bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poorly differentiated neuroendocrine carcinoma (NEC G3): Prognostic factors and potential novel targets.
Authors: Heetfeld Maximilian , Kasajima Atsuko , Koch Arend , Milone Francesco , Steffen Ingo , Dietel Manfred , Sasano Hironobu , Wiedenmann Bertram , Pavel Marianne E. 
Published: March 2020

e15071 Background: Poorly differentiated neuroendocrine carcinomas (NEC G3) represent a subgroup of neuroendocrine neoplasms with aggressive clinical behavior and poor prognosis, but showing quite variable clinical courses. In metastatic disease objective response to first-line therapy with cisplatin/ etoposide ranges between 40-67%, however median duration of response is short (4 to 9 months). There is no established second-line therapy. Methods: Clinical data of 42 patients with gastro-entero-pancreatic NEC G3 were analyzed in retrospect. In 26 cases tissue was analyzed for cell size, expression of p-mTOR and downstream effectors (p-eIF4E and p-4EBP1), somatostatin receptor (SSTR)-subtypes and growth factor receptors (EGFR and IGF-1R). Histopathological findings were analyzed using Kaplan-Meier curve, log rank test and Cox regression. Results: Patients with large cell NEC showed a more favorable survival than patients with small cell NEC. Median overall survival (mOS) was 31 versus 11 months (P=0.034). Expression of p-mTOR and p-eIF4E was seen in 64% and 24% of cases. High expression levels of p-mTOR (mOS 9 vs 25 months, P=0.026) and expression of p-eIF4E (mOS 9 vs 25 months, P=0.015) was significantly associated with shorter survival. In multivariate Cox regression p-mTOR and p-eIF4E proved to be independent prognostic factors for survival taking cell size and TNM staging into account. EGFR (cytoplasmatic and nuclear) and IGF-1R expression was found in 73.1%, 65.4% and 69.2% of the cases respectively, without significant association to survival. Expression of SSTR subtypes, Ki67 value and response to first line chemotherapy was not of prognostic value analyzed by log rank test. Conclusions: The clinical impact of cell size discrimination requires further evaluation in NEC G3. The mTOR pathway seems to play a role in tumor growth in some NEC and may represent a novel therapeutic target.
Primary tumor histology and location as predictive factors for clinical outcome in metastatic gastric cancer (GC) patients receiving first-line chemotherapy.
Authors: Bittoni Alessandro , Scartozzi Mario , Giampieri Riccardo , Faloppi Luca , Bianconi Maristella , Mandolesi Alessandra , Del Prete Michela , Pistelli Mirco , Cecchini Luca , Bearzi Italo , Cascinu Stefano 
Published: March 2020

e15081 Background: Recently, a new classification for GC has been proposed, based on Lauren’s histology and on anatomic tumour location, identifying three subtypes of disease: type 1 (proximal non diffuse GC), type 2 (diffuse GC) and type 3 (distal non diffuse GC). Aim of our analysis was to compare clinical outcome, in terms of response rate (RR), progression-free survival (PFS), and overall survival (OS), according to different GC subtypes (1, 2, 3) in metastatic GC patients (pts) receiving first-line chemotherapy. Methods: Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2, and type 3) as previously defined. Results: A total of 248 advanced GC pts were included: most of pts belonged to type 2 (45.15%) and type 3 (43.55%); type 1 included 28 pts (11.30%). The majority of pts (65.4%) received a fluoropyrimidine-based chemotherapy doublet while the remaining 88 pts received a three drugs regimen including a platinum derivate and a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C. Most of pts (55.5%) received a second-line treatment, with FOLFIRI o taxanes. The three subgroups resulted comparable for relevant clinical factors such as ECOG PS, tumour stage, number of metastatic sites, previous surgical resection, first-line combination and use of second-line treatments; as expected peritoneal carcinosis was more common in type 2 pts. RR was found to be higher in type 1 pts (RR= 46.1%) and type 3 (34,3%) compared to type 2 (20,4%), (p= 0.015). Type 2 pts presented a shorter PFS, median PFS 4.2 months, compared to type 1, mPFS= 7.5 months, and type 3, mPFS= 5.9 months (p= 0.007) and also a shorter OS with a median OS of 9,8 months vs 11.5 months for type 1 and 11.0 for type 3 (p= 0.024). Conclusions: Our analysis suggests that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients. Biomarkers analysis on tumour samples are ongoing.
HPV in upper aerodigestive tract tumors in southern Brazil.
Authors: Antunes Luis Carlos Moreira , Lopes Antonio de Barros , Muller Leandro Bizarro , Fagundes Renato Borges 
Published: March 2020

e15083 Background: The highest rates of esophageal cancer in Brazil occur in Rio Grande do Sul (18/100,000/year for men), where squamous cell carcinoma is the most common. Furthermore, the incidence of head and neck squamous cell carcinoma (HNSCC) is significant in this region (11/100,000/year for cancer of the oral cavity and 10/100,000/year for laryngeal cancer in men). Tobacco smoking and alcohol consumption are the major risk factors for esophageal squamous cell carcinoma (ESCC) and HNSCC. The role of HPV in the development of ESCC remains controversial. Otherwise, there is some evidence that HPV-related HNSCC is a distinct entity compared with HNSCC associated with smoking and alcohol consumption. Methods: Polymerase chain reaction (PCR) was used to evaluate the presence of HPV from 218 samples from three groups of patients. Group 1 comprised 51 patients with ESCC who underwent esophagectomy, in which two samples from each patient were analyzed: one tumor sample and another from normal esophageal mucosa. Group 2 comprised 37 patients with HNSCC who underwent Lugol chromoendoscopy. In this group, we took biopsies from the primary tumor and from esophageal mucosa (unstained areas and middle esophagus when the esophageal mucosa was evenly stained). Thirty-seven dyspeptic patients, non-smokers and without alcohol consumption who underwent endoscopy, comprised Group 3, in which we took one biopsy from middle esophagus. All samples were fixed in formalin and stored in paraffin blocks. Nested-PCR with MY09/11 and GP5/6 primers was used to detect HPV L1 in those samples. Results: Of a total of 224 samples fixed in formalin and stored in paraffin, only 6 samples had insufficient material for PCR analysis: one sample from normal distal epithelium in Group 1, one sample from a stained area and 2 samples from unstained areas in Group 2 and 2 samples from normal esophageal mucosa in Group 3. PCR was positive for one of conserved genes GAPDH, G3PDH or B-globin in 218 samples, showing that DNA was adequate for analysis. The PCR results were negative for HPV DNA in all esophageal samples, as well as in all biopsies from the primary tumor of HNSCC. Conclusions: There is no evidence that HPV is involved in carcinogenesis of the upper aerodigestive tract in southern Brazil.
Final analysis of efficacy and safety of dose-dense chemotherapy with modified TCF regimen (TCF-dd) in elderly patients (pts) with metastatic gastric cancer (MGC).
Authors: Tomasello Gianluca , Liguigli Wanda , Poli Rossana , Ratti Margherita , Toppo Laura , Brighenti Matteo , Maltese Mariangela , Perrucci Bruno , Panni Stefano , Negri Federica , Lazzarelli Silvia , Colombi Chiara , Curti Alessandra , Donini Maddalena , Martinotti Mario , Rovatti Massimo , Passalacqua Rodolfo 
Published: March 2020

e15086 Background: Gastric cancer is more common in elderly pts with its highest incidence around the seventh decade of life. Most oncologists are reluctant to treat this population with the most active polichemotherapy combinations because of safety concerns. Subgroup analyses of elderly pts enrolled in European studies show limited and conflicting data.We previously reported on the feasibility and high activity of a dose-dense TCF regimen (Tomasello 2010). This is a retrospective analysis of efficacy and safety of this schema in the elderly pts subgroup (≥ 65 years). Methods: From Nov 2004 to Jan 2013, 119 consecutivepts with MGC, PS 0-2, not previously treated, received Docetaxel 70 mg/m2 d1, Cisplatin 60 mg/m2 d1, l-Folinic Acid 100 mg/m2 d1-2, followed by 5-FU 400 mg/m2 bolus d1-2, and then 600 mg/m222 h c.i. d1-2, every 2 weeks, plus Pegfilgrastim 6 mg on day 3. Pts aged ≥ 65 years (60) received the same schedule with doses reducted by 30%. Results: Overall pts characteristics: 76% male, 24% female; median age: 65, range 31-81. A median of 4 cycles was administered. 102 pts were evaluable for response (86%) and all for toxicity. In pts aged ≥ 65 y, we observed 5 CR (8%), 26 PR (43%), 10 SD (17%) and 7 PD (12%); in younger pts: 3 CR (5%), 32 PR (54%), 9 SD (15%) and 10 PD (17%); ORR by ITT was 56% (95% CI 45-64). Median OS was 11,2 months (95% CI 9,4-14,1); in elderly and younger pts was 11,2 (95% CI 7,3-15,1) and 11,8 (95% CI 9,2-16,2), respectively. Out of 48 evaluable pts aged ≥ 65 years, 24 (50%) were treated at full doses without any delay. In the elderly most frequent grade 3-4 toxicities were: neutropenia (13%, p<0.0001), leucopenia (7%), thrombocytopenia (18%), anemia (3%, p=0.02), febrile neutropenia (8%), asthenia (27%), diarrhea (10%), nausea/vomiting (10%) and hypokalemia (17%); in the younger: neutropenia (56%), leucopenia (31%), thrombocytopenia (22%), anemia (15%), febrile neutropenia (15%), asthenia (41%), diarrhea (15%), nausea/vomiting (22%) and hypokalemia (20%). Conclusions: This study shows that elderly pts can be safely treated with a TCF-dd regimen with a 30% dose reduction achieving similar efficacy results as younger pts with lesser toxicity.
The relationship between collapsin response mediator protein-1 (CRMP 1) expression and histopathogic parameters and survival in patient with gastric cancer.
Authors: Gumus Mahmut , Yasar Nurgul , Kayahan Sibel , Yuksel Sinemis , Balvan Ozlem , Guven Mert Aslihan , Dinc Nur , Aydin Dincer , Aydin Kubra , Odabasi Hatice , Korkmaz Taner , Aliustaoglu Mehmet 
Published: March 2020

e15100 Background: Biomarkers which indicate invasion and metastasis in patients with gastric cancer are important. Collapsin response mediator protein (CRMP) family proteins are cytosolic phosphoproteins involved in semaphorin 3A-mediated neuronal cell growth cone collapse and cancer invasion. CRMP1 over expression levels were found to have negative association with invasion and metastasis in lung cancer tissue samples. The aim of the study was to investigate relationship between CRMP1 expression and histopathological parameters and prognostic value of CRMP1 expression in patients with gastric cancer. Methods: We analyzed 52 patients who were diagnosed with gastric cancer. The CRMP1 expression was examined by performing immunohistochemical staining. High CRMP1 expression in gastric tumor samples was defined as being immunoreactive to CRMP1 antibody in more than 50% of the cancer cells. The correlation between CRMP1 expression and age, gender, tumor grade, lenfovascular-perineural invasion, t stage and nodal involvement was investigated. Results: Among the 52 patients (CRMP1 positive/CRMP1 negative= 24/28), median age was 56 years (27-84). Thirty-five patients were male and 17 patients were female. The median follow-up time was 14 (2-60) months. The median disease-free survival time (DFS) was 20 (SE: 4; 95% CI: 13-27) months. In addition, the median overall survival time (OS) was not reached. The significant relationship was found between CRMP1 high expression levels and high grade tumors (p:0.03), and nodal metastasis (p:0.019). In univariate analysis, only high CRMP1 expression was associated with poor disease-free survival (p:0.004). Also, male gender (p:0.023), high grade tumors (p:0.044), nodal involvement (p:0.028) and high CRMP-1 expression were associated shorter overall survival. In multivariate analysis, no independent prognostic factor was found in this group. Conclusions: We found that high expression of CRMP1 was associated with tumor aggressiveness of tumor and poor survival. Larger studies and further clinical trials are warranted to confirm these findings.
Impact of multidisciplinary cancer care on the postoperative mortality and survival of patients with esophageal and esophagogastric junction cancer.
Authors: Galán Maica , Farran Leandre , Aliste Luisa , Hormigo Gloria , Calvo Mariona , Aranda Humberto , Boladeras Ana Maria , Botargues Josep Maria , de Lama Eugenia , Paúles Maria Jose , Robles Javier , Serra Olbia , Virgili Núria , Borràs Josep Maria 
Published: March 2020

e15111 Background: Modern management of Oesophageal and oesophagogastric junction (OGJ) cancers requires a multidisciplinary approach, which was implemented at our health centre in 2005. This study aimed to assess the impact of this change on clinical outcomes. Methods: A retrospective cohort study was conducted, covering all patients treated for oesophageal and OGJ cancer at the cancer centre established by the Bellvitge University Hospital and Catalonian Institute of Oncology, over two time periods, i.e., 2000-2004 and 2005-2008. Descriptive and multivariate analyses were performed using survival at 1 and 3 years as dependent variables. Results: Between 1 January 2000 and 31 December 2008, 586 patients were included. Number of patients with unknown stage at diagnosis was significantly reduced. Neoadjuvant strategies at the oesophageal location clearly increased in the recent period. A multidisciplinary approach resulted in a significant reduction in surgical mortality (11.8% vs. 2%) in the period 2005-2008. Analysis restricted to patients undergoing surgery with curative intent indicated a significant increase in 1- and 3-year survival in the latter period (68.4% vs. 89.8% and 38.2% vs. 57.1% respectively). Multivariate analysis showed that variables associated with improved survival were: age; tumour stage; radical intent of treatment (surgery and radical combined chemoradiotherapy); and therapeutic strategy. Conclusions: Better selection of patients for therapy together with improved staging resulted in a significant improvement in 1- and 3-year survival in cases undergoing surgery with curative intent. These changes would support the adoption of a multidisciplinary approach to clinical decision-making in cases of oesophageal and OGJ cancer.
CRM1 expression in pancreatic carcinoma.
Authors: Mahipal Amit , Coppola Domenico , Gupta Shilpa , Centeno Barbara , Malafa Mokenge Peter 
Published: March 2020

e15115 Background: Increased expression of chromosomal region maintenance (CRM1) protein, also known as exportin 1, has been described in several human cancers. It is an important regulator of subcellular localization of tumor suppressor proteins and growth regulatory proteins. Direct inhibition of CRM1 blocks cell proliferation and induces apoptosis leading to the current evaluation of CRM1 inhibitors as anticancer agents in early phase clinical trials. There is a paucity of data regarding the prevalence of CRM1 expression in pancreatic cancer. Methods: We analyzed the expression of CRM1 by immunohistochemistry (IHC) in pancreatic tissue microarray (TMA) samples (malignant and non-malignant) obtained from patients who underwent potentially curative resection for pancreatic ductal adenocarcinoma. CRM1 antibody (Santa Cruz Biotechnology) was used for immunostaining the formalin fixed paraffin embedded core sections in the TMA samples. The intensity of staining and percentage of cells stained were graded on a scale of 0 to 3, with 3 being highest. The final IHC score was obtained using the product of immunostain intensity and percentage of cells stained (Range: 0-9). Low and high CRM1 expression was considered if the IHC score was 0 to 4 and 6 to 9 respectively. Results: Seventy nonmalignant and 91 pancreatic carcinoma samples were evaluated in this study. The median IHC score was 6 (range: 0-9) and 3 (range: 1-9) in malignant and nonmalignant pancreatic tissue samples respectively (P<0.0001). High CRM1 expression was found in 11% (8/70) of normal tissue samples and 69% (63/91) of tumor samples (P<0.0001). There were 48 paired samples of pancreatic cancer tissue and normal tissue obtained from same patient. Among these patients, 33 (69%) patients had higher CRM1 expression, 7 (15%) patients had similar expression and 8 (17%) patients had lower expression in malignant tissue sample as compared to their adjacent normal tissues. Conclusions: Higher CRM1 expression occurs frequently in pancreatic cancer as compared to nonmalignant pancreatic tissue, reinforcing its putative tumor oncogenic activity, and raising the value of targeting it for pancreatic cancer therapy.
Prognostic significance of the recurrence pattern and risk factors for recurrence in patients with proximal gastric cancer.
Authors: Bilici Ahmet , Selcukbiricik Fatih , Oven Ustaalioglu Bala Basak , Tural Deniz , Seker Mesut , Gumus Mahmut , Serdengecti Suheyla 
Published: March 2020

e15117 Background: The proximal gastric cancer (GC) is usually diagnosed at advanced stage and it had relatively high recurrence rate after curative resection due to high incidence of lymph node metastasis. This study aimed to investigate the pattern and time of recurrence and to evaluate the risk factors for relapse of proximal GC. Methods: Between 2000 and 2012,110 patients with recurrent proximal GC undergoing radical gastrectomy were retrospectively analyzed.The prognostic significance of the recurrence time and pattern at the diagnosis of relapse and the relationship between the pattern of recurrence and the other clinicopathological factors were evaluated. Results: The median time to recurrence was 34 months, 52.7% of patients had relapse within 2 years. The most recurrence patterns were hematogenous and peritoneal metastasis, respectively (47.3 and 39.1%). Hematogenous and loco-regional recurrence were significantly associated with younger age (p=0.04) and proximal resection was related with higher incidence of all recurrence patterns (p<0.001). Moreover, advanced pT stage was significantly correlated with increased hematogenous and peritoneal recurrence (p=0.002). The median disease-free survival (DFS) and overall survival (OS) times for patients with distant-lymph nodes and hematogenous recurrences were significantly worse than those of patients with loco-regional and peritoneal recurrences (DFS, 9.7 vs. 23.4 vs. 35.4 vs. 43.9 months, p=0.014; OS, 19 vs. 46.4 vs. 70.2 vs. 66.8 months, p=0.04, respectively). Multivariate analysis showed that the time of recurrence [p<0.001, HR: 0.37), pN stage, clinical stage and surgery type were independent prognostic factors for OS. The presence of lymph node metastasis was an independent risk factor for both overall and early recurrence (p=0.004, OR: 0.51). Conclusions: Our results indicate that the time of recurrence, surgery type, lymph node metastasis and clinical stage were independent prognostic indicators for OS, while only the presence of lymph node metastasis was an independent risk factor for early recurrence. Total gastrectomy and adequate lymph nodes dissection were rational curative treatment option for proximal GC.
Dose-escalated image-guided radiation and weekly cisplatin for inoperable squamous cell carcinoma of thoracic esophagus.
Authors: Chilukuri Srinivas , Pawar Yeshwanth S. , Subramanian Sai Shanmugam , Kiran Kumar K. , Yadala Nalini , Tike Pramod K. , Kathirvel M. , Gandhi Arun , Swamy Thirumalai , Ghadyalpatil Nikhil 
Published: March 2020

e15120 Background: This study evaluates feasibility, toxicity and early outcomes of image guided volumetric modulated arc therapy (IG-RA) and weekly cisplatin for locally advanced inoperable squamous cell carcinoma (LAI-SCC) of thoracic esophagus. Methods: 41 patients diagnosed with LAI-SCC were included. Patients with performance status (ECOG) more than 1, involvement of cervical esophagus or gastroesophageal junction, distant metastasis were excluded from study. Radiotherapy was planned in two phases to a dose of 5940cGy. Phase I CTV was generated by expanding the GTV-primary craniocaudally(CC) by 4cm and laterally to include electively, the corresponding level mediastinal nodes. In the Phase II, GTV was expanded by 2cm CC and 1cm radially. ITV was generated by expanding the CTV by 0.5cm which was then expanded by 0.5cm to yield PTV. Chemotherapy consisted of 4-6 cycles of weekly cisplatin 40mg/m2. Results: The median age of patients was 53 yrs (43-72). The median length of involvement was 6cm with 80% of lesions in upper and middle third. 37/41(90%) patients completed planned chemotherapy with atleast 4 cycles of cisplatin and 40/41 patients completed full dose of radiotherapy. 10% of patients required tube feeding and 5% required hospital admission for supportive care. Endoscopy at 8 weeks post treatment was performed in 38/41 patients of whom 53% had CR, 42% had PR and 5% had stable disease locally. With a median follow up of 19 (6-32) months, 41% of total patients (17/41) are alive at last follow-up of which 32% (13/41) are disease free with no dysphagia, the 1 and 2 year overall survival are 70% and 40% respectively and median survival of 14 months. 16% alive patients have post radiotherapy stricture. The analysis of CBCT and KV image data sets showed a significant intra-fraction and inter-fraction motion of the target. The ITV and PTV margins of 0.5cm each were found to be adequate with current imaging protocol. Conclusions: IG-RA to a dose of 60Gy with concurrent weekly cisplatin is a feasible treatment option for LAI-SCC of thoracic esophagus with low acute and late toxicity and with promising early clinical outcomes. The ITV and PTV margins of 0.5cm were found to be adequate only with image guidance.