bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of concomitant chemoradiotherapy with 5-fluorouracil (5-FU) single agent as neoadjuvant treatment regimen in mexican patients with stage III rectal cancer: Experience in the Oncology Hospital
Authors: Gomez Rangel J. , Alvarez Ordorica O. , Villalobos Valencia R. , Silva J. A. 
Published: August 2020

e15144 Background: To analyze overall survival, free disease survival, complete and partial pathologic response, effect of stage reduction, toxicity profile and number of anus preservative surgery in patients treated with concurrent chemo radiotherapy with a modified 5-FU single agent regimen as neoadjuvant modality treatment. Methods: Historic Cohort of patients treated in the Oncology Hospital, CMNSXXI between January 1999 to December 2004. The scheme used was a bolus of 5FU 425mg/m2 without leocovorin in three consecutive days each two weeks (days 1–3, 15 -17 and 29–31). Results and Conclusions: There were identified 96 consecutive patients with clinical stage III. The median age was 57.5 years. Ninety and two patients were operated and 51% was candidates to conservative surgery. There were 12.5% of complete pathologic responses and 35% of partial responses. The median of survival has not been reached. The five years of overall survival was 62% and the five-years of disease free survival was 55%. Stage reduction had impact in overall survival with 65% vs 40% at 9.5 years of follow up, and DFS was 58% vs 48% at 9.5 years. We report 16 cases of gastrointestinal toxicity grade 3 and two cases with grade 4. There was reported fourth cases of afebril neutropenia grade 4. Results in OS, DFS and number of complete pathological response were similar to reported by another oncology groups. Stage reduction was traduced in an increased of OS. This schedule can be feasible and applicable in another institutions in develop countries. No significant financial relationships to disclose.
Phase II study of NGR-hTNF, a selective vascular targeting agent (VTA), in previously treated patients with hepatocellular carcinoma (HCC)
Authors: Santoro A. , Citterio G. , Pressiani T. , De Braud F. G. , Gregorc V. , Rossoni G. , Donadoni G. , Caligaris-Cappio F. , Lambiase A. , Bordignon C. 
Published: August 2020

e15500 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to aminopeptidase N (CD13) overexpressed on tumor blood vessels. In preclinical models, NGR-hTNF has shown potent anti-vascular and antitumor activity, both at low and at high doses. Methods: Patients with recurrent or metastatic HCC were treated with NGR-hTNF given intravenously at 0.8 μg/m2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and a total of 27 patients to be enrolled after first and second stage, respectively. Progression-free survival (PFS) was the primary endpoint with reassessment performed q6w according to WHO criteria. Results: 27 patients with progressive disease following prior loco- regional treatment (59%), systemic therapy (56%), or both (33%) were evaluated over 86 cycles (range, 1 to 14). Patient characteristics were: median age 67 years (range, 53 to 79); M/F 21/6; PS 0/1 18/9; Child-Pugh class A/B: 21/6. No grade 3–4 treatment-related adverse events were observed. Main grade 1–2 toxicities were short-lasting infusion-related constitutional symptoms, including chills (55%). Median PFS was 2.3 months (95% CI, 1.7–2.9 months). One complete response (4%) lasting 9.0+ months was observed in a sorafenib-refractory patient and one partial response (4%) was reported in a Child-Pugh class B patient. Additionally, a 28% tumor shrinkage was detected in one out of six patients (22%) experiencing stable disease. The median PFS duration in stable or responder patients was 4.3 months (95% CI, 2.7–5.8 months). With a median follow-up of 7.6 months, the overall survival rates at 3 and 6 months were 82% and 60%, respectively. Conclusions: NGR-hTNF given at 0.8 μg/m2 every 3 weeks is well tolerated and appears to have promising antitumor activity in previously treated patients with advanced HCC. The drug will be further developed in this setting and, currently, an additional cohort of 12 patients has been enrolled and treated at same dose with a weekly schedule. [Table: see text]
KRAS and BRAF mutational status as response biomarkers to cetuximab combination therapy in advanced gastric cancer patients
Authors: Stella G. , Rojas Llimpe F. , Barone C. , Falcone A. , Di Fabio F. , Martoni A. , Lamba S. , Ceccarelli C. , Siena S. , Bardelli A. , Pinto C. 
Published: August 2020

e15503 Background: The prognosis of advanced gastric cancer (GC) patients (pt) is still poor despite the introduction of new chemotherapy regimens. In colorectal cancer (CRC) it has been demonstrated that KRAS or BRAF mutations are associated with resistance to treatment with the anti-EGFR mAbs. We have assessed whether, and to what extent, the mutational profile of KRAS and BRAF genes affects the response to cetuximab combination therapy in GC. Methods: We have collected 44 tumor samples from pts affected by locally advanced or metastatic GC undergoing cetuximab combination therapy as first-line treatment in two consecutive phase II studies. Thirteen pts received cetuximab plus FOLFIRI (FOLCETUX Study) and 31 pts cetuximab plus cisplatin and docetaxel (DOCETUX Study). Genomic DNA was extracted from paraffin-embedded tumor specimens from all cases. The mutational status of KRAS (exon 2) and BRAF (exon 15) was ascertained by PCR amplification followed by direct sequencing. The objective response was evaluated every 6 weeks by CT according to RECIST criteria. Results: KRAS and BRAF mutations were detected in 5 (11.4%) and 1 (2.3%), respectively, of the 44 tumors analyzed. These frequencies are consistent with those previously reported in GC. In the case of KRAS, 3 cases displayed amino acid substitutions of codon 12 and 1 of codon 13. One case had the A11V variant that had been reported in hematopoietic and lymphoid tissue of the stomach. The only BRAF mutation found in 1 sample was the classic V600E substitution. As a whole, 13.6 % of the analyzed tumors carried a mutation in either KRAS or BRAF genes. K-RAS and BRAF mutations were, as expected, mutually exclusive. In this pt cohort oncogenic activation of KRAS/BRAF-signaling pathways was not significantly associated to objective response (p= 0.757). Also, we found no correlation between KRAS/BRAF mutations and clinical outcome measured as overall survival. Conclusions: In advanced GC the frequency of mutations in KRAS and BRAF is lower as compared with CRC cancer. In our cases, the mutational status of KRAS and BRAF genes does not correlate with the response to cetuximab-based therapy in advanced gastric cancer patients. No significant financial relationships to disclose.
Preoperative chemoradiation and postoperative adjuvant tetrathiomolybdate for patients with resectable esophageal cancer
Authors: Urba S. , Schneider B. J. , Hayman J. A. , Orringer M. , Chang A. , Pickens A. , Pan C. , Lee J. , Foster J. , Merajver S. 
Published: August 2020

e15504 Background: Tetrathiomolybdate (TM) is an oral copper chelator. Copper is necessary for blood vessel growth, and so TM functions as an antiangiogenic agent. Methods: Pts with resectable esophageal cancer were treated at the University of Michigan with chemoradiation followed by surgery, and then 2 years of TM. Chemoradiation was cisplatin 60 mg/m2 on days #1 and 22, paclitaxel 60 mg/m2 on days #1, 8, 15, and 22, and radiation 1.5 Gy fractions b.i.d. x 3 weeks to a total of 45 Gy. Transhiatal esophagectomy was performed on approximately day #50. TM 20 mg p.o. q.d. was started approximately 4 weeks post-op, and continued for 2 years. Doses were adjusted to maintain the ceruloplasmin level between 5 and 15. Results: Between 1/23/02 and 1/24/06, 69 pts were enrolled. Pt characteristics: males - 62 (90%), females - 7 (10%); median age - 60 (range 42–74); adenocarcinoma - 56 (81%), squamous cell carcinoma 13 (19%). The chemoradiation was well tolerated: grade 3 leukopenia in 15 pts (22%), and 17 pts (25%) required feeding tubes. 66 pts went to surgery. 61 pts had a complete resection; 4 pts had metastases discovered at surgery, and 1 pt had extensive positive margins. Histologic complete response rate was 10%. 21 pts never received TM because of metastases noted in the peri-operative period, long post-op recovery time, or pt refusal. 48 pts started TM after surgery and it was well tolerated. Grade 3 toxicities were diarrhea -2 (3%), nausea - 2 (3%), dizziness - 2 (3%). 13 pts completed the full 24 mos of treatment, 12 completed 10–23 mos, 15 completed 2–8 mos, and 8 completed only 1 month or less. 27 pts have had disease recurrence, the majority (23 of the 27) of which was distant. Current status of pts with median follow-up time of 55 months: 25 alive and disease-free, 1 alive with disease, and 43 have died. 3-year survival probability is 47% (95% CI 35%-58.6%). 3-year recurrence-free probability is 51% (95% CI 38%- 62.7%). Conclusions: TM is an antiangiogenic agent which is fairly well tolerated. Prolonged adjuvant treatment over 2 years is difficult but not impossible to complete. Disease-free survival and overall survival are promising when compared to historical controls treated with a very similar chemoradiation regimen without TM in the past at the University of Michigan. [Table: see text]
A phase I study of gemcitabine plus dasatinib (GD) or gemcitabine plus dasatinib plus cetuximab (GDC) in refractory solid tumors
Authors: Uronis H. E. , Bullock K. , Blobe G. , Hsu S. , Morse M. , Nixon A. , Haley S. , O’Neill M. , Hurwitz H. , Bendell J. 
Published: August 2020

e15506 Background: Dasatinib (D) is a small molecule tyrosine kinase inhibitor with activity against both bcr-abl and src. Cetuximab (C) is a monoclonal antibody that blocks EGFR. Preclinical models suggest D reverses resistance to G. In addition, src and EGFR pathways interact; synergism of dual blockade by D + C is possible. We evaluated two combination regimens, GD and GDC, in a Phase I dose escalation study. Methods: Patients (pts) with advanced solid tumors were enrolled in cohorts of 3–6 to either GD or GDC. G was dosed in mg/m2 weekly for 3 of 4 weeks, D was dosed in mg PO BID, and C was dosed at 250 mg/m2 weekly after loading dose of C=400; cycle length was 28 days. Dose levels were as follows: 1) G 1000 + D 50 ± C; 2) G 1,000 + D 70 ± C; 3) G 1,000 + D 100 ± C. Standard cycle 1 DLT definitions were used. Eligible pts had advanced solid tumors, adequate organ and marrow function, and no co-morbidities that would increase risk of toxicity. Serum, plasma, and skin biopsy biomarkers were obtained pre- and on treatment. Results: 25 pts have been enrolled, including 21 with pancreatic adenocarcinoma, 3 of whom had received prior G. 21 pts were evaluable for toxicity and 18 for efficacy. Four DLT were observed: Gr 3 ANC with infection (GDC1, n=1), Gr 3 ALT (GD2, n=2), and Gr 5 pneumonitis (GDC2, n=1). Possible treatment-related adverse events in later cycles included: Gr3–4 ANC (n=4), Gr4 colitis (n=1), Gr3 bilirubin (n=2), Gr3 Hgb (n=2), Gr3 Plt (n=2), Gr3 edema/fluid retention syndrome (n=1), and Gr3 vomiting (n=2). One previously untreated pt had a partial response. Eight of 18 pts, 3 of whom had received prior G, had stable disease as best response, median duration = 5 months (range 1–7). Biomarker results are pending. Conclusions: The MTD of the GD arm is G1000/D50BID. Stable disease in previous G-refractory pts was noted. Hematologic toxicities were dose-limiting; later toxicities including hematologic, LFT changes, pneumonitis, and fluid retention were seen. To address these toxicities, once daily dosing of D will be explored, followed by an expanded cohort of G + daily D vs G + bid D in pts with treatment-naïve pancreatic cancer. [Table: see text]
A multicenter randomized phase II study of full-dose gemcitabine and concurrent radiotherapy comparing gemcitabine alone for the unresectable locally advanced pancreatic adenocarcinoma
Authors: Ioka T. , Takakura R. , Nakaizumi A. , Tanaka S. , Iishi H. , Nakamura S. , Nishiyama K. , Oohigashi H. , Ishikawa O. , Watanabe A. , Mukai S. 
Published: August 2020

e15512 Background: Some of locally advanced pancreatic cancers (LAPC) are considered to include a potential micro metastasis. We think that full-dose of gemcitabine (GEM) improve the outcome of LAPC. We report the efficacy of full-dose GEM and concurrent radiotherapy, comparing GEM alone for unresectable LAPC. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma were eligible for this study. We decide that LAPA which involved a major artery with CT imaging was unresectable. Patients were randomized into a concurrent chemoradiotherapy (CRT) group and a chemotherapy alone (CTX) group. GEM was given intravenously at a dose of 1,000 mg/msq over 30 min on days 1, 8 and 15 of each 28-day cycle and repeated until disease progression in both groups. Patients randomized into CRT group received a limited field irradiation with a total dose of 50 Gy in 25 sessions during first two cycles. The two groups were compared for mean survival, progression free survival and safety. Results: From September 2002 to April 2005, 80 patients were randomized at two institutions into the two arms of the trial (40 patients to CRT group and 40 patients to CTX group). The CRT group had better results than the CTX group as measured by mean survival time (391 vs 372 days, P< 0.02) and progression free survival (237 vs 128 days, P< 0.01). There were no differences in the safety between both groups. Conclusions: The concurrent chemoradiotherapy with full-dose GEM is effective and feasible in patients of LAPC compared with full-dose GEM alone. No significant financial relationships to disclose.
Response assessment of HCC undergoing chemoembolization by necrosis-adjusted models
Authors: Rosen M. A. , Ruutiainen A. , Siegelman E. , Jones L. , Sun W. , Reddy R. , Shaked A. , Olthoff K. , Soulen M. 
Published: August 2020

e15528 Background: Chemoembolization (CE) is an accepted therapy for unresectable HCC. As treated tumors may not shrink in size, response assessment via measurement of the enhancing tumor (EASL) has been proposed as an alternate to whole tumor (RECIST) measures. However, the reliability of this model has not been tested in clinical practice. Methods: We identified 29 HCC patients treated with CE with known overall survival (OS) in whom MRI before and after initial CE therapy was available for review. Three radiologists evaluated the imaging, measuring the largest liver lesion in three dimensions and the largest enhancing region in two dimensions. Readers also assessed percent tumor necrosis and overall tumor response qualitatively. Response models in 1-, 2-, or 3- dimensions, with or without necrosis adjustment, were created to assign patients to CR/PR/SD/PD classes, based on majority classification. Predictive value for OS was assessed for PD vs. other, and for PR/CR vs. SD/PD by the Students’ t-test. Inter-reader concordance was assessed by the Fleiss κ statistic. Results: For non-necrosis adjusted models, OS for progressors vs. non-progressors was statistically significant (p values: 0.0002–0.04), but could not identify early responders. Necrosis adjusted models failed to identify early progressors, but identified responders with improved OS (p values: 0.02–0.12). Inter-reader concordance was higher for necrosis adjusted models (κ range: 0.36–0.52) than for non-necrosis adjusted models (0.16–0.23). Viable tumor response by a two-dimensional product was superior to a one-dimensional diameter for predicting OS (p=0.04 vs. 0.74), and demonstrated higher inter-reader concordance (κ=0.46 vs. 0.30). Qualitative assessment of hepatic tumor could predict differences in OS for both PD vs. others (p=0.0001) and responders vs. non-responders (p=0.04), with acceptable inter-reader concordance (κ=0.34). Conclusions: Two- dimensional, but not one-dimensional, viable tumor measurement can identify response of HCC to chemoembolization and predict OS. Models which incorporate qualitative reader assessment of tumor necrosis may be more flexible than direct measures of viable tumor, and should be considered as alternatives for tumor assessment in chemoembolization. No significant financial relationships to disclose.
Renal atrophy secondary to chemoradiation treatment of abdominal malignancies
Authors: Salerrno May K. S. , Yang G. Y. , Iyer R. V. , Chandrasekhar R. , Wilding G. , Khushalani N. I. , Yendamuri S. S. , Gibbs J. F. , Fakih M. 
Published: August 2020

e15532 Background: Information on renal atrophy following abdominal chemoradiation (CRT) is limited. Methods: Patients who received concurrent CRT to the abdomen between 2002 and 2008 were identified for this study to evaluate change in renal size (RS) and function following CRT. Imaging and biochemical data were obtained prior to radiation (RT) and after RT in 6 month intervals. RS was defined by craniocaudal measurement on CT images. Renal function was assessed by serum creatinine and creatinine clearance (CrCl) using the Cockcroft-Gault formula. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Results: Median patient age was 64 years (range 31–87), 51.5% of 130 patients were male. Primary disease sites were pancreas (61.5%), periampullary (16.1%), stomach (10.8%), gastroesophageal junction (10%), and retroperitoneum (1.5%). Median follow up was 9.4 months (range 0–55.4 mos). Median radiation dose was 50.4Gy (range 12.6- 55.8Gy). Mean dose to the PK was 18.6 Gy. Compensatory hypertrophy of the non-PK was not seen. Age, gender, hypertension, diabetes, smoking, pre-RT CrCl, and pre-RT RS were not associated with renal atrophy at 12 months post RT. Percent volumes of the PK receiving ≥10Gy (V10), 15Gy (V15), and 20Gy (V20) were significantly associated with renal atrophy at 12 months post RT (p=0.0030, 0.0041, and 0.0046 respectively). Conclusions: Significant detriments in PK size and renal function were seen following abdominal CRT. V10, V15, and V20 were associated with renal atrophy at 12 months post RT. These observations can assist with renal dose constraints in CRT treatment planning for patients at increased risk for renal complications. [Table: see text] No significant financial relationships to disclose.
Influence of microscopic malignant peritoneal mesothelioma on posttreatment survival
Authors: Kluger M. D. , Chabot J. A. , Hesdorffer M. , DeRosa C. M. , Taub R. N. 
Published: August 2020

e15534 Background: Progression of malignant peritoneal mesothelioma to clinically evident disease is poorly understood. Operative cytoreduction and post-operative intraperitoneal chemotherapy, followed by a second operative cytoreduction with heated intraoperative intraperitoneal chemotherapy is protocol at Columbia University. Our ability to assess presence of microscopic disease at a unique second operation provides in vivo insight into disease progression. Methods: Operative, pathology and oncologist records were reviewed for 98 consecutive patients with peritoneal mesothelioma treated between 5/95 and 1/08. Microscopic disease was defined as positive pathology on random biopsies in the absence of gross disease at second operation, and disease-free as absence of gross and microscopic disease. Survival was defined as time from first operation to death or last follow-up. Survival and recurrence were compared using the Kaplan Meier and log-rank methods, and correlations by Fisher's exact method. Results: 98 first and 69 second operations were performed. Patients were 59% male, 88% Caucasian and mean age was 52. At the second operation, 38 had gross disease, 23 were disease-free and 8 had microscopic disease. Median follow-up was 21 months, median overall survival was 48 months, and median survival for the epithelial subtype was 64 months. There was no significant difference in survival between disease- free and microscopic pathologies (log-rank p<0.69). 72% of disease-free (SE 11%) and 80% (SE 18%) of those with microscopic disease were alive at 96 months. 16% of disease-free and 7% of patients with microscopic disease had a recurrence (p<0.4). The time to clinical recurrence for both disease-free and microscopic disease was not significantly different (log-rank p<0.88). Conclusions: Survival and clinical recurrence in those with microscopic disease, none of whom were treated for this entity, were not significantly different from those who were disease-free at the second operation. These in vivo after treatment findings suggest that malignant peritoneal mesothelioma may progress slowly from microscopic to clinical disease and can be closely monitored rather than aggressively treated after initial cytoreduction and intraperitoneal chemotherapy. No significant financial relationships to disclose.
Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: A phase II trial
Authors: Ng T. , DiPetrillo T. , Suntharalingam M. , Fontaine J. , McNulty B. , Akerman P. , Chen W. , Horiba M. N. , Burrows W. , Safran H. 
Published: August 2020

e15542 Background: Paclitaxel poliglumex (PPX) is a drug conjugate that links paclitaxel to poly-L-glutamic acid thereby increasing its radiation enhancement factor to 4.0 to 8.0 compared to 1.5–2.0 for paclitaxel. The Brown University Oncology Group previously performed a phase I study establishing the dose of single agent PPX with radiation, and the combination of PPX, cisplatin and radiation for esophagogastric cancer. A phase II study was therefore initiated to evaluate the pathologic response rate of neoadjuvant PPX, cisplatin and radiation for patients with esophageal cancer. Methods: Eligible patients had pathologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or GE junction with no evidence of distant metastasis. Celiac nodal disease was allowed. Patients received weekly PPX 50mg/m2 and cisplatin 25mg/m2 for 6 weeks with concurrent with 50.4Gy of radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Results: Twenty-three eligible patients have been enrolled. The median age is 63 years. Grade 3/4 treatment related toxicities in the first 15 patients include dehydration (n=5), anorexia (n=5), esophagitis/dysphagia (n=4), electrolyte abnormalities (n=3), nausea (n=2), hypersensitivity (n=2), weight loss (n=1), and anemia (n=1). One patient developed carcinomatous meningitis during treatment. Five of the first 11 patients (45%) undergoing resection had a pathologic complete response. Conclusions: This preliminary data suggests that PPX may provide enhanced radiosensitization as compared to standard paclitaxel, consistent with the preclinical data of PPX and radiation. No significant financial relationships to disclose.