Node Clinical Stage Research Articles

Frequency and Consequences of Cervical Lymph Node Overstaging in Head and Neck Carcinoma.

Clinical lymph node staging in head and neck carcinoma (HNC) is fraught with uncertainties. Established clinical algorithms are available for the problem of occult cervical metastases. Much less is known about clinical lymph node overstaging. We identified HNC patients clinically classified as lymph node positive (cN+), in whom surgical neck dissection (ND) specimens were histopathologically negative (pN0) and in addition the subgroup, in whom an originally planned postoperative radiotherapy (PORT) was omitted. We compared these patients with surgically treated patients with clinically and histopathologically negative neck (cN0/pN0), who had received selective ND. Using a fuzzy matching algorithm, we identified patients with closely similar patient and disease characteristics, who had received primary definitive radiotherapy (RT) with or without systemic therapy (RT ± ST). Of the 980 patients with HNC, 292 received a ND as part of primary treatment. In 128/292 patients with cN0 neck, ND was elective, and in 164 patients with clinically positive neck (cN+), ND was therapeutic. In 43/164 cN+ patients, ND was histopathologically negative (cN+/pN−). In 24 of these, initially planned PORT was omitted. Overall, survival did not differ from the cN0/pN0 and primary RT ± ST control groups. However, more RT ± ST patients had functional problems with nutrition (p = 0.002). Based on these data, it can be estimated that lymph node overstaging is 26% (95% CI: 20% to 34%). In 15% (95% CI: 10% to 21%) of surgically treated cN+ HNC patients, treatment can be de-escalated without the affection of survival.

National guideline concordance and outcomes for pathologic N2 disease in non-small cell lung cancer.

BackgroundReal-world treatment practices for positive mediastinal nodal disease in non-small cell lung cancer (NSCLC) continues to vary despite guidelines. We aim to assess national trends in the treatment of pathologic-N2 disease, and evaluate the association with clinical nodal staging and timing of systemic therapy.MethodsThe National Cancer Database was queried for patients with NSCLC who underwent lobectomy and had pathologic-N2 disease from 2010–2017. National Comprehensive Cancer Network (NCCN) guideline concordance was evaluated. cN2 patients were analyzed based on timing of systemic therapy and response. Multivariable logistic regression evaluated outcomes by type of systemic therapy. Survival analysis utilized Cox proportional hazards regression and Kaplan-Meier methods.Results10,225 patients met inclusion criteria. Fifty-four percent of patients were understaged prior to surgery as either cN0 or cN1. Of clinically staged N2 patients, 56% received NCCN recommended neoadjuvant therapy. Annual guideline concordance increased until 2016 to a max of 62.9%. Neoadjuvant and adjuvant systemic therapy showed an overall survival benefit compared with no systemic therapy (HR 0.54 & 0.57), but no difference when compared against each other. Complete response after neoadjuvant therapy was associated with improved survival (5-year OS 56.1%, P<0.001), while partial response, no-response, and adjuvant therapy were similar. All systemic treatment strategies improved survival compared with no systemic therapy (5-year OS 24.5%).ConclusionsGuideline concordance for treatment of cN2 disease has been increasing, but still not followed in over 1/3 of patients. Responsiveness to neoadjuvant therapy appears to be a predictor of survival, and may become a prognostic adjunct for determining which patients would benefit from additional systemic therapy.

Nodal Metastases in Pediatric and Adult Acinic Cell Carcinoma of the Major Salivary Glands.

Acinic cell carcinoma (AciCC) is a rare, usually low-grade salivary malignancy. Evidence on rates of lymph node metastases (LNMs) is limited in pediatric patients and varies significantly (4%-45%) in adults. We set out to determine and compare rates of LNMs in pediatric and adult AciCC and to analyze their impact on survival, using the National Cancer Database. Historical cohort study. National Cancer Database. All AciCCs of the major salivary glands with complete clinical and pathologic nodal staging were selected between 2010 and 2016. Patient demographics, tumor characteristics, treatment, and survival were analyzed. Univariable and multivariable regression were performed to determine factors associated with LNMs and survival. We identified 57 (4.6%) pediatric patients (<18 years) and 1192 (95.4%) adults with AciCC. Clinical LNMs were rare in pediatric patients (n < 10) and adults (n = 88, 7.4%). Occult LNMs were uncommon in pediatric patients (n < 5) and adults (n = 41, 4.6%). Three-year overall survival for pediatric patients was 97.8%. Adults with LNM had worse 3-year overall survival than those without (66.0% vs 96.3%, P < .001). In multivariable regression, high-grade disease (hazard ratio, 10.15 [95% CI, 5.60-18.80]; P < .001) and T3-T4 tumors (hazard ratio, 2.80 [95% CI, 1.56-4.97]; P < .001) were associated with LNM in adult patients. LNMs in AciCC of the major salivary glands are rare in children and adults. However, high-grade and T3-T4 tumors are associated with an increased risk of LNM. LNM is associated with worse survival.

Carcinoma ex pleomorphic adenoma of the submandibular gland: A retrospective analysis of 86 patients.

To evaluate the prognostic and locoregional metastatic features of carcinoma ex pleomorphic adenoma of submandibular gland (SMG-CXPA) and improve the understanding of this uncommon condition. We retrospectively reviewed patients who were diagnosed with SMG-CXPA. The survival data of SMG-CXPA patients were statistically analyzed using Cox regression and Kaplan-Meier method. The associations between cervical metastasis and clinicopathological parameters were evaluated using chi-squared test. Additionally, two different histological categories (histological grade and invasiveness) and their combination were evaluated with the Kaplan-Meier method and receiver operating characteristic curves. In total, 86 patients were diagnosed: 38clinically node-negative, 31 pathologically node-negative, and 17 node-positive patients. Clinical tumor stage and histological grade were two independent prognostic factors for SMG-CXPA. There were significant correlations between sex, tumor size, clinical tumor stage, clinical lymph node stage, histological grade, invasiveness, malignant components, perineural invasion, and no specific criteria exist for the clinical outcome. SMG-CXPA is a high-grade malignancy with an unfavorable prognosis. Elective neck dissection should be performed in SMG-CXPA patients with a risk of locoregional metastasis. Histological grade seems to be a more valuable predictor of lymph node involvement than invasiveness.

Imaging for the Initial Staging and Post-Treatment Surveillance of Penile Squamous Cell Carcinoma.

Although relatively rare in the United States, penile squamous cell carcinoma is encountered worldwide at a higher rate. Initial diagnosis is often made on clinical exam, as almost all of these lesions are externally visible and amenable to biopsy. In distinction to other types of malignancies, penile cancer relies heavily on clinical nodal staging of the inguinal lymph node chains. As with all cancers, imaging plays a role in the initial staging, restaging, and surveillance of these patients. The aim of this manuscript is to highlight the applications, advantages, and limitations of different imaging modalities in the evaluation of penile cancer, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography.

Pathological responses and survival outcomes in patients with locally advanced breast cancer after neoadjuvant chemotherapy: a single-institute experience

BackgroundPathological complete response (pCR) is a surrogate for the efficacy of neoadjuvant chemotherapy (NCT) in locally advanced breast cancer (LABC). We analyzed the predictive clinical factors for pathological responses and survival outcomes in a cohort of Egyptian patients.MethodsWe evaluated the medical records of patients with breast cancer who received NCT in our academic institute. Survival curves were estimated with the Kaplan-Meier method. Cox proportional models were used for multiple regression analysis.ResultsOur cohort included 368 patients with a median age of 48 years (range 21–70). The median follow-up time was 3 years. The clinical tumor stage (T3–4) represented 58%, with 80% having positive axillary nodes. The luminal subgroup prevailed by 68%. The objective response rate (ORR) reached 78%, and 16% of patients achieved pCR. The clinical node stage and optimal chemotherapy were associated with higher ORR (p = 0.035 and p = 0.001, respectively). Predictors of pCR were clinical T-stage (p = 0.026), high Ki-67 index > 20 (p = 0.05), and receiving optimal chemotherapy (p = 0.014). The estimated 3-year disease free-survival (DFS) was 53%. Receptor status, achieving ORR, and pCR were associated with better DFS with hazard ratios of 0.56, p = 0.008; 0.38, p = 0.04; and 0.28, p = 0.007, respectively.ConclusionsLuminal tumors still draw benefit from neoadjuvant chemotherapy in terms of clinical response and breast conservative surgery. Treatment escalation to those who did not achieve pCR requires more investigation, given a higher recurrence rate in real-world experience.

Systemic inflammatory response in predicting outcomes of patients undergoing curative resection for oral squamous cell carcinoma

This study aimed to evaluate the prognostic significance of the modified Glasgow prognostic score (mGPS), neutrophil:lymphocyte ratio (NLR), and platelet:lymphocyte ratio (PLR) in patients undergoing resection of oral squamous cell carcinoma (OSCC) with curative intent. We also aimed to explore the relation between activated systemic inflammation and adverse tumour characteristics. Between February 2006 and December 2019, data on 825 patients undergoing curative resection of OSCC were retrospectively gathered. Preoperative C-reactive protein and serum albumin levels were obtained to calculate a mGPS. Full blood count parameters were collected to calculate NLR and PLR values. Categorical factors were analysed using the chi squared test. Multivariate regression was performed to identify independent prognostic variables and the predictive value of each model generated. For disease-specific survival (DSS) and overall survival (OS), mGPS (DSS and OS both p<0.001), NLR (DSS and OS both p<0.001) and PLR (DSS and OS both p<0.001) were significant on univariate analysis. Independent predictive variables for DSS included mGPS, clinical node stage, categorised depth of tumour invasion, non-cohesive invasive front, and lymphovascular invasion. The concordance index was acceptable (0.756) for this model. Replacing mGPS with NLR or PLR as a marker of systemic inflammation demonstrated the same preoperative variables as independently predictive for DSS. The concordance index for these models were acceptable (NLR 0.76 and PLR 0.756). The systemic inflammatory response is prognostically significant in patients undergoing curative resection of OSCC. The potential link between an inflammatory tumour microenvironment and activated systemic inflammation merits further investigation.

Clinical Prognostic Factors for Patients With Esophageal Cancer Treated With Definitive Chemoradiotherapy.

BackgroundTreatment with definitive chemoradiotherapy (CRT) is the best option for patients with locally advanced esophageal tumors considered unresectable or for patients without clinical conditions to undergo surgical treatment. Technological advances in radiotherapy in the last decades have made treatment more accurate with less toxicity, and the association with more effective systemic treatment has been gradually improving survival rates.AimEvaluate clinical prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with esophageal cancer treated with definitive radiotherapy (RT) and chemotherapy (ChT).Material and methodsThe clinical records of 60 patients treated from April 2011 until December 2019 with esophageal cancer considered unresectable and/or without clinical conditions for surgery, treated with definitive CRT, were analyzed. All patients had upper digestive endoscopy (UDE) with positive biopsy, neck, chest, and abdominal CT scan, and 18F-fluorodeoxyglucose positron-emission tomography (PET-CT). Patients were followed with physical examination and CTs every three months in the first and second years and every six months from the third year of follow-up. UDE was made every three to six months after the end of the treatment or in suspicion of tumor recurrence. PET-CT was also performed in the follow-up when clinically necessary. Local and regional failure (LRF) was defined as abnormalities in the image tests within the planning target volume (PTV) and/or positive biopsy on UDE. Any other failure was defined as a distant failure (DF). PFS was defined in the record of the first tumor recurrence site and OS in the death record from the date of the start of treatment.ResultsThe median age of the patients was 66 years (range: 33 to 83 years) and 46 patients (76.7%) were male. Squamous cell carcinoma (SCC) was the most frequent histological type (85%). Most patients had tumors located in the mid-thoracic esophagus (53.3%) and stage III or IV (59.9%). All patients were treated using 3D (76.7%) or intensity-modulated radiotherapy (IMRT; 23.3%). The median total dose was 50.4Gy (41.4-50.4). All patients received platinum-based ChT concomitant with RT. The most common regimen used was carboplatin and paclitaxel, with a median of five cycles. With a median follow-up of 19 months, the median PFS and OS were 10 and 20 months, respectively. LRF and DF as the first site of failure were observed in 22 (36.6%) and 26 (43.3%) patients, respectively. In the univariate analysis, tumor length lower than 2.6 cm, gross tumor volume (GTV) volume lower than 28 cm3, clinical tumor stages T1 and T2, clinical node stage N0, clinical prognostic stage groups I and II, and complete response to treatment, were statistically significant factors for better PFS and OS. In the multivariate analysis, the presence of clinical nodal stage N0 was related to better PFS (p=0.02).ConclusionNode clinical status was the most important clinical factor for PFS. Despite all the technical progress observed in radiotherapy, treatments concomitant with platinum-based chemotherapy are associated with high levels of LRF and DF. New strategies in systemic therapy and radiotherapy are necessary for improving outcomes.

Impact of COVID-19 on presentation, staging, and treatment of head and neck mucosal squamous cell carcinoma

ObjectivesDuring the COVID-19 pandemic, maintenance of safe and timely oncologic care has been challenging. The goal of this study is to compare presenting symptoms, staging, and treatment of head and neck mucosal squamous cell carcinoma during the pandemic with an analogous timeframe one year prior. Materials and methodsRetrospective cohort study at a single tertiary academic center of new adult patients evaluated in a head and neck surgical oncology clinic from March -July 2019 (pre-pandemic control) and March - July 2020 (COVID-19 pandemic). ResultsDuring the pandemic, the proportion of patients with newly diagnosed malignancies increased by 5%, while the overall number of new patients decreased (n = 575) compared to the control year (n = 776). For patients with mucosal squamous cell carcinoma (SCC), median time from referral to initial clinic visit decreased from 11 days (2019) to 8 days (2020) (p = 0.0031). There was no significant difference in total number (p = 0.914) or duration (p = 0.872) of symptoms. During the pandemic, patients were more likely to present with regional nodal metastases (adjusted odds ratio (OR) 2.846, 95% CI 1.072-3.219, p = 0.028) and more advanced clinical nodal (N) staging (p = 0.011). No significant difference was seen for clinical tumor (T) (p = 0.502) or metastasis (M) staging (p = 0.278). No significant difference in pathologic T (p = 0.665), or N staging (p = 0.907) was found between the two periods. ConclusionHead and neck mucosal SCC patients presented with more advanced clinical nodal disease during the early months of the COVID-19 pandemic despite no change in presenting symptoms.

PD57-02 NATIONAL CANCER DATABASE ANALYSIS ASSESSING THE IMPACT OF TREATMENT MODALITIES ON SURVIVAL OUTCOMES IN LOCALIZED NEUROENDOCRINE PROSTATE ADENOCARCINOMA

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD57)1 Sep 2021PD57-02 NATIONAL CANCER DATABASE ANALYSIS ASSESSING THE IMPACT OF TREATMENT MODALITIES ON SURVIVAL OUTCOMES IN LOCALIZED NEUROENDOCRINE PROSTATE ADENOCARCINOMA Chandler Bronkema, Sohrab Arora, Jacob Keeley, Nikola Rakic, Akshay Sood, Deepansh Dalela, Maxwell Stricker, Phil Olson, Craig G. Rogers, Mani Menon, and Firas Abdollah Chandler BronkemaChandler Bronkema More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Nikola RakicNikola Rakic More articles by this author , Akshay SoodAkshay Sood More articles by this author , Deepansh DalelaDeepansh Dalela More articles by this author , Maxwell StrickerMaxwell Stricker More articles by this author , Phil OlsonPhil Olson More articles by this author , Craig G. RogersCraig G. Rogers More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002091.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neuroendocrine (NEC) adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this malignancy, optimal treatment strategies for men with nonmetastatic NEC PCa is largely unknown. We sought to describe the impact of initial surgery, radiotherapy (RT), systemic therapy (ST) and observation on overall survival (OS) in men with nonmetastatic NEC PCa. METHODS: We selected 456 cases of localized NEC PCa, diagnosed between 2004 and 2015, within the National Cancer Database. Covariates included age, race, Charlson comorbidity score, clinical T stage, clinical lymph node stage, serum prostate specific antigen (PSA), and income. Cox regression analysis tested the impact of treatment (surgery, RT, ST and observation) on OS after adjusting for all covariates. Adjusted Kaplan-Meier estimates were used to visualize the impact of treatment modality on OS. RESULTS: In men with nonmetastatic NEC PCa, median (IQR) age and PSA were 70 (63-78) years and 5.3 (2.1-11.1) ng/mL, respectively. Advanced local stage (≥cT3a) was most frequently observed in patients treated with ST (52.6%), followed by those treated with RT (40.2%), observation (20.0%) and surgery (15.9%, p<0.001). Serum PSA at presentation was highest in the ST cohort (median 15.6 ng/ml, IQR: 1.6-49.1), followed by the surgery (median 5.9 ng/ml, IQR: 4.0-9.6) and observation cohorts (median 5.9 ng/ml, IQR: 1.6-11.3), and finally, the RT cohort (median 4.6 ng/ml, IQR: 1.9-11.3, p=0.002). Estimated 5-year OS was highest in the surgery cohort (58.1%), followed by the RT (33.8%), observation (13.6%) and ST cohorts (7.9%; all p<0.001). Adjusted Kaplan-Meier estimates are displayed in the figure below. Multivariable analysis showed that compared to men treated surgically, OS was significantly lower for patients under observation (HR 5.2; 95% CI: 2.5-10.6); however, OS was not significantly different for patients receiving RT (HR 1.0; 95% CI: 0.6-1.6) or ST (HR 1.7; 95% CI: 0.9-3.2). CONCLUSIONS: In men diagnosed with localized neuroendocrine PCa, initial surgical treatment is associated with more favorable OS outcomes compared to observation but not RT or ST. Our findings should be interpreted within the framework of a retrospective study design. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1009-e1010 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chandler Bronkema More articles by this author Sohrab Arora More articles by this author Jacob Keeley More articles by this author Nikola Rakic More articles by this author Akshay Sood More articles by this author Deepansh Dalela More articles by this author Maxwell Stricker More articles by this author Phil Olson More articles by this author Craig G. Rogers More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial

For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up. From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT. Patients were stratified by PSA, tumor grade, and surgical versus clinical nodal staging. ADT was flutamide with either goserelin or leuprolide for 4 months. Prostate RT (66.6 Gy) was started after 2 months. OS was calculated at the date of death from any cause or at last follow-up. Secondary endpoints were DSM, BF, local progression, and DM. Acute and late toxic effects were assessed using RTOG toxicity scales. Median follow-up in surviving patients was 14.8 years (range, 0.16-21.98). The 10-year and 18-year OS was 56% and 23%, respectively, with RT alone versus 63% and 23% with combined therapy (HR 0.94; 95% confidence interval [CI], 0.85-1.05; P=.94). The hazards were not proportional (P=.003). Estimated restricted mean survival time at 18 years was 11.8 years (95% CI, 11.4-12.1) with combined therapy versus 11.3 years with RT alone (95% CI, 10.9-11.6; P=.05). The 10-year and 18-year DSM was 7% and 14%, respectively, with RT alone versus 3% and 8% with combined therapy (HR 0.56; 95% CI, 0.41-0.75; P < .01). DM and BF favored combined therapy at 18 years. Rates of late grade ≥3 hepatic, gastrointestinal, and genitourinary toxicity were ≤1%, 3%, and 8%, respectively, with combined therapy versus ≤1%, 2%, and 5% with RT alone. Further follow-up demonstrates that OS converges at approximately 15 years, by which point the administration of 4 months of ADT had conferred an estimated additional 6 months of life.

Combination of 35-Gene Mutation Profile and Radiotherapy Dosimetry Predicts the Therapeutic Outcome of Definitive Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma.

