Significant Difference In Recurrence-free Survival Research Articles

Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: First results of the randomised MATADOR trial (BOOG 2004-04)

BackgroundDose-dense administration of chemotherapy and the addition of taxanes to anthracycline-based adjuvant chemotherapy have improved breast cancer survival substantially. However, clinical trials directly comparing the additive value of taxanes with dose-dense anthracycline-based chemotherapy are lacking. Patients and methodsIn the multicentre, randomised, biomarker discovery Microarray Analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens (MATADOR) trial, patients with pT1-3, pN0-3 breast cancer were randomised (1:1) between six adjuvant cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks (ddAC) and six cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks (TAC). The primary objective was to discover a predictive gene expression profile for ddAC and TAC benefit. Here we report the preplanned secondary end-point recurrence-free survival (RFS) and overall survival (OS). ResultsBetween 2004 and 2012, 664 patients were randomised. At 5 years, RFS was 87% (95% confidence interval [CI] 83%–91%) in the ddAC-treated patients and 88% (84–92%) in the TAC-treated subgroup (hazard ratio [HR] 0.89, 95% CI 0.62–1.28, P = 0.53). OS at 5 years was 93% (90%–96%) in the ddAC-treated and 94% (91%–97%) in the TAC-treated patients (HR 0.89, 95% CI 0.57–1.39, P = 0.61). Anaemia was more frequent in ddAC-treated patients (62/327 patients [18.9%] versus 15/319 patients [4.7%], P < 0.001) and diarrhoea (21 [6.4%] versus 53 [16.6%], P<0.001) and peripheral neuropathy (15 [4.6%] versus 46 [14.4%], P < 0.001) were observed more often in TAC-treated patients. ConclusionsWith a median follow-up of 7 years, no significant differences in RFS and OS were observed between six adjuvant cycles of ddAC and TAC in high-risk breast cancer patients. Trial registration numbersISRCTN61893718 and BOOG 2004-04.

Impact of the controlling nutritional status (CONUT) score on the prognosis after curative resection of pancreatic adenocarcinoma

Introduction: The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to retrospectively investigate the impact of the CONUT score on short- and long-term outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Methods: Between April 2002 and April 2016, 344 consecutive patients who underwent curative resection of PDAC without neoadjuvant therapy were analysed. After the best predictive value of the CONUT score for survival was explored, predictors of overall survival (OS) were identified using Kaplan-Meier analyses, the log-rank test and Cox multivariable analysis. Correlations between the CONUT score and postoperative complications were analysed using the Mann-Whitney U test and Spearman`s rank correlation. Results: The median survival times of patients with high and low CONUT scores were 18.0 and 26.8 months, respectively. The high CONUT score group showed significantly lower OS than that of the low CONUT score group in the univariate analysis (P = 0.002). In contrast, no significant difference in recurrence-free survival was found (P = 0.43). The multivariate analysis demonstrated that a high CONUT score was an independent prognostic risk factor for OS (hazard ratio: 1.64, P = 0.003). The CONUT score showed no association with postoperative pancreatic fistula, the Clavien-Dindo grade or the postoperative hospital stay. Conclusion: The CONUT score, which is a measure of immune-nutritional status, was an independent prognostic risk factor for OS in patients with PDAC after pancreatectomy and was not associated with RFS or postoperative complications.

Post transplant survival in patients with hepatocellular carcinoma within and beyond Milan criteria

Introduction: Living donor liver transplantation(LDLT) is an established treatment for patients with cirrhosis and hepatocellular carcinoma within Milan criteria. Acceptable outcomes have been demonstrated in patients fulfilling extended criteria. Here, we share our experience with LDLT for patients with HCC within and beyond Milan criteria with emphasis on poor prognostic factors. Methods: We retrospectively reviewed patients who underwent LDLT between 2012 and 2017 and had HCC proven on explant liver histopathology . A total of 117 patients were included. Patients who experienced early post transplant death (<30 days) were excluded. Demographics, patient and tumor characteristics were recorded. For outcomes, patients were divided into prognostic groups. These groups were based on 1) Poor differentiation 2) AFP > 600 and 3) presence of lympho vascular invasion. Recurrence free survival (RFS) was determined using Kaplan Meier curves. Results: Median age was 53(30–73) years. Median follow up was 20.3(1–63.2) months. Median MELD score was 19 (9–34). Out of total 117 patients, 74 (63.2%) patients fulfilled Milan criteria.Recurrence rate was 12/117 (10.3%). Actuarial 5 year RFS was 88% and 82%(P = 0.3) in patients within and outside Milan criteria. There was no difference in 3 year RFS in patients with 0, 1 or 2 poor prognostic factors within Milan criteria (92%, 87% and 75%)(P = 0.3). However, a significant difference in RFS was seen in patients outside Milan criteria (92%, 93% and 53%)(P = 0.03). Conclusion: Patients within Milan criteria have acceptable RFS even in presence of poor prognostic factors. However, presence of two or more poor prognostic variables significantly impacts RFS outside Milan criteria.

Effect of KI-67 positive cellular index on prognosis after hepatectomy in Barcelona Clinic Liver Cancer stage A and B hepatocellular carcinoma with microvascular invasion

ObjectiveThis study aimed to explore the relationship between KI-67 positive cellular index and recurrence-free survival (RFS) in Barcelona Clinic Liver Cancer (BCLC) stage A and B hepatocellular carcinoma (HCC) patients, particularly those with microvascular invasion (MVI).MethodsA total of 333 patients who underwent curative hepatectomy had their immunohistochemistry analyzed retrospectively for KI-67 positive cellular index.ResultsIn total, 41.1% (137/333) of HCC patients displayed high KI-67 positive cellular index (>35%). Patients with high KI-67 positive cellular index had poorer RFS than those with low index (P<0.0001). Patients were then subdivided into an MVI positivity group (n=192) and an MVI negativity group (n=141). In the MVI positivity group, patients with high KI-67 positive cellular index had a shorter RFS after operation as compared to those with low index (P<0.0001). However, there was no significant difference in RFS between high- and low-index subgroups within the MVI negativity group (P>0.05). Additionally, patients with high KI-67 positive cellular index combined with MVI positivity had the shortest RFS of all those with MVI negativity, regardless of KI-67 cellular index level (P<0.0001). Multivariate analysis showed that node number >1, capsule absence, high KI-67 positive cellular index, and alpha-fetoprotein >400 ng/mL were independent risk factors for a recurrence of HCC with MVI.ConclusionOur results suggested that high KI-67 positive cellular index may represent a poor prognostic factor in BCLC stage A and B HCC patients, especially those with MVI.

Impact of the Controlling Nutritional Status Score on the Prognosis After Curative Resection of Pancreatic Ductal Adenocarcinoma.

The controlling nutritional status (CONUT) score is a useful tool to evaluate immune-nutritional status. This study aimed to investigate the impact of the CONUT score on short- and long-term outcomes after curative resection of pancreatic ductal adenocarcinoma (PDAC). Consecutive 344 PDAC patients receiving pancreatectomy without neoadjuvant therapy were examined retrospectively. After the best predictive value of the CONUT score for survival was identified, association between the CONUT score and long-term outcomes was evaluated using log-rank tests and a Cox regression model. Then correlations between the CONUT score and postoperative complications were analyzed. The optimal cutoff value of the CONUT score was 4. The high CONUT score group showed significantly lower overall survival than the low CONUT score group (P = 0.002). In contrast, no significant difference in recurrence-free survival was found (P = 0.43). A multivariate analysis demonstrated that high CONUT score had an independent association with overall survival (hazard ratio, 1.64; P = 0.003). The CONUT score showed no association with postoperative pancreatic fistula, Clavien-Dindo grade, or postoperative hospital stay. The CONUT score had an independent association with survival in patients with PDAC after pancreatectomy and was not associated with recurrence or postoperative complications.

Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial

The optimal frequency of prostate cancer image guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. This phase 3 randomized trial recruited patients with N0 localized prostate cancer. The total IGRT doses in the prostate ranged from 70Gy to 80Gy, sparing the lymph nodes. Patients were randomly assigned (1:1) to 2 prostate IGRT frequency groups: daily and weekly (ie, on days 1, 2, and 3 and then weekly). The primary outcome was 5-year recurrence-free survival. Secondary outcomes included overall survival and toxicity. Post hoc analyses included biochemical progression-free interval, clinical progression-free interval, and other cancer-free interval. Between June 2007 and November 2012, 470 men from 21 centers were randomized into the 2 groups. Median follow-up was 4.1years. There was no statistically significant difference in recurrence-free survival between the groups (hazard ratio [HR]=0.81; P=.330). Overall survival was worse in the daily group than in the weekly group (HR=2.12 [95% confidence interval (CI), 1.03-4.37]; P=.042). Acute rectal bleeding (grade ≥1) was significantly lower in the daily group (6%) (n = 14) than in the weekly group (11%) (n = 26) (P=.014). Late rectal toxicity (grade ≥1) was significantly lower in the daily group (HR=0.71 [95% CI, 0.53-0.96]; P=.027). Biochemical progression-free interval (HR=0.45 [95% CI, 0.25 - 0.80]; P=.007) and clinical progression-free interval (HR=0.50 [95% CI, 0.24-1.02]; P=.057) were better in the daily group, whereas other cancer-free interval was worse in the daily group (HR=2.21 [95% CI, 1.10-4.44]; P=.026). Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.

Predicting prognosis of post-chemotherapy patients with resected IIIA non-small cell lung cancer.

Recently, nomogram has been widely used in cancer prognoses. However, the predicting model for post-chemotherapy patients with resected IIIA non-small cell lung cancer (NSCLC) still remains scarce. Here, we tried to develop nomograms for predicting the recurrence and survival of these patients. We retrospectively analyzed our database from October 2007 to May 2013 at Fudan University Shanghai Cancer Center. 437 qualified patients were included. Univariable and multivariable analyses of cox regression were performed successively to select prognostic factors and nomograms for recurrence-free survival (RFS) and overall survival (OS) were developed. Concordance indexes (C-index) and calibration curves were created to measure the consistency between predicted and actual survivals. Finally, risk group stratifications according to risk scores calculated from nomograms were delineated. With a total of 437 patients, five independent prognostic factors related to RFS and two to OS were selected to develop nomograms, respectively. Both 3- and 5-year RFS and OS calibration curves indicated a moderate concordance between the predicted and actual outcomes, consisted with the C-index 0.656 (95% CI: 0.626-0.687) for RFS and 0.651 (95% CI: 0.611-0.691) for OS. Different risk groups showed significant differences in RFS and OS. We developed nomograms of RFS and OS for predicting recurrence and survival of post-chemotherapy patients with resected IIIA NSCLC. These nomograms could help doctors more easily estimate the prognosis and choose optimal decisions for individual during clinical practices.

Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma.

ObjectivesTo develop a surveillance protocol with improved cost-effectiveness after radical nephroureterectomy (RNU), as the cost-effectiveness of oncological surveillance after RNU remains unclear.ResultsOf 426 patients, 109 (26%) and 113 (27%) experienced visceral and intravesical recurrences, respectively. The pathology-based protocol found significant differences in recurrence-free survival in the visceral recurrence but not in the intravesical recurrence. The medical costs per visceral recurrence detected were high, especially in normal-risk (≤ pT2N0, LVI-, SM-) patients. We developed a risk score associated with visceral recurrence using Cox regression analysis. The risk score-based protocol was significantly more cost-effective than the pathology-based protocol. Estimated cost differences reached $747,929 per recurrence detected, a suggested 55% reduction.Materials and MethodsWe retrospectively evaluated 426 patients with RNU for upper tract urothelial carcinoma (UTUC) without distant metastasis at 4 hospitals. Patients with routine oncological follow-up were stratified into normal-, high- and very high-risk groups according to a pathology-based protocol utilizing pathological stage, lymphovascular invasion (LVI) and surgical margin (SM). Cost-effectiveness of the pathology-based protocol was evaluated, and a risk score-based protocol was developed to optimize cost-effectiveness. Risk scores were calculated by summing up risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate- and high-risk score. Estimated cost per recurrence detected by pathology-based and risk score-based protocols was compared.ConclusionsA risk score-stratified surveillance protocol has the potential to reduce over investigation during follow-up, making surveillance more cost-effective.

A long-term experience with expansion of Milan criteria for liver transplant recipients.

The Milan criteria (MC) have historically determined eligibility for transplantation for hepatocellular carcinoma (HCC). The United Network for Organ Sharing (UNOS) Region 4 expanded the criteria for transplantation in HCC to include a single tumor ≤6cm or up to 3 tumors with the largest diameter ≤5cm and total additive diameter ≤9cm (R4C). The aim of this study was to report the 10-year outcomes of this expanded criteria compared to MC. Transplants performed for HCC in Region 4 between October 2007 and December 2016 were reviewed using the UNOS database. Recipients were categorized based on imaging findings at initial evaluation. A total of 2068 patients were included in the study. There was no significant difference in 10-year patient survival between the groups (53% MC vs 48% R4C, P=.23). There was also no significant difference in recurrence-free survival (54% MC vs 47% R4C, P=.15) or allograft survival (53% MC vs 48% R4C, P=.16). Finally, there was no significant difference in outcomes between the MC and R4C groups when stratifying patients by locoregional therapy. This study demonstrates promising data that the criteria for liver transplantation in HCC can be safely expanded to the R4C without compromising outcomes.

Value of KRAS mutation predicting prognosis of patients with colorectal liver-only metastasis after hepatectomy

Objective To explore the value of KRAS mutation predicting prognosis of patients with colorectal liver-only metastasis after hepatectomy. Methods The retrospective case-control study was conducted. The clinicopathological data of 79 patients with colorectal liver-only metastasis who underwent hepatectomy in the Sun Yat-sen University Cancer Center between October 2010 and October 2016 were collected. KRAS mutation in colorectal cancer tissue was detected by fluorescent quantitative polymerase chain reaction (PCR) and laser flight mass spectrometer. Observation indicators: (1) KRAS mutation; (2) relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis; (3) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect recurrence-free survival and overall survival up to June 30, 2017. The relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis was analyzed by the chi-square test or Fisher exact probability. The survival curve and time were respectively drawn and calculated by the Kaplan-Meier method, and COX regression model was used for survival analysis. Results (1) KRAS mutation: 79 patients received KRAS gene detection of surgical tumor tissues, including 54 in wide-type mutation and 25 in mutant-type mutation. Of 25 patients in mutant-type mutation, mutation at codon 12 of KRAS exon 2 was in 21 patients, and GGT>GAT (G12D), GGT>GTT (G12V), GGT>TGT (G12C), GGT>GCT (G12A) and GGT>CGT (G12R) of mutation types were respectively detected in 13, 4, 2 , 1 and 1 patients; mutation at codon 13 of KRAS exon 2 was in 3 patients, with a mutation type of GGC>GAC (G13D); mutation at codon 61 of KRAS exon 3 was in 1 patient, with a mutation type of CAA>CAT (Q61H). (2) Relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis: primary tumor located in right and left hemicolon were detected in 11, 14 patients with mutant-type mutation and 7, 47 patients with wide-type mutation, respectively, with a statistically significant difference (χ2=9.357, P 0.05]. Further analysis: of patients with low clinical risk score (CRS) of Memorial Sloan Caitlin Cancer Center (MSKCC), median recurrence-free survival time was 11.3 months in 17 patients with mutant-type mutation and 23.5 months in 26 patients with wide-type mutation, with a statistically significant difference in recurrence-free survival of patients (HR=2.082, 95%CI: 1.006-4.307, P 0.05). Of patients with high CRS of MSKCC, median recurrence-free survival time and median overall survival time were respectively 5.6 months, 28.7 months in 7 patients with mutant-type mutation and 4.5 months, 36.7 months in 24 patients with wide-type mutation, with no statistically significant difference in recurrence-free and overall survivals (HR=0.402, 1.197, 95%CI: 0.284-1.656, 0.371-3.866, P>0.05). Conclusions KRAS mutation is often detected in patients with right colon cancer. Recurrence-free survival time is obviously reduced in patients with KRAS mutation and low CRS of MSKCC. Key words: Colonic neoplasms; Rectal neoplasms; Liver metastases; Translational medicine; KRAS gene; Gene mutations; Surgical procedures, operative; Prognosis

Effect of neoadjuvant chemotherapy regimen on relapse-free survival among patients with breast cancer achieving a pathologic complete response: an early step in the de-escalation of neoadjuvant chemotherapy

BackgroundPatients with breast cancer who have a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize that once pCR has been achieved, there is no difference in subsequent postsurgical recurrence-free survival (RFS), whichever NACT regimen is used.MethodsData from patients with breast cancer who achieved pCR after NACT between 1996 and 2011 were reviewed. RFS was estimated by the Kaplan-Meier method, and differences between groups were assessed using log-rank testing. Cox proportional hazards regression analysis adjusted for age, menopausal status, stage, grade, tumor subtype, and adjuvant endocrine HER2-targeted radiation treatment.ResultsAmong 721 patients who achieved pCR after NACT, 157 (21.8%) were hormone receptor-positive (HR), 310 (43.3%) were HER2-amplified, and 236 (32.7%) were triple-negative; 292 (40.5%) were stage IIA, 153 (21.2%) were stage IIB, 78 (10.8%) were stage IIIA, 66 (9.2%) were stage IIIB, and 132 (18.3%) were stage IIIC. Most patients (367 [50.9%]) had been treated with adriamycin-based chemotherapy plus taxane (A + T), 56 (7.8%) without taxane (A no T), 227 (31.5%) with HER2-targeted therapy, and 71 (9.8%) provider choice. Median follow-up was 7.1 years. Adjuvant chemotherapy was employed in 196 (27%) patients, adjuvant endocrine in 261 (36%), and adjuvant radiation in the majority (559 [77.5%]). There was no statistically significant difference in RFS by NACT group. Adjusted RFS hazard ratios, comparing each treatment with the reference group A + T, were 1.25 (95% CI 0.47–3.35) for A no T, 0.90 (95% CI 0.37–2.20) for HER2-targeted therapy, and 1.28 (95% CI 0.55–2.98) for provider choice.ConclusionsThese data suggest that postsurgical RFS is not significantly influenced by the choice of NACT or cancer subtype among patients achieving pCR.

Appropriate lymphadenectomy significantly reduced recurrence after segmentectomy for patients with non-small cell lung cancer.

Segmentectomy has been widely used for small-sized non-small cell lung cancer (NSCLC). The objective of this study is to determine the impact of number of harvested lymph nodes (LNs) on survival for patients undergoing segmentectomy. The clinicopathologic data of patients undergoing segmentectomy for NSCLC from July 2011 to December 2014 were retrospectively analyzed. Survival analysis was performed by Kaplan-Meier method and Cox regression analysis. A total of 259 patients with NSCLC were eligible for analysis. Patients with harvested LN ≥6 had higher frequency of nodal metastasis in pathologic examination (9.4% vs. 1.5%, P=0.005). The 3-year recurrence-free survival (RFS) of patients with harvested LN ≥6 (90.2%) was significantly higher than that of patients with harvested LN <6 (73.7%, log-rank P=0.038). Multivariable Cox analysis identified harvested LN ≥6 as an independent predictor for improved RFS [hazard ratio (HR) =0.35; 95% confidence interval (CI): 0.14-0.90; P=0.029]. There was no significant difference in RFS between patients with harvested LN station ≥3 and <3 (log-rank P=0.34). The number of harvest LN ≥6 was independently associated with improved RFS for NSCLC patients undergoing segmentectomy, supporting the National Comprehensive Cancer Network (NCCN) guidelines of appropriate LN sampling.

Association of dividing pathologically upstaged T3a renal cell carcinoma with improved alignment of outcomes: A call for TMN revision.

642 Background: Incidental pathological upstaging to pT3a disease can occur after surgical treatment of clinical T1 and T2 Renal Cell Carcinoma (RCC), and upstaged pT3a disease is associated with worsened outcomes. Oncologic and survival outcomes within the pT3a category are heterogeneous. We investigated recurrence and survival outcomes in pT3a disease, and aimed to better categorize this cohort for improvement on current TMN staging. Methods: Multi-center retrospective analysis of patients with renal cell carcinoma (cT1-3aN0M0) from 1987-2016. After initial comparison of outcomes between pT1, pT2 and pT3a, patients were substratified within the pT3a category based on presenting clinical stage. Comparison was drawn between pT1, pT2 and the subdivided pT3a group (cT1 → pT3a, cT2 → pT3a, and cT3a → pT3a). Primary outcome was recurrence free survival (RFS). Secondary outcome was overall survival (OS). Kaplan−Meier (KM) analysis was utilized. Results: 2640 patients were analyzed (2125 cT1, 448 cT2, 67 cT3a, mean follow up 67.8 months). Rate of incidental T3a upstaging from cT1-2 was 14.7%. Compared to pT1-2 disease, patients with incidental pT3a upstaging had higher rate of recurrence (7.5% vs. 29.6%, p &lt; 0.001) and all-cause mortality at last follow up (15.9% vs. 25.4%, p &lt; 0.001). With regards to RFS, when pT3a was subdivided based on presenting clinical stage, significant differences in RFS emerged which aligned differently. Compared to 5 year RFS of pT1 (94.4%), cT1 → pT3a aligned with pT2 (76.6% and 81.2%, p = 0.346) while cT2 → pT3a aligned with cT3a → pT3a 47.4% and 44.0%, p = 0.815). With regards to OS, a similar alignment was noted for 5 year OS after subdivision, where pT1 was 89.9%, while cT1 → pT3a correlated with pT2 (79.8% and 83.1%, p = 0.640) and cT2 → pT3a correlated with cT3a → pT3a 67.0% and 64.2%; p = 0.893). Conclusions: Patients with cT1 → pT3a have outcomes more similar to pT2, than patients with cT2 → pT3a which align more closely to cT3a → pT3a. Future refinements of the TNM staging system for RCC should consider re-grouping cT1 → pT3a into the pT2 group. Further confirmation is requisite.

Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer.

430 Background: The cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost effectiveness after radical cystectomy. Methods: We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal- and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. Results: Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival, but the medical expense was high, especially in normal-risk (≤pT2pN0) patients. Cox regression analysis identified six factors that associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. Conclusions: Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.

Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma in Elderly Patients: Special Reference to Postoperative Adjuvant Chemotherapy.

The benefit of pancreatectomy for elderly patients with pancreatic ductal adenocarcinoma (PDAC) remains controversial. Moreover, adjuvant chemotherapy (AC) for elderly patients has not been fully evaluated. We investigated the long-term outcomes after pancreatectomy for PDAC in elderly patients with special reference to AC. The medical records of 123 patients who underwent pancreatectomy for PDAC from 2007 to 2016 were retrospectively reviewed. The patients were divided into two groups: young (<75years) and elderly patients (≥75years). The study population comprised 91 young and 32 elderly patients. The postoperative clinical courses were not different between the two groups. AC was more frequently administered to young (85%) than elderly patients (66%; P=0.04). The weekly dose of tegafur/gimeracil/oteracil potassium (S1) for AC was significantly lower in elderly (median 423mg/m2) than young patients (median 491mg/m2; P=0.02). The prevalence of adverse events and the completion rate of AC were not significantly different between the two groups. There were no significant differences in recurrence-free survival (P=0.73) or overall survival (P=0.68) between the two groups in univariate analysis. Receipt of AC was not a significant independent factor for survival, and completion of planned AC was a significant independent factor for recurrence-free survival and overall survival in multivariate analysis. The benefit of pancreatectomy for PDAC was the same between young and elderly patients. Completion of planned AC was important, and lowered-dose AC using S1 for elderly patients might be safe and therapeutically useful.

Transurethral endoscopic submucosal en bloc dissection for nonmuscle invasive bladder cancer: A comparison study of HybridKnife-assisted versus conventional dissection technique.

The aim of this study is to compare the efficacy and safety of en bloc bladder tumor-endoscopic submucosal dissection (BT-ESD) and conventional transurethral resection of BT (TURBT) in nonmuscle invasive bladder cancer (NMIBC) patients. A retrospective cohort study was carried out in Shaanxi Provincial People's Hospital. A total of 193 eligible NMIBC (Ta/T1) patients were enrolled in this study (95 cases in BT-ESD group and 98 cases in TURBT group), between November 2013 and January 2017. The operation time, blood loss, postoperative bladder irrigation time, catheter indwelling time, hospital stay time, and complications were compared. Data were presented as median (range). Chi-squared or rank-sum test, two-way ANOVA, and Mantel-Cox (Log-Rank) test were performed using statistical software. A threshold of P < 0.05 was defined as statistically significant. The average operation time in the BT-ESD group was longer than that of in the TURBT group (40.0 [5.0, 100.0] min vs. 19.5 [3.0, 55.5] min); however, no significant longer operating time (P < 0.05) were observed in the smaller tumor (0 cm-3 cm). The postoperative bladder irrigation time, catheter indwelling time, and hospital stay in BT-ESD group were significantly shorter than that of in TURBT group (9.0 [5.0, 18.0] h, 2.5 [1.0, 4.0] d and 3.5 [2.0, 5.0] d for BT-ESD; 18.0 [12.0, 48.0] h, 3.5 [2.0, 7.0] d, and 4.5 [3.0, 8.0] d for TURBT). In addition, the BT-ESD group showed the decreased overall incidence of complications (2.1% vs. 9.2%). The univariate and multivariate analyses indicated an association between surgical option and tumor recurrence (hazard ratio = 5.624, odds ratio = 95% confidence interval = 1.582-19.991), Kaplan-Meir analysis showed significant difference in recurrence-free survival (RFS) (94.7% for ESD group vs. 78.4% for TURBT group) at 33 months. The application of the HybridKnife lead to a decrease in complications and RFS rate, which was a more safe and effective approach for NMIBC than conventional TURBT.

