter methylation status was significantly associated with OC (P=0.0266), early-onset BC (P=0.0003) and triple-negative BC (P=0.0066). Notably, 9.4% of the CF group exhibited WBC BRCA1 promoter methylation. In addition, high levels of miR-126 in WBCs were detected in all three groups. The increased level of miR-126 was significantly associated with a lower risk of distant metastasis (P=0.045) in BC, but a higher risk of disease progression and death (P=0.0029) in OC. There was a positive correlation between BRCA1 mRNA and miR-126 levels in the WBCs of all three groups, regardless of BRCA1 promoter methylation status. Notably, circulating miR-126 level was decreased in the BC and OC groups, but not in the CF group. Together, these results suggest the likely involvement of miR-126 in the constitutional methylation of BRCA1 promoter-related malignancies. Therefore, miR-126 may be a candidate biomarker for the early prediction of BC and OC risk in CF BRCA1 methylation carriers.

MP24-05 OUTCOMES OF PARTIAL NEPHRECTOMY FOR NON-METASTATIC cT2 RENAL TUMORS: RESULTS FROM A CANADIAN MULTI-INSTITUTIONAL COLLABORATIVE

You have accessJournal of UrologyCME1 May 2022MP24-05 OUTCOMES OF PARTIAL NEPHRECTOMY FOR NON-METASTATIC cT2 RENAL TUMORS: RESULTS FROM A CANADIAN MULTI-INSTITUTIONAL COLLABORATIVE Rahul Bansal, Ryan Sun, Frederic Pouliot, Ranjeeta Mallick, Simon Tanguay, Darrel Drachenberg, Richard Rendon, Alan So, Luke Lavallee, Antonio Finelli, Lucas Dean, Anil Kapoor, Bimal Bhindi, Lori Wood, Naveen Basappa, and Rodney Breau Rahul BansalRahul Bansal More articles by this author , Ryan SunRyan Sun More articles by this author , Frederic PouliotFrederic Pouliot More articles by this author , Ranjeeta MallickRanjeeta Mallick More articles by this author , Simon TanguaySimon Tanguay More articles by this author , Darrel DrachenbergDarrel Drachenberg More articles by this author , Richard RendonRichard Rendon More articles by this author , Alan SoAlan So More articles by this author , Luke LavalleeLuke Lavallee More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , Lucas DeanLucas Dean More articles by this author , Anil KapoorAnil Kapoor More articles by this author , Bimal BhindiBimal Bhindi More articles by this author , Lori WoodLori Wood More articles by this author , Naveen BasappaNaveen Basappa More articles by this author , and Rodney BreauRodney Breau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002563.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of PN is not well defined for cT2 renal cell carcinoma (RCC) as compared to radical nephrectomy (RN). The aim of this study was to examine oncological outcomes of PN as compared to RN for non-metastatic cT2 RCC. METHODS: The Canadian Kidney Cancer information system was used to define patients who underwent surgery for non-metastatic cT2 RCC from January 2011 to October 2021. Patients with clear-cell, papillary, and chromophobe RCC were included. Other histology, multiple tumours, and hereditary RCC syndrome patients were excluded. Each PN patient was individually matched to RN up to 1:4 depending on availability of patients based on tumor size (±1 cm), histology, grade (clear cell and papillary), and necrosis (clear cell). Matched patients were analyzed as clusters. RESULTS: A total of 1347 patients were identified, and 42 PN patients met study criteria who were then matched to 145 RN patients. Both groups had similar age, gender, smoking status, BMI, Charlson comorbidity index score, symptoms at presentation, baseline eGFR, hemoglobin and pathological characteristics. PN patients had smaller tumors (7.6 cm [IQR 7.2, 9.2] vs. (8.5 cm [IQR 7.6, 10.3], p=0.048), had higher likelihood of undergoing open surgery (75% vs. 30% p <0.0001), less likely received adrenalectomy (0 vs. 21%, p=0.0001) and had higher likelihood of positive surgical margin (PSM) (10% vs. 1%, p=0.025). Median follow up was not significantly different in either group (3.7yrs [IQR 1.1, 5.4] in PN vs. 2.8yrs [IQR 1.2, 5.6] in RN, p=0.79). During the follow up period, PN patients had higher risk of local recurrence (HR 4.38 95% CI 1.51-12.71) and lower risk of metastasis (HR 0.39; 95% CI 0.16-0.95), improved cancer specific survival (HR 0.65; 95% CI 0.22-1.87) and overall survival (HR 0.47; 0.17-1.27) as compared to RN (Fig. 1). CONCLUSIONS: In this multi-institutional Canadian cohort of patients with non-metastatic cT2 RCC undergoing surgery, PN was associated with higher likelihood of PSM and local recurrence as compared to RN and lower risk of distant metastasis, cancer related death or death from any cause. Despite individual patient matching, there is likely unadjusted selection bias resulting in superior cancer survival associated with PN. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e394 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rahul Bansal More articles by this author Ryan Sun More articles by this author Frederic Pouliot More articles by this author Ranjeeta Mallick More articles by this author Simon Tanguay More articles by this author Darrel Drachenberg More articles by this author Richard Rendon More articles by this author Alan So More articles by this author Luke Lavallee More articles by this author Antonio Finelli More articles by this author Lucas Dean More articles by this author Anil Kapoor More articles by this author Bimal Bhindi More articles by this author Lori Wood More articles by this author Naveen Basappa More articles by this author Rodney Breau More articles by this author Expand All Advertisement PDF DownloadLoading ...

Clinical experience following implementation of routine SPECT-CT imaging following 131-iodine administration for thyroid cancer.

BackgroundPlanar scintigraphy has long been indicated in patients receiving I-131 therapy for thyroid cancer to determine the anatomic location of metastases. We studied our experience upon implementing additional single-photon emission (SPECT)-CT scanning in these patients.MethodWe performed a retrospective study of consecutive adult patients with newly diagnosed thyroid cancer treated with I-131 between 2011 and 2017. Radiologic findings detected with planar scintigraphy alone vs those identified with SPECT-CT scanning were primary endpoints.ResultIn this study, 212 consecutive patients with thyroid cancer were analyzed in two separate cohorts (107 planar scintigraphy alone and 105 planar scintigraphy with SPECT-CT). The addition of SPECT-CT resulted in more findings, both thyroid-related and incidental. However, we identified only 3 of 21 cases in which SPECT-CT provided an unequivocal additional benefit by changing clinical management beyond planar scintigraphy alone. No difference in the detection of distant metastatic disease or outcome was identified between cohorts.ConclusionSynergistic SPECT-CT imaging in addition to planar nuclear scintigraphy adds limited clinical value to thyroid cancer patients harboring a low risk of distant metastases, while frequently identifying clinically insignificant findings. These data from a typical cohort of patients receiving standard thyroid cancer care provide insight into the routine use of SPECT-CT in such patients.

Outcome without any adjuvant systemic treatment in stage I ER+/HER2− breast cancer patients included in the MINDACT trial

Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST.Patients with estrogen receptor-positive, HER2-negative, lymph node-negative tumors ≤2 cm who received no AST were matched 1 : 1 to patients with similar tumor characteristics treated with adjuvant endocrine therapy (ET), using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade. In a post hoc analysis, distant metastasis-free interval (DMFI) and overall survival (OS) were assessed by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence (LRR) and contralateral breast cancer (CBC) were assessed with competing risk analyses.At 8 years, DMFI rates were 94.8% [95% confidence interval (CI) 92.7% to 96.9%] in 509 patients receiving no AST, and 97.3% (95% CI 95.8% to 98.8%) in 509 matched patients who received only ET [absolute difference: 2.5%, HR 0.56 (95% CI 0.30-1.03)]. No statistically significant difference was seen in 8-year OS rates, 95.4% (95% CI 93.5% to 97.4%) in patients receiving no AST and 95.6% (95% CI 93.8% to 97.5%) in patients receiving only ET [absolute difference: 0.2%, HR 0.86 (95% CI 0.53-1.41)]. Cumulative incidence rates of LRR and CBC were 4.7% (95% CI 3.0% to 7.0%) and 4.6% (95% CI 2.9% to 6.9%) in patients receiving no AST versus 1.4% (95% CI 0.6% to 2.9%) and 1.5% (95% CI 0.6% to 3.1%) in patients receiving only ET.In patients with stage I low-risk breast cancer, the effect of ET on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received ET, after the relatively short follow-up of 8 years. These benefits and side-effects of ET should be discussed with all patients, even those at a very low risk of distant metastasis.

Tumor-infiltrating lymphocytes predict improved overall survival after post-mastectomy radiotherapy: a study of the randomized DBCG82bc cohort

Background The predictive value of tumor-infiltrating lymphocytes (TILs) on the benefit from radiotherapy (RT) remains unclear. Our aim was to investigate the association between TILs and post-mastectomy RT (PMRT) regarding the risk of recurrence and survival in a randomized cohort. Material and methods Stromal TILs were histologically estimated in 1011 tumors from high-risk breast cancer (BC) patients from the DBCG82bc trial. Patients were diagnosed between 1982 and 90, treated with total mastectomy and partial axillary lymph node dissection, randomized to ± PMRT followed by adjuvant systemic treatment. A competing risk model, Kaplan–Meier analysis and multivariate Cox regression analysis were used for correlating TILs and clinical outcome. Results 106 of 1011 patients (10.5%) showed high TILs using a 30% cut-off. In multivariate regression analysis, a high level of TILs was an independent factor associated with lower risk of distant metastasis (DM) and improved overall survival (OS), but without association with loco-regional control. High TILs were associated with a significantly greater OS after PMRT at 20 years compared to low TILs (8% improvement for low TILs (23% to 31%) vs. 22% for high TILs (26% to 48%), interaction-test: p = 0.028). The association between TILs and PMRT was more pronounced among estrogen-receptor negative (ER–) tumors, and patients having ER–/low TILs tumors showed no OS benefit from PMRT at 20 years (–4% improvement for low TILs (28% to 24%) vs. 23% for high TILs (20% to 43%). A similar trend in the association between high TILs and reduced risk of DM after PMRT was seen. Conclusion High TILs predict improved OS from PMRT in BC patients, and the association appeared especially strong for ER– tumors. A trend in the association between high TILs and reduced risk of DM after PMRT was seen. These findings may indicate that RT triggers an immune response inducing a systemic effect outside the treatment field.

Recurrent neck myxofibrosarcoma: a case report\xa0

BackgroundMyxofibrosarcoma (MFS) is a rare soft tissue sarcoma with a high recurrence rate and a low risk of distant metastasis. It occurs mainly in the extremities of elderly men. Head and neck MFS is extremely rare. Surgery is the cornerstone of treatment. The role of radiotherapy (RT) and chemotherapy (CHT) on MFS is still debated.Case presentationA 67-year-old Caucasian man presented to our sarcoma referral center (SRC) with a history of MFS of the neck excised with microscopic positive surgical margins in a non-referral center. Staging imaging exams did not reveal distant metastasis. After a multidisciplinary discussion, preoperative RT was administered with a total dose of 50 Gy followed by wide surgical excision. Histological examination was negative for viable tumor cells. No relapse occurred during the 24-month postoperative follow-up.ConclusionsThe case described suggests the importance of planned combined treatments with both RT and surgery for high-grade soft tissue sarcoma. RT seems to be promising within this specific histotype. Close follow-up is advisable in all cases. Further studies are needed to confirm if the observed efficacy of combined treatments results in a prolonged time of disease-free survival and overall survival.

Association of IDO immune suppression with brain metastasis in non-small cell lung cancer.

e21215 Background: Indoleamine 2, 3-dioxygenase (IDO), a known immunoinhibitory enzyme, plays an important role on tumor metastasis through manipulation of host immune status. We have demonstrated that IDO level has prognostic value and low IDO level is associated with low risk of distant metastasis in patients with non-small cell lung cancer (NSCLC). However, the association between IDO immune status in patients with brain metastasis (BrM) is unknown. We hypothesized that the IDO1 activity are different in the NSCLC patients of various stages and in patients with or without BrM and the IDO mRNA expression in brain metastatic lesion differ from the primary tumor or metastasized regional lymph nodes. Methods: This was part of a prospective study of blood immune biomarkers for prognosis and prediction. Newly diagnosed or recurrent NSCLC patients were eligible. Blood samples were obtained before treatment start and plasma were used for the Kynurenine (Kyn) and tryptophan (Trp) measurement by the high-performance chromatography. Kyn and trp was detected with more than 95% re-productivity. IDO activity was defined as ratio of kyn/Trp. Student T-test and One-way anova were applied for group comparison. CI: confidence interval. P &lt; 0.05 was considered as statistical significance. The IDO cellular expression was analyzed by the http://ureca-singlecell.kr/ website tool using the GEO dataset GSE131907. Results: Between July 2019 and Dec 2020, a total of 121 patients with NSCLC were eligible. The mean concentration of Kyn was 1.69 uM in patients with stage IV (n = 60, CI: 1.38-2.00), compared with 1.57 in patients with stage I (n = 38, CI: 1.03-2.10), 1.63 in stage II (n = 13, CI: 1.03-2.23) and 2.01 in stage III (n = 10, CI: 0.72-3.30, mean = 2.01). The mean ratio of Kyn:Trp was 0.10 in stage IV (n = 60, CI: 0.07-0.12), compared with 0.13 in patients with stage I (n = 38, CI: 0.06-0.20), 0.15 in stage II (n = 13, CI: 0.03-0.29) and 0.15 in stage III (n = 10, CI: 0.12-0.29). In patients with stage IV, there was no significant difference in the kyn concentration in patients with BrM (n = 13) and those without BrM (n = 47) (mean: 1.74, CI: 0.47-2.41 v.s 2.03 mean: 1.12-3.08; p = 0.45). The IDO activity in the patients with BrM was not significantly different from that of patients without BrM (mean: 0.11, CI: 0.03-0.20 v.s mean: 0.13, CI: 0.08-0.17; p = 0.74). Interestingly, GEO dataset analysis of the IDO1 mRNA expressions in 44 patients showed enrichments in myeloid cells in primary lung cancer tumor, natural killer cells in metastasized lymph nodes, and B cells in brain metastatic lesion. Conclusions: This study demonstrated no significant differences in circulating IDO expressions in patients with brain metastasis but differential IDO patterns of cellular expression in brain metastasis from that of primary tumor in NSCLC patients. This finding suggests the need of new strategy of research for immune status in the brain metastatic process of non-small cell lung cancer.