Esophageal cancer is a common malignancy worldwide and a leading cause of cancer-related mortality. Definitive concurrent chemoradiotherapy (CCRT) has been widely used to treat locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we evaluated the predictive power of a 35-gene mutation profile and radiation parameters in patients with ESCC. Data from 44 patients with ESCC who underwent definitive CCRT were retrospectively reviewed. A 35-gene mutation profile, derived from reported ESCC-specific next-generation sequencing results, and radiation dosimetry parameters were examined using the Kaplan–Meier curve and Cox proportional hazards model. All patients were native Chinese and underwent CCRT with a median follow-up time of 22.0 months. Significant prognostic factors affecting progression-free survival in the multivariable Cox regression model were clinical nodal staging ≥2 (hazard ratio, HR: 2.52, 95% CI: 1.15–5.54, p = 0.022), ≥10% lung volume receiving ≥30 Gy (V30) (HR: 2.36, 95% CI: 1.08–5.17, p = 0.032), and mutation of fibrous sheath interacting protein 2 (FSIP2) (HR: 0.08, 95% CI: 0.01–0.58, p = 0.013). For overall survival, significant prognostic factors in the multivariable Cox regression model were lung V30 ≥10% (HR: 3.71, 95% CI: 1.48–9.35, p = 0.005) and mutation of spectrin repeat containing nuclear envelope protein 1 (SYNE1) (HR: 2.95, 95% CI: 1.25–6.97, p = 0.014). Our cohort showed higher MUC17 (79.5% vs. 5.7%), FSIP2 (18.2% vs. 6.2%), and SYNE1 (38.6% vs. 11.0%) mutation rates and lower TP53 (38.6% vs. 68.7%) mutation rates than the ESCC cohorts from The Cancer Genome Atlas. In conclusion, by using a combination of a 35-gene mutation profile and radiotherapy dosimetry, mutations in FSIP2 and SYNE1 as well as lung V30 were identified as potential predictors for developing a prediction model for clinical outcomes in patients with ESCC administered definitive CCRT.

Intra- and Interlaboratory Reproducibility of the Sensitivity to Endocrine Therapy Assay for Stage II/III Breast Cancer.

The sensitivity to endocrine therapy assay (SET2,3) predicts treatment outcomes in Stage II-III breast cancer. SET2,3 measures transcription related to estrogen and progesterone receptors (SETER/PR index) and the molecular subtype (RNA4: ESR1, PGR, ERBB2, AURKA) from formalin-fixed paraffin-embedded (FFPE) tissue sections. We designed a nested study across 3 pathology laboratories, each testing 60 breast cancers twice in controlled batches. Laboratories macrodissected and directly homogenized the unstained FFPE tumor sections, then performed the QuantiGene Plex bead-based hybridization assay. SET2,3 was calculated centrally using predefined statistical R-scripts and applying pre-defined cutpoints. Concordance correlation coefficient (CCC) was calculated from continuous measurements and Kappa statistic from categorical results. A mixed-effects model estimated contributions to bias (fixed effects) and variance (random effects) from the replicated design. Intralaboratory (CCC 0.96-0.99) and interlaboratory (CCC 0.98-0.99) SET2,3 results were concordant, with rates of agreement for high/low categorization within (Kappa 0.83-0.93) and between laboratories (Kappa 0.87-0.88). The relative contributions to overall variance of SET2,3 measurements were 96.90% from biological differences between cancers, 0.67% from interlaboratory variability, and 2.44% from residual causes including intralaboratory replicates. Similar results were obtained with SETER/PR, the baseline prognostic index calculated using pathological or clinical tumor and nodal staging information, and the 4 individual genes (ESR1, PGR, ERBB2, and AURKA). Intra- and interpathology laboratory measurements of SET2,3 and its components were highly reproducible when tested from FFPE tumor sections.

Invasive Lobular Breast Cancer: Data to Support Surgical Decision Making

Invasive lobular carcinoma (ILC) is thought be a unique entity with higher rates of multifocal/multicentric and bilateral disease. This study aimed to evaluate the true extent of the disease, risk of bilaterality, lymph node involvement, and impact of preoperative imaging to help guide surgical decisionmaking. A retrospective analysis identified patients treated for ILC between 2004 and 2017. Clinical staging and pathologic results were compared. Follow-up details including local recurrence, contralateral breast cancer (CBC), and survival outcomes were evaluated. The study identified 692 patients with ILC, including 43 patients (6%) with a diagnosis of CBC and 232 patients (33%) with a diagnosis of multifocal/multicentric disease at presentation. Preoperative magnetic resonance imaging (MRI) led to an identification of additional disease in 20% of the patients. Preoperative MRI resulted in a more accurate prediction of tumor size staging but did not improve the discordance between clinical and pathologic nodal staging. Overall, the rate of imaging occult lymph node disease was 24%. At the 6-year follow-up evaluation, a local recurrence had developed in 2.3%, a CBC in 2.3, and a distant metastasis in 9.4% of the patients. The overall survival rate was 96% at 3 years and 91% at 5 years. Invasive lobular carcinoma is a distinct subset of cancer that poses a diagnostic staging challenge. The results of this study favor MRI for accurate tumor staging and for improving detection of multicentricity and bilaterality. However, clinicians should be aware of the higher likelihood of occult lymph node involvement with ILC and subsequent early metastasis.

Pre-Operative Prediction of Mediastinal Node Metastasis Using Radiomics Model Based on 18F-FDG PET/CT of the Primary Tumor in Non-Small Cell Lung Cancer Patients.

Purpose: We investigated whether a fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics model (RM) could predict the pathological mediastinal lymph node staging (pN staging) in patients with non-small cell lung cancer (NSCLC) undergoing surgery.Methods: A total of 716 patients with a clinicopathological diagnosis of NSCLC were included in this retrospective study. The prediction model was developed in a training cohort that consisted of 501 patients. Radiomics features were extracted from the 18F-FDG PET/CT of the primary tumor. Support vector machine and extremely randomized trees were used to build the RM. Internal validation was assessed. An independent testing cohort contained the remaining 215 patients. The performances of the RM and clinical node staging (cN staging) in predicting pN staging (pN0 vs. pN1 and N2) were compared for each cohort. The area under the curve (AUC) of the receiver operating characteristic curve was applied to assess the model's performance.Results: The AUC of the RM [0.81 (95% CI, 0.771–0.848); sensitivity: 0.794; specificity: 0.704] for the predictive performance of pN1 and N2 was significantly better than that of cN in the training cohort [0.685 (95% CI, 0.644–0.728); sensitivity: 0.804; specificity: 0.568], (P-value = 8.29e-07, as assessed by the Delong test). In the testing cohort, the AUC of the RM [0.766 (95% CI, 0.702–0.830); sensitivity: 0.688; specificity: 0.704] was also significantly higher than that of cN [0.685 (95% CI, 0.619–0.747); sensitivity: 0.799; specificity: 0.568], (P = 0.0371, Delong test).Conclusions: The RM based on 18F-FDG PET/CT has a potential for the pN staging in patients with NSCLC, suggesting that therapeutic planning could be tailored according to the predictions.

The Correlation between Clinical and Pathological Lymph Node Status in Oral Squamous Cell Carcinoma

Abstract Introduction: The presence of nodal metastasis from OSCC is the single most important prognostic feature. Extranodal extension further decreases survival by approximately half. Clinical evaluation of the nodal basin has been found to correlate poorly with pathological nodal status. Objectives: Determine the congruency between clinical and pathological nodal status and the incidence of extranodal extension (ENE). Describe the frequency distribution of age, sex, smoking habits, anatomical location, and histology in a South African population. Methods: Ninety-one consecutive cases of oral squamous cell carcinoma were retrospectively studied and the clinical (cN) and pathological (pN) TNM nodal staging compared using the 8th edition of the AJCC/UICC TNM staging system. Extranodal extension was determined in all patients with OSCC, as well as in the subgroup with clinically nodal negative (cN0) disease. The socio-demographical information was described. Results: The cN and pN were congruent in 41.7% (n = 38/91), upstaged in 35.2% (n = 32/91), and down staged in 23.1% (n = 21/91) of cases. Twenty-two patients (24.2%) had pathological evidence of ENE. Males and females constituted 67% and 33% of the study sample, respectively. The median age at the time of diagnosis was 57.3 years (range 5-85 years). A smoking history was present in 73.6%, absent in 14.3%, and unknown in 12.1% of patients. The tongue (38.4%) and floor of mouth (29.7%) were the most common anatomical subsites for primary tumours. Most tumours were conventional squamous cell carcinomas with poorly differentiated grade (62.6%). Conclusion: There is poor correlation between clinical and pathological nodal status when the 8th TNM staging is used. ENE at the time of diagnosis is common among patients with OSCC.

The predictive value of neutrophil-to-lymphocyte ratio on overall survival and pathological complete response in breast cancer patients receiving neoadjuvant chemotherapy.

e12625 Background: Neutrophil-to-lymphocyte ratio (NLR) has been found to offer clear predictive utility for the overall survival (OS) and pathologic complete response (pCR) in breast cancer (BC) patients receiving neoadjuvant chemotherapy(NAC). However, previous studies mainly focused on pre-NLR. The aim of this study was to explore the role of pre-/post-NLR towards OS and longitudinal NLR kineticsonpCR for BC patients undergoing NAC. And we also tried to build a nomogram for OS prediction based on these parameters. Methods: In this study, we retrospectively collected 501 female patients with locally advanced BC receiving 4-8 cycles of NAC from 2009 to 2018. Clinicopathological characteristics, NLR at pre-, mid-(every two cycles of NAC) and post-treatment were collected. The primary endpoint was OS. Among the patients, 421 patients with available pre- and post-NLR were included in the survival analysis. These patients were randomly divided into a training cohort (n = 224) and a validation cohort (n = 197). Multivariate survival model was built by including all the significant prognostic factors from the univariate analysis in the training cohort, and a nomogram model was established by “R” version 3.4.3. The performance of the model was further tested in the validation cohort by the concordance index. The second endpoint was pCR. Longitudinal analysis of NLR was performed using a mixed-effects regression model to predict pCR among 176 patients who finished 8 cycles of NAC. Results: The median follow-up time was 43.2 months for 421 patients. In the training cohort, multivariate analysis revealed that ER status, clinical node stage , pCR , pre-NLR, and post-NLR (all Ps＜0.05) were independent predictors of OS. Nomogram for OS prediction was established by combining all these significant factors. The C-indexes of the nomogram were 0.764 and 0.693, respectively in the training and validation cohort. In the longitudinal analysis, patients achieved pCR experienced a reduction of NLR every 2 cycles (Coef = -0.032, std error = 0.014, P = 0.024). Conclusions: This study demonstrated the prognostic value of pre-NLR and post-NLR towards BC patients received NAC. Based on that , a novel nomogram was established to predict the 3- and 5- year OS for BC patients. And we also found patients who experienced a decline of NLR during NAC seems to be more likely to achieve pCR from chemotherapy. Routine assessment of NLR may be an easy and affordable tool for defining prognosis.

Lower neck organs at risk sparing in nasopharyngeal carcinoma using hybrid volumetric-modulated arc therapy (hybrid-VMAT): a case report

AbstractIntroduction:Nasopharyngeal carcinoma (NPC) is a prevalent disease in Southern China. Radiation therapy remains the primary treatment modality for NPC due to its high radiation sensitivity. Conventional volumetric-modulated arc therapy (VMAT) can achieve excellent target volume coverage and superior conformal dose distributions while sparing organs at risk (OARs). However, VMAT may also produce substantial volume of low-dose region in the surrounding normal tissue. Our oncology centre has incorporated the concept of anterior cervical field with VMAT in clinical practice of NPC treatment planning. The purpose of this treatment-comparison case study is to demonstrate the lower neck OARs sparing ability of hybrid volumetric-modulated arc therapy (hybrid-VMAT) over conventional VMAT for NPC.Methods:Four patients diagnosed with NPC of different clinical lymph node staging (N staging) were enrolled for this treatment-comparison case study. Planning target volumes and OARs were delineated with reference to Radiation Therapy Oncology Group (RTOG) 0225/0615. Additional OARs from lower neck region, including thyroid, trachea, cervical spine and pharyngeal constrictor muscles (PCMs), were also delineated. Two treatment techniques, hybrid-VMAT and VMAT, were created for each patient’s dataset.Results and findings:Both treatment techniques produced adequate target coverage and reduced radiation dose to the OARs as suggested in RTOG 0225/0615. Hybrid-VMAT plans achieved superior dose reduction in larynx, oesophagus, middle PCM, inferior PCM, cervical spine and trachea comparing with VMAT plans. Hence, the clinical usability and functional outcome of hybrid-VMAT should be further investigated for NPC radiation therapy.

Navigating Nodal Metrics for Node-Positive Gastric Cancer in the United States: An NCDB-Based Study and Validation of AJCC Guidelines.

The optimal number of examined lymph nodes (ELNs) and the positive lymph node ratio (LNR) for potentially curable gastric cancer are not established. We sought to determine clinical benchmarks for these values using a large national database. Demographic, clinicopathologic, and treatment-related data from patients treated using an R0, curative-intent gastrectomy registered in the National Cancer Database during 2004 to 2016 were evaluated. Patients with node-positive (pTxN+M0) disease were considered for analysis. A total of 22,018 patients met the inclusion criteria, with a median follow-up of 2.2 years. Mean age at diagnosis was 65.6 years, 66% were male, 68% were White, 33% of tumors were located near the gastroesophageal junction, and 29% of patients had undergone preoperative therapy. Most primary tumors (62%) were category pT3-4, 67% had a poor or anaplastic grade, and 19% had signet features. Clinical nodal staging was inaccurate compared with staging at final pathology. The mean [SD] number of nodes examined was 19 [11]. On multivariable analysis, the pN category, ELNs, and LNR were independently associated with survival (all P<.0001). Using receiver operating characteristic (ROC) analysis, an optimal ELN threshold of ≥30 was established for patients with pN3b disease and was applied to the entire cohort. Node positivity and LNR had minimal change beyond 30 examined nodes. Stage-specific LNR thresholds calculated by ROC analysis were 11% for pN1, 28% for pN2, 58% for pN3a, 64% for pN3b, 30% for total combined. By using an ELN threshold of ≥30, prognostically advantageous stage-specific LNR values could be determined for 96% of evaluated patients. Using a large national cancer registry, we determined that an ELN threshold of ≥30 allowed for prognostically advantageous LNRs to be achieved in 96% of patients. Therefore, ≥30 examined nodes should be considered a clinical benchmark for practice in the United States.

Abstract PS13-19: Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype

Abstract Introduction: Axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) confers higher overall and recurrence-free survival, compared to residual axillary disease. Recent findings suggest that pCR in the breast (ypT0) post-NAC is associated with a pathologically negative axilla (ypN0) in patients (pts) presenting with lower stage HER2+ and triple negative breast cancer (TNBC). Additional studies are needed to understand how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes, including hormone-receptor (HR) positive tumors. The ability to reliably predict axillary pathologic response post-NAC may allow identification of a subset of pts for whom axillary staging may be safely omitted. We hypothesize that tumor subtype and lower clinical stage at presentation are associated with ypN0. Methods: A single institution cancer registry was retrospectively reviewed for pts receiving NAC followed by surgery from January 2010-June 2018. Fisher’s exact tests were used to compared proportion of breast and axillary pCR by tumor subtype (TNBC, HR+/HER2-, HR+/HER2+ and HR-/HER2+). Univariable logistic regression determined factors associated with ypN0. Multivariable logistic regression determined the association between ypN0 and tumor subtype adjusting for factors that retained significance on univariable analysis. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. Results: Of the 1348 pts who received NAC followed by surgery, median age was 54 (IQR 44-63); 59% (n=738) were postmenopausal. Proportion of tumor subtypes were: 15% (n=197) TNBC, 12% (n=155) HR+/HER2-, 48% (n=653) HR+/HER2+, and 25% (n=343) HR-/HER2+. Tumor size at diagnosis was: 1% (n=18) T0, 20% (n=272) T1, 53% (n=713) T2, 17% (n=230) T3 and 9% (n=111) T4. Clinical nodal staging at diagnosis was: 52% cN0 (n=695), 41% cN1 (n=550), 5% cN2 (n=61), and 3% cN3 (n=43). TNBC and HER2+ subtypes were associated with the highest rate of breast pCR and ypN0. On univariable analyses of the cN positive pts, younger age at diagnosis, non-postmenopausal status, oral contraceptive use, alcohol consumption, cT stage, cN stage and tumor subtype were significantly associated with ypN0 (Table1A). In the adjusted model, postmenopausal status, cT, and tumor subtype were associated with ypN0. Lower cT and HR- subtypes had significantly higher odds of ypN0 (Table 1B). In sensitivity analyses, cN2/cN3 was associated with lower odds of ypN0 compared to cN0/cN1 disease in TNBC (OR0.11 95%CI 0.03,0.40, p=0.001), HR-/HER2+ disease (OR0.42, 95%CI 0.22,0.77, p=0.005), and HR+/HER2+ (OR0.26 95%CI 0.11,0.61 p=0.002), but not in HR+/HER2- disease (OR1.17, 95%CI 0.25,5.57, p=0.838). Conclusion: HR- and low cT stage at diagnosis are associated with ypN0 in this large cohort. Younger age, pre-menopausal status and cN stage may be important considerations in future investigations aimed at defining the subset of patients most likely to achieve ypN0 and ultimately to be considered for de-escalation of axillary staging post NAC. A.Univariable logistic regression analysisVariableOdds Ratio95% Confidence Intervalp valueAge at diagnosis0.990.98, 0.99&amp;lt;0.001RaceWhite1.060.70, 1.600.777Black0.600.17, 2.080.421Asian1.200.36, 4.000.768Postmenopausal0.760.60, 0.960.023BMI1.000.99. 1.000.424Oral contraceptive use1.250.95, 1.630.114Alcohol consumption1.601.05, 2.440.027 Tobacco use1.130.99, 1.290.064Family history of cancer1.250.92, 1.680.148Grade12.170.75, 6.250.15320.950.45, 2.010.89131.700.81, 3.590.163HistologyIDC1.451.10, 1.890.007ILC0.370.23, 0.60&amp;lt;0.001Mixed0.950.68, 1.320.764Other0.440.18, 1.080.073Clinical T stage11.370.47, 3.980.56920.760.27, 2.160.60530.350.12, 1.020.05540.150.05, 0.450.001Clinical N stage10.140.11, 0.18&amp;lt;0.00120.130.07, 0.23&amp;lt;0.00130.110.06, 0.21&amp;lt;0.001Tumor subtypeTNBC1.591.00, 2.530.049HR+/ HER2 -0.550.35, 0.870.010HR+/ HER2+0.690.47, 1.000.049HR-/ HER2 +1.641.09, 2.460.019B.Multivariable logistic regression analysisAge at diagnosis0.980.97, 0.99&amp;lt;0.001Alcohol use1.190.74, 1.930.476HistologyIDC1.150.82, 1.610.414ILC0.570.32, 1.010.053Mixed1.080.71, 1.630.721Other0.790.28, 2.220.660Clinical T stage11.190.39, 3.580.76120.740.25, 2.160.58530.510.17, 1.540.23540.290.09, 0.910.034Clinical N stage10.130.10, 0.18&amp;lt;0.00120.140.08, 0.26&amp;lt;0.00130.100.05, 0.20&amp;lt;0.001Tumor subtypeTNBC1.440.84, 2.470.181HR+/ HER2 -0.540.31, 0.940.028HR+/ HER2+0.600.39, 0.930.024HR-/ HER2 +1.701.05, 2.730.030 Citation Format: Sara P Myers, Gillian M Ahrendt, Joanna S Lee, Jennifer G Steiman, Atilla Soran, Ronald R Johnson, Priscilla F McAuliffe, Emilia J Diego. Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype [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 PS13-19.