Recurrence of Optimally Treated Malignant Peritoneal Mesothelioma with Cytoreduction and Heated Intraperitoneal Chemotherapy.

The prognosis for patients with diffuse malignant peritoneal mesothelioma has dramatically improved with cytoreductive surgery and intraperitoneal chemotherapy. Little is known about disease recurrence after treatment. We analyzed the time to and predictors of recurrence in a large cohort of optimally treated patients. We examined 113 patients completing a two-stage cytoreduction and intraperitoneal chemotherapy protocol. All patients achieved optimal surgical resection with completeness of cytoreduction (CC) score≤1 and were divided into two groups based on absence (Group A) or presence (Group B) of gross disease at the outset of the second operation. Predictors of disease recurrence and recurrence-free survival (RFS) were determined using Cox proportional hazard regression modeling, and estimates were obtained by using the Kaplan-Meier method. Forty-six percent of patients had no gross evidence of disease at the second operation; the remaining 54% were cytoreduced to CC≤1 (Group B). Forty-two percent of patients developed disease recurrence with a median recurrence-free survival of 38.5months for the cohort; 79% of these received a form of iterative treatment. There was no statistically significant difference in recurrence-free survival between Group A (median RFS: 44.6months) and B (median RFS: 35.5months) (log-rank test, p=0.06). Additionally, the only variable significantly associated with RFS was male gender (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.16-3.38). Absence of gross disease at the second operation was not statistically protective against recurrence compared with presence of quantifiable residual disease (Group B) that was effectively cytoreduced. Long-term disease surveillance is recommended, because recurrence continues years after treatment. Where a question of recurrence arises on surveillance, males may benefit from a higher degree of suspicion.

P3-132 - High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence

Recent reports have shown that endoplasmic reticulum (ER) stress is associated with cancer. However, the impacts of ER stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of ER stress-related genes (ERO1L, PERK, ATF6 and IRE1) and the outcome of lung adenocarcinoma. One hundred and twenty-six patients with surgically resected lung adenocarcinomas were subjected to an ER stress-related mRNA expression analysis using quantitative RT-PCR. The following parameters were analyzed for all the study patients: age, sex, disease stage, smoking status, lymph node invasion (ly), vascular invasion (v), and EGFR mutation status. We assigned patients to either a high expression group (H group) or a low expression group (L group) according to the expression levels of ER stress-related genes. High expressions of ER stress-related genes were observed in patients with lower stages of lung adenocarcinoma and minimal vascular invasion. A Kaplan-Meier analysis showed significant differences in recurrence-free survival (RFS) and overall survival between H group and L group. High IRE1 expression was an independent predictor of RFS among patients with lung adenocarcinoma (hazard ratio, 0.396; 95%confidence interval, 0.188 - 0.834; P = 0.015). IRE1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients.

Intraoperative Fentanyl Consumption Does Not Impact Cancer Recurrence or Overall Survival after Curative Colorectal Cancer Resection

Whether opioid use in cancer surgery would promote tumor dissemination in humans is inconclusive. We investigated the effect of intraoperative fentanyl dose on colorectal cancer (CRC) prognosis following resection in this retrospective study. A total of 1679 patients with stage I-III CRC undergoing tumor resection between January 2011 and December 2014 were evaluated through August 2016. Postoperative recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox regression models. Multivariable Cox regression analysis demonstrated no dose-response association between the amount of fentanyl dose and RFS (adjusted hazard ratio: 1.03, 95% CI: 0.89–1.19) or OS (adjusted hazard ratio: 0.84, 95% CI: 0.64–1.09). Patients were further classified into the high- and low-dose groups by the median of fentanyl dose (3.0 μg·kg−1), and there was no significant difference in RFS or OS between groups, either (adjusted hazard ratio: 0.93, 95% CI: 0.74–1.17 for RFS; 0.79, 95% CI: 0.52–1.19 for OS). We concluded that intraoperative fentanyl consumption has no impact on recurrence-free or overall survival in patients after curative CRC resection.

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan

BackgroundThe optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy.MethodsWe retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis.ResultsMedian recurrence-free survival was 1146 days (95% confidence interval [CI], 885–1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464–1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91–1.84).ConclusionsThere was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue.