T1a Disease Research Articles

DNA Damage Response Pathway Alteration in Locally Advanced Clear-Cell Renal-Cell Carcinoma Is Associated With a Poor Outcome.

Advanced clear-cell renal-cell carcinoma (ccRCC), which is the most common subtype of kidney cancer, is considered to be lethal despite recent advancements in therapeutic agents. The benefit of adjuvant or neoadjuvant therapy with currently available agents remains controversial. We investigated the clinical implications of DNA damage response (DDR) pathway for locally advanced ccRCC. Localized ccRCC cases were selected from the Provisional TCGA (The Cancer Genome Atlas) database. Presence of mutation or copy-number alteration of DDR pathway-related genes were evaluated. Disease-free survival and overall survival according to disease progression were evaluated. From TCGA database, 312 cases were identified of a localized ccRCC with full data on mutation and copy-number alteration. Alteration in the DDR pathway was present in 25.0% of cases. Female subjects were more likely to have alterations in the DDR pathway (34.6% vs. 48.7%, P= .026). DDR pathway alteration was associated with decreased disease-free survival in cases of locally advanced T3-4 disease (median, 123.7 vs. 23.0 months, T3 and T4 disease, P= .031). The association was more prominent in cases of T3a disease (normal group median not reached, altered group median 17.7 months, P< .001). DDR pathway alteration was an independent factor predicting a shorter disease-free survival on Cox regression analysis (odds ratio= 4.41; 95% confidence interval, 1.47∼13.28; P= .008). Alteration in the DDR pathway was associated with increased recurrence in locally advanced ccRCC, and investigation of therapeutic agents targeting the DDR pathway for this population should be considered.

Upstaging of head and neck cancers due to extranodal extension: An Indian study.

e17553 Background: Latest AJCC staging has included extranodal extension (ENE) in nodal staging of head and neck cancers (HNC) in view of its prognostic significance. Presence of clinical ENE makes the disease N3b and the stage grouping will be stage IVB. This retrospective analysis was done with an objective to find out the percentage of patients with HNC getting upstaged because of ENE and their treatment outcome. Methods: A retrospective analysis of all HNC patients registered in our department from January 2018 to January 2019 were done to identify the presence of ENE and their staging. AJCC criteria was used for defining clinical and radiological ENE. The site, subsite, stage and presence of ENE were documented. Results: A total of 562 patients were registered with HNC. Among them 40 patients were identified to have ENE (7.1%). There were 35 males and 5 females. There were 17 cases with ca oropharynx, 13 oral cavity, four hypopharynx, three supraglottis, two glottis, and one maxillary carcinoma. Tumour size varied from 1.5 cm to 8 cm with an average of 4.9cm. Majority of the patient had a T4a disease, with 18 patients in the category. T stage varied from T1 – 1, T2 – 7, T3 – 7, T4b – 6, missing data – 1. 33 patients had clinically documented ENE and six were radiological and one patient had pathological ENE. Nine had skin involvement and the rest (24) had either muscle invasion or soft tissue involvement. Various treatment approaches were tried. Two patients received neoadjuvant chemotherapy (NACT) followed by chemoradiation (CTRT). On treatment at present. One NACT followed by surgery and later CTRT. Developed recurrence. Four patients received palliative chemotherapy, but developed progressive disease (PD), on best supportive care (BSC). Nine patients received palliative radiotherapy, six patients are on treatment and one had PD. Five patients received radical CTRT, 5 on treatment and one had PD. One received palliative RT followed by palliative chemo, but developed PD. 13 patients are on treatment and rest of the patients are either dead, lost to follow up or on BSC. Conclusions: Majority of the patients with ENE had a T4a disease. No special site predilection was identified. Various treatment modalities tried but none of them produced any significant difference in outcome. In conclusion, patients with ENE had a poor prognosis irrespective of the treatment modality selected.

A pilot presurgical study evaluating anti-PD-L1 durvalumab (durva) plus anti-CTLA-4 tremelimumab (treme) in patients (pts) with high-risk muscle-invasive bladder carcinoma (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy (NAC).

4551 Background: In MIBC pts, especially in those with high risk features including lymphovascular invasion, hydronephrosis, T3b disease, or variant histology, cisplatin-based NAC followed by cystectomy improves overall survival as compared with cystectomy alone. However, it is estimated that over 50% of pts with MIBC are ineligible for cisplatin-containing therapy. Therefore, we propose this pre-surgical trial with durva + treme for this population of pts. Methods: This is a single-arm, pre-surgical clinical trial with durva + treme in pts with localized, high-risk MIBC (cT2-T4a) who are ineligible for cisplatin-based NAC due to decreased renal function, neuropathy, hearing loss, or heart failure; or refuse cisplatin-based NAC (NCT02812420). Each patient receives durva (1500 mg) plus treme (75 mg) on weeks 1 and 5. Pts then undergo surgery at week 9-11. Pre- and post-treatment blood and tumor samples are collected for correlative biological analyses. Results: Twenty eight of 35 pts have been enrolled on this trial. Twenty-one pts have completed cystectomy as of 11/16/19. Of these 21 pts, 9 (43%) had pathologically complete response (pCR) and two (10%) had pathologic T1N0 (pT1) disease (≤pT1N0 rate = 52%). Fourteen of 21 (67%) had down-staging of disease. Of note, 10 of these 21 pts had 3-D mass (T3) on exam under anesthesia or clinical T4a disease; 5 of these 10 pts (50%) had pCR and one (10%) had pT1 disease (≤pT1N0 rate = 60%). Only 5 of 28 (17%) pts developed grade 3 immune related toxicity including hepatitis and amylase/lipase elevation, and two (7%) resulted in surgery delay for &gt; 30 days. Immune profiling with CyTOF analysis of baseline peripheral blood indicates that pts with pCR have significantly lower frequency of a Th2 subset as compared to pts with up-staging of disease. In addition, gene expression profiling analysis of baseline tumor tissues demonstrates a significantly less immunosuppressive microenvironment in pts with pCR as compared to pts with up-staging of disease. Conclusions: Our data indicate that durva plus treme is an effective and safe neoadjuvant therapy for pts with MIBC ineligible for cisplatin-based therapy. Therefore, neoadjuvant therapy with durva + treme and a number of potential biomarkers warrant testing in a larger phase 3 trial. Clinical trial information: NCT 02812420.

Optimal Monitoring of Prostate-Specific Antigen Detects Prostate Cancer at the Localized Stage after Photoselective Vaporization for Benign Prostatic Hyperplasia

Introduction: Photoselective vaporization of the prostate (PVP) does not provide prostate tissue for pathologic analysis. Here, we carried out early monitoring for prostate cancer by measuring prostate-specific antigen (PSA) levels and assessing clinicopathological features after PVP. Materials and Methods: Patients (n = 800) who underwent PVP and were followed-up for more than 12 months were analyzed retrospectively. After PVP, PSA levels were measured at 3 and 12 months and each year thereafter. Prostate biopsies were performed when PSA levels increased continuously. We assessed the characteristics of patients diagnosed with prostate cancer. Results: The mean follow-up period was 49 months. After PVP, 54 patients underwent biopsies, and 23 patients were diagnosed with prostate cancer. Overall, 10, 10, and 3 patients had clinical stage T1c, T2a, and T2b disease, respectively, and there were no cases of stage T2c disease or greater. Conclusions: We found that it was possible to diagnose prostate cancer at a localized stage under our optimal PSA monitoring schedule before and after PVP.

Optimal Lymph Node Examination and Adjuvant Chemotherapy for Stage I Lung Cancer

ObjectiveTo determine the optimal number of lymph nodes (LNs) examined and the role of adjuvant chemotherapy in stage I lung cancer. MethodsThe National Cancer Database was queried for surgically treated patients with pathologic stage I lung cancer between 2006 and 2014 (N = 65,438). The optimal LN numbers were determined in the multivariate Cox model and were further validated in the cohort with clinical stage I disease (N = 117,112) in terms of nodal upstaging and prognostic stratification. The role of adjuvant chemotherapy in patients with suboptimal staging (number of LNs examined was less than than the optimum) was evaluated in each T stage. ResultsThe number of LNs examined correlated with tumor size (p < 0.001). There were increasing survival benefits with each additional LN examined—up to eight, nine, 10, and 11 nodes for patients with T1a, T1b, T1c, and T2a, respectively. Validation from the cohort with clinically staged disease showed that the threshold of eight to 11 LNs was an independent predictor of nodal upstaging (OR = 1.706, 95% confidence interval [CI] 1.608–1.779) and survival outcome (hazard ratio = 0.890, 95% CI: 0.865–0.916). After propensity matching, adjuvant chemotherapy was associated with improved survival in patients with stage T2a disease having suboptimal staging (hazard ratio = 0.841, 95% CI: 0.714–0.990), but not in patients with stage T1a to T1c disease. ConclusionLN evaluation was important for accurate staging and adequate treatment, and examinations of an increasing number of nodes for progressively higher T components (i.e., eight, nine, 10, and 11 nodes for T1a, T1b, T1c, and T2a tumors, respectively) seemed crucial to predict upstaging and survival outcomes. Adjuvant chemotherapy might be beneficial to patients with stage T2a disease who have suboptimal nodal staging.

