bluuebunny/crossref_metadata_2025 huggingface dataset:
Sorafenib in hepatocellular carcinoma (HCC) patients after liver transplantation
Authors: Feun L. G. , Levi D. , Moon J. , Nishida S. , Island E. , Selvaggi G. , Martin P. , Savaraj N. , Mendes F. , Tzakis A.
Published: August 2020

e15579

Background: Sorafenib has been approved for the treatment of advanced HCC. However, there is no data on its use for HCC patients (pts) after liver transplantation (OLT). Pts at high risk for tumor recurrence (native liver showing vascular invasion, multiple tumors >3 in number, size >6 cm, or lymph node involved) after OLT or who develop recurrence after OLT have worse prognosis. These pts may potentially benefit from sorafenib. Methods: We reviewed our experience with HCC pts after OLT treated with sorafenib. 15 pts had a starting dose of 400 mg po bid and 3 had a starting dose of 200 po bid. Sorafenib was started 3 months (mo) after OLT as adjuvant therapy (7 pts) or at the time of tumor recurrence after OLT (11 pts). CT or MRI scans of the chest/abdomen and physical exams were performed every 2–3 mo. Lab tests including serum AFP were performed monthly. Results: Median age was 60 (range 53–75). Median performance status was 90%(range 80–100). In terms of toxicity, 4 of the 15(27%) pts on the initial dose of 400 mg bid stopped sorafenib due to unacceptable toxicity and 5 (33%) had dose reduction due to toxicity. Grade 3/4 toxicity included skin rash, fatigue and anorexia, hyperbilirubinemia, chest/abdominal pain. Only 40% could continue at the full recommended starting dose of sorafenib.For the 11 pts with recurrent disease after OLT treated with sorafenib, the sites of evaluable disease include liver (5 pts), lung (3), others (3). One pt (9%) had a partial response in lung metastases for 10 mo. and the median time to tumor progression (TTP) was 4 mo. (range 2–10 mo). For pts on adjuvant sorafenib after OLT, no pt has relapsed so far with a median followup of 6+ mo. (range 2+ to 15+ mo). Conclusions: The response rate and TTP for pts treated with sorafenib for recurrent HCC after OLT is similar to HCC pts without OLT (Llovet, NEJM 2008). Since the majority of HCC pts after OLT treated with sorafenib required either dose reduction or stoppage due to toxicity which is higher than previously reported, a lower starting dose with dose escalation may be preferred. Contributing factors for toxicity may include the anti-rejection drugs (tacrolimus, mycophenolate, steroids) used for OLT which might affect pharmacokinetics(PK) of sorafenib. Further PK studies with sorafenib in HCC pts after OLT for future clinical trials are indicated.

No significant financial relationships to disclose.
Fixed dose rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced biliary cancer
Authors: Lee S. , Ryoo H. , Bae S. , Song H. , Kim M. , Lee K. , Lee W. , Park K. , Kim J. , Baek J.
Published: August 2020

e15581

Background: Biliary cancer is diagnosed at advanced stage and recurrence is common after surgical resection. Gemcitabine and UFT combination chemotherapy showed promising results in advanced pancreatic cancer(APC) and fixed dose- rate(FDR) infusion(10mg/m2/min) of gemcitabine is more effective than 30min-infusion in APC patients. We conducted a prospective multicenter phase II study to evaluate the efficacy and toxicity of FDR gemcitabine and UFT combination chemotherapy in advanced biliary cancer(ABC) patients. We evaluated the quality of life(QOL) and relationship between treatment outcome and polymorphisms of DNA repair gene such as RecQ1, RAD54L, XRCC1 and ATM. Methods: We included the chemo-naive patients with measurable metastatic or recurrent biliary adenocarcinoma except gall bladder cancer. Patients received gemcitabine infusion of rate of 10mg/m2/min on day 1, 8, and 15 plus oral UFT (400mg/m2) on day 1 to 21. We used modified PCR-RFLP method to evaluate the polymorphism of DNA repair gene. The primary endpoint was response rate. Results: From October 2006 to March 2008, 47 patients were enrolled and 33 of them were included in this analysis. Median age was 58 years(range 33–73 years) and 18 patients were male. Partial response was 24.2% and disease control rate was 51.5%. The estimated median time to progression(TTP) was 87 days(95% CI 51–123). Median overall survival was 243 days(95% CI 114–372). Grade 3/4 neutropenia was observed in 12 of 33 patients(36.4%) and 17 times of 114 cycles of chemotherapy(14.9%). No febrile neutropenia was observed. Grade 3/4 thrombocytopenia occurred in 5 patients(15.2%). Non-hematologic toxicities were mild. Polymorphism of XRCC1 was related to TTP(TTP of wild, heterozygous variant and homozygous variant type was 162, 71 and 25 days, respectively. p=0.0039). QOL as a secondary endpoint was not analyzed at this time. Conclusions: FDR infusion of gemcitabine and UFT combination chemotherapy in chemo-naïve patients with ABC is a well-tolerated and effective regimen.

No significant financial relationships to disclose.
Discovery of a tumor-specific biomarker for gastric cancer using proteomic analysis in tissue and serum
Authors: Mohri T. , Mohri Y. , Ward D. G. , Wei W. , Qi Y. , Martin A. , Kusunoki M. , Johnson P. J.
Published: August 2020

e15582

Background: Gastric cancer is curable at an early stage. However, most cases are diagnosed at an advanced stage because of the lack of screening programs. Therefore, for early detection, there is a need for serum biomarkers to be identified. Methods: We explored surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to elucidate potential protein biomarkers of gastric cancer. Twenty-one resected gastric cancer samples were compared with matched adjacent normal mucosa samples. Serum from patients with gastric cancer (n=51) was compared with patients with benign gastric diseases (n=29). Samples were analyzed on Cu2+-loaded IMAC protein chips via surface-enhanced laser desorption /ionization time-of-flight mass spectrometry. Results: Comparisons of surface-enhanced laser desorption /ionization time-of-flight mass spectrometry spectra of 21 gastric cancer tissue extracts with paired adjacent normal mucosa showed a total of 56 differentially expressed protein peaks (p<0.05; Wilcoxon test). Twenty-two were up-regulated in gastric cancer tissue, whereas 34 were down-regulated. The surface- enhanced laser desorption /ionization time-of-flight mass spectrometry spectra of serum contained 130 peaks, of which 67 were significantly associated with gastric cancer (p<0.05; Wilcoxon test). We found five proteomic features (mass charge values of 2273, 3143, 3372, 3444, 3485) that were significantly up-regulated in both gastric cancer tissue and serum from gastric cancer patients. The peak intensities of tumor-specific proteomic features were used to develop a linear regression model for calculating a diagnostic index. The area under the receiver operating characteristic curve of the corresponding diagnostic index was 0.87. Conclusions: Serum biomarker panels associated with tumor tissue are capable of distinguishing gastric cancer patients from non-cancer ones.

No significant financial relationships to disclose.
Control of cancer-associated inflammation and survival: Results from a prospective randomized phase II trial in gastric cancer
Authors: Reichle A. , Lugner A. , Ott C. , Klebl F. , Vogelhuber M. , Berand A. , Andreesen R.
Published: August 2020

e15584

Background: An angiostatic approach was used to assess the impact of anti-inflammatory therapy in combination with metronomic low-dose chemotherapy. Methods: A randomized multi-institutional phase II trial was designed to select metronomic chemotherapy (arm A: capecitabine 1 g orally twice daily for 14 days with one week break until tumor progression) or combined anti-inflammatory/angiostatic treatment (arm B: capecitabine as mentioned above plus etoricoxib 60 mg orally, day 1+, and pioglitazone 60 mg orally, day 1+) for further evaluation. Patients with refractory or progressive disease following any first-line therapy except capecitabine or frail were eligible. According to the one stage design, a sample size of 64 patients was calculated for the primary objective, improvement of response rate. Results: As similar response rates were observed (arm A/B 15/14%) after the accrual of 42 patients, the study was closed (n=20 (A), n=22 (B); median age 69 years (range 46 to 86ys); frail A/B n=9/11). Median progression- free survival for arm A/B was 3.0/2.9 months (P=0.878), and overall survival 5.0/6.1 months (P=0.778). In both treatment arms a significant decline of serum C-reactive protein (CRP) levels was observed within the first 4 to 6 weeks on treatment, A/B P= 0.01/0.04, respectively. CRP response > 50% from baseline was associated with a significantly improved overall survival in arm A/B (3.1 versus 11.0 months, P= 0.023/ 3.3 versus 7.1 months, P= 0.078) indicating an impact of inflammation-control on survival. WHO grade 3 (no grade 4) toxicities were reported in arm A/B in 20% and 23%, respectively, mostly due to hand-foot-syndrome. Conclusions: Metronomic low- dose chemotherapy in gastric cancer may induce anti-inflammatory response, but the chosen additional anti-inflammatory approach neither has impact on tumor-associated inflammation nor on response or survival rate. In a historical comparison, CRP-responder have similar outcome as patients treated with combination chemotherapy in first-line.

No significant financial relationships to disclose.
Repeated transarterial chemoperfusion and -embolization (TACE) in primary hepatic cholangiocarcinoma (CCC): Local tumor control and survival rate
Authors: Vogl T. J. , Naguib N. , Zangos S. , Eichler K. , Gruber T.
Published: August 2020

e15595

Background: To evaluate local tumor control and survival data in the palliative and symptomatic treatment of hepatic cholangiocarcinoma (CCC) using repeated transarterial chemoperfusion and -embolization (TACE) with two different chemotherapy protocols. Methods: 41 patients with primary cholangiocarcinoma (CCC) were repeatedly treated with transarterial chemoembolization (TACE) in 4-week intervals. In total, 291 TACE sessions were performed with a mean of 7.1 sessions per patient (mean age: 57.1 years; range, 37–80 years). 22 patients had multiple tumors, 6 showed 1 lesion, 5 had 2 lesions and 8 presented 3 to 4 lesions. The local chemotherapy protocol consisted of Mitomycin C alone (n=20), or in combination with gemcitabine (n=18). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI) in 3-month intervals. Results: Evaluation of local tumor control according to the RECIST criteria was as follows: partial response 9.8%, stable disease 43.6%, and progressive disease 46.6%. The 1-year survival rate after TACE was 58%, the 2-year survival rate was 21%. The mean survival time from the date of diagnosis of liver involvement was 34.1 months (according to Kaplan-Meier), after first TACE treatment 16.7 months. The median survival time of the palliative group was 14.5 months and of the symptomatic group 6 months. Conclusions: Our data indicated that repeated TACE using the protocols is well tolerated and yields respectable results in patients with unresectable liver lesions from CCC.

No significant financial relationships to disclose.
Hedgehog signaling: Gli2 and its influence in squamous esophageal cancer
Authors: Manickavasagam K. , Servarayan C. M. , Rao S. , Chandramohan A.
Published: August 2020

e15596

Background: Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and are implicated as potent oncogenes. Gli2 plays a dual role as activator of keratinocyte proliferation and repressor of epidermal differentiation. This study is to determine the expression pattern and the extent of Hh-signaling molecule(Gli2) in squamous cell carcinoma of oesophagus. Methods: A prospective immunohistochemical experimental study was done to identify the expression of Gli2 in 64 cases of squamous cell carcinoma of oesophagus. The study population consisted of patients of the age group 38–87 yrs. The cases consisted of 29 cases of keratinised squamous cell carcinoma.. Of the 64 cases, 20 were well differentiated, 9 moderately differentiated and 35 poorly differentiated tumours. Results: See Table . Gli2 expression was 25%. The cytoplasmic expression is positive in 9 cases and nuclear expression is positive in 5 cases. The average intensity of cytoplasmic expression was more than that of nuclear expression.Gli2 is less expressed in elderly cancers.Gli2 expression is comparatively more in upper third tumours. There were no obvious differences amongst the sex, differentiation and keratinization. The reason can be attributed to the fact that Hh signalling pathway works in a time, concentration and position dependent manner.Conclusions: Deregulation of Hh signalling will result in defective proliferation and differentiation of cells. These findings can be used for better prognosis of the patients by using stem cell therapy and HH pathway inhibitors in the treatment for squamous cell carcinomas of oesophagus. Protein kinase A (Pka) maintains the Gli transcription factors in an inactive state, so activation of Pka with agonists such as forskolin would prevent Gli-mediated activation of target-gene transcription. Gli can also be inhibited at the RNA level by targeting its transcripts with antisense oligonucleotides. To the best of our knowledge, this is the first study of expression of Gli2 in squamous cell carcinoma of oesophagus. [Table: see text]

No significant financial relationships to disclose.
Early predictive value of 18F-FDG-PET assessment in advanced esophagogastric junction and gastric cancer patients treated with cetuximab-containing therapy
Authors: Di Fabio F. , Pinto C. , Rojas Llimpe F. , Castellucci P. , Fanti S. , Mutri V. , Giaquinta S. , Di Tullio P. , Pini S. , Compagnone G. , Martoni A.
Published: August 2020

e15601

Background: 18F-FDG-PET/CT (PET) was reported to predict the pathological response during preoperative chemotherapy in esophagogastric junction (GEJ) or gastric (G) cancer pts. The aim of this study is to evaluate the usefulness of an early change in PET at several time-points in predicting response to cetuximab-containing therapy in pts with advanced GEJ or G cancer. Methods: We evaluated 51 pts with locally advanced/metastatic GEJ or G adenocarcinoma who underwent a first line cetuximab- treatment in two Italian phase II studies. Twenty nine pts (GEJ/G = 5/24; locally advanced/metastatic = 2/27) received cetuximab in combination with cisplatin/docetaxel (DOCETUX study) and 22 pts (GEJ/G = 2/20; locally advanced/metastatic = 3/19) received cetuximab in combination with FOLFIRI (FOLCETUX Study). PET scans were performed at baseline, and in FDG-avid pts, again on day 21 in the DOCETUX study and on day 42 in the FOLCETUX study. Metabolic response was defined as a decrease in maximum standard uptake value (SUV) ≥35% on the basis of our previous study (Di Fabio et al., Gastric Cancer 10:221–227, 2007).Objective response, according to RECIST criteria, was assessed by CT scan at baseline and every 6 weeks. Results: Five pts (10.2%) had FDG non- avid tumor (all pts with signet cell carcinoma). In the 46 FDG-avid tumor pts, the median SUV at baseline was 10.3 (range 5.0 - 36.4). The response rate (RR) was significantly higher in pts with a drop ≥35% in SUV from baseline to day 42: 83% (10/12 pts) in metabolic responders vs. 25% (2/8 pts) in non-metabolic responders (p= 0.019). In contrast, the SUV change at day 21 did not correlate with objective response: RR 57.1% (8/14 pts) in metabolic responders vs. 41.7% (5/12 pts) in non-metabolic responders (p= 0.695). The RR in non-avid tumor pts was 20% (1/5 pts). Conclusions.Our study suggests that in advanced gastric cancer pts with FDG-avid tumor the PET predicts objective response at day 42, but not at day 21. A PET response assessment can provide an opportunity to change the treatment in non-responder pts. Prospective trials defining the role of PET in gastric cancer are warranted.

No significant financial relationships to disclose.
Real world treatment patterns of gastrointestinal stromal tumor patients
Authors: Morgan J. A. , Guo A. , Williams D. , Guérin A. , Latremouille-Viau D. , Tsaneva M. , Yu A. P. , Wu E. , Signorovitch J. , Demetri G. D.
Published: August 2020

e15602

Background: Imatinib is accepted as the standard first-line therapy to treat gastrointestinal stromal tumor (GIST) in patients with unresectable or metastatic disease. In the case of disease progression, physicians may consider increasing imatinib dose or switching to another second-line agent, such as sunitinib. The aim of this study was to analyze the real-world long term treatment patterns of GIST patients. Methods: Two large claims databases from 01/1999 to 03/2008 were combined (MarketScan and Ingenix Impact) to extract patients diagnosed with GIST who initiated on imatinib ≥400 mg/day. Patients were followed from the first observed imatinib prescription to the end of data availability. Patients who dose increased during the study period were defined as dose escalators, while patients who later switched to sunitinib with or without dose escalation were defined as switchers. Kaplan Meier analyses were used to estimate the rate of treatment changes over time including imatinib discontinuation, defined as a lack of imatinib supply for ≥60 days, and switching back to initial treatment. Results: Among the 1,508 GIST patients who initiated on imatinib, 253 patients had a dose increase and 153 patients switched to sunitinib during the study period. 20.1% patients on imatinib discontinued by the end of the first year, and 43.0% discontinued by the end of the third year. Among the 153 switchers, 61 patients had a dose escalation prior to the switch, of which 82.0% reached 800 mg before switching. Among all the switchers, 20.3% switched back to imatinib within 6 months. Conclusions: These claims-based findings on the duration of first-line imatinib therapy of GIST patients supports data on imatinib efficacy in treating GIST from formal clinical research studies. Most of GIST patients who initiated imatinib continued on this therapy without undergoing dose increase or switch to sunitinib. Among switchers, most did not dose escalate before switching and many eventually switched back to imatinib. It appears that physicians tend to not always follow clinical practice guidelines developed based on expert consensus, with respect to decision rules for dose escalation, or for the appropriate time to change kinase inhibitor therapy.

[Table: see text]
A phase II trial of the proteasome inhibitor bortezomib in patients with recurrent or metastatic adenocarcinoma of the bile duct or gallbladder (NCI #6135)
Authors: Costello M. R. , Meropol N. J. , Denlinger C. S. , Engstrom P. F. , Wright J. J. , Li T. , Mclaughlin S. , Beard M. , Cimildoro R. , Cohen S. J.
Published: August 2020

e15605

Background: There is currently no standard therapy for recurrent or metastatic cancers of the bile duct or gallbladder and available chemotherapy is of uncertain benefit. As activation of NF-κB has been described in these tumors, we initiated a phase II trial of the proteasome inhibitor bortezomib in patients with recurrent or metastatic disease. Methods: Patients with measurable metastatic or unresectable adenocarcinoma of the bile duct or gallbladder who had received up to 2 prior chemotherapy regimens were eligible. Other eligibility criteria included ECOG PS 0–2, total bilirubin ≤1.5X ULN, and ALT/AST ≤2.5 X ULN. Patients with baseline neuropathy ≥grade 2 were excluded. Bortezomib was administered at a dose of 1.3 mg/m2 as an intravenous bolus on days 1, 4, 8, and 11 of 21 day cycles with CT evaluation every 6 weeks. The primary endpoint was response rate. Null hypothesis: PR/CR≤5%. Alternative hypothesis: PR/CR ≥20%. 35 patients were required for 90% power with an early stopping rule at 20. Results: 20 patients were enrolled: 11M/9F, PS 0/1 (7/13), 6 gallbladder /14 bile duct. There was one patient with an unconfirmed partial response, 9 patients with stable disease, and 10 patients with progressive disease. Accrual was halted after 20 patients were enrolled as the early stopping rule for futility was met. Median PFS was 48 days (95% CI [32,124]) and median OS was 284 days (95% CI [155, 513]). Grade 3/4 toxicities were observed in 13 patients (65%), most commonly fatigue (4 patients), thrombocytopenia (3 patients), hyperbilirubinemia (3 patients), and hypotension (2 patients). Other SAEs at least possibly related to bortezomib included grade 3 vasculitis (1 patient) and grade 2 meningitis (1 patient). Conclusions: Bortezomib is not an active agent in the treatment of metastatic gallbladder or biliary tract cancer.

No significant financial relationships to disclose.
Phase II study of postoperative chemoradiotherapy for esophageal carcinoma
Authors: Wu S. , Deng X. , Zhang P. , Xie C. , Zhang X. , Jin Z.
Published: August 2020

e15606

Background: Esophageal squamous cell carcinoma is still a virulent disease diagnosed at late stage and remains a major cause of carcinoma mortality in China. The preoperative chemoradiotherapy had been applied to patients with esophageal carcinoma in an effort to reduce the relapse and improve survival. However, randomized controlled trails have shown conflicting results. Intergroup study 0116 demonstrated that postoperative chemoradiotherapy significantly improved overall survival in gastric carcinoma patients. The question remains whether postoperative chemoradiotherapy can improve overall survival in patients with esophageal carcinoma. Our planning study was to investigate the role of postoperative chemoradiotherapy in the multimodality treatment for locally advanced esophageal carcinoma. Methods: From October 2000 to October 2007, Fifty-two patients who underwent esophagectomy with stage II-III esophageal carcinoma were enrolled. All patients received 50Gy of postoperative radiotherapy over 25 fractions in 5 weeks. Two cycles of chemotherapy (Paclitaxel 135mg/m2 d1,cisplatin 20mg/m2d1–3) were administered concurrently on days 1–3 and days 29–31 of radiotherapy. Results: Of the total 52 patients, 28 (54%) developed grade 3 or 4 toxicity.At the time of analysis, 23 patients died. The median follow-up for surviving patients was 23.5 months. The median survival time was 37.2 months. Incidences of tumor recurrence were 53.8 % (28/52) of patients. As expected, distant metastasis was predominant. The 2-year local-regional control survival, distant metastasis-free survival and relapse-free survival were 60.01%, 71.38% and 42.01%, respectively. 1-year and 3-year overall survival were 82.19% and 47.13%, respectively. Conclusions: This novel postoperative chemoradiation regimen for treatment of patients with stage II-III esophageal cancer has a tolerable toxicity and promising 3-year overall survival.

No significant financial relationships to disclose.
COX-2 inhibition in combination with preoperative chemoradiation for CA esophagus
Authors: Kwong D. L. , Law S. Y. , Tong D. K. , Wong K. H. , Nicholls J.
Published: August 2020

e15607

Background: Squamous cell carcinoma of the thoracic esophagus (ESCC) is often diagnosed in advanced stage. Pre-operative chemoradiation is employed to downstage the disease before operation. Pathological complete response (pCR) was observed in around 20–40% of patients and was associated with improved survival. Cyclooxygenase 2 (COX-2) is overexpressed in ESCC and may contribute to chemo- and radio-resistance. This pilot study evaluates if COX-2 inhibition in combination with pre-operative chemoradiation will improve the response rate in ESCC. Methods: Patients with histologically confirmed ESCC undergo endoscopic ultrasound, ultrasound of neck and PET/ thoracic, abdominal CT for staging. Patients with disease which is considered potentially resectable are eligible. The primary and involved lymph nodes are irradiated to 40Gy in 20 fractions over 4 weeks with 2 cycles of concurrent cisplatin (100mg/sqm, D1, D22) and 5 fluorouracil (500mg/sqm, D1–5, D22–26). Celecoxib, a specific COX-2 inhibitor, 400mg bid, is started for 2 weeks before chemoradiation, continued throughout chemoradiation and for 4 more weeks after completion of chemoradiation. Patients are re-evaluated and esophagectomy is performed 6–8 weeks after completion of chemoradiation. Results: From 2004 to 2008, 32 patients were recruited. Pre-operative staging was stage II in 4, stage III in 25 and stage IVA in 3 patients. Celecoxib was well tolerated. 3 patients did not have full course of celecoxib: 1 complained of epigastric pain, 1 died early of disease, 1 had renal impairment after chemotherapy. 29 patients had esophagectomy performed after chemoradiation. Median follow-up after completion of chemoradiation was 11 months (range: 3 to 43 months). 23 patients (79.3%) had downstaging of the primary compared with pre-operative staging. The pCR rate in primary tumor was 51.7% (15/29 patients) and pCR rate in lymph nodes was 65.4% (17/26 patients). 3 years overall survival of patients who had esophagectomy was 79.3%. Conclusions: COX-2 inhibition in combination with pre-operative chemoradiation is well tolerated. Preliminary results of the pCR rates and survival are encouraging. Incorporation of COX-2 inhibition into multi-modality treatment of ESCC should be further investigated in a randomized trial.

No significant financial relationships to disclose.
Phase II study with preoperative oxaliplatin (O), cisplatin (P), 5-fluorouracil (F) (OPF) and radiation (XRT) in patients with esophageal (ES), gastroesophageal (GE), and gastric (G) cancer
Authors: Pera M. , Gallego R. , Martin-Richard M. , Montagut C. , Iglesias M. , Conill C. , Balaguer C. , Petriz L. , Momblan D. , Maurel J.
Published: August 2020

e15612

Background: A phase I study showed the feasibility of the triplet combination (OPF) with XRT in ES and GE cancer (Maurel et al, IJRBOP, 2005). We conducted a phase II study to evaluate the efficacy of the regimen. Methods: Enrolled pts had resectable, high-risk (HR) based on endoscopic ultrasonography (EUS) (uT3, uN1 or uT4 if deemed resectable) ES, GE and G cancer. The primary objective was to determine the pathologic complete response (pCR). If 2 or more pCR were reported in the first 18 pts treated, enrollment continues with 23 additional pts. Eligibility criteria: squamous cell or adenocarcinoma of the ES, GE or G cancer and ECOG Performance status (PS) 0–1. Staging was done with EUS and computed spiral tomography. Laparoscopic staging was mandatory for pts with ES, GE and G adenocarcinoma. Pts received 2 cycles of O 85 mg/m2, P 55 mg/m2, F (3 g/m2 in 96h CI) q4w, with concomitant 45 Gy XRT in 25 fractions; surgery was planned 5–8 weeks after XRT. All pathological specimens were reviewed by a unique pathologist and regression analysis was recorded using Cologne (C) and M.D.Anderson (MDA) classification for ES and European Journal of Surgical Oncology (EJSO) for GE and G. Results: Between 5/04 to 12/07, 41 pts were enrolled in 5 Spanish Institutions. Median age 62 yrs (39–75 yrs); Male/female 83%/17%; PS 0/1 27%/73%; ES/GE/G 39%/32%/29%; EUS stageT3N0 (20%), T2–3N1 (65%) and T4 (10%). G3/4 adverse events included asthenia (27%), infection (7%), diarrhea (7%) and stomatitis (5%). There were 2 toxic deaths. Of the 31 pts who underwent surgery, there were R0=94%/R1=3%/R2= 3%. 7/41 pts (17%) achieved pCR. Using C and MDA classification, 9/14 (61%) and 12/14 (85%) ES achieved grade IV/III and P0/P1 regression, respectively. With EJSO classification 3/17 (18%) GE and G tumors achieved pCR. Median time to progression or death (PFS) was 16.2 (CI:12.2-NR) months (mo). Median overall survival (OS) was 28.9 mo. (CI: 22.5-NR). Conclusions: Although in the whole group pCR, PFS and OS does not appear superior to results achieved in other trials with preoperative P/F/XRT in HR pts, the OPF regimen seems specially active in ES cancer.

No significant financial relationships to disclose.
Preliminary results of a multicenter phase II study of imatinib and fluorourcail/leucovorin (FU/LV) in patients with unresectable or metastatic gallbladder or biliary tract cancer
Authors: Schuette K. , Moehler M. , Kettner E. , Al-Batran S. , Hegewisch-Becker S. , Steffens C. , Pustowka A. , Goekkurt E. , Ehninger G. , Stoehlmacher J.
Published: August 2020

e15622

Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status < 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease.

[Table: see text]
Biweekly cetuximab and irinotecan as second-line therapy to patients with platinium-resistant gastroesophageal cancer
Authors: Bjerregaard J. K. , Schønnemann K. R. , Jensen H. A. , Vestermark L. W. , Hansen T. P. , Pfeiffer P.
Published: August 2020

e15624

Background: There is no established 2nd line therapy for patients (pts) with advanced gastroesophageal (GE) cancer. In 2004, the Danish government initiated a national health programme for pts with advanced cancer. Non- proven therapy may be offered after approval by an expert panel appointed by the National Board of Health that subsequently finances the cost of treatment. This programme has had a major impact on the management of cancer pts in Denmark and has accelerated the introduction and implementation of new therapies. Inspired by the excellent results in colorectal cancer a combination of cetuximab and irinotecan (CetIri) was chosen for platinum-resistant GE cancer. While awaiting approval of a phase II protocol CetIri was offered at a single institution. We report our preliminary experience with biweekly CetIri as 2nd line therapy in pts with GE cancer. Methods: All pts had histologically confirmed GE cancer (adeno- or squamous cell carcinoma) and all pts had previously received first line platinum based therapy. Pts received CetIri (cetuximab 500 mg/m2and irinotecan 180 mg/m2day 1) every 2nd week until progression or unacceptable toxicity. Response rate was evaluated by the investigator according to RECIST every 8th week. Toxicity was prospectively evaluated according to NCIC-CTC 3.0. Results: From December 2007 to August 2008, 31 consecutive pts was treated with CetIri. Median age was 62 years (33–76). Median performance status was 1 (0–2). Localisation of primary was: Esophagus 10%, GE junction 64%, gastric 26%. Twenty-seven pts (87%) had adenocarcimona. Median number of cycles were 6 (1–21). Most important grade 2–4 toxicities were non-haematological toxicity as diarrhea (25%), nausea (21%) and vomiting (11%). Three pts (11%) had grade 3 leukopenia, 1 had febrile neutropenia. Two pts had PR. Median PFS was 3.2 months. Fourteen pts (45%) received at least 6 courses (3 month of therapy). After a median follow-up of 6 month 5 pts continue CetIri without sign of PD. Conclusions: Biweekly CetIri is a convenient and well-tolerated 2nd line regimen in pts with GE cancer. Predictive factors are needed to select which pts will benefit from therapy. A confirmatory phase II study is ongoing.

[Table: see text]
A phase II study of IMGN242 (huC242-DM4) in patients with CanAg-positive gastric or gastroesophageal (GE) junction cancer
Authors: Goff L. W. , Papadopoulos K. , Posey J. A. , Phan A. T. , Patnaik A. , Miller J. G. , Zildjian S. , O'Leary J. J. , Qin A. , Tolcher A.
Published: August 2020

e15625

Background: IMGN242 is a conjugate of the cytotoxic maytansinoid DM4 and the monoclonal antibody huC242, which binds to CanAg. In a Phase I study, the maximum tolerated dose for IMGN242 was determined to be 168 mg/m2, with ocular changes the primary dose-limiting toxicity. This Phase II study was initiated to assess IMGN242 for the treatment of gastric cancer. Methods: In this open-label, multi-center study, IMGN242 is given as a single IV infusion every three weeks to patients with CanAg-expressing metastatic or locally-advanced gastric or GE junction cancer. Patients must have been treated with at least one prior therapy to qualify for enrollment. The study has a 2-step design: If ≥1 objective response is achieved among the first 23 patients (Step 1), a total of 39 response-evaluable patients will be enrolled (Step 2). Results: Overall, 9 patients have received IMGN242. The first 6 were treated with 168 mg/m2, and 1 of these patients showed a marked biologic response by the FDG-PET scan in Cycle 1 followed by an unconfirmed partial response based on CT scan in Cycle 2. However, 3 of these 6 patients developed ocular toxicities assessed to be study drug related. Only patients with low plasma CanAg levels (<1000 U/ml) developed ocular toxicities, and clinical pharmacokinetic and pharmacodynamic (PK/PD) analyses revealed that plasma CanAg affects study drug exposures. The study was amended to differentiate the IMGN242 doses (126 mg/m2 or 168 mg/m2) administered based on the patient's plasma CanAg levels (< or >1000 U/mL). To date, 3 patients have received IMGN242 with this dosing strategy and no ocular toxicities have been reported. Conclusions: IMGN242 showed preliminary evidence of activity in this patient population. A novel Phase II dosing strategy is being used that should enhance tolerability. Patient enrollment is ongoing and updated results will be reported.

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Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma
Authors: Wu J. , Muggia F. , Henderson C. , Feun L. , Veldhuizen P. V. , Gold P. , Zheng H. , Abbadessa 66201 G. , Lewis J. , Zhu A. X.
Published: August 2020

e15630

Background: Inorganic arsenic has reported activity in advanced hepatocellular carcinoma (HCC) in Asia, yet its efficacy is limited by liver toxicity. Darinaparsin is a novel organic arsenic that is capable of reaching higher intracellular concentration in cells with decreased toxicity compared to inorganic arsenic. It is highly active as a single agent in HCC cell lines and animal tumor models. We conducted a multi-center phase II study with darinaparsin in patients with advanced HCC. Methods: Eligibility criteria included unresectable or metastatic measurable HCC, up to two prior systemic treatments, ECOG performance status ≤2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was given at 420 mg/m2 intravenously administered over 60 minutes through a central line, twice weekly at least 72 hours apart for three weeks followed by one-week rest in a four-week cycle. The primary end point of the study was response rate. A Simon two-stage design was used to assess the efficacy of darinaparsin and the study would be terminated if no responses were observed after the first stage. Results: The planned 15 patients of the first stage were enrolled: median age = 60 (35 - 79). M/F = 14/1, ECOG performance status 0/1= 4/11, Child Pugh class A/B = 11/4. Seven patients received prior systemic chemotherapies. No objective responses were observed. Three patients had stable disease. The median number of cycles on study per patient was 2 (1–6). The median progression free survival and overall survival were 55 days (95% confidence interval: 50 - 59) and 190 days (95% confidence interval: 93–227), respectively. Treatment was well tolerated. No treatment related hospitalizations or deaths occurred. Treatment related grade 1–2 toxicities included nausea/vomiting (31%), fatigue (23%), anorexia (15%) and diarrhea (15%). Grade 3 anorexia, wheezing, agitation, right upper quadrant pain and SGPT were observed in 1 patient each (8%), 1 patient experienced grade 4 hypoglycemia (8%). Conclusions: Darinaparsin was safely administered with tolerable toxicity profiles in HCC patients. However, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis.

[Table: see text]
Palliative systemic chemotherapy with gemcitabine (GEM) and 5-fluorouracil (5-FU) as 24h-infusion in patients with advanced inoperable biliary tract cancer (UICC stage IV)
Authors: Kersten S. , Wein A. , Albrecht H. , Reulbach U. , Maennlein G. , Wolff K. , Ostermeier N. , Hohenberger W. , Hahn E. G. , Boxberger F.
Published: August 2020

e15633

Background: Due to the late diagnosis of biliary tract carcinomas in an advanced tumor stage, the application of palliative chemotherapy frequently remains as a possible treatment option. The aim of this study is to evaluate the efficacy and toxic side effects of a chemotherapy schedule consisting of GEM combined with 5-FU in patients (pts.) with metastatic biliary tract cancer. Methods: Evaluation of 35 pts. based on our prospective tumor registry data; essential inclusion criteria: histologically proven adeno-carcinoma, UICC stage IV, chemonaivity; all the pts. were presented in the interdisciplinary tumorboard of Erlangen University and were primarily non-curatively-resectable (n = 35); evaluation period: 11/1998 - 09/2008; treatment schedule: 1.000 mg/m2 of GEM as a 0.5h-infusion (inf.) combined with 2.000 mg/m2 of 5-FU as a 24h-inf. via port catheter on day 1, 8, 15 qd 22. Results: Median age: 64 years; men/women: n=18/17; ECOG 0/1/2: n=10/21/4; localisation: intrahepatic bile ducts: n=19, extrahepatic bile ducts: n=11; gall bladder: n=4; metastases: liver: 91.4%, lymph nodes: 51.4%, peritoneum: 28.8%, bones: 8.6%, intestine: 8.6%, skin: 2.9%, lungs: 2.9%; chemotherapy applications: total number: 486, average value/patient: 13.9; CA 19–9 elevated yes/no: n=13/22 (37.1%/62.9%); CEA elevated yes/no: n=15/9 (42.9%/25.7%, not evaluable: 11); higher grade toxicity (III or IV): leukocytopenia III: 14.3%, thrombocytopenia III: 2.9%, weariness III: 2.9%, diarrhea III: 5.7%, diarrhea IV: 2.9%, vomiting IV: 2.9%, pain III: 5.7%, ascites III: 5.7%, infections III: 2.9%, thromboembolia IV: 2.9%, elevated bilirubin value III: 1.7%, grade IV: 8.3%; deep leg vein thrombosis: 15%; median TTP: 5.1 months (95% CI: 2.9 - 7.2); median overall survival: 10.4 months (95% CI: 7.9 - 12.9); 6-months-/1-year-/2-year-survival rate: 65.7%/45.7%/17.1%; response rate: PR: n=5 (14.3%), SD: n=18 (51.4%), PD: n=7 (20%), not evaluable: n=5 (14.3%); tumor control (PR/SD): n=23 (65.7%); median follow-up: 10.4 months. Conclusions: Combination chemotherapy with weekly GEM as a 0.5h-inf. and 5-FU as a 24h-inf. on an out-patient basis is an effective palliative treatment schedule with solely low grade toxicity.

No significant financial relationships to disclose.
Phase IIb trial of fluorouracil, leucovorin, oxaliplatin, and paclitaxel (POF) compared with fluorouracil, feucovorin, and irinotecan (IF) as first-line treatment for advanced gastric cancer (AGC)
Authors: Lin R. , Chen Q. , Fan N. , Ye Y. , Guo Z. , Wang X. , Liu J. , Chen L.
Published: August 2020

e15642

Background: Primary results of POF as 1st and 2nd line treatment for AGC have been presented at ASCO 2007 and 2008. We report here data on the feasibility and the toxicity of POF versus IF(Dank, et al, ASCO 2005) in 1st line treatment of AGC. Methods: Patients with previously untreated, advanced, unresectable, and histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction were randomly assigned to POF or IF regiment. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. Results: 25 patients were entered in this study between March 2007 and July 2007: 13 in the POF group and 12 in the IF group. The median patient age was 55 years (range, 36 to 67 years), 18 were males and 7 were females. No complete response was observed. The response rate was 62.5% (POF) and 33.3% (IF) respectively. At a median follow-up of 285 days, 7(POF) versus 6(IF) patients were still alive. Hematological toxicity was the most frequent toxicity in both groups. Grade 3 to 4 neutropenia were 38.5% (POF) versus 8.3% (IF). Diarrhea was found 0% and 8.3% in POF and IF group respectively. No grade 3 peripheral neurotoxicity was observed. Conclusions: Compared with IF regiment, POF could also be used as first-line treatment for AGC with acceptable safety profile, good efficacy, and more encouraging results.

No significant financial relationships to disclose.
The evaluation of peritoneal lavage tumor markers for gastric cancer
Authors: Yamamoto M. , Ishida T.
Published: August 2020

e15643

Background: We have found that elevation of preoperative peritoneal lavage CEA levels is associated with an earlier detection of recurrent peritoneal dissemination and a poor prognosis. Methods: We have now examined findings with the combined of peritoneal lavage CEA, CA125 and CA72–4 levels with regard to prediction of the prognosis of gastric cancer patients. Ninety-four patients who were underwent surgery with gastric cancer were intraoperatively measured for tumor markers, CEA, CA125 and CA72–4 in peritoneal lavage using a chemiluminescent enzyme immunoassay. We examined whether the stage with patients were related with tumor markers in peritoneal lavage. Results: The averages of peritoneal lavage CEA, CA 125 and CA72–4 levels in patients with peritoneal carcinoma were 24.3, 299, 6.70, respectively, while those in patients without peritoneal carcinoma were 0.77, 258, 0.95, respectively. The averages of peritoneal lavage CEA and CA72–4 levels in patients with peritoneal carcinoma were significantly increased with those in patients without peritoneal carcinoma (p<0.0001). In patients who were performed a curative surgery, the averages of peritoneal lavage CEA level were 0.55, 0.51, 0.51, 1.98, 0.50, 11.0 in cases of stage IA, IB, II, IIIA, IIIB and IV. Similarly, the averages of peritoneal lavage CA125 level were 254, 260, 307, 148, 366 and 280, and the average of peritoneal lavage CA72–4 level were 0.88, 1.06, 0.98, 0.90 and 3.23. The peritoneal lavage CEA or CA72–4 level in cases of stage IV was increased than in cases of other stages. The RFS of patients in the CEA level above cut-off was shorter than that in the CEA level below cut-off. However, the RFS of patients in the CA72–4 level above cut-off was not differ with that in the CA72–4 level below cut-off. In a multivariate analysis, the peritoneal lavage both CEA and CA72–4 levels above cut-off were found to be significant and independently prognostic factor (p= 0.0427). Conclusions: This combined assay of peritoneal lavage both CEA and CA72–4 levels will aid in estimating the prognosis.

No significant financial relationships to disclose.
Radiologic detection of bone metastasis in patients with hepatocellular carcinoma: A single-center experience
Authors: Farrand E. , Ferrante L. , Staron R. B. , Brown R. S. , Siegel A. B.
Published: August 2020

e15644

Background: We investigated current practices and their relative abilities to effectively screen for and detect bone metastases (mets). It is unknown what percentage of HCC bone mets are blastic versus lytic, and what imaging modality best identifies them. Methods: We retrospectively assessed all adults diagnosed with HCC at our center from 1/1997 - 8/2008. Primary outcomes were the percentage of lytic lesions, and the sensitivity and specificity of bone scans in detecting bone mets. Results: 462 patients were included. Mean age at diagnosis was 60 years; 80% were male, and hepatitis C was the most common etiology of HCC (58%). 54% of all patients received bone scans. 67% were considered diagnostic, whereas the remaining scans required a confirmatory test(s) (23% PET, 41% plain X-ray, 54% CT, and 10% MRI). 5% of all patients were diagnosed with bone mets (n=24), of which 42% were diagnosed at presentation, 20% during continued follow-up, and 38% during post-operative surveillance. 96% of all bone lesions were lytic, of which 13% were undetected by bone scan (sensitivity = 79%, specificity = 98%). None of the lesions were blastic and 4% remained indeterminate after independent review with an attending bone radiologist. Of those patients who underwent resection or liver transplantation (n=205) 35 patients recurred (31% with bone recurrence and 6% with bone mets as their only site of disease). Within this surgical group, patients with bone mets only had higher 1,3,and 5 year survival rates compared to patients with other extrahepatic lesions, although only significant for 3 year survival (p=0.013). 4 of the 24 patients with bone mets received a biopsy. All 4 confirmed metastatic HCC. Conclusions: Due to the high specificity, bone scans serve as a good initial screening test to rule out bone mets in the HCC population. However in populations at higher risk of presenting with bone mets (post-tranplantation/resection) a more sensitive test may be needed. Additional studies are warranted to determine whether other modalities, such as PET/CT or skeletal survey, are more sensitive tests for the detection of bone mets.

No significant financial relationships to disclose.