bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and severity of postoperative complications following neoadjuvant therapy and full-thickness local excision for moderately advanced rectal cancer.
Authors: Abdalla Ahmed , Aref Amr , Alame Amer , Barawi Mohammed , Hawasl Abdelkader , Yakan Adli
Published: May 2019

e15167

Background: Trans-anal full-thickness local excision (LE) for patients with moderately advanced rectal cancer (MARC) whose tumors respond well to neoadjuvant therapy, is one approach for organ preservation. Some authors call for abandoning this procedure because it causes frequent and severe complications. We aim to report our post-operative complications rate and severity following this procedure. Methods: This is a retrospective review of the complications observed in 10 patients who underwent LE at our center between May 2017-January 2019. Primary outcomes were the presence and nature of complications associated with the treatment course. Results: Five patients were treated according to Phase II trial and received three months of FOLFOX chemotherapy followed by concurrent chemo-RT. Five additional patients received only concurrent chemo-radiotherapy as they were treated off protocol. Radiation therapy (RT) dose ranged between 45-54 Gy and the interval between completion of RT and LE ranged between 6-15 weeks; median 11.5 weeks. Gross residual disease was resected with no margin in nine patients. The size of removed specimens ranged between 6.8-1.4cm; median 2.2 cm with a depth of resection of 1.5-0.4 cm; median .6 cm. Two patients had a very low residual gross abnormality and the surgical resection extended to the dentate line. Both patients experienced grade III complications of severe pain, infection and fistula formation. Of the remaining 8 patients with tumors located between 3-8 cm from the anal verge, two patients developed grade II complications requiring a short course of antibiotics and symptomatic treatment. In both cases, symptoms resolved within one week. Conclusions: Post-operative complications in this setting are not prohibitive if LE doesn’t extend to the dentate line and the resection is limited to only residual abnormality with no mucosal margin. A complete pathological response, confirmed by LE after neoadjuvant therapy provides valuable prognostic information and can influence the intensity and burden of future follow up. The risk of surgical complications is acceptable in view of these advantages. LE remains a viable option in pursuing organ preservation for MARC when complete remission is achieved by neoadjuvant therapy.
Current treatment strategies and patterns of recurrence in locally advanced colon cancer.
Authors: Huynh Caroline , Minkova Stephanie , Kim Diane , Stuart Heather , Hamilton Trevor D
Published: May 2019

e15171

Background: Locally advanced colon cancer (LACC) is a frequent presentation and has a high rate of recurrence. The aim of this study was to evaluate current population-based strategies in LACC patients, and to analyze patterns of recurrence. Methods: We conducted a retrospective review of all patients treated at a regional cancer agency with a diagnosis of LACC between 2005 and 2015 treated with curative intent resection. Inclusion criteria were adults with T4 colon cancer, 16 cm above the anal verge, with no evidence of distant metastases. Descriptive statistics were used to define the study population. Kaplan-Meier and Cox-proportional hazards modeling were used for survival analysis. Results: 1394 patients with LACC were reviewed. Median age was 69 [IQR 60-77] and 49.3% were female. Primary tumor location was right-sided in 57.1% of cases. Most tumors were T4a (69.4%) and 39.4% were node positive. A total of 35.4% had urgent/emergent surgery, 46.4% were at least partially obstructed, 22.0% were perforated and 1.9% had a diverting ostomy as an initial operation. En-bloc multi-visceral resection occurred in 23.5% of cases. Positive margins were present in 14.3%. Only 1.6% had neoadjuvant chemotherapy and 0.8% had neoadjuvant chemoradiation. Adjuvant chemotherapy was delivered in 59.8% and adjuvant chemoradiation in 2.8%. Median follow up was 37 months. During follow up 681 (48.9%) patients died and 584 (41.9%) patients developed recurrence. In the entire cohort, rates of recurrences were local-regional (14.7%) and distant metastatic (35.1%). Overall survival for the entire cohort was 63 months [95% CI 55.7-70.3] and recurrence-free survival was 61 months [95% CI 38.8-83.2]. Multivariate analysis identified age (HR 1.03, 95% CI [1.02-1.05] p < 0.001), node negative status (HR 0.62, 95% CI [0.45-0.84] p = 0.002) and positive margin (HR 1.79, 95% CI [1.24-2.57] p = 0.002) as predictive of overall survival after adjusting for confounding factors. Predictive factors for recurrence-free survival were node negative status (HR 0.55, 95% CI [0.39-0.77] p < 0.001) and positive margin (HR 1.51, 95% CI [1.02-2.23] p = 0.038). Conclusions: Recurrence after curative intent treatment for LACC is common. Recurrence and survival patterns are significantly influenced by tumor nodal status and margin positivity.
LONG TERM opioid use in RURAL NON-metastatic colon cancer patients.
Authors: Araujo-Mino Emilio Paul , Bulbul Ajaz , Minhas Hamza , Bautista Adriana , Lentkowski Lisa , Khorsand-Sahbaie Masoud
Published: May 2019

e15174

Background: Cancer related pain and subsequent long-term opioid (LTO) use worsens the opioid epidemic and facilitates abuse. Non-metastatic colon cancer (CC) is a potentially curable malignancy and prescription opioid (PO) may increase risks of adverse events when CC has been eradicated. Methods: A retrospective study evaluated stage I-III CC patients between January 2013 and January 2018 across rural cancer clinics in New Mexico who received PO during their cancer diagnosis and treatment. It excluded patients with stage IV CC, concurrent malignancies and non-cancer pain. Descriptive statistics, Chi-square and logistic regression were performed to identify correlation and predictors of LTO use. Results: Among 197 patients identified, opioids were prescribed in 24% (48/197); 22 patients met inclusion criteria. Mean age was 65.1±9.8 years; 68% male; Stage I (4.5%), II (36.3%), III (59.1%). Adjuvant chemotherapy was given in 91% (20/22). Oxaliplatin regimen was used in 63.6% (14/22). One year after therapy, 27.3% (6/22) still had neuropathy. The rate of opioid use was 72.7% (16/22) at 3 months, 54.5% (12/22) at 6 months and 41% (9/22) at 12 months; 56.2% (9/16) of opioid users at 3 months were also using opioids at 12 months from initial prescription (X2 5.71 p = 0.046). Also, 75% (9/12) of opioid users at 6 months, continued using opioids at 12 months (X2 12.7 p = 0.0001). Patients with smoking history, unemployed and PO from a surgeon, were more likely to be LTO users at 12 months; however, it was not statistically significant. Conclusions: Non-metastatic CC patients who continue to use opioids at 3 months are at a significantly higher risk of LTO use at one year. Biological and social factors in rural communities can be important determinants of this use pattern. The challenges surrounding opioid use and the need for safe and effective alternative analgesics require urgent attention and regulatory discourse.
Liver findings and risk of recurrence in locally-advanced rectal cancer (LARC): An Italian retrospective cohort study.
Authors: Damato Angela , Besutti Giulia , Bonelli Candida , Venturelli Francesco , Giorgi Rossi Paolo , Vicentini Massimo , Pattacini Pierpaolo , Pinto Carmine
Published: May 2019

e15175

Background: Despite the combination of fluoropyrimidine chemotherapy and long course radiotherapy (50.4 Gy) followed by TME, LARC still results in 30% distant recurrence within 2-3 years after surgery. One of the most affected organs is the liver. We aimed to analyze if basal liver pathological alterations and drug-induced liver damages influence the liver recurrence. Methods: 50 patients (pts) with LARC treated with neoadjuvant chemoradiotherapy (NACRT) between June 2010 and June 2017 in a single center were included. Liver function tests (LFTs) including AST, ALT and GGT at baseline and after NACRT were evaluated. The first staging CT scan and, when available, post-NACRT CT scan were reviewed to assess steatosis (unenhanced liver density < 48 HU or liver-to-spleen ratio < 1.1), and liver volume. Associations of baseline LFTs and CT liver alterations and changes after NACRT with liver metastasis (LM) during follow-up were evaluated with Hazard Ratio (HR) and respective 95%CI calculated with Cox analysis. Results: The characteristics of pts were: 68% males, median age 60.4 ys (range 34-84), cTN stage II (32%) and stage III (64%). During a follow-up ranging from 1.5 to 7 ys, 17(34%) pts developed distant recurrence and 7(14%) LM. At baseline, 2 pts had GGT > 73 U/l and 11(22%) had steatosis. After NACRT, 4(9%) pts had AST > 40 U/I and/or ALT > 49 U/l with > 2-folds increase, 6 (40%) of the 15 pts with available unenhanced post-NACRT CT had steatosis development, or increase (≥10 HU density decrease), and 9 (27%) of 33 pts with available post-NACRT CT had a > 10% increase in liver volume. LM was associated with female sex (p = 0.016). Baseline steatosis, post-NACRT steatosis development or increase, > 10% liver volume and transaminase increase were associated with LM (HR = 3.36, 95%CI = 0.75-15.1; HR = 3.67, 95%CI = 0.33-40.7; HR = 2.91, 95%CI = 0.59-14.5; HR = 3.05, 95%CI = 0.33-27.72, respectively). All the reported associations almost disappeared, when considering all-sites of distant recurrence. Conclusions: Even if small numbers cannot exclude that associations are due to chance, baseline liver steatosis and post-NACRT liver damage may be involved in LM during follow-up of LARC.
Prognostic factors for severe diarrhea in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiation with capecitabine: A single-center cohort study.
Authors: Hartman Wesley , De Hoop Esther Oomen , Verhoef Cornelis , Nuyttens Joost , van Meerten Esther
Published: May 2019

e15176

Background: Chemoradiation with concomitant capecitabine (CRT) followed by total mesorectal excision is the standard of care for locally advanced rectal carcinoma (LARC). Grade ≥ 3 diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiotherapy. The aim of this study is to describe the risk factors of grade ≥ 3 diarrhea in patients with LARC during CRT. Methods: A single centre retrospective cohort study was conducted in our tertiary center. All patients with LARC treated with CRT from 2009 to 2015 were included. Patients with local recurrence who received CRT for the first time were also included. Univariate logistic regression analyses were used, followed by a multivariate analysis of the significant factors with backward selection at p < 0.05. Results: A total of 738 patients were included: 67% male, median age 64 years (range 17-88), 95% primary presentation. DPYD-testing was not performed upfront. In this cohort 69 patients (9%) developed ≥3 grade diarrhea. In the univariate analysis, factors significantly associated with ≥3 grade diarrhea were; female gender, age ≥65 years, body weight and decreased renal function (defined as MDRD GFR < 60 ml/min/1,73 m2). The following factors remained significantly associated with ≥3 grade diarrhea in the multivariate analysis; female gender (odds ratio (OR) 2.77, 95% confidence interval (CI) 1.54-4.99, p 0.001), age ≥65 years (OR 2.85, 95% CI 1.63-4.98, p < 0.001) and a lower bodyweight (OR 0.98, 95% CI 0.96-1.00, p 0.015). Conclusions: Female gender and age ≥65 years significantly increase the risk of grade ≥ 3 diarrhea caused by neoadjuvant CRT for LARC. So, older female patient must be closely watched during this treatment to intervene on time. The difference in toxicity between females and males might be explained by the pelvic anatomical differences between men and women. The found prognostic factors will be validated in a second cohort of patients with LARC treated with CRT. Besides, sarcopenia will be tested as a prognostic factor as well.
Neoadjuvant treatment of adenocarcinoma of the rectum: Historical analysis and correlation between pathological regression rate and the outcomes.
Authors: Basso Jeziel , Azevedo Sergio Jobim , Nassif Pereira Lima Marta , Damin Daniel C. , Liedke Pedro Emanuel Rubini , Moreira Luis Fernando , de Souza Pereira Fernando , Pereira Rodrigo Perez
Published: May 2019

e15177

Background: Treatment of locally advanced rectal cancer is based on chemoradiation associated with surgery. This treatment has high potential for curability. Tumor regression grade appears to be a prognostic factor and be influenced by the timing of surgery. Methods: A retrospective database was formed. We included patients submitted to neoadjuvant chemoradiotherapy and rectal surgery, treated at the Hospital de Clínicas, Porto Alegre. We analyzed outcomes, pathologic and treatment toxicity data. TRG was mensurated by the modified Ryan method, as the AJCC. We sought to analyze the better timing for surgery after chemotherapy, comparing the weeks after surgery with the rate of pCR. Statistical analysis was done with Kaplan Meier, Pearson's Chi-square and the Cox regression method. Results: We accrued 156 patients between 2006 and 2018. The rate of PFS at 3 and 5 years were 75% and 70%, respectively. The 5-year overall survival was 91%. The rate of pCR was 12.8%. TRG was an important prognostic factor. The absence of a pathological response (TRG 3) was associated with an increase in mortality, HR 3,148 (95% CI 1.6-12.2 P 0.003) and a decrease in PFS, HR 3,148 (95% CI 1, 7-5.8 P 0.0001). The 5-years PFS with TRG 0,1, 2 and 3 were 95%, 87%, 73.3% and 48%, respectively. Comparing the time between neoadjuvant treatment and surgery of less than 8 weeks versus 8 and 12 weeks versus above 12 weeks, the rates of pCR were 4.3%, 18.6% and 7.1% and the rates of TRG 3 were 32,6%, 18,6% and 57,1% (P 0.016). The chemotherapy regimens included 5FU bolus (75.1%) and capecitabine (19.1%). Doses of radiotherapy above 45 Gy were received by 80.5% of patients. Adjuvant treatment was not performed in 30.6% and 16.6% of these cases had positive pathological lymph nodes. The grade 3/4 adverse event rate was 21.6%. Conclusions: The outcomes found are favorable. The pathological tumor regression grade is an important prognostic factor. New strategies such as total neoadjuvant may play a role considering the rate of patients who cannot perform adjuvant chemotherapy. The time after neoadjuvant treatment seems to influence the tumor regression rate, especially between 8 and 12 weeks.
Investigating the effect of chemotherapy combined with ketogenic diet on stage IV colon cancer.
Authors: Furukawa Kenji , Shigematsu Kyousuke , Katsuragawa Hideo , Tezuka Toru , Hataji Kenichiro
Published: May 2019

e15182

Background: The effectiveness of carbohydrate restriction to limiting cancer growth has often been observed in in vitro and in vivo experiments; however, few cases of clinical efficacy have been reported. We examined the clinical effectiveness of chemotherapy with ketogenic diet for advanced cancer treatment. Methods: We administered chemotherapy with a modified medium-chain triglyceride (MCT) ketogenic diet at a ratio of 1.4:1 in 10 patients with stage IV recurrent colon cancer for one year and performed a conversion surgery in five of the cases. We followed-up for the next 3 years, compared the overall survival (OS) of the chemotherapy-only group of the stage IV colon cancer patients, and investigated the factors contributing to an improved OS. Results: Evaluations in the first year revealed a response rate of 21% and disease control rate of 64% for patients in the chemotherapy-only group. Patients in the ketogenic diet-chemotherapy combination group exhibited a response rate of 60%, disease control rate of 70%, and complete response rate of 50% for the five conversion surgeries. The time to conversion surgery was 4.0±0.9 months and the time to postoperative recurrence was 6.2±2.6 months. Regarding the duration of overall survival, there was no significant difference ( p value = 0.98) upon comparing the ketogenic diet group with the chemotherapy-only group (32.5 months and 37.9 months, respectively). However, overall survivals were 50 months, 23.0 months, and 32.5 months for the ketogenic diet-chemotherapy combination response group, ketogenic diet-chemotherapy combination non-response group, and chemotherapy-only group, respectively ( p value = 0.07). The ketogenic diet-chemotherapy combination response group tended to have a longer OS than the chemotherapy-only group. In addition, in the ketogenic diet-chemotherapy combination response group, introduction time was earlier than the ketogenic diet-chemotherapy combination non-response group for 5.7 months, with high serum ketone body levels and low blood sugar levels. Conclusions: Chemotherapy with ketogenic diet resulted in higher response and disease control rates than chemotherapy alone. Additionally, the conversion surgery rate was high and an improved OS could be expected. Therefore, ketogenic diet may be a supportive therapy to chemotherapy. Clinical trial information: 000029527.
Apatinib affects the proliferation, migration and apoptosis of esophageal cancer cells both in vitro and in xenografts by regulating Ras/Raf/MEK/ERK and JAK2/STAT3 signaling pathways.
Authors: Yu Jingping
Published: May 2019

e15501

Background: To investigate the effects of apatinib on esophageal cancer cells in vitro and xenograft models, and discuss the mechanisms of its actions. Methods: Used various assays to measure the different biological processes of esophageal cancer cells: used MTT assay to measure the proliferation rate; used transwell assay to determine the migration capacity and used colony formation assay to assess the clone formation rate. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression levels of VEGF and VEGFR2 were measured by qRT-PCR. The concentration of VEGF in the supernatant of cancer cell was assessed by ELISA. The expression levels of MEK, ERK, p-MEK, p-ERK, STAT3, p-STAT3, CHK2 and CDC2 after VEGF stimulation were detected by western blot. We also established human esophageal squamous carcinoma xenograft model in nude mice. The mice were randomly divided into healthy control group, low dose group (250mg) and high dose group (500mg), with 6 mice in each group. The tumor growth rate of each group was calculated, and the expression levels of VEGF and VEGFR2 in tumor tissues were detected by immunohistochemistry. Results: Apatinib inhibited the proliferation of esophageal cancer cell in a time-dependent (P < 0.05) and concentration-dependent (P < 0.05) manner; it also inhibited the cell migration capacity (P < 0.05) and colony formation rate (P < 0. 05). In addition, apatinib induced apoptosis in esophageal cancer cells and increased the proportion of cells in G2 / M phase (P < 0.05). The mRNA levels of VEGF (P < 0.05) and VEGFR2 (P < 0.05) and the protein levels of VEGF (P < 0.05) were also suppressed by apatinib. Western blot showed that apatinib could down-regulate the expression of p-MEK, p-ERK, STAT3, p-STAT3, CHK2 and CDC2 (P < 0.05). The inhibition rates of apatinib in esophageal carcinoma xenograft model was 29.25% and 19.96% for 250mg and 500mg drug treatment groups. Compared with healthy control group, the VEGF levels in drug treatment groups were not significantly different (P > 0.05), but the VEGFR2 levels were significantly decreased (P < 0.05). Conclusions: Apatinib can induce apoptosis of esophageal cancer cell KYSE-150 and ECA-109, and inhibit the cell proliferation, migration and colony formation. Moreover, apatinib can inhibit the tumor growth in esophageal carcinoma xenograft models. This inhibitory action of apatinib is related to the alterations in VEGF-related pathways such as Ras / Raf / MEK / ERK and JAK2 / STAT3 pathways.
Clinical implication of telomere length-related polymorphisms in gastric cardia adenocarcinoma.
Authors: Zhang Nasha , Yang Ming
Published: May 2019

e15502

Background: Aberrant telomere lengthening is a critical feature of malignant cells. Short leukocyte telomere length (LTL) confers elevated risk of gastric cardia adenocarcinoma (GCA). Multiple genome-wide association studies (GWAS) identified various single nucleotide polymorphisms (SNPs) associated with LTL in different ethnic populations. However, it remains largely unexplored how these genetic variants are involved in GCA susceptibility. Methods: We systematically screened GWAS-identified candidate SNPs and tested the impact of thirty polymorphisms in genes associated with interindividual LTL variation on GCA using two-stage case-control comparisons consisting of 1,024 GCA patients and 1,118 controls. Results: We observed that CXCR4 rs6430612, TERT rs10069690 and rs2853676 as well as VPS34 rs2162440 are significantly associated with GCA development. A 0.64-fold decreased risk of GCA is associated with the CXCR4 rs6430612 CT genotype compared with the CC genotype ( P= 0.002). On the contrary, the TERT rs10069690 TT genotype carriers had a 1.83-fold increased risk to develop GCA compared to the CC genotype carriers ( P= 5.8×10-6). We also detected a 2.17-fold increased OR for GCA that was associated with the TERT rs2853676 TT genotype ( P= 2.6×10-6). In addition, the odds of having the VPS34 rs2162440 GA genotype in GCA patients was 1.35 compared with the GG genotype ( P= 0.002). In stratified analyses, the association between TERT rs10069690 polymorphism and GCA was more pronounced in nonsmokers ( Pinteraction=9.7×10-5) and nondrinkers ( Pinteraction= 4.6×10-5). Conclusions: Our results highlight the importance of both LTL and LTL-related genetic variants to GCA predisposition.
A multicenter, single-armed, prospective phase II study of apatinib combined with chemotherapy neoadjuvant for locally advanced gastric cancer.
Authors: Lin JianXian , Huang Changming
Published: May 2019

e15508

Background: Molecular targeted therapy has made great progress in the treatment of gastric cancer. In some previous studies, apatinib, an oral small molecular of VEGFR-2 tyrosine kinase inhibitor, had been confirmed can improve OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, there is limited evidence about the safety and feasibility of apatinib combined with SOX regimen as neoadjuvant therapy for locally advanced gastric cancer (LADG). Methods: This is a multicenter, single-armed, prospective study. Patients with LAGC (cT2-4N+M0) without prior anti-cancer strategies were included. Patients were received 3 to 5 cycles (21 days a cycle) of neoadjuvant therapy using S-1 (po, 40-60 mg bid, day1-day14), oxaliplatin (iv, 130 mg/m2, day1), and apatinib (po, 500 mg qd). Apatinib was prohibited in the last cycle. The operation should be performed 2 to 4 weeks later of the neoadjuvant therapy. The primary outcome was safety of the neoadjuvant therapy. The secondary outcomes included R0 resection rate, objective response rate (ORR), and disease control rate (DCR). Results: A total of 30 patients from 7 centers in China were recruited between Sep. 1, 2017 and Aug. 31, 2018. There were 21 males and 9 females. The median age was 66 years (range 41-75 years). There were 25 patients with tumor response evaluation, 18 patients had partial response (PR), 6 patients had stable disease (SD), and 1 patient had progressive disease (PD). The ORR and DCR were 72.0% (18/25) and 96.0% (24/25), respectively. 10 patients discontinued the study (withdrew consent 8 patients, physical deterioration in performance status 1 patient, and Disease progression 1 patient). 20 patients received gastric surgery, the R0 resection rate was 100%, 3 patients had postoperative complication: one had intestinal obstruction and two had pneumonia (all Clavien-Dindo classification less than grade II). All patients were included for safety analysis. The incidence of adverse events (AEs) and grade 3/4 AEs were 56.7% (17/30) and 6.7% (2/30), respectively. The most common AEs were leucopenia (33.3%), liver function damage (6.7%), up-GI hemorrhage (6.7%), and hypertension (6.7%). Conclusions: This prospective study shows that neoadjuvant therapy using apatinib plus SOX brings clinical benefit to LAGC with a high disease control rate and tolerable adverse reactions. This study is registered at ClinicalTrials.gov and carries the following ID number: NCT 03192735. Clinical trial information: NCT 03192735.
Efficacy and safety of conversion therapy using chemotherapy plus anti-angiogenic therapy in unresectable gastric cancer.
Authors: Chen Lu chuan
Published: May 2019

e15510

Background: Conversion therapy has been a promising option for patients with unresectable gastric cancer (GC) (including Phase IV gastric cancer, N3, lymph node fusion and local progression patients). We aimed to investigate the efficacy and safety of S1/oxaliplatin chemotherapy plus apatinib, a novel inhibitor of VEGFR-2, in the conversion therapy for unresectable GC. Methods: This was a single-center, single-arm, open-label study. unresectable GC patients with unresectable factors were eligible for this study. Apatinib (500mg, qd) was administrated continuously, oxaliplatin (130mg/m2) on day 1, and S1 (<1.25m2, 40mg*2/d; 1.25-1.5m2, 50mg*2/d; >1.5m2, 60mg*2/d) on day 1-14 every 3 weeks. Treatment was given for 4-6 cycles preoperatively, but the last cycle did not include apatinib. The primary objective included R0 resection rate and safety profile of preoperative treatment. Results: Total 17 patients were enrolled, the median age was 57 (55.12±10.08) years old. The histological types were mainly signet ring cell carcinoma 10 (58.82%), poorly differentiated adenocarcinoma 5 (29.41%), and moderately differentiated adenocarcinoma 2 (11.76%). Among the 17 patients eligible for preoperative efficacy evaluation, 13 achieved partial response (PR), 3 achieved stable disease (SD), and 1 had progressive disease (PD), the overall response rate (ORR) was 76.5% and disease control rate was 94.1%. Of the 13 pts with PR, 1 refused consents for surgery, 12 patients underwent surgery and 9(75%) achieved R0 resection. During preoperative treatment, the incidence of adverse events (AEs) was 76.5%. The common hematologic AEs were neutropenia (64.7%), leukopenia (64.7%) and hemoglobin decrease (11.8%), and nonhematologic AEs included hyperbilirubinemia (11.8%), hand-foot syndrome (17.6%), oral mucositis (29.4%), fatigue (70.6%), proteinuria (5.9%). Conclusions: Combination of apatinib with S1/oxaliplatin chemotherapy could induce a sufficient conversion rate and achieve a relative high R0 resection rate for initially unresectable GC, with tolerable safety profile. Clinical trial information: ChiCTR-ONC-17010430 trial.
Impact of adjuvant treatment according to gastric cancer molecular subtypes.
Authors: De Castria Tiago Biachi , Amorim Larissa Costa , Ramos Marcus Fernando Kodama Pertille , Pereira Marina Alessandra , de Mello Evandro Sobroza , Faraj Sheila , Sabbaga Jorge , Hoff Paulo Marcelo
Published: May 2019

e15513

Background: The four subtypes of gastric adenocarcinoma (GC) identified by the Cancer Genome Atlas project (TCGA) have different molecular signatures and prognosis. Several centers have tried to classify GC using immunohistochemistry (IHC) and in situ hybridization (ISH), examining the tumors according to Epstein–Barr virus (EBV) status, microsatellite instability (MSI), aberrant E-cadherin expression and TP53 status. Here we aim to verify the impact of adjuvant/perioperative chemotherapy (ACT/PCT) or adjuvant chemoradiation (CRT) according to the molecular subtypes profile. Methods: We retrospectively reviewed all GC patients who underwent gastrectomy and D2-lymphadenectomy at our institution from a prospective collected medical database. Deficient DNA mismatch repair (dMMR), E-cadherin and p53 were evaluated by IHC for determining the MSI, genomically stable (GS) and chromosomal instability (CIN, with and without p53 aberrant) subtypes, respectively. EBV positivity was detected by ISH. Results: Among the 178 stage II/III patients included, 67 had surgery alone, 47 received ACT/PCT and 64 CRT. 16 had aberrant E-cadherin (GS, 9%), 33 dMMR (MSI, 18.5%), 74 aberrant p53 expression (CIN p53-aberrant, 41.6%), 104 normal p53 expression (CIN p53-normal, 58.4%) and 18 EBV-positivity (EBV, 10.1%). Two or more altered status were present in GC of 16 patients. When analyzed independently, Kaplan-Meier survival analysis showed that EBV, dMMR, CIN p53-normal and GS subtypes did not obtain any benefit of ACT/PCT or CRT in disease free survival (DFS) (p = 0.71; p = 0.33; p = 0.41; p = 0.21, respectively). Meantime, those treatments impact positively in DFS for EBV-negative, proficient MMR and non-GS (p = 0.01; p = 0.007; p = 0.01). CIN subtype with p53 aberrant obtained most benefit for ACT/PCT or CRT (p < 0.001). Conclusions: In accordance with other studies we achieved no benefit for adjuvant chemotherapy in patients with EBV, dMMR and GS GC subtypes. Patients with p53 aberrant expression had greater benefit for ACT/PCT or CRT. This simple method of classification can potentially help to tailor adjuvant treatment.
Apatinib in the treatment of non-operable or advanced gastric cancer: Evidence of efficacy and safety in a real-world study.
Authors: Xing Ligang , Cao Wei , Cui Gang , Zhang Huanhu , Shi Yiran , Wei Xin , Dong Yuting , Guo Chengye , Wang Bingping , Zhang Shu , Zou Zhiqiang , Zhang Zizhi , Sun Yahong , Yu Guohua , Guo Hongliang , Wang Deyou , Meng Qi , Li Changzheng , Wang Xixun , Yu Jinming
Published: May 2019

e15515

Background: Apatinib, a small molecule tyrosine kinase inhibitor, has been approved to use in patients with advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma after at least two systemic chemotherapy regimens in China. This study aims to observe the efficacy and safety of apatinib in real word clinical practice and preliminarily explore the characteristics of population with more clinical benefit. Methods: This study included patients with non-operative or advanced gastric cancer confirmed by histopathology or cytology, and did not intervene the regimen which was entirely determined by the clinicians and patients. Results: From April 16, 2018 to January 12, 2019, 732 patients enrolled, and all patients had been followed up at least once. Total 342 patients were eligible for efficacy evaluation. Among them, 43 patients achieved partial response (PR), 209 patients achieved stable disease (SD) and 90 patients experienced progression disease (PD). The overall response rate (ORR) was 12.55%, and the disease control rate was 73.6%. The mPFS have not yet reached. For patients ≥65 years, the ORR was 26.32%, and for patients < 65 years, ORR was 8.33%. For patients with non-signet ring cell carcinoma and signet ring cell carcinoma, the ORRs were 15.22% and 6.0%. For patients with and without organ metastasis, the ORRs were 15.25% and 3.75% respectively. The PFS analysis showed that, Combined chemotherapy and age > 65 may predict longer PFS. The OS analysis showed that, ECOG 0-1, combined chemotherapy, AFP positive and male predict longer OS. The overall incidence of adverse events was 84%. The most common adverse events were hypertension (28.8%), fatigue (22.4%), hand-foot syndrome (17.3%), anorexia (12.8%) and nausea (10.5%). Conclusions: Apatinib showed promising antitumor activity in patients with non- operable or advanced Gastric Cancer in this real word study. The prolonging survival benefits maybe could be attenuated by age <65, without organ metastasis, ECOG score >1, treatment regimen, normal AFP, and pathological diagnosis of non-signet ring cell carcinoma. Clinical trial information: ChiCTR1800015701.
Neoadjuvant versus adjuvant chemoradiotherapy for stage II–III esophageal squamous cell carcinoma: A propensity score-matched analysis.
Authors: Lv Jiahua , Li Tao , Wang Qifeng , Han Yongtao , Song Yuzhe , Liang Long , Chen Meihua , Fan Yu , Wu Lei , Peng Lin , Lang Jinyi
Published: May 2019

e15524

Background: Many clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation therapy in stage II–III squamous cell carcinoma (ESCC). However, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. Methods: A total of 206 patients with clinical stage II and III ESCC who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation were included. On the basis of the sequence of surgery and chemoradiation, the patients were divided into two groups: Neoadjuvant chemoradiation followed by surgery (neoadjuvant CRT group) and surgery followed by postoperative chemoradiation (adjuvant CRT group). Propensity score matching analysis was used to identify 62 well-balanced patients in each group for outcome comparison. Results: In all, 69 and 137 patients were in the neoadjuvant CRT group and adjuvant CRT group, respectively. Before matching, no differences were observed in the overall survival among the patients in these two groups (P = 0.209). After matching, the survival was similar between neoadjuvant CRT group and adjuvant CRT group (P = 0.933). The median survival times and 1, 3, 5-year overall survival (OS) rates for the neoadjuvant and adjuvant CRT groups were 40.4 versus 41.0 months, 83.3% versus 95.1%, 54.6% versus 54.0%, 37.0% versus 30.7%, respectively. In the subgroup analysis, patients with clinical T3/4 stage and N1 stage tumors were more likely to demonstrate an overall survival benefit from neoadjuvant CRT compared with adjuvant CRT. Conclusions: No survival and perioperative complications difference were observed among esophageal cancer patients in the neoadjuvant CRT and adjuvant CRT groups. However, neoadjuvant CRT is recommended for patients with clinical T3/4 stage and N1 stage tumors.
Paratracheal lymph node metastasis in operable localized esophageal and gastroesophageal junction adenocarcinoma.
Authors: Harada Kazuto , Hwang Hyunsoo , Wang Xuemei , Abdelhakeem Ahmed , Iwatsuki Masaaki , Blum Murphy Mariela A. , Maru Dipen M. , Weston Brian , Lee Jeffrey H , Rogers Jane E. , Thomas Irene , Shanbhag Namita , Bhutani Manoop S. , Nguyen Quynh , Ikoma Naruhiko , Badgwell Brian D. , Hofstetter Wayne Lewis , Baba Hideo , Ajani Jaffer A.
Published: May 2019

e15526

Background: Paratracheal lymph node (LN) is considered regional for esophageal cancer, but its metastatic rate and influence to survival remain unclear. We aimed to evaluate the frequency of paratracheal LN metastasis and its prognostic influence. Methods: 1199 patients with localized esophageal or gastroesophageal junction adenocarcinoma (EAC) (January 2002 and December 2016) in our Gastrointestinal Medical Oncology Database were analyzed. 1R, 1L, 2R, 2L, 4R, and 4L according to 8th AJCC classification were defined as paratracheal LN. Results: Of 1199 patients, 73 (6.1%) had positive parataracheal LN at diagnosis. The median overall survival (OS) in 73 patients with initial paratracheal LN involvement was 2.10 years (range, xx). Of 1071 patients who were eligible for recurrence evaluation, 70 patients (6.5%) developed positive paratracheal LN recurrences as first recurrence. The median time to recurrence was 1.28 years (range; 0.28-5.96 years) and the median OS after recurrence was 0.95 years (range; 0.03-7.89). OS in 35 patients who had only patatracheal LN recurrence was significantly longer than in patients who had with other distant recurrences (median 2.26 vs 0.51 years; p < 0.0001). Higher T stage (T3/T4) was an independently risk factor for paratracheal LN recurrence (OR 5.10, 95% CI 1.46-17.89). We segregated patients in 3 groups based on the distance from esophagogastric junction to tumor proximal edge (lower; ≤2cm, middle; 2.0-7.0cm, higher; > 7.0cm), positive paratrachal LN metastases were more frequent in the proximal tumors (lower 4.2%, middle 12.0%, higher 30.3%; Cochran-Armitage Trend test, p < 0.001). Conclusions: Paratracheal LN metastases were associated with shorter survival in localized EAC patients. Careful investigation and surveillance for paratracheal LN are warranted.
Predictors of peritoneal metastasis in gastric cancer.
Authors: Kaplieva Irina V. , Kit Oleg I. , Frantsiyants Elena M. , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Samoylenko Nikolay S. , Kharagezov Dmitry A.
Published: May 2019

e15528

Background: Carcinogenesis is a complex process with still poorly understood mechanisms allowing cancer cells to disseminate from the primary tumor, spread in the body and colonize other organs forming secondary tumors – metastases. The ability of some distant organs to attract malignant cells may be caused by factors released by primary tumors. The purpose of the study was to determine levels of oncofetal proteins CA-19.9, CA-125, CA-72.4 and He-4 in tissues of gastric cancer (GC) and its metastatic niches, the peritoneum and omentum. Methods: The study included 62 patients: 21 (10 men, 11 women) – gastric cancer with peritoneal and omental metastases T3-4аN0-3M1; 24 (15 men, 9 women) – gastric cancer without metastases T3-4аN0-3M0; 17 (6 men, 11 women) – non-cancer patients (controls). Levels of oncofetal proteins were measured by ELISA in tissues of the peritoneum, greater omentum, and gastric tumors. Results: Levels of practically all studied factors were elevated in tissues of GC, omentum and peritoneum. Levels of He-4 and CA-19.9 in all tissues of patients with T3-4аN0-3M1 increased higher than in the majority of patients with T3-4аN0-3M0: in GC – respectively by 2.6 and 1.8 times (p < 0.05), in the omentum – respectively by 24.4 and 4.8 times, in the peritoneum – respectively by 2.1 and 8.5 times. Omental tissues of patients with advanced cancer showed a higher increase in levels of CA-72.4 and CA-125 as well – by 6.1 and 2.1 times, respectively. A small number of patients with T3-4аN0-3M0 gastric cancer, who had CA-19.9 in the omentum and peritoneum as high as in patients with T3-4аN0-3M1, developed metastases in the corresponding tissues 4-6 months after the study. Conclusions: The content of oncoprotein markers in tissues of the peritoneum and omentum is one of the factors associated with metastatic characteristics of GC, and CA-19.9 level can serve as an informative laboratory test for the predictive assessment of the further disease development.
Urokinase secretion by gastrointestinal adenocarcinoma.
Authors: Kozlova Larisa S. , Kit Oleg I. , Frantsiyants Elena M. , Gevorkyan Yuriy A. , Maslov Andrey A. , Dzhenkova Elena A. , Samoylenko Nikolay S. , Aleynov V. I. , Duritskiy Maksim N.
Published: May 2019

e15529

Background: The serine protease urokinase plasminogen activator (uPA) plays an important role in growth and invasion of malignant tumors. The purpose of the study was a comparative analysis of uPA activity (uPA-act) and its antigen (uPA-Ag) content in adenocarcinoma (A) of the esophagus (EA), stomach (SA), pancreatic head (PHA), sigmoid colon (SCA) and rectum (RA). Methods: Tissues of A, perifocal tissues (PT) and resection line tissues were studied by ELISA in 144 patients (39-73 years) with EA (n = 12, G2, T2-3N0-1M0), SA (n = 28, G2, T2-3N0-1M0), PHA (n = 46, G2, Т2-4N0M0), SCA (n = 31, G2, T2-3N0-1M0) and RA (n = 26, G2,T2-3N0-1M0). Statistical analysis was performed using the Statistica 10 program. Results: The levels of uPA-Ag in gastrointestinal A decreased from SA to PHA: SA˃RA˃SCA˃EA˃PHA (p < 0.01). The uPA-Ag levels in A were higher than in the resection line in all cases (p < 0.01). PT levels of uPA-Ag decreased from SA to PHA: SA˃SCA˃RA˃EA˃PHA (p < 0.01). In EA and PHA, PT levels of uPA-Ag were lower than in resection line tissues (p < 0.01), while in SA, SCA and RA they were higher (p < 0.01). Levels of uPA-act were similar in SA and SCA, while in EA and RA they were 1.2 (p = 0.4324) and 1.3 (p = 0.4012) times lower, and in PHA – 40.0-52.5 times lower (p < 0.01) compared to all A samples. The uPA-act in PT was the highest in SCA; 1.4 times lower in SA and RA; 1.7 times lower in EA; 30.9 times lower in PHA. The levels in PT were higher than in the resection line in all cases (p < 0.01). The resection line tissues in EA showed the maximal uPA-Ag content, while their uPA-act was similar to that in other tumors. Levels of uPA-Ag and uPA-act in resection line tissues in other tumors varied but were comparable. Estimated uPA-Ag/uPA-act coefficients in the resection line in SCA and RA were 20.4 and 29.5, respectively; in EA and PHA – 102.0 and 34.8, respectively. Conclusions: Adenocarcinomas of the esophagus, stomach, pancreatic head, sigmoid colon and rectum secrete uPA-Ag and uPA-act into surrounding tissues. The rate of uPA-Ag secretion by the tumor and its activation into uPA-act in pancreatic head cancer differ from that in other tumors.
Esophageal cancer: Five years of experience in an oncological reference center.
Authors: Cessa-Zanatta José Carlos , Alcorta-Nuñez Fernando , Salazar-Mejía Carlos Eduardo , Muñoz-Ayala Juan Manuel , Gonzalez-Alcorta Celia Beatriz , Hernandez Barajas David , Gonzalez-Guerrero Juan Francisco , Vidal-Gutiérrez Oscar , Alcorta-Garza Adelina
Published: May 2019

e15536

Background: Squamous cell carcinoma and adenocarcinoma represent approximately 95% of malignant tumors of the esophagus. For most cases of the 20th century, squamous cell carcinoma was the predominant lineage. In the 1960s, squamous cell carcinoma accounted for more than 90% of all esophageal tumors in the United States of America, and adenocarcinoma was considered so uncommon that some oncological associations questioned its existence. However over time the incidence of esophageal adenocarcinoma (predominantly in the distal esophagus and gastroesophageal junction) has increased dramatically in Western countries, with adenocarcinoma now causing more than 60% of all esophageal cancers in the United States of America, unlike the rest of the world, where squamous cell carcinoma continues to predominate. Squamous cell carcinoma and adenocarcinoma differ in a significant number of clinical features, including tumor location and predisposing factors. Smoking and alcoholism are major risk factors for the development of squamous cell carcinoma, while the Barrett's esophagus with intestinal metaplasia (a complication of gastroesophageal reflux disease), obesity, and smoking are the risk factors related to adenocarcinoma of the esophagus. Objectives: To determine the incidence of esophageal adenocarcinoma in Mexico and its main characteristics, such as epidemiology, histological type and main risk factors. Methods: A descriptive analysis was conducted in which the histological type, age of diagnosis, location, age of the patients and risk factors were compared. Results: Average age on the studied population was 67.4 years (minimum 37, maximum 91); 74.3% of the subjects were male and 20.4%, female. It was found that the predominant histological type was Adenocarcinoma in 40.7% against 28.3% of the Epidermoid. Average age of diagnosis was at 65.88 years (minimum 37, maximum 89). In frequency of localization, lower third in 22.1%, union GE in 20.4%, middle third in 15%, and upper third in 12.4%). The predominant risk factors in our study were smoking (31%), alcoholism (36.3%) and GERD (12.4%). Conclusions: Oesophageal adenocarcinoma continues to be the most prevalent presentation of esophageal cancer in our population, despite epidemiological changes over time.
Postoperative adjuvant chemotherapy for thoracic pathological T3N0M0 esophageal cancer: A propensity score-matched analysis (APEC Study 1).
Authors: Wang Qifeng , Li Tao , Han Yongtao , Li Qiang , Peng Lin , Xie Tianpeng , Fang Qiang , Yang Xiaojun , Zhuang Xiang , Dai Wei , Jiang Yingchun , Wang Yi , Lv Jiahua , Wu Lei , Cao Bangrong , Lan Mei , Lang Jinyi
Published: May 2019

e15537

Background: The role of postoperative chemotherapy (POCT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed . The aim of this study was to investigate whether POCT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with operation alone. Methods: This study included 604 patients with pT3N0M0 TESCC who were treated at Sichuan Cancer Hospital from January 2009 to December 2017. The patients were divided into two groups: a surgery plus postoperative chemotherapy group (PORT group) comprising Surgery alone patients who underwent after an R0 resection and a surgery group (S group). Propensity score matching was used to create patient groups that were balanced across several covariates (n= 246 in each group). Outcome measures included overall survival (OS), disease free survival (DFS). Results: In the whole group 5-year OS and PFS were 58.4% and 56.0%. In the overall study cohort, 5-year OS (68.3% versus 50.4%, p < 0.0001) and DFS (65.5% versus 45.8%, p < 0.0001) rates were significantly higher in the POCT group than in the S group. These data were confirmed in the matched samples (5-year OS, 68.3% versus 49.5% [p < 0.0001]; DFS, 65.5% versus 42.5% [p < 0.0001]). Multivariate Cox analyses in the matched samples revealed that surgery and postoperative POCT were independently associated with longer OS (hazard ratio = 0.553, 95% confidence interval: 0.391–0.726, p < 0.0001) and longer DFS (hazard ratio = 0.556, 95% confidence interval: 0.416–0.744, p < 0.0001) than resection alone. Subgroup analysis found : POCT with IIA in pT3N0M0 have not longer OS and DFS ( p = 0.122 and p = 0.193). POCT with IIB in pT3N0M0 have the longer OS and DFS(p < 0.0001 both). Conclusions: Postoperative adjuvant Chemotherapy is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.