8th Edition AJCC Staging Research Articles

RB1, p16, and Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma.

While P16 immunohistochemistry (IHC) is a well-established surrogate marker of Human Papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC), Retinoblastoma 1 (RB1) loss may lead to p16 overexpression in the absence of HPV. We determined the proportion of p16-positive/HPV-negative OSCC with RB1 loss and other alterations in RB1/p16 pathway, and tested RB1 IHC as a prognostic biomarker for OSCC, along with the 8th edition of AJCC staging manual. P16 and RB1 IHC and HPV DNA in situ hybridization (ISH) were performed on 257 OSCC. High risk HPV RNA ISH, RB1 fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) were done on p16-positive/HPV DNA ISH-negative OSCC. Disease free survival (DFS) was used as an endpoint. In the entire cohort and in p16-positive (n = 184) and p16-negative (n = 73) subgroups, AJCC 8th edition staging correlated with DFS (p < 0.01). RB1 IHC showed RB1 loss in p16-positive OSCC only (79/184, 43%). RB1 loss by IHC is associated with a better DFS, without providing additional prognostic information for patients with p16-positive OSCC. HPV RNA ISH was positive in 12 of 14 HPV DNA ISH-negative cases. RB1 IHC showed loss in 10 of 15 HPV DNA ISH-negative cases and in 1 of 2 HPV RNA ISH-negative cases. Overall, only one case of p16-positive/HPV RNA ISH-negative OSCC showed RB1 loss by IHC (1/184, 0.5%). Of the 10 p16-positive and HPV DNA ISH-negative cases with RB1 loss by IHC, 2 had RB1 hemizygous deletion and 3 showed Chromosome 13 monosomy by FISH. No RB1 mutations were detected by NGS. Other molecular alterations in p16-positive/HPV DNA ISH-negative cases included TP53 and TERT mutations and DDX3X loss. HPV-independent RB1 inactivation rarely results in false positive p16 IHC. RB1 inactivation by high risk HPV E7 oncoprotein may co-exist with RB1 deletion. RB1 loss is a favorable prognosticator and occurs exclusively in p16-positive OSCC. The 8th edition of the AJCC staging manual satisfactorily predicts DFS of OSCC patients.

Oral Cancer in the Indian Subcontinent-Survival Outcomes and Risk Factors with Primary Surgery.

To assess the oncological outcome and prognostic factors for primary Oral Squamous Cell Cancer (OSCC) staged as per AJCC 8th pTNM, and treated by the contemporary standard of primary surgery and pathology directed adjuvant radiation-chemoradiation. A single institution cohort from a tertiary care academic institution in North India. Case inclusion 2013 to 2016; n=218, median follow-up 35 months. All patients were restaged as per the AJCC 8th pTNM classification. Analysis for Overall Survival (OS), Disease-free Survival(DFS), and factors impacting outcome (Cox proportionate model Multivariate analysis). AJCC pTNM 7th to 8th edition conversion led to upstaging in 16.5%. Stage-II demonstrated greatest stage migration and apparent improvement in OS and DFS (P < .09). Discordance was noted between the presurgical (clinico-radiologic) and postsurgical (pathological) nodal status in 40.3% (88/218; 54 pathologically upstaged;34 downstaged). Pathological downstaging was particularly significant with advanced stage Gingivo-Buccal Cancers (25/73-34.7%). Stage-I-II early cancers had 3 years. OS-86.7% and DFS-78.8%; Stage-III-IV advanced cancers had 3 years. OS-56.7% and DFS-46.6%. Multivariate analysis identified poorer OS and DFS for age < 40 years (HR-1.8; 2.0), skin involvement (HR-2.1; 2.6) and pN+ status (HR-2.4; 3.5). Bone involvement did not compromise survival in this surgically treated set of patients. Age < 45 is newly identified as significantly compromising DFS and OS in Oral Cancer. Established factors of skin involvement and pN+ are confirmed as impacting DFS-OS. An apparent improvement in survival in Stage II Cancers is noted as consequent to adoption of AJCC 8th edition staging. 2 (OCEBM 2011-Inception Cohort Study for Prognosis) Laryngoscope, 131:2254-2261, 2021.

Evaluation of the prognosis for N2 status in patients with small bowel neuroendocrine tumors

BackgroundThe 8th edition AJCC Staging for small bowel neuroendocrine tumors created a novel N2 classification. This study investigates if it is independently prognostic. MethodsRecords of patients from 2008 to 2019 were reviewed. Survival rates were estimated by Kaplan-Meier method and compared by log-rank. The Cox Proportional Hazards model was used to determine factors associated with overall survival (OS) via multivariate analysis. ResultsAmong 300 patients, 225 were N2 and 60 were N1. No differences were seen in pathologic markers for N1 compared to N2. N2 were more likely to have liver metastases (LM) (p = 0.048) but rates of resectability were similar. Median OS for N1 with >70% liver cytoreduction was not yet reached compared to 121 months for N2 (p = 0.005). On multivariate analysis, LM was associated with shorter survival (p = 0.028), but nodal status was not. ConclusionsUnlike LM, N2 status is not independently prognostic, but a marker for aggressive LM.

Proposed Modification of the pN2 Classification of the 8th Edition AJCC Staging System for Esophageal Squamous Cell Carcinoma: A Preliminary Study Based on the Chinese Population.

Objective To evaluate the efficacy of the nodal staging of the 8th edition AJCC staging system for esophageal squamous cell carcinoma (ESCC) and propose a modification of the current pN2 classification. Methods 1188 patients who underwent esophagectomy for ESCC at Sun Yat-sen University Cancer Center in Guangzhou (Guangdong, China) between January 2005 and June 2010 were reviewed. We used the X-tile software to determine the optimal cutoff points. Kaplan–Meier method and log-rank test were used to compare the differences of survival. Multivariate Cox regression analysis was performed for the factors that were statistically significant in univariate analysis. Result In multivariate Cox regression analysis, alcohol consumption, pT status, and pN status were independent prognostic factors for overall survival (OS) according to the current pN classifications. And the observed 5-year OS rates for groups pN0, pN1, pN2, pN3 were 66.7%, 45.0%, 31.5%, and 21.5%, respectively (P<0.001). Based on the above results, the current pN2 classification was further subdivided as pN2a [3 metastatic lymph nodes (LNs)] and pN2b (4−6 metastatic LNs) groups. The 5-year OS rates for groups pN0, pN1, pN2a, pN2b, and pN3 were 66.7%, 45.0%, 37.7%, 26.3% and 21.5%, respectively (P<0.001). The rate of 5-year disease-free survival (DFS) was 60.0% for patients with pN0, compared with 36.8%, 29.3%, 20.8%, and 14.3% for those with pN1, pN2a, pN2b, and pN3, respectively (P<0.001).The current pN2 classification should be subdivided as pN2a (3 metastatic LNs) and pN2b (4–6 metastatic LNs) groups. The modified pN2 classification could better discriminate the survival differences between patients with 3–6 metastatic LNs for ESCC in the Chinese population.

Stereotactic body radiotherapy for synchronous early stage non-small cell lung cancer

Introduction In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions. Material and methods Patients with synchronous AJCC 8th Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009–2018 were reviewed. SPLC was defined as patients having received two courses of SBRT within 180 days for treatment of separate early stage tumors. In total, 36 patients with 73 lesions were included. Overall survival (OS), progression-free survival (PFS), cumulative incidence of local failure (LF), and regional/distant failure (R/DF) were estimated and compared with a control cohort of solitary early stage NSCLC patients. Results Median PFS was 38.8 months (95% CI 14.3-not reached [NR]); 3-year PFS rates were 50.6% (35.6–72.1). Median OS was 45.9 months (95% CI: 35.9-NR); 3-year OS was 63.0% (47.4–83.8). Three-year cumulative incidence of LF and R/DF was 6.6% (3.7–13.9) and 35.7% (19.3–52.1), respectively. Patients with SPLC were compared to a control group (n = 272) of patients treated for a solitary early stage NSCLC. There was no statistically significant difference in PFS (p = .91) or OS (p = .43). Evaluation of the patterns of failure showed a trend for worse cumulative incidence of R/DF in SPLC patients as compared to solitary early stage NSCLC (p = .06). Conclusion SBRT alone to multiple lung tumors with SPLC results in comparable PFS, OS, and LF rates to a cohort of patients treated for solitary early stage NSCLC. Those with SPLC had non-significantly higher R/DF. Patients with SPLC should be followed closely for failure and possible salvage therapy.

Failure rate in the untreated contralateral node negative neck of small lateralized oral cavity cancers: A multi-institutional collaborative study

ObjectivesThe importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment. Materials and methodsWe performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS). Results176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2–7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4–32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2–95.0%) and 80.6% (95% CI 74.5–86.8%), respectively. ConclusionObservation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging.

Prognostic impact of retropharyngeal lymphadenopathy in early-stage HPV-associated oropharyngeal cancer: Implications for staging optimization.

We analyzed the prognostic impact of retropharyngeal lymphadenopathy (RPL) in stage I node-positive HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We performed a centralized and blinded radiographic review of the pre-treatment images of 234 consecutive patients with AJCC 8th edition stage I cT1-2N1 HPV-associated OPSCC treated with definitive chemoradiation from 2006 to 2016. Five-year disease control and survival outcomes were reported. The prognostic significance of RPL was evaluated through multivariable analysis adjusting for age, smoking history (<10 vs. >10 pack-years), and systemic regimen received. Median follow-up for surviving patients was 49 months (range: 16-121). RPL was associated with increased locoregional recurrence (LRR) (17.0% v. 3.4%, p = 0.01) and distant metastasis (DM) (29.1% v. 5.9%, p = 0.001) and inferior progression-free survival (PFS) (55.6% v. 88.2%, p < 0.001) and overall survival (OS) (60.6% v. 91.2%, p < 0.001). In stage I patients who did not receive high-dose cisplatin (HDC), RPL was associated with worse LRR (p = 0.04), DM (p = 0.03), PFS (p < 0.001), and OS (p < 0.001), whereas in those who did receive HDC, RPL was only associated with increased DM (p = 0.002) and inferior PFS (p = 0.04). This study suggests that RPL portends a poor prognosis in stage I node-positive HPV-associated OPSCC. The negative impact on LRR may have been mitigated by receipt of HDC. Outcomes of stage I disease with RPL were comparable to historical reports of patients with more advanced-stage disease. Incorporation of RPL into future disease staging should be considered in order to optimize risk-stratification and exclude unsuitable candidates from treatment de-intensification efforts.

Laparoscopic liver resections for gallbladder cancer and intrahepatic cholangiocarcinoma: the Mayo clinic experience

Presenter: Ron Pery MD | Mayo Clinic, Rochester Background: Gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (ICC) are aggressive malignancies where surgical resection offers the only meaningful chance of cure. Complete tumor removal with negative margins and adequate porta hepatis lymphadenectomy for tumor staging is the surgical standard of care in resectable cases according to the national comprehensive cancer network (NCCN) guidelines. The safety and oncological adequacy of laparoscopic liver resections for GBC and ICC have been questioned in the past and many surgeons were hesitant to consider it. Being a high-volume center of minimal invasive liver surgeries, this study aimed to describe the Mayo clinic experience with laparoscopic liver resections for GBC and ICC and to specifically ascertain their safety and oncological adequacy. Methods: The Mayo clinic database was used to identify patients who underwent curative intent laparoscopic liver resection for GBC or ICC between 01/2016 to 12/2020. Clinicopathological characteristics, operative details and outcomes of 33 patients were collected and analyzed with specific emphasis on resection margins, porta hepatis lymphadenectomy and post-operative complications. Results: 33 patients with GBC or ICC underwent curative-intent laparoscopic liver resection with or without porta hepatis lymphadenectomy in Mayo clinic between 01/2016 and 12/2020. The median age of patients was 65±11.8. Six (18%) patients underwent major liver resection with porta hepatis lymphadenectomy, fourteen (42%) patients underwent minor liver resection with porta hepatis lymphadenectomy; while five (16%) patients underwent major liver resection and eight (24%) patients underwent minor liver resection without portal lymphadenectomy. The mean operative time was 193 minutes (range 83-881) and the mean estimated blood loss (EBL) was 250cc (range 25-1700). There were two conversions (6%) to laparotomy due to failure to progress. Nineteen (58%) patients had no post-operative complications, five (15%) patients had minor post-operative complications (Clavien Dindo score ≤2) and nine (27%) patients had major post-operative complications (Clavien Dindo score ≥3) including one post-operative mortality (3%) due to portal vein thrombosis leading to fatal liver failure. The median in hospital length of stay was three days (range 1-39). On pathology, the mean tumor size was 36.5mm (range 15-150) and resection margins were negative in all specimens. Amongst the patients who underwent porta hepatis lymphadenectomy, the mean number of harvested lymph nodes was 4.5 (range 1-19) and eight (40%) patients have met the AJCC 8th edition staging manual cutoff of at least six harvested lymph nodes. Conclusion: When done by experienced minimal invasive liver surgeons in a high-volume center, laparoscopic liver resections for GBC and ICC are both feasible, safe and oncologically appropriate. While operative times, EBL and post-operative complications profiles are comparable to historic open controls, the in-hospital length of stay is shorter. As in open surgeries, an effort should be made to meet the AJCC 8th edition recommendation of at least six harvested lymph nodes for adequate tumor staging.

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non–Small Cell Lung Cancer

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Study of cutaneous melanoma recurrences after sentinel node biopsy: Patterns of dissemination and use of complementary test in follow-up.

To investigate the patterns of melanoma recurrence in the local population, including factors that may influence in this event and timing of relapse, and to determine the mode of detection of them. This is a retrospective cohort study of patients with melanoma who underwent sentinel lymph node biopsy at the Complejo Hospitalario de Navarra (Spain) from 2002 to 2012. The following data were collected of each patient: age, gender, date of diagnosis, location of melanoma, histological subtype, Breslow thickness, ulceration, mitosis, sentinel node status, AJCC 8th edition stage, site of first diagnosed metastasis, mode of relapse, date of first relapse and time of death. Of 308 patients, 30% people suffered metastasis. The mean follow-up time was 68.63months. 51.1% of relapses were locoregional and 48.9% haemato-visceral. Sentinel node status was the only variable associated with higher risk of haemato-visceral metastasis (p<0.001). The mean time between diagnosis of melanoma and recurrence was 2.7years. Most recurrences were detected by the patient himself or had any type of symptoms and were consequently selected for a complementary test. It is important to follow-up all patients with diagnosis of cutaneous melanoma, essentially during the first 5years after diagnosis.

Validation of the AJCC 8th Edition Staging System for Appendiceal Cancer Using a Multi-Institutional Cohort of Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC)

Validation of the AJCC 8th Edition Staging System for Appendiceal Cancer Using a Multi-Institutional Cohort of Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC)

Multi-institutional development and validation of a nomogram to predict recurrence after curative resection of gastric neuroendocrine/mixed adenoneuroendocrine carcinoma.

To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). The median follow-up time was 40months (1-169months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.

A new face of the HPV epidemic: Oropharyngeal cancer in the elderly.

As the human papillomavirus (HPV) epidemic continues to grow, the number of elderly patients with oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing. Despite this observation, this cohort remains understudied. We aimed to understand HPV prevalence and characteristics within this cohort as well as its impact on disease control in elderly patients. We identified patients aged ≥70 with newly diagnosed, non-metastatic, OPSCC treated with curative intent at our institution from 2007 to 2018. Logistic regression and survival analyses were used for outcome-specific endpoints. In total, 88 patients were identified with a median age of 73 (interquartile range [IQR]: 71-78) and a median Charlson Comorbidity Index of 6 (IQR: 5-7). Eighty-two percent were ECOG 0 or 1 performance. Of note, 70% of the cohort had HPV+ tumors. Fifty-one percent of patients were AJCC 8th edition stage I/II and 49% were stage III/IV. Median follow-up time was 2.5 years (IQR: 0.9-4.7). Eight percent had surgery alone, 27% underwent adjuvant RT, and 64% received definitive RT. Sixty-four percent received concurrent chemotherapy. By both univariate and multivariable analyses, HPV+ status was significantly associated with improved locoregional control (LRC), overall survival (OS), and disease specific survival (DSS). In our cohort of elderly patients with OPSCC, the majority was HPV+, which was associated with improved clinical outcomes. There are many challenges when managing elderly patients with OPSCC, but as the population ages and the HPV epidemic evolves, these patients should be considered for elderly specific clinical trials.

Effectiveness of the AJCC 8th edition staging system for selecting patients with T1\u20132N1 breast cancer for post-mastectomy radiotherapy: a joint analysis of 1986 patients from two institutions

BackgroundThe role of post-mastectomy radiotherapy (PMRT) in the treatment of patients with T1–2N1 breast cancer is controversial. This study’s purpose was to evaluate the risk of recurrence of T1–2N1 breast cancer and the efficacy of PMRT in low-, medium- and high-risk groups of patients.MethodsPost-mastectomy patients with T1–2N1 breast cancer were restaged according to the American Joint Committee on Cancer Staging Manual, 8th edition (AJCC 8th ed.) staging system. Recurrence scores were generated using prognostic factors identified for loco-regional recurrence and distant metastasis in patients without PMRT, and three risk groups were identified. Rates of loco-regional recurrence and distant metastasis were calculated with a competing risk model and compared using Gray’s test. Disease-free survival and overall survival were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis.ResultsData from 1986 patients (1521without PMRT; 465 with PMRT) were analyzed. Patients without PMRT were stratified into low-, intermediate- and high-risk groups by age, tumor location, AJCC 8th ed. stage, number of positive nodes and lympho-vascular invasion. The 5-year loco-regional recurrence rate and distant metastasis rates for the three risk groups were significant at 2.5, 5.4 and 16.2% (p < 0.001) respectively, and 4.9, 8.4 and 18.6% (p < 0.001) respectively. In the high-risk group, loco-regional recurrence (p < 0.001), and distant metastasis (p = 0.044) were significantly reduced, and disease free survival (p = 0.004), and overall survival (p = 0.029) were significantly improved after PMRT. In the low- and intermediate-risk groups, PMRT had no significant effect on loco-regional recurrence (p = 0.268), distant metastasis (p = 0.252), disease free survival (p = 0.608) or overall survival (p = 0.986).ConclusionOur results showed no benefits of PMRT in the low-risk group, and thus, omitting PMRT radiotherapy in this population could be considered.

Postsurgical radiotherapy in stage IIIB gallbladder cancer patients with one to three lymph nodes metastases: A propensity score matching analysis

BackgroundThe effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB. MethodsThe data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT. Results726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup. ConclusionsPSRT provides no survival benefit for IIIB GBC.

Impact of extrinsic tongue muscle invasion on stage migration in AJCC 8th edition staging of oral cavity carcinoma.

Impact of extrinsic tongue muscle invasion on stage migration in AJCC 8th edition staging of oral cavity carcinoma.

P-133 Extramural venous invasion detected with an elastin stain is a powerful predictor of cancer-specific mortality in STAGE I-IIIB resected colorectal cancer

Extramural venous invasion (EMVI) is considered an indicator of poor prognosis in patients who have undergone resection of primary colorectal cancer (CRC), but its use has not been widely adopted in staging systems or nomograms. In particular, EMVI is not reported in most large case series, is not included in most large CRC databases, and is not incorporated into the current AJCC TNM staging system. Staining for elastin may facilitate the accurate detection of EMVI and minimize inter-observer variability. We examined the prognostic potential of EMVI detected by elastin staining at a tertiary center that performs a high volume of CRC resections. This is a single-institution, observational study of consecutive patients who underwent resection of primary CRC between 01/01/2011 and 31/12//2016. All pathology specimens were re-assessed by reviewers who were blinded to patient outcomes. Venous invasion was detected using an elastin trichrome stain and classified as Intramural or Extramural. Overall and disease-specific survival (OS, DSS) were estimated using the Kaplan-Meier method. Differences between groups were assessed using the Mantel-Cox log-rank test. For the present analysis, we excluded all patients with stage IV (n=80) or IIIC (n=34) CRC. The cohort for analysis included 428 patients (248M, 190F; AJCC 8th edition Stage I n=107; Stage II n=185; Stage IIIA and B n=146) with a median follow-up time of 61 months (0.1-104). For the entire cohort, OS and DSS at 5 years were 82% and 90%, respectively. AJCC stage (p=0.04), but not T stage (p=0.08) or N stage (p=0.09), was prognostic of DSS. Neither grade (p=0.1) nor IMVI (p=0.4) were prognostic, whereas EMVI was highly prognostic of inferior DSS (p< 0.001). In this cohort of Stage I - III CRC patients with complete follow-up, EMVI as assessed by elastin staining was a powerful predictor of death from CRC. Elastin staining, which improves the accuracy and objectivity of EMVI detection, may allow validation of EMVI as an independent prognostic variable that should be incorporated into staging systems and nomograms. Accurate assessment of EMVI would permit refinement of risk estimation, and inform individualized decision-making regarding adjuvant therapy in patients who have undergone resection of CRC.

Eyelid sebaceous gland carcinoma: An assessment of the T classification of the American Joint Committee of Cancer TNM staging system 8th versus 7th edition.

To assess the prognostic values of the T classification of the 8th edition of the American Joint Committee of Cancer staging system and compare it to the 7th edition. Multicenter retrospective study of patients with eyelid sebaceous gland carcinoma. The primary outcome measure was the differences between outcomes when tumors were staged with either 7th or 8th edition. The measures evaluated included presenting features, management, histopathology, metastasis, recurrence, and mortality. Of the 60 patients (median age 73 years), 31 (51.7%) were females. A change in T staging occurred in 39 patients (65%) when the 8th edition was applied. Advanced categories (T3/T4) were significantly associated with nodal metastasis (p = 0.037) using the 8th edition criteria but not with the 7th edition (p = 0.066). The 8th edition T categorization significantly correlated with eye survival (p = 0.022) while the 7th edition did not (p = 0.058). Applying the 8th edition, category T4 at presentation was associated with a higher risk of nodal metastasis (p = 0.037) but not associated with local recurrence, distant metastasis, or tumor-related death (p = 0.281, p = 0.737, p = 0.319, respectively). T3/T4 category tumors were significantly associated with poor tumor differentiation (p = 0.001), and papillary histologic pattern (p = 0.024) but not with pagetoid spread (p = 0.056). The application of the 8th edition AJCC staging system for eyelid SGC may accurately predict nodal metastasis. Local recurrence and distant metastasis were not significantly associated with T classification, using either edition. Poor tumor differentiation and papillary pattern were associated with T3/T4 categories suggesting that pathological features may assist in determining prognosis.

Evaluation of pathologic staging using number of nodes in p16-negative head and neck cancer.

The 8th edition AJCC staging guidelines for head and neck squamous cell carcinoma (HNSCC) recently introduced pathologic staging criteria for nodal disease among p16-positive patients. In this study we evaluate pathologic staging in p16-negative HNSCC. We compared pathologic staging to the 7th and 8th edition AJCC staging systems using a statewide population-based cohort. All M0 p16-negative surgical patients were included. The outcome was five-year overall survival. Of 304 patients identified, 113 were N0, 157 had 1-4 positive nodes, and 34 had ≥4 nodes. Survival was 71% (95% CI 61-78%) with no nodes, 48% (36%-60%) for 1-4 nodes, and 24% (11 - 39%) for>4 nodes. When compared to the AJCC systems, the pathologic staging yielded a larger total survival gradient, more montonic survival, better consistency across primary sites, and a slightly lower Bayesian information criterion (1510 vs 1538). After adjusting for disease characteristics, demographics, and tobacco use, hazard ratios for survival were similar using pathologic and AJCC criteria. In this cohort, pathological staging was more prognostic than AJCC staging. This is the first study to evaluate pathologic staging in p16-negative cancer; if these findings are verified, a universal nodal staging system could be introduced.

Role of adjuvant chemotherapy in patients with pathological stage I NSCLC with high-risk features.

9022 Background: Lobectomy is the current standard of care for patients with stage I non-small cell lung cancer (NSCLC). There is a lack of prospective data on the benefit of adjuvant chemotherapy (CT) in patients with negative margins but with high-risk features: lympho-vascular invasion (LVI) or visceral pleural invasion (VPI). We aimed to investigate the benefit of adjuvant CT in patients with pathological stage I NSCLC with high-risk features. Methods: The 2016 National Cancer Database was queried to identify patients with pathological stage I NSCLC (8th edition AJCC staging) diagnosed from 2010-2015 who received lobectomy/pneumonectomy with clear surgical margins. Patients were stratified into high risk (tumor size ≥2 cm with LVI and/or VPI) or low risk group. Multivariate Cox proportional hazards regression and propensity score matched Kaplan-Meier survival analysis were used to compare overall survival between those who received adjuvant CT and those who did not. Results: 34,556 patients were identified with 1114 (3.2%) receiving adjuvant CT. On multivariate Cox regression analysis, high risk tumors (hazard ratio [95% confidence interval] = 1.31 [1.25-1.38]) and lack of adjuvant chemotherapy (1.25 [1.09-1.44]) were associated with worse overall survival (OS). Additionally, male sex, age ≥ 60 years, higher comorbidity burden, lack of insurance, low facility volume, low median income, non-squamous histology were associated with worse OS. After propensity score matching, Kaplan-Meier survival analysis of the high risk subgroup (n = 2923) showed a significant difference in overall survival (OS) between those who received adjuvant CT (n = 1032, 5 year OS, 74.7%; 95% CI, 70.9%-78.0%) and those who did not (n = 1891, 5 year OS, 66.9%; CI, 63.9%-69.6%; p = 0.0002). In patients with no high risk factors for recurrence (n = 384), OS was not significantly different between the patients who received adjuvant CT (n = 78, 5 year OS, 75.8%; CI, 61.3%-85.5%) and those who did not receive adjuvant CT (n = 306, 5 year OS, 77.1%; CI, 70.0%-82.7%; p = 0.3). Conclusions: Our study showed better survival with adjuvant CT in patients with pathological stage I NSCLC who have tumor size greater than 2 cm, LVI and/or VPI.