Stage Ta Research Articles

T3 versus T4a staging challenges in deeply invasive colonic adenocarcinomas and correlation with clinical outcomes

Despite the latest 8th edition American Joint Committee on Cancer Staging Manual guidelines, disagreement still exists among pathologists regarding staging deeply invasive colonic adenocarcinomas ≤1 mm to the serosal surface. In this retrospective study, 151 untreated colonic adenocarcinomas staged initially as either pT3 or pT4a and with available 5-year follow-up data were retrieved and re-categorized: Group 1 (38 cases): pT4a with tumor at the serosa; Group 2 (49 cases): tumor ≤1 mm from the serosa, with intervening reactive fibrosis (40/49) or inflammation (9/49); Group 3 (64 cases): pT3 tumor >1 mm from the serosa. Clinical outcomes were analyzed. Groups 1 and 2 tumors showed significantly lower 5-year recurrence-free survival and lower overall survival rates (log-rank p < 0.001 for both), when compared with Group 3 tumors. Even after adjusting for adjuvant therapy and nodal metastases, the proportional hazards ratios for the risk of death (p < 0.001) and risk of recurrence (p = 0.005) showed significantly higher risk in Groups 1 and 2 compared with Group 3. The synchronous nodal (p = 0.012) and metachronous distant metastases (p = 0.004) were also significantly more in Groups 1 and 2 versus Group 3. Colonic adenocarcinomas ≤1 mm from the serosal surface behaved more akin to “bona fide” pT4a tumors at the serosal surface in our study with regards to clinical outcomes. We recommend these tumors be staged as pT4a rather than pT3, as supported by outcome data in our study. We hope this will also ensure reproducibility and consistency in staging these tumors across institutions.

Варианты оценки почечной функции после органосохраняющих операций у пациентов с почечно-клеточным раком

Introduction. Despite the improvement of various methods of surgical and ablative methods of treating kidney cancer, the question remains about the functional state of the kidney after surgical treatment. Along with the achievement of oncological results, the preservation of renal function is the main task in the treatment of tumorous diseases of the kidneys. Aim. To evaluate the functional results of organ-preserving operations with a preventive suture with preserved blood flow, as well as in patients who underwent a resection of the kidney with compression of the renal pedicle, using nephroscintigraphy. Material and Methods. The study included 175 patients in stages pT1a-T2bN0M0, which are divided into 2 groups. Group 1 – 150 patients who underwent organ-preserving options with the use of preventive hemostatic sutures, allowing operations to be performed without clamping the kidney leg. 25 patients underwent a resection of the kidney with compression of the renal pedicle. To assess renal function, patients underwent dynamic nephroscintigraphy. In the first group, the tumor was located in the central segment in 64 patients, in the upper segment in 45 patients, in the lower segment in 41 patients. Stage T1a was established in 74 patients, stage T1b in 53 patients, stage T2a in 4 patients. In 19 patients diagnosed with cystic T1a cancers. In the second group in the central segment – in 10 patients, in the upper segment in 7 patients and in 8 patients in the lower. According to the stages, patients were divided as follows – T1a – 16, T1b – 8, T2a – 1. Results. Organ-preserving operations were performed for all patients. In the first group, in no case did the renal pedicle be pinched. The average time of thermal ischemia in the second group was 13 ± 2 min. The perfusion and renal index for the operated kidney in both groups was comparable, and amounted to 54.13 ± 2% and 53.24 ± 4%. However, after surgical treatment, the indicators were significantly different. In the first group, the perfusion index was 46.82 ± 2.39% against 35 ± 1.52% in the second, the renal index in the first group was 46.82 ± 2.39%, against 39 ± 0.88% in the second. Conclusion. Thus, even short-term thermal ischemia leads to significant impairment of renal function. Preventive suture allows you to remove a tumor from any part of the kidney, while maintaining blood flow, and allows you to protect the renal parenchyma from ischemic damage.

