bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological trends of HPV-related anal cancers amongst males globally: A systematic literature review.
Authors: Walia Anuj , Wang Xuan , Nicholson Martha , Sun Lucy , Wong Jessica R. , Eriksson Jennifer , Kothari Smita , Morais Edith 
Published: January 2019

492 Background: Anal cancer is associated with human papillomavirus (HPV), a sexually transmitted infection, which can be prevented by the HPV vaccination. Few countries do recommend vaccination for the male population, but all males are at risk of contracting HPV. This study aimed to identify the latest evidence on the incidence of anal cancer and pre-cancer related to HPV in males globally and to analyze the epidemiological trends. Methods: A systematic literature search was performed using Medline and EMBASE. Studies containing original anal cancer incidence data in males published between January 1, 2008 and March 23, 2018 in English were included. Results: The global incidence of anal cancers and pre-cancers among the general male population was identified in 25 studies with observations ranging between 1968 and 2014. Incidence over time was reported in Australia and Europe. In an Australian national study, anal cancer incidence increased from 0.77 to 1.3 per 100,000 persons from 1982-2005, and in the UK from 0.79 to 1.06 per 100,000 persons from 1962-2002. In Denmark, the anal cancer range increased from 0.20-0.41 to 0.69-1.3 per 100,000 person-years (PYs) from pre-2000 to post-2000, and in France from 0.2 to 0.5 per 100,000 PYs from 1982-2012. In two national US studies, the mean incidence of pre-cancers was 1.5 in the period 1997-2009, and 0.41 from 1978-2007 per 100,000 PYs. The burden of anal cancers and pre-cancers increased the most among high-risk males reported in US studies. For HIV-positive males, mean incidence of cancer increased from 10.5 during 1980-1989 to 42.3 in 1996-2004 per 100,000 PYs, and for HIV-positive MSM, incidence increased from 47 to 270 per 100,000 PYs between 1984 and 2013. The mean pre-cancer incidence among HIV-positive males increased from 1.7 during 1980-1989 to 29.5 in 1996-2004 per 100,000 PYs. Conclusions: This systematic literature review demonstrates the increase in anal cancer and pre-cancer incidences over time in men, especially in high-risk male populations. The burden of anal cancers and pre-cancers increase over time in all male populations highlights the unmet medical need and the importance of preventative interventions such as HPV gender-neutral vaccinations.
Use of MLH1 methylation analysis versus BRAF V600E mutation testing to select patients for Lynch syndrome genetic testing in a Chinese population: A large consecutive cohort study.
Authors: Wang Wenmiao , Dong Lin , Zou Shuangmei , Lu Ning 
Published: January 2019

493 Background: Within MLH1-deficient colorectal cancer (CRC), BRAF mutation and MLH1 promotor hypermethylation strongly suggest a sporadic origin, providing exclusion criteria for Lynch syndrome (LS). However, the prevalence of BRAF mutation in Chinese CRCs are lower than that reported in Western countries, leading to concerns on the specificity of BRAF mutation for LS screening. The aim of this study was to assess the clinical usefulness of BRAF V600E mutation tesing and MLH1 promoter hypermethylation analyses to improve the yield of the diagnostic algorithm for discriminating LS in Chinese population. Methods: 4104 consecutive patients who had undergone surgery for CRCs between December 2011 and December 2014 in Chinese National Cancer Center were reviewed. 169 patients with MLH1 deficiency were analyzed. The MLH1 methylation status was evaluated by methylation-specific PCR; the BRAF mutation status was assessed by real-time PCR. Germline mutation testing was performed on 28 patients with BRAF-negative staining/MLH1 hypermethylation and family cancer history. Results: 52.9% (89/169) of patients displayed MLH1 hypermethylation. However, the BRAF mutation was found in 17.2% (29/169) of patients, and only 29.2% (26/89) of CRCs displaying MLH1 promoter hypermethylation harbored BRAF mutation, much lower from that reported by the western countries. Somatic methylation was identified in five LS patients. A CRC history in at least one first-degree relative had an outstanding ability to select patients with MLH1 hypermethylation for germline mutation testing, with 100% sensitivity and 82.6% specificity. Conclusions: The prevalence of BRAF mutation in Chinese CRCs are lower than that reported in Western countries leading to a decreased efficacy on triage patients for germline mutation. On the countary, MLH1 methylation analysis can improve the diagostic yield of LS, therefore play an indispensable role in LS screening among Chinese population.
Population pharmacokinetics (popPK) of Sym004 to evaluate the effect of intrinsic and extrinsic factors on exposure in metastatic colorectal cancer (mCRC).
Authors: Alifrangis Lene , Schoemacker Rik , Skartved Niels Jorgen Ostergaard , Hald Rikke , Düring Maria , Montagut Clara , Argiles Guillem , Kopetz Scott , Horak Ivan David , Kragh Michael , Wade Janet R 
Published: January 2019

496 Background: Sym004 consists of two anti-EGFR monoclonal antibodies (futuximab and modotuximab) directed against non-overlapping epitopes in the EGFR domain III. Sym004 induces rapid and efficient removal of the EGFR from the cancer cell surface by triggering EGFR internalization and degradation and has shown promising efficacy in mCRC patients. Based upon a post-hoc analysis of a Phase 2 study, a Phase 3 trial in genomically selected mCRC patients is in preparation. Methods: The aim was to establish a popPK model for Sym004 in order to i) evaluate impact of covariates (intrinsic and extrinsic factors) on Sym004 exposure and ii) provide exposure metrics for a PK/PD analysis. Sym004 serum concentrations were obtained from 330 patients with mCRC (n = 247) or advanced solid tumors (studies Sym004-01, Sym004-02, Sym004-05 and Sym004-06). Sym004 (0.4-18 mg/kg) was dosed by i.v. infusion weekly or every 2nd week, or as a 9 mg/kg loading dose followed by 6 mg/kg weekly (9/6 mg/kg weekly). Non-linear mixed effects modelling was done in NONMEM v7.3.0. Covariates evaluated included body weight, age, sex, race, albumin, renal function, hepatic function, tumor type and size, ECOG and previous anti-EGFR treatments. Results: The base popPK model was a 2-compartment model with linear and non-linear Michaelis-Menten-type elimination and a priori inclusion of body weight on CL, Vmax, V1 and V2. The model captured the non-linear PK well. The final covariate model retained covariates whose point estimates were outside the range of 0.8 to 1.25 and whose 90% confidence intervals did not overlap with the null value and included only body weight and albumin. Inter-individual variability was estimated for CL, Vmax and V1 and was in the range of 18-30%. Simulations were used to assess the clinical relevance of the covariates as judged by the magnitude of the change in exposure of the Phase 3 dose regimen of 9/6 mg/kg weekly. Conclusions: The popPK model described the Sym004 PK data well. No covariates were present that changed the Sym004 exposure in a clinically significant manner which would necessitate a dose modification. The model is suitable for simulating the Sym004 PK for PK/PD analyses. Clinical trial information: NCT01117428,NCT01417936,NCT02083653,NCT01955473.
Outcomes of younger patients diagnosed with locally advanced rectal cancer.
Authors: Habib Rosemary , Gebski Val , Toh James , Pathma-Nathan Nimalan , Khoury Toufic El , Ctercteko Grahame , Jayamohan Jayasingham , Wong Ka Yeung Mark , Wilcken Nicholas , Nagrial Adnan 
Published: January 2019

500 Background: The incidence of rectal cancer is higher in the older population. In developed nations there has been a rise in incidence in young onset rectal cancer (yRC). We evaluated and compared the presentation and survival outcomes of treatments for locally advanced rectal cancer in yRC patients to that of older patients. Methods: All cases of rectal cancers referred to a large tertiary referral cancer centre in Western Sydney between 2009-2016 were examined. Patient demographics, presenting symptoms, treatment, clinico-pathological characteristics, progression free survival (PFS) and overall survival (OS) were obtained. Under 50 years old was used as the cut-off age for defining yRC. Results: One hundred sixty-two patients were identified, 33 in the yRC and 129 in the older patient group. The median age at diagnosis was 62 (24 – 92). Median follow-up was 40 months. There was no difference in presenting symptoms between the two groups, with per rectal bleeding being the most common symptom at presentation. 17.5% of yRC presented with stage IV disease, compared with 22.1% of older patients. yRC were more likely to complete neoadjuvant therapy (97% vs 81%; P=0.02). yRC were more likely to proceed to surgery (91% vs 72%, P=0.02). There were no significant differences in surgical outcomes, including complications and postoperative TNM staging. yRC were more likely to have microsatellite high tumours (18% vs 4%; P=0.01). No statistical differences were seen in survival outcomes (PFS 57.1 vs 62.9 months, P=0.26; OS 85.1 Vs 92.8 months, P=0.57) between older and yRC patients. Eight progressions (eight deaths) were observed in the yRC group and 40 progressions (36 deaths) were observed in the older patient group. Conclusions: 20% of rectal cancers were considered yRC. These patients were more likely to complete neoadjuvant therapy and proceed to surgery. In this cohort, median PFS and OS were longer compared to the older patient group, although this was not statistically significant. yRC were more likely to have MMR deficiency. Patients under 50 years with alarm symptoms including per rectal bleeding require vigilance in investigations to allow for earlier detection and appropriate management of rectal cancer.
Safety of compression therapy using newly developed gloves for oxaliplatin induced neuropathy prevention.
Authors: Koyama Yukinori , Morioka Michina , Tobaru Yuri , Sakura Yusuke , Fukumoto Mikiko , Nagamine Ayana , Hattori Kuniaki , Taira Itsuki , Shimada Norimitsu , Kawakami Koshi , Tsuyuki Shigeru , Kanazawa Akiyoshi 
Published: January 2019

501 Background: Oxaliplatin (l-OHP) is a key drug commonly used in primary and metastatic colorectal cancer treatment. However, l-OHP is associated with non-hematological adverse effects, including peripheral neuropathy (PN). About 90% of patients who received l-OHP experience PN after single dose of l-OHP and PN is likely to be negatively associated with quality of life. There is no established effective prophylactic management for chemotherapy induced PN according to the 2014 American Society of Clinical Oncology (ASCO) guideline. Recently, compression of hands during injection of drugs has been reported to be effective for chemotherapy induced PN. We developed new gloves for compression therapy which are reusable and low cost. We prospectively analyzed the safety of the gloves. Methods: Patients who received l-OHP were eligible for this phase Ⅰ study. Wrist and hand size were measured and appropriate size of gloves were selected. The pressure of hands is estimated as 20-33 hPa. Patients start to wear the gloves on both hands, from 30 min before the injection of l-OHP until 30 min after the injection. Peripheral neuropathy was evaluated at each treatment cycle using common terminology criteria for adverse events (CTCAE) version 4.0. Results: Between October 2017 and August 2018, fourteen patients (median age 66 years [range 39– 79years], 7 male and 7 female) were enrolled and were evaluated. No patients withdrew from this study. No safety concerns were identified for any safety variables assessed during the trial. CTCAE grade 2 or higher sensory PN was observed in four (28.6%) patients. The average time until grade 1 or more neuropathy appeared was 27.8 days and average dose of l-OHP was 225mg. Conclusions: Compression therapy by the new gloves had no safety concerns, demonstrating a profile favorable for further development for prevention of oxaliplatin induced PN. Clinical trial information: 000029671.
Survival outcomes of left-sided versus right-sided colon cancer.
Authors: Gowarty Jasmine Lizette , Durham Charis , Wong Lucas , Chen Wencong 
Published: January 2019

502 Background: Right-sided colon cancers (RCC) are defined up to the splenic flexure where as left-sided colon cancers (LCC) involve the descending, sigmoid, and rectosigmoid regions. The landmark CALGB/SWOG 80405 study concluded that sidedness was an independent prognostic factor for survival in stage IV adenocarcinoma of the colon or rectum, with a poorer prognosis in RCC. This raises the question as to whether or not stage of malignancy plays a role. We performed a retrospective analysis on survival for stage I to IV colon cancer treated at our institution in order to assess if tumor location is an independent prognostic factor as described in previous studies. Methods: Primary site of cancer, sex, age at diagnosis, vital status, and year of diagnosis for stage I, II, III, and IV colon cancer was collected from our institution’s tumor registry from 2007 to 2017. The inclusion criteria included those diagnosed with stage I to IV colon cancer at 18 years of age and above. Exclusion criteria included a diagnosis of both RCC and LCC and patients under age 18. The median of overall survival and time to recurrence between LCC and RCC were compared using Wilcoxon Rank Sum Test with two-sided significance level at 0.05. Results: Time to overall survival and time to recurrence was shown to have no significant difference between RCC and LCC (p = 0.3398 and 0.9467, respectively). Cox proportional hazards model adjusted for age and sex also support the claim (p = 0.1725 and 0.0633). There was a statistically significant difference in age between the two groups with the older mean age seen in RCC (68 versus 62). The distribution of recurrence was statistically significant with a higher recurrence in RCC (p = 0.0105). Conclusions: Unlike CALGB/SWOG 80405, our analysis included the transverse colon as part of RCC and examined stage I to IV colon cancer to ultimately conclude that there was no significant difference in overall survival or time to recurrence. Our study suggests that tumor location is not an independent prognostic factor on survival for all stages of colon cancer. However, a higher suspicion for recurrence may be needed for those diagnosed with RCC. Future investigations involving molecular subtypes and mutations are needed to further clarify prognosis and tumor sidedness.
Streamlining universal screening for lynch syndrome (LS): Towards improved yield of genetic counseling (GC).
Authors: Sciallero Stefania , Damiani Azzurra , Zupo Simonetta , Battistuzzi Linda , Puccini Alberto , Bruzzone Carla , Gonella Edoardo , Gismondi Viviana , Dono Mariella , Mastracci Luca , Sobrero Alberto F. , Varesco Liliana , Grillo Federica 
Published: January 2019

503 Background: LS is largely underdiagnosed although Universal Screening (US) in colorectal cancer (CRC) patients through MisMatch Repair deficiency (MMR-d) testing is widely endorsed. Low adherence to guidelines among oncologists may be partly due to a lack of consensus on whether all MMR-d patients should be referred to GC/Genetic Testing (GT). As BRAF mutation rules out LS, we estimated the increased yield of LS diagnosis from GC /GT which could be obtained by selecting candidates for GC through BRAF testing. Methods: From 2011 to 2016, 1447 consecutive stage I-IV CRC surgical patients at a single institution, underwent immunohistochemistry (IHC) for LS using anti MLH1, MSH2, MSH6 and PMS2 antibodies. Oncologists were invited to refer all MMR-d patients to GC/GT. BRAFV600E testing was carried out only in case of MLH1 protein loss at IHC. Results: MMR-d was found in 194 patients (13%), with 171 showing loss of MLH1 expression (88%). Oncologists referred 27 (16%) to GC. Among the 21 who underwent GC, BRAF testing and GT, 9 were BRAF wild type (wt) (43%) and none had LS. Among the 23 MMR-d patients with loss of expression of MSH2, MSH6 or PMS2 (≠MLH1), oncologists referred 9 to GC (39%): 7 underwent GC / GT and 3 carried LS (43%) at GT. Median age was 76 years (range 30-97) in the MMR-d group, 78 (range 41-97) in the MLH1 group and 63 (range 30-86) in the ≠MLH1 group. Overall, LS was diagnosed in 3 of the 28 MMR-d patients (11%) who underwent GC /GT, possibly an underestimate due to the advanced median age of our MLH1 loss patients. Had we only offered GC to the 9 BRAF wt patients among the 21 with MLH1 loss, we could have avoided 12 (57%) of the GC sessions conducted, increasing the yield of LS diagnosis from 3/28 (11%) to 3/16 (19%) (75% increase). Conclusions: When US for LS is adopted, a GC referral rate reduction of 57% among MLH1 loss patients, and an overall increase in the yield of GC of about 75% can be obtained by testing for BRAF mutation before oncologist referral to GC rather than after. As multistep selection of patients by oncologists may be unfeasible, CRC pathology reports with combined MMR-d and BRAF testing (for MLH1 loss at IHC) and an ‘LS suspicion alert’ could improve oncologists’ awareness of LS and compliance with guidelines.
Real-world fusion landscape in advanced Chinese gastric cancer using next generation sequencing: A multicenter study.
Authors: Lin Rongbo , Zhao Shen , Cai Lisheng , Chen Shaoqin , Lai Jinhuo , Fang Yong , Cai Xiuyu , Wang Liping , Fang Mei-yu , Xu Chunwei , Lin Li , Li Penquan , Xu Qi , Fang Xuefeng , Yu Genhua , Shan Jianzhen 
Published: January 2019

51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.
Financial distress amongst older adults with gastrointestinal (GI) malignancies.
Authors: Varnado William , Kenzik Kelly , McDonald Andrew Michael , Parman Mariel , Paluri Ravi Kumar , Navari Rudolph M. , Smith Crystal Young , Robertson Matthew , Bhatia Smita , Williams Grant Richard 
Published: January 2019

517 Background: Many patients with cancer report financial distress (FD); however, the magnitude of FD in the growing number of older adults with cancer remains less clear, particularly in those with GI malignancies. The purpose of this study was to evaluate the proportion of older adults with GI malignancies reporting FD and to characterize geriatric assessment (GA) and cancer-related factors associated with FD. Methods: Older adults ( ≥ 60yrs) seen in the GI oncology clinic at the University of Alabama Birmingham (UAB) were asked to fill out a patient-reported GA, entitled the Cancer & Aging Resilience Evaluation (CARE), at their visit. The CARE includes questions pertaining to patient’s independence in Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), falls, physical function, polypharmacy, and comorbidity. A single item question regarding FD from the patient satisfaction questionnaire (PSQ-18) was included. FD was defined as agreement with the phrase “Do you have to pay for more medical care than you can afford.” Demographic and GA characteristics were compared between those with and without FD using Chi-square and t-tests. Results: 233 patients completed the CARE a median of 71 days after diagnosis. Median age 68y (60-96); 54.5% male and 76.0% non-Hispanic white. Most common cancer types included colorectal (39.1%) and pancreatic cancers (20.6%). A total of 62 patients (26.6%) had FD. Patients with FD were more likely to be younger (68.1 vs. 70.1y, p = 0.04), of black race (37.1% vs. 15.8%, p = 0.007), have low education ( ≤ high school: 74.2% vs. 59.6%, p = 0.02), have one or more falls (31.5% vs. 19.9%, p = 0.077), to be limited a lot in walking 1 block (54.4% vs. 27.4%, p = 0.0003), take more than 4 medications (88.3% vs. 70.8%, p = 0.007), to have more than one comorbid condition (93.1% vs. 82.6%, p = 0.052), to report impaired IADLs (61.3% vs. 43.9%, p = 0.055), and impaired ADL (27.4% vs. 14.6%, p = 0.069). No associations were found with GI cancer type or stage, marital status, time from diagnosis, or hearing/vision impairments. Conclusions: Over a quarter of the older adult population with GI malignancies report FD. Several GA and demographic factors were associated with FD that may help identify older patients at risk for FD.
Incidence of pulmonary metastasis among patients with colorectal adenocarcinoma: Correlation between sidedness and RAS mutations.
Authors: Diniz Lara Azevedo , De Brito Sales Diogo , Machado Larissa , Karani Amanda , Barros Milton Jose , Taboada Rodrigo Gomes , Pandolfi Natasha Carvalho , de Andrade Poliana , Freitas Helano C. 
Published: January 2019

527 Background: Sidedness alongside with RAS status in colorectal adenocarcinoma has been proved to correlate with survival and response to systemic therapy. There are few data reporting how these clinical characteristics can predict the dissemination of metastasis. We hypothesize that lung metastasis were more common among those with RAS mutations and left colon primary cancers. Methods: In this study, 609 patients with stage I to IV colorectal adenocarcinoma were enrolled retrospectively. Patients were divided by sidedness, right and left and were also classified according to KRAS and NRAS status. The frequencies of lung metastasis were analyzed among the different groups. Results: Of the 609 patients analyzed, 129 (21.1%) had recurrent disease and 206 (33.8%) had synchronous metastasis. RAS status was available in 311 (92.8%) of the metastatic patients and 138(44.4%) were wild type. We found that 60 (34.7%) of the patients with RAS mutated tumors presented with metachronic or synchronous lung metastasis compared with 31 (22.5%) of the wild-type population (p = 0.019). Focusing only on sidedness, excluding rectal cancer since its already described increased incidence of lung metastasis, 47 (29.7%) of the patients with left sided colon cancer had lung metastasis compared with 8 (11.1%) of the right sided primary population (p = 0,002). It was observed similar frequencies of RAS mutations among patients with left (54.1%) and right (57.6%) sided tumor. Conclusions: RAS mutated colorectal adenocarcinoma is associated with an increased incidence of lung metastasis as well as left sided tumors where this finding seems to be independent of RAS status.