Significant Difference In Disease-specific Survival Research Articles

Abstract B23: FGFR3 mutations and their relation to FGFR3 expression and clinical outcome in a large radical cystectomy cohort: Implications for anti-FGFR3 bladder cancer treatment?

Abstract Objective: Fibroblast growth factor receptor 3 (FGFR3) is a potentially actionable target in bladder cancer (BC). FGFR3 mutations are associated with favorable prognosis in non-muscle invasive (NMI) BC and MIBC. Overexpression of FGFR3 was reported in up to 40% of FGFR3 wild-type MIBC. p53 alterations rarely coincide with FGFR3 mutations. We analyzed FGFR3 mutations and protein-expression of FGFR3 and p53 and assessed their prognostic value in a multicenter, multilaboratory setting. Methods: We included 1,000 cN0M0, chemotherapy-naive patients who underwent radical cystectomy (RC) with pelvic node dissection. Specimens were reviewed by eight uropathologists. At seven laboratories, FGFR3 mutation status was examined using PCR-SNaPshot. p53 and FGFR3 expression were determined by immunohistochemistry (IHC). FGFR3 mutation status, p53 and FGFR3 protein expression were correlated to each other, clinicopathologic parameters, and disease-specific survival (DSS). Results: FGFR3 mutations were found in 107/1,000 RCs (11%), of which 67 were S249C. Overexpression of FGFR3 was found in 279/1,000 (28%) of tumors. p53 overexpression (cut-off>10%) was found in 638/926 (69%) of available cases. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression. Among FGFR3 wild-type tumors, 22% had FGFR3 overexpression. FGFR3 mutations were associated with lower pT-stage (P<0.001), lower grade (G2-WHO 1973) (P<0.001), absence of CIS (P=0.009), pN0 (P<0.001), normal p53 (P<0.001), and prolonged DSS (Plog-rank=0.001). FGFR3 overexpression was associated with lower pT-stage (P<0.001) and G2 (P<0.001) but not with absence of CIS (P=0.860), pN0 (P=0.230), normal p53, (P=0.330) nor prolonged DSS (Plog-rank=0.204). We found no significant difference in DSS for patients with FGFR3 mutant tumors comparing normal vs. overexpression of FGFR3 (Plog-rank=0.444). Furthermore, we also found no significant difference in DSS for patients with FGFR3 wild-type tumors comparing normal vs. overexpression of FGFR3 (Plog-rank=0.754). Conclusions: FGFR3 mutations identified patients with favorable BC with fewer p53 alterations at RC. FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. Our results suggest that FGFR3 mutations (driver effect) have a distinct functional role than FGFR3 overexpression (passenger effect). Hence, patients with FGFR3 mutations may be more likely to benefit from anti-FGFR3 therapy than patients with only overexpression of FGFR3. Citation Format: Bas van Rhijn, Laura Mertens, Roman Mayr, Peter Bostrom, Mirari Marques, Geert van Leenders, Stefanie Gotz, Michiel van der Heijden, Michael Jewett, Francisco Real, Robert Stohr, Alexandre Zlotta, Markus Eckstein, Yanish Soorojebally, Max Burger, Wolfgang Otto, Francois Radvanyi, Damien Pouessel, Theo van der Kwast, Nuria Malats, Arndt Hartmann, Yves Allory, Deric van der Schoot, Ellen Zwarthoff, Tahlita Zuiverloon. FGFR3 mutations and their relation to FGFR3 expression and clinical outcome in a large radical cystectomy cohort: Implications for anti-FGFR3 bladder cancer treatment? [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 B23.

Characteristics of Japanese elderly patients with pulmonary arterial hypertension

Previous nationwide Japanese data suggested that pulmonary arterial hypertension (PAH) predominantly affects young women. However, the number of elderly patients diagnosed with PAH has been increasing in western countries. There have been no reports on elderly PAH patients in Asian countries. This study aimed to investigate the clinical characteristics of elderly PAH patients in a Japanese cohort. Idiopathic/heritable PAH (I/H-PAH) was included in the national research project on intractable diseases. The patients were required to submit a clinical research form completed by their attending physicians. We analyzed the characteristics of Japanese I/H-PAH using the newly registered forms in 2013 (Study 1, n = 148). Also, we did a retrospective, observational cohort study at Chiba University Hospital (Study 2, n = 42). We compared the characteristics of elderly PAH patients (≥65 years old) with younger patients (<65) in both studies. Study 1 revealed a predominance of males (51% male), better hemodynamics and poorer exercise capacity in the elderly group (n = 72), compared with the younger group (n = 76) in study 1. In Study 2, elderly patients showed a male predominance (63% male), a higher ratio of smokers, a lower % carbon monoxide diffusing capacity, and poorer exercise tolerance. Elderly patients in Study 2 showed less improvement in hemodynamics with therapy. There was no significant difference in disease-specific survival between elderly and younger patients. Japanese elderly patients with I/H-PAH showed poorer exercise capacity and impaired gas exchange, but better pulmonary hemodynamics than younger patients.

Preservación de órgano en pacientes con tumores avanzados de laringe. Resultados de la quimioterapia de inducción versus quimio-radioterapia en la práctica clínica real

Introduction and objectivesA high percentage of patients with locally advanced larynx carcinomas are candidates for inclusion in organ preservation protocols. The objective of this study is to compare the results of two schemes of preservation, induction chemotherapy versus chemoradiotherapy, in patients with locally advanced larynx carcinomas in the context of actual clinical practice. MethodsOur retrospective study included 157 patients with locally advanced tumours of the larynx (T3-T4) treated with induction chemotherapy (n = 121) or chemoradiotherapy (n = 36). ResultsFrom 121 patients who began treatment with induction chemotherapy, 6 died due to toxicity, 37 were treated with surgery, and 78 completed the preservation scheme; 36 patients received treatment with chemoradiotherapy. There were no significant differences in 5-year disease-specific survival between both treatments: 68.9% in induction chemotherapy versus 75.7% in chemoradiotherapy (p = 0.259). In 45.9% of patients the laryngeal function was preserved. Patients treated with chemoradiotherapy had a tendency to have better 5-year laryngeal dysfunction-free survival than patients treated with induction chemotherapy (55.6% versus 44.8%, p = 0.079). ConclusionPatients included in a protocol of organ preservation achieved a 5-year laryngeal dysfunction-free survival of 45.9%. There were no significant differences in disease-specific survival among patients treated with induction chemotherapy or chemoradiotherapy.

SUN-626 Survival of Patients with Gastroenteropancreatic Neuroendocrine Tumors and Diabetes Mellitus in a Seer-Medicare Cohort

Background: The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) is increasing globally and has been associated with diabetes mellitus (DM). In this study we aimed to compare tumor characteristics, disease-specific survival (DSS) and overall survival (OS) of GEP-NET patients (pts) with and without DM. Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER) linked to Medicare claims, we identified pts diagnosed with GEP-NET between January 1995 and December 2010, aged ≥65 years at the time of GEP-NET diagnosis. We included patients who were in exclusive Medicare coverage without healthcare management organizations and had Medicare Parts A and B coverage for ≥1year after GEP-NET diagnosis or until death. Within the pts with GEP-NET diagnosis, we identified those without a diagnosis of DM prior to the GEP-NET diagnosis. We compared baseline sociodemographics, co-morbidities, and GEP-NET location, stage, grade and treatment between pts with and without DM using χ 2 analysis. Kaplan Meier (KM) curves were used to compare OS and DSS up to 10 years between the DM and non-DM groups. We used Cox proportional hazards analysis to compare the DSS between the groups, adjusting for confounding variables. Results: We identified a cohort of 1,969 well-characterized GEP-NET patients with accurate tumor stage, grade, comorbidities, and treatment data. 478 (25.7%) had DM and 1,383 (74.3%) did not have DM. There were no statistically significant differences in gender or age at the time of GEP-NET diagnosis in the DM (mean age 74.7±SD 6.6 yrs) and non-DM (74.9±7.4 yrs) groups. Significant differences in race were found in the DM (80.6% white, 13.6% black, 1.3% hispanic) and non-DM (86.8% white, 8.2% black, 1.8% Hispanic) groups (p=0.002). Patients with DM had more gastric (14.7%), duodenal (10.9%) and pancreatic (21.0%), and less jejunal/ ileal (12.8%) NETs compared with the non-DM group (9.7%, 6.4%, 16.9%, 18.2%, respectively, p<0.0001). Patients with DM had earlier stage disease than those without DM (p=0.0012), but no difference in tumor grade or treatment was found. KM curves revealed no differences in OS and DSS in the GEP-NET patients with and without DM across all stages. Multivariate adjusted Cox proportional-hazards model found no significant difference in DSS between those with and without DM (HR=0.97, 95%CI: 0.76–1.24). Compared with pts with pancreatic NETs, pts with colon (HR=1.39, 95%CI: 1.04–1.86) had worse survival, while those with jejunal/ileal (HR = 0.59, 95%CI: 0.42–0.83) NETs had a better survival. Discussion: This is the first study to investigate the effect of DM on survival of pts GEP-NETs. We found a high prevalence of pre-existing DM in pts with GEP-NETs, but no difference in OS or DSS in pts with and without DM. Interestingly, pts with DM had more foregut GEP-NETs which may suggest mechanistic links between DM and GEP-NETs at these sites.

The impact of surgery refusal on thyroid cancer survival: a SEER-based analysis.

In the current era of de-escalation of surgical treatment for low-risk thyroid cancer, it is important to ensure that the natural history of thyroid cancer is as benign as has been suggested previously. We therefore compared the impact of surgery refusal and surgery on disease-specific survival (DSS) in patients with local or regional, papillary thyroid cancer (PTC). Local and regional stage PTC patients in the Surveillance, Epidemiology, and End Results Program (1988-2015) were included. Cox proportional hazard modeling and propensity score matching were conducted to evaluate DSS. There were 45,136 patients who received surgery and 146 patients who had surgery recommended but refused. Adjusted analysis showed a significantly better DSS for the surgery group compared with the refusal group (HRadj: 3.07 (95% CI: 1.54-6.11). After stratification for stage, no statistically significant difference in DSS was found (HRadj: 3.03 (0.89-10.35) when including only local stage PTC. Propensity matching showed a 10-year DSS of 94.0% (95% CI: 87.7-97.1%) and 96.4% (95% CI: 93.2-98.1%) for the refusal and surgery group (p = 0.060). Propensity matching of local stage PTC showed a 10-year DSS of 96.7% (95% CI: 89.9-98.9%) and 100%, respectively (p = 0.002). Although no significant difference in survival was found between surgery and no surgery in local stage PTC, a 3.3% improvement of 10-year DSS was found in the surgery group. Overall, these results suggest that local stage PTC has a benign natural history, and that conservative management strategies such as active surveillance may be appropriate.

Predictive value of the modified systemic inflammation score in patients undergoing curative resection of squamous cell carcinoma of the esophagus.

447 Background: Inflammation plays a critical role in the development and progression of cancers. Here we aimed to evaluate the clinical significance of the preoperative modified systemic inflammation score (mSIS) to predict long-term outcomes of patients with esophageal squamous cell carcinoma (ESCC). Methods: We included 443 patients who underwent curative resection of ESCC. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥4.0 g/dL and LMR ≥3.4), mSIS 1 (ALB &lt; 4.0 g/dL or LMR &lt; 3.4), and mSIS 2 ( ALB &lt; 4.0 g/dL and LMR &lt; 3.4). Results: Patients were categorized into preoperative mSIS 0 (n = 165), mSIS 1 (n = 183), and mSIS 2 (n = 95) groups. Preoperative mSIS was significantly associated with age, preoperative body mass index, and pathological disease stage. The disease-specific survival times of patients in preoperative mSIS 0, 1, and 2 sequentially shortened ( P = 0.009), and mSIS 2 was identified as an independent prognostic factor (hazard ratio 2.63, 95% confidence interval 1.33–5.27, P = 0.0053). In most patient subgroups, the mSIS was associated with greater risk of disease-specific death. A stepwise increase in the prevalence of hematogenous recurrences was directly proportion to the mSIS. When patients were subdivided by mSIS before neoadjuvant treatment, there were no significant differences in disease-specific survival. Conclusions: Our findings demonstrate that the preoperative mSIS may serve as a powerful prognosticator of ESCC that definitively stratifies clinical outcomes as well as a tool for selecting treatment strategies.

Podoplanin is an efficient predictor of neck lymph node metastasis in tongue squamous cell carcinoma with low tumor budding grade.

