bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of KRAS, NRAS, and BRAF testing and timing among mCRC patients treated at community cancer centers in the United States.
Authors: Lowe Kimberly , Kelsh Michael Anthony , McCarl Kevin , Bohac Gerry C.
Published: February 2017

695

Background: The requirement to establish RAS status prior to administration of an EGFR inhibitor has increased the need to understand which patients are tested for RAS and the length of time it takes for the treating oncologist to receive the RAS test result. Our objective was to evaluate factors that may influence RAS testing among patients with metastatic colorectal cancer (mCRC) and the turn-around time for RAS testing among patients who are treated at community cancer centers in the United States (U.S.). Methods: The sample includes 1550 patients in the Oncology Services Comprehensive Electronic Records (OSCER) database who were diagnosed with mCRC between 1/1/2011 and 8/31/2015. Patient demographics and clinical characteristics were evaluated at the time of mCRC diagnosis. The median number of days and interquartile range (IQR) between the following dates was summarized: diagnosis for mCRC, tissue collection for biomarker testing, tissue was received by the lab for biomarker testing, and biomarker results returned to the oncologist. Results: The frequency of RAS testing was as follows: KRAS (n = 964; 62%), NRAS (n = 116; 7%), BRAF (n = 231; 15%), all three simultaneously (n = 94, 6%). There were significant differences in KRAS testing by age and type of insurance, with young (p < 0.001) and commercially-insured (p = 0.01) patients more likely to receive testing. The median number of days and IQR between specimen collection and diagnosis of mCRC was as follows: KRAS (0; 0 to 443), NRAS (0; -18.5 to 362), and BRAF (-3; -474 to 0). The median number of calendar days between the date the specimen was collected and the date it was received by the lab was as follows: KRAS (19; 1 to 303), NRAS (34.5, 8 to 518), and BRAF (29; 2 to 428). The median number of days between the date the specimen was received by the lab and the date the result was returned to the oncologist was as follows: KRAS (7; 5 to 13), NRAS (10; 7 to 15), and BRAF (8; 6 to 14). Conclusions: Many patients had a specimen collected for biomarker testing at the time of mCRC diagnosis and the results were generally returned to the treating oncologist within one week of it arriving at the lab.
Evaluation of hypersensitivity reactions to oxaliplatin in gastrointestinal malignancies.
Authors: Markey Kelly , Gatewood Tyra , Valone Tiffany , Strosberg Jonathan R.
Published: February 2017

709

Background: Oxaliplatin is an important component of therapy for multiple gastrointestinal cancers. The incidence of hypersensitivity reaction (HSR) to oxaliplatin is approximately 10%, and about 3% are serious in nature (Grade 3 or 4). Data on management of hypersensitivity reactions is limited to small case series, with scarce information on the success rates of rechallenging patients who have previously reacted. Methods: We conducted a retrospective review of patients who had a documented hypersensitivity (HSR) to oxaliplatin utilizing our internal adverse event reporting system from January 1, 2007 until December 31, 2012. Results: 44 patients met inclusion criteria for this study. The majority had a grade 1 or 2 reaction (n = 36 or 81.82%). Seven patients had a grade 3 reaction and one patient experienced a grade 4 reaction. 29 patients were rechallenged with oxaliplatin during subsequent courses. Infusion durations were extended in 79% of cases, and additional premedications were administered in 90%. Two patients were treated with a desensitization protocol, which consisted of serial dilutions of oxaliplatin (given over approximately 8 hours) with a two-stage premedication regimen. With these measures, seventeen of the twenty-nine patients (66%) were able to receive 3 or more additional infusions, thirteen (45%) received 5 or more additional infusions, and 4 (14%) we able to receive 10 or more additional infusions. Conclusions: Our review of hypersensitivity reactions to oxaliplatin demonstrates that the majority of patients experience mild (Grade 1 or 2) reactions and are able to be successfully rechallenged in subsequent courses with modifications in the infusion rate and premedications. The use of these treatment strategies may prevent premature discontinuation of an important backbone drug for the treatment of gastrointestinal malignancies.
Dihydro pyrimidine dehydrogenase deficiency in patients treated with capecitabine-based regimens: A retrospective tertiary care centre experience.
Authors: Sahu Arvind , Ostwal Vikas S. , Ramaswamy Anant
Published: February 2017

712

Background: Capecitabine is an integral part of treatment of gastrointestinal cancers. Dihydropyrimidine dehydrogenase (DPD) enzyme is rate limiting in the metabolism of capecitabine, deficiency of which leads to myelsuppression, mucositis, diarrhea, hand foot syndrome (HFS) and rarely, death. Data regarding the toxicity of capecitabine in patients with DPD deficiency in the Indian context is scarce. Methods: 506 patients were treated with capecitabine containing regimens with a dose range of 1250 mg/m2/day to 2000 mg/m2/day during the period from June 2013 to May 2015 in the Gastrointestinal Medical Oncology Unit of our institution. Patients with Grade 3/4 toxicities requiring in-patient care (life threatening complications) were planned for DPD activity testing by Peripheral Blood PCR sequencing. Results: 27 patients developed Gr 3/4 toxicities during cycle 1 of capecitabine. It included mucositis in 22 (81.5 %), diarrhea in 25 (92.6%), HFS in 10 (37%) and myelosuppression in 4 (14.8%). 19 were found to be DPD deficient with 5 patients negative for DPD mutation. 3 patients did not do the DPD analysis as advised. Homozygous mutations were seen in 9 (33.3%) and heterozygous mutations in 10 (27%) of patients. More than one mutation was seen in 10 patients (37%). The relative frequencies of mutation were Exon 14 (44.4%), Exon 2 (25.9%), Exon 13 (25.9%), Exon 6 (11.1%) and Exon 18 (7.4 %). Post Cycle 1 of capecitabine, the drug was stopped in 5 patients (18.5%), regimen changed in 2 (7.4%) and dose reduction by 50% of the drug was done in the remaining patients. Despite dose reduction and change in therapy during Cycle 2, patients still had Grade 3/4 toxicities including mucositis in 7(25.9%), diarrhoea in 10 (37%), HFS in 7 (25.9 %) and myelosuppression in 6 (22%) of patients. Conclusions: Capecitabine can also lead to severe toxicities in DPD-deficient patients. Dose reduction of capecitabine in DPD deficient patients may not completely ameliorate the future risk of life – threatening complications. Screening for DPD deficiency prior to administration of capecitabine in toxicity prone nutritionally deficient Indian patients should be further evaluated based on this data.
Pathologic complete response rates after neoadjuvant treatment in rectal cancer: An analysis of the NCDB.
Authors: Lorimer Patrick D. , Kirks Russell C. , Boselli Danielle , Crimaldi Anthony Joseph , Hill Joshua S. , Salo Jonathan C.
Published: February 2017

713

Background: Pathologic complete response (pCR) of rectal cancer following neoadjuvant therapy is associated with decreased local recurrence and increased overall survival. The present study utilizes a large national dataset to identify predictors of pCR in rectal cancer. Methods: The NCDB was queried for patients with non-metastatic rectal cancer (2004-2011) who underwent neoadjuvant therapy (regional radiation dose 4500 cGy, boost dose 540 cGy) followed by surgical resection. Generalized linear mixed models were used to analyze the probability of pCR by hospital volume with adjustments for demographic, socioeconomic, staging, and tumor characteristics. Hospitals were separated into groups based on the number of resections performed per year <2, 2-5, and 5+. To account for clustering of cases at individual hospitals, a random effect was used at the hospital level and covariates were included as fixed effects. Results: 7,859 patients met inclusion criteria from 951 participating hospitals. Generalized linear mixed models demonstrated that the odds of achieving pCR was independently associated with more recent diagnosis, female gender, private insurance, smaller tumor size, lower grade, lower clinical T-classification, increasing interval between the end of radiation and surgery, and treatment at higher volume institutions (Table). Conclusions: The incidence of pCR was associated with favorable tumor factors (size, grade, T classification), demographics (insurance status) as well as treatment factors (time between radiation and surgery and institutional volume). With the data available, it is not clear what is driving the higher rates of pCR at high volume institutions. Research specifically targeted at understanding processes which are associated with pCR in high volume institutions is needed so that similar results can be achieved across the spectrum of facilities caring for patients in this population. [Table: see text]
Colorectal cancer patient outcomes in Nigeria: Results from the African Colorectal Cancer Group.
Authors: Alatise Olusegun Isaac , Komolafe Akinwunmi O. , Famurewa Olusola C , Katung Aba Ibrahim , Ariyibi Olufemi O , Egberoungbe Adedeji A , Olatoke Samuel Adegboyega , Agodirin Olayide S , Olaofe Olaejinrinde O , Kolawole Oladapo Adedayo , Eaton Anne , Kingham T. Peter ,   African Colorectal Cancer Group (ARGO)
Published: February 2017

729

Background: Colorectal cancer (CRC) is a growing problem in sub-Saharan Africa. There are, however, limited data describing the demographics, risk factors, presentation, treatments, and outcome of patients with CRC there. We established the African Colorectal Cancer Group (ARGO) to prospectively capture data and tissue from patients with CRC in Nigeria. This is vital to guide screening and treatment trials. Methods: The Consortium consists of 5 hospitals in Nigeria and MSKCC (USA). We have been prospectively collecting data since 2013. Tissue and blood samples were obtained. Ultrasounds and CT scans were provided by an NCI grant. Overall survival from date of diagnosis was estimated using Kaplan-Meier methods. Results: 152 patients have been accrued. The majority was male (56.8%), the median BMI was 22, the majority were non-smokers (89.1%) and non-drinkers (73.5%). Many patients had symptoms, as 65.8% of patients presented with obstruction or bleeding, 52.1% of patients had pellet like stool, and 88.4% had weight loss. 33.3% saw a traditional healer prior to presentation. The common locations of the primary tumor were rectum (52%) and right colon (23%). 8 patients (6.4%) had CEA > 30 ng/mL. The majority of patients presented with advanced disease. 43 (32.3%) patients had T3 tumors; 87 patients (66.9%) had T4 tumors. AJCC stage was II (n = 12, 9.3%), III (n = 34, 26.4%), and IV (n = 83, 64.3%). 97 patients (66%) had surgery. The most common operations were right hemicolectomy (23.1%) and diverting colostomy (22.4%). 110 patients (88.7%) had chemotherapy recommended; only 71 patients (61.2%) received chemotherapy. The reasons for not receiving chemotherapy included patient finances (n = 19) and mortality (n = 12). The commonly utilized chemotherapies were FOLFOX (n = 24) and XELOX (n = 15). 62 patients died with a median follow-up among survivors of 4.4 months. Overall 12-month survival from date of diagnosis (N = 138), was 48.4% (95% confidence interval 38.9-60.1). Conclusions: The majority of patients that present to hospitals in Nigeria with CRC are stage IV. The mortality rate is high. These data serve as a baseline to judge current screening trials. Identifying high-risk patients for screening is vital to improve outcomes.
Use and impact of selective internal radiation therapy (SIRT) in routine care patients with metastatic colorectal cancer (mCRC).
Authors: Lee Belinda , Wong Hui-Li , Field Kathryn Maree , Nott Louise M. , Shapiro Jeremy David , Wong Rachel , Power Jeremy David , Kosmider Suzanne , Lim Lionel , Gibbs Peter
Published: February 2017

742

Background: The liver is the dominant site of metastasis in patients (pts) with mCRC. Radioembolisation is a potential option in the multidisciplinary management of these patients. Recently initial analysis of a randomised controlled trial (RCT) in the 1st line setting demonstrated no overall progression free survival (PFS) benefit from adding SIRT, but prolongation of liver PFS (HR 0.69, p=0.002) was seen. Methods: Consecutive pts with mCRC enrolled from January 2009 were identified from a prospective multi-site Australian registry. Characteristics and outcomes for pts selected for treatment with SIRT were analysed. Results: Of 1,694 pts with mCRC, 580 (34.2%) had liver only disease at diagnosis, 409/580 (70.5%) with synchronous vs 166/580 (28.6%) with metachronous disease. Of pts with liver only disease, 187 (32.2%) were considered resectable at diagnosis, 100 (17%) as potentially resectable and 293 (51%) were treated with palliative intent. Overall 47 pts received SIRT with 1stline chemotherapy (CT). SIRT treated pts were more likely to have a synchronous presentation (85% vs 68%, p=0.01), liver only disease (83.0% vs 27.3%, p=<0.01), to be ECOG 0 (51.1% vs 34.6%, p=0.01), to be younger (60.8 years vs. 65.9 years, p=0.008) and to be enrolled on a RCT (38.3% vs 7.3%, p=<0.01). In the liver only population treated with palliative intent, SIRT treated pts (n=30) vs CT only pts (n=188) had a median PFS of 10.6 months vs 9.9 months (HR 0.87, p = 0.18) and a median OS of 24.3 months vs 19.3 months (HR 0.73, p = 0.04). Conclusions: SIRT is rarely used in the 1st line treatment of mCRC in routine practice. The available data suggests that OS gains can be seen in the absence of differences in PFS. However, this observed differential effect on survival maybe due to selection biases. SIRT treated patients were significantly younger and fitter than the CT alone group. Future analyses will include a multivariate analysis and examine the impact of the recently presented SIRFLOX trial data on the use of SIRT in clinical practice.
An open-label, randomized, parallel-group study of the pharmacokinetics of trifluridine as a component of TAS-102 versus FTD alone.
Authors: Sun Weijing , Rosen Lee S. , Rasco Drew W. , Yoshida Kenichiro , Seraj Jabed , Shapiro Geoffrey , Cleary James M.
Published: February 2017

751

Background: TAS-102 is a novel oral combination therapy of FTD plus tipiracil hydrochloride (TPI) with FTD:TPI molar and weight ratios of 1:0.5 and 1:0.471, respectively. FTD is a thymidine-based nucleoside analog that has shown antitumor effects in preclinical and clinical studies. TPI stabilizes orally administered FTD by inhibiting thymidine phosphorylase and TAS-102 has shown efficacy in refractory metastatic colorectal cancer. The objective of this study was to show that TPI, administered with FTD as TAS-102, increases exposure to FTD in patients with advanced solid tumors. Methods: This is a Phase 1, randomized, open-label, pharmacokinetic study of TAS-102 in patients with advanced solid tumors. On the morning of Day 1, one group received TAS-102 35 mg/m2 and the other group received FTD 35 mg/m2. Both groups received TAS-102 35 mg/m2 on the evening of Day 1, then twice daily on Days 2-5 and 8-12 in a 28-day cycle. Blood samples were collected to evaluate FTD AUC0-last and Cmax (primary endpoints). Results: Overall, 44 patients (50% male, mean age 57 years) were treated. After a single dose, the ratio of the geometric mean of FTD AUC0-last and Cmax were 38- and 22-fold higher, respectively (Table) following TAS-102 vs FTD alone. After multiple doses (Day 12 in Cycles 1, 2, or 3), FTD AUC and Cmax were ~3- and 2-fold higher, respectively, than after a single dose of TAS-102 (Day 1). For TPI, AUC and Cmax were similar after single and multiple doses of TAS-102. After Cycle 1, FTD did not accumulate with successive cycles of TAS-102 treatment. The most commonly reported treatment-related adverse events were nausea (47.7%), fatigue (31.8%), and anemia (27.3%), with Grade 3-4 events at 4.5%, 2.3%, and 18.2%, respectively. Grade ≥ 3 decreases in neutrophil counts were observed in 42.9% of the TAS-102 group. Conclusions: TPI, in combination with FTD, substantially increased exposure to FTD vs FTD alone. Clinical trial information: NCT01867866. [Table: see text]
Risk evaluation of postoperative complication in patients undergoing rectal cancer surgery.
Authors: Miyakita Hiroshi , Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Okada Kazutake , Saito Gota
Published: February 2017

756

Background: Colorectal cancer patients with postoperative complications have poor long-term outcomes. Rectal cancer is associated with a higher incidence of complications than colon cancer. Reliable predictors of complications would facilitate determination of surgical procedures such as stoma creation. We examined the relations between five kinds of risk score and postoperative complications in patients(pts) with rectal cancer. Methods: The subjects were 261 pts with cStage II/III rectal cancer from 2003 to 2013. We categorized complications into all complications, leakage, infectious complications and intestinal obstruction. Estimation of physiologic ability and surgical stress comprehensive risk scores (E-PASS CRS), surgical Apgar scores (SAS), prognostic nutritional index (PNI), colorectal physiological and operative severity scores for the enumeration of mortality and morbidity (CR-POSSUM), and neutrophil-lymphocyte ratios (NLR) were assessed. Clavien-Dindo (CD) Grade 3a or higher requiring surgically invasive treatment were considered complications. For leakage, CD Grade 3b or higher were considered complications. Results: Complications occurred in 56 pts (21%), leakage (L) in 12 (14%), infectious complications (IC) in 19 (7%), and intestinal obstruction (IO) in 16 (6%). E-PASS CRS significantly correlated with all complications (OR 3.45; p < 0.001), IC (OR 0.26; p = 0.008), L (OR 4.94; p = 0.027), and IO (OR 3.92; p = 0.007). PNI correlated with all complications (OR 0.38; p = 0.002) and IO (OR 3.08; p = 0.024). NLR correlated with all complications (OR 0.40; p = 0.003), IC (OR 0.25; p = 0.004), L (OR 8.66; p < 0.001), and IO (OR 3.86; p = 0.007). SAS correlated with IC (OR 0.19; p = 0.004). CR-POSSUM correlated with all complications, (OR 2.26; p = 0.009), IC (OR 5.02; p < 0.001), and IO (OR 0.28; p = 0.014). Multivariate analysis revealed E-PASS CRS (OR 6.17 p = 0.020) and NLR (OR 7.11 p = 0.011) were independent risk factors for L. Conclusions: Five kinds of risk score were all useful for assessing the risk of complications in rectal cancer. NLR was the only risk factor for leakage that could be used before surgery. Our results suggest NLR might be an auxiliary means of evaluating the need for creation of diverting stoma.
Prediction of the long-term outcomes associated with body mass index and advanced gastric cancer.
Authors: Kim Jae Gyu , Kim Beom Jin , Chi Kyong-Choun , Park Jung Min , Kim Mi Kyoung , Hwang In Kyu
Published: February 2017

82

Background: Radical gastrectomy followed by adjuvant chemotherapy for advanced gastric cancer brings about serious nutritional impairment. Recent studies have shown an association between body mass index (BMI) and perioperative outcomes of gastric cancer. However, little is known about the association between BMI and long-term outcomes of advanced gastric cancer. Our study evaluated the clinical impact of BMI on the long-term outcomes of gastric cancer staged at II and III, treated by radical gastrectomy followed by adjuvant chemotherapy. Methods: We analysed a total of 211 cases of advanced gastric cancer stage II and III between January 2005 and December 2010 at Chung-Ang University Hospital. The patients were divided into 4 groups according to BMI; underweight, normal, overweight, and obese. In addition, they were divided into two groups (BMI-High vs BMI-Low). We assessed age, sex, tumor location, lymph node involvement, operation method, initial cancer stage, recurrence, and survival (overall survival and disease free survival) between two groups. Results: We classified them into 4 groups according to BMI; underweight, normal, overweight, and obese. There was no difference in overall survival between normal, overweight, and obese group. However, there was significant difference between underweight group and the other groups. As for disease free survival, similar findings were observed. Among 211 patients, 154 patients (72.9%) were included in BMI-L (body mass index < 25), whereas 57 patients (27.1%) in BMI-H (body mass index ≥ 25). There was no difference in age, sex, tumor location, stage, lymph node involvement, operation method, recurrence, and cancer-related death between two groups. When classified into 4 groups as stage II in BMI-H, stage II in BMI-L, stage III in BMI-H, and stage III in BMI-L, overall survival showed significant difference in stage, however, no difference between BMI-H and BMI-L. Disease free survival showed no significant difference in stage and BMI, especially, no significant difference between stage II in BMI-L and stage III in BMI –H. Conclusions: Our findings suggest that preoperative BMI may predict the long term outcomes of advanced gastric cancer after radical surgery and chemotherapy.
Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.
Authors: Tsai Franklin C , Ghorbani Shireen , Greenwald Bruce D , Jang Sunguk , Dumot John A. , McKinley Matthew J , Shaheen Nicholas J. , Habr Fadlallah , Wolfsen Herbert C. , Abrams Julian A. , Lightdale Charles , Nishioka Norman S , Johnston Mark H. , Zfass Alvin , Coyle Walter
Published: February 2017

83

Background: Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity and mortality. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study was to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal cancer. Methods: This study includes patients enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from twelve academic and community practices. Endoscopic spray cryotherapy was performed until local tumor eradication was confirmed by biopsy or until treatment was halted due to progression of disease, patient withdrawal or co-morbidities. Results: One-hundred and eight patients (median age 75.5, 79.6% male, 93.5% adenocarcinoma, mean length 5.2 cm) underwent 442 treatments (mean 4.2 per patient). Tumor stages included 40 with T1a, 27 with T1b, 10 with unspecified T1, 15 with T2, and 16 with no T stage reported. One-hundred and six patients completed treatment with complete response of intraluminal disease in 54.7%, including complete response in 74.4% for T1a, 50% for T1b, 65.3% for all T1, 6.7% for T2, and 50% for those with no T stage reported. Mean follow-up was 17.3 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 11 of 108 patients (10.2%) but were present before spray cryotherapy in 3 of 11. Conclusions: This study suggests that endoscopic spray cryotherapy is safe, well tolerated and effective for early esophageal cancer in patients who are not candidates for conventional therapy.
Outcomes and toxicity in patients treated with bimodality or trimodality therapy for esophageal carcinoma with intensity modulated radiation therapy (IMRT).
Authors: Patel Ajay , Ko Stephen , James Sarah Elizabeth , Ashman Jonathan Ben , Rule William G. , Hobbs Corey James , Hallemeier Christopher Leigh , Brennan Emily R. , Heckman Michael , Tzou Katherine S. , Vallow Laura , Peterson Jennifer Layton , Miller Robert Clell , Buskirk Steven J.
Published: February 2017

88

Background: There is not yet a consensus on the efficacy and safety of IMRT for the treatment of patients with esophageal carcinomas. We report on our experience with outcomes and toxicity with IMRT for these patients. Methods: Fifty-five patients with esophageal carcinoma were treated with IMRT at our institution from 12/2008 and 12/2014. Medical records were retrospectively reviewed. All patients received concurrent chemotherapy (majority 5-FU with oxaliplatin). Thirty-one (56%) patients underwent surgery. Fifty (91%) received 50.4 Gy in 28 fractions. Seventy-three percent of cases were adenocarcinoma. Regions include mid-thoracic (15%), lower thoracic (64%), and GE junction (22%). Clinical uT-stages were as follows: T1 (2%), T2 (20%), T3 (69%), and T4a (5%). Clinical N-stages were as follows: N0 (33%), N1 (53%), N2 (13%), and N3 (2%). Results: Median follow-up for all patients was 15 months (1.5 - 64.5) and 25.5 months (1.5 - 64.5) for patients who were alive at follow-up (n = 31). Fifty-one (93%) patients completed RT. Of the 31 patients who underwent surgery, 9 (29%) were found to have a complete pathologic response. Site of first recurrence was local (n = 2, 4%), regional (n = 3, 6%), and distant (n = 14, 26%). At 12 and 24 months, overall survival was 72% and 58%, freedom from recurrence was 78% and 65%, and freedom from distant recurrence was 78% and 68%. On univariate analysis, improved OS was noted with patients who underwent surgery (RR 0.29) or were cN0 (RR 0.27). Twenty eight patients (51%) experienced > / = CTCAE v.4grade 3 acute toxicity; notable were hematologic (n = 14, 25%), esophagitis (n = 6, 11%), acute coronary event (n = 1, 2%), and post-chemoRT pneumonia (n = 1, 2%). Fifteen patients (31%) experienced > grade 3 late toxicity; notable were esophageal stricture (n = 7, 14%), post-op pneumonia (n = 3, 6%), post-CRT pneumonia (n = 2, 4%), and COPD exacerbation (n = 1, 2%). Conclusions: Patient receiving IMRT with concurrent chemotherapy for esophageal carcinomas have good LC rates, with or without surgery. Majority of patients are able to finish treatment with acceptable rates of late toxicity. Patient who underwent surgery or were cN0 had better OS.
Changes of weight and body composition after gastrectomy in the elderly gastric cancer patients.
Authors: Segami Kenki , Aoyama Toru , Maezawa Yukio , Kano Kazuki , Sato Tsutomu , Ogata Takashi , Cho Haruhiko , Yoshikawa Takaki
Published: February 2017

89

Background: Body weight, especially lean body mass, significantly reduces after gastrectomy for gastric cancer due to surgical invasion, reduced food intake, or decreased mobility, which could decrease quality of life and toxicity / compliance of adjuvant chemotherapy. These risks might be high especially in the elderly gastric cancer patients. However, it remains unclear whether changes of weight and body composition are different between the elderly and the non-elderly. Methods: This retrospective study examined patients who underwent curative surgery for gastric cancer between June 2010 and March 2014. Body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery (first measurement), at 1 week after surgery (second measurement), at 1 month after surgery (third measurement), and at 3 months after surgery (forth measurement). Patients were classified to the elderly (> 75 years) and the non-elderly ( < 75 years). Results: Four-hundred forty three patients (100 for the elderly and 343 for the non-elderly) were entered in the present study. Patients backgrounds, surgical factors, clinicopathological factors, surgical complications and adjuvant chemotherapy were not significantly different between the two groups. %Body weight loss until 1week, 1month, 3 months after surgery, defined as the proportion of the difference between 1st measurement and each measurement after surgery against 1st measurement, was 3.3%, 6.6%, and 9.7%, respectively in the elderly and 3.7%, 5.4%, and 8.2%, respectively in the non-elderly with significant difference (p = 0.05, 0.01, and 0.01, respectively). %Lean body mass loss until 1 week, 1 month, 3 months after surgery was 3.2%, 5.6%, and 6.1%, respectively in the elderly and 3.2%, 4.5%, and 4.2%, respectively in the non-elderly with p value of 0.36, 0.08, and 0.01, respectively. %Fat loss was not significantly different between the two groups at any time. Conclusions: Decreases in body weight and lean body mass after gastrectomy were more serious in the elderly patients as compared with the non-elderly. Surgical indication for the elderly must be carefully determined considering the risk and the benefit.
Alteration of recurrence patterns and prognostic factors by adjuvant S-1 monotherapy in patients with stage II/III gastric cancer.
Authors: Kanda Mitsuro , Kobayashi Daisuke , Tanaka Chie , Iwata Naoki , Yamada Suguru , Fujii Tsutomu , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro
Published: February 2017

90

Background: Survival benefit of adjuvant S-1 monotherapy among East Asian patients with stage II/III gastric cancer (GC) has been demonstrated by the ACTS-GC trial. Little is known about the changes in prognostic factors and recurrence patterns after it has become widespread as a standard of care. Methods: We enrolled 171 patients with stage II/III GC, 92 patients who underwent gastrectomy alone, and 79 patients treated with S-1 adjuvant. To balance more strictly the essential variables including stage of progression, we conducted propensity score analysis and 70 pairs of patients were generated from each group. Prognostic factors were compared between the groups and initial recurrence patterns were investigated to explore reasons for the change. Results: In concordance with the previous phase 3 trial, overall and recurrence-free survival were better for the S-1 adjuvant group. In the surgery alone group, carcinoembryonic antigen > 5 ng/mL, total gastrectomy, vessel invasion, pT4, and stage 3 were identified as significant prognostic factors. In striking contrast, macroscopic tumor size > 50 mm was the only significant prognostic factor for the S-1 adjuvant group. The lower overall recurrence rate of the S-1 adjuvant group was attributable mainly to a significant decrease of peritoneal recurrence. Conclusions: Prognostic factors changed substantially after implementation of S-1 adjuvant treatment. Macroscopic tumor size should be considered for patient stratification and selection of treatment options for patients with stage II/III GC.
Clinicopathological features of ruptured GIST in the ReGISTry study of high risk GIST patients after complete resection in Japan.
Authors: Nishida Toshirou , Kondo Masato , Ozaka Masato , Cho Haruhiko , Komatsu Yoshito , Doi Toshihiko , Baba Hideo , Kitagawa Yuko , Kurokawa Yukinori , Kanda Tetsuo , Sugiyama Toshiro , Sawaki Akira , Kakeji Yoshihiro , Hirai Toshihiro , Hato Shinji , Shirao Kuniaki , Ishioka Chikashi , Hirota Seiichi , Kagimura Tatsuo , Takagi Masakazu ,   STAR ReGISTry Gtoup
Published: February 2017

96

Background: Ruptured GIST, either preoperatively or intraoperatively, has ominous prognosis and is classified as high risk GIST in the modified Fletcher risk stratification. Although patients (pts) with these GISTs are recommended for 3-year imatinib adjuvant therapy, their clinicopathological features and compliance of guidelines are unknown. Methods: Between Dec. 2012 and Aug. 2015, 474 pts with high-risk GISTs locally diagnosed were prospectively registered. Among them, 453 pts with GISTs histologically confirmed by central review were analyzed. There were 243 males and 210 females with median age of 65 yrs. In the central review, H&E, immunohistochemistry, and genotyping were tested. Results: Disease was located in the stomach (n = 279), small intestine (n = 137), large intestine (n = 25), or others (n = 12). Median tumor size was 7.7 cm and median mitosis (local pathology) was 10/50HPF. Tumor rupture was seen in 54 pts (12%) who had preoperative rupture (28 pts) or intraoperative rupture (25 pts). After surgery, adjuvant therapy was administered for 342 pts (75%) and withheld for 89 pts (20%). Tumor rupture was frequently observed in small intestinal GIST (23.6%) other than the duodenum and in epithelioid and/or mixed features (24%). Mitosis of ruptured GIST (median = 5.0/50 HPF) was significantly lower than that of non-ruptured (11/50 HPF). Age, gender, tumor size and genotype are not related with rupture. There was no difference in postoperative complications and adhibition of adjuvant therapy in pts who have ruptures vs pts who don’t. Preoperative rupture was associated with small intestinal GIST and R1 surgery. Mitosis was significantly lower in GIST with preoperative rupture (5/50 HPF) than that without rupture (11/50 HPF). GIST with intraoperative rupture (11.8 cm) was larger than that without rupture (7.5 cm) although there was no difference in mitosis, location and genotype. Frequency of intraoperative rupture was not different between laparoscopic surgery (4.8%) and open one (6.3%). Conclusions: Tumor rupture was not infrequent in high risk GIST and half of rupture was occurred during surgery, which may be related to large tumor size but not with laparoscopic surgery. Clinical trial information: UMIN000009531.
An investigator sponsored phase Ia/Ib trial of selinexor in combination with irinotecan in patients with adenocarcinoma of stomach and distal esophagus.
Authors: Soares Heloisa P. , Kim Richard D. , Almhanna Khaldoun , Willians-Elson Irene , Kothari Nishi , Mahipal Amit
Published: February 2017

TPS176

Background: The karyopherin protein Exportin 1 (XPO1) is highly expressed and associated with poor prognosis in gastroesophageal tumors. XPO1 is responsible for nuclear export of major tumor suppressor proteins and other proteins including topoisomerases leading to carcinogenesis and drug resistance. KPT-330 (selinexor) is an oral, first in class, covalent Selective Inhibitor of Nuclear Export that specifically blocks XPO1. In gastric cancer xenograft models, treatment with selinexor resulted in > 75% inhibition of tumor growth. Synergistic activity has been observed with the combination of XPO1 inhibitors and topoisomerase inhibitors. Methods: This is a phase I study with cohort expansion that utilizes the standard 3+3 design for dose escalation. The primary endpoint is to evaluate the safety, tolerability and determine the maximally tolerated dose (MTD) of selinexor in combination with irinotecan. Patients with recurrent, metastatic or unresectable histologically confirmed gastric or distal esophageal adenocarcinomas are eligible for this study. Patients must have received at least one line but less than three lines of prior systemic therapies. Secondary endpoints are to explore the safety, tolerability and efficacy of this combination at the established MTD and characterize its pharmacokinetics. Correlative studies will be performed to assess if differential levels of serum and tissue biomarkers including XPO1, cytokine levels and changes in gene expression, before and after selinexor dosing, correlate with clinical outcomes. Circulating tumor cells will be collected in the expansion cohort. Up to 18 patients will be enrolled in 3 dose level cohorts (40, 50 and 65mg/m2) of selinexor in combination with irinotecan (125mg/m2). Selinexor will be given orally on days 1, 3, 8 and 10 of a 21 days cycle. Irinotecan will be given on days 1 and 8. The MTD is defined as the highest dose level at which 1 or less of 6 patients experience a DLT. An additional cohort of 15 patients will be accrued once the recommended dose for expansion is determined. As per September 2015, 3 patients have been included on cohort 1. Clinical trial information: NCT02283359 Clinical trial information: NCT02283359.
A phase II study of laparoscopic hyperthermic intraperitoneal chemoperfusion (HIPEC) for gastric carcinomatosis or positive cytology.
Authors: Badgwell Brian D. , Blum Mariela A. , Das Prajnan , Elimova Elena , Mansfield Paul F. , Ajani Jaffer A.
Published: February 2017

TPS186

Background: Over the last 2 decades, intraperitoneal chemotherapy has been found to have activity for select subgroups of patients with carcinomatosis from colon, ovarian, appendiceal, and recently, gastric origins. However, there is little data to support an aggressive surgical approach of cytoreduction (debulking) and HIPEC for patients with gastric cancer and positive cytology or carcinomatosis. The morbidity and mortality rates of cytoreduction and HIPEC, in combination with gastrectomy, are significant and the survival rates of this approach may not extend beyond that of treatment with systemic chemotherapy. The purpose of this clinical trial, therefore, is to perform HIPEC in a neoadjuvant fashion via a minimally invasive approach without cytoreduction for patients with gastric cancer and positive cytology or low volume carcinomatosis. Patients found to have resolution of all extra-gastric disease will then be candidates for gastrectomy. Methods: Patients with gastric and gastroesophageal adenocarcinoma and positive peritoneal cytology or radiologically-occult carcinomatosis that have completed treatment with systemic chemotherapy are offered participation in the study. Type and duration of systemic chemotherapy is left to the discretion of the treating medical oncologist. Laparoscopic HIPEC consists of Mitomycin C 30 mg and Cisplatin 200 mg in 3-7 liters of infusate circulated using an extracorporeal circulation device at a flow rate of 700-1500 mL/minute for 60 minutes, performed no sooner than 3 weeks after completion of systemic chemotherapy. The Laparoscopic HIPEC procedure may be performed up to 5 times, with a minimum of 3 weeks between procedures. After laparoscopic HIPEC, subjects whose disease did not progress will proceed to surgery with diagnostic laparoscopy and possibly exploratory laparotomy to assess resectability, and if their cancer is resectable will undergo gastrectomy. After completion of study–related treatment, subjects will be followed until recurrence and/or death for up to five years. Fourteen of planned 30 patients have been enrolled (NCI-2014-01105). Clinical trial information: NCI-2014-01105.
PLATFORM: Planning treatment of oesophago-gastric (OG) cancer—A randomised maintenance therapy trial.
Authors: Cafferkey Catherine , Chau Ian , Thistlethwaite Fiona , Petty Russell D. , Starling Naureen , Watkins David , Rao Sheela , Saffery Claire , Patel Bijal , Peckitt Clare , Cunningham David
Published: February 2017

TPS187

Background: Outcomes for patients with advanced OG cancer remain poor, median overall survival for fit patients treated with platinum and fluoropyrimidine based chemotherapy is less than one year, with second line chemotherapy resulting in a modest (approximately 6 weeks) survival benefit for selected patients. Evidence from NSCLC trials suggests a survival benefit from maintenance treatment following first line chemotherapy. Emerging data also supports the use of immunotherapy in previously treated OG cancer. The PLATFORM study aims to evaluate maintenance therapy in patients with advanced OG cancer. Methods: This is a prospective, open label, multicentre, randomised phase II clinical trial which will recruit at multiple UK cancer centres. Eligible patients are those who have measurable stable disease or better following completion of first line chemotherapy (at least 6 cycles) for locally advanced unresectable or metastatic disease. First line chemotherapy regime should contain a platinum and 5-fluoropyridimine (with trastuzumab if HER2 +), doublet or triplet drug combinations are permitted. Maintenance strategies are split by HER 2 status. For HER2 negative patients these are: Arm A1: surveillance, Arm A2: capecitabine, Arm A3: MEDI 4736 (anti PDL1 inhibitor) and for HER2 positive patients; Arm B1: trastuzumab, Arm B2: in development. Target recruitment is six hundred and sixteen patients, 154 patients will be recruited to each arm, with an interim analysis following recruitment of 61 patients to each arm. An adaptive trial design enables ineffective treatments to be discontinued early, with the opportunity to add novel treatment arms as the trial progresses. Primary endpoint is progression free survival. Secondary endpoints are progression free rate at 3, 6 & 12 months, overall survival, objective response rate by RECIST 1.1, toxicity and analysis of efficacy endpoints according to biomarker status for selected arms. Thirty two patients have been registered for the study with 3 patients randomised, recruitment is ongoing. Clinical trial information: EUDRACT: 2014-002169-30.
A phase I study of veliparib (ABT-888) in combination with capecitabine (C) and temozolomide (T) in patients (pts) with advanced well-differentiated unresectable neuroendocrine tumors (wdNET).
Authors: Thota Ramya , Dahlman Kimberly Brown , Koyoma Tatsuki , Berlin Jordan
Published: February 2017

TPS466

Background: Veliparib (V) is a novel orally bioavailable PARP-1 and -2 inhibitor which potentially synergizes with temozolomide (T). A single arm phase II study combining C and T has shown promising activity in well-differentiated NETs with overall response rate of 43%. Hence, we propose to combine V with C and T optimizing the interaction of V with T by dosing the V during the T to produce improved clinical activity in pts with wdNETs. Methods: This is an investigator initiated, single institution, phase I, dose-escalation trial using a modified Toxicity Probability Interval (mTPI) design. The primary objective is to estimate the maximum tolerable dose (MTD), which is defined as the dose level at which the probability of dose limiting toxicities (DLTs) is 0.33. Secondary objectives include assessing safety profile, antitumor activity and progression free survival. Inclusion criteria: Pathologically confirmed metastatic unresectable well-differentiated (low grade and intermediate grade) NETs that demonstrate progressive disease in the prior 12 months, ECOG PS 0-2 and adequate organ function. Exclusion criteria: severe hypersensitivity reaction to C, 5-FU, T or dacarbazine or uncontrolled chronic illness. Prior treatment with both C and T. Administration and design: We initially will fix doses of C and T at C: 750 mg/m2 po twice a day (BID) on days 1-14 and T at 100 mg/m2 po BID on days 10-14. V is given orally on days 10-14 along with T. We have 5 planned V dose levels (20, 40, 60, 80, 100 mg). If dose level 1 is too toxic we will go to C 600 mg/m2, T 75 mg and V 20 mg. Patients will be enrolled in cohorts of 3. The dose escalation/de-escalation will be as per pre-specified guidelines from the mTPI design. The planned sample size is 21 based on the anticipated number of patients available for this study within 18 months. This trial will be terminated when the maximum sample size (21) is reached or if the lowest dose is deemed too toxic. The study will start enrolling patients October 2015.
APACT: Phase III randomized trial of adjuvant treatment with nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with resected pancreatic cancer (PC).
Authors: Tempero Margaret A. , Cardin Dana Backlund , Goldstein David , O'Reilly Eileen Mary , Philip Philip Agop , Riess Hanno , Macarulla Teresa , Yung Lotus , Li Mingyu , Lu Brian D. , Biankin Andrew
Published: February 2017

TPS473

Background: Gem therapy improves outcomes in pts with resected PC. However, disease recurrence is common, prompting a need for improved regimens. nab-P + Gem was superior to Gem alone in MPACT, a phase III trial of pts with metastatic PC (mPC) for all endpoints, including overall survival (OS; median, 8.7 vs 6.6 months; hazard ratio [HR] 0.72; P < 0.001). Toxicities were manageable and consistent with prior studies. The APACT trial will compare adjuvant nab-P + Gem vs Gem alone in pts with resected PC. Methods: Pts (≈ 800) with confirmed PC (R0 or R1 resection); stage T1 - 3, N0 - 1, M0; Eastern Cooperative Oncology Group performance status ≤ 1; adequate organ function; and CA19-9 < 100 U/mL within 14 days of randomization are eligible. Pts with mixed-origin tumors; present or previous mPC; any other malignancy within 5 years of randomization; HIV or hepatitis B or C infection; or prior neoadjuvant treatment or radiotherapy for PC are ineligible. Randomization should occur once pts adequately recover from surgery but ≤ 12 weeks after surgery. Pts will receive 6 cycles of either nab-P 125 mg/m2 plus Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Stratification factors are resection (R0 vs R1) and nodal (LN+ vs LN−) status and geographic region (North America vs Europe vs Australia vs Asia Pacific). Pts with > 2 dose reductions will be discontinued. The primary endpoint is independently assessed disease-free survival (DFS). Secondary endpoints are OS and safety. Quality of life and correlation of tumor heterogeneity with clinical outcome are exploratory outcomes. At least 489 DFS events from 800 pts will allow 90% power to detect an HR for DFS of 0.74 at a 2-sided significance level of 0.05. Interim analyses, 1 for safety (after 100 pts are treated for ≥ 2 cycles) and 2 for efficacy (the first for futility and the second for futility and superiority), will be performed. As of July 2015, > 400 pts were enrolled, and 80% of all activated study sites (n = 141) randomized ≥ 1 pt. Of the 674 screened pts, ≈ 25% were ineligible, mainly due to postsurgical disease recurrence identified at screening. Pt enrollment is ongoing. ClinicalTrials.gov: NCT01964430. Clinical trial information: NCT01964430.
A randomized, multicenter, double-blind, placebo-controlled study of the Bruton tyrosine kinase inhibitor, ibrutinib, versus placebo in combination with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).
Authors: Tempero Margaret A. , Coussens Lisa M , Fong Lawrence , Manges Robert , Singh Priyanka , Li Yunfeng , Cole George W. , James Danelle Frances , Tabernero Josep
Published: February 2017

TPS483

Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred regimen for front-line treatment. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) shows antitumor activity in preclinical PDAC models, in part, due to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia with simultaneous enhanced presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015). This randomized trial will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind RESOLVE trial (NCT02436668; PCYC-1137-CA) will compare ibr vs. placebo in combination with Nab-P/GCB in approximately 320 patients with untreated metastatic PDAC. Key eligibility criteria include histologically confirmed metastatic PDAC; stage IV diagnosis within 6 weeks of randomization; adequate hematologic, hepatic, and renal function; and Karnofsky performance score ≥ 70. Key exclusion criteria include prior therapies (chemotherapy for primary PDAC, BTK inhibitor, or radiotherapy), neuroendocrine or acinar pancreatic carcinoma, known brain or leptomeningeal disease, and history of stroke or intracranial hemorrhage < 6 months prior to enrollment. Patients will be randomized to oral ibr (560 mg) or matched placebo given daily in combination with Nab-P (125 mg/m2) and GCB (1,000 mg/m2) on days 1, 8, and 15 of a 28-day cycle until disease progression or treatment is no longer tolerated. A safety run-in phase will evaluate the ibr combination prior to the randomization portion of the study. The primary endpoint is progression-free survival; secondary endpoints include overall survival and safety. Enrollment in the trial has been initiated. Clinical trial information: NCT02436668.