T1N0 Patients Research Articles

Non-adherence to recommended adjuvant radiation after total laryngectomy

ObjectivesInvestigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). MethodsPreviously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. ResultsAmong 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72–0.93) analysis. ConclusionsWithin the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Thymoma resection and myasthenia gravis: what is the neurological outcome in patients older than 65years?

To increase the neurological results in patients older than 65years with myasthenia gravis after thymectomy, we retrospectively analysed this outcome in a large bicentric cohort of patients with myasthenia gravis (MG)years, for which surgery was indicated for a concurrent thymoma. From 1/2000 to 2/2022, 502 patients underwent thymectomy for thymic epithelial tumours (TETs) in two high-volume Institutions (167aged more than 65years). Among them, 66 patients were affected by TET and MG, representing our final study group. The mean age for MG onset was 68.3 ± 6years.At surgery, the Osserman score 2 was the most diffuse in our cohort (43, 65.1%), followed by 1 (20, 30.3%). In 11 cases, the MG diagnosis coincided with thymoma diagnosis. In the other cases, the interval between MG diagnosis and surgery was 1.7years ± 1.9. The most common surgical approach was sternotomy (41,62.1%), followed by RATS (14,21.2%). The most frequent TNM stage was T1N0 (75.7%) and most patients had WHO type-B tumour. After radical thymectomy, 58 patients (88%) reported a significant neurological improvement. According to MGFA-PIS, after surgery we had 4 (6%) complete stable remission, 11 (16.7%) pharmacological remission, 43 (65.2%) minimal manifestation, 2 (3%) worsening/death for MG, and 5 (7.6%) unchanged. No association was found between neurological outcome and age of MG onset, kind of pharmacological therapy before surgery, surgical approach (sternotomy vs others), tumour dimension, the ITMIG stage and the preoperative Osserman score. For MG and thymoma-afftected patients over 65years, thymectomy seems to be an effective treatment to improve neurological symptoms. We suggest to set up clinical trials to explore the neurological efficacy of mini-invasive thymectomy in clinically selected MG patients aged over 65years.

Effects of Chemotherapy and Radiation Therapy on Early Laryngeal Cancers.

Treatments for early laryngeal squamous cell carcinoma (SCC) include radiotherapy (RT), chemoradiotherapy (CRT), and larynx-preserving surgery. In this study, early laryngeal SCC was treated with RT in patients with stage I (T1N0) tumors and with CRT and docetaxel (DOC) in patients with stage II (T2N0) tumors and the treatment results and effectiveness of the chemotherapy were compared. A total of 78 patients with early-stage laryngeal SCC were enrolled in this study. The T1N0 patients received radiation for the primary lesions as outpatients at a total dose of 63-70 Gy. By contrast, the T2N0 patients were hospitalized and treated with CRT, receiving a total radiation dose of 66-70 Gy. Docetaxel (DOC, 10 mg/m2) was administered intravenously once a week for 6-8 consecutive weeks concurrently with radiotherapy. The adverse events and survival rates with local control rates were examined. The number of non-glottic T2N0 patients was significantly higher than that of T1N0 patients. Although all patients completed their treatment schedule, significantly more grade 3 adverse events were observed in the T2N0 patients, in particular mucositis and dermatitis, than in T1N0 patients. The 5-year overall survival rate, disease specific survival rate, local control rate, and laryngeal preserve rate of the T1N0 and T2N0 patients were 86.1, 93.3, 88.6, and 94.3% and 85.9, 88.0, 93.1, and 93.1%, respectively. CRT with docetaxel showed the best therapeutic outcomes for the treatment of laryngeal SCC in patients with T2N0 tumours, with a higher local control rate, effective laryngeal preservation, and relatively few adverse events.

Therapeutic impact of 18F-FDG PET/CT for initial staging in patients with clinical stage I and IIA, HER2-positive, or triple-negative breast cancer.

While 18F-FDG PET/CT (FDG-PET/CT) is consensual for clinical stage ≥ IIB breast cancers (BC), its benefit for stage I or IIA HER2+ or triple-negative breast cancer (TNBC) patients lacks sufficient evidence. We reported a single-institution, retrospective study evaluating FDG-PET/CT impact on patient management and staging for stage I or IIA HER2+ or Triple-Negative BC. Patients who underwent FDG-PET/CT staging before any treatment between January 2015 and December 2020 at Oscar Lambret Center were included. patients with symptoms or conventional imaging suggestive of metastatic dissemination, or with prior malignancies. Initial stage was determined from mammography, breast ultrasound, breast MRI, and clinical examination. Staging and therapeutic impact based on FDG-PET/CT findings collected, including intra- (modification of dose/site/strategy in a type of management previously indicated) and inter-modality (modification of planned treatment strategy) changes. The cohort included 287 female patients with clinical stage I or IIA, HER2+ , or TNBC. Therapeutic impact observed for 18% of patients (n = 52), with 2% (n = 7) undergoing inter-modality change with omission of planned surgery. The impact on patient management was higher for stage IIA patients (20%, 47/237) than for stage I patients (10%, 5/50). Among stage IIA disease, changes in management were more important for T2N0 patients (22%, 44/205) than for T1N1 patients (9%, 3/32). While not statistically significant, trends suggest usefulness of FDG-PET/CT for T2N0 patients. Considering substantial therapeutic implications, our study suggests the usefulness of FDG-PET/CT for patients with stage IIA, HER2-positive, or Triple-Negative BC with tumor size > 2cm (T2N0).

Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Impact of deep muscle invasion on nodal status and survival in patients with pT2 esophageal squamous cancer.

Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan‒Meier analysis and a Cox proportional hazard regression model. A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.

444. SHOULD T2 ESOPHAGEAL SQUAMOUS CELL CARCINOMA BE SUBCLASSIFIED WITH RESPECT TO LYMPH NODE INVOLVEMENT AND SURVIVAL?

Abstract Background Whether T2 esophageal squamous cell carcinoma should be subclassified into circular muscle (T2a) and longitudinal muscle (T2b) remains controversial. We aimed to investigate the effect of the depth of muscularis propria invasion on the incidence of lymph node involvement and patient survival outcomes in T2 esophageal squamous cell carcinoma. Methods We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. The pathological information of the depth of muscularis propria invasion was reassessed, and patients were grouped into the T2a group and T2b group. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan–Meier analysis and a Cox proportional hazard regression model. Results This study included a total of 750 patients from three institutes. The depth of muscularis propria invasion (OR: 3.95, 95% CI: 2.46–6.35; P &amp;lt; 0.001) was correlated with lymph node metastases using logistic regression. T substage (OR: 1.37, 95% CI: 1.05–1.79; P &amp;lt; 0.001) and N status (OR: 1.51, 95% CI: 1.05–2.17; P &amp;lt; 0.001) were independent risk factors in multivariate Cox regression analysis. The T2a group had better overall survival (OR: 1.52, 95% CI: 1.19–1.94; P = 0.001) than the T2b group, specifically in T2N0 patients (OR: 1.38, 95% CI: 1.08–1.94; P = 0.035). Conclusions The depth of muscularis propria invasion should be subclassified to T2a and T2b with respect to lymph node involvement and survival outcomes in T2 esophageal squamous cell carcinoma.

Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.

To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS). Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model. We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients. In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.

Conditional survival after radical cystectomy for non-metastatic muscle-invasive squamous cell carcinoma of the urinary bladder: A population-based analysis.

To assess the effect of event-free survival duration on cancer-specific mortality (CSM) after radical cystectomy (RC) in nonmetastatic muscle-invasive squamous cell carcinoma of the urinary bladder. RC patients treated for non-metastatic muscle-invasive squamous cell carcinoma of the urinary bladder were identified within the Surveillance, Epidemiology, and End Results database (2000-2018). Independent predictor status for CSM of T and N stage groupings (i.e., T2N0, T3N0, T4N0, and TanyN1-3) was tested in multivariable Cox-regression models. Conditional 5-year CSM-free estimates were assessed at baseline and at 4 specific event-free survival times (i.e. 6, 12, 18 and 24 months), within each of the 4 examined stage groups. Of 981 RC patients, 206 (21%), 416 (42%), 152 (16%), and 207 (21%) were T2N0, T3N0, T4N0, and TanyN1-3, respectively. In multivariable Cox-regression models T3N0 (HR 1.94), T4N0 (HR 5.22), and TanyN1-3 (HR 6.62) were independent predictors of CSM, relative to T2N0. In conditional survival analyses based on 24 months event-free status, survival estimates were: 89% for T2N0 vs. 76% at baseline (Δ = 13%), 84% for T3N0 vs. 58% at baseline (Δ = 26%), 69% for T4N0 vs. 25% at baseline (Δ = 44%), 69% for TanyN1-3 vs. 22% at baseline (Δ = 47%). Event-free status at 24 months of follow-up is associated with substantially higher CSM-free survival than when CSM-free survival is predicted at baseline. The magnitude of this effect is most pronounced in TanyN1-3 and T4N0 patients, intermediate in T3N0 and more modest, nonetheless important, in T2N0.

A comparative analysis of recurrence risk predictions in ER+/HER2− early breast cancer using NHS Nottingham Prognostic Index, PREDICT, and CanAssist Breast

AimsClinicians use multi-gene/biomarker prognostic tests and free online tools to optimize treatment in early ER+/HER2− breast cancer. Here we report the comparison of recurrence risk predictions by CanAssist Breast (CAB), Nottingham Prognostic Index (NPI), and PREDICT along with the differences in the performance of these tests across Indian and European cohorts.MethodsCurrent study used a retrospective cohort of 1474 patients from Europe, India, and USA. NPI risk groups were categorized into three prognostic groups, good (GPG-NPI index ≤ 3.4) moderate (MPG 3.41–5.4), and poor (PPG > 5.4). Patients with chemotherapy benefit of < 2% were low-risk and ≥ 2% high-risk by PREDICT. We assessed the agreement between the CAB and NPI/PREDICT risk groups by kappa coefficient.ResultsRisk proportions generated by all tools were: CAB low:high 74:26; NPI good:moderate:poor prognostic group- 38:55:7; PREDICT low:high 63:37. Overall, there was a fair agreement between CAB and NPI[κ = 0.31(0.278–0.346)]/PREDICT [κ = 0.398 (0.35–0.446)], with a concordance of 97%/88% between CAB and NPI/PREDICT low-risk categories. 65% of NPI-MPG patients were called low-risk by CAB. From PREDICT high-risk patients CAB segregated 51% as low-risk, thus preventing over-treatment in these patients. In cohorts (European) with a higher number of T1N0 patients, NPI/PREDICT segregated more as LR compared to CAB, suggesting that T1N0 patients with aggressive biology are missed out by online tools but not by the CAB.ConclusionData shows the use of CAB in early breast cancer overall and specifically in NPI-MPG and PREDICT high-risk patients for making accurate decisions on chemotherapy use. CAB provided unbiased risk stratification across cohorts of various geographies with minimal impact by clinical parameters.

Expression of Neighbor of Punc E11 (NOPE) in early stage esophageal adenocarcinoma is associated with reduced survival

Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2–19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.

Abstract PD9-01: Expanding downstaging criteria in AJCC pathologic prognostic staging using OncotypeDx Recurrence Score® assay in T1-2N0 hormone-receptor positive patients enrolled in the TAILORx trial

Abstract Background: The AJCC 8th edition pathologic prognostic staging (PPS) system, which incorporates both anatomic and biologic factors, was developed using data from patients captured in the National Cancer Database diagnosed 2010-2012 in whom complete anatomic (T, N and M category) as well as biologic data (grade, ER, PR, HER2) were available. The clinical endpoint was 3-year overall survival. In addition, the use of genomic assays was incorporated based on the initial report from the TAILORx trial, with patients with T1-2N0 hormone-receptor positive, HER2 negative (HR+,HER2-) breast cancer and an Oncotype DX Recurrence Score® (RS) result &amp;lt;11 being staged as PPS IA. Given availability of long-term prospective followup data from TAILORx, we undertook this study to examine if the RS criteria for downstaging to PPS IA can be expanded using the patients enrolled on this trial. Methods: TAILORx assigned T1-2N0 HR+HER2- breast cancer patients with RS &amp;lt;11 to endocrine therapy (ET) alone and RS &amp;gt;25 to chemotherapy followed by ET (CET). Those with RS 11-25 were randomized to ET or CET. 10,273 patients were enrolled. Patients with incomplete HR status or grade and those with T3 disease were excluded for this analysis. Recurrence-free survival (RFS) in patients with RS &amp;lt;11 were compared between patients that did and did not fall into current AJCC PPS IA category using the Kaplan-Meier method. Results: 9,535 patients were included for analysis. The majority were &amp;gt; 50 years old (n=6893, 72.3%), had T1 tumors (n=6561, 68.8%), grade 2 disease (n=5291, 55.5%), and underwent lumpectomy (n=6855, 71.9%). RS breakdown was &amp;lt;11 in 1539 (16.1%), 11-17 in 3423 (35.9%), 18-25 in 3088 (32.4%) and &amp;gt;25 in 1485 (15.6%). 8,698 (91.2%) patients were AJCC PPS IA (including all T1N0 patients regardless of RS), and 837 (8.8%) were not PPS IA. Median follow-up time was 95 months. PPS IA patients had 8-yr RFS of 94.2% which was statistically similar to patients with RS 11-17 that were not PPS IA (91.7%, p=0.07) and better than patients with RS &amp;gt;18 that were not PPS IA (85.4% for RS 18-25, 76.0% for RS &amp;gt;25, p&amp;lt;0.01). For patients with a RS 11-17 that were not PPS IA receiving ET alone, 8-yr RFS was 93.3% which was statistically similar to PPS IA patients receiving ET alone (94.9%, p=0.24). There was no RFS benefit with CET for patients with RS 11-17 not PPS IA (Table). Conclusions: Patients with T1-2N0 HR+HER2- breast cancer and RS&amp;lt;18 have similar RFS to patients staged as PPS IA by the current AJCC staging system, regardless of treatment, suggesting that consideration could be given to expanding the criteria for pathologic prognostic stage IA to include RS&amp;lt;18. Comparison of RFS in patients with Stage IA and not Stage IA by AJCC PPS, n=9535Stage IANot stage IA, RS 11-17Not stage IA, RS 18-25Not stage IA, RS &amp;gt;25All Patients, n=9535n=8698n=169n=269n=3998yr RFS % (95% CI)94.2 (93.6-94.8)91.7 (87.0-96.4)85.4 (80.3-90.5)76.0 (69.1-82.9)P-value*Ref0.07&amp;lt;0.01&amp;lt;0.01ET, n=5370n=5123n=88n=135n=248yr RFS % (95% CI)94.9 (94.1-95.7)93.3 (87.6-99.9)85.1 (77.8-92.4)58.3 (77.8-92.4)P-value*Ref0.24&amp;lt;0.01&amp;lt;0.01CET, n=4165n=3575n=81n=134n=3758yr RFS % (95% CI)93.2 (92.2-94.2)90.0 (82.4-97.6)85.8 (78.7-92.9)76.9 (69.8-84.0)P-value*Ref0.019&amp;lt;0.01&amp;lt;0.01ET endocrine therapy; CET chemoendocrine therapy*compared to T1-2N0 patients with PPS IA Citation Format: Olga Kantor, Harold J Burstein, Tari King, Steven Shak, Christy Russell, Armando E Giuliano, Gabriel N Hortobagyi, Eric P Winer, Larissa A Korde, Joseph A Sparano, Elizabeth A Mittendorf. Expanding downstaging criteria in AJCC pathologic prognostic staging using OncotypeDx Recurrence Score® assay in T1-2N0 hormone-receptor positive patients enrolled in the TAILORx trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-01.

Impact of radiotherapy for local control in T3 N0 rectal cancer managed with total mesorectal excision: A systematic review and meta-analysis.

3604 Background: Total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy (RT) is recommended for T3N0 rectal cancers, though benefit has not been demonstrated in combination with TME for this specific population. This meta-analysis could provide evidence to ameliorate toxicities from treatment. Methods: Randomized clinical trials and observational studies published until October 18, 2020 were identified via PubMed and Embase. Objective: To determine whether RT decreased the risk of local recurrence (LR) in T3N0 rectal cancer managed with TME. Study Selection and Extraction: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for literature search, extraction, and screening. Studies with LR data specific to T3N0M0 rectal cancer, treated with and without RT, were included. Reviews, non-English articles, and non-TME studies were excluded. Newcastle Ottawa Scale (NOS) evaluated quality. Meta-analysis was done with a random-effects model. Main outcome: Meta-analysis of the relative risk of LR was conducted. Results: 7,246 studies were screened, 134 full-text studies assessed for eligibility, 5 studies were included in the final analysis. No randomized data reported results specific to our study population. Five retrospective cohort studies involving 932 participants reported LR outcomes. The median follow-up ranged from 38.4 months up to 71 months. Four studies took place in Asia (797 participants) and one in North America (135 participants) (Table). Quality according to NOS ranged from 7–9. The estimated average relative risk for LR at 5 years was 0.63 (95% CI 0.31–1.29; I2=41.8%) when RT was used. Conclusions: This meta-analysis’ supports that there is no clear benefit to LR with the addition of RT in T3N0 patients with rectal adenocarcinoma undergoing TME. As meta-analysis was limited to retrospective cohort studies, there is concern for bias. Registration Prospero number CRD42020216058 .[Table: see text]

Molecular Subtype May Be More Associated With Prognosis and Chemotherapy Benefit Than Tumor Size in T1N0 Breast Cancer Patients: An Analysis of 2,168 Patients for Possible De-Escalation Treatment

PurposeBreast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments.Patients and MethodsT1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)−; 2) HER2+; and 3) triple negative (TN) (HR−/HER2−). Patients’ characteristics and relapse events were reviewed. Kaplan–Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models.ResultsIn total, 2,168 patients (1,435 HR+/HER2−, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2−, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11–2.84, P = 0.018] had a higher recurrence risk than HR+/HER2− patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68–7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95–5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005).ConclusionMolecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC.

Staging esophageal cancer: low EUS accuracy in t2n0 patients.

Background and study aims Esophageal cancer (EC) is one of the most lethal malignancies worldwide. Staging of EC is performed with computed tomography (CT), positron-emission tomography (PET), and endoscopic ultrasonography (EUS). Patient management mostly depends on lymph node status. Compared to histopathology, the accuracy of EUS for T and N parameters is about 85 % and 75 %, respectively. Errors in staging may change prognosis. The aim of this study was to assess the role of EUS in T2-N0 EC considering the experience of two high-volume digestive endoscopic centers. Methods Two prospectively collected databases were queried to identify all patients with EC, staged as cT2N0 by EUS, with no distant metastases at CT/PET scan and who underwent transthoracic esophagectomy. Preoperative EUS staging (cTNM) was compared to histopathology of the surgical specimen (pTNM) to evaluate accuracy. Results Of 729 consecutive patients with EC between January 2011 and September 2018, 72 (49 men) had cT2N0 disease. CT and PET scans confirmed the absence of distant metastasis. In 43 of 72 patients (60 %), the evaluation was correct, 23 of 72 (31,7 %) were understaged, and six of 72 patients (8,3 %) were overstaged. Among the understaged patients, eight were understaged by tumor depth (35 %), seven by nodal involvement (30 %), and eight by both (35 %). All six patients who were overstaged had T1b-N0 disease. EUS accuracy was 77 % in staging for tumor depth and 82 % in staging for nodal metastases. The positive predictive value (PPV) for cT2N0 EC was 60 % (43 pT2N0 /72 cT2N). Conclusions The accuracy of EUS staging of T2N0 EC is low, with only 60 % of patients undergoing appropriate therapy based on histopathology.

Abstract PS4-47: Multi-country clinical validation of can assist breast in Europe indicates robustness of the test

Abstract Background: CanAssist Breast (CAB) is a prognostic test for early stage hormone receptor positive breast cancer patients, that predicts risk of distant recurrence in five years post-diagnosis. Its support vector machine-based algorithm utilizes immunohistochemistry profiles of five biomarkers involved in tumor biology (CD44, ABCC4, ABCC11, N-Cadherin and pan-Cadherin) and three clinical parameters (tumor size, grade, and node status) to categorize patients into low- or high-risk of distant recurrence. CAB was developed on Indian patients, and has been validated in Indian and US patients. The current study presents first ever multi-country, blinded, retrospective validation of CAB. Methods: A total of 669 patients’ breast tumors from Austria (n=327), Spain (n=292) and Italy (n=50) diagnosed 5-10 years ago along with known clinical parameters were included. CAB was performed on the formalin fixed tumor samples using Roche’s automated immunohistochemistry platform at OncoStem’s CAP accredited reference laboratory in India. CAB risk predictions were matched with the clinical outcomes by the respective hospitals. Distant Metastasis Free Survival (DMFS), negative predictive value (NPV) and Hazard Ratio (HR) were computed from Kaplan-Meier survival curves using MedCalc software. Results: The median age of the cohort was 60 years (range: 28-92 years), with only 28% of patients aged &amp;lt; 50 years. The cohort had equal proportions of stage I and stage II patients and 19% of patients with poorly differentiated tumors (G3). Amongst stage II patients 57% had three nodes positive (N1) disease. Total cohort had of 72% N0 patients and 28% N1 patients. The DMFS of this cohort was 95% in low-risk versus 82% in high-risk category (p &amp;lt; 0.0001). The recurrence rate was 5% in low-risk category as against 18% in high-risk category. The risk stratification of patients treated with endocrine therapy alone (68%) was similar to chemo-endocrine therapy (32%) treated patients, both had 95% DMFS in low-risk category. Subtle differences in the NPV was observed across different European patient cohorts: Spain-96%, Italy-100%, Austria-93%. The performance of CAB in European cohort was comparable to the mixed validation cohort of ~1100 patients from India and US, with identical DMFS of 95% in the low-risk category. In a sub-cohort of T1N0 patients (50%), the DMFS in low-risk group was still higher at 97%. In the multivariate Cox proportional hazards model, CanAssist Breast risk score had the highest and significant hazard ratio of 2.9 (p=0.0013, CI: 1.5-5.5) over clinical parameters (node, grade, tumor size), age and type of therapy (endocrine vs. chemo-endocrine). Conclusion: The current study demonstrates the robustness of risk prediction by CAB in an European cohort of diverse nationalities and ethnicities. Similar accuracy of CAB in the Indian and European cohort emphasizes that CAB based risk predictions are driven by tumor biology and are independent of conventional prognostic factors. Citation Format: Somashekhar SP, Aparna Gunda, Chandra Prakash V Serkad, Aditya K Sengupta, Patricia Gomez, Cristina Saura, Vicente Peg, Jose Jimenez, Susanne Sprung, Heidelinde Fiegl, Christine Brunner, Daniel Egle, Manjiri M Bakre. Multi-country clinical validation of can assist breast in Europe indicates robustness of the test [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 PS4-47.

Staging Paradox and Discrepancy in Adjuvant Chemotherapy in Patients with T4N0, T1‐2N1, and T3N1 Colon Cancer

A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages. Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors. The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor. T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients.

Is there a requirement for a staging CT thorax in T1N0 and T2N0 oral squamous cell carcinomas?

Introduction: At the time of diagnosis 1 in 10 patients with oral squamous cell carcinoma has a secondary cancerous lesion or metastasis in the local lymph nodes. The incidence of occult metastasis in patients with T1 and T2 tumours has been 7–33% and 28–53% respectively. The 2016 NICE recommendation was that all people with cancer of the upper aero digestive tract should be offered systemic staging except those with T1N0 or T2N0 disease. In this study we review the staging scans for our T1N0 and T2N0 patients.

Racial disparities in low-value surgical care and time to surgery in high-volume hospitals.

The objective of this study is to examine racial differences in receipt of low-value surgical care and time to surgery (TTS) among women receiving treatment at high-volume hospitals. Stage I-III non-Hispanic Black (NHB) and Non-Hispanic White (NHW) breast cancer patients were identified in the National Cancer Database. Low-value care included (1) sentinel lymph node biopsy (SLNB) among T1N0 patients age ≥70 with hormone receptor-positive cancers, (2) axillary lymph node dissection (ALND) in patients meeting ACOSOG Z0011 criteria, and (3) contralateral prophylactic mastectomy (CPM) with unilateral cancer. TTS was days from biopsy to surgery. Bivariate and logistic regression analyses were used to compare the groups. Compared to NHWs, NHBs had lower rates of SLNB among women age ≥70 with small hormone-positive cancers (NHB 58.5% vs. NHW 62.2% p < .001) and CPM (NHB 26.3% vs. NHW 36%; p < .001). ALND rates for patients meeting ACOSOG Z0011 criteria were similar between both groups (p = .13). The odds of surgery >60 days were higher among NHBs (odds ratio, 1.77; 95% confidence interval, 1.64-1.91; NHW ref). NHBs treated at high-volume hospitals have higher rates of surgical delay but are less likely to undergo low-value surgical procedures compared to NHW women.

Comparison between T1 with lymph node metastases and T3-4 without lymph node metastases in patients with non-small cell lung cancer.

e21074 Background: Patients with small tumor size but lymph node metastases (T1N1-N3, T1N1+) and patients with large tumor size but without lymph node metastases (T3-4N0, T3+N0) mainly belong to stage IIB to IIIA according to the 8th version TNM staging. However, whether the contradictory between tumor size and lymph node may influence the survival and the underlying genomic differences have not been fully studied. Methods: Whole-exome sequencing and RNA sequencing data for 1001 patients with NSCLC including 514 lung adenocarcinoma (LUAD) and 487 lung squamous cell carcinoma (LUSC) were downloaded from TCGA. The prognosis between patients with T1N1+ and T3+N0 has been investigated. The DNA sequencing data and RNA sequencing data from TCGA were used to study the underlying mechanism. Results: Patients with T3N0+ consisted of 80.2% Stage IIB and 17.4% Stage IIIA and patients with T1N1+ consist of 66.7% Stage IIB and 25.9% Stage IIIA. There were no differences in race, age, staging or neoadjuvant history between T1N1+ and T3+N0 cases. T1N1+ patients were more frequent among females (P = 0.02) and were more likely to be adenocarcinomas (P = 0.01) compared to T3+N0. Patients with T1N1+ was associated with a prolonged disease-free survival (DFS) (HR, 0.47; 95% CI, 0.28-0.79; P &lt; 0.05) and progression-free survival (PFS) (HR, 0.31; 95% CI, 0.17-0.56; P &lt; 0.001) than patients with T3+N0. In the multivariable cox proportional hazards regression model including stage, patients with T1N1+ still had increased PFS (HR, 0.45; 95% CI, 0.26-0.82; P = 0.009) and DFS (HR, 0.38; 95% CI, 0.16-0.95; P = 0.04) compared to T3+N0 cases. Moreover, patients with T1N2, belong to Stage IIIA according to AJCC 8th edition TNM staging, had a superior DFS (P = 0.01) and PFS (P = 0.04) compared with the patients with T3N0, who are in Stage IIB. Further investigation revealed that the tumor mutation burden was no significant difference between two groups (P &gt; 0.05). There was no difference in genomic alterations between groups in LUSC and LUAD. GSEA analysis revealed that gene expression involved in DNA repair signaling was enriched in T1N1+ patients in LUSC and LUAD. Conclusions: Patients with T1N1+ shows a longer DFS and PFS compared with patients with T3+N0, especially T1N2 cases who belong to Stage IIIA show a better prognosis compared with T3N0 patients who are in Stage IIB, indicating the AJCC 8th edition TNM staging need to be refined. Moreover, the better prognosis in T1N1+ patients may be related with DNA repair signaling genes enrichment.