Microscopic positive margins strongly predict reduced disease‐free survival in pT4a papillary thyroid cancer

Although microscopic positive margins appear to have no independent prognostic impact in papillary thyroid cancer (PTC), this may not be the case in pT4a tumors. Retrospective analysis of 610 patients with PTC, 39 with pT4a tumors, to determine if microscopic positive margins impact disease-free survival (DFS) in pT4a PTC. On univariate analysis, microscopic positive margins were not associated with reduced DFS in patients with no extrathyroidal extension (ETE) (hazard ratio [HR], 1.7; P = 0.32), microscopic ETE (HR, 1.6; P = 0.36), or macroscopic ETE limited to strap muscles (HR, 1.2; P = 0.87). In contrast, microscopic positive margins were associated with reduced DFS in T4a disease (HR, 4.1; P = 0.04). Disease recurrence was nodal, distant, or biochemical, and did not occur directly at the site of positive margins. Although microscopic positive margins do not influence DFS in the majority of patients with PTC, they are associated with a fourfold increased risk of recurrence in pT4a disease.

Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes

ObjectiveMucinous borderline ovarian tumor (mucinous-BOT) and invasive well-differentiated mucinous ovarian cancer (mucinous-OC) are often histopathologically misclassified. The objective of this study was to examine differences in clinico-pathological characteristics and outcomes of these two entities. MethodsThis is a retrospective population-based study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Stage I mucinous-BOTs and stage I well-differentiated mucinous-OC were compared for patient demographics, tumor characteristics, and outcomes. Propensity score matching and multivariable analysis were used to assess cause-specific survival (CSS). ResultsA total of 2130 mucinous-BOT and 581 mucinous-OC cases were examined for analysis. On multivariable analysis, women with mucinous-OC were more likely to be older, Eastern U.S. residents, and have undergone hysterectomy or lymphadenectomy compared to those with mucinous-BOT, and the number of women diagnosed with mucinous-OC decreased over time (all, P < 0.05). Mucinous-OCs were more likely to be stage T1c and have a smaller tumor size as compared to mucinous-BOT (both, adjusted-P < 0.05). After propensity score matching, women with mucinous-OC had significantly poorer CSS compared to those with mucinous-BOT on multivariable analysis (10-year rates: 92.7% versus 97.5%, adjusted-hazard ratio [HR] 2.03, P = 0.007). Similar results were observed among subgroups for reproductive age, stage T1a disease, large tumor, and unstaged cases (all, P < 0.05). ConclusionStage I mucinous-BOT and stage I invasive well-differentiated mucinous-OC have distinct differences in clinical characteristics and patient survival. The inability to conduct centralized pathology review in our study limits our conclusions given the recognized issue of misclassification of mucinous-BOT and mucinous-OC, but further highlights the importance of making the proper histopathological diagnosis for invasive cancer when the ovarian tumor is of mucinous histology.

Neoadjuvant cisplatin-based chemotherapy in “primary” and “secondary” muscle-invasive bladder cancer—is it a surrogate for molecular subtypes?

Perioperative cisplatin-based combination chemotherapy is a first-line treatment strategy for muscle-invasive bladder cancer (MIBC) patients with or without metastasis. According to current European Association of Urology (EAU) guidelines, the use of neoadjuvant chemotherapy (NAC) is strongly recommended to patients with clinical T2–T4a and N0M0 disease (1).

A Relook at the T Stage of Differentiated Thyroid Carcinoma with a Focus on Gross Extrathyroidal Extension.

The recently published eighth edition of the American Joint Committee on Cancer (AJCC) staging system has emphasized the importance of gross extrathyroidal extension (gETE) while classifying the tumor (T) stage in differentiated thyroid carcinoma (DTC). However, the clinical impact of gETE invading only the strap muscles or the recurrent laryngeal nerve (RLN) remains unclear due to scarce and conflicting data. A retrospective cohort study was carried out in patients with DTC who underwent thyroid surgery from 1996 to 2005. In total, 3104 patients were included, and disease-specific survival (DSS) was compared according to the degree of gETE, with a median follow-up duration of 10 years. Patients with gETE invading only the strap muscles and with a tumor size ≤4 cm (T3b [≤4 cm]) showed no difference in DSS compared to patients with T2 stage disease (hazard ratio [HR] = 0.81 [confidence interval (CI) 0.24-2.77]; p = 0.737) but rather showed a better DSS than patients with T3a disease (HR = 0.19 [CI 0.05-0.72]; p = 0.014). Conversely, patients with gETE invading to the posterior direction showed significantly poorer DSS than patients with T3 stage disease, even when only the RLN was invaded (HR = 7.78 [CI 3.41-17.75]; p < 0.001). However, there was no difference in DSS between gETE invading only the RLN and that invading other posterior organs beyond the RLN (p = 0.563). A modified T classification was suggested to downgrade patients with T3b (≤4 cm) disease to the T2 stage, which revealed higher predictability of survival than the T classification according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (proportion of variation explained: 3.6% vs. 2.65%). gETE invading only the strap muscles did not significantly affect DSS, while that invading the posterior organs significantly affected DSS, even when only the RLN was invaded. The data support the applicability of downgrading patients with T3b (≤4 cm) disease to the T2 stage for a better predictability of survival.

Oncological and functional outcomes following transoral laser microsurgery in patients with T2a vs T2b glottic squamous cell carcinoma.

BackgroundThere is a paucity of evidence comparing oncological and voice outcomes between T2a and T2b glottic squamous cell carcinoma (SCC) patients treated with transoral laser microsurgery (TLM). This study identified functional and oncological outcomes in this cohort.MethodsRetrospective review of prospectively collected data of patients treated with TLM for T2 glottic SCC from 2003 to 2017.ResultsIn total, 75 patients were included. Five-year local control rates were significantly different between T2a and T2b patients (75.2% vs 57.0%, p = 0.022). There was no difference in five-year survival between patients with T2a disease and T2b disease (69.5% vs 73.4%, p = 0.627). There was no significant difference in mean VHI-10 scores in the pre-operative period (18.3 vs 21.4, p = 0.409). However, patients with T2b disease had significantly worse perceived voice outcomes post-operatively (6.6 vs 21.3 p = 0.001). Patients with T2a disease saw significant improvements in mean VHI-10 scores following surgery (18.3 vs 6.6, p = 0.000), while T2b patients did not (21.4 vs 21.3, p = 0.979). The overall laryngeal preservation rate was 94.7%, with 11.5% of T2b patients requiring salvage organ sacrifice.ConclusionsThis study highlights positive functional outcomes for T2a glottic SCC. Patients with T2b disease appear to have significantly worse oncological and functional outcomes, including worse voice quality following surgery and higher rates of salvage laryngectomy.

Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines.

The clinical implications and contemporary management of T1b penile cancer are unknown. National treatment guidelines advocate surgical lymph node examination (SLNE) for T1b disease. The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines. We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses. In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003). T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.

Efficacy and safety of primary surgery with postoperative radiotherapy in head and neck mucosal melanoma: a single-arm Phase II study.

BackgroundThere still remains no well-established treatment strategy for head and neck mucosal melanoma (HNMM). We aim to evaluate the effectiveness and safety of primary surgery with postoperative radiotherapy for this disease.Patients and methodsA single-arm, Phase II clinical trial was conducted at Sun Yat-Sen University Cancer Center. Patients with nonmetastatic, histologically proven HNMM were prospectively enrolled. Patients received primary surgery followed by intensity-modulated radiotherapy with an equivalent dose at 2 Gy per fraction of 65–70 Gy to CTV1 (high-risk regions including tumor bed) and 50–55 Gy to CTV2 (low-risk regions). Additional use of adjuvant chemotherapy (AC) depended on consultation from a multidisciplinary team. This trial is registered with ClinicalTrials.gov, number NCT03138642.ResultsA total of 33 patients were enrolled and analyzed between July 2010 and November 2016. There were 18 (54.5%) patients with T3 disease and 15 (45.5%) patients with T4a disease. The median age at diagnosis was 58 years (range 27–83 years), and 61% of the cohort were males. The overall median follow-up duration was 25.3 months (range 5.3–67.1 months). The 3-year overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were 44.4, 91.7, 78.1, and 41.7%, respectively. Patients with T4a disease showed significantly inferior OS (P=0.049) and DMFS (P=0.040) than those with T3 disease. Prophylactic neck radiation (PNR) was nearly associated with superior RRFS (P=0.078). However, there was no significant difference in OS, LRFS, RRFS, and DMFS for patients treated with or without AC (P>0.05 for all). Toxicities were generally mild to moderate.ConclusionPrimary surgery with postoperative radiotherapy yielded excellent local control and acceptable toxicity profile for HNMM. Nevertheless, high rates of distant metastases resulted in limited survival.

Prognosis of Young Survivors of Gastric Cancer in China and the U.S.: Determining Long-Term Outcomes Based on Conditional Survival.

Young survivors of gastric cancer (GC) have better prognoses than elderly patients, yet their disease-specific survival (DSS) has received little attention. Data on young patients (aged ≤40 years) with GC undergoing resections at three Chinese institutions (n = 542) and from the SEER database (n = 533) were retrospectively analyzed. Three-year conditional disease-specific survival (CS3) was assessed. The effects of well-known prognostic factors over time were analyzed by time-dependent Cox regression. Overall, young Chinese patients with GC had a better 5-year DSS than U.S. patients (62.8% vs. 54.1%; p < .05). The disease-specific mortality likelihood of the entire cohort was not constant over time, with most deaths occurring during the first 3 years after surgery but peaking at 1 and 2 years in China and the U.S., respectively. Based on 5-year survivorship, the CS3 rates of both groups were similar (90.9% [U.S.] vs. 91.5% [China]; p > .05). Cox regression showed that for Chinese patients, site, size, T stage, and N stage were independent prognostic factors at baseline (p < .05). For U.S. patients, grade, T stage. and N stage significantly affected DSS at baseline (p < .05). In both groups, only T stage continuously affected DSS within 3 years after gastrectomy. However, for both groups, the initial well-known prognostic factors lost prognostic significance after 5 years of survival (all p > .05). Although the 5-year DSS rates of young Chinese patients with T3 and T4a disease were significantly better than those of young U.S. patients, in each T stage, the CS3 of both regions trended toward consistency over time. For young patients with GC, the factors that predict survival at baseline vary over time. Although the initial 5-year DSS is heterogeneous, insight into conditional survival will help clinicians evaluate the long-term prognoses of survivors while ignoring population differences. With the increasing number of young survivors of gastric cancer (GC), it is essential for clinicians to understand the dynamic prognosis of these patients. Based on large data sets from China and the U.S., this study found that the prognostic factors that predict survival for young patients with GC at baseline vary over time. Although the initial 5-year disease-specific survival is heterogeneous, insight into conditional survival will help clinicians evaluate the long-term prognoses of survivors while ignoring population differences. This knowledge may be more effective in helping young patients with GC to manage future uncertainties, especially when they need to make important life plans.

Hepatocellular Carcinoma: Patterns of Care and Outcomes for Patients receiving Stereotactic Radiation Therapy

This study aims to analyze the patterns of care, including fractionation and utilization, of hypofractionated stereotactic body radiotherapy (SBRT) in the treatment of hepatic cellular carcinoma The NCDB was queried for patients diagnosed with hepatocellular carcinoma (HCC) in 2004-2014 and treated with radiotherapy in 3, 4, or 5 fractions in 15-20, 10-13, or 6-12 Gy per fraction respectively. Patients with stage IV and Charlson-Deyo Comorbidity Index >0 were excluded in order to avoid bias resulting from selection of poorer prognosis patients. The patients were then stratified based on several characteristics including Biologically Equivalent Doses (BEDs) of >100 Gy and <100 Gy to determine whether there was an association with overall survival (OS) benefit and a multivariable analysis (MVA) was performed to assess for potential confounding factors. There were 462 patients identified in whom the most common SBRT fractionation regimen was 10 Gy x 5 fractions (25.3%), followed by 8 Gy x 5 (17.7%), and 15-16 Gy x 3 (26.4%). One hundred fifty-two patients were treated to a BED <100 Gy, which was associated with a median overall survival (OS) of 20.8 months (95% CI 14.551-27.109). Three hundred ten patients were treated to a BED >100 Gy, which was associated with a median overall survival (OS) of 30.8 months (95% CI 5.251-32.083). On MVA, BED >100 Gy was not significant associated with improved OS (HR 0.852 CI 0.638-1.137, p=0.277). Factors that were associated with significantly worse survival were tumor size in the largest quartile (HR 2.197 CI 1.440-3.354, p<0.0001) and T3a disease (HR 2.474 CI 1.472-4.158, p=0.001 compared to T1). The most common SBRT fractionation regimen was 10 Gy x 5 fractions. BED dose ≥100 Gy was not associated with a significant survival benefit. However, local control data are not available within the NCDB.

Impact of Induction Chemotherapy on Nodal and Distal Disease Control in Locally Advanced Buccal Mucosa Cancer

Background: Buccal mucosa squamous cell cancer is the most common cancer in India. Majority of them presenting in advanced stage whose prognosis after surgery depends significantly upon the regional and distal spread. We studied the impact of neoadjuvant chemotherapy (NACT) on nodal and distal control of disease in operated cases of advanced buccal mucosa cancer. Aim: A retrospective study to evaluate the impact of induction chemotherapy (NACT) on nodal and distal failure in locally advanced buccal mucosa cancer. Methods: A total of 224 patients of advanced buccal mucosal cancer who underwent surgery between 2014 and 2015 were evaluated retrospectively with a follow-up of two years. Total 111 of the above had received NACT prior to surgery while 113 patients underwent upfront surgery. The CT scans and histologic reports were then compared for evaluation and analysis. Results: Among patients with T4a disease, 45.85% in upfront surgery group compared with 54% in NACT group showed metastatic pathologic nodes, while in T4b patients, the rates were 83.33% compared with 49.18% respectively. In patients with clinical/radiologic positive neck nodes at presentation, 87.5% in upfront surgery group as compared with 55.55% in NACT group showed metastatic nodes in histopathologic evaluation. 13.27% patients in the upfront surgery group had nodal and/or distal failure in the two years follow-up, whereas only 3.6% patients in the NACT group. 25% patients with peri-nodal extension in upfront surgery group showed nodal and/or distal failure, while only 6% in NACT group. The results in different nodal-ratio strata was evaluated. It showed that NACT has equal failure rate as in upfront group in nodal-ratio &gt; 50, which is considered as very advanced and aggressive tumor. But in patients with nodal-ratio &lt; 50, NACT group showed lesser failure rate than upfront group. Conclusion: We show regressional effect of NACT on nodal metastases. This study also shows NACT to be having a significantly positive impact on nodal and distal control. Hence role of induction chemotherapy needs to be considered in advanced cases of buccal mucosa cancer with nodal metastases.

The role of regional flaps in locally advanced cancer larynx with skin invasion

IntroductionLaryngeal cancer with invasion of soft tissues of the neck including the skin is staged as T4a disease according to the TNM classification by the AJCC in 2010. The traditional treatment for this locally advanced disease is through total laryngectomy and en-bloc removal of the involved cervical skin followed by reconstruction by one of the regional flaps. In this study, we present our experience with the use of two regional flaps, namely, the pectoralis major myocutaneous flap and the deltopectoral flap, for reconstruction of T4a laryngeal cancer infiltrating the cervical skin.Patients and MethodsA total of 11 patients were included in the study during the period from January 2013 to October 2016. Ours was a retrospective analytic study that included analysis of the preoperative, operative, postoperative, and follow-up patient data.ResultsBoth flaps proved to be versatile for reconstruction of the locally advanced cancer larynx and provided a simple alternative for the more complex free flap surgery.

Successful Cryoablation Eradication of an Esophageal Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are most commonly found in the stomach but have also been described in other segments of the gastrointestinal tract, including the small intestine and more rarely, the esophagus. For gastric and intestinal GISTs, the current standard of care involves surgery and tyrosine kinase inhibitors. However, the appropriate treatment strategy for the management of esophageal GISTs are less well-established. In this case report, we present a case of an esophageal GIST successfully treated by cryoablation therapy. A 69-year-old male with a prior history of Barrett's esophagus and esophageal adenocarcinoma (T1a disease), previously successfully treated with resection, was found to have a ulcerated 13x5 mm mid esophageal GIST on surveillance esophagogastroduodenoscopy (EGD) and endoscopic ultrasound (EUS). The patient was deemed a poor surgical candidate due to his multiple medical comorbidities and a prior history of a complicated post-operative course following his prior esophageal resection, and so cryoablation therapy was offered. The TruFreeze spray cryotherapy system (CSA Medical Inc, Lexington, MA, USA) was used for this procedure. The tumor was treated for 3 freeze-thaw cycles lasting 30 seconds each. On first followup EUS, the GIST was noted to have decreased in size to 10x2 mm on EUS. At 3-month follow up EGD, the GIST had shrunken considerably, with only a slight bump and subtle vessel dilation noted at the site. Cryotherapy was again performed over this area with three 30-second cycles. The patient did report some post-procedure discomfort this time, which self-resolved over a period of 2 weeks. On subsequent EGD/EUS, the previous site of the GIST was replaced by a small scar. No residual lesion was identified on EUS. Biopsy from the scar had no evidence of GIST, dysplasia or malignancy. Case Highlights: Our case demonstrates the potential for cryoablation therapy to resolve esophageal GISTs without invasive surgical intervention. Cryoablation therapy was successful and well-tolerated by the patient, and no significant adverse events were noted during the procedure or on follow up aside from mild discomfort that self-resolved. Cryotherapy is generally a safe procedure and is associated with low rates of serious adverse events and has the advantage of allowing for repeat sessions or other treatments if necessary.1824_A Figure 1. Endoscopic view of esophageal gastrointestinal stromal tumor1824_B Figure 2. Cryotherapy being applied to GIST1824_C Figure 3. Appearance of GIST at 3-month EGD follow up. Mild bump with dilated vessels noted at site of esophageal GIST

Survival in Differentiated Thyroid Cancer: Comparing the AJCC Cancer Staging Seventh and Eighth Editions.

The American Joint Committee on Cancer Cancer Staging System for differentiated thyroid cancer has been recently revised. The purpose of this study was to compare survival prognostication between the seventh and eighth editions. We retrospectively reviewed 2579 differentiated thyroid cancer patients who underwent surgery at MD Anderson Cancer Center between 2000 and 2015. Disease-specific survival (DSS) and overall survival were estimated using the Kaplan-Meier method and compared using log rank test. The effect of potential predictor was estimated using Cox proportional hazards model. Power of survival prediction was estimated using Harrell's C concordance index (C-index), and predictive capacities for DSS were estimated using proportion of variance explained (PVE). Revision of tumor-node-metastasis (TNM) categories, age cutoff, and stage reassignment in the 8th edition caused reclassification of overall stage compared with the seventh edition. The proportion of patients in stage I and II increased from 62% to 83% and 5% to 12%, respectively, while the proportion of patients in stage III and IV decreased from 20% to 2% and 14% to 3%, respectively. Ten-year DSS for stages I-IV based on the seventh edition were 100%, 97.5%, 98.3%, and 82.6%, respectively, while 10-year DSS for the corresponding stage in the eighth edition were 99.8%, 88.3%, 72.4%, and 71.9%, respectively. In multivariate analysis for both seventh edition (C-index 0.94, PVE 4.6%) and eighth edition (C-index 0.94, PVE 4.8%), the factors predictive of worse outcome for DSS were older age, advanced tumor size category, and distant metastasis while cervical lymph node metastases did not predict worse survival. For the eighth edition, patients <55 years of age with stage II disease had significantly worse DSS (p < 0.001) than patients ≥55 years with stage II disease but appeared to be similar to patients ≥55 years with stage III (p = 0.742) and IV disease (p = 0.566). Patients ≥55 years old with T3a and T3b disease had 10-year DSS of 67% and 92%, respectively (p = 0.390). The AJCC eighth edition is similar to the seventh edition in disease-specific survival prediction. Potential modifications that may improve disease-specific survival prediction in future renditions include reconsideration of T3b tumor category and upstaging classification of patients <55 years of age with distant metastases.

Submucosal Saline Injection Followed by Endoscopic Ultrasound versus Endoscopic Ultrasound Only for Distinguishing between T1a and T1b Esophageal Cancer: A Single-Blind, Superiority, Phase 3, Randomized Controlled Trial

Background: Traditional endoscopic ultrasound's (EUS) accuracy in distinguishing between T1a and T1b stage esophageal cancer (EC) is inadequate. As such, we examined whether submucosal saline injection (SSI) can improve its diagnostic accuracy. Methods: We conducted a randomized controlled phase 3 trial at Sun Yat-sen University Cancer Center. A total of 180 patients aged 18-85 years old with T1N0M0 stage EC indicated by prior EUS and radiologic imaging were enrolled and randomly assigned (1:1) to receive either EUS examination after SSI (EUS examination after 3-5 ml submucosal saline injection) or EUS only examination. The randomization sequence was computer-generated and no stratification factor was used. All the patients were referred to thoracic surgeons to receive endoscopic submucosal dissection (ESD) or esophagectomy within one week after EUS examination. Patients, research assistants, thoracic surgeons, pathologists, and statisticians were masked to the allocated examination. Standard EUS criteria were used to preoperatively stage the EC cases, while surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1a staging (defined as the sum of the true positive [T1a] and true negative [T1b] cases divided by the total number of cases) analyzed in the per-protocol population. Findings: Between February 14, 2012 to October 23, 2017, 180 patients were enrolled and randomly assigned to receive SSI EUS (n=90) or EUS only (n=90) examination. Among the per-protocol population, the SSI EUS group (n=81) was superior to the EUS-only group (n=87) in terms of the diagnostic accuracy for T1a staging (86.4% [95% CI, 79.0-93.9] vs. 66.7% [95% CI, 56.8-76.6]; p=0.003). The specificities with SSI EUS and EUS-only were similar (92.3% [95% CI, 82.1-100.0] vs. 90.5% [95% CI, 81.6-99.4]; p>0.999), whereas the sensitivity of SSI EUS was significantly higher than EUS-only (83.6% [95% CI, 73.9-93.4] vs. 44.4% [95% CI, 29.9-59.0]; p<0.001). Adverse events during examination were recorded in one patient in the SSI EUS group and one in the EUS-only group (grade 1 esophageal hemorrhage for both). Compared with those in the EUS-only group, patients with postoperative T1a disease in the SSI EUS group had more commonly received ESD (38 [69.1%] of 55 patients vs. 16 [35.6%] of 45, p<0.001) and had a lower median total medical cost (4,913.8 vs. 11,717.7 USD, p<0.001) and shorter median hospital stays (13.0 vs. 23.0 days, p=0.003). With a median follow-up time of 40.0 months (range, 8.4-71.2 months) in the SSI EUS group and 35.7 months (range, 8.3-76.0 months) in the EUSonly group, the 3-year overall survival rates were comparable between the SSI EUS and EUS-only groups (91.5% vs. 84.7%, p=0.510) for postoperative T1a stage EC patients. Interpretation: SSI significantly improves the diagnostic accuracy of EUS for T1a staging and might be of great value for optimizing treatment strategies for T1 stage EC patients. Clinical Trial Number: This trial is registered at ClinicalTrials.gov, number NCT01555801. The trial is ongoing but no longer recruiting participants. Funding Statement: The study is supported by the National High Technology Research and Development Program of China (863 Program, 2015AA020103); Science and Technology Plan Projects of Guangdong Province, China (2011B080701015, 2012B061700076, and 2014A020212146); Sun Yat-sen University Cancer Center Clinical Research 308 Program, and Plan Project of Guangdong Esophageal Cancer Institute (2014). The funding agencies will not affect the study results. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved by the institutional review board of SYSUCC. This trial was conducted in accordance with the Declaration of Helsinki, the guidelines for Good Clinical Practice, the European Union Clinical Trial Directive, and local regulations. All participants provided written informed consent.

PS02.093: LYMPH NODE METASTASES IN T1 OESOPHAGEAL ADENOCARCINOMA: WHAT IS THE REAL RISK IN EARLY OESOPHAGEAL CANCER?

Abstract Background Lymph node status is regarded as the most important factor for prognosis for oesophageal cancer. T1 oesophageal adenocarcinoma management has shifted from oesophagectomy only to include endoscopic management as part of the algorithm, with some bodies (National Comprehensive Cancer Network (NCCN) 2016) recommending it for management of T1a disease and selected T1b disease. We reviewed the literature to assess the true risk of lymph node metastasis in patients with T1 oesophageal adenocarcinoma. Methods Medline, Embase, Pubmed and Cochrane where searched for manuscripts in english reviewing the lymph node metastasis in superficial (T1) oesophageal adenocarcinoma. The main outcome was reviewing the risk of lymph node metastasis in T1a and T1b oesophageal adenocarcinoma. Secondary outcomes looked at the rate of lymph node metastasis for T1b cancers based on degree of submucosal involvement (SM1, SM2 and SM3). Studies were excluded if neo-adjuvant chemotherapy or radiotherapy were received and if the surgical lymph node yield was &lt; 15 lymph nodes. Results 38 Studies were identified. 22 studies were excluded due to low lymph node yield (&lt; 15) or insufficient statistical analysis. For the 16 studies, a total of 1422 cases were included. 533 patients had T1a adenocarcinoma with 11 patients demonstrating positive lymph nodes (2%). 849 had T1b adenocarcinoma with 189 patients demonstrating positive lymph nodes (22%). Eight Studies did subgroup analysis of T1b lesions with a total of 365 patients identified. The rate of lymph node positivity for SM1, SM2 and SM3 was 17.9%, 16.6% and 29.6% respectively. Conclusion Early oesophageal adenocarcinoma (T1) is increasing in prevalence due to surveillance of pre-malignant conditions (Barrett's Oesophagus). Recently some bodies recommend the use of endoscopic mucosal resection as first line therapy for T1a disease. It is important to inform our patients the risk of lymph node metastasis is low but significant (2%). Given in specialised units, oesophagectomy can be performed with low mortality (&lt; 1%) and morbidity with good quality of life it is justifiable to recommend oesophagectomy or endoscopic management in patients who are fit enough for surgery. For T1b disease an oesophagectomy is the gold standard of treatment given the significant risk of lymph node positivity (22%). Disclosure All authors have declared no conflicts of interest.