bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro-acquired resistance gene expression profile and in vivo response to oxaliplatin-based treatment
Authors: Martinez Cardús A. , Martinez-Balibrea E. , Musulén E. , Ginés A. , Manzano J. L. , Layos L. , Quiroga V. , Aranda E. , Abad A. 
Published: August 2020

e15041 Background: Resistance to oxaliplatin is one of the main problems of colorectal cancer (CRC) treatment success. It is not clear if intrinsic and acquired resistance processes are developed by related mechanisms. In a previous work (Martinez-Cardús et al. Mol Cancer Ther, January 2009), we determined a profile of oxaliplatin-acquired resistance related genes by using an in vitro model. In the present work, we analyzed this genetic profile in paraffin-embedded primary adenocarcinomas from CRC patients treated with oxaliplatin-fluoropyrimidine. mRNA expression data was correlated with response rate and time to progression (TTP) in order to determine the role of these genes as markers of resistance to oxaliplatin-based treatment. Material and Method: mRNA levels were analyzed by using Real Time PCR. β-actin and 18s were used as housekeeping genes and, as a reference sample, we used commercial pool of mRNA from different human tumours. Chi- square and Fisher test were used in order to value differences in response rate to treatment. TTP was studied by using Kaplan Meyer curves and Log rank test. Median and percentile 33 and 66 were used as threshold values to determine both high and low expression level groups for each gene analyzed. We considered statistically significant a two-sided p-value lower than 0.05. Results: Forty-four advanced CRC patients treated with fluoropyrimidine plus oxaliplatin were analyzed. 54.5% of them were males; primary tumour was localized in colon in a 65.9% of cases. According to qRT-PCR analysis, the in vitro oxaliplatin acquired resistance related genes could be detected in the tumours but the expression of any of them correlated significantly with in vivo resistance to oxaliplatin-based treatment by using the three different threshold values to define groups. Conclusions: According to our results, these genes could not be used as markers of resistance to oxaliplatin-based treatment in non-treated tumours. Thereby, oxaliplatin resistance acquisition genes seems not to be involved in intrinsic drug resistance probably due to the fact that acquired and intrinsic oxaliplatin resistance are not related mechