8th Edition TNM Research Articles

121P Treatment of unresectable stage III NSCLC: Real-world study and literature review

The standard treatment of unresectable stage III non-small cell lung cancer (NSCLC) is combined chemoradiotherapy (CRT), delivered either concurrently (cCRT) or sequentially (sCRT). There is, however, limited data on the outcomes and safety of CRT in real-world setting. We performed an analysis of the Leuven Lung Cancer Group (LLCG) experience with CRT for unresectable stage III NSCLC prior to the era of consolidation treatment with immunotherapy. We conducted a retrospective, monocentric cohort study at the university hospital UZ Leuven, Belgium, and retrieved 163 consecutive patients who were treated with CRT for unresectable stage III NSCLC between January 1st 2011 and December 31st 2018. Patient and tumor characteristics, treatment patterns, toxicity, and primary outcome parameters were analyzed. Chemotherapy was given concurrently in 108 patients, sequentially in 55. Overall tolerability was good with two thirds of patients having no severe adverse events: severe febrile neutropenia (9,2%), ³ grade 2 pneumonitis (16%), or ³ grade 3 esophagitis (19%). Adverse events were more frequent in the cCRT than sCRT group. Median PFS was 13.2 months (95% CI 10.3-16.2). In the patients with progressive disease, the site of first progression was locoregional in 36% and distant in 64%, with no significant difference between cCRT and sCRT. Median OS was 23.3 months (95% CI 18.3-28.0), with a 47.5% survival rate at 2 years and 29.4% at 5 years. In multivariate Cox regression analysis, Karnofsky performance status, stage (UICC TNM 8th edition) and COPD were significant factors for OS, while sequence of therapy (cCRT versus sCRT) lost significance in multivariate testing. Our real-world PFS, OS and toxicity results are comparable to those reported in randomized controlled trials (RTOG 0617, PROCLAIM). Sequence of therapy did not independently associate with OS, likely since the choice for a sequential versus concurrent approach is strongly influenced by other main drivers of survival such as performance status. This study provides a clinically relevant real-world benchmark on the outcomes of cCRT and sCRT before the start of the immunotherapy era in this setting.

Oral tongue carcinoma: prognostic changes according to the updated 2020 version of the AJCC/UICC TNM staging system.

SUMMARYBackgroundThis study aimed to evaluate the performance of the 2017 8th TNM edition and the latest update in 2020 compared to the 7th in a large cohort of patients affected by oral tongue squamous cell carcinoma (OTSCC), considering all stages.Materials and methodsThe cohort involved 300 patients affected by OTSCC treated with surgery. All cases were classified according to the 7th, 8th (2017), and the latest updated TNM edition (October 2020),. Patients were grouped based on the shift in tumour (T) category, lymph nodal (N) category and final pathological stage. Overall survival (OS) and disease-free survival (DFS) were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were carried out.ResultsAccording to the 7th edition, multivariate analysis OS revealed that stage IV patients had an almost 4-fold risk of death compared to stage I (HR = 3.81 95% CI: 2.32-6.25; p < 0.001). Regarding DFS, stage IV patients had a 2-fold greater risk of relapses, or second primary, than patients in stage I (HR = 2.51 95% CI: 1.68-3.74; p < 0.001). According to 2017 8th edition for OS, stage IV patients presented a 5-fold higher risk of death compared to patients in stage I (HR = 5.18 95% CI: 2.96-9.08; p < 0.001) and almost 4-old greater risk of relapses or second primary compared to patients in stage I considering DFS (HR = 3.61 95% CI: 2.28-5.71; p < 0.001). Regarding the recent edition of 8th TNM (2020), stage IV patients had an almost 5-fold greater risk of death compared to patients in stage I considering OS (HR = 4.84 95% CI: 2.74-8.55; p < 0.001), while for DFS they had 3-fold greater risk of relapse or second primary compared to patients in stage I (HR = 3.13 95% CI: 1.99-4.91; p < 0.001).ConclusionsThis study confirmed that the recent update of the 8th edition of the TNM (2020) improves stratification and identification of advanced tumours, reducing the number of T3 compared to the 2017 edition and increasing the number of patients with pT4. This improvement made by the updated edition may reduce the risk of skipping adjuvant therapy.

