bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of complications after cytoreductive surgery associated with HIPEC in the treatment of peritoneal carcinomatosis.
Authors: Ferreira Fabio Oliveira , Aguiar Samuel , Lima Alessandro , Santos Erika Maria Monteiro , Nakagawa Wilson Toshihiko , Bressan Alexsander Kurowa , Mello Celso Lopes , Lopes Ademar
Published: March 2020

e14119

Background: A select group of patients with peritoneal carcinomatosis (PC) has been treated with curative intent by cytoreductive surgery (CCS) associated with intraperitoneal hyperthermic chemotherapy (HIPEC). The objective of this study is to identify predictors of postoperative complications in patients undergoing CCS + HIPEC. Methods: We analyzed data from 136 procedures of CCS + HIPEC in 128 patients with PC, from March 2001 to December 2010. Variables clinical, surgical, and the scores obtained by rating scales of risk (ASA, POSSUM and ACE-27), were correlated with scores obtained by rating scales of morbidity and postoperative results (Bennett-Guerrero, NCI and McPeek). Carcinomatosis was caused by tumors of the appendix in 54 cases (39.7%), ovary in 43 (31.6%), colorectal in 22 (16.2%), peritoneal mesothelioma in 14 (10.3%) and others in three (2.2%). All patients were classified as ECOG 0 and 1 and had KPS> 80%. Complete cytoreduction (CC0) was performed in 93 (68.4%), CC1 30 (22.1%) and CC2 or CC3 in 13 (9.5%). Results: The rates of OS and the median follow-up were respectively 79.6% and 102 months for patients with CP of origin in tumors of the appendix, 78.6% and 74.8 months for source of peritoneal mesotheliomas, 73,9% and 55.9 months for ovarian origin and 36.4% and 31.1 months for colorectal origin. The morbidity (serious complications NCI - grade 3, 4, and 5) and postoperative mortality (30 days) were respectively 16.9% and 2.9%. The duration of surgery (> 9 hours) and ASA classification Scale (ASA class III) were the main predictors of postoperative complications in multivariate analysis. Age was a predictor of cardiovascular complications and one of the variables responsible for longer ICU stay. The number of anastomoses performed per procedure (2 or 3) was associated with the occurrence of infectious complications systemic and wound. Conclusions: The duration of surgery, ASA classification in scale, age and number of anastomoses were the factors most often related to the occurrence of severe postoperative complications after cytoreductive surgery associated with intraperitoneal hyperthermic chemotherapy.
Sex as a predictive factor in metastatic colorectal cancer treated with bevacizumab containing chemotherapy.
Authors: Jeong Jae-Heon , Baek Sun Kyung , Chae Jung Min , Lee Gil Yeon , Park Sun Jin , Kim Si-Young , Yoon Hwi Joong , Cho Kyung Sam
Published: March 2020

e14128

Background: Recently, bevacizuamb induced hypertension was suggested as being a predictive factor for bevacizumab in metastatic colorectal cancer (mCRC) patients. However, there wasn’t any useful pretreatment predictive factor for bevacizumab in our clinic. So, in this study, we investigated the predictive factors for bevacizumab in mCRC. Methods: From 2002 to 2011, thirty mCRC patients received bevacizumab containing chemotherapy in Kyung HeeUniversity Hospital, Seoul. Among them, 27 patients had a measurable disease which adequate for response evaluation using Response Evaluation Criteria for Solid Tumors. We analyzed predictive factors for bevacizumabin these 27 patients using chi-squaretest and binary logistic regression analysis. Results: Median age was 57.0. Thirteen patients (48.1%) were male. ECOG performance status was 0,1,2 (29.6%/59.3%/11.1%). Eight patients had right side tumor and nineteen patients had left sided tumor. Fifteen patients had two metastatic sites. Sixteen patients received bevacizumab containing chemotherapy as first or second line treatment. Fourteen patients received oxaliplatin based chemotherapy with bevacizumab. We analyzed predictive factors for bevacizumab containing chemotherapy. In the univariate analysis, response rate was higher (53.8% vs 14.3%) in male patients (p= 0.092, Fisher’s exact test). In the multivariate analysis (binary logistic regression analysis), gender was a significant predictive factor (p=0.046). Progression-free survival was 6.3 months (CI95%:2.14 – 10.46 months) and 5.2 months (CI95%: 3.92 –6.49 months) in male and female patients, respectively (log-rank, p=0.503). Overall survival was 9.4 months (CI95%:7.2 – 11.63 months) and 11.7 months (CI95%:10.3 – 13.08 months) in male and female patients, respectively (log-rank, p=0.773). Conclusions: Although sex is not a modifiable predictive factor, it appears that sex is an important predictive factor in metastatic colorectal cancer patients treated with bevacizumab containing chemotherapy.
Review of the current status of KRAS mutation testing in France in 2011: The Flash-KRAS study.
Authors: Artru Pascal , Ducreux Michel , Lièvre Astrid , Guiu Michel , Merlin Jean-Louis , Sabourin Jean-Christophe , Viguier Jérôme , Bastie Anne , Seronde Audrey , Laurent-Puig Pierre
Published: March 2020

e14129

Background: KRAS testing is required before treatment initiation of cetuximab in the management of metastatic colorectal cancer (mCRC). The objective of the study was to examine the current situation in 2011 regarding KRAS testing in the initial management of mCRC. Methods: This observational, retrospective, national study was carried out between March 28th and April 8th 2011. During this period 538 patients with mCRC were included across 160 french hospitals. The main objective was to assess the rate of KRAS testing in patients who had started first line (L1) treatment for mCRC. The secondary objectives were to describe the time taken and techniques used for KRAS testing, the possible reasons this test was not requested, to describe and analyse the clinical characteristics of the patients and the planned L1 treatments and those finally received. Results: KRAS testing was carried out for 433 patients (81.1%) and not carried out for 101 patients (18.9%). The main reasons for not requesting the KRAS status were (several answers possible): anti-EGFR not prescribed (n=58), candidate for surgery (n=8), samples not useable (n=5), age of the patient (n=3), other (n=24), data missing (n=13). The genotyping results were available after a mean delay of 23.6 ± 28.2 days. The KRAS testing was requested by an oncologist (45.5%), a gastroenterologist (31%), a surgeon (11.2%), a pathologist (7.2%) or a multidisciplinary group (5.1%) approximately 15 days (-66.5;33.6) median (min ; max) after the diagnosis of metastases, and 15 days (-66.9;3.7) median (min ; max) before the start of L1 treatment. Result of KRAS status had not been received before the L1 treatment was chosen in 56.6% of the patients. For patients with wild-type KRAS status whose therapeutic management was modified after the result of KRAS testing (n=108), this change was a prescription of an anti-EGFR in 77.8% of the cases. Conclusions: The Flash-KRAS study is the first one to assess the current modalities of KRAS genotyping in France. It shows that in 2011 the KRAS test is an integral part of the management of patients with mCRC. Nonetheless, it shows disparities between regions in terms of time to obtain results, which need to be improved to be compatible with the therapeutic management.
MR-guided laser-induced thermotherapy (LITT) in liver metastases of colorectal cancer: Long-term survival data.
Authors: Vogl Thomas J. , Dommermuth Alena , Eichler Katrin , Zangos Stephan
Published: March 2020

e14131

Background: To evaluate retrospectively long-term survival of 594 patients with colorectal liver metastases treated with MR-guided laser-induced thermotherapy (LITT) depending on different factors. Methods: 594 patients with liver metastases from colorectal carcinoma treated with MR-guided LITT between 01/99 and 12/10 were included. For survival analysis tumor localization, TNM classification, number of metastases, diameter and volume of metastases and necrosis, lobular spread, number of treatment sessions, performance of adjuvant chemotherapy and transarterial chemoembolisation were considered. The Kaplan-Meier method was used to conduct this survival analysis. Results: Log-rank test showed statistically significant differences between survival curves, multivariate Cox-regression-analysis (p<0.05) showed prognostic factors regarding overall survival like number of metastases pre intervention, adjuvant chemotherapy, diameter of metastases, ratio of volumes of necrosis and metastases, and affected lymph nodes. Median overall survival rate at the time of first LITT was 25 months, 1-year survival: 78%, 2-year survival: 50.1%, 3-year survival: 28%; 4-year survival: 16.4%; 5-year survival: 7.8%. Numbers of metastases pre intervention: 1-2 metastases with a median survival rate of 60 months; 3-4 metastases: 45 months; ≥5 metastases: 42 months. Median survival rate for metastases <20mm in diameter 36 months; 20-30mm 27 months, 30-40mm 24 months and >40mm 21 months. Affected lymph nodes: median survival rate for patients with N0-classification 30 months, N1-classification 24 months; N2/N3/N4-classification 22 months. Conclusions: Multivariate Cox regression model provided the minimal number of significant variables with the maximal prognostic value concerning overall survival for MR-guided LITT, i.e., diameter and number of metastases and primary classification of lymph nodes.
Perineal morbidity and functional results of pseudocontinent perineal colostomy for low rectal cancer surgery: Retrospective study of 149 cases.
Authors: Souadka Amine , Souadka Abdelilah
Published: March 2020

e14133

Background: This retrospective study was designed to evaluate morbidity and functional results of pseudocontinent perineal colostomy (PCPC) using Schmidt’s technique in North African patients undergoing APR for managing low rectal adenocarcinoma. Methods: During 15 years, 380 Abdominoperineal resections for low rectal cancer were performed. One hundred forty nine cases among them had PCPC. There were 76 women, with an average age of 47 years old. All patients received néoadjuvante radiotherapy with or without chemotherapy. Functional results were evaluated prospectively at regular intervals. Results: There was no postoperative mortality. Operative Morbidity rate was only 18.3%, essentially dominated by perineal suppuration (40%). According to Kirwan score on a Functional level, 95 patients had gaz incontinence and 46 patients an occasional minimal soiling. At one year surveillance, the graft was clinically well detected in 72% of cases and anorectal manometric study on 15 cases showed a hypotonic pseudosphincter. Colic irrigation rhythm was, in 74% of cases, every 24 to 48h, and 15% of patients didn’t need irrigations any more 6 months after surgery. Except for major postoperative complications, no other conversion from perineal colostomy to an iliac colostomy was performed for dissatisfactory functional results since 77% of the patients were satisfied and 23% half-way satisfied of this technique. Conclusions: Pseudocontinent perineal colostomy is a simple, safe and reliable technique that represents an interesting alternative to permanent iliac colostomy after APR for low rectal adenocarcinoma. It improves perineal healing and provides good functional results and high degree of patient satisfaction in addition to body image preservation. it is well adapted to north-african cultural economical and religious coditions.
The prognostic value of an early response in chemoradiation of locally advanced rectal cancer.
Authors: Ploeen John , Lindebjerg Jan , Joergensen Jens Christian Riis , Jakobsen Anders Kristian Moeller
Published: March 2020

e14134

Background: Preoperative chemoradiation is standard treatment of locally advanced rectal cancer, and there is an obvious need for new methods of assessing the effect. Evaluation by clinical examination with endoscopy is controversial. In most papers the assessment of effect has been performed after the end of treatment. The aim of the present study was to investigate the clinical value of an examination during chemoradiation. Methods: The study included 128 patients with histopathologically verified rectal cancer. Further inclusion criteria were a T3 tumor with a circumferential margin ≤ 5 mm by MRI or a T4 tumor, a distance of < 10 cm from the anal verge and localized diseased only by abdominal and chest CT scan. The treatment was 50.4 Gy/28 fractions or the same treatment with the addition of endorectal brachytherapy 10 Gy/2 fractions in a randomized trial. The concomitant chemotherapy was UFT 300 mg/m2 and L-leucovorin 22.5 mg daily. Both drugs were given five days a week. Clinical examination with endoscopy was performed week 4 during treatment. The clinical effect was classified into complete response (CR) or not complete response with clinical residual tumor (NCR). The patients were operated eight weeks after end of treatment and the pathological tumor response was classified according to Mandard (TRG). Results: CR was found in 14% of the patients. Comparison with TRG showed that 82% with CR had TRG1 as compared to the NCR group where only 9% had TRG1 (p<10-4). The risk of lymph node metastasis was also different with 94% pN0 in the group with CR compared to 57% in the NCR group (p=0.02). The rate of CR translated to a major difference in the risk of recurrence (local and distant). No patients with CR experienced recurrence as compared to 19% in the NCR group (p<0.05). The CR also correlated with cancer specific survival. None of the patients with CR died from rectal cancer with a median observation time of 36 months compared to 30% in the NCR group. Conclusions: CR is a major prognostic parameter in locally advanced rectal cancer treated with chemoradiation. Early CR should be considered in the selection of patients for Watchful Waiting.
Survival patterns by line of treatment of stage IV colorectal (CRC) patients from local U.S. oncology practice.
Authors: Kreilick Charles , Foltz Boklage Susan H , Sullivan Sean D , Ramsey Scott David , Haislip Sally , Gilmore James W. , Szabo Stephen , Sarma Syam , Asche Carl V , Valluri Satish , Seal Brian S.
Published: March 2020

e14141

Background: Stage IV CRC patients have varying survival results from multiple lines of treatment. The objective of this study was to evaluate in a real world context, the impact of adding a third line of chemotherapy to a stage IV CRC population. Methods: The Georgia Cancer Specialist database (2005-2011) was used. Patients with stage IV colon or rectal cancer and treated with chemotherapy were followed from initial CRC diagnosis until death, study end or lost to follow-up. Patients were stratified into lines and type of protocol for treatments. Kaplan-Meier curves were used to compare the overall survival results between lines of therapy. Results: There were 335 patients with confirmed stage IV CRC of which 35% received one protocol, 27% two protocols, and 38% received three or more protocols. The most common first line agents consisted of FOLFOX with or without bevacizumab or FOLFIRI with or without bevacizumab. Some single agent 5FU or 5FU with bevacizumab was observed in first line. The most common second agents were the FOLFOX or FOLFIRI not given in first line. However single agent capecitabine, cetuximab and bevacizumab were observed. In third line similar single agents but more panitumumab and capecitabine combinations were observed. Of those treated with second line (45) and three or more lines (75). The median survival was no different between the patients that received second line and those that went on to a third line (Log-Rank p=0.1249). Conclusions: The addition of adding a third line to a stage IV population that already received a second line failed show an association to increase survival. The benefit of adding a third line may benefit some patients and the particular combination of therapy needs to be explored in future studies.
Clinical and biologic factors associated with time to progression in patients treated by first-line palliative FOLFOX chemotherapy in metastatic colorectal cancer.
Authors: Bal Wieslaw , Jarzab Michal , Stobiecka Ewa , Zebracka Jadwiga , Mianowska Marta , Oczko-Wojciechowska Malgorzata , Rusinek Dagmara , Tyszkiewicz Tomasz , Nowara Elzbieta , Jarzab Barbara , Tarnawski Rafal
Published: March 2020

e14159

Background: Chemotherapy is the mainstay of treatment patients with metastatic colorectal cancer. The choice of first-line treatment is difficult, especially when cost-effectiveness is the primary constraint. Thus, the optimal use of the clinical and biological factors influencing prognosis would be beneficial. The aim of our study was to identify factors affecting the time to progression (TTP) after first-line FOLFOX chemotherapy in palliative setting. Methods: The study is a retrospective analysis of the series of consecutive patients from large cancer center in south of Poland. The analysis was carried out in the group of 180 patients (37.2% of women), treated between 2007-2010 by FOLFOX-4 regimen and followed-up with the median time of observation 16.3 month. Patients received chemotherapy with median time of 5.0 months, median 10 cycles. Progression was defined as PD by RECIST criteria, death due to disease or sympomatic deterioration. 94 paraffin blocks were available for KRAS testing and gene expression analysis by real-time PCR. Results: The median TTP (counted from beginning of chemotherapy) was 8.6 month, the median TTP from the end of treatment was 3.4 month. We tested the wide range of clinical variables associated with both disease and and patient status by multivariate Cox regression analysis. Two most potent independent negative predictors were identified: the presence of massive lymph node involvement as assessed in CT scan before palliative treatment (>10 nodes enlarged) – hazard ratio 2.82, p<0.001; and tumor grade in histopathological assessment (grade 3 vs. grade 1-2) – hazard ratio 2.76, p=0.003. KRAS status was not prognostic for the TTP; Ki67 gene expression measurement by quantitative RT-PCR did not predict better that the routine assessment of grade. Patients with either grade 3 or lymph node involvement showed significantly shorter TTP (median 5.7 months vs 9.7 months in patients with none of these factors). Conclusions: High tumor grade and the massive involvement of lymph nodes worsen prognosis and shorten time to progression in patients treated with first line palliative FOLFOX chemotherapy.
Use of cetuximab (CTX) in first-line therapy of metastatic colorectal cancer (mCRC): Patient characteristics, safety, and effectiveness in the EREBUS cohort.
Authors: Smith Denis , Rouyer Magali , Mitry Emmanuel , François Eric , Monnereau Alain , Sa Cunha Antonio , Bignon Emmanuelle , Le Monies Alise , Jove Jeremy , Noize Pernelle , Moore Nicholas , Fourrier-Réglat Annie
Published: March 2020

e14168

Background: CTX has demonstrated improved survival outcomes in mCRC but information in real-life is sparse. Methods: EREBUS is a French multicentre (n=92) cohort. Patients (pts) initiating CTX 1st-line therapy for unresectable mCRC in 2009 and 2010 were identified from dispensation registries and followed 12 months. Presented here is preliminary data for those included in 2009. Results: A total of 205 pts were included, all had wild-type (wt) KRAS gene. Median age: 64 yrs, 67.3% male, 65.8% ECOG=0-1, 61% cardiovascular history, 78.5% colon primary site, 55.6% primary tumor resection, 73.7% synchronous metastasis, single metastatic site: 52.7% (39% exclusively liver). A multidisciplinary team considered 1st-line as palliative for 61.5% of pts, and 37.1% as potentially resectable. CTX was combined with oxaliplatin-based regimens: 37.6%, irinotecan-based regimens: 55.6%, and other regimens: 6.8%. For those receiving CTX+oxaliplatin (n=77): median duration of CTX use was 3.6 months and 63.6% were treated every 2 weeks. For those receiving CTX+irinotecan (n=114): it was 4.7 months and 81.6% treated every 2 weeks. Response rate (CR+PR) according to physician evaluation was 48.6% for CTX+oxaliplatin and 46.8% for CTX+irinotecan. 1-yr OS was 59.9% (95%CI 47.6-70.2) and median PFS was 8.6 months (6.3-10.5) for CTX+oxaliplatin. 1-yr OS was 69.1% (59.6-76.7) and median PFS was 9.3 months (7.4-10.5) for CTX+irinotecan. Incidence of any grade 3/4 event was 58% for CTX+oxaliplatin and 57% for CTX+irinotecan: neutropenia (18.2% and 19.3%, respectively), skin reaction (11.7% and 14%), asthenia (11.7% and 14.9%), hypokalaemia (13% and 4.4%), diarrhoea (6.5% and 10.5%) and infusion-related reactions (1.3% and 0.9%). Surgical evaluation was performed in 27.8%: 31.2% CTX+oxaliplatin and 24.6% CTX+irinotecan Conclusions: In France, CTX was frequently combined with irinotecan-based regimens in 1st-line wt KRAS mCRC. These results indicate a high proportion of exclusive liver metastases, and a high proportion of patients undergoing surgery. Effectiveness and safety profile of CTX in real life were in line with pivotal trials
Study of tumor-infiltrating T-cell reactivity to metastatic gastrointestinal cancers.
Authors: Turcotte Simon , Gros Alena , Wunderlich John R , Hogan Katherine , Wang Qiong J. , Fetsch Patricia , Dudley Mark E. , Rosenberg Steven A.
Published: March 2020

e14179

Background: A high density of tumor-infiltrating lymphocytes (TIL) found in gastrointestinal cancers has been associated with improved prognosis. Evidence supporting specific autologous tumor recognition by TIL remains sparse and limits the development of innovative immunotherapy approaches. Methods: Metastases from 15 GI cancer patients (13 colorectal, 1 gastric, 1 cholangiocarcinoma) processed into fragments and fresh tumor cell suspensions (FrTu) were used to grow TIL and cancer cell lines. TIL phenotype was assessed by flowcytometry and reactivity by coculture with available cryopreserved FrTu and cancer cell lines. Limiting dilution techniques were used to isolate reactive CD8+ TIL clones. T-cell receptors (TCR) were sequenced using PCR amplification. Results: TIL were expanded successfully in all 15 cases. TIL phenotype studied from 7 freshly resected colorectal cancer metastases revealed a higher percentage of immunosuppressive T cells (CD4+CD25HIFoxP3+) compared to adjacent normal tissue and blood (respectively 5.4 ± 1.0%, 1.3 ± 0.5%, and 1.0 ± 0.4% of CD3+ cells). Interferon-gamma release by TIL after their first outgrowth upon coculture with cryopreserved FrTu was significant in all 6 cases studied, with positive results ranging from 7% (3/42) to 89% (8/9) of patient’s distinct cultures. Two newly established cancer cell lines allowed extensive investigation of TIL reactivity. In a case of gastric cancer, 65% of the CD3+CD8+ TIL expanded from liver metastases expressed the same TCR. TIL clones expressing this TCR could recognize the autologous cancer cell line with a high degree of specificity, suggesting that within this tumor a productive immune response occurred. In a case of metastatic cholangiocarcinoma, two TIL clones with distinct TCR represented less than 1% of the CD3+CD8+ cells grown from an omental metastasis and the malignant ascites, but could nonetheless lyse the autologous tumor with specificity. Conclusions: Despite the immunosuppressive microenvironment of GI cancer metastases, CD8+ TIL that recognize autologous tumor with specificity can be identified and expanded in vitro. The adoptive transfer of TIL for the therapy of metastatic GI cancer patients is currently being studied.
Phase I study of ursodeoxycholic acid in combination with 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab for metastatic colorectal cancer.
Authors: Lai Lily L. , Chiu Ken , Chung Vincent M. , Lim Dean , Chao Joseph , Frankel Paul Henry , Shibata Stephen
Published: March 2020

e14182

Background: Significant treatment advances have doubled the median survival in patients with metastatic colorectal cancer (mCRC). An emerging body of literature links cancer with aberrant metabolism. These findings suggest that treatment directed against CRC metabolism may add to improved survival outcomes. The bile acid, ursodeoxycholic acid (UDCA), lowers cholesterol and improves insulin sensitivity when used clinically. Moreover, UDCA protects against intestinal polyp development in animal and human studies. UDCA effects may be mediated through activation of FXR, since bile acids are the endogenous ligands for this nuclear receptor. FXR is a tumor suppressor in mouse models of colon cancer and a prognostic biomarker in patients with CRC. Activation of FXR with bile acids in mouse models suppresses intestinal tumorigenesis. We propose to determine the dose and safety of UDCA when added to standard therapy for mCRC. Methods: Trial Design: UDCA doses will be escalated using a 3+3 design which will stop at the MTD or at two levels above an Active Dose (AD), whichever is the lowest. The AD is defined as the dose that will activate FXR. After a 7 day run-in period of UDCA only, cytotoxic combination chemotherapy and antiangiogenic agent for mCRC will be given along with the UDCA. The use of a run-in period allows for metabolic studies to identify serum biomarkers of FXR activation and to determine an AD. Treatment or intervention planned: UDCA is given during a run-in period of 7 days. At the end of the run-in period, standard doses of 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab are added. Patients are treated until excessive toxicity, progression of disease, or surgical resection. Major eligibility criteria: Patients with mCRC are eligible. Patients with greater than 10% body weight loss within 6 months of entering the protocol, a diagnosis of diabetes and active diabetes treatment are excluded from the study. Results: Current enrollment: Cohorts 1, 2, 3 have been completed without DLT. Enrollment to Cohort 4 began in 12/2011. Conclusions: Continue dose escalation until MTD or 2 levels above AD.Clinical trial registry number: NCT00873275.
Multivariate analysis of factors affecting overall survival in minority-based population of young colorectal cancer patients: A single-institution experience.
Authors: Jain Shivi , Agrawal Kireet , Pattali Shinoj , Singh Abhijai , Agrawal Kamal , Cleveland Barbara , Mullane Michael Russell
Published: March 2020

e14186

Background: Overall survival in colorectal cancer is influenced by obesity, age, gender and stage at diagnosis. However, in minority based populations, effect of the above factors on overall survival has not been studied in any detail. Hence, we undertook this retrospective study to evaluate effect of above factors on overall survival in young colorectal cancer patients. Methods: 1,195 subjects with colorectal cancer treated at John H. Stroger Hospital of Cook County between 2000 and 2008 were retrospectively analyzed. 179 subjects with age 50 years and younger were identified. 146 of 179 subjects with available Body Mass Index (BMI) in kg/m2 were included in the study. Effect of BMI, age, sex, race, LDH and CEA levels, stage, site of tumor, smoking and family history on overall survival was evaluated using standard statistical multivariate analysis. Results: In our population, 22 of 146(15%) were underweight (BMI<20), 56 of 146(38.4%) were normal weight (BMI 20-24.9), 46 of 146(31.5%) were overweight (BMI 25-29.9) and 22 of 146(15%) were obese (BMI >30). Male: female ratio was 1.4:1. 75 of 146(51.7%) were African American, 23 of 146(15.9%) were Caucasians. 50 of 146(34.2%) were stage IV colorectal cancer at diagnosis. On univariate analysis, BMI<20(p=0.031, HR 2.1, 95% CI 1.15-3.82), CEA >4ng/ml (p=0.005, HR 1.93, 95% CI 1.21-3.08) and stage IV colorectal cancer (p<0.001, HR 6.1, 95% CI 2.42-15.53) were significantly associated with decreased overall survival. LDH<200 U/L was significantly associated with improved overall survival (p 0.029, HR 0.6, 95% CI 0.391-0.950). On multivariate analysis, stage IV colorectal cancer was a single significant independent predictor of overall survival (p=0.001, 95% CI 2.47-27.78). CEA>4ng/ml was marginally significant for decreased overall survival (p=0.06, 95% CI 0.978-3.015). On the contrary, no statistically significant difference was found on overall survival with age, BMI>20, gender, race, tumor location, smoking and family history. Conclusions: Advanced stage and CEA >4ng/ml are independent prognostic variables for decreased overall survival in minority based population of young colorectal cancer.
A phase II study of biweekly paclitaxel and cisplatin chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma: Role of ERCC1 expression.
Authors: Huang Jing , Zhou Yi , Qu Tao , Zhang Hong-Tu , Mao You-Sheng , Zhu Hong-Xia , Quan Lan-Ping , Xing Pu-Yuan , Wang Jin-Wan , Jie He , Xu Ning-Zhi
Published: March 2020

e14502

Background: Recurrent or metastatic esophageal cancer has poor prognosis. Currently, the standard of care for esophageal cancer includes treatment with triweekly cisplatin-based chemotherapy. However, not all patients benefit from the treatment. To improve the response and identify specific marker for patient-personalized treatment, we designed this study to assess the efficacy and safety of biweekly paclitaxel and cisplatin combination for patients with recurrent or metastatic esophageal squamous cell carcinoma. The excision repair cross-complementation group 1 (ERCC1) expression to predict response is also assessed. Methods: Forty-six eligible patients were enrolled. Paclitaxel was given at 150 mg/m2 over 3 hours on day 1 and cisplatin was given at 50 mg/m2 on day 2, every 2 weeks as one cycle. ERCC1 protein expression was assessed by immunohistochemistry staining. Results: The overall response rate was 56.5% (26/46, 95% CI 42.2 %- 70.8%). Progression-free survival was 5.6 months (95% CI, 2.8-8.4 months) and the median actuarial survival time was 17.0 months (95% CI, 12.3-21.7months). There was a significant difference in median actuarial survival between the patients with a response compared to the non-responders (22.8 months vs. 7.4 months, p<0.0001). Overall survival at 1 year was 65.0%, and at 2 years was 34.0%, respectively. The most frequent toxicity for all patients was neutropenia (37.0% and 23.9% for grades 3 and 4, respectively). Patients with ERCC1 negative tumors had a higher treatment response than the ERCC1 positive group (radiological response rates; 92.3% vs.50%, p=0.013). Conclusions: Biweekly chemotherapy with paclitaxel and cisplatin was found to be active and generally well-tolerated. Our study indicates that expression of ERCC1 evaluated by immunohistochemistry is a promising predictive marker for response in patients with metastatic ESCC receiving cisplatin-paclitaxel regimen.
Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGF-i) following stereotactic body radiotherapy (SBRT).
Authors: Barney Brandon M. , Markovic Svetomir , Laack Nadia N. , Miller Robert C. , Sarkaria Jann Nagina , Macdonald Orlan Kenneth , Olivier Kenneth R
Published: March 2020

e14507

Background: Serious gastrointestinal injury (SGI) is a rare but documented side effect that can occur independently with agents that affect the vascular endothelial growth factor (VEGF) receptor or with stereotactic body radiotherapy (SBRT). The risk of SGI in patients treated with the combination of SBRT sequentially followed by a VEGF inhibitor (VEGF-i) is not yet quantified. We explored the incidence of SGI in patients treated with SBRT with or without VEGF-i therapy at a single institution. Methods: From May 2008 to August 2011, 76 patients with 84 primary or metastatic intraabdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Twenty of these patients (26%) received a VEGF-i within two years of completing SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The most common site treated with SBRT was the liver (n=43, 57%), and the most common histology was colorectal adenocarcinoma (n=18, 24%). Other common histologies included melanoma of the skin (n=14, 18%) and non-small cell lung cancer (n=10, 13%). The incidence of SGI (CTCAE v4.0 grade 3 to 5 ulceration or perforation) after SBRT was obtained, and the relationship between SGI and VEGF-i was examined. Other factors that could potentially contribute to SGI, such as radiotherapy dose to bowel, were also analyzed. Results: Seven patients (9%) experienced SGI at a median 4.6 months (range, 3-17 months) after SBRT. All seven had received a VEGF-i prior to SGI and within 13 months of completing SBRT, and five received the VEGF-i within three months of SBRT. The six-month estimate of SGI in patients receiving a VEGF-i within three months of SBRT was 38%. No SGI was noted in the 63 patients not receiving VEGF-i therapy after SBRT. The Log-Rank test showed a significant correlation between SGI and VEGF-i therapy within three months of SBRT (p=0.0006) but not between SGI and maximum radiotherapy bowel dose (p=0.20). Conclusions: The combination of SBRT and VEGF-i therapy results in a much higher risk of SGI than would be expected with either treatment given independently. Local therapies other than SBRT should be considered if a patient is likely to be treated with a VEGF-i in the future.
Cost-effectiveness of treating patients with advanced progressive pancreatic neuroendocrine tumors with everolimus versus sunitinib in the United States.
Authors: Chulikavit Maruit , Casciano Roman , Perrin Allison , Liu Zhimei , Wang Xufang , Babigumira Joseph , Grzegorzewski Kris , Garrison Louis P
Published: March 2020

e14525

Background: Everolimus and sunitinib were recently approved to treat patients with advanced, progressive pancreatic neuroendocrine tumors (pNETs). This analysis examined the projected cost-effectiveness of everolimus versus sunitinib in this disease setting from a US payer perspective. Methods: A lifetime (20-year) Markov model was developed to simulate a cohort of advanced, progressive pNET patients and to estimate the cost per life-year (LY) gained and quality-adjusted life-year (QALY) gained when treating with everolimus as compared to sunitinib. Absent head-to-head trials, efficacy data were based on a weight-adjusted indirect comparison of the two agents using the respective phase 3 trial data. Disease or health states considered in the model included: stable disease with no adverse events, stable disease with adverse events, disease progression, and death. Costs of anti-tumor therapies, symptomatic care drugs, and post-progression therapy were based on wholesale acquisition cost. Other costs including physician visits, tests, infusions, hospitalizations, adverse event costs, and end-of-life care costs were obtained from literature and/or standard sources such as the Healthcare Cost & Utilization Project and Medicare reimbursement rates. Utility inputs were based on a time trade-off study conducted in the United Kingdom. Sensitivity analyses were conducted to test the model’s robustness. Results: In the base case analysis, the estimated gain of everolimus over sunitinib was 0.448 LYs (0.304 QALYs) at an incremental cost of $12,673, resulting in an incremental cost-effectiveness ratio (ICER) of $28,281/LY ($41,702/QALY gained), which fell within the cost per QALY range for many other widely used oncology drugs. The ICER was most sensitive to the uncertainty of the sunitinib trial outcomes: however, a probabilistic sensitivity analysis found consistent results across simulations. Conclusions: While the analysis is limited by its reliance on an indirect comparison of two phase 3 studies rather than a single head-to-head trial, everolimus is projected to be cost-effective relative to sunitinib in advanced pNET.
CONKO-008: Oxaliplatin (O)/folinic acid (FA)/5-fluorouracil (5-FU) (24h) in combination with lapatinib as second-line therapy in pancreatic cancer after gemcitabine failure: A phase I trial.
Authors: Stieler Jens , Pelzer Uwe , Sinn Marianne , Striefler Jana Kaethe , Dörken Bernd , Riess Hanno
Published: March 2020

e14533

Background: ErbB-1 and ErbB-2 as its enhancer are expressed in pancreatic cancer. Based on the results of the 2nd-line chemotherapy (CT) with Oxaliplatin, 5-FU and Folinic acid (OFF) (CONKO-003; ASCO 2008) and the activity of EGFR- tyrosine kinase inhibition in pancreatic cancer (Moore JCO 2007), this trial aims to further improve therapeutic options for patients after Gemcitabine failure by combining OFF with lapatinib, a combined ErbB-1 and ErbB-2 tyrosine kinase inhibitor which showed preclinical synergy with 5-FU (Kim PloS One 2009). Methods: The daily dose of lapatinib combined with oxaliplatin 85 mg/m2 (2-4 h infusion d 8, 22), 5-FU 2000 mg/m2 (24 h continuous infusion d1,8,15,22 q d 42) and FA 200 mg/m2 (30 min infusion d1,8,15,22 q d 42). was expected to be between 750 to 1,500 mg, further dose intensification was not planned. Starting dose for lapatinib was set on 1,000 mg/day, with a minimum of 3 pts. on each level and extension to 6 pts. in case of a dose limiting toxicity (DLT). Maximum tolerated dose (MTD) was defined as a dose level (DL) below the level where 2/6 patients would show DLTs during cycle 1. Results: 18 Pts (12m/6w). have been enrolled in the trial.7 pts. were treated on 1,000 mg/d (DL 1), 5 pts. on level 1,250 mg/d (DL 2), and 6 pts. on 1,500 mg (DL 3). DLTs were met on DL 3 with diarrhea CTC grade 4 and concomitant neutropene enterocolitis in one patient and diarrhea CTC grade 3 in another patient. MTD is thus limited to 1,250 mg lapatinib in combination with OFF. Conclusions: With diarrhea as most prominent cumulative toxicity of the regimen, the maximum dose of lapatinib in combination with OFF is 1,250 mg. This dose may find further use in future phase II trials.
Dosing patterns of octreotide LAR among elderly patients with neuroendocrine tumors: Analysis of the SEER-Medicare database.
Authors: Xu Ying , Shih Ya-Chen T. , Leary Colleen , Shen Chan , Yao James C.
Published: March 2020

e14550

Background: Octreotide LAR is used for treatment of hormonal syndromes associated with NETs and may delay tumor progression. Although various dosages and schedules of administration have been reported, a systematic analysis has not been performed. Methods: Using the SEER-Medicare database, we identified patients diagnosed with NETs between July 1999 and December 2007. We then excluded those patients with poorly differentiated histology, under age 65 at diagnosis, enrolled in HMOs, and who did not have continuous Part A & B enrollment between NET diagnosis and the end of 12 months after the initial octreotide LAR use. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR from Medicare claims. For each patient, mean octreotide LAR dose per month was calculated and classified into five dosing categories, ≤ 10, 11-20, 21-30, 31-40, >40 mg, for the initial 3 months and every subsequent 3 months during the first year. Results: A total of 3,543 octreotide LAR treatments were observed among 355 patients during their first year of therapy. Dose given on a single day ranged from 10 mg to 90 mg. 86 (24.2%) patients required a ≥ 30% escalation in dose during the first year of therapy. The distributions of the mean monthly doses by dosing categories for the initial 3 months and the highest use 3 months during the first year are included in the Table below. 134 (37.7%) patients required doses greater than 30 mg per month. Conclusions: Our analyses showed that patients frequently required the escalation of octreotide LAR dose during their course of illness. A substantial number of patients required doses greater than the FDA approved dose of 30 mg per month. [Table: see text]
MEK/ERK pathway characterization and its prognostic implication in gastric cancer (GC).
Authors: Martin-Richard Marta , Tibau Ariadna , Ferre Malena , Castillo-Martin Mireia , Colomer Anna , Erill Nadine , Sancho Francesc , Gich Ignasi , Barnadas Agust
Published: March 2020

e14552

Background: MEK/ERK pathway is considered one of the main controllers of cell proliferation and survival and its deregulation has been involved in several tumors. Different mechanisms have been described leading to ERK activation and nuclear translocation including mutations on genes encoding pathway constituents', or upstream factors overexpression. Little is known about the status of this pathway in GC. The aim of our study was to evaluate the expression of different factors of this pathway in GC and their correlation with patient outcome. Methods: Fifty-eight patients with localized stage Ib-III GC who underwent radical surgery followed by adjuvant chemoradiotherapy were selected. ERK and its activated form (pERK) expression were analyzed by IHC, and KRAS and BRAF mutations were determined by PCR. Additionally, expression of upstream factors such as EGFR, HER2, VEGFR and downstream factor such as MST2 was evaluated by IHC. Finally, EGFR and HER2 copy number alterations were analyzed by FISH. Association of these markers to overall survival was assessed using the log rank test, and survival curves were plotted with Kaplan-Meier methodology. Results: Among the 58 tumors analyzed, 7% arose from the cardias and 33% corresponded to signet ring cell carcinomas. ERK and pERK expression was observed in the majority of tumors (86 and 64%, respectively, p=0.002). Cytoplasmic pERK expression did not show any association with the clinico-pathological characteristics. Notably, nuclear pERK (pERKnc) expression was observed in 12% of the cases and it showed a significant correlation with patient survival (p=0.05), conferring a worse prognosis. Moreover, EGFR overexpression (p=0.03) correlated with pERKnc. Finally, multivariate Cox analysis for survival confirmed that stage (HR 0.31, p=0.01) and pERKnc (HR 2.7, p=0.04) are unique independent prognostic factors. Conclusions: MEK/ERK pathway is commonly activated in localized GC, backed up by ERK and pERK being highly expressed in these tumors. Moreover, EGFR expression correlates with nuclear ERK expression, suggesting that ERK translocation to the nucleus could be mediated by this factor. More importantly, nuclear ERK has appeared as an independent marker of poor prognosis.
Treatment outcomes of peritoneal carcinomatosis arising from gastric cancer with no measurable disease using systemic chemotherapy.
Authors: Lee Guk Jin , Hong Sook Hee , Roh Sang Young , Hong Young Seon , Song Kyo Young , Park Cho Hyung , Lee Myung Ah , Kang Jin Hyoung , Lee Hee Yeon , Hong Ji Hyung , Jung Yun Hwa , You Si Young
Published: March 2020

e14558

Background: Although many clinical trials of newly developed chemotherapeutic drugs have been conducted, limited studies have focused on gastric cancer patients specifically diagnosed with peritoneal carcinomatosis (PC) without measurable regions. In the current study, we characterized the outcomes of systemic chemotherapy and prognostic factors for patients with gastric cancer PC, particularly in cases without measurable disease. Methods: Clinical data from 211 gastric cancer PC patients (137 without and 74 with measurable disease) subjected to systemic chemotherapy between January 2000 and December 2010 at a single center were reviewed. Results: Median OS rates of gastric cancer PC patients with no measurable disease were significantly longer than those of patients with measurable disease (18.2 vs 12.0 months, p=0.011). In multivariate analysis, poor PS (Hazard ratio (HR) = 2.33, 95% CI, 1.42-3.8, P=0.001), presence of metastatic lymphadenopathy (LAP) (HR=2.23, 95% CI, 1.42-3.5, p=0.002) and high-grade PC (HR=1.82, 95% CI, 1.09-3.04, p=0.025) were associated with significantly decreased OS. Combined with clinical PC grade and measurability of disease, median OS of patients with low-grade PC without measurable disease was 19.6 months (95% CI, 15.5-23.7 months). Median OS rates of 12.6, 13.7 and 6.8 months were estimated in high-grade PC without measurable disease, low-grade PC with measurable disease, and high-grade PC with measurable disease, respectively. Median OS of low-grade PC patients with no measurable disease was significantly higher than that of patients in all other groups (p=0.001, p=0.029 and p<0.001, respectively). Conclusions: Gastric cancer PC is a heterogeneous disease entity. In our study, clinically low-grade PC without measurable disease was associated with better outcomes than other groups following systemic chemotherapy. According to the carcinomatosis grade, specific groups of patients may benefit from systemic chemotherapy. Despite the difficulties of response assessment, further clinical trials for newer treatment strategies and molecular studies focusing on the heterogeneity of gastric cancer PC should be introduced.
Preoperative chemoradiation and cetuximab for resectable, locally advanced esophageal cancer: Preliminary results of a prospective phase Ib/II trial.
Authors: Brenner Baruch , Kundel Yulia , Purim Ofer , Medalia Gal , Olshinka Liran , Kashtan Hanoch , Menasherov Nikolai , Fenig Eyal , Sulkes Aaron , Idelevich Efraim
Published: March 2020

e14571

Background: This prospective phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative chemoradiation (CRT) in locally advanced esophageal cancer (LAEC). We hereby report its preliminary results. Methods: Patients (pts) with potentially resectable LAEC, defined as T2-4N0-1M0, T1-4N1M0 or T1-4N0-1M1A tumors, received an induction cycle of cisplatin 100 mg/m2, day 1, and 5-FU 1000 mg/m2/day as a continuous infusion (CI), days 1–5, followed 4 weeks later by 50.4 Gy radiotherapy (RT) given concurrently with 2 cycles of cisplatin 75 mg/m2 and escalating doses of CI 5-FU, days 1–4 and 29-32. Pts received also 10 weekly infusions of cetuximab, 250 mg/m2, with a loading dose of 400 mg/m2, starting from the induction. The phase II part of the study started when the 5-FU dose during CRT was defined. Surgery was planned 6-8 weeks after CRT. Results: Thirty-six pts have been enrolled to date and 32 completed CRT. The median age was 65 years and 60% were males. The ratio of squamous/adeno histologies was 53%/47%. Pts had very advanced tumors: 95% T3-T4, 63% N1 and 28% M1A. In the absence of dose limiting toxicity, 31 pts received the phase II dose of 5-FU, defined as 1000 mg/m2/day. The most common grade >3 toxicities were leucopenia (51% of pts) and neutropenia (48%). There was one toxic death, due to neutropenic sepsis. Among the 27 operated pts, R0 resection was achieved in 24 (89%). There were 4 cases (15%) of postoperative mortality, due to infection (3 pts) or respiratory failure (1). Downstaging was noted in 83% of pts and pathological complete response (pCR) in 32%. Pts with squamous histology had a higher pCR rate (53% vs 7%, p=0.007). At the time of the analysis, 14 pts (40%) remain free of disease and the local control rate is 92%. Updated results will be presented at the meeting. Conclusions: Preliminary results from this prospective study suggest that the addition of cetuximab to standard CRT is safe. The R0, pCR and local control rates are encouraging. Squamous cell tumors may gain more benefit from the addition of cetuximab.