Clinical T1N0 Research Articles

Predictive and prognostic factors in patients with anaplastic lymphoma kinase rearranged early-stage lung adenocarcinoma.

This study aimed to evaluate the predictive and prognostic factors in clinical stage I, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients. A multicentric, retrospective, case-control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy. Data were collected from 5 high-volume oncological centres. An external cohort of ALK wild-type patients was also analysed for comparison. Survival analyses were performed using the Kaplan-Meier method, and multivariable Cox regression analysis was used to identify prognostic factors. From January 2016 to December 2022, 63 patients with ALK-rearranged lung adenocarcinoma were included. High-grade tumours (G3) significantly associated with upstaging (odds ratio = 3.904, P = 0.04). Disease-free survival (DFS) and overall survival were significantly improved in upstaged patients receiving adjuvant treatment [hazard ratio (HR) = 0.18, P = 0.0042; HR = 0.24, P = 0.0004, respectively]. The solid or micropapillary histological subtypes were independently associated with worse DFS (HR = 3.41, P = 0.022). Comparison with 435 ALK wild-type patients showed worse DFS in the ALK-rearranged group (HR = 2.09, P = 0.0003). ALK-rearranged patients had higher rates of nodal upstaging, systemic and brain recurrences. Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumours are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and overall survival in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort.

Staging accuracy in patients with clinical T2N0 gastric cancer: Implications for treatment sequencing

BackgroundPatients with clinical T2N0 (cT2N0) gastric adenocarcinoma are recommended to undergo either perioperative chemotherapy or upfront resection. If T2N0 disease is pathologically confirmed, patients may be observed without chemotherapy. These guidelines create the possibility of both systemic therapy overuse and underuse depending on clinical staging accuracy. Our objectives were to define factors associated with upstaging after upfront resection and describe the association between postoperative chemotherapy and survival. MethodsPatients with cT2N0 gastric adenocarcinoma were identified using the National Cancer Database. Factors associated with upstaging were assessed by logistic regression. Survival was assessed using Kaplan-Meier and Cox proportional hazard analyses. ResultsOf 4,076 patients undergoing upfront resection for cT2N0 gastric cancer, 1,933 (47.4%) were pathologically upstaged. Patients were more likely to be upstaged if they had >3.0-cm (adjusted odds ratio [aOR] 2.31, 95% confidence interval [CI] 1.97–2.70; P < .001) or poorly differentiated tumors (aOR 2.22, 95% CI 1.89–2.60; P < .001). Patients were less likely to be upstaged if they had distal tumors (aOR 0.77, 95% CI 0.64–0.93; P = .006). Of those pathologically upstaged (n = 1,933), 1,111 (57.4%) received adjuvant chemotherapy that was associated with improved survival (HR 0.55, 95% CI 0.47–0.63; P < .001). Among those not upstaged (n = 2,143), 247 (11.5%) received adjuvant chemotherapy that was not associated with improved survival (HR 0.92, 95% CI 0.70–1.21; P = .54). ConclusionsPathologic upstaging after upfront resection in patients with cT2N0 gastric cancer is associated with patient and tumor characteristics. Adjuvant chemotherapy is associated with improved survival only in the patients upstaged at surgery. An upfront surgical approach may be preferred in select patients, especially if avoiding chemotherapy is desired.

Survival outcomes of adjuvant treatment in upstaged clinical T2N0 rectal cancer: are we underutilizing therapy?

BackgroundPatients with rectal cancer staged as clinical T2N0 (cT2N0) are recommended to undergo upfront resection. However, when the tumor is subsequently upstaged to pathologic T3N0 (pT3N0), there are no clear guidelines for adjuvant treatment. This study aimed to analyze national trends in adjuvant management and to identify differences in morbidity or survival. MethodsUsing the National Cancer Database (2004–2020), adult patients with cT2N0 rectal adenocarcinoma that were upstaged to pT3N0 after resection were identified. The treatment groups included (i) surgery alone, (ii) surgery + postoperative (post-op) chemotherapy alone, (iii) surgery + post-op chemoradiation (CRT), and (iv) surgery + chemotherapy + CRT. Cox proportional hazard models and Kaplan-Meier curves (6-month landmark analysis) were used to compare survival outcomes. ResultsThe analytic cohort included 800 patients who received the following treatments: surgery alone (496 [60%]), surgery + post-op chemotherapy (139 [17%]), surgery + post-op CRT (137 [15%]), and surgery + chemotherapy + CRT (69 [8%]). Patients who underwent post-op chemotherapy or chemotherapy + CRT had higher rates of poor/undifferentiated tumors (15.7% and 15.4%, respectively) than those who underwent surgery alone (8.8%) (P = .047). Over the study period, surgery alone decreased from 86.7% to 65.6%, with concomitant increases in post-op adjuvant therapy. Post-op chemotherapy (hazard ratio [HR], 0.336; 95% CI, 0.196–0.575) and chemotherapy + CRT (HR, 0.447; 95% CI, 0.231–0.866) remained independently associated with improved overall survival. Of note, 5-year survival was the lowest in the surgery-alone group (62.5%). ConclusionPost-op adjuvant regimens, including chemotherapy, were independently associated with improved survival in patients with cT2N0 rectal cancer upstaged to pT3N0. Adjuvant therapy may be underutilized in this setting.

Prevalence and Risk Factors for Malignant Nodal Involvement in Early esophago-gastric Adenocarcinoma: Results from the Multicenter Retrospective Congress Study (endosCopic resectiON, esophaGectomy or Gastrectomy For Early Esophagogastric Cancers).

The aim of this study was to quantify LNM risk and outcomes following treatment of early esophago-gastric (EG) adenocarcinoma. The standard of care for early T1N0 EG cancer is endoscopic resection (ER). Radical surgical resection is recommended for patients perceived to be at risk of lymph node metastasis (LNM). Current models to select organ-preserving vs. surgical treatment are inconsistent. CONGRESS is a UK-based multicentre retrospective cohort study. Patients diagnosed with clinical or pathological T1N0 EG adenocarcinoma from 2015-2022 were included. Outcomes and rates of LNM were assessed. Cox regression was performed to assess the impact of prognostic and treatment factors on overall survival. 1,601 patients from 26 centres were included, with median follow-up 32 months(IQR 14-53). 1285/1612(80.3%) underwent ER, 497/1601(31.0%) underwent surgery. Overall rate of LNM was 13.5%. On ER staging, tumour depth (T1bsm2-3 17.6% vs. T1a 7.1%), lymphovascular invasion (17.2% vs. 12.6%), or signet cells (28.6% vs. 13.0%) were associated with LNM. In multivariable regression analysis, these were not significantly associated with LNM rates or survival. Adjusting for demographic and tumour variables, surgery after ER was associated with significant survival benefit, HR 0.33(0.15-0.77),P=0.010. This large multicentre dataset suggests that early EG adenocarcinoma is associated with significant risk of LNM. This data is representative of current real clinical practice with ER-based staging, and suggests previously held beliefs regarding reliability of predictive factors for LNM may need to be reconsidered. Further research to identify patients who may benefit from organ-preserving vs. surgical treatment is urgently required.

Comparative analysis of organ preservation attempt and radical surgery in clinical T2N0 mid to low rectal cancer

PurposeDebate persists regarding the feasibility of adopting an organ-preserving strategy as the treatment modality for clinical T2N0 rectal cancer. This study aimed to compare the outcomes of attempting organ-preserving strategies versus radical surgery in patients with clinical T2N0 mid to low rectal cancer.MethodsPatients diagnosed with clinical T2N0 rectal cancer, with lesions located within 8 cm from the anal verge as determined by pre-treatment magnetic resonance imaging between January 2010 and December 2020 were included.ResultsOf 119 patients, 91 and 28 were categorized into the organ-preserving attempt group and the radical surgery group, respectively. The median follow-up duration was 48.8 months (range, 0–134 months). The organ-preserving attempt group exhibited a reduced incidence of stoma formation (44.0% vs. 75.0%; p = 0.004) and a lower occurrence of grade 3 or higher surgical complications (5.8% vs. 21.4%; p = 0.025). Univariate analyses revealed no significant association between treatment strategy and 3-year local recurrence-free survival (organ-preserving attempt 87.9% vs. radical surgery 96.2%; p = 0.129), or 3-year disease-free survival (79.6% vs. 84.9%; p = 0.429). Multivariate analysis did not identify any independent prognostic factors associated with oncologic outcomes.ConclusionCompared with radical surgery, attempted organ preservation resulted in lower incidences of stoma formation and severe surgical complications, whereas oncological outcomes were comparable. Attempting organ preservation may be a safe alternative to radical surgery for clinical T2N0 mid to low rectal cancer.

Impacts of Positive Margins and Surgical Extent on Outcomes After Early-Stage Lung Cancer Resection

BackgroundSublobar resection of early-stage non-small cell lung cancer (NSCLC) is increasingly considered appropriate but may compromise margins compared with lobectomy. This study evaluated resection extent, margin status, and survival in patients with clinical stage I NSCLC. MethodsPatients with clinical T1-2 N0 M0 NSCLC in the National Cancer Database (2006-2020) who were treated with primary surgery were compared stratified by margin status. The potential benefit of radiation was explored in subgroup analysis of patients who underwent sublobar resection with positive margins. ResultsPositive margins occurred in 5089 (2.8%) of 181,824 patients and were more common in sublobar resections compared with lobectomy (4.3% vs 2.4%; P < .001). Sublobar resection had the strongest association with positive margins in multivariable analysis (odds ratio, 2.06; 95% CI, 1.91-2.23; P < .001). Patients with positive margins were more likely to undergo both adjuvant chemotherapy (16% vs 13%; P < .001) and radiation (17% vs 1%; P < .001) but had worse survival in univariate analysis (44.0% 5-year overall survival vs 69.2%; P < .001) and multivariable Cox analysis (hazard ratio, 1.71; 95% CI, 1.63-1.78; P < .001) in the entire cohort, as well as in a univariate subset analysis of lobectomy (46.9% vs 70.4%; P < .001) and sublobar resection (37.5% vs 64.1%; P < .001). Postoperative radiation for patients who underwent sublobar resection with positive margins did not improve 5-year overall survival (36.3% for irradiated patients vs 38.3% for nonirradiated patients; P = .57), and patients who underwent sublobar resection with positive margins who were treated with radiation had survival inferior to that of patients who underwent lobectomy with negative margins. ConclusionsPositive margins occur more frequently after sublobar resection of clinical stage I NSCLC compared with lobectomy. Patients with positive margins have worse survival than patients who undergo complete resection and are not rescued by postoperative radiation.

Does clinical T1N0 GGN really require checking for distant metastasis during initial staging for lung cancer?

BackgroundAccurate clinical staging is crucial for selection of optimal oncological treatment strategies in non-small cell lung cancer (NSCLC). Although brain MRI, bone scintigraphy and whole-body PET/CT play important roles in detecting distant metastases, there is a lack of evidence regarding the indication for metastatic staging in early NSCLCs, especially ground-grass nodules (GGNs). Our aim was to determine whether checking for distant metastasis is required in cases of clinical T1N0 GGN.MethodsThis was a retrospective study of initial staging using imaging tests in patients who had undergone complete surgical R0 resection for clinical T1N0 Stage IA NSCLC.ResultsA total of 273 patients with cT1N0 GGNs (n = 183) or cT1N0 solid tumors (STs, n = 90) were deemed eligible. No cases of distant metastasis were detected on initial routine imaging evaluations. Among all cT1N0M0 cases, there were 191 incidental findings on various modalities (128 in the GGN). Most frequently detected on brain MRI was cerebral leukoaraiosis, which was found in 98/273 (35.9%) patients, while cerebral infarction was detected in 12/273 (4.4%) patients. Treatable neoplasms, including brain meningioma and thyroid, gastric, renal and colon cancers were also detected on PET/CT (and/or MRI). Among those, 19 patients were diagnosed with a treatable disease, including other-site cancers curable with surgery.ConclusionsExtensive staging (MRI, scintigraphy, PET/CT etc.) for distant metastasis is not required for patients diagnosed with clinical T1N0 GGNs, though various imaging modalities revealed the presence of adventitious diseases with the potential to increase surgical risks, lead to separate management, and worsen patient outcomes, especially in elderly patients. If clinically feasible, it could be considered to complement staging with whole-body procedures including PET/CT.

A phase III randomized trial of radiotherapy optimization for low-risk HER2-positive breast cancer (HERO): NRG-BR008.

TPS613 Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative, HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (≤2 cm) N0 disease, while patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T≤3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (&lt;60; ≥60), tumor size (≤1 cm; &gt;1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant vneoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete one year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March 2023. Accrual is 13/1,300 as of 02-05-2024. Clinical trial information: NCT05705401 .

Is a completion axillary dissection in patients with early breast cancer with a positive sentinel node necessary? An NCDB-based trial emulation of ACOSOG Z0011.

e12592 Background: The ACOSOG Z0011 Study is a practice-changing phase III clinical trial that promotes the de-escalation of axillary surgery in early breast cancer patients, which supports no completion axillary lymph node dissection (ALND) in clinically node negative patients with 1 or 2 positive sentinel lymph nodes (pSLN). Strong evidence for patients with 3 positive SLN was still lacking. We emulated the Z0011 trial using the National Cancer Database (NCDB) to validate the post-trial evidence in the real-world setting followed by a deeper investigation in the subgroups by the number of pSLN. Methods: NCDB PUF 2020 was queried for clinical T1-2 N0 M0 breast cancer patients diagnosed 2010-2017. The inclusion and exclusion criteria were the same as in the Z0011 trial except for the inclusion of 3 positive sentinel lymph nodes. Sentinel lymph node biopsy (SLNB) alone and ALND were defined using Site-Specific Factor 19. The primary endpoint, overall survival (OS), was modeled by the Cox proportional hazard model. The propensity score-based average treatment effect on the treated (ATT) weighting schema was implemented to generate pseudo samples based on this eligible study population and its subgroups as pSLN = 1, 2, and 3, where covariate balance between the two cohorts was achieved for all observed demographic and disease characteristics. Results: 25,774 patients were included in the analysis. 20311 (78.8%) patients were in the SLNB alone group, and 5463 (21.2%) patients were in the ALND group respectively. The utility rate of SLNB increased steadily over the years from 53.7% in 2010 to 91.0% in 2017. The median age was 60, which was older than that in the Z0011 trial (55). The median follow-up time was 6.78 [95% CI: 4.98-8.81] years. By multivariable analysis using the original sample, SLNB alone and the ALND group had similar survival (HR = 0.99 [95% CI: 0.90-1.09]; P = 0.83). By ATT weighting, the SLNB group had significantly improved survival (HR= 0.88 [95% CI: 0.82-0.95]; P = 0.001). The magnitude of HR is close to that in the Z0011 trial (HR= 0.87 [95% CI: 0.62-1.23]), but the statistical significance was mainly driven by a much larger sample size in this study. In the subgroup ATT weighting analysis for pSLN = 1, the SLNB group had significantly better survival compared to the ALND group (HR = 0.85 [95% CI: 0.79-0.93]; P &lt; 0.001). Survival was equivalent for subgroup patients with pSLN = 2 (HR = 1.04 [95% CI: 0.91-1.19]; P = 0.54), while in the subgroup of pSLN = 3 patients, the SLNB group had a significantly worse survival when compared to the ALND group (HR, 1.22 [95% CI, 1.04-1.45]; P = 0.02). Conclusions: This NCDB-based Trial-Emulation study validates the result of the ACOSOG Z0011 clinical trial through a post-trial and real-world setting, where we confirmed that patients with 1 or 2 pSLN are suitable for SLNB alone, but for patients with 3 pSLN, ALND may still maintain a viable option.

Adjuvant Chemotherapy After Neoadjuvant Therapy and Surgery for Non-Small Cell Lung Cancer

BackgroundThere is a dearth of data on outcomes of postoperative chemotherapy after neoadjuvant therapy followed by surgery in patients with locally advanced non-small cell lung cancer (NSCLC). The objective of this study was to compare survival outcomes in patients who did and did not receive adjuvant chemotherapy. MethodsA retrospective chart review was performed using our multicenter database to identify patients who received neoadjuvant therapy followed by surgery for clinical T3 N0 or N1-N2 resectable NSCLC between 2009 and 2016. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. Propensity score matching (PSM) was used to control for selection bias in evaluation of overall survival (OS) and recurrence-free survival (RFS) by matching age, sex, smoking history, Charlson Comorbidity Index, histologic type, and pathologic nodal status and stage. ResultsThe participants were 156 patients with a median age of 65 years. The median RFS of the whole cohort was 66.3 months; OS was not reached. Before PSM, patients receiving adjuvant chemotherapy had significantly shorter RFS (hazard ratio [HR], 1.79; 95% CI, 1.13-2.82) and showed a trend for shorter OS (HR, 1.37; 95% CI, 0.78-2.39). After PSM, 50 patients were used for comparison in each group, and those receiving adjuvant chemotherapy did not have a more favorable RFS (HR, 1.33; 95% CI, 0.75-2.34) or OS (HR, 1.25; 95% CI, 0.62-2.51). ConclusionsAdjuvant chemotherapy was not associated with favorable survival outcomes in patients treated with surgery after neoadjuvant therapy for locally advanced NSCLC.

Abstract PO1-19-01: NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-risk HER2-positive Breast Cancer (HERO)

Abstract Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (&amp;lt; 2 cm) N0 disease, while patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T&amp;lt; 3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (&amp;lt; 60; ≥60), tumor size (≤1 cm; &amp;gt;1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant vs neoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete a year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include the time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March, 2023. NCT05705401. Support: U10CA180868, -180822, UG1CA189867, U24CA196067; Susan G. Komen Foundation (JR) Citation Format: Lior Braunstein, Melissa Mitchell, Hanna Bandos, William Sikov, Atif Khan, Peter Chen, Patricia Ganz, Reshma Jagsi, Julia White, Reena Cecchini, Hyejoo Kang, Shannon Puhalla, Kelly Bolton, Eileen Connolly, Erica Stringer-Reasor, Kimberly Gergelis, Thomas Julian, Eleftherios Mamounas, Norman Wolmark. NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-risk HER2-positive Breast Cancer (HERO) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-01.

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging

BackgroundInaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. MethodsFrom 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. ResultsOf the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. ConclusionsThe presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Adjuvant Chemotherapy in Addition to Neoadjuvant Chemotherapy for Locally Advanced Non-small Cell Lung Cancer.

The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear. A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazard model. Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93). Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies.

CT radiomics in the identification of preoperative understaging in patients with clinical stage T1-2N0 esophageal squamous cell carcinoma.

Predicting preoperative understaging in patients with clinical stage T1-2N0 (cT1-2N0) esophageal squamous cell carcinoma (ESCC) is critical to customizing patient treatment. Radiomics analysis can provide additional information that reflects potential biological heterogeneity based on computed tomography (CT) images. However, to the best of our knowledge, no studies have focused on identifying CT radiomics features to predict preoperative understaging in patients with cT1-2N0 ESCC. Thus, we sought to develop a CT-based radiomics model to predict preoperative understaging in patients with cT1-2N0 esophageal cancer, and to explore the value of the model in disease-free survival (DFS) prediction. A total of 196 patients who underwent radical surgery for cT1-2N0 ESCC were retrospectively recruited from two hospitals. Among the 196 patients, 134 from Peking University Cancer Hospital were included in the training cohort, and 62 from Henan Cancer Hospital were included in the external validation cohort. Radiomics features were extracted from patients' CT images. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection and model construction. A clinical model was also built based on clinical characteristics, and the tumor size [the length, thickness and the thickness-to-length ratio (TLR)] was evaluated on the CT images. A radiomics nomogram was established based on multivariate logistic regression. The diagnostic performance of the models in predicting preoperative understaging was assessed by the area under the receiver operating characteristic curve (AUC). Kaplan-Meier curves with the log-rank test were employed to analyze the correlation between the nomogram and DFS. Of the patients, 50.0% (67/134) and 51.6% (32/62) were understaged in the training and validation groups, respectively. The radiomics scores and the TLRs of the tumors were included in the nomogram. The AUCs of the nomogram for predicting preoperative understaging were 0.874 [95% confidence interval (CI): 0.815-0.933] in the training cohort and 0.812 (95% CI: 0.703-0.912) in the external validation cohort. The diagnostic performance of the nomogram was superior to that of the clinical model (P<0.05). The nomogram was an independent predictor of DFS in patients with cT1-2N0 ESCC. The proposed CT-based radiomics model could be used to predict preoperative understaging in patients with cT1-2N0 ESCC who have undergone radical surgery.

230. SURVIVAL OUTCOMES OF ROBOT-ASSISTED TRANS-MEDIASTIONAL ESOPHAGECTOMY IN PATIENTS WITH CT1N0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background We have developed a robot-assisted trans-mediastinal esophagectomy (RATME) to reduce the surgical invasiveness of open trans-thoracic esophagectomy (oTTE). However, the long-term outcome of esophageal cancer patients who underwent RATME remains unclear. Methods Patients who underwent RATME or oTTE for clinical T1N0 esophageal squamous cell carcinoma were enrolled in this study. The clinicopathological and surgical details, overall survival (OS), disease-free survival (DFS), and cause-specific survival (CSS) were compared between the RATME and oTTE groups. Results Forty-three and 47 patients who underwent RATME and oTTE, respectively, were included in this analysis. The RATME group included more male patients and had a significantly lower comorbidity index. There was no significant difference in age, tumor location, preoperative ESD rates, and pathological TNM factors between the two groups. The RATME group showed a longer operation time, less blood loss, low incidence of pneumonia, and shorter hospital stays. The OS and DFS rates in the RATME tended to be higher than in the oTTE group; The 5-year OS rates were 88.4 vs 71.5%, and the 5-year DFS rates were 81.4 vs 62.8% (RATME vs oTTE group, p = 0.09 and p = 0.11). The CSS in both groups were equivalent; The 5-year CSS rates were 93.7 vs 92.4% in the RATME and oTTE groups respectively. The RATME group had significantly fewer deaths than the oTTE group (p = 0.032). Conclusions The RATME group tended to show better OS and DFS than the oTTE group. The OS of the RATME group was equivalent to that of the comprehensive registry data in Japan, indicating that RATME radicality is guaranteed.

Sub-Lobar Resection: The New Standard of Care for Early-Stage Lung Cancer.

The Lung Cancer Study Group previously established lobectomy as the standard of care for treatment of clinical T1N0 NSCLC. Advances in imaging technology and refinements in staging have prompted a re-investigation to determine the non-inferiority of sub-lobar resections to lobectomies. Two recent randomized studies, JCOG 0802 and CALGB 140503, are reviewed here in the context of LCSG 0821. The studies confirm non-inferiority for sub-lobar resection (wedge or segmentectomy) compared to lobectomy for peripheral T1N0 NSCLC less than or equal to 2 cm. Sub-lobar resection should therefore be considered the new standard of care in this sub-set of patients with NSCLC.

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients.

To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers. In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test. A total of 964 women comprised the development (603 women, 54 ± 11years) and validation (361 women, 53 ± 10years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts. Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

Selective Mediastinal Lymph Node Dissection Strategy for Clinical T1N0 Invasive Lung Cancer: A Prospective, Multicenter, Clinical Trial

IntroductionWe aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC. MethodsThis is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10–12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an “inaccurate” case. ResultsA total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11–20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status. ConclusionsThis is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.

Abstract P021: Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database

Abstract Total neoadjuvant therapy (TNT) is a treatment strategy for rectal cancer that includes a course of chemotherapy and a separate course of chemoradiation before definitive surgery. The use of TNT has increased in recent years and carries the potential for improved sphincter preservation and a significant risk reduction of locoregional recurrence. One criterion of the National Accreditation Program for Rectal Cancer is to begin definitive treatment within 60 days of a patient’s diagnosis of rectal cancer. The objective of this study was to evaluate the association of social determinants of health and healthcare-related factors with starting TNT 60 days or more after diagnosis using data from the National Cancer Database (NCDB). Patients aged 18 years and older diagnosed with primary rectal cancer between 2016 and 2019, who underwent NCCN recommended TNT regimen followed by definitive surgery at a Commission on Cancer (CoC)-accredited facility and did not die before receiving surgery were eligible for the current study. We included 3,210 patients in the analytic sample who did not have the following conditions: clinical stage IV, clinical stage T1N0 or lower, non-adenocarcinoma histology, and adjuvant therapy use. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for factors potentially associated with starting TNT more than 60 days after a cancer diagnosis. The median age of patients included in the study was 57 years old, with a majority of them starting TNT within 60 days (87.5%), were males (62.3%), and reported as Non-Hispanic White race and ethnicity (76.7%). Furthermore, 35.0% had a median household income of $63,333 or more, 57.7% had private insurance/managed care, 65.0% traveled within 30 miles to their treatment facility, and 49.1% lived in a zip code where less than 10.9% of adults age 25 or older did not graduate from high school. In multivariable models, factors positively associated with starting TNT after 60 days or more were uninsured status (OR 2.93, CI: 1.84, 4.67), living in a zip code with more than 10.8% of adults age 25 or older not graduating from high school (OR 1.66, CI: 1.22, 2.25), traveling more than 30 miles to the treatment facility (OR 1.63, CI: 1.20, 2.20), treatment with an academic/research program (OR 1.51, CI: 1.13, 2.02), Medicaid as primary insurance (OR 1.50, CI: 1.03, 2.19), Hispanic ethnicity (OR 1.44, CI: 1.00, 2.07), male (OR 1.28, CI: 1.00, 1.65) and age (1.02, CI: 1.01, 1.04). In conclusion, results from this study show that social determinants of health and other healthcare-related factors are significantly associated with those who started TNT more than 60 days after a rectal cancer diagnosis. Further investigation is ongoing to understand the impact of delays in TNT and other treatment regimens for rectal cancer. Citation Format: Megan T. Mai, Zheng Shi, Duke Appiah. Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P021.

Ultrasound contrast-enhanced patterns of sentinel lymph nodes: predictive value for nodal status and metastatic burden in early breast cancer

In the post-Z0011 era, sentinel lymph node (SLN) status and metastatic burden determine whether axillary management entails conservative sentinel lymph node biopsy (SLNB) or radical axillary lymph node dissection (ALND) in breast cancer patients. However, SLN status and metastatic burden cannot be evaluated preoperatively in clinical practice. This study explored the predictive value of contrast-enhanced ultrasound (CEUS) patterns of SLN to assess the nodal status and metastatic burden in early breast cancer patients. A retrospective study was conducted on 88 consecutive patients who were diagnosed with clinical T1-2N0 breast cancer between December 2020 and November 2021 at the Lanzhou University Second Hospital and scheduled for SLNB. Preoperative CEUS was performed to confirm the location and enhancement pattern of the SLN, and the conventional ultrasonic characteristics of the primary breast lesions and SLN were recorded. Intraoperative localized SLN and postoperative pathological results were used as the gold standard for comparison with preoperative ultrasound findings. CEUS successfully identified at least 1 SLN in 88 patients, with a total of 118 SLNs identified in the entire cohort. Univariate analysis showed that lesion size, blood flow grade, SLN longitudinal diameter, cortical thickness, and enhancement pattern were significant predictive features of SLN metastasis. Further multiple regression analysis indicated that the enhancement pattern of the SLN was an independent risk factor for SLN metastasis, with a sensitivity and a specificity of 84.2% (32/38) and 80.0% (40/50), respectively. Meanwhile, the SLN enhancement pattern could predict the lymph node metastasis burden (P<0.001). In patients presenting with a type I (homogeneous enhancement) or type II (heterogeneous enhancement) SLN, 91.5% (65/71) had ≤2 positive SLNs, whereas in patients with a type III (no enhancement) SLN, 70.6% (12/17) had >2 metastatic nodes. The contrast-enhanced pattern of the SLN is an independent risk factor for SLN status. Patients presenting with a type I or type II SLN enhanced pattern are unlikely to have high-burden metastases detected at their final surgical treatment and omission of ALND may be appropriate.