Importance of tumor size in resectable stage III-N2 non–small cell lung cancer

ObjectiveThe 8th TNM edition classifies stage III-N2 disease as IIIA and IIIB based on a tumor size cutoff of 5 cm. However, the importance of tumor size on survival in patients with resectable stage III-N2 disease has not been analyzed systematically. MethodsSurvival analysis based on tumor size (>5 cm vs ≤ 5 cm) for 255 consecutive patients with nonbulky (maximal lymph node diameter of 1.5 cm) stage III-N2 non–small cell lung cancer treated with surgery in our institution. ResultsNinety patients (35.3%) underwent induction chemoradiation therapy (n = 72, 28%) or induction chemotherapy (n = 18, 7%), and 165 patients underwent primary surgery followed by adjuvant chemotherapy (n = 52, 32%), adjuvant chemoradiation therapy (n = 47, 29%), or adjuvant radiation therapy (n = 14, 13.2%). After a median follow-up of 6.5 years, the overall survival was 46.5% at 5 years and 28.9% at 10 years. In tumors 5 cm or less, there was no difference in survival between patients treated with induction or adjuvant therapy. However, in tumors greater than 5 cm, the survival was significantly better after induction therapy compared with adjuvant therapy or surgery alone. Pathologic multi-station N2 disease was more frequently detected in tumors greater than 5 cm (31% vs 18% in tumors ≤5 cm, P = .042), and the rate of R1 resection was lower after induction therapy (2.2% vs 8.5% in primary surgery, P = .048). ConclusionsThese results support the redefinition of tumors greater than 5 cm with resectable N2 disease to stage IIIB. This change should help to refine the multimodality approach for stage III-N2 lung cancer.

P-OGC23 Significance of neoadjuvant downstaging in gastric adenocarcinoma

Abstract Background Neoadjuvant chemotherapy is established in the treatment of gastric adenocarcinoma. Histopathological regression as a result of neoadjuvant treatment can potentially have important prognostic implications in gastric cancer. There is little data comparing the clinical outcomes of patients with gastric adenocarcinoma at the same pathological stage with and without neoadjuvant treatment. The aim of this study is to determine the impact of neoadjuvant chemotherapy upon the prognosis of patients being treated for gastric adenocarcinoma. Methods Consecutive patients with gastric cancer treated in a single, tertiary high-volume centre between 2007 and 2017 were evaluated. All patients with gastric adenocarcinoma were treated with either a subtotal or total gastrectomy with D2 lymphadenectomy. A stage-by-stage comparison of the extent of pathological downstaging was conducted for patients who received neoadjuvant treatment (ypTNM) and those that did not (pTNM). The pTNM and ypTNM stages were defined as per the TNM 8th Edition. Results Among 384 patients undergoing gastrectomy for gastric adenocarcinoma, 141 patients received neoadjuvant chemotherapy. Of them, 86 patients (58.1%) benefitted from a downstaging effect. Patients with downstaged disease had improved overall survival compared to patients who did not respond to neoadjuvant chemotherapy (NR vs 66 months, p &amp;lt; 0.001). Downstaging by &amp;gt; 3 stages was the strongest independant predictor of overall survival (hazard ratio: 0.17; 95% Confidence Interval (CI) 0.062-0.44). Overall survival was significantly better when a stage-by-stage comparison was performed between patients in the ypTNM and pTNM groups. Conclusions Pathological staging following neoadjuvant chemotherapy is a more accurate predictor of prognosis compared to pre-neoadjuvant chemotherapy clinical stage with downstaged patients benefitting from lower recurrence rates and improved overall survival. Patients downstaged due to neoadjuvant chemotherapy receipt can potentially have more favourable clinical outcomes compared to stage-matched patients who did not receive this.

AB008. Synchronous thymic and breast malignancies: a single institutional experience

: Breast cancer is the most frequent neoplasm in female population. Conversely, thymic epithelial tumors (TETs) are rare diseases, often discovered in late stages. TET patients have a high risk of developing secondary malignancies compared with general population, with an incidence rate from 8 to 31%. We recently observed the synchronous appearance of both these neoplasms in two patients. The first patient, a 60-year-old female, was diagnosed with breast cancer. She underwent quadrantectomy and sentinel axillary lymph node dissection. Pathological diagnosis was invasive breast cancer non special type (NST), G2 pT1 N0, estrogen receptor (ER) 95%, progesterone receptor (PR) 90%, human epidermal growth factor receptor 2 (Her2) negative, Ki67: 30%. Staging work-up (chest X-ray followed by CT scan) discovered a solid mass of 70 mm in the anterior mediastinum, suspect for thymic tumor lesion, that also showed a tracer uptake at FDG scan (SUVmax 10). Patient underwent thymectomy with pathologic diagnosis of thymoma, subtype B2/B3, stage pT1a pN0 (AJCC TNM 8th edition). The second patient, a 62-year-old woman experiencing post-COVID persistent dyspnea, underwent a CT scan and an FDG PET scan. Imaging showed a thoracic lesion suspicious for thymic neoplasm infiltrating the chest wall (tracer uptake SUVmax 6.7) and simultaneously two contrast-enhanced nodules, one in each breast (left breast: 15 mm, SUVmax 2; right breast: 20 mm, SUVmax 2.6). Surgical biopsies were performed in all the 3 lesions. The pathological diagnoses were: (I) non keratinizing squamous cell carcinoma of the thymus; (II) invasive left breast cancer (NST) ER 90 %, PR 30%, Her2 negative, Ki67: 10%; (III) invasive right breast cancer (NST) ER 90%, PR 30%, Her2 positive (3+), Ki67 10%. The presence of synchronous thymic and breast malignancies appears to be very singular and requires personalized treatment strategies. Furthermore, additional studies are needed to understand if TETs and their related immune system dysregulation could increase the risk of secondary tumors, or whether genetic disorders might be responsible for an increased predisposition to develop synchronous malignancies. In both scenarios, future studies should explore the utility of tailoring screening procedures for TET patients.

Effect of epidermal growth factor receptor gene mutation on the prognosis of pathological stage II–IIIA (8th edition TNM classification) primary lung cancer after curative surgery

ObjectivesThis retrospective study aimed to elucidate the effect of epidermal growth factor receptor (EGFR) gene mutations on the prognosis of patients with pathological stage II–IIIA primary lung cancer after curative surgery. Materials and methodsWe enrolled 539 patients with p-stage II–IIIA (8th edition tumor–node–metastasis [TNM] classification) lung cancer who underwent curative resection at Kanagawa Cancer Center between January 2010 and December 2020 and whose tumors were tested for EGFR mutations. Relapse-free survival (RFS) and overall survival (OS) of patients with EGFR-mutant lung cancer (Mt, n = 126) including EGFR exon 21 L858R point mutation and EGFR exon 19 deletion mutation and EGFR mutation-wild lung cancer (Wt, n = 413) were analyzed using Kaplan–Meier curves and compared using a log-rank test. Cox regression analysis was performed to evaluate the effects of EGFR gene mutations on RFS and OS at each stage. ResultsThere were 56/256 patients with p-stage II EGFR-Mt/Wt and 70/157 patients with p-stage IIIA EGFR-Mt/Wt. The 5-year RFS rate of patients with EGFR-Mt/Wt was 46.6%/52.0% (p = 0.787) for p-stage II and 17.4%/29.7% (p = 0.929) for p-stage IIIA. The 5-year OS rate was 92.0%/65.7% (p = 0.001) for p-stage II and 56.0%/39.3% (p = 0.016) for p-stage IIIA. EGFR-Mt was not an independent prognostic factor for OS of patients with p-stage IIIA lung cancer (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.51–1.76; p = 0.872); however, EGFR-Mt was an independent favorable prognostic factor for OS of patients with p-stage II lung cancer (HR, 0.59; 95% CI, 0.36–0.96; p = 0.034). ConclusionThe OS of lung cancer patients with p-stage II or IIIA, classified according to the 8th edition TNM classification, was remarkably favorable. Incorporating EGFR mutations to the anatomical TNM classification may lead to a more accurate prognosis prediction.

Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma.

PURPOSEUnder common therapeutic regimens, the prognosis of human papillomavirus (HPV)–positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.METHODSPatients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.RESULTSThe study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.CONCLUSIONThe rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

Comparison of Recurrence With High Retropharyngeal Nodal-Sparing Intensity-Modulated Radiation Therapy in HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Patients with HPV-related oropharyngeal cancers (HPV+OPC) are known to have a superior locoregional control when compared to HPV-unrelated oropharyngeal cancers (HPV-OPC). The introduction of intensity-modulated radiation therapy (IMRT) has allowed dose painting and sparing of bilateral uninvolved high retropharyngeal nodes (RP). We reviewed outcomes and patterns of recurrence in patients with oropharyngeal cancer (OPC) treated with IMRT in patients with HPV+OPC and those with HPV-OPC. We hypothesize that high-RP sparing RT can reduce morbidity in HPV+OPC without sacrificing disease control.We retrospectively reviewed all adults with OPCs treated with curative intent IMRT ± chemotherapy from 2012-2017 at a single institution. HPV status was tested by p16 staining for all OPCs and patients were staged per the TNM 8th edition. All patients were treated with high-RP sparing, meaning omission of the nodal basin from the caudal limit of C2 to the base of skull bilaterally. Patients who did not complete prescribed treatments, with multiple primaries or with less than 3 months of follow up were excluded. Patients, disease, treatment and outcome data were retrieved. Date and location of local, regional, retropharyngeal and distant recurrences were recorded. Time to events, including RP recurrence-free survival (RP-RFS), regional recurrence-free survival (R-RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test were performed, for HPV+OPC vs HPV-OPC.The final analysis included 240 patients. Median follow-up was 4.18 years (0.25- 8.46). HPV+OPC patients accounted for 81% while HPV-OPC 19%. Median age was of 60 years (40 - 94.6) and 85.2% of patients were male. The most common primary subsites were tonsil (66.5%), and base of tongue (32.8%). Patients had stage I disease in 43%, stage II in 29%, stage III in 18% and stage IV in 10%; 84.6% of patients had nodal disease. Concurrent systemic treatments were delivered in 74% of patients. Overall, there were 3 patients (1.5%) with RP recurrences in HPV+OPC vs 2 patients (4.4%) in HPV-OPC. The 2-year RP and 5-year RP-RFS was 98% for HPV+OPC and 94% for HPV-OPC (P = 0.169). The 2-year and 5-year R-RFS was 92%/89% for HPV+OPC vs 80%/74% for HPV-OPC (P = 0.015) and 2-year and 5-year overall survival was 92%/78% for HPV+OPC vs 81%/59% for HPV-OPC (P = 0.009).High-RP sparing IMRT technique is associated with less than 5% of isolated recurrence in the high RP nodal region, despite most patients presenting with involved nodal disease. Our data showed no statistically significantly difference in the HPV+OPC vs HPV-OPC patients. As a result, these data suggest that continuing this practice is associated reasonable disease control and further studies are needed to evaluate patients' long-term quality of life and morbidity.

OA06.04 Constructing a Global Molecular Database for Thoracic Malignancies: The IASLC Molecular Subcommittee Lung Cancer Dataset

Biomarker-directed treatment and prognostication are changing lung cancer care. Differences in the prevalence, and disparities in use, of biomarkers inhibit dissemination of personalized cancer care on a global scale. For the first time, the IASLC’s Staging and Prognostic Factors Committee (SPFC) is accumulating molecular biomarker data to complement TNM-based prognostication. We provide a snapshot below. We collected lung cancer cases diagnosed from 2010 to 2019, staged by 8th edition TNM, from consenting institutions. We describe data sources, NSCLC characteristics and biomarker data (ALK, BRAF, EGFR, KRAS, ROS1, MET, RET, NTRK1, ERBB2 or PD-L1) submitted by Electronic Data Capture (EDC). We compared EDC cases with and without biomarker data as of April 1, 2021. Of 64,434 cases in the SPFC NSCLC database, 6611 (10%) were EDC cases (Figure), of which 2068 (31%) had biomarker data. Almost all cases were submitted from Asia, Australia, North America and Europe (Table). All biomarker data came from 14 countries, including China (28%), Canada (25%), Spain (15%), Australia (10%), and India (5%). Cases with biomarker data were more likely to be adenocarcinoma, advanced stage and non-surgical, although 46% had had surgery. Single gene tests predominated, EGFR (70%) was most common. Most cases were wildtype, ranging from 68% of KRAS to 100% of NTRK tested cases (Table).Tabled 1VariableBiomarker Data Not Available, N= 4543Biomarker Data Available, N - 2068PAge, years (%) <65 ≥652129 (46) 2414 (53)1113 (53) 955 (46)< 0.001Female Sex (%)1890 (41)853 (41)0.79Continent (%) Asia/Australia North America Europe South/Central America Africa/Middle East1373 (30) 1645 (36) 1239 (27) 266 (5) 20 (0)1014 (49) 586 (28) 444 (21) 23 (1) 1 (0)<0.001Histology (%) Adenocarcinoma Squamous NSCLC NOS Adenosquamous Large cell neuroendocrine2889 (36) 1352 (29) 94 (2) 79 (1) 34 (0)1573 (76) 355 (17) 90 (4) 27 (1) 12 (0)<0.001Aggregate clinical stage (%) 0 – IB IIA – IIIB IIIC – IVB2642 (61) 1264 (29) 420 (9)549 (27) 623 (30) 844 (41)<0.001Aggregate pathologic stage (%) 0 – IB IIA – IIIB IIIC – IVB2224 (63) 1169 (33) 125 (3)407 (44) 447 (49) 55 (6)<0.001Treatment (%) Surgery Chemotherapy Immunotherapy Radiation therapy3626 (82) 1268 (30) 73 (2) 642 (15)945 (46) 983 (52) 291 (15) 424 (22)<0.001Genomic data available: Tested (%); percentage wildtypeALK BRAF EGFR KRAS ROS-1 MET RET NTRK ERBB2291 (14); 92% 139 (6); 88% 1461 (70); 77% 306 (14); 68% 176 (8); 88% 78 (3); 90% 31 (1); 94% 24 (1); 100% 73 (3); 92%PDL1 tested (%) Percentage with Tumor Proportion Score: >50% 1-50%1237 (59) 15% 21% Open table in a new tab Most of the EDC cases with biomarker data are from a few institutions in Asia, Australia, Europe and North America. This database will expand as we include non-EDC cases. However, given the potential for a global database to create insights into patterns and outcomes of lung cancer care, a more comprehensive recruitment of additional institutions, countries and continents is needed, to ensure that the dataset reflects the global epidemiology of lung cancer. We will analyze the full SPFC data sample in future reports.

Characterization of Outcomes by Surgical Management of Lung Neuroendocrine Tumors Associated With Cushing Syndrome

Ectopic adrenocorticotropic hormone secretion from lung tumors causing Cushing syndrome are associated with high rates of morbidity. Optimal management remains obscure because knowledge is based on rare reports with few patients. To characterize the outcomes of lung neuroendocrine tumors associated with Cushing syndrome. An observational case series review from 1982 to 2020 was conducted in a single institution referral center. Kaplan-Meier analysis estimated disease-free survival (DFS). Participants underwent curative-intent surgery for a lung neuroendocrine tumor causing Cushing syndrome. Lobectomy or pneumonectomy vs sublobar resection. Disease-free survival, disease persistence/recurrence. Of the 68 patients, the median age was 41 years (range, 17-80 years), 42.6% (29 of 68) were male, 81.8% (54 of 66) were White, with a mean follow-up after surgery was 16 months (range, 0.1-341 months). Lobectomy was the most common procedure (48 of 68 [70.6%]), followed by wedge resection (16 of 68 [23.5%]) and segmentectomy (3 of 68 [4.4%]). Video-assisted thoracoscopic surgery was performed in 19 of 68 (27.9%) of patients. Surgical morbidity was 19.1% (13 of 68), and perioperative mortality was 1.5% (1 of 68). Lymph node positivity was 37% (22 of 59) when evaluable. The overall incidence of persistence/recurrence was 16.2% (11 of 68) with a median time to recurrence of 55 months (range, 18-152 months). The median DFS was reached in 12.7 years (0.1-334 months). There were no statistical differences in DFS based on tumor size, stage (8th edition TNM), whether full systematic lymphadenectomy was performed or not, nodal status, or surgical approach. In this case series study, neuroendocrine pulmonary tumors associated with Cushing syndrome had increased nodal metastasis, higher recurrence, and lower DFS than quiescent bronchopulmonary carcinoid tumors, but many patients experienced favorable outcomes. This observation is underscored by the discordance of TNM-stage classifications vs prognosis. Observing no difference in surgical techniques, the implication may be that a lung-sparing approach could suffice. These results may reflect the intrinsic importance of the hormone physiology instead of the carcinoid biologic factors.

Prognostic relevance of pleural invasion for resected NSCLC patients undergoing adjuvant treatments: A propensity score-matched analysis of SEER database

BackgroundAdjuvant chemotherapy demonstrated a clear benefit in resected non-small cell lung cancer (NSCLC) with nodal disease (stages II-III), and a minimal benefit in tumors >4 cm (stage II, TNM 8th edition). Pleural invasion (PL), classified as visceral pleural invasion (VPI, which includes PL1 and PL2, and parietal pleural invasion (PL3), is an established negative prognostic factor. However, whether PL should influence the decisional algorithm of postoperative chemotherapy is controversial. MethodsA survival analysis of NSCLC patients who underwent radical surgery between 2010 and 2015 included in the SEER database was performed. Tumor stage and size, number of examined and positive nodes, histology, PL, and treatment data were extracted. Propensity score matching was performed. The benefit of chemotherapy was analyzed in two subgroups: standard of care (SOC), including patients with positive nodes or tumors ≥ 4 cm; non-SOC, including patients with tumors < 4 cm and negative nodes. ResultsRecords of 30,858 patients were extracted. 11,708 patients were included in the propensity score-matched analysis. In the SOC subgroup, including 8089 patients, all pleural invasion degrees were associated with progressively increased risk for death and shorter overall survival (OS), independently from chemotherapy administration. However, chemotherapy significantly improved the median OS regardless of the extent of PL. In the non-SOC subgroup, including 3619 patients, only PL3 was associated with increased mortality. The administration of chemotherapy did not improve survival outcomes. ConclusionChemotherapy should be strongly recommended in patients in the SOC-subgroup with pleural invasion. VPI is not associated with unfavorable prognosis in the non-SOC subgroup.

Mandatory Nodal Evaluation During Resection of Clinical T1a Non-Small Cell Lung Cancers

BackgroundRecommendations for intraoperative lymph node evaluation are uniform regardless of whether a primary tumor is clinical T1a or T2a according to TNM 8th edition for stage I non-small cell lung cancer (NSCLC). We quantified nodal disease risk in patients with T1a disease (≤1 cm). MethodsThe National Cancer Database was queried for clinical T1a N0 M0 primary NSCLCs ≤1 cm undergoing lobectomy with mediastinal nodal evaluation from 2004-2014. Nodal disease risk was analyzed as a function of demographics and tumor characteristics. ResultsAmong 2157 cases, 6.7% had occult nodal disease: 5.1% occult N1 and 1.6% N2. Adenocarcinoma (7.5%), large cell carcinoma (25%), and poor differentiation (11.8%) or undifferentiated/anaplastic (25.0%) had high rates of combined pN1 and N2 disease (P < .001). In univariable analysis, odds of pathologic N1, N2, or N1/N2 nodal disease with respect to N0 was greatest for large cell carcinoma (ref. adenocarcinoma odds ratio [OR] 4.31, 3.62, 4.12 respectively; all P < .05), and anaplastic grade (OR 10.71, 13.09, 11.55). Bronchoalveolar adenocarcinomas had the lowest odds (OR 0.41, 0.11, 0.32) and squamous cell carcinoma had lower odds for N2 (OR 0.29, all P < .05). In multivariable analysis only bronchoalveolar adenocarcinomas had lower odds of pathologic N2 and N1/N2 disease with respect to N0. Worsening grade remained significant for pathologic N1 and N1/N2 disease (both P < .05). ConclusionsA significant rate (6.7%) of occult nodal disease is present in primary NSCLCs ≤1 cm. Risk increases with certain histology and worsening grade. We recommend mandatory systematic hilar and mediastinal nodal evaluation for T1a NSCLC tumors for accurate staging and adjuvant therapy.

P-20 Concurrent chemo-radiotherapy in anal squamous cell carcinomas: A 10-year retrospective review of a tertiary centre experience

Anal cancer is an uncommon form of gastrointestinal malignancy and treatment is often confined to specialist centres. It has a high cure rate with a non-surgical approach resulting in organ preservation. Chemo-radiotherapy (CCRT) remains the standard treatment for these cancers. The current accepted schedule is CCRT with 5FU mitomycin C (5FUMC) and radiotherapy doses between 50.4-53.2 Gray in 28 fractions. This study included patients who had histological confirmation of squamous cell carcinoma and had completed the full CCRT course in our centre for anal cancer between 2008 and 2017. The concurrent chemotherapy was mitomycin C with either 5FU or capecitabine. Some patients received neoadjuvant chemotherapy and some had adjuvant chemotherapy. Data was collected retrospectively assessing basic demographics, staging, surgery, relapse, latest follow-up, and date of death, as well as CCRT regimen. All TNM stages were included and original staging was revised on review of imaging based on TNM 8th edition. Outcome data and stoma reversal rate were analysed. Overall, 87 patients were included in the study. The median age of patients was 60 years. At diagnosis, 94.3% of patients had T2-T4 disease and 44.8% had involvement of positive loco-regional lymph nodes. Overall survival (OS) probability at 1, 3, and 5 years were 98.8%, 87.4%, and 83.7%, respectively. Results also revealed a statistically significant effect of time from diagnosis to radiotherapy start on OS (p=0.039). Sixty-nine (79.3%) patients achieved complete remission at last follow-up. Three (3.4%) patients had a local relapse and 9 (10.3%) relapsed systemically. Six patients (6.9%) had persistent disease. The mean time to relapse was 16 months, and Median OS was 52.3 months. Twenty-one patients (24%) underwent surgery for a defunctioning stoma, only five of these patients subsequently received stoma reversal. Our data reflects the efficacy of CCRT as the primary modality of treatment in the management of anal squamous cell carcinoma with effective organ preservation and disease control. Further studies with increased dose to primary may improve outcomes even further. Early stoma reversal would also improve quality of life.

Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma.

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is associated with poor prognosis. The 8th edition of TNM has implemented new nodal staging criteria. We assess the prognostic utility of the lymph node ratio (LNR) and compare it to that of pN in the TNM 8th edition. One hundred and forty-two patients with OSCC were retrospectively studied. Nodal staging was performed using the TMN 8th edition and the prognostic value of the LNR in terms of overall survival (OS) and disease-free survival (DFS) was evaluated. Fifty-seven patients were eligible for inclusion. The LNR was independently prognostic of OS (p=0.02). Instead N classification was not significantly predictive of OS (p=0.10). High LNRs resulted in decreases in OS of approximately 40% within 6months after surgery. The LNR identifies patients with poor outcomes better than N classification. The lack of reliable LNR cutoffs compromises its utility in clinical practice.

A potential survival impact of blood immune cells in patients with locoregionally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy.

e18027 Background: To exam the changes of blood immune cells during concurrent chemoradiotherapy (CCRT) and explore their effects on survival in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Study population included stage III-IVA (TNM-8th edition) locoregionally advanced nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy followed by CCRT from January 2015 to October 2019. Patients received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles or 40mg/m2 weekly for a total of 6 weeks concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. All had complete blood counts with differentials at baseline and before each chemotherapy. The primary endpoint was progression-free survival (PFS). “Immune cells” of our interest included lymphocytes, neutrophils and platelets. Results: A total of 139 patients were eligible and recruited. The median follow-up was 34 months (range 4-72). All immune cells decreased significantly during CCRT; the rate of grade 3/4 lymphopenia, neutropenia and thrombocytopenia during CCRT were 96.4%, 25.2% and 9.4%, respectively. The median (interquartile range, IQR) time to nadir from the start of CCRT were 40 (32-44), 26 (20-42) and 30 (15-39) days for lymphocytes, neutrophils and platelets, respectively. The median PFS was not reached and estimated 2-year PFS was 90.2%. Patients with lymphocyte nadir ≤ 0.2×109/L had better PFS compared with those with lymphocyte nadir &gt; 0.2×109/L（2-yr PFS 95.5% vs. 87.5%, P=0.048). Patients with platelet nadir &lt; 100×109/L had better PFS compared with those with platelet nadir ≥ 100×109/L(2-yr PFS 96.9% vs. 84.2%, P=0.011). Neutrophil nadir was not associated with PFS in univariate analysis. Multivariate analysis including prognostic variables in univariate analysis showed that platelet nadir (&lt; 100 × 109/L vs ≥ 100 × 109/L, hazard ratio [HR] 0.279, 95% confidence interval [CI] 0.091-0.857, P=0.026), stage (III vs IVA, HR 0.321, 95% CI 0.115-0.901, P=0.031) and cumulative concurrent cisplatin dose (&lt; 180mg/m2 vs ≥ 180mg/m2, HR 3.422, 95% CI 1.366-8.577, P=0.009) were prognostic of PFS by adjusting lymphocyte nadir and baseline hemoglobin. Conclusions: Blood immune cells decreased during CCRT and thrombocytopenia was prognostic of PFS in patients with LANPC. Longer follow-up is warranted to identify prognostic factors of overall survival.

Molecular characteristic of proximal and distal esophagogastric junction adenocarcinomas.

e16077 Background: Esophagogastric junction adenocarcinomas (EGJA) are devastating diseases with increasing incidence. The 8th Edition TNM staging of American Joint Committeeon Cancer and Union for International Cancer Control defined that the epicenter of EGJA within 2 cm of the cardia (hereinafter referred to proximal EGJA) is staged according to the staging standard of esophageal cancer, while that more than 2 cm distal from the EGJA (hereinafter referred to distal EGJA) is staged according to the staging standard of stomach cancer. However, the rationality of the new definition in clinical practice is still controversial. Methods: A randomized retrospective study was conducted. Targeted next-generation sequencing of 450 cancer-related genes was performed, by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China, for genomic alteration identification. Results: A total of 198 EGJ patients were included in this study with a median age of 63 years (ranged from 39 to 88 years). Among them, 140 were distal EGJA and 58 were proximal EGJA. Genomic alterations with a high mutation frequency in EGJ include There is no significant difference in the frequencies of these genes between proximal EGJA and distal EGJA. Mutation frequencies of FGFR2 and ZEN217 in distal EGJ were significantly higher than those in proximal EGJA (15.8% vs 5.0%, P = 0.02 and 7.0% vs 0.7%, P = 0.03, respectively). Multivariate regression analysis showed that tumor stage and lymph nodes number were the main factors positively associated with the poor prognosis. However, we found that there was no significant difference in OS between proximal and distal (P = 0.139). Furthermore, our results showed that LRP2 and SPTA1 mutations were significantly associated with better OS of the EGJA patients. Conclusions: In conclusion, with the identification of the mutation landscape of EGJA, the FRFR2 and ZNF127 genes mutations were potential biomarkers to distinguish distal EGJA from proximal EGJA, whereas the LRP2 and SPTA1 gene mutations were potential biomarkers for prognosis prediction in EGJA.

The Poor Prognosis of Patients with Stage III Gastric Cancer after D2 Dissection Is Mainly due to Lymphatic Metastasis, Especially the Metastasis of No.12a LN: A Nested Case-Control Study

Background: The prognosis of stage III gastric cancer (GC) patients based on the 8th edition TNM staging system after D2 dissection was still heterogeneous. We aimed to explore clinicopathological reasons that led to the poor prognosis of these patients, especially from a surgical aspect. Methods: We divided 320 stage III GC patients who underwent distal or total gastrectomy with D2 lymphadenectomy into group 1 and group 2, according to the disease-free survival (DFS), and compared the clinicopathological features between these 2 groups. Then, we divided group 1 into group 1D and group 1T and group 2 into group 2D and group 2T, according to distal or total gastrectomy. Finally, we compared the status of lymph node (LN) metastasis in each group of perigastric LN between the subgroups, respectively. Results: Univariate analyses revealed that patients’ LN metastasis was the only significant difference between group 1 and group 2 (p < 0.05). Compared with group 1D, the percentage of patients who had metastatic LN in all groups of the perigastric LN (included No.1, 3, 4sb, 4d, 5, 6, 7, 8a, 9, 11p and 12a) increased in group 2D. A similar tendency was found in group 2T (included No.1, 2, 3, 4sa, 4sb, 4d, 5, 6, 7, 8a, 9, 10, 11p, 11d and 12a) compared with group 1T. Further multivariate regression analyses revealed that the increases of group No.12a and 5 LN were significant (p < 0.05) in group 2D, the increases of group No.12a, 8a and 6 LN were significant (p < 0.05) in group 2T, respectively. Among these, the increases of group No.12a LNs were the most significant (p < 0.01). Conclusions: The poor prognosis of patients with stage III GC after D2 dissection is mainly due to lymphatic metastasis. The status of LN metastasis in the prognostic value of GC needs to be further enhanced in present staging systems. Maybe the metastasis of No.12a LN is the most significant poor prognostic factor of these patients. It points out that the dissection of No.12a LN should be carefully performed in radical gastrectomy.

Impact of the new TNM Staging System (8th edition) on oral tongue cancers.

For tumours of the oral tongue, the most recent 8th edition of the AJCC/UICC staging system has introduced depth of infiltration (DOI) as a novel parameter. With this study we wanted to investigate its impact regarding this risk stratification compared with the preceding 7th edition. Between 2008 and 2017, 161 patients of two tertiary referral centres in Switzerland (Kantonsspital St. Gallen and University Hospital Zurich) with T1 N0 or T2 N0 tongue cancers were enrolled in this study. The primary tumours were restaged according to the 8th edition of the TNM classification. Kaplan-Meier curves for overall and disease-specific survival were calculated. According to the 7th edition, of the 161 patients, 102 were staged after surgery as pT1 (stage I) and 59 as pT2 (stage II). According to the 8th edition, 36 patients (22.4%) were re-staged to a higher stage. Of these 36 patients, 8 (22.2%) experienced a recurrence, and 9 (25%) died. In the remaining, not re-staged group, 20 patients (16.0%) experienced a recurrence (p = 0.55) and 14 (11.2%) died (p = 0.025*). The 7th edition showed a statistically significant difference between pT1 and pT2 tumours for overall survival (p = 0.025), but not for disease-specific survival (p = 0.091), whereas the 8th edition was able to well discriminate between pT1, pT2 and pT3 for both overall (pT1 vs pT2, p = 0.016*; pT2 vs pT3, p = 0.031*) and disease-specific survival (pT1 vs pT2, p = 0.037*; pT2 vs pT3, p = 0.023*). The recent TNM 8th edition provides a more accurate prediction of overall and disease-specific survival for this subgroup of patients. Hence, a more aggressive treatment should be considered for patients re-staged to pT3 due to depth of infiltration.

Differences between TNM classification and 2-[18F]FDG PET parameters of primary tumor in NSCLC patients.

BackgroundThe aim of the study was to compare the TNM classification with 2-[18F]FDG PE T biological parameters of primary tumor in patients with NSCLC.Materials and methodsRetrospective analysis was performed on a group of 79 newly diagnosed NSCLC patients. PET scans were acquired on Gemini TF PET/CT scanner 60–70 min after injection of 2-[18F]FDG with the mean activity of 364 ± 75 MBq, with the area being examined from the vertex to mid-thigh. The reconstructed PET images were evaluated using MIM 7.0 Software for SUVmax, MTV and TLG values.ResultsThe analysis of the cancer stage according to TNM 8th edition showed stage IA2 in 8 patients, stage IA3 — 6 patients, stage IB — 4 patients, IIA — 3 patients, 15 patients with stage IIB, stage IIIA — 17 patients, IIIB — 5, IIIC — 5, IVA in 7 patients and stage IVB in 9 patients. The lowest TLG values of primary tumor were observed in stage IA2 (11.31 ± 15.27) and the highest in stage IIIC (1003.20 ± 953.59). The lowest value of primary tumor in SUVmax and MTV were found in stage IA2 (6.8 ± 3.8 and 1.37 ± 0.42, respectively), while the highest SUVmax of primary tumor was found in stage IIA (13.4 ± 11.4) and MTV in stage IIIC (108.15 ± 127.24).ConclusionTNM stages are characterized by different primary tumor 2-[18F]FDG PET parameters, which might complement patient outcome.

Depth of invasion in early oral cancers- is it an independent prognostic factor?

IntroductionDepth of invasion (DOI) has been incorporated into oral cancer staging. Increasing DOI is known to be associated with an increased propensity to neck metastasis and adverse tumor factors and hence may not be an independent prognosticator but a surrogate for a biologically aggressive tumor. Methods570 patients, median follow up 79.01 months from a previously reported randomized trial (NCT00193765) designed to establish appropriate neck treatment [elective neck dissection (END) vs therapeutic neck dissection (TND)] in clinically node-negative early oral cancers were restaged (nT) according to AJCC TNM 8th edition. Overall survival (OS) was estimated for the entire cohort, END, and TND arms. Multivariate analysis performed for stratification and prognostic factors, and interaction term between revised T-stage and neck treatment, for tumours with DOI≤10mm. Presence of adverse factors was compared between nT3 (DOI>10 mm) and those with DOI≤10 mm. ResultsStage migration occurred in 44.38% of patients. 5-Year OS was nT1-79%, nT2-69.4% and nT3-53.8%, (p < 0.001). In TND arm 5-year OS was nT1-81.1% versus nT2-65%,p = 0.004, while that in END arm was nT1 -76.9% versus nT2 -73.7%,p = 0.73. There was a significant interaction between T stage and neck treatment (p = 0.03). T3 tumors (>10 mm) were associated with a higher proportion of adverse factors (occult nodal metastasis, p = 0.035; LVE/PNI, p = 0.001). ConclusionElective neck treatment negates the prognostic impact of DOI for early oral cancers (T1/T2 DOI≤10 mm). T3 tumors with DOI>10 mm have a higher association with other adverse risk factors resulting in poorer outcomes in spite of elective neck dissection.