The current study investigated the efficacy of podoplanin expression in tumor budding cells as a predictor of neck lymph node metastasis (NLM) in patients with tongue squamous cell carcinoma (SCC) of low tumor budding grade (TBG). A total of 99 patients with early T-stage tongue SCC of any clinical N status who received the initial curative treatment were enrolled. The association between podoplanin expression and NLM was immunohistochemically analyzed, with a focus on tongue SCC with low TBG. The disease-specific survival (DSS) rate was 77% at 5 years, and a significant difference was observed between the NLM-positive and NLM-negative groups, and between the low (n=77) and high (n=22) TBG groups. In the low TBG group, there was a significant difference in DSS between the NLM-positive and NLM-negative groups. The multivariate analysis showed that lymphatic vessel invasion (ly) [odds ratio (OR)=11.5, 95% confidence interval (CI): 1.50–87.6; P=0.02] and podoplanin expression (OR=7.07, 95% CI: 1.80–27.7; P=0.005) were significantly correlated with NLM. Furthermore, negative predictive values (NPV) of ly and podoplanin expression for NLM were 75% and 88%, respectively. Considering the balance of stratification case number adding to ratio, NLM-negative prediction by podoplanin was more significant than that by ly for the low TBG group. The results of the present study demonstrated that podoplanin expression in tumor budding is an independent and efficient predictor of NLM in the tongue SCC with low TBG. The low TBG and podoplanin-negative cases may be candidates for the wait and watch policy, therefore, reducing inappropriate elective neck lymph node dissections.

Comparison of surgical intervention to Cyberknife® radiotherapy in the treatment of liver malignancies

Surgical resection is the method of choice in treating liver malignancies. In patients who are not suitable for radical surgical treatment, the radiotherapeutic system Cyberknife® is aviable treatment option. The aim of this study is to compare short- and long-term results of both treatment methods. Aretrospective analysis of prospectively collected data was performed, focused on patients undergoing treatment of liver malignancies either by surgical resection or by the Cyberknife® system from 2013 to 2016. Only patients treated using asingle treatment method were included in the study. Atotal of 260 patients were analysed; 142 were treated by performing surgical resection and the remaining 118 using Cyberknife® radiotherapy. Median survival was 30.65 months for the surgical resection and 22.93 for the Cyberknife® therapy; median overall survival was 27.63 months. Three-year cumulative survival was 47.4% for the resection and 19.9% for radiotherapy. Kaplan-Meier analysis did not demonstrate astatistically significant difference in disease-specific survival between both groups (p=0.082, CI 95%). Results limited only to colorectal liver metastases showed astatistically significant difference in disease-specific survival (p=0.031, CI 95%). Results of this study show statistically indifferent overall disease-specific survival of both groups. However, the significant difference in 3-year survival still indicates apredominant position of surgery in the diagnostic and therapeutic management of patients with liver malignancies. Nevertheless, Cyberknife® radiotherapy may actually represent aviable treatment alternative, particularly in patients unable to undergo surgical resection, although alonger follow-up period is necessary to obtain more robust results.

Modified Systemic Inflammation Score is Useful for Risk Stratification After Radical Resection of Squamous Cell Carcinoma of the Esophagus.

Inflammation plays a critical role in the development and progression of cancers. We evaluated the clinical significance of the preoperative modified systemic inflammation score (mSIS) to predict long-term outcomes of patients with esophageal squamous cell carcinoma (ESCC). We included 443 patients who underwent curative resection of ESCC. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥ 4.0g/dL and LMR ≥ 3.4), mSIS 1 (ALB < 4.0g/dL or LMR < 3.4), and mSIS 2 (ALB < 4.0g/dL and LMR < 3.4). Patients were categorized into preoperative mSIS 0 (n = 165), mSIS 1 (n = 183), and mSIS 2 (n = 95) groups. Preoperative mSIS was significantly associated with age, preoperative body mass index, and pathological disease stage. The disease-specific survival times of patients in preoperative mSIS 0, 1, and 2 sequentially shortened (P = 0.009), and mSIS 2 was identified as an independent prognostic factor (hazard ratio 2.63, 95% confidence interval 1.33-5.27, P = 0.0053). In most patient subgroups, the mSIS was associated with greater risk of disease-specific death. A stepwise increase in the prevalence of hematogenous recurrences was directly proportion to the mSIS. When patients were subdivided by mSIS before neoadjuvant treatment, there were no significant differences in disease-specific survival. Our findings demonstrate that the preoperative mSIS may serve as a powerful prognosticator of ESCC that definitively stratifies clinical outcomes as well as a tool for selecting treatment strategies.

Effects of HER2 status on the prognosis of male breast cancer: a population-based study.

ObjectiveThis study was designed to analyze the effects of human epidermal growth factor receptor-2 (HER2) status on the prognosis of male breast cancer (MBC).MethodsThe SEER database was used to identify MBC patients diagnosed between 2010 and 2015. Patients were divided into HER2-negative and HER2-positive groups and chi-square test was used to compare the demographics. Propensity score matching (PSM) was used to remove confounding factors. The log-rank test was used to compare the overall survival (OS) and disease-specific survival (DSS) between the two groups. Univariate and multivariate Cox regression analyses were used to evaluate the effects of different variables on the prognosis of MBC patients. Subgroup analysis was conducted by using R software to explore the benefit of OS and DSS in the subgroup of MBC patients.ResultsIn the matched cohort, the log-rank test showed that there was a longer OS (P=0.044) in the HER2-negative group, and the 4-year OS rate in HER2-negative patients was significantly improved (P=0.008), but there was no difference in the DSS (P=0.408) and the 4-year DSS rates (P=0.198) between the two groups. Univariate and multivariate Cox regression also showed that the HER2 status did not independently associate with DSS (P=0.444). Subgroup analysis showed that HER2-negative patients experienced a longer OS in the subgroup of tumors 2–4 cm in size, no distant metastasis and who had received radiotherapy, but none of subgroup was found a significant difference in DSS between different HER2 status.ConclusionThis study identified that HER2 status had a clear influence on OS in patients with MBC, and there was a longer OS and a higher 4-year OS rate in the HER2-negative group. In addition, we observed that HER2 status had no significant effect on DSS in patients with MBC.

Impact of age and sex on chemotherapy (CTx) efficacy, toxicity and survival in early oesophagogastric (OG) cancer: A pooled analysis of 3265 patients from four large randomised trials (OE02, OE05, MAGIC &amp; ST03).

4022 Background: No large scale randomised data exists evaluating the impact of age and sex in patients (pts) undergoing potentially curative surgery and CTx for OG cancer. However, differences in age and sex may be contributing factors to variability in CTx dose-response and toxicity which could also impact survival. Methods: Data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival data, hazard ratios were calculated for pts &lt;70 and ≥70 years and between males and females. Pts were allocated to receive neoadjuvant platinum and fluoropyrimidine +/- anthracycline and bevacizumab. Mandard tumour regression grade (TRG) and prevalence of ≥G3 toxicities were compared according to the same subgroups using Chi-squared test. Results: 3265 pts were included for survival analysis (2668 (82%) M, 597 (18%) F; 2626 (80%) &lt;70, 639 (20%) ≥70). A significant improvement in disease specific survival (DSS) (HR 0.78; p&lt;0.001) and OS (HR 0.78; p&lt;0.001) was observed in females vs males. Although OS was worse in older vs younger pts (HR 1.15; p=0.01) no significant difference in DSS was observed (HR 1.04; p=0.52). For those pts who underwent resection following neoadjuvant CTx, older patients (19 vs 13%; p=0.01) and female patients (19% vs 13%, p=0.02) were more likely to achieve more favourable Mandard TRG 1&amp;2 scores. Older pts experienced significantly more ≥G3 neutropaenia (30 vs 22%; p=0.004). Females experienced significantly more ≥G3 nausea (12 vs 7%; p=0.006), vomiting (10 vs 5%; p≤0.001) and diarrhoea (9 vs 4%; p=0.001). Conclusions: This study represents the largest pooled analysis of age and sex differences on safety of neoadjuvant CTx and survival in early OG cancer. Females had significantly improved survival while experiencing more GI toxicities. Older pts achieved comparable DSS and thus, dependent on fitness, should be offered the same treatment paradigm as younger pts.

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure. All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed. A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1cm, 36 patients (15%) had a margin of 1.1-1.9cm, and 135 patients (56.2%) had a margin of 2cm or more. The median follow-up period was 21months. The LR rate was 2.9% for a margin of 1cm, 2.8% for a margin of 1.1-1.9cm, and 5.2% for a margin of 2cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1cm, 66.2% for a margin of 1.1-1.9cm, and 91.8% for a margin of 2cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2cm or more (p = 0.006). A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

A study of treatments and outcomes in elderly women with cervical cancer

ObjectiveWith the population aging, development of safe and effective treatments for elderly patients with cancer is needed. Although old age is considered a poor prognostic factor, this is not only because of the patient’s disease condition or response to treatment, but also because of treatment strategy and intensity. The purpose of this study was to clarify the influence of age on treatment and prognosis in patients with cervical cancer. MethodsWomen with stage Ib–IV cervical cancer treated at our institution between 1997 and 2014 were retrospectively analyzed. Patients were stratified by age into groups for analysis, <65 years and ≥65 years. Categorical variables were compared using chi-squared and Fisher’s exact tests. Survival analyses were performed using the Kaplan–Meier method, and comparisons were made using the log-rank test. Subsequently, Cox proportional hazards models were developed to find independent prognostic factors. ResultsOf 959 patients included in our study, 247 were ≥65 and 712 were <65 years of age. Elderly patients tended to be at a more advanced stage than younger patients (p < 0.001). Elderly patients more commonly had comorbidities. More received standard treatment in the younger patient group at any disease stage than in the elderly patient group (p < 0.001). Similar rates of adverse effects caused by surgery or radiotherapy were seen in patients from both groups. Although overall survival was statistically shorter in elderly patients (74.7 vs. 57.1%, p < 0.001), there was no significant difference in disease-specific survival for patients treated only with standard treatment. In multivariate analyses, clinical stage, histological type, treatment intensity, and primary surgery remained independent prognostic factors. Age was not an independent prognostic factor. ConclusionsThe influence of age on prognosis in patients with cervical cancer was less than we expected. Elderly patients might have better outcomes depending on the type of standard treatment they receive. The appropriate modality and intensity of treatment should be based on the patient’s general condition and background.

Survival Analysis in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Chemoradiotherapy Followed by Surgery According to the International Consensus on the 2017 Definition of Borderline Resectable Cancer

Background: The aim of this study was to validate a new definition of borderline resectable pancreatic ductal adenocarcinoma (PDAC) provided by the 2017 international consensus on the basis of three dimensions of anatomical (A), biological (B), and conditional (C) factors, using the data of the patients who had been registered for our institutional protocol of chemoradiotherapy followed by surgery (CRTS) for localized patients with PDAC. Methods: Among 307 consecutive patients pathologically diagnosed with localized PDAC who were enrolled in our CRTS protocol from February 2005 to December 2016, we selected 285 patients who could be re-evaluated after CRT. These 285 patients were classified according to international consensus A definitions as follows: R (resectable; n = 62), BR-PV (borderline resectable, superior mesenteric vein (SMV)/portal vein (PV) involvement alone; n = 27), BR-A (borderline resectable, arterial involvement; n = 50), LA (locally advanced; n = 146). Disease-specific survival (DSS) was analyzed according to A, B (serum CA 19-9 levels and lymph node metastasis diagnosed by computed tomography findings before CRT), and C factors (performance status (PS)) factors. Results: The rates of resection and R0 resection were similar between R (83.9 and 98.0%) and BR-PV (85.2 and 95.5%), but much lower in BR-A (70.0 and 84.8%) and LA (46.6 and 62.5%). DSS evaluated by median survival time (months) showed a similar trend to surgical outcomes: 33.7 in R, 27.3 in BR-PV, 18.9 in BR-A and 19.3 in LA, respectively. DSS in R patients with CA 19-9 levels > 500 U/mL was significantly poorer than in patients with CA 19-9 levels ≤ 500 U/mL, but there were no differences in DSS among BR-PV, BR-A, and LA patients according to CA 19-9 levels. Regarding lymph node metastasis, there was no significant difference in DSS according to each resectability group. DSS in R patients with PS ≥ 2 was significantly worse than in patients with PS 0-1. Conclusions: The international consensus on the definition of BR-PDAC based on three dimensions of A, B, and C is useful and practicable because prognosis of PDAC patients is influenced by anatomical factors as well as biological and conditional factors, which in turn may help to decide treatment strategy.

Comparative Study between Sentinel Lymph Node Biopsy and Axillary Dissection in Patients with One or Two Lymph Node Metastases.

PurposeSentinel lymph node biopsy (SLNB) is a standard axillary surgery in early breast cancer. If the SLNB result is positive, subsequent axillary lymph node dissection (ALND) is a routine procedure. In 2011, the American College of Surgeons Oncology Group Z0011 trial revealed that ALND may not be necessary in early breast cancer with one or two positive sentinel lymph nodes. The purpose of this study was to compare outcomes among Korean patients with one or two positive axillary lymph nodes in the final pathology who did and did not undergo ALND.MethodsA total of 131,717 patients from the Korea Breast Cancer Society registry database received breast cancer surgery from January 1995 to December 2014. Inclusion criteria were T stage 1 or 2, one or two positive lymph nodes, and having received breast-conserving surgery (BCS), whole breast radiation therapy, and no neoadjuvant therapy. We analyzed the differences in disease-specific survival (DSS) and overall survival (OS) between patients who received SLNB only and those who underwent SLNB+ALND.ResultsA total 4,442 patients met the inclusion criteria, with 1,268 (28.6%) in the SLNB group and 3,174 (71.4%) in the SLNB+ALND group. There were no differences in DSS and OS between the two groups (p=0.378 and p=0.925, respectively). The number of patients who underwent SLNB alone for one or two positive lymph nodes increased continuously from 2004 to 2014.ConclusionKorean patients with early breast cancer and 1 or 2 positive axillary lymph nodes who received BCS plus SLNB showed no significant difference in DSS and OS regardless of whether they received ALND. The findings of this retrospective study demonstrate that omitting ALND can be considered when treating selected patients with early breast cancer who have one or two positive lymph nodes.

Is definitive concurrent chemoradiotherapy effective for locally advanced head and neck cancer in the elderly aged≥75 years: A single-institute, retrospective, cohort study.

Definitive chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer (HNC). However, for very elderly patients, the comparison of benefit/risk between definitive radiotherapy (RT) with and without systemic chemotherapy was equivocal. The study was a single-institute, retrospective, cohort study. Seventy patients aged ≥75 years who had a locally advanced HNC were enrolled. The patients were divided into those with CRT and those with RT alone. Survival, compliance/adverse events and independent prognostic factors were analyzed. For baseline characteristics, the patients who received RT alone had worse performance status, comorbidity score and neutrophil-to-lymphocyte ratio. However, during definitive therapy, the CRT group had more adverse events such as neutropenia, febrile neutropenia and thrombocytopenia. There were no significant differences in disease-specific survival (DSS) and overall survival (OS) (P=0.864 and 0.788, respectively). As to OS, several independent prognostic factors were identified. Performance status (hazard ratio [HR], 2.312; confidence interval [CI], 1.176-4.546; P=0.015), clinical T staging (HR, 2.240; 95% CI, 1.021-4.913; P=0.004) and total RT dose (HR, 2.555; 95% CI, 1.246-5.238; P=0.010) were independent prognostic factors of OS. Definitive RT with or without systemic chemotherapy did not significantly influence DSS and OS for very elderly patients. Therefore, for elderly patients aged≥75 years who have HNC, conservative RT might be sufficient for treatment purposes.

New suggestion for clinical downstaging of nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy

Objective To propose a new suggestion for the clinical downstaging of nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT) without changing the current T, N, and M staging system. Methods We reviewed the records of 536 NPC patients treated in Sun Yat-Sen University Cancer Center from January 2002 to December 2006.The Kaplan-Meier method was used to calculate the disease-specific survival (DSS) rate, and the log-rank test was used for survival difference analysis. The Cox regression model was used to calculate the hazard ratio (HR) of each subset. Results According to the 7th edition of UICC/AJCC staging system, the 5-year DSS rates of stage Ⅰ-Ⅲ patients (except T3N2M0) were all more than 85%(P>0.05), those of stage ⅣA and ⅣB patients were 71.8% and 46.2%, respectively (P=0.171), and that of stage ⅠVC patients was only 24.0%.In stage Ⅲ, the 5-year DSS rate of non-T3N2M0 patients (91.5%) was significantly higher than that of T3N2M0 patients (78.6%)(P=0.042), but there was no significant difference in DSS between T3N2M0 patients and stage ⅣA and ⅣB patients. Based on the above results, new stage Ⅰ included T1-3N0-1M0 and T1-2N2M0, new stage Ⅱ included T3N2M0, T4N0-2M0, and TxN3M0, and new stage Ⅲ included TxNxM1.The 5-year DSS rates of new stage Ⅰ, Ⅱ, and Ⅲ patients were 93.3%, 72.7%, and 24.0%, respectively (P=0.000). Compared with new stage Ⅰ patients, new stage Ⅱ and Ⅲ patients had HRs of 4.01 and 16.76, respectively, for 5-year DSS. Conclusions In the era of IMRT, the new clinical staging system (stages Ⅰ, Ⅱ, and Ⅲ) helps with prognostic evaluation and clinical treatment. Key words: Nasopharyngeal neoplasms/intensity modulated radiotherapy; Down-staging; New suggestion

External Validation of the New International Association for the Study of Lung Cancer Tumor, Node, and Metastasis 8th Edition Staging System and Updated T Descriptors in Determining Prognosis for Patients With Non–Small Cell Lung Cancer Patients With N3 Disease

ObjectiveThe objective of this study is to externally validate the 8th Edition of the Tumor, Node, and Metastasis staging system and its updated T descriptors in patients with non–small cell lung cancer with N3 disease. MethodsData were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test, Kaplan–Meier method, and Cox regression models were used in SPSS 23.0 (IBM Corp, Armonk, NY). ResultsA total of 7732 patients with non–small cell lung cancer with T1-4N3M0 disease from 1988 to 2013 were identified. A total of 1410 patients (18.2%) had T1N3 disease, 2491 patients (32.2%) had T2N3 disease, 1563 patients (20.2%) had T3N3 disease, and 2268 patients (29.3%) had T4N3 disease. The 5-year overall survival (OS) for the entire cohort was 8.4%. There was a significant difference in OS concerning T stage (T1N3: 10.8% vs. T2N3: 8.3% vs. T3N3: 8.1% vs. T4N3: 7.3%; P < .001). When stratified by the median age of patients (66 years), a significant difference in OS by stage of disease (IIIB vs. IIIC) was still observed in both the younger (P < .001) and older (P < .001) patient populations. A significant difference in disease-specific survival (DSS) was observed by T stage (T1N3: 14.7% vs. T2N3: 11.6% vs. T3N3: 11.3% vs. T4N3: 9.7%; P < .001). On multivariate analysis, T stage, year of diagnosis, age, gender, histology, and receipt of radiotherapy remained independent prognostic factors for both OS and DSS. ConclusionsThe 8th Edition of the Tumor, Node, and Metastasis staging system significantly stratifies both overall and DSS between stages IIIB and IIIC among those with N3 disease. However, small absolute differences in 5-year outcomes between T stage may suggest limited clinical relevance.

Incidence and survival differences in esophageal cancer among ethnic groups in the United States.

ObjectivesThis study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences.ResultA total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups.Materials and MethodFrom the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared.ConclusionHistological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect.

Relationship between response to induction chemotherapy and disease control in patients with advanced laryngeal carcinoma included in an organ preservation protocol.

The aim of the study is to analyze the relationship between the degree of response to induction chemotherapy and the disease control in patients with locally advanced laryngeal carcinomas candidates to total laryngectomy. This retrospective study includes 389 patients with T3-T4 laryngeal tumors candidates to total laryngectomy, diagnosed between 1985 and 2013, treated with induction chemotherapy in an organ preservation protocol. Five-year local recurrence-free survival for patients receiving conservative treatment with radiotherapy after a complete response to induction chemotherapy was 75.4%; for patients with partial response greater than 50%, it was 62.0%; and for patients with the absence of response, it was 32.7%. There were significant differences in local recurrence-free survival and laryngeal dysfunction-free survival according to the response to induction chemotherapy (P = 0.0001) at the expense of patients with absence of response to induction chemotherapy. Patients with partial response greater than 50% treated with radiotherapy had a tendency to have worse local recurrence-free survival and laryngeal dysfunction-free survival than patients with complete response, but the differences did not reach statistical significance. Patients with the absence of response after induction chemotherapy had significant differences in disease-specific survival according to the second treatment: for patients treated with surgery it was 70.2%, whereas for patients treated with radiotherapy, it was 28.2% (P = 0.0001). In patients with the absence of response to induction chemotherapy, conservative treatment with radiotherapy implies a significant decrease in survival.