Laparoscopic Versus Open Distal Gastrectomy for Locally Advanced Gastric Cancer: Five-Year Update from the Class-01 Randomized Controlled Trial

BACKGROUND: It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes in patients with locally advanced gastric cancer. Data from a multicenter, randomized, controlled trial (CLASS-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Here, we present 5-year overall survival data from this trial. METHODS: From September 2012 through December 2014, we randomly assigned 1056 patients with clinical stage T2, T3, or T4a gastric cancer (without bulky nodes or distant metastases) to undergo either laparoscopic distal gastrectomy or open distal gastrectomy with D2 lymphadenectomy in a 1:1 ratio. We compared 5-year overall survival between groups in the intent to treat population. RESULTS: We analyzed data from 1039 patients who received curative therapy. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P =0.19; hazard ratio [HR], 1.17; 95% CI, 0.93–1.48; P =0.187). After we compared for competing risk events, gastric cancer-related deaths (HR, 1.14; 95% CI, 0.87–1.49; P =0.34) and deaths from other causes (HR, 1.23; 95% CI, 0.74–2.05; P =0.42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. CONCLUSIONS: Laparoscopic distal gastrectomy with D2 lymphadenectomy results in similar 5-year overall survival compared to open distal gastrectomy in patients with locally advanced gastric cancer by experienced surgeons in high-volume specialized institutions. TRIAL REGISTRATION: ClinicalTrials.gov. number, NCT01609309 FUNDING STATEMENT: This work was supported by the National Natural Science of China, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, the Key Clinical Specialty Discipline Construction Program from the National Health and Family Planning Commission of China, and the Program of Global Medical Affairs Department of Johnson & Johnson Medical Ltd. DECLARATION OF INTERESTS: None. ETHICS APPROVAL STATEMENT: Each participating center obtained institutional review board approval, according to local regulations. Patients provided written informed consent.

Endoscopic full thickness resection vs. transanal endoscopic microsurgery for local treatment of rectal neuroendocrine tumors\u2009-\u2009a retrospective analysis

PurposeLocal treatment of small well-differentiated rectal neuroendocrine tumors (NETs) is recommended by current guidelines. However, although several endoscopic methods have been established, the highest R0 rate is achieved by transanal endoscopic microsurgery (TEM). Since a recently published study about endoscopic full thickness resection (eFTR) showed a R0 resection rate of 100%, the aim of this study was to evaluate both methods (eFTR vs. TEM).MethodsWe retrospectively analyzed all patients with rectal NET treated either by TEM (1999–2018) or eFTR (2016–2019) in two tertiary centers (University Hospital Wuerzburg and Ulm). We analyzed clinical, procedural, and histopathological outcomes in both groups.ResultsTwenty-eight patients with rectal NET received local treatment (TEM: 13; eFTR: 15). Most tumors were at stage T1a and grade G1 or G2 (in the TEM group two G3 NETs were staged T2 after neoadjuvant chemotherapy). In both groups, similar outcomes for en bloc resection rate, R0 resection rate, tumor size, or specimen size were found. No procedural adverse events were noted. Mean procedure time in the TEM group was 48.9 min and 19.2 min in the eFTR group.ConclusioneFTR is a convincing method for local treatment of small rectal NETs combining high safety and efficacy with short interventional time.

Robot-assisted partial nephrectomy: 7-year outcomes.

BACKGROUND The role of robot-assisted partial nephrectomy (RAPN) in the management of renal masses has exponentially grown over the past 10 years. Nevertheless, data on long term outcomes of the procedure remains limited. Herein we report oncological and functional outcomes of patients who underwent RAPN for a malignant mass with a median follow-up of 7 years, the longest follow-up to date. METHODS A retrospective analysis of an international multicenter database was performed. All consecutive patients undergoing surgery between 2009 and 2013 with a minimum of 3-year follow-up and complete data on renal function were included. Demographics, surgical and perioperative outcomes were analyzed. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analysis. RESULTS Overall, our study cohort was composed of eighty-five patients with a median follow-up of 88 months. Median clinical tumor size was 3 cm, with mostly (74.1%) clinical stage T1a, and median RENAL score 6. Final histopathologic analysis revealed clear cell RCC in 76.5% of cases. PSM was present in seven patients (8.2%). Eleven overall deaths (12.9%) occurred in the cohort during the follow-up period. Two of these (2.33%) were attributed to metastatic RCC. The OS, CSS, and DFS rates were 91.7%, 97.7%, and 91.7% at 84 months, respectively. Regarding the renal functional outcomes, seventeen patients (20.1%) presented a CKD upstaging in our cohort. CONCLUSIONS Our findings show excellent 7-year oncologic and functional outcomes of the procedure, which duplicate those achieved in historical series of open and laparoscopic surgery.

Is partial nephrectomy safe and effective in the setting of frail comorbid patients affected by renal cell carcinoma? Insights from the RECORD 2 multicentre prospective study

BackgroundTo investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project). MethodsClinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared. ResultsOverall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6–8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery.Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74). ConclusionIn selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease.

Endoscopic resection versus esophagectomy for patients with small-sized T1N0 esophageal cancer: A propensity-matched study

Endoscopic resection (ER) has been rapidly adopted in the treatment of early-stage esophageal cancer. We aimed to compare the outcomes of ER with esophagectomy for patients with small-sized (≤2 cm) stage T1a and T1b esophageal cancer in a population-based cohort. We queried the Surveillance, Epidemiology, and End Results database for patients with T1N0M0 esophageal cancer who underwent ER or esophagectomy and generated a balanced cohort with 217 matched pairs using propensity score matching (PSM). Kaplan-Meier method and multivariable Cox regression analysis were employed to investigate the matched cohort. Subgroup analyses of T stage were also performed. We identified 702 patients; 309 (44.0 %) underwent ER, and 393 (56.0 %) underwent esophagectomy. In the unmatched cohort, patients who underwent ER were older, more likely to have a T1a stage, and less likely to receive lymph node sampling. In the entire matched cohort, multivariate analysis found esophagectomy were associated with better overall survival (OS) (HR: 0.62, 95 % CI: 0.40-0.96, p = 0.032) than ER, but no significant difference in esophageal cancer-specific survival (ECSS) (HR: 1.37, 95 % CI: 0.64-2.96, p = 0.420) between the two procedures. The results were similar for subgroup analyses of stage T1b patients. However, ER and esophagectomy were associated with similar OS (HR: 0.74, 95 % CI: 0.41-1.36; p = 0.334) and ECSS (HR: 3.69, 95 % CI: 0.95-14.39; p = 0.060) in patients with stage T1a disease. In patients with stage T1 esophageal cancer, ER was similar to esophagectomy in terms of oncologic outcomes. More prospective studies should be implemented to determine the optimal treatment for T1b esophageal cancer patients with risk factors.

Stereotactic radiotherapy with focal boost for intermediate and high-risk prostate cancer: Initial results of the SPARC trial

IntroductionDose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR). Materials and methodsPatients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured. ResultsAn interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50–74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87–36.99) and 46.62 Gy (range 44.85–48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission. ConclusionThe first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway.

Utility of the gastric window in computed tomography for differentiation of early gastric cancer (T1 stage) from muscularis involvement (T2 stage).

To analyze the diagnostic value of using the gastric window in computed tomography for differentiation of early gastric cancer (T1 stage) from muscularis involvement (T2 stage). All patients with pathologically confirmed T1 stage and T2 stage gastric cancer and who underwent endoscopic resection or gastrectomy at our institution from January 2011 to November 2018 were examined. Each patient received an enhanced CT scan of the abdomen before the operation. T staging of tumors based on the CT scans was performed independently by two radiologists using the gastric window (width 150-200 HU, level 80-100 HU) and the abdominal window (width 350-400 HU, level 50 HU). Use of the gastric window to diagnose stage T1 EGC led to an accuracy of 88.9% for observer1 and 91.5% for observer2; use of the abdominal window led to an accuracy of 53.6% for observer1 and 51.6% (38/106) for observer2. Use of the gastric window to diagnose stage T2 led to an accuracy of 85.6% for observer1 and 82.4% for observer2; use of the abdominal window led to an accuracy of 52.3% for both observer1 and observer2. For observer1, use of the gastric window had a diagnostic accuracy of 69.2% for stage T1a and 62.5% for stage T1b; for observer2, the diagnostic accuracy was 65.1% for stage T1a and 67.0% for stage T1b. A Kappa test indicated moderate and substantial inter-observer agreement for T staging with gastric window (κ = 0.598, P < 0.001) and abdominal window (κ = 0.745, P < 0.001). Use of the gastric window in computed tomography provided more accurate staging for T1 and T2 stages of gastric cancer than the conventional abdominal window.

271 OESOPHAGO-GASTRIC CANCER SURVIVAL IN SCOTLAND: LESSONS LEARNT FROM ESTABLISHING A NATIONAL NETWORK

Abstract Oesophageal cancer is the 9th most common cancer in Scotland, with 972 new cases in 2017. It remains the 4th most common cause of cancer death, with an estimated 5 year survival of 12.1%. Scotland’s oesophago-gastric cancer network consists of 3 regional divisions, serving a population of 5.44 million. In 2017, survival data indicated survival differences across the 3 networks. This work analyses these outcomes and provides insight into the challenges faced by national collaboration. Methods Upper GI Cancer Quality Performance Indicators (QPIs) for patients diagnosed between January 1st 2013 and December 2015 were collected by clinical audit staff in each NHS Board and submitted centrally to the Information Services Division (ISD). Twelve QPIs are assessed and include: % discussed at MDT, % undergoing neo-adjuvant chemotherapy/CRT, 30/90 day mortality, length of stay, and R1 resection rates. Quality assurance of the dataset was assessed by analysing 20% of records submitted. Both univariate (log rank testing and Kaplan–Meier survival curves) and multivariate survival analysis (Cox’s proportional hazards model) were then performed on all patients across the networks. Results —Quality assurance of the dataset was high—96% accuracy of those records analysed.—Univariate analysis showed that increased age, higher deprivation scores, poor performance status, high tumour grade, an R1 resection, and a poor Charlson comorbidity index, had worse survival. Gender was not a significant survival factor. There was no difference at either network or health board level for all patients with oesophageal cancer.—multi-variate analysis revealed survival differences across the networks for radical treatment of oesophageal adenocarcinoma. In addition, the survival of patients receiving radical radiotherapy in one network appeared better than chemoradiotherapy for SCC. Conclusion This body of work highlights the challenges and pitfalls of establishing a national clinical network. Importantly, data collection and accuracy are high. Moreover, unlike other national collaboratives, data submission is compulsory. Whilst survival differences were detected across the clinical networks, further in depth analysis revealed confounding factors e.g. 23% of oesophageal cancers were stage “unknown”. The algorithm used at ISD did not capture stage T4a or b accounting for most of these patients.

An Audit of the Procedure of Open Thyroidectomy at A Tertiary Care Centre.

We plan to evaluate the various variables associated with the complications of thyroidectomy performed at our department in the last 5years. Medical records of the patients who underwent thyroidectomy during 2014-2018 were collected. Complications of hypocalcemia and recurrent laryngeal nervepalsy were analysed in terms of the demography, cytopathology and the extent of surgery. Student's t-test, Mann-Whitney U-test, Fisher exact test and chi square test were applied to look for any significant associations. P value < 0.05 was considered significant. 123 patients were analysed (87 females, 38 males). Mean age was 38.3years (range 11-71years). Most common cytopathology was papillary carcinoma thyroid (Bethesda VI) - 43/123 (35%). 107 of these 123 patients underwent primary surgery, 10 underwent revision surgery while 6 underwent completion thyroidectomy. Seven patients incurred RLN palsy out of which 3 were temporary. RLN palsy was seen in only malignant cases (p < 0.05). Incidence was higher in T4a stage (p < 0.05). However, it had no association with a simultaneous central or lateral neck dissection. Hypocalcemia was seen in 22 patients (17.8%), out of whom 9 patients developed permanent hypocalcemia. It was seen significantly higher in patients undergoing central neck dissection (p < 0.05) and in malignant thyroid lesions (p < 0.05). Gender, age and the cytopathology had no bearing on RLN palsy and hypoparathyroidism. Malignant thyroid lesions had a significantly higher incidence of RLN palsy and hypoparathyroidism. A thorough anatomical knowledge canreduce the incidence of these complications.

Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection

BackgroundBoth the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear.Methods178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.ResultsThere was no significant difference in OS between T2a and T2b groups, and the median OS duration were 37 and 31 months (P = 0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (≥85.0 IU/L) and CA19–9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.ConclusionThe newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection.

Evaluation of antioxidant network proteins as novel prognostic biomarkers for head and neck cancer patients.

Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins). Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas's transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers. APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p=0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p<0.015). Increased PPARGC1A in invasive tumor correlated with reduced survival (p=0.0281). Patients with lymph node invasion at diagnosis had significantly increased APE1 protein in the primary sites (p<0.05). Patients with poorly differentiated invasive tumors had reduced PPARGC1A in CIS proximal to the invasive tumor and had elevated DCN and SOD3 in proximal benign tissue (p<0.05). The expression of APE1, DCN, and SOD3 is a potential prognostic signature that identifies patients with worsened survival.

TNM Classification: Are Cancers With Extrinsic Tongue Muscle Involvement Systematically T4a?

In the Union for International Cancer Control classification, extrinsic muscle involvement in oropharyngeal cancers is systematically defined as a T4a tumor, although the term extrinsic may incorrectly imply that these muscles are outside the tongue. Our aim was to describe the topography of extrinsic tongue muscles and show that their involvement in oropharyngeal cancers does not always correspond to T4a staging. This cadaveric study was based on dissections of the tongues of ten healthy subjects. Dissections were carried out using sections, and careful macroscopic examination with a 3.5-diopter magnifying glass allowed the identification of muscles from their origin to their termination. Imagery and histology were excluded to stay as close as possible to the clinical evaluation. The sample comprised seven men and three women, with a mean age 82years. In all the ten cases, the extrinsic muscles were located at the periphery of the tongue. The genioglossus was the only deep extrinsic muscle, extending to the periphery and under the mucous membrane of the tongue. As a result, a T1 tumor can invade the mucous membrane and affect the extrinsic muscles without transforming into a T4a tumor. As extrinsic tongue muscles are peripheral and submucosal, the use of the term "deep" is erroneous, as is the systematic usage of extrinsic muscles to define T4a oropharyngeal cancers. This study attempts to explain this error, which is recurrent in the different editions of the Union for International Cancer Control and American Joint Committee on Cancer.

Prognostic significance of acral lentiginous histologic type in T1 melanoma.

Acral lentiginous melanoma (ALM) is a rare type of cutaneous melanoma with a poor prognosis. It is unclear whether the poor outcome of ALM is due to its inherent disease characteristics or advanced stage at initial diagnosis. To address this question, we retrospectively analyzed the clinicopathologic factors of 828 thin (T1; Breslow thickness ≤1.0 mm) melanomas [129 (15.6%) ALMs and 699 (84.4%) non-ALMs] and their nodal and distance metastases and local recurrence rates and determined their relationship with the disease-specific (DSS), overall (OS), and recurrence-free survivals (RFS) at the pathologic stages T1, T1a, and T1b with a median follow-up time of 84.5 months. With the exception of OS at T1b stage, ALM patients showed significantly lower 5- and 10-year DSS, OS, and RFS rates at every pathologic stage when compared with non-ALM. In multivariable analysis, ALM histologic type, SLN positivity, age, and the use of systemic therapy were detected as independent poor prognostic factors associated with significantly lower survival rates. ALM histologic type was associated with lower DSS and OS rates at T1 and T1a stages and lower RFS rates at T1b stage. SLN positivity was associated with lower DSS, OS, and RFS rates at T1, T1a, and T1b stages. Age was associated with lower OS rates at T1 and T1b stages. Whereas the use of systemic therapy was associated with lower DSS rates at T1a stage and RFS rates at T1b stage. In addition, the ALM group showed significantly older median age patients and higher rates of female sex, Hispanic ethnicity, nevoid cytology, non-brisk tumor-infiltrating lymphocytes, nodal metastasis, and local recurrence at every pathologic stage of thin melanoma. Our findings suggest that ALM is inherently more aggressive than other types of cutaneous melanoma. This information may be useful for prognostic stratification of patients with thin melanomas, especially to help guide the clinical decision-making for SLN biopsy and patients entering clinical trials.

Abstract PR03: Can immunologic biomarkers (CD4/CD8/CD25/CD138) predict tumor recurrence and progression in NMIBC?

Abstract Urothelial carcinoma is the most common type of carcinoma of the urinary bladder in the Western world. Currently TNM stage and WHO grade are the most important histopathologic parameters to classify patients into low- and high-risk groups and to decide appropriate treatment. However, as differentiating between stage Ta and T1 on surgical specimens is difficult and grade has only poor to fair reproducibility, these parameters do not precisely predict tumor recurrence or stage progression. As a consequence, patients undergo an intensive follow-up regimen and as such the treatment cost per patient for bladder cancer is one of the highest among all cancer types. Therefore, better prognostic and predictive markers are warranted. The aim of the present study was to clarify whether CD8+, CD4+, CD25+, and/or CD138+ immune cell markers, as well as quantitative features Ki67, mitotic activity index (MAI), and mean nuclear area of the 10 largest nuclei (MNA), can identify non-muscle invasive bladder cancer (NMIBC) patients at high risk for tumor recurrence and stage progression. Tissue samples from 183 patients diagnosed with primary NMIBC were obtained by transurethral resection of the bladder (TURB) or from biopsies. Sections were stained by immunohistochemistry using monoclonal antibodies for T lymphocyte subsets (CD4+, CD8+, and CD25+), plasma cells (CD138+) and Ki67. MAI and MNA were assessed on HES (hematoxylin, erythrosine, and saffron) stained sections. A highly reproducible, interactive image analysis system was used for quantification of all immune cell markers and Ki67. MAI and MNA were counted manually. Out of all the investigated markers, only Ki67 showed significance with tumor recurrence (95% CI, 0.4-0.9; p=0.05) in a 10-year follow-up. The group with high Ki67 (&amp;gt;39%) had significantly longer recurrence-free survival than the group with lower values. Furthermore, out of all the examined immunologic markers, only CD25+ was significantly associated with stage progression in a survival analysis (95% CI, 1.8-106.2; p=0.001). The group of patients with high CD25+ (&amp;gt;0.24%) had significantly shorter progression-free survival than the group with lower values. The median values of MAI and CD25+ were significantly higher in pT1 tumors than pTa tumors (median 16.0, 2.5 for MAI and 0.1%, 0.95% for CD25+ respectively; p&amp;lt;0.001). In univariate analysis age, WHO73, WHO04, Stage, MAI10, and CD25 were all correlated with significant differences in progression-free survival. Furthermore, using survival analysis, the combination of MAI and CD25+ could define a group of patients with 100% (N=81/183) progression-free survival (95% CI, 1.6-4.1; p&amp;lt;0.001). In a multivariate analysis including (age, WHO73, WHO04, combination CD25/MAI10), the combination of CD25/MAI10 was the single most prognostic feature. In conclusion, our study suggests that MAI and CD25+ could be used to identify NMIBC at risk for progression of disease. In addition, Ki67 could be a candidate for assessing the risk of recurrence in NMIBC. This abstract is also being presented as Poster A06. Citation Format: Melinda Lillesand, Vebjørn Kvikstad, Ok Målfrid Mangrud, Einar G. Gudlaugsson, Bianca van Diermen-Hidle, Ivar Skaland, Jan P.A. Baak, Emiel A.M. Janssen. Can immunologic biomarkers (CD4/CD8/CD25/CD138) predict tumor recurrence and progression in NMIBC? [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr PR03.

Time trend of mediastinal lymph node dissection in stage IA non-small cell lung cancer patient who undergo lobectomy: a retrospective study of surveillance, epidemiology, and end results (SEER) database

BackgroundAlthough lobectomy with mediastinal lymph node dissection (MLND) is the first option for early-stage non-small cell lung cancer (NSCLC) patients, the time trends of MLND in stage IA NSCLC patients who undergo a lobectomy are not clear still.MethodsWe included stage IA NSCLC patients who underwent lobectomy or lobectomy with MLND between 2003 and 2013 in the SEER database. The time trend of MLND was compared among patients who underwent a lobectomy.ResultsFor stage T1a patients, the lobectomy group and lobectomy with MLND group had no differences in postoperative overall survival (OS) (P = 0.34) or lung-cancer specific survival (LCSS) (P = 0.18) between 2003 and 2013. For stage T1b patients, the OS (P = 0.01) and LCSS (P = 0.01) were different between the lobectomy group and the lobectomy with MLND group in the period from 2003 to 2009; however, only OS (P = 0.04), not LCSS (P = 0.14), was different between the lobectomy group and the lobectomy with MLND group between 2009 and 2013. For T1c patients, the OS (P = 0.01) and LCSS (P = 0.02) were different between the two groups between 2003 and 2009 but not between 2009 and 2013 (P = 0.60; P = 0.39). From the Cox regression analysis, we found that the factors affecting OS/LCSS in T1b and T1c patients were age, sex, year of diagnosis, histology, and grade, in which year of diagnosis was the obvious factor (HR = 0.79, CI = 0.71–0.87; HR = 0.73, CI = 0.64–0.84).ConclusionsThere was a time trend in prognosis differences between the lobectomy group and lobectomy with MLND group for T1b and T1c stage NSCLC patients.

Malignant peritoneal cytology and increased mortality risk in stage I non-endometrioid endometrial cancer

ObjectiveTo examine the survival of women with stage I non-endometrioid endometrial cancer with malignant peritoneal cytology. MethodsA retrospective observational cohort study was conducted to examine the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I serous, clear cell, carcinosarcoma, undifferentiated, and mixed endometrial cancer with known peritoneal cytology results at hysterectomy were examined (N = 4506). Propensity score inverse probability of treatment weighting was used to balance the measured covariates, and survival outcomes were assessed according to peritoneal cytology results. ResultsMalignant peritoneal cytology was reported in 401 (8.9%) women. In multivariable analysis, older age, serous histology, and large tumors were associated with an increased likelihood of malignant peritoneal cytology (all, P < 0.05). In a propensity score weighted model, malignant peritoneal cytology was associated with a nearly two-fold increase in all-cause mortality risk compared to negative peritoneal cytology (5-year rates, 63.4% versus 80.2%, hazard ratio 2.18, 95% confidence interval 1.78–2.66). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in old and young age groups, serous, clear cell, carcinosarcoma, and mixed histology groups, stage T1a disease, and staged and unstaged cases, but not for stage T1b disease. Difference in 5-year overall survival rates between the malignant and negative peritoneal cytology groups was particularly large among those with clear cell histology (24.0%), stage T1a disease (19.4%), aged >78 years (18.2%), and serous tumors (17.6%). ConclusionMalignant peritoneal cytology can be prevalent in stage I non-endometrioid endometrial cancer. Our study suggests that malignant peritoneal cytology is a prognostic factor for decreased survival in stage I non-endometrioid endometrial cancer.

Histopathological distinction of non-invasive and invasive bladder cancers using machine learning approaches

BackgroundOne of the most challenging tasks for bladder cancer diagnosis is to histologically differentiate two early stages, non-invasive Ta and superficially invasive T1, the latter of which is associated with a significantly higher risk of disease progression. Indeed, in a considerable number of cases, Ta and T1 tumors look very similar under microscope, making the distinction very difficult even for experienced pathologists. Thus, there is an urgent need for a favoring system based on machine learning (ML) to distinguish between the two stages of bladder cancer.MethodsA total of 1177 images of bladder tumor tissues stained by hematoxylin and eosin were collected by pathologists at University of Rochester Medical Center, which included 460 non-invasive (stage Ta) and 717 invasive (stage T1) tumors. Automatic pipelines were developed to extract features for three invasive patterns characteristic to the T1 stage bladder cancer (i.e., desmoplastic reaction, retraction artifact, and abundant pinker cytoplasm), using imaging processing software ImageJ and CellProfiler. Features extracted from the images were analyzed by a suite of machine learning approaches.ResultsWe extracted nearly 700 features from the Ta and T1 tumor images. Unsupervised clustering analysis failed to distinguish hematoxylin and eosin images of Ta vs. T1 tumors. With a reduced set of features, we successfully distinguished 1177 Ta or T1 images with an accuracy of 91–96% by six supervised learning methods. By contrast, convolutional neural network (CNN) models that automatically extract features from images produced an accuracy of 84%, indicating that feature extraction driven by domain knowledge outperforms CNN-based automatic feature extraction. Further analysis revealed that desmoplastic reaction was more important than the other two patterns, and the number and size of nuclei of tumor cells were the most predictive features.ConclusionsWe provide a ML-empowered, feature-centered, and interpretable diagnostic system to facilitate the accurate staging of Ta and T1 diseases, which has a potential to apply to other types of cancer.

Variability in Synoptic Reporting of Colorectal Cancer pT4a Category and Lymphovascular Invasion.

Serosal involvement (pT4a category) and lymphovascular invasion have prognostic significance in colorectal carcinoma, but are subject to interobserver variation in assessment. To provide the first large-scale assessment of interobserver variability in pT4a category and lymphovascular invasion reporting in real-world practice and to explore the impact of information from guidelines on variability in reporting these features. Analysis of 1555 consecutive synoptic reports of colorectal carcinoma was performed using multivariate logistic regression. Interobserver variability before and after the presentation of guideline information was assessed using an image-based survey. Significant differences in the odds of reporting pT4a versus pT3 category, detecting lymphovascular invasion of any type, and detecting large vessel invasion were identified among hospital sites and for individual pathologists compared with the median pathologist at the same site. Consistent with these results, interobserver agreement was only moderate in the image-based survey regarding T4a staging and lymphovascular invasion (all κ ≤ 0.57). The provision of information from guidelines did not tend to increase interobserver agreement in the survey, though responses in favor of using an elastic stain increased following recommendations for their use. However, when observers were provided with elastic-stained images, interobserver agreement remained only moderate (κ = 0.55). Real-world reporting of pT4a category and lymphovascular invasion shows substantial variability at both local and regional levels. Our study underscores the need to address these features in quality initiatives, and provides a novel method through which existing synoptic data can be harnessed to monitor reporting patterns and provide individualized feedback.