bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating multiple “omics” analyses, on a triage concept, for effective case selection followed by diagnostic colonoscopy.
Authors: Thyparambil Sheeno P. , You Jin , Liu Kang , Sun Hui , Peng Junjie , Cai Sanjun , Li Yaqi , Bao Pingping , Li Qing , Zhang Yani , Li Zheng , Yang Jingzhi , Yin Ziyu , Yao Xiaoming , Zhu Xiurui , Hao Shiying , Heaton Robert , Schilling James , Sylvester Karl G. , Ling Xuefeng B. ,   OncoPlex Diagnostics
Published: February 2020

244

Background: Implementation of population screening for colorectal cancer (CRC) before colonoscopy can reduce the challenge of the overall capacity of bowel examination and improve survival. Blood based CRC assessment biomarkers, on a triage concept, can lead to improved selection to colonoscopy and cost-effective CRC care. Methods: Innovative multi-omics approaches, with global and targeted LCMS data production (metabolomics, lipidomics, and 2D proteomics) and integrative data analytics, were applied to discover serological biomarkers to assess nonadvanced adenoma and identify stage I/II colorectal bowel lesions. A cohort of 2396 normal, 660 adenoma, 953 stage I, and 101 stage II blood samples, was constructed to discover screening biomarkers to support case finding of patients at high risk for nonadvanced adenoma and stage I/II cancer for subsequent diagnostic colonoscopy. Results: A three-analyte mProbe panel was constructed which outperformed the commercial assays of plasma methylated septin 9 and fecal Cologuard tests. Sensitivity: (1) nonadvanced adenoma–Cologuard 17.2%, mProbe 76.0%; (2) stage I-III-Cologuard 93.3%, stage I-II Septin 9 (ARUP laboratories) 77%, stage I-II mProbe: 92.3%. Specificity–Cologuard 89.8%, Septin 9 (ARUP laboratories) 88%, mProbe 90.7%. Conclusions: mProbe triage concept of a blood-based protein biomarker panel promises the precision to allow future CRC screening, and reduce the low-risk utilization of unnecessary, unpleasant and risk-associated bowel examinations.
The potential in artificial intelligence-driven radiomic signature to predict survival in patients with metastatic colorectal cancer treated with cetuximab-based therapy.
Authors: Dercle Laurent , Lu Lin , Schwartz Lawrence Howard , Qian Min , Tejpar Sabine , Eggleton Peter , Zhao Binsheng , Piessevaux Hubert
Published: February 2020

247

Background: This analysis was undertaken to forecast survival and enhance treatment decisions for patients (pts) with colorectal cancer (CRC) with liver metastases sensitive to folinic acid, fluorouracil and irinotecan (FOLFIRI) alone [F] or in combination with cetuximab [FC] using simple quantitative radiomic changes between CT scans at baseline and 8 weeks. Methods: We retrospectively analyzed 667 pts with KRAS-unselected metastatic CRC in NCT00154102 treated with F and FC. CT quality was classified as high (HQ) or standard (SQ), and four data sets were created and named by treatment quality. Pts were randomly assigned 1:2 to training or validation sets: FCHQ, 38/78 pts; FCSQ, 62/124 pts; FHQ, 51/78 pts; FSQ, 78/158 pts. A machine-learning signature was trained using data set FCHQ to classify pts as treatment-sensitive or treatment-insensitive using just 4 of 3,499 potential radiomic imaging features. Performance was calibrated/validated using ROC curves. Hazard ratios (HRs) and Cox regression models were used to evaluate association with overall survival (OS). Results: The signature used decrease in tumor heterogeneity plus boundary infiltration to successfully predict sensitivity to FC (FCHQ: AUC, 0.80; FCSQ: AUC, 0.72) but failed with non-cetuximab regimens (FHQ: AUC, 0.59; FSQ: AUC, 0.55). The radiomic signature outperformed existing biomarkers ( KRAS mutational status and tumor shrinkage by RECIST 1.1) for sensitivity to cetuximab-based therapy and was strongly associated with OS in the cetuximab-containing sets FCHQ (HR, 44.3; p = 0.0001) and FCSQ (HR, 6.5; p = 0.005). Conclusions: This signature, derived from simple radiomic analysis of tumor imaging phenotype using only standard-of-care CT scans, appeared to be treatment-specific and was superior to all tested prognostic biomarkers. The signature provided early prediction of sensitivity and survival and could be used to guide treatment continuation decisions.
Effect of weight, obesity, and other co-morbidities on mortality of colon cancer patients.
Authors: Sing Kevin , Tran Valerie , McClish Donna , Matin Khalid
Published: February 2020

25

Background: There have been reports implicating underweight status as well as obesity with lower survival in colorectal cancer patients, but data has been inconsistent. Methods: In this retrospective observational study, we gathered pre-treatment data on BMI and other co-morbidities from 423 colon cancer patients who underwent surgical resection (stages I to III) or were metastatic at diagnosis (stage IV) at VCU Medical Center from 2005 to 2018 and analyzed their survival outcomes. Results: Compared to patients with a normal BMI, patients with underweight status (BMI < 18.5) have a trend towards higher all-cause mortality (HR 1.66, 95% CI 0.67-4.12). Patients with overweight BMI (25-29.9) and obese BMI ( > 30) have a trend towards improved mortality (HR 0.67, 95% CI 0.46-0.98) (HR 0.75, 95% CI 0.53-1.07) respectively. The p-value was 0.0675. We also found that pre-existing diabetes mellitus is associated with increased all-cause mortality (HR 1.43, CI 1.03 to 1.98, p < 0.05), as well as the use of aspirin at diagnosis (HR 1.60, CI 1.16 to 2.21, p < 0.05). Conclusions: Our results are similar to previous findings that patients with underweight status have worse mortality outcome, suggesting the importance of nutritional status prior to starting treatment. We also found that overweight and obese patients have trends towards improved survival compared to normal weight patients. Future focus can be directed to see whether overweight or obesity status past diagnosis affect survival trends. Aspirin use at diagnosis in our study population is associated with worse mortality outcome; literature is conflicting with outcomes and pre-diagnosis aspirin use. Our findings are similar for both locoregional colon cancers as well as metastatic disease. Research should be directed at seeing what kind of interventions such as nutrition or rehabilitation can be used to ameliorate the increased mortality trend in the underweight status group of patients.
Changes in the proportion of patients presenting with early stage colon cancer over time among Medicaid expansion and nonexpansion states.
Authors: Hao Scarlett , Snyder Rebecca A , Irish William , Parikh Alexander A.
Published: February 2020

251

Background: In 2010, the Affordable Care Act required insurance plans to cover preventative screening, and the Medicaid expansion provision enabled participating states to increase Medicaid coverage of uninsured individuals. The aim of this study was to determine whether the proportion of patients diagnosed with early vs. late stage colon cancer (CC) at Commission on Cancer (CoC) facilities differed over time within states that expanded Medicaid in January 2014 (MES) vs. non-Medicaid expansion states (NMES). Methods: A hospital-based cohort study of patients diagnosed with CC from 2006-2016 was performed using the National Cancer Database. Uninsured and Medicaid-insured patients in MES were compared with patients in NMES. Patients with Medicare, private, or government insurance were excluded. The observed proportions of patients with early (AJCC I-II) vs late (III-IV) stage within each cohort were compared over time. Propensity score adjusted probability of early stage at presentation was determined among patients residing in MES and NMES. Results: The study cohort included 10,289 patients in MES and 15,173 patients in NMES. Compared to MES, a greater proportion of patients in NMES were black (33.4% vs 24.0%), had a median income < $38,000 (39.7% vs 28.2%), and resided in a state with ≥21% of the population without a high school degree (37.4% vs 28.1%). The proportions of early stage CC in both cohorts in 2006 were similar. In NMES, this proportion remained constant over time until 2014 and declined by 0.8% per year after 2014. Within MES, the proportion of early stage CC increased by 0.6% per year until 2014 and 0.9% per year after 2014. By 2016, the absolute difference in the propensity adjusted proportion of early stage CC between cohorts was 8.8% (39.7% vs 30.9%, p < 0.001). Conclusions: Following Medicaid expansion in 2014, the proportion of patients presenting to a CoC facility with early stage CC increased over time within MES and declined in NMES. Further investigation, including population-based research, is warranted to determine if enrollment in Medicaid improves access to colorectal cancer screening and leads to earlier stage at diagnosis.
Bowel anastomosis before or after HIPEC: A prospective comparative study in patients undergoing CRS+HIPEC for peritoneal surface malignancy at a tertiary care cancer center in India.
Authors: Somashekhar S.P. , C. Rohit Kumar , Rajgopal Ashwin K. , Zaveri Shabber , Yethadka Ramya , Rauthan Amit
Published: February 2020

254

Background: To do bowel anastomosis before or after HIPEC has been debated since the time heat is being used for intraperitoneal chemotherapy after cytoreductive surgery. We report our experience of impact of heat on anastomosis and leak rates. Methods: All patients diagnosed with peritoneal surface malignancy eligible for CRS+ HIPEC as per institution protocol had bowel restoration being performed with stapler & second layer taken. Our institution has two teams, of which one performs anastomosis before and one after HIPEC. All the data was entered prospectively in the HIPEC registry and is being analyzed to see the effect of heat on anastomosis. Results: 220 patients underwent CRS+ HIPEC of which organ of origin was colorectal 39%, stomach 20%, mesothelioma 11%, ovary 20% and others 10%. Upfront cases were 12%, interval 58% & recurrent 30%. Prior surgical score was 0 (62%), 1 (11%), 2 (23%), 3 (4%). 100 patients were in group that had anastomosis before HIPEC and 120 patients in other. Mean PCI 13.4±4.5, blood loss 1250±553.9 ml, duration of surgery 9.5±2.4 hrs, duration of hospital stay 9±3.5 days. Overall 57.05% had bowel resections, of which large bowel was 47.8%, small bowel 17.7%, stomach 6.13%. 19.6% required multivisceral resection & stoma rate was 11.1% for whole group. Both the group had almost same number of total (55.4 %vs 58.6%), small (15.3%vs16.5%) & large bowel resections (44.3%vs 49.5%). We had 4 (1.84%) leak overall, of which 2 were in either groups. Overall G3-4 morbidity was 28.4%, surgical G3-4 was 12.5%, perforation 3.6%, obstruction 1.84%, re exploration was 9.2%. 30-day mortality was 4.9%. Conclusions: We conclude that anastomotic integrity, leak rates & complications related to small or large bowel restoration is same either before or after HIPEC as we observed no difference in our study. However, since this is not a randomized study a well-designed multi-institutional randomized study needs to be planned for stronger evidence of the same.
Results of the JAVELIN Gastric 100 phase 3 trial: avelumab maintenance following first-line (1L) chemotherapy (CTx) vs continuation of CTx for HER2− advanced gastric or gastroesophageal junction cancer (GC/GEJC).
Authors: Moehler Markus H. , Dvorkin Mikhail , Ozguroglu Mustafa , Ryu Min-hee , Muntean Alina Simona , Lonardi Sara , Nechaeva Marina , Campos Bragagnoli Arinilda Silva , Coskun Hasan Senol , Cubillo Gracián Antonio , Takano Toshimi , Wong Rachel , Safran Howard , Vaccaro Gina M. , Boku Narikazu , Conti Ilaria , Hong Janet , Xiong Huiling , Taieb Julien , Bang Yung-Jue
Published: February 2020

278

Background: We report the primary analysis of JAVELIN Gastric 100, which compared avelumab (anti–PD-L1) maintenance after 1L CTx vs continued CTx in patients (pts) with GC/GEJC. Methods: In this global, open-label, phase 3 trial (NCT02625610), eligible pts had previously untreated, unresectable, locally advanced/metastatic (LA/M) HER2− GC/GEJC. Pts without progressive disease (PD) after 12 weeks of 1L oxaliplatin/fluoropyrimidine induction were randomized 1:1 to avelumab 10 mg/kg Q2W switch maintenance or continued CTx, stratified by region (Asia vs non-Asia). Primary endpoint was overall survival (OS) post induction in all randomized or PD-L1+ (≥1% of tumor cells, 73-10 assay) pts. Results: 805 pts received induction CTx and 499 pts were randomized (avelumab, n = 249; CTx, n = 250). At data cutoff (Sep 13, 2019), minimum follow-up was 18 months. In the avelumab and CTx arms, median OS post induction/randomization was 10.4 months (95% CI 9.1-12.0) vs 10.9 months (95% CI 9.6-12.4), hazard ratio (HR) 0.91 (95% CI 0.74-1.11; p = 0.1779); 24-month OS rates were 22.1% (95% CI 16.8-28.0) vs 15.5% (95% CI 10.8-20.9), respectively. The HR for OS in PD-L1+ pts (n = 54) was 1.13 (95% CI 0.57-2.23). No OS trend was seen in Asian pts (n = 114; HR 0.90 [95% CI 0.59-1.36]) or other subgroups, except for a potential benefit with avelumab in pts with no metastatic sites at randomization (n = 60; HR 0.52 [95% CI 0.28-0.98]). Progression-free survival was similar between arms (HR 1.04 [95% CI 0.85-1.28]). In the avelumab vs CTx arms, objective response rates (post randomization only) were 13.3% (95% CI 9.3-18.1) vs 14.4% (95% CI 10.3-19.4), and 12-month rates for duration of response were 62.3% (95% CI 40.9-77.9) vs 28.4% (95% CI 13.2-45.7), respectively. Treatment-related adverse event rates (all grades/grade ≥3) were 61.3%/12.8% with avelumab and 77.3%/32.8% with CTx. Conclusions: Avelumab maintenance showed clinical activity and favorable safety vs continued CTx in pts with LA/M GE/GEJC; however, JAVELIN Gastric 100 did not meet its primary objective of demonstrating superior OS in the randomized or PD-L1+ population. Clinical trial information: NCT02625610.
Hyperthermic intraperitoneal chemotherapy post cytoreductive surgery in management of peritoneal carcinomatosis of colorectal primaries: Tertiary center experience.
Authors: Sobh Ahmed Badran , Al-Wusaibie Ahmed , Elshenawy Mahmoud Abdelsatar , Abdelgawad Marwa Ismail , Hakeam Hakeam , Azzam Ayman , AbdelRehem Rania Naguib , Al-Yahya Zyad , Amin Tarek
Published: February 2020

28

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to Cytoreductive surgery (CRS) has survival benefit observed in management of Peritoneal Carcinomatosis (PC) from Colo-rectal cancer (CRC)origin. We report the outcomes and prognostic factors of patients with CRC, who presented with PC and underwent CRS and HIPEC at King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia. Methods: Patients presented with PC from CRC origin and underwent CRS and HIPEC; from February 2009 to September 2015 were recruited. Results: 52 patients identified. A total of 55 CRS procedures were performed, where 3 patients underwent repeated CRS and HIPEC for tumor recurrence. All except 3 used mitomycin-C for HIPEC, the remaining received either melphalan (2 patients) or cisplatin plus mitomycin-C regimen (1 patient). Melphalan used for patients who underwent repeated HIPEC as 2nd line chemotherapeutic agent. Intraoperative Radiation therapy performed in 5 patients with tumor invading the surrounding structures, where performing a safe or complete resection was either technically difficult or carried high risk. Complication assessment by Clavien-Dindo score, 62 % grade (I-II), while 31% had grade (3–4). Two patients (3.6%) died postoperatively; both from sepsis. Respiratory complications were the most commonly encountered morbidities. The 5-year overall survival(OS) was 50% with disease free survival (DFS) 29.5%. Univariate analysis showed poor OS and DFS encountered in; Signet-ring tumors (p < 0.0001) for both, peritoneal cancer index (PCI) ≥ 6 (p < 0.0009) for both, completeness of cytoreduction(CC) score >1 (p < 0.0001) for both, and high 3-month postoperative carcinoembryonic antigen value (p <0.0001) for both. In multivariate analysis; DFS was significant for (PCI) ≥ 6 (p < 0.0131) and (CC) score >1 (p < 0.0031) while PCI > 6 was the only significant factor (p < 0.0030) for OS. Conclusions: Addition of HIPEC to CRS was safe, and improved survival in patient with peritoneal Carcinomatosis of colo-rectal origin. PCI and CC score are prognostic factors of survival, signet-ring subtype may not benefit of this procedure.
Early results of the randomized, multicenter, controlled evaluation of S-1 and oxaliplatin as neoadjuvant chemotherapy for Chinese advanced gastric cancer patients (RESONANCE Trial).
Authors: Wang Xinxin , Li Shuo , Xie Tianyu , Lu Yixun , Guo Xin , Lin Chen
Published: February 2020

280

Background: Perioperative chemotherapy brings potential benefits to growing patients with gastric cancer based on several clinical trials including MAGIC, ACTS-GC, CLASSIC and INT-0116. However, the effect of neoadjuvant therapy before D2 gastrectomy remains pending. According to phase II clinical trials, SOX regimen as neoadjuvant chemotherapy is associated with increased rate of D2 lymph nodes dissection and R0 resection. We hypothesize that SOX regimen can improve survival of patients with gastric cancer. Methods: Through CT, EUS and laparoscopic exploration, patients with gastric cancer on the stage IIA-IIIC were included in the study and divided into 2 groups randomly. Patients in neoadjuvant group received 2-4 cycles of SOX before surgery and 4-6 cycles after surgery, while patients in no neoadjuvant group received 8 cycles after surgery. The primary endpoint was 3-y DFS and the secondary endpoint were 5-y OS, ORR, D2/R0 resection rate and side effect. Results: A total of 772 patients were enrolled in the study between September 2012 and July 2019. After neoadjuvant therapy, the downstaging was found in neoadjuvant group (261/386, 67.6%). The pathological efficiency rate and pCR rate of neoadjuvant group were 67.8% and 23.6% respectively. The R0 resection rate in neoadjuvant group was significantly higher than that in adjuvant group(73.1% vs 58.1%, p < 0.05). There was no difference in terms of surgical time, blood loss, postoperative complications and hospital stay. Conclusions: SOX makes increased rate of R0 resection, acceptable adverse effect and no impression on surgeries, which suggest that perioperative chemotherapy using SOX can prolong median survival time, DFS and OS. Clinical trial information: NCT01583361.
Access to care and outcomes for noncurative esophagogastric cancer: A population-based geographic study.
Authors: Yee Elliott Kenneth , Coburn Natalie , Zuk Victoria , Davis Laura E , Mahar Alyson , Liu Ying , Gupta Vaibhav , Darling Gail Elizabeth , Hallet Julie
Published: February 2020

284

Background: Esophagogastric cancer (EGC) carries a heavy mortality burden owing largely to high rates of unresectable disease at diagnosis. Among patients not undergoing curative-intent therapy, access to care may vary. We examined the geographic distribution of care delivery and survival across a jurisdiction, and its relationship with distance to cancer centres (CCs), for non-curative EGC. Methods: We conducted a population-based analysis of adults with non-curative EGC from 2005-2017 using linked administrative healthcare datasets in Ontario, Canada. Outcomes were medical oncology consultation, receipt of chemotherapy, and overall survival (OS). We used geographic information system analysis to map locations of CCs and outcomes across census divisions. Regions of discordance between care use and OS were identified with bivariate choropleth maps. Multivariable modified Poisson models assessed the relationship between distance to the nearest CC and outcomes, adjusting for demographic, clinical, and socioeconomic factors. Results: Of 10,228 patients surviving a median of 5.1 months (IQR: 2.0-12.0), 68.6% had medical oncology consultation and 32.2% received chemotherapy. Regions of comparable OS and care delivery were clustered throughout the province. CCs were distributed unevenly, with higher levels in Southern Ontario. Higher-level CCs clustered in regions with higher rates of consultation, chemotherapy use, and OS. Each increment in distance from location of residence to the nearest CC (11-50, 51-100, and ≥101 km) was associated with lower likelihood of seeing medical oncology and receiving chemotherapy, and inferior OS, compared to ≤10 km. Conclusions: A third of patients with non-curative EGC did not see medical oncology, and the majority did not receive chemotherapy. Care delivery and OS exhibited high geographic variability. Location of residence influenced access to care and OS, with inferior outcomes for those living further from a CC. These findings are important for designing interventions and policies to reduce disparities in access to care and outcomes for non-curative EGC.
Prognostic value of circulating tumor DNA (ctDNA) detection during adjuvant chemotherapy in patients with stage III colorectal cancer: The interim report of a prospective, observational study.
Authors: Peng Junjie , Li Yaqi , Mo Shaobo , Ma Xiaoji , Hu Xiang , Zhang Long , Huang Dan , Cai Sanjun
Published: February 2020

29

Background: Adjuvant chemotherapy (ACT) is the standard treatment for stage III colorectal cancers (CRC). However, optimal biomarker were still needed for individualized adjuvant strategies. Here, we conducted a prospective study in patients with stage III CRCs with combined ACT, to explore the prognostic effect of circulating tumor DNA (ctDNA) before and after ACT. Methods: The study enrolled 130 patients with stage III colon and rectal cancer (≥10cm from anal) who received curative resection without neoadjuvant therapy at Fudan University Shanghai Cancer Center. All patients received 3 or 6 months of ACT. The Roche AVENIO Surveillance Kit was used to assess somatic mutations by next-generation sequencing (NGS) in tissue, pre- and post-chemo plasma samples. The plasmas were collected 3-5 weeks after surgery and after last cycle of ACT, respectively. Patients were classified as ctDNA (+) or (-) based on the detection of SNVs identified in tumor tissue at an AF of at least 5%. Results: In the interim analysis, 116 tissues, 123 pre-chemo and 98 post-chemo plasmas were prospectively collected and detected, and a total of 86 matched samples were analyzed with a median follow-up of 12.0 months. ctDNA was detectable in 14 of 86 patients (16.3%) before ACT, and in 10 (11.6%) patients after ACT. After 1-year follow-up, longitudinal ctDNA analysis identified 6 of 12 early relapses (50.0%), while 6 in 69 patients (8.7%) who were both ctDNA (-) in pre- and post-chemo samples had early relapse. Before ACT, ctDNA(+) patients were 7 times more likely to relapse early than ctDNA(-) patients (HR, 7.372; 95% CI, 1.543-35.22; P = 0.012). Similarly, after ACT, ctDNA(+) patients were 13 times (HR, 13.37; 95% CI, 2.026-88.23; P = 0.007) more likely to relapse. Monitoring after ACT indicated that 7 of the 14 ctDNA(+) patients (50.0%) were cleared, and the early relapse rate decreased from 43.9% (3/7) to 28.6% (2/7) if ctDNA turned negative. Conclusions: ctDNA analysis can potentially change the postoperative management and surveillance strategies for stage III CRC by enabling risk stratification, monitoring ACT efficacy, and detecting early relapse. Clinical trial information: ChiCTR1800018754.
Is preoperative screening colonoscopy useful in patients with gastric cancer?
Authors: Koseki Yusuke , Hikage Makoto , Ikegame Ko , Itamoto Kouta , Isobe Yujiro , Yagi Taisuke , Nagata Masato , Waki Yuhei , Nakamura Kenichi , Kenichiro Furukawa , Fujiya Keiichi , Kamiya Satoshi , Tanizawa Yutaka , Bando Etsuro , Terashima Masanori
Published: February 2020

290

Background: In patients with gastric cancer (GC), the most common double cancer is colorectal cancer (CRC). However, the meaning of screening colonoscopy has not been established. The aim of this retrospective study was to evaluate the useful of screening colonoscopy in preoperative patients with GC. Methods: This study included 689 patients who received screening colonoscopy before gastric surgery between 2012 and 2016. Multivariate analysis using logistic regression model was conducted to elucidate independent risk factors of CRC. Then, we investigated the clinicopathological factors for CRC. Results: Colorectal adenomas and CRC were observed in 315 patients (46%) and 37 patients (5.4%), respectively. The clinical T classification of the CRC were as follows; Tis: 24 patients (65%), T1: 8 patients (21%), T2: 2 patients (6%), and T3: 3 patients (8%). In multivariate analysis, male (OR 5.04, 95% C.I. 1.29-19.6, p = 0.020) was revealed as risk factor for affecting CRC. The treatments for CRC were as follows; EMR was performed in 27 patients, simultaneous resection with GC was performed in 9 patients, resection after gastrectomy was performed in 1 patient, respectively. Pathological stage of CRC was as follows; Stage 0: 24 patients, Stage I: 10 patients, and Stage IIA: 3 patients, respectively. As for the patients who underwent surgery for CRC, all of them received radical colectomy. No patient died for CRC who received colonoscopy before gastric surgery. Conclusions: Screening colonoscopy is useful for GC patients. Because most of the synchronous CRC were found early stage and curatively treated.
Conditional survival of patients with rectal cancer undergoing Watch and Wait: The risk of recurrence over time.
Authors: Fernandez Laura Melina , Figueiredo Nuno , Beets Geerard , Valk Maxime Van Der , Bahadoer Renu , Hilling Denise , Renehan Andrew , Van De Velde Cornelis J. H. , Habr-Gama Angelita , Perez Rodrigo O ,   International Watch & Wait Database (IWWD)
Published: February 2020

30

Background: Patients with rectal cancer and complete clinical response (cCR) after neoadjuvant chemoradiation (nCRT) have been offered non-operative management (W&W). Risk factors for local regrowth (RG) include baseline cT and type of nCRT. However, the influence of risk factors for RG over time and the extent in time that patients need to be followed with the rectum in situ after a cCR are unknown. Objective: Analyze the risk of recurrence over time through conditional survival (cDFS/cLRFS) estimates for rectal cancer patients under W&W. Methods: Retrospective analysis of all patients from the largest multicenter database of patients managed non-operatively (International Watch and Wait Database–IWWD). Only patients with cCR after nCRT and W&W with a median of >3 years of follow-up were included. cDFS was used to investigate the evolution of recurrence-odds, as patients remain disease-free after nCRT. 2-year cDFS was estimated at “x” years after nCRT based on the formula cDFS2=DFS(x+2)/DFS(x). Results: 768 patients treated between 1991-2015 were included. Using cDFSestimates, the probability of remaining disease-free for 2 additional years once cCR was achieved and sustained for 1, 3, and 5 years, were 85%, 97%, and 95%, respectively. These contrast with the actuarial DFS for similar intervals of 70%, 68% and 65% respectively. Baseline cT was associated with the risk of RG at 1 year after a cCR (cT2 aLRFS 89% vs. cT3 82%; p=0.004). However, after sustaining a cCR for 1 year, baseline cT becomes irrelevant at 2 years (cLRFS; 94% vs. 90%; |d| 0.14). Also, total dose of RT (≤50 vs >50Gy) was associated with the risk of RG (aLRFS 76% vs 85%; p=0.03) at 1 year. Dose of RT becomes irrelevant (at 2 years; cLRFS 93% vs. 90%; |d| 0.10) once patients sustained a cCR for 1 year. Conclusions: Conditional survival estimates suggests that patients have significantly lower risks (≤5%) of developing late RG (at 5 years) after sustaining cCR for 3 years. A sustained cCR over time may be more relevant for long-term risk of RG than cT-stage or RT dose. The present data can have significant consequences for the recommendation of intensive surveillance after sustaining 3ys of cCR.
Treatment burden following standard of care open versus robotic D2 gastrectomy plus neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC).
Authors: Rodriguez Mariana Juanita , Ore Ana Sofia , Schawkat Khoschy , Kennedy Kevin F. , Bullock Andrea J. , Critchlow Jonathan F. , Moser James
Published: February 2020

303

Background: Phase III trials demonstrate improved short-term outcomes after laparoscopic gastrectomy for LAGC compared to open. We hypothesized that robotic D2 gastrectomy after NAC (NAC/RG) yields benefits across multiple outcome domains vs standard of care treatment for LAGC. Methods: Single institution, interrupted time series comparing SOC plus open gastrectomy (OG,2008-2013) for LAGC (T2-4Nany/TanyN+) vs universal neoadjuvant plus RG (2013-2018). Treatment burden was a composite of adverse events affecting: efficiency (postoperative length of stay, reoperation or 90 d readmission), oncology (positive margins, < 16 resected nodes), cumulative major morbidity (90 d comprehensive complication index) and pain (narcotic consumption). Predictors were evaluated via multivariate modeling, and 2-year overall survival was estimated by Kaplan-Meier/log-rank tests. Results: After exclusions, 87 subjects underwent surgical resection (55 OG; 32 RG) with equivalent baseline characteristics: demographics, BMI, comorbidity (Charlson), tumor size, and clinical AJCC staging; male sex was more likely in RG (69% vs. 44%, p = 0.02). NAC administration increased from 35% in SOC/OG cohort to 100% in NAC/RG. All four domains of efficiency, oncologic efficacy, morbidity, and pain (narcotic use) improved. Treatment burden declined from 86% in OG to 56% after RG (p = 0.003). Multivariable modeling demonstrated OR 0.23 for treatment burden in RG compared to OG (95% CI 0.07-0.72, p = 0.012), whereas sex, extent of resection (total vs subtotal), tumor size, and T stage had no effect. These differences persisted in NAC subgroup (n = 51) comparisons between RG and OG treatment burden, as well as pathologic T stage, tumor size, and AJCC stage. No detriment in 2-year overall survival was observed after adoption of NAC/RG (80% RG vs. SOC 60%, p = 0.048). Conclusions: After NAC, robot-assisted D2 gastrectomy was associated with decreased treatment burden relative to OG. Frequencies of unfavorable hospitalization, adverse oncological outcomes, major morbidity, and narcotic consumption all improved after RG in this interrupted time series. Prospective trials are needed.
Clinical impact of postgastrectomy sarcopenia on the prognosis in patients with gastric cancer.
Authors: Kim Beom Jin , Lee Eun Sun , Park Joong-Min , Hwang In Gyu
Published: February 2020

311

Background: There is a lack of research on newly developed sarcopenia postoperatively. The purpose of this study was to investigate the risk factors and the clinical impact of postgastrectomy sarcopenia on the prognosis in patients undergoing radical gastrectomy for gastric cancer (GC). Methods: We retrospectively reviewed clinicopathological data from 430 consecutive GC patients who underwent surgical resection at Chung-Ang University Hospital between January 2011 and December 2015. Their skeletal muscle mass and abdominal fat volume were measured by abdominal CT imaging. Results: A total of 425 patients were analyzed in the study. The mean age was 62 years old and male were 301 (70.8%). Of these, 42 patients (9.9%) were diagnosed as pre-operative sarcopenia. Compared with non-sarcopenic group, pre-operative sarcopenia groups showed more female, higher BMI, less alcoholic, and less smoking. However, there was no significant difference in 5 - year overall survival and disease free survival between the groups (p = 0.836 and p = 0.638, respectively). Among 381 non-sarcopenic patients, 48 patients (12.6%) were diagnosed as newly developed sarcopenia in one year after gastric resection. Compared with non-sarcopenic group, the newly developed sarcopenic group showed more male, more undifferentiated tumor, lower hemoglobin level, less alcoholic, less smoking, and presence of diabetes mellitus. However, there was no significant difference in the 5 - year overall survival and disease free survival among non-sarcopenic, sarcopenic, and newly developed sarcopenic groups (p = 0.521 and p = 0.534, respectively). The relationship between preoperative body fat volume and postoperative muscle mass showed a significant correlation (rho = 0.296, p < 0.001), but only BMI was significantly associated with long term survival. Conclusions: Although newly developed sarcopenia after surgery did not affect the survival rate, patients with nutritional risk of sarcopenia after surgical resection may require early evaluation of nutritional status and nutritional support.
Development and validation of a pretreatment nomogram to predict disease-specific mortality in gastric cancer.
Authors: Bando Etsuro , Ji Xinge , Kattan Michael W. , Bencivenga Maria , De Manzoni Giovanni , Terashima Masanori
Published: February 2020

312

Background: The American Joint Committee on Cancer (AJCC) has increasingly recognized the need for individual risk prediction model. The AJCC has emphasized the attractiveness of disease-specific mortality (DSM), which can properly control for competing events. as an endpoint of risk model, as well as overall survival (OS) and disease-specific survival (DSS). For the era of tailored therapy, we aimed to develop a new pretreatment gastric cancer nomogram for prediction of DSM. Methods: The nomogram was developed using data of 5,231 patients with primary gastric cancer treated at Shizuoka Cancer Center (Shizuoka, Japan), and it was created with a Fine and Gray competing-risks proportional hazards regression model. Fifteen clinical variables, which were obtained at pretreatment, were collected and registered, to develop the nomogram. Data of independent cohort of patients from the University of Verona (Italy; 389 patients) formed the external validation cohort. The model was validated internally and externally using measures of discrimination (Harrell’s C-index), calibration and decision curve analysis. Results: In the development procedure, multivariable analysis for DSM selected 14 variables for constructing the nomogram. The developed nomogram showed good discrimination, with a C-index of 0.887 (95%CI; 0.881-0.894); that of the American Joint Committee on Cancer (AJCC) clinical stage was 0.794 (0.784-0.804). In the external validation procedure, the C-index was 0.713 (0.680-0.746) (AJCC, 0.582, 0.539-0.622) in the University of Verona cohort. The nomogram performed well in the calibration and decision curve analyses when applied to both the internal and external validation cohorts. Conclusions: This new pretreatment risk model accurately predicts DSM in gastric cancer and can be used for patient counseling in clinical practice and stratification in clinical trials.
Real-world treatment attrition rates in advanced esophagogastric cancer.
Authors: Tsang Erica S. , Lim Howard John , Renouf Daniel John , Davies Janine Marie , Loree Jonathan M. , Gill Sharlene
Published: February 2020

317

Background: Over the last decade, multiple agents have demonstrated efficacy for advanced esophagogastric cancer (EGC), including ramucirumab, irinotecan, trifluridine/tipiracil, and immunotherapy. Despite the availability of later lines of therapy, there remains limited real-world data about the treatment attrition rates between lines of therapy. We sought to characterize the use and attrition rates between lines of therapy for patients with advanced EGC. Methods: We identified patients who received at least one cycle of chemotherapy for advanced EGC between July 1, 2017 and July 31, 2018 across 6 regional centers in British Columbia (BC), Canada. Clinicopathologic, treatment, and outcomes data were extracted by chart review. Results: Of 169 patients who received at least one line of therapy, median age was 65.2 years (IQR 58-72) and 128 (76%) were male, ECOG PS 0/1 (84%), gastric vs GEJ (35% vs 65%). Histologies included adenocarcinoma (76%), squamous cell carcinoma (10%) and signet ring (14%), with 26% HER2 positive. 62% presented with de novo disease, and 35% had received previous chemoradiation. There was a high level of treatment attrition, with patients receiving only one line of therapy (n = 73, 43%), two lines (n = 65, 38%), three lines (n = 25, 15%), and four lines (n = 6, 4%). Kaplan-Meier survival analysis demonstrated improved survival with increasing lines of therapy (median overall survival 9.6 vs. 18.5 vs. 25.8 vs. 40.7 months, p< 0.05). On multivariable Cox regression, improved survival was associated with better baseline ECOG, longer duration of first-line therapy, and increased lines of therapy ( p< 0.01). Conclusions: The steep attrition rates between therapies highlight the unmet need for more efficacious earlier-line treatment options for patients with advanced EGC.

[Table: see text]
Treatment modalities and oncological outcomes in Mexican patients with localized gastric cancer.
Authors: Verduzco-Aguirre Haydee Cristina , Meneses Medina Mónica Isabel , Valenzuela Ana Karen , Rosas Camargo Vanessa , Anaya Sánchez Luis Guillermo , Cortez Dominguez Edwin Ulises , Huitzil-Melendez Fidel David
Published: February 2020

319

Background: gastric cancer is common in Mexico. Evaluation of treatment strategies is greatly important in early gastric cancer. National institutions rarely report their outcomes, limiting feedback and policy improvements. Methods: single-center retrospective review of patients with histologically confirmed localized gastric cancer diagnosed from Jan 2005 to Dec 2017. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier curves and compared with log-rank rest. A p value < 0.05 was significant. Results: we included 78 cases, median age 63 years, 52.6% men. Surgery was the initial treatment in 46 patients (59%) and 87% achieved R0 resection. Adjuvant treatment was administered to 63% of patients. 29 patients (37.2%) started perioperative chemotherapy with 86.2% of them being resected, and 75.9% having R0 resection. 13 patients (44.8%) also received postoperative chemotherapy. Better performance status (p=0.036) and lower albumin levels (p=0.039) were found in patients with initial surgery vs those with perioperative chemotherapy. At the time of surgery, most patients had stage III disease in both groups but 5 patients had M1 disease despite negative initial laparoscopy in the chemotherapy group and 5 patients did not require aduvant tx given early stage in the surgery first group. Median OS and RFS are reported in table. Conclusions: Most patients in our center undergo initial surgery. We report a differential survival according to initial treatment. More advanced disease in chemotherapy first group may explain differences. Given non-random assignment, we could not show survival benefit of chemotherapy treated patients.

[Table: see text]
Informing metastatic colorectal cancer patients by quantifying multiple scenarios for survival based on real-life data.
Authors: Hamers Patricia , Elferink Marloes A.G. , Stellato Rebecca K. , Punt Cornelis J. A. , May Anne Maria , Koopman Miriam , Vink Geraldine R.
Published: February 2020

32

Background: Reported median overall survival (mOS) in trials of metastatic colorectal cancer (mCRC) patients receiving systemic therapy has increased to over 30 months. When informing patients, many clinicians quote the mOS reported in these trials. It is uncertain whether trial results translate to real-life populations. Moreover, patients prefer presentation of multiple survival scenarios over presentation of just mOS. Therefore, we quantified multiple scenarios for survival time of real-life mCRC patients. Methods: Nationwide population-based data of all stage IV CRC patients diagnosed between 2008 and 2016 were obtained from the Netherlands Cancer Registry. We calculated percentiles (scenarios) of OS per year of diagnosis for the total population, and for treatment subgroups: 10th (best-case), 25th (upper-typical), 50th (median), 75th (lower-typical), and 90th (worst-case). Results: The total study population comprised 27,275 patients. Twenty-five percent these patients did not receive any antitumor treatment. From 2008-2016, mOS of the total population remained unchanged at approximately 12 months. OS improved only for the upper-typical and best-case patients; by 4.2 to 29.1 months (p<0.001), and by 6.0 months to 62.0 months (p<0.001), respectively. No clinically relevant change was seen among patients who received systemic therapy, with mOS close to 15 months and best-case scenario approximately 40 months. mOS and worst-case scenario for survival were highest in patients who underwent both metastasectomy and systemic therapy: around 48 and 15 months, respectively. A clinically relevant improvement in survival over time was observed only in patients who initially received metastasectomy without systemic treatment. Conclusions: In contrast to the wide belief that mOS of mCRC patients receiving systemic therapy has improved substantially, improvement could not be demonstrated in our real-life population. Clinicians should consider quoting multiple scenarios for survival based on real-life data, instead of point estimates from clinical trials, when informing patients about their life expectancy.
Blood-based-inflammation-markers, body mass index, and survival of nonmetastatic esophageal cancer.
Authors: Wang Wanning , Soriano Joelle , Soberano Tyler , Hueniken Katrina , Brown M. Catherine , Taylor Kirsty , Bajwa Jaspreet K. , Dong George , Chen Eric Xueyu , Knox Jennifer J. , Jang Raymond Woo-Jun , Wong Rebecca , Darling Gail Elizabeth , Xu Wei , McInnis Micheal , Liu Geoffrey , Rozenberg Dmitry , Elimova Elena , Fares Aline Fusco
Published: February 2020

324

Background: Blood-based-inflammation-markers (BBIM) and Body Mass Index (BMI) have been associated with overall survival (OS) in a number of cancers. Inflammation and obesity have biological interactions. We evaluated the role of Neutrophil-to-Lymphocyte-Ratio (NLR), Platelet-to-Lymphocyte-Ratio (PLR) and Systemic-Inflammation-Index (SII) in conjunction with BMI as predictors of OS in localized/locally-advanced-esophageal cancer (LEC/LAEC). Methods: LEC/LAEC patients treated from 2006-2014 had the following variables analyzed both as continuous and categorical: BMI (low <25 kg/m2, high ≥25 kg/m2), NLR (low <4, high ≥4), PLR (low <232, high ≥232), and SII (low <1375, high ≥1375), with OS. Univariate (UVA) and Multivariate analysis (MVA) were analyzed using Cox regression (adjusted hazard ratios, aHR; 95% Confidence Intervals, CI). MVA models of OS were built, assessing different categorical combinations of BBIM factors with and without BMI. Results: Of 411 pts, 79% were males, median age was 63.5 years, 67% were adenocarcinomas; Stage I/II/III: 14%, 28%, 59%; Median BMI was 26.5kg/m2 and BMI distribution was: 3% underweight, 40% normal weight, 37% overweight and 20% obese. After a median follow-up of 87 months, 204 pts recurred, and 257 died. In MVA, BMI alone had no impact on OS (aHR 0.89, CI 0.7-1.1, p=0.15); individually as continuous variables, higher SII (p=0.03) and higher NLR (p=0.006) were inversely associated with OS whereas higher PLR was not (p=0.10). In an MVA of categorical combinations of BMI and BBIM on OS, patients in the high-BMI/low-PLR group were at lower risk of death when compared to all other groups (aHR=0.65, 95%CI:0.5-0.8, p=0.007). Similar non-statistically significant trends were shown when SII and NLR were individually combined with BMI (aHR=0.77, 95%CI:0.6-1.0, p=0.09; aHR=0.74, 95%CI:0.5-1.0, p=0.05, respectively). Conclusions: Our results suggest that in LEC/LAEC pts, high BMI and low PLR together are associated with improved OS when compared to pts with low BMI and/or high PLR. NLR and SII alone were associated with OS. Further studies evaluating the underlying mechanisms of BBMI, in particular PLR and inflammation/obesity are warranted.
Tumor size and the risk for lymph node metastases in T1 esophageal adenocarcinoma.
Authors: Sadaps Meena , Mehta Neal , McNamara Michael J. , Khorana Alok A. , Bhatt Amit
Published: February 2020

332

Background: Adjuvant therapy after endoscopic resection (ER) of T1 EAC in non-surgical candidates is largely based on the risk of LNM. Risk factors for LNM in T1 EAC are not clearly defined. Our aim is to evaluate risk factors for LNM in T1 EAC patients following esophagectomy or ER with ≥ 5 years of follow-up. Methods: This is a retrospective analysis at a large tertiary referral center. Our pathology database identified patients who underwent esophagectomy or ER with ≥ 5 years follow-up, with histologically proven T1 EAC from 2010-2017. Patients were excluded if they (a) received chemoradiation prior to esophagectomy or before/after ER (b) had any other primary cancer treated within the previous 5 years. Specimens were reviewed by an expert GI pathologist for accuracy. Results: Of 80 patients [85% males], 61 (76%) underwent esophagectomy and 19 (24%) underwent ER. Twelve (15%) developed LNM per study criteria. Tumor size was significantly (p-value 0.014) associated with risk of LNM (Table). No other factors including lymphovascular invasion, differentiation on pathology, macroscopic appearance, infiltration growth pattern, or tumor distance from the gastroesophageal junction were significant risk factors for LNM. Conclusions: In T1 EAC, tumor size appears to be a significant risk factor for LNM at five years following surgical or endoscopic resection. Adjuvant therapy should be considered in patients with larger tumor size. [Table: see text]
Exploring the epidemiology of gastric cancer in a Tibetan population.
Authors: Mehta Krisha K. , Sadutshang Tsetan D. , Namdon Tenzin , Woesal Tenzin , Grollman Arthur P. , Dickman Kathleen G. , Dorjee Kunchok
Published: February 2020

335

Background: Gastric cancer is the 3rd leading cause of death from cancer and the 5th most common cancer world-wide. It is the primary cause of death for people of Tibetan origin in the Himalayan belt, with incidence (and death) rates between 60-140/100,000 people per year. Despite such a high disease burden, the epidemiology of gastric cancer has not been studied in this population. In this study, we explore gastric cancer risk factors among Tibetan refugees residing in India. Methods: Patients diagnosed with gastric cancer were identified by reviewing admission, discharge and out-patient endoscopy records between 2013-2019 at the Tibetan Delek hospital in Dharamshala, India. Risk factors not captured in the records were collected through interviews of patients or their relatives. Results: A total of 52 gastric cancer cases were identified, mostly males (77%). Median age was 78 (range: 30-91 years). Of the gastric cancer cases, 32% (n = 12/37) were retired military, 19% (n = 7/37) were monks or nuns, and 95% (n = 36/38) were born in Tibet. Sixty-five percent (n = 34/52) of the cases had histories of dyspepsia, 49% (n = 21/43) had used alcohol, and 40% (n = 17/43) were past smokers. Ninety-five percent (n = 20/21) of cases had been treated with traditional Tibetan medicines for various reasons in the past. Of the 17 patients (or relatives) interviewed for dietary risk factors, 76% (n = 13) reported frequent ingestion of stale and unrefrigerated food, 30% (n = 5) did not eat fresh fruit, and 47% (n = 8) reported intake of fresh fruit < 3 times per month. Most (83%, n = 24/29) patients had non-cardia cancers located in the fundus/body (n = 12) and antrum/pylorus (n = 12). Fifty-two percent (n = 16/31) had been treated with either chemotherapy, radiotherapy, or surgery, and 34% (n = 11/32) of the patients were receiving traditional Tibetan medicine as treatment for gastric cancer. Conclusions: Tibetan people have socio-cultural, behavioral and dietary risk factors that may be associated with gastric cancer. Investigations of causal factors (genetic, infective ( Helicobacter pylori), environmental) with possible synergistic interactions could inform clinical and public health practice for this population and globally.