bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and impact of K-ras mutation in colorectal cancer (CRC) in a minority population.
Authors: Dietz Donny , Braverman Albert S. , Axiotis Constantine A , Khillan Ratesh , Sidhu Gurinder Singh 
Published: March 2020

e14690 Background: K-ras mutation in CRC is known to occur in around 40% of the general population. It implies a poor prognosis, and resistance to anti- EGFR monoclonal therapy. The incidence of Kras mutation in African American (AA) patients with CRC is not known. Methods: Records of patients treated for CRC at Kings County Hospital and Downstate Hospital; in Brooklyn from 2005-12 were reviewed. Results: Of 116 patients’ records, 90 were informative for presenting stage, K-ras expression or both; all but one were AA, and 60 of 90 (67%) were male. Their ages ranged from 36 to 86 (median 64) years. The stages at presentation were known in 76; 3% were stage I, 17% stage II, 35% stage III and 45% stage IV. Follow-up periods ranged from 14 to 2381 days (median 409). K-ras mutation analysis was performed by a single commercial laboratory in 68 patients who had, or were suspected of having advanced disease. Codons 12 and 13 in K-ras exon 2 were analyzed. Of these 68 patients 31 (45%) bore K-ras mutations. K-ras mutation status was known in 9 stage I and II pts, and 6 of 9 pts (67%) bore mutations. After 233-967 days follow-up (median 474) 8 of 9 patients were alive. The 3 pts with wild type K-ras were a median of 70 years of age, 67% were female, and all were alive at median of 266 days (range 239-122-) follow up. Of the 16 stage III patients whose K-ras was analyzed, 7 (44%) were mutated. These 7 pts were a median of 66 years of age, and 86% were male. After 398 days median follow up 57% had relapsed and 45% had died. The 9 stage III pts with wild type K-ras were a median of 70 years of age and 78% were male. After a median follow up of 600 days, 2 were relapse-free, 7 had relapsed and 6 had died. Of the 34 stage IV pts, K-ras was analyzed in 29 and mutated in 12 (41%). Of the mutated patients, 83% were female and the median age 57. Their median survival was 557 days (56-1627). The 17 pts with wild type K-ras were 67% female with a median age of 59. Their median survival was 711 days (25-2040). The presenting CEA levels were similar in wild type and mutated patients. Conclusions: The prevalence of K-ras mutations, and the better prognosis of wild type K-ras in advanced CRC in AA patients, is similar to that of the general American population. The relapse rate of stage 3 AA patients seems higher in both wild type and mutated pts.
Can PET CT predict response in locally advanced rectal cancer patients treated with induction FOLFOX?
Authors: Gunduz Seyda , Coskun Hasan Senol , Goksu Sema Sezgin , Arslan Deniz , Tatli Ali Murat , Uysal Mukremin , Savas Burhan , Ozdogan Mustafa 
Published: March 2020

e14696 Background: The aim of this study was to determine the pathological complete response rates in a group of locally advanced rectal cancer patients who underwent chemoradiotherapy after treatment with induction FOLFOX chemotherapy and the relationship between the complete response and Positron emission tomography - computed tomography (PET-CT). Methods: The files of 239 patients who were diagnosed with rectal cancer between January 2008 and January 2012 were evaluated retrospectively. Of these, there were 24 locally advanced rectal cancer patients who met the following criteria: they were administered chemoradiotherapy after receiving four courses induction oxaliplatin, folinic acid and 5-Florouracil (FOLFOX) and they underwent PET-CT for staging and for the evaluation of their response to FOLFOX treatment. Of these 24 patients, 20 operable patients were included in the study. Results: The pathological complete response was obtained in 7 patients (35%) who were operated on, and then given induction four courses FOLFOX chemotherapy and chemoradiotherapy. We determined that age, gender, clinical stage at diagnosis, and PET-CT before and after induction chemotherapy were not predictive of the pathological complete response to tumor fluorodeoxyglucose (FDG) uptake activity. Conclusions: The rates of pathological complete response were increased in locally advanced rectal cancer patients who underwent short-term induction chemotherapy. Although the PET-CT has retained its importance in predicting pathological complete response, there is still a need for studies with a larger number of patients and long-term follow-ups.
Intergroup randomized phase III study of postoperative irinotecan, 5-fluorouracil, and leucovorin versus oxaliplatin, 5-fluorouracil, and leucovorin versus 5-fluorouracil and leucovorin for patients with stage II or III rectal cancer receiving either preoperative radiation and 5-fluorouracil or postoperative radiation and 5-fluorouracil: ECOG E3201—An updated survival analysis.
Authors: Nimeiri Halla Sayed , Feng Yang , Catalano Paul J. , Meropol Neal J. , Giantonio Bruce J. , Sigurdson Elin R. , Martenson James A. , Whitehead Robert P. , Sinicrope Frank A. , Mayer Robert J. , O'Dwyer Peter J. , Benson Al Bowen ,   Eastern Cooperative Oncology Group
Published: March 2020

e14711 Background: Postoperative adjuvant chemotherapy has been historically limited to single agent 5FU in stage II/III rectal cancer pts. This phase III trial evaluated differences between pts treated with adjuvant FOLFOX versus FOLFIRI versus FU alone in stage II/III rectal cancer. Methods: Eligibility: resectable (T3-4 N0,Tany N1-3) adenocarcinoma rectum ≤12cm from anal verge. Pts had the option to receive FU with pre or postoperative XRT (50.4Gy). Preoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm A), FOLFOX (arm B), FU/LV(arm C). Postoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm D), FOLFOX (arm E), FU/LV (arm F). Pts received 8 cycles. Overall survival (OS) was the primary endpoint. Secondary endpoints included toxicity, sphincter preservation and patterns of failure. Results: 225pts out of planned 3150 were enrolled (10/03 to 10/05). Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). 179 pts were randomized; (A:28, B:25, C:30, D:31, E:33, F:32). There was increased grade 3/4 toxicity, mainly diarrhea,in postoperative FU/XRT arms (D:39%), (E:28%), (F:48%). Twenty-two (12%) pts did not receive adjuvant therapy. At a median follow up of 7.4yrs, the five-year recurrence free rate was 69%. Median OS was 8.3 yrs. There was no statistical difference in OS between all randomized groups. Five-year OS in arms (A:B:C:D:E:F) were (73%, 83%, 83%, 73%, 78%, 73%) respectively. Conclusions: FOLFOX can be safely administered to rectal cancer pts following chemo radiation. Given limitations of early trial closure and small sample size, there was no difference in OS between pts who received FU alone, oxaliplatin based or irinotecan based adjuvant therapy. Clinical trial information: NCT00068692.
Preoperative chemoradiotherapy (QT-RT) with capecitabine and oxaliplatin (CAPOX) or capecitabine alone (CAP) in patients (PTS) with locally advanced rectal cancer (LARC).
Authors: Marrodan Ines , Rubio Itziar , Buque Aitziber , Sancho Aintzane , Fuente Natalia , Carrera Sergio , Arruti Mikel , Mane Joan Manel , Gutierrez Eddy Isabel , Iruarrizaga Eluska , Azkona Eider , Lopez-Vivanco Guillermo 
Published: March 2020

e14712 Background: Preoperative concomitant QT-RT has shown to improve sphincter preservation and local control in LARC. We analyzed two cohorts of pts diagnosed of LARC treated with QT-RT with CAP or CAPOX. Methods: Pts with LARC (T3-T4 and/or N+) were treated with pelvic radiotherapy (45Gy in 25 fractions) concomitant with oxaliplatin (50mg/m2 day 1, 8, 22 and 29) and capecitabine (1650mg/m2 on days 1 to 14 and 22 to 35) or CAP (825mg/m2 bid for 5 days/week). Surgery was scheduled 6 weeks after completion QT-RT. Main end points assessed were: toxicity of preoperative chemotherapy, rate of sphincter preservation, pathological complete response (pCR) rate, and progression-free survival (PFS). Results: From Aug 2002 to Nov 2012, 254 pts with LARC were included; 53 pts received preoperative chemotherapy with CAP (cohort A) and 201 pts with CAPOX (cohort B). Median age: 65. Pts characteristics in cohort A: ECOG 0/1/2: 13/35/5; upper/mid/distal rectum 5/25/23; stage II/III 10/43. Pts characteristics in cohort B: ECOG 0/1/2: 48/149/4; upper/mid/distal rectum 29/105/67; stage II/III 27/174. 51 pts in cohort A (96.2%) and 192 (95%) in cohort B received full dose of preoperative QT-RT. Main toxicities in cohort A were diarrhea grade 2/3: 2/3 and neutropenia grade 2/3: 1/0; in cohort B were diarrhea grade 2/3: 42/24, neutropenia grade 2/3: 2/1 and neurotoxicity grade 1/2: 94/7. Surgery: 53 pts (100%) in cohort A and 198 pts (98.5%) in cohort B. Sphincter preservation and R0 resections were achieved in 58% pts and 98% pts respectively in cohort A, and 62% pts and 91.5% pts in cohort B. pCR was achieved in 11% pts in cohort A and 17% pts in cohort B. 3-year PFS and overall survival were 62% and 82% respectively in cohort A, and 75% and 83% in cohort B. Adding oxaliplatin in pts cT4/N- or N+ does not improve PFS (p=0.73). Downstaging in cohort A and B was achieved in 69.8% pts and 65% pts respectively. Conclusions: Combination QT-RT based in CAP or CAPOX is a well tolerated regimen and achieved encouring rates of pCR, R0 resection, sphincter preservation and tumor downstaging without differences in PFS in high risk pts with LARC.
Incidence and risk of hand foot skin reaction (HFSR) in patients receiving regorafenib for cancer: A meta-analysis.
Authors: Belum Viswanath Reddy , Wu Shenhong , Lacouture Mario E. 
Published: March 2020

e14713 Background: Regorafenib (BAY 73-4506) is a potent oral multi-kinase inhibitor with targeted activity against (VEGFR) -1,-2, and -3, TIE-2, FGFR-1, PDGFR-α/β and ret, c-Kit, raf-1 kinases. Currently it is approved for treatment in previously treated patients with metastatic colorectal cancer (mCRC) and in locally advanced gastrointestinal stromal tumors (GIST), and is being explored in other cancers. We conducted a meta-analysis to ascertain the incidence and risk of HFSR, a commonly reported AE. Methods: Our search was performed on electronic databases (PubMed, Scopus, Web of Knowledge) and the ASCO website for presented abstracts. We searched for studies published until December 2012. Eligible Phase II-III clinical trials utilizing a 160mg dose of Regorafenib were included in the analysis. Relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: In these trials, regorafenib was investigated in mCRC, gastrointestinal stromal tumor (GIST), and renal cell carcinoma (RCC). A total of 1,078 patients were analyzed. The overall incidence of all-grade and high-grade HFSR was 60.5% (95% CI: 48.3–71.6%) and 20.4% (95% CI: 15.4–26.6%), respectively. The relative risks of all-grade and high-grade HFSR to regorafenib monotherapy in comparison with controls were increased for all-grade (RR=5.40, 95% CI: 3.76-7.76, p<0.001) and high-grade (RR=41.99, 95% CI: 5.88–299.93, p<0.001) HFSR. The incidence of the HFSR based on tumor type was 62.9% (95% CI: 46.9–76.5%) for mCRC, 69.5% (95% CI: 29.7–92.5%) for GIST and 46.6% (95% CI: 42.3–51.0%) for RCC, which was not very significant (p=0.08) suggesting that tumor type does not seem to influence the incidence of HFSR in patients treated with regorafenib. Conclusions: The incidence and risk of developing HFSR is highest with regorafenib, when compared to other multikinase inhibitors (e.g. sorafenib, sunitinib, pazopanib, axitinib). This toxicity warrants further investigation and evidence-based management strategies, in order to ensure adherence and most favorable clinical outcome.
Efficacy and safety of single agent (SA) or combination (CO) adjuvant chemotherapy (AC) in elderly patients with colon cancer: A Canadian Cancer Institute experience.
Authors: Kim Christina , Spratlin Jennifer L. , Ghosh Sunita , Armstrong Dawn Elizabeth , Mulder Karen E. 
Published: March 2020

e14715 Background: AC for colon cancer is recommended in the fit elderly. The pattern of AC use in elderly patients (pts), the toxicity profile, and survival benefit is unclear. We sought to: 1) determine whether patients ≥65 years old with stage III colon cancer were being offered SA or CO AC; 2) evaluate the reason for selecting SA vs. CO AC; 3) evaluate the toxicity profile of SA and CO in the elderly; and 4) determine whether a survival benefit exists for elderly pts receiving CO AC. Methods: Pts ≥65 diagnosed with stage III colon cancer at the Cross Cancer Institute from 2004-2010 were identified from the provincial cancer registry. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, AC protocols used, toxicity, dose reductions, dose delays and survival. Results: 258 pts ≥65 years old were diagnosed and treated with AC from 2004-2010. Of these, 168 were treated with SA and 90 with CO AC. The most common reasons for choosing SA AC were patient preference (64%), comorbidities (17%), and lack of drug coverage by provincial formulary (16%). 93 pts ≥age 75 were treated with SA AC, whereas only 20 pts ≥75 were treated with CO AC. Grade 3 and 4 non-hematologic toxicity was more common with CO AC (43% vs. 27%). 20% of all pts had initial dose reductions, with most common reasons being age and comorbidities. 67%, 71% and 29% received dose delays, reductions or drug discontinuation in the SA group, respectively. 72%, 58% and 34% received dose delays, reductions or drug discontinuation in the CO group respectively. 76% of pts received ≥75% of the expected cumulative dose in the SA group, and 81% in the CO group. The 5 year overall survival (OS) of pts who received <75% of expected AC cycles was 63%, compared to 79% in those who received >75% of expected cycles. The 5 year OS was 73% in pts who received SA AC, compared to 84% in those who received CO AC. Conclusions: In elderly pts treated with AC for stage III colon cancer, SA AC is used more frequently than CO AC, based on age, comorbidities, and patient choice. Toxicity with CO AC in elderly pts is high, but may carry a potential a survival benefit for those who receive it.
A retrospective analysis of the role of gefitinib in the definitive management of esophageal/gastroesophageal junction (E/GEJ) cancer.
Authors: Sohal Davendra , Rice Thomas W. , Rybicki Lisa A. , Rodriguez Cristina P. , Videtic Gregory M. M. , Saxton Jerrold P. , Murthy Sudish C. , Mason David P. , Phillips Brooke Elizabeth , Tubbs Raymond R. , Plesec Thomas , McNamara Michael J. , Ives Denise I. , Bodmann Joanna , Adelstein David J. 
Published: March 2020

e15000 Background: The role of epidermal growth factor receptor (EGFR) inhibition in resectable E/GEJ cancer is uncertain. We update and retrospectively compare results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery; the second study differing only by the addition of gefitinib (G) to the treatment regimen. Methods: Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma (ACA), with an endoscopic ultrasound stage of at least T3, N1, or M1a (AJCC 6th). Patients (pts) in both trials received 5-FU (1000mg/m2/d) and cisplatin (20mg/m2/d) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250mg/d, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Results: Clinical characteristics were similar between the 80 pts on the G trial (2003-2006) and the 93 pts on the no-G trial (1999-2003): median age (58 vs. 59 years), male gender (91% vs. 86%), ACA (94% vs. 83%), and HER2 positivity (28% vs. 18%). Minimum follow-up for all pts was 5 years. Multivariable Cox analyses comparing the G vs. no-G pts and adjusting for statistically significant covariates demonstrated improved overall survival (HR 0.62, 95% CI 0.44-0.88, p=0.008), relapse-free survival (RFS) (HR 0.59, 95% CI 0.41-0.84, p=0.003), and distant metastatic recurrence (HR 0.64, 95% CI 0.43-0.96, p=0.03), but not locoregional recurrence. Further subgroup analyses demonstrated improved RFS with G in pts not experiencing a pathologic response (HR=0.59, 95% CI 0.38-0.92, p=0.021), with T4 or M1a disease at surgery (HR=0.33, 95% CI 0.13-0.87, p=0.024), or with HER2-negative tumors (HR=0.65, 95% CI 0.42-0.99, p=0.048). Conclusions: Although this retrospective comparison can only be considered exploratory, it suggests that gefitinib may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer. Clinical benefit may be greatest in pts with a poor response to preoperative chemoradiation, and in those with HER2-negative tumors. Clinical trial information: NCT00258323.
Pharmacokinetic (PK)/pharmacodynamic (PD) results from a phase Ib study of pegylated hyaluronidase PH20 (PEGPH20) in combination with gemcitabine (Gem) in patients with pancreatic cancer.
Authors: Harris William Proctor , Hingorani Sunil R. , Beck Joseph Thaddeus , Berdov Boris A. , Wagner Stephanie Ann , Pshevlotsky Eduard M. , Tjulandin Sergei , Gladkov Oleg , Holcombe Randall F. , Jiang Ping , Maneval Daniel C. , Zhu Joy , Devoe Craig E. 
Published: March 2020

e15005 Background: Enzymatic degradation of hyaluronan (HA) is a novel strategy to target the desmoplastic stroma of pancreatic cancer. PEGPH20, a pegylated form of recombinant human hyaluronidase PH20, is an investigational drug in clinical trials. Preclinical studies demonstrate that sustained HA removal by PEGPH20 inhibits tumor growth and enhances chemotherapeutic activity in HA-rich xenografts and genetically engineered mouse tumor models. Ph1 PEGPH20 monotherapy studies show increased tumor perfusion by DCE-MRI, metabolic partial responses by FDG-PET, and stromal remodeling in tumor biopsies from selected advanced cancer patients (pts). Methods: This was a dose-escalation study to find the recommended Ph2 dose of PEGPH20 in combination with Gem in pts with Stage IV previously untreated pancreatic cancer. Pts received Gem at 1000 mg/m2 IV qwk for Wks 1-7 plus PEGPH20 at 1, 1.6, or 3 μg/kg IV twice a week for Wks 1-4 and qwk for Wks 5-7. Wk 8 was a rest week. Thereafter, PEGPH20 + Gem were given qwk for 3 wks in 4-wk cycles. Serial plasma samples were collected and hyaluronidase activity measured by an ultrasensitive assay to assess PEGPH20 exposure. Plasma HA catabolites were measured by quantitative HPLC to assess PD. Results: 28 pts were enrolled. Plasma PEGPH20 concentrations were proportional to dose, and kinetics were well-characterized by a 2-compartment PK model. Estimates for clearance (0.5-2 mL/hr/kg) were consistent with long t1/2 (1-2 days) previously seen with single-dose PEGPH20 monotherapy. Wks 1 and 4 PK profiles were similar, suggesting no changes to PEGPH20 clearance mechanisms after multiple doses or effects of Gem on PEGPH20 exposure. Most pretreatment plasma HA levels were <1 μg/mL and increased in a time- and dose-dependent manner after dosing. Circulating HA concentration was >500 µg/mL in several pts given 3 μg/kg PEGPH20. Conclusions: PEGPH20 plasma levels can be predicted using a linear PK model and circulating HA catabolites can be used as a quantitative measure of PEGPH20 PD. Results are consistent with the mechanism of action of hyaluronidase and support further study of PEGPH20 with anticancer agents. Clinical trial information: NCT01453153.
Multivariate analysis of prognostic factors in cancer of unknown primary (CUP) patients treated with site-specific therapy based on the 92-gene cancer classifier.
Authors: Schnabel Catherine A. , Zhang Yi , Hainsworth John D. , Spigel David R. , Greco F Anthony , Erlander Mark G. 
Published: March 2020

e15006 Background: Results from a single arm prospective study demonstrated overall survival of 12.5m in 194 patients that received first-line therapy directed by tumor classification using the 92-gene assay (JCO, 31:217-23). When the molecular assay predicted tumor types that were clinically more responsive, median survival was significantly improved when compared with predictions of more resistant tumors (13.4 v 7.6 m; p= 0.04).In this analysis, the survival benefit of assay-directed therapy was further evaluated after adjusting for pre-treatment prognostic factors. Methods: Cox proportional hazards regression was used to examine survival benefit of responsive tumor types (n=115) vs resistant tumor types (n=79) predicted by the molecular assay, after controlling for traditional prognostic factors. Results: Univariate Cox regression analysis (n=194) showed that ECOG status, responsive vs resistant tumor type, and assay probability were each significant prognostic factors. In multivariate analyses, the prognostic value of only ECOG status and the assay prediction of responsive vs resistant tumor type were maintained. Conclusions: These data demonstrate that the 92-gene assay results remained a significant independent variable affecting survival outcome in these patients after adjustment for prognostic heterogeneity, and provide further support of assay accuracy in molecular classification of CUP. Clinical trial information: NCT00737243. [Table: see text]
Frequency of relapse over time based on baseline stage in esophageal cancer patients treated with definitive chemoradiation (DCRT).
Authors: Wadhwa Roopma , Xiao Lianchun , Sudo Kazuki , Taketa Takashi , Blum Mariela A. , Skinner Heath D. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Komaki Ritsuko , Rice David C. , Swisher Stephen , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: March 2020

e15013 Background: Evidence for definitive chemoradiotherapy (bimodality therapy [BMT]) has been established for patients with Esophageal and Gastroesophageal Junction cancers (EGEJC) who do not qualify for surgery. Frequency of relapse over time based on baseline clinical stage is not well described. Methods: We analyzed 276 patients with EGEJC who underwent BMT. All the patients had pre- and post- chemoradiation, endoscopic biopsy and imaging study. The type and timing of first relapse or persistent disease after BMT was analyzed using 12-month intervals and was grouped by the baseline stage. Multiple statistical methods were used. Results: For 276 patients, the median follow-up time was 53.0 months (95% confidence interval [CI], 47.3-58.7) and the median overall survival was 27.0months (95% CI, 20.7-33.3). A total of 184 (66.7%) patients had a persistent disease or relapse after BMT: 120 distant metastases (43.5% of 276) and 64 local-regional disease (23.2% of 276). The table below demonstrates that baseline clinical stage has a great deal of influence on the frequency and timing of relapse (see Table). Conclusions: These data demonstrate that relapse timing and patterns are associated with the baseline clinical stage. Our data can contribute to an evidence-based surveillance strategy.[Table: see text]