Larger Primary Tumor Size Research Articles

Dermatofibrosarcoma Protuberans: An Updated Review of the Literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes. Its genetic background is a reciprocal translocation t(17;22)(q22;q13) that produces COL1A1-PDGFB gene fusion. Complete resection is the primary treatment. The aim of this review is to outline the pathogenesis, diagnosis, and management of DFSP. A clear-cut distinction between low-to-moderate-grade DFSP with excellent prognosis and high-grade fibrosarcomatous DFSP with a much worse prognosis is underlined. Malignant transformation within DFSP (or high histologic grade), older age, being female, large primary tumor size (≥10 cm), narrow surgical margins of excision (<3 cm), surgical margin positivity for tumor cells, short time to recurrence, numerous recurrences, tumor that was recently rapidly enlarging, and presence of pain in the tumor have all been proposed as clinicopathological risk factors for recurrence and metastasis. A tendency for local growth and local relapses of well- and moderately differentiated DFSPs is an argument for their surgical excision, possibly combined with reconstructive surgery, even in patients of advanced age. Another main point of this review is that cases of DFSP with fibrosarcomatous transformation are a challenge and require careful medical attention. Both anatomopathological evaluation of the presence of lymphovascular space invasion and sentinel lymph node biopsy at DFSP surgery merit further study.

BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07)cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

Особенности экспрессии CD163+ и HLA-DR+ на моноцитах крови при раке молочной железы

Circulating monocytes are important actors of the tumor growth pathogenesis. It has been shown that some features of the monocyte populations expressing endocytosis receptors or the major histocompatibility complex components are observed in blood of patients with breast cancer. The study was aimed to assess the relationship of tumor parameters and blood cytokine profile with the composition of circulating monocyte populations in patients with localized and locally advanced breast cancer. The study has shown that the circulating monocytes’ phenotypic characteristics are correlated to the clinical and morphological features of the neoplastic process. The content of populations with the CD14+CD16++CD163+ and CD14++CD16+CD163+ phenotypes positively correlates with the disease stage, while larger primary tumor size is associated with lower CD14+CD16++ monocyte levels. Elevated serum levels of IL8 and МСР-1 are observed in breast cancer patients. High IL6 levels in patients with breast cancer are associated with the reduced percentage of CD14++CD16-HLA-DR+, CD14+CD16++HLA-DR+ and CD14++CD16-СD163+ monocytes. Thus, CD163+ and HLA-DR+ monocytes are associated with the clinical and morphological parameters and blood levels of cytokines, which suggests that these populations are involved in breast cancer progression and indicates that further research is advisable for translation of the findings into clinical practice.

CT-Based Radiogenomics of P4HA3 Expression in Clear Cell Renal Cell Carcinoma

The sequencing of the renal cell carcinoma (RCC) genome identified several mutations with prognostic significance. Genomic analysis, collected in The Cancer Genome Atlas Research Network, revealed several clear cell renal cell carcinoma (ccRCC) gene mutations and gene expressions. Radiogenomics is a new branch of diagnostic imaging based on the association between imaging phenotypes and genomics of diseases. P4HA3 expression has recently been shown to correlate with increased aggressiveness of ccRCC, with poor prognosis, proliferation, migration, invasion, and metastases, suggesting P4HA3 as a prognostic marker and therapeutic target in ccRCC. The aim of this study is to investigate the computed tomography (CT) imaging phenotype of P4HA3 expression in ccRCC patients. In this retrospective study we enrolled 196 ccRCC patients divided into two groups: ccRCC patients with P4HA3 expression (n =13) and ccRCC patients without P4HA3 expression (n=183). Several imaging features were evaluated on preoperative CT scan. The statistical significance threshold was set at P<.05. A statistically significant association was found with larger primary tumor size (P=.033), tumor infiltration (P=.023), ill-defined tumor margins (P=.025), and advanced tumor stage American Joint Committee of Cancer (P=.014). This study demonstrates CT imaging features associated with P4HA3 expression in ccRCC. These results could contribute to better understand P4HA3 expression with a noninvasive approach and could be applied to the development of targeted therapies.

Impact of Age on Overall Survival Among Children With Wilms Tumor: A Population-based Registry Analysis.

International trials have reported conflicting findings on whether the association between age and worse overall survival (OS) among children with Wilms tumor (WT) is due to age as an independent prognostic factor or the observation of more advanced disease at older ages. We sought to further elucidate this relationship using a population-based registry analysis. The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with WT under the age of 20. The association between age and OS was assessed using multivariable Cox proportional hazards regression. In this study, 3463 patients (54% female) were diagnosed with WT between 1975 and 2016. More advanced stage, larger primary tumor size, lymph node involvement, disease requiring radiotherapy, and omission of surgery were associated with worse OS ( P <0.05). More advanced stage, larger primary tumor size, and disease requiring radiotherapy were also associated with older age, whereas bilateral disease was associated with younger age ( P <0.001). On average, each year of age conferred an incremental hazard ratio (HR) of 1.07 (95% CI, 1.01 to 1.12, P =0.018) independent of relevant covariates. The rise in adjusted OS HR was most pronounced after the transitions in diagnosis age from 2 to 3 (HR age 3-15 vs. 0-2 1.77, 95% CI, 1.11 to 2.82, P =0.016) and from 15 to 16 (HR age 16-19 vs. 3-15 2.58, 95% CI, 1.06 to 6.25, P =0.036). Diagnosis of pediatric WT at an older age was found to be independently associated with worse OS. Although additional prospective studies are warranted to examine tumor biology and other potential correlates, more aggressive treatment of older children based on age, especially as they approach early adulthood, may be considered in the multidisciplinary management of WT.

Bilateral multifocality is an independent predictor of patients' outcome in Middle Eastern papillary thyroid carcinoma.

Tumor multifocality is frequently seen in Papillary thyroid carcinoma (PTC). However, few studies have analysed the impact of bilateral multifocality in PTC. The incidence of bilateral multifocality, its clinico-pathological associations and prognostic impact in PTC from Middle Eastern ethnicity remains unestablished. We retrospectively evaluated 1283 patients who underwent total thyroidectomy for PTC. Bilateral and unilateral multifocality were decided based on the final pathology result. Primary outcome was recurrence free survival (RFS). Risk factors for bilateral multifocality were analyzed by multivariate logistic regression analysis. Multifocal PTC was found in 54.3% (697/1283) of patients. Among the 697 multifocal PTCs, 210 patients (30.1%) had unilateral multifocal PTC and 487 patients (69.9%) had bilateral multifocality. Bilateral multifocality was significantly associated with older age at diagnosis (p = 0.0263), male gender (p = 0.0201), gross extrathyroidal extension (p = 0.0332), larger primary tumor size (>4cm; p = 0.0002), lateral lymph node metastasis (p = 0.0008), distant metastasis at diagnosis (p = 0.0195) and recurrence (p = 0.0001). Bilateral multifocality was also found to be an independent predictor of RFS (Hazard ratio = 1.60; 95% Confidence Interval = 1.05 - 2.55; p = 0.0300). Multivariate logistic regression analysis demonstrated tumor diameter >4cm to be the only independent risk factors for bilaterality in multifocal PTC (Odds ratio = 1.86; 95% Confidence Interval = 1.13 - 3.07; p = 0.0155). Incidence of bilateral multifocality is high in Middle Eastern PTC. Tumor diameter >4cm can be considered as a predictive factor for bilateral multifocal PTC. Bilateral multifocality appears to be an important prognostic factor for PTC and an independent predictor of RFS. Therefore, patients with bilateral multifocal PTC may benefit from more frequent follow-up to identify recurrences earlier.

Relapse-free survival in Sudanese women with non-metastatic breast cancer.

Breast cancer (BC) is the most frequently diagnosed cancer and a major cause of cancer mortality in Sudan. However, there is lack of data related to BC relapse. Therefore, this study was undertaken to estimate the 5-year relapse free survival (RFS) rate and factors related to BC relapse in Sudanese women with non-metastatic BC. Data of BC women with BC diagnosed and treated at the National Cancer Institute-University of Gezira during 2012 were retrieved from medical records. The cases were followed-up through hospital records and telephone contact. Survival functions were calculated using Kaplan-Meier method and compared by log-rank test. The prognostic factors were tested using univariate and multivariable Cox regression analyses. We included 168 women with median age of 45years (range, 22-83years). 53.5%of women had stage III at time of diagnosis, whereas 4.2% and 42.3% of women presented with stage I and stage II, respectively. At the end of 5years follow-up, with median follow-up period of 64months, 94 (56.0%) women were alive in remission, 11 (6.5%) were alive with BC relapse, 49 (29.2%) were dead, and survival status was unknown in 14 (8.3%) women. Most of the occurred relapses were distant relapses. The 5-year RFS was 59%. The independent predictors of relapse were: larger primary tumor size (HR:1.84, 95% CI: 1.54-5.48, p=0.018); involved axillary lymph nodes with tumour (HR: 2.91, 95% CI: 1.53-7.91, p=0.001); not receiving adjuvant radiotherapy (HR: 2.2, 95% CI: 1.22-3.95, p=0.009); and not receiving hormone therapy (HR: 1.67, 95% CI: 1.01-2.76, p= 0.046). We found a high risk of BC relapse in our resource-constrained settings. Advanced stages, not receiving adjuvant radiotherapy, and not receiving adjuvant hormone therapy were independent predictors associated with worse 5-year RFS. Therefore, enhancing the early diagnosis of BC and improving timely access to appropriate treatments represent key approaches to achieving better treatment outcomes.

Prognostic impact of extranodal extension (ENE) in surgically managed treatment-naive HPV-positive oropharyngeal squamous cell carcinoma with nodal metastasis

AbstractExtranodal extension (ENE) is a significant prognostic factor for human papilloma virus (HPV)-negative head and neck squamous cell carcinoma and is incorporated into AJCC 8th edition pN stage. It remains controversial whether ENE or the degree of ENE is prognostically relevant in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). A detailed clinicopathologic review was conducted in a large retrospective cohort of 232 surgically treated patients with HPV-positive OPSCC and nodal metastasis. Fifty-six patients (24%) had nodal metastasis with ENE. The median vertical extent of ENE was 2.9 mm (range 0.2–20.3 mm), and the median horizontal span of ENE was 2.5 mm (range: 0.3–14.0 mm). Comparing with patients without ENE, those with ENE were associated with a higher number of positive lymph nodes, lymphovascular invasion, perineural invasion, adjuvant chemotherapy, larger primary tumor size, and shorter follow up period. Patients with ENE had shortened overall survival (OS), disease specific survival (DSS), disease free survival (DFS), distant metastasis free survival (DMFS), and regional recurrence free survival (RRFS) on univariate survival analysis. The 5-year OS, DSS, and DFS were 95%, 97%, and 90% respectively for the group without ENE, and 64%, 71%, and 65% respectively for the group with ENE. On Multivariate survival analysis, the presence of ENE was an independent adverse prognostic factor for OS, DSS, and DFS. Additionally, major ENE defined as a vertical extent of ≥4 mm or irregular soft tissue deposit independently predicted shortened OS, DSS, and RFS. In conclusion, the presence of ENE, in particular major ENE, is an independent prognostic factor in HPV-positive OPSCC. Therefore, we propose to document the presence and extent of ENE for these tumors. Consideration may be given for AJCC 9th edition to include ENE into pN stage of HPV-positive OPSCC.

Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance.

While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with the emergence of immune checkpoint inhibitors (ICIs) and VEGFR-targeting drugs, sizable proportions of patients still do not respond to upfront therapy and long-term responses only occur in a minority of patients. There is therefore a great need for the development of better predictors of response and an increased understanding of mechanisms of resistance to these therapies. Alternative immune checkpoints outside the PD-1/PD-L1 axis, such as LAG3, have been implicated as one mechanism of resistance to ICIs. These checkpoints thus represent attractive therapeutic targets, and indeed the LAG3 inhibitor relatlimab was recently approved for the treatment of metastatic melanoma in combination with anti-PD-1 therapy. LAG3 inhibitors are being evaluated for RCC as well. In this context, a better understanding of LAG3 expression patterns in RCC and how they relate to clinicopathologic features of disease and response to immunotherapy may give insight into mechanisms of resistance to PD-1 inhibitors and aid in the identification of subgroups of patients more likely to benefit from certain drug regimens. In this study, we assessed LAG3 protein levels in leukocytes in normal kidney adjacent to RCC, primary RCC tumors, and matched metastatic tumors, including large numbers of brain metastases. We found that LAG3 protein levels are on average lower at metastatic sites compared to matched primary tumors, and that the difference was more pronounced in patients with high-risk clinical characteristics, including those with larger primary tumor size, grade 4 tumors, IMDC poor-risk disease, and initial presentation with brain metastases. We further saw that the prognostic value of LAG3 levels varies depending on the tissue site queried (i.e., primary tumor versus metastases), and that relatively higher LAG3 levels at metastatic sites may predict a better response to immunotherapy and longer overall survival after the development of metastatic disease. These findings may have important implications for the design of future studies involving LAG3 or other immunotherapies in RCC.

Utilizing Computed Tomography to Analyze the Morphomic Change between Patients with Localized and Metastatic Renal Cell Carcinoma: Body Composition Varies According to Cancer Stage.

Background: This study aimed to elucidate the change of body composition in different clinical stages of renal cell carcinoma (RCC) by analyzing computed tomography (CT) images. Methods: We enrolled patients diagnosed with RCC in a tertiary medical center who did not mention body weight loss or symptoms of cachexia. We grouped patients into those with localized RCC and those with metastatic RCC. Analyses of the volume of skeletal muscles tissue (SMT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) calculated based on CT images were performed and included subgroup analyses by sex and age. The correlation between tumor size and body composition in localized RCC was also examined. Results: A total of 188 patients were enrolled in this study. There was significantly lower VAT (p = 0.015) in the metastatic group than in the localized group. SAT, body weight, and body mass index (BMI) were not significantly different between these two groups. In the subgroup analysis, a significant difference in SMT and VAT was noted in the male and younger subgroups but not in the female and older subgroups. Regarding primary tumor size in localized RCC, VAT was significantly higher in patients with larger tumors (p = 0.003). Conclusions: In localized RCC, VAT volume was significantly larger in those with large primary tumor size. However, the VAT was significantly lower in those with metastatic status comparing to those with localized disease. The clinical course of cancers closely correlates with body composition.

Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients.

BackgroundTelomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients.MethodsWe prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma.ResultsOf 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences.ConclusionThis study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

Clinical Outcome of Patients with Pelvic and Retroperitoneal Bone and Soft Tissue Sarcoma: A Retrospective Multicenter Study in Japan.

Simple SummaryWe aimed to clarify the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma. The 3-year overall survival (OS), local control (LC) rate, and progression-free survival (PFS) were 71.7%, 79.1%, and 48.6%, respectively. The most influential poor prognostic factor for OS was distant metastasis, and for PFS, this was higher age (≥60 years). Larger primary tumor size (≥10 cm) was the only poor prognostic factor for LC. In the histological analysis, osteosarcoma showed significantly worse OS and PFS than other sarcomas in the pelvis and retroperitoneum.This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

Abstract 5857: Systematic literature review of prognostic factors associated with overall survival among advanced synovial sarcoma and myxoid/round cell liposarcoma subjects

Abstract Objective: Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) are rare subtypes of soft tissue sarcoma. Reported prognostic factors of survival for SS and MRCLS include tumor size/grade, tumor depth, and round cell component specifically for MRCLS. However, these publications refer to both localized and advanced disease, and there is a lack of a systematic review of these factors. The objective is to systematically review prognostic factors associated with overall survival (OS) in subjects with advanced (metastatic or unresectable) SS and MRCLS. Methods: Literature searches were conducted in PubMed and Embase using search strings for advanced/metastatic SS and MRCLS, and survival, and included English language articles (2000-2020), complemented with clinical trial registry summaries and oncology conference proceedings (most recent 3 years). Studies with multivariable (MV) analyses were prioritized. Results: Sixteen studies investigated prognostic factors associated with OS (13 SS, 2 MRCLS and 1 SS/MRCLS). Five studies were conducted in the US, two in the UK and three in the EU; three SS studies and one MRCLS study included at least 100 subjects in the analyses. Advanced SS: Among six studies with MV analyses of OS, the factors in the models varied by study. Age was studied in three analyses with older age being associated with worse OS in one analysis. Metastasectomy was included in two analyses and found to be associated with longer OS in one analysis. Larger primary tumor size was associated with shorter survival in two analyses. Other factors associated with worse OS and occurring in one analysis include: males, no chemotherapy/radiotherapy/surgery of primary tumor, extra-pulmonary metastasis, lymph node metastasis, shorter time to metastasis and higher performance status. Univariate analyses showed similar results. Advanced MRCLS: While no MV analyses were conducted, the following factors were investigated in two univariate analyses each but had p-values &amp;gt;0.05: primary tumor grade, primary tumor size, percentage of round cells and location of metastases. Only one study identified factors associated with worse OS: stage IV at diagnosis, ≥3 metastatic lesions at start of first-line therapy and a high number of organs involved during first-line therapy. Conclusion: Limited evidence exists for prognostic factors of OS among advanced SS and MRCLS subjects. Large tumor size was the most common factor associated with poor OS in MV analyses among advanced SS subjects; other factors associated with poorer prognosis included older age, males, and metastasis characteristics. Among advanced MRCLS subjects, there were very few prognostic factors reported and all stemmed from univariate analyses in a single study, underscoring the scarcity of data available and the need for further explorations with this subtype. Funding: GSK Citation Format: Samantha St Laurent, Judith van den Bosch, Hilde Vroling, Huifen Wang, Shibani Pokras. Systematic literature review of prognostic factors associated with overall survival among advanced synovial sarcoma and myxoid/round cell liposarcoma subjects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5857.

Contralateral Breast Screening with Preoperative MRI: Long-Term Outcomes for Newly Diagnosed Breast Cancer.

Background The diagnostic value of screening the contralateral breast with MRI in patients with newly diagnosed breast cancer is poorly understood. Purpose To assess the impact of MRI for screening the contralateral breast on long-term outcomes in patients with newly diagnosed breast cancer and to determine whether subgroups with unfavorable prognoses would benefit from MRI in terms of survival. Materials and Methods Data on consecutive patients with newly diagnosed breast cancer seen from January 2008 to December 2010 were reviewed retrospectively. Patients with neoadjuvant chemotherapy, previous breast cancer, distant metastasis, absence of contralateral mammography at diagnosis, and no planned surgical treatment were excluded. Groups that did and did not undergo preoperative MRI were compared. Survival analysis was performed using the Kaplan-Meier method for propensity score-matched groups to estimate cause-specific survival (CSS) and overall survival (OS). A marginal Cox proportional hazards model was used to evaluate association of MRI and clinicopathologic variables with OS. Results Of 1846 patients, 1199 fulfilled the inclusion criteria. Median follow-up time was 10 years (range, 0-14 years). The 2:1 matched sample comprised 705 patients (470 in the MRI group and 235 in the no-MRI group); median ages at surgery were 59 years (range, 31-87 years) and 64 years (range, 37-92 years), respectively. MRI depicted contralateral synchronous disease more frequently (27 of 470 patients [5.7%] vs five of 235 patients [2.1%]; P = .047) and was associated with a higher OS (hazard ratio [HR], 2.51; 95% CI: 1.25, 5.06; P = .01). No differences were observed between groups in metachronous disease rate (MRI group: 21 of 470 patients [4.5%]; no-MRI group: 10 of 235 patients [4.3%]; P > .99) or CSS (HR, 1.34; 95% CI: 0.56, 3.21; P = .51). MRI benefit was greater in patients with larger tumor sizes (>2 cm) (HR, 2.58; 95% CI: 1.11, 5.99; P = .03) and histologic grade III tumors (HR, 2.94; 95% CI: 1.18, 7.32; P = .02). Conclusion Routine MRI screening of the contralateral breast after first diagnosis of breast cancer improved overall survival; the most pronounced benefit was found in patients with larger primary tumor size and primary tumors of histologic grade III. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taourel in this issue.

Pheochromocytoma: A Clinicopathologic and Molecular Study of 390 Cases From a Single Center.

Pheochromocytomas are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. They may occur sporadically or in the context of hereditary syndromes. All pheochromocytomas are considered to have malignant potential (defined as risk of metastasis, not local invasion). The use of grading systems with incorporated clinical and histopathologic parameters can help but not definitively predict the metastatic potential of pheochromocytomas. The recent discovery of susceptibility genes provided new insights into the pathogenesis and introduced additional approaches to estimate the metastatic risk of pheochromocytoma. However, the prevalence of these genetic signatures in pheochromocytomas has yet to be fully addressed. Therefore, in the present study, we retrospectively reviewed cases of pheochromocytoma from 1980 to 2018 in the archives of our institution. Three hundred ninety cases were identified, and their clinicopathologic characteristics and genetic statuses were analyzed. About 25% of the cases had metastases, which were more common in older patients (median, 49 y) than in younger ones. Univariate and multivariate analyses revealed that older age, Hispanic ethnicity, metastasis, and large primary tumor size were markedly associated with poor overall survival. In contrast, family history of pheochromocytoma, lack of symptoms, and bilateral adrenal involvement were associated with better survival. About 37% of the pheochromocytomas were associated with inherited syndromes. About 52% of tested patients had pathogenic mutations of pheochromocytoma susceptibility genes. Of these, succinate dehydrogenase B gene mutation had the strongest association with metastasis. These data support that genetic testing should be offered to all patients with pheochromocytoma.

Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors - a single Brazilian center experience.

The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Abstract PS4-34: Multi-country study of the use of genomic assays in HR+, HER2- early breast cancer and characteristics of patients tested

Abstract Background Recognized prognostic factors associated with increased risk of recurrence in patients (pts) with HR+, HER2- early breast cancer (EBC) are higher histologic grade, larger primary tumor size, and greater lymph node involvement. Genomic assays like Oncotype DX obtain prognostic information to indicate benefit of adjuvant therapy. The objective was to examine use of genomic assays and describe demographic, clinical, and pathological characteristics of pts tested. Methods Real-world data was drawn from the Adelphi EBC I Disease Specific Programme, a cross-sectional observational study in France, Germany, Italy, Spain, United Kingdom (UK), United States (US) and Japan. 765 consulting physicians were surveyed, including questions on use of genomic assays to assess risk of recurrence. In each country, 20-64 of the physicians also completed patient record forms from Mar-Sep 2019 for up to 8 eligible pts with HR+, HER2- EBC. Results Physicians in US (n=176), UK (n=52) and Spain (n=100) reported highest use of genomic assays to categorize patients from low to intermediate risk (US 61%; Spain 57%; UK 65%) and from intermediate to high risk of recurrence (US 64%; Spain 67%; UK 65%). Lowest use was in Japan (n=134), 13% and 20%, respectively. Oncotype DX was consistently reported as the most frequently used genomic assay to assess the risk of recurrence (see table). Patient record forms were completed for 2447 pts (98% female, mean age 59.6 years, SD 13.0). Frequency of Oncotype DX testing varied by stage, with less testing in stage III pts (stage I 26% (194/755); stage II 20% (221/1130); stage III 11% (56/505) p&amp;lt;0.0001). Similar patterns were seen across most countries, but often not statistically significant. Germany had similar use across stages (~20%). Oncotype DX testing was less frequent in pts with grade 3 tumors (grade 1 21% (100/484); grade 2 22% (203/908); grade 3 12% (44/384); p&amp;lt;0.0001). Similar patterns were seen across countries except UK and Spain where testing was less in pts with grade 1 tumor, but not statistically significant. Oncotype DX testing was less frequent in large tumors (size &amp;lt;2cm 19% (161/865); size 2-5cm 20% (254/1265); size &amp;gt;5 cm 11% (11/105); p=0.0503). Similar patterns were seen across countries except Italy, but generally not significant. Oncotype Dx testing was less frequent in pts &amp;gt;50 years (age ≤50 25% (161/657); age &amp;gt;50 18% (318/1790); p=0.0003). Similar patterns were seen across countries, and significant in Germany (p=0.0029) and Italy (p&amp;lt;0.0001), except for US and Japan where testing was very similar between age groups. Oncotype DX testing was less frequent in node +ve pts, 14% of 733 pts, compared with 23% of 1593 node -ve patients (p&amp;lt;0.0001). Similar patterns were seen in most countries, with some statistically significant differences. Germany and Japan were exceptions, Oncotype DX testing was used for node +ve pts more than node -ve pts. Difference was statistically significant in Japan (p=0.032). Conclusion Use of genomic assays to assess pt risk of recurrence varied across countries. The most commonly used assay was Oncotype DX. Oncotype DX testing was less frequent amongst stage III, grade 3, large, node +ve tumors or age &amp;gt;50, although there were some important country variations. These data contribute to the understanding of drivers in adopting multi-gene assays within clinical practice. Genomic AssayTotal(n=729)*US (n=171)Japan (n=122)France (n=93)Germany (n=97)Italy (n=96)Spain (n=100)UK (n=50)Oncotype DX67%91%45%54%64%60%63%94%Adjuvant! Online30%23%25%29%29%34%43%42%Mammaprint29%37%30%17%24%21%52%0%Breast Cancer Index17%29%25%13%14%17%2%4%EndoPredict13%8%20%20%12%11%8%18%Prosigna11%8%11%22%4%6%21%8%*729/765 physicians who assessed all or some of their patients with EBC for risk of recurrence Citation Format: Jacqueline Brown, Rhys Williams, Alex Rider, Rosie Wild, Michael Method. Multi-country study of the use of genomic assays in HR+, HER2- early breast cancer and characteristics of patients tested [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-34.

The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: A gene expression-based study.

Whether tumor mutation burden (TMB) affects prognosis and immune infiltration of tumor patients is controversial. We designed and conducted a multi-omics study with the aim of investigating the prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma (HNSCC). TMB scores were calculated from the mutation data of 506 HNSCC samples from The Cancer Genome Atlas (TCGA), and the patients were divided into low- and high-TMB groups according to the TMB score quartiles. Differentially expressed genes (DEGs) between the low-TMB and high-TMB groups were identified. Immune cell infiltration and survival analyses were conducted between groups. High TMB in HNSCC patients was associated with a poor prognosis, large primary tumor size, advanced clinical stage and a human papillomavirus (HPV)-negative status. A total of 576 DEGs were identified, and gene set enrichment analysis (GSEA) revealed that the DEGs in the low-TMB group were enriched in immune-related pathways. Four hub genes were significantly associated with prognosis, and mutations in these genes affected immune infiltration. The estimated fractions of B memory cells and CD4+ memory resting cells were higher in the low-TMB group than in the high-TMB group, and B cell and CD4+T cell infiltration was positively correlated with prognosis in HNSCC patients. HNSCC patients with low TMB have better prognoses than those with high TMB, and TMB might affect B cell and CD4+T cell infiltration.

Association of angiogenesis and inflammation-related gene functional polymorphisms with early-stage breast cancer prognosis.

Genetic variations in inflammation- and angiogenesis-related genes may alter the coded protein level and impact the pathogenesis of breast cancer (BC). The present study investigated the association of functional single nucleotide polymorphisms (SNPs) in the VEGFA, IL-1β, IL-1α and IL-6 genes with the early-stage BC phenotype and survival. Genomic DNA and clinical data were collected for 202 adult Eastern European (Lithuanian) women with primary I–II stage BC. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Nine VEGFA, IL-1β, IL-1α and IL-6 polymorphisms were analysed. The VEGFA and IL-6 haplotypes were inferred using Phase software. Patients were prospectively followed-up for recurrence, occurrence of metastasis and mortality until April 30, 2019. All studied genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for European population. Significant associations of the studied SNPs with clinicopathologic variables were observed between IL-1α rs1800587 C allele and larger primary tumour size; IL-6 rs1800797 A allele, rs1800797 GA genotype, rs1800795 C allele, IL-6 (rs1800797-re1800795) AC diplotype and hormonal receptor-positive disease; IL-6 rs1800797 A allele and HER2 negative status. In univariate Cox survival analysis, IL-1α rs1800587 CC and IL-6 rs1800797 GG genotype carriers exhibited worse disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS). The IL-6 rs1800795 GG genotype was associated with worse OS. IL-6 (rs1800797, rs1800795) GG/GG diplotype carriers had shorter MFS and OS. Multivariate Cox survival analysis revealed that the IL-1α rs1800587 CC genotype was an independent negative prognostic factor for DFS, MFS and OS, and the IL6 GG/GG diplotype was an independent negative prognostic factor for MFS and OS. According to the present study, functional SNPs in the IL-1α and IL-6 genes may contribute to the identification of patients at higher risk of BC recurrence, development of metastases and worse OS among early-stage patients with BC.

Lymph node metastasis in the space between the right carotid artery and jugular vein in papillary thyroid carcinoma

BackgroundThe oblique brachiocephalic trunk and right common carotid artery constitute the right carotid sheath space (RCSS). The aim of this study was to detect the clinicopathologic factors associated with RCSS lymph node metastasis.MethodsIn total, 232 papillary thyroid carcinoma (PTC) patients with preoperative contrast-enhanced computed tomography scans were analyzed for associations between RCSS lymph node metastasis and clinicopathological factors.ResultsAmong the 232 cases, 18 (7.76%) had suspicious RCSS lymph nodes, which was correlated with the presence of >5 metastatic lymph nodes, a larger thoracic inlet, and primary tumor size >2.15 cm. All pathologically confirmed metastatic lymph nodes were >1 cm in diameter.ConclusionsThe concept of “RCSS lymph node metastasis” was first introduced by this study. For PTC patients, a larger thoracic inlet, increased number of metastatic lymph nodes, and larger primary tumor size were related to RCSS lymph nodes, and more attention should be paid to patients who have lymph nodes >1 cm. A future prospective study will be designed to identify the potential risk factors for RCSS lymph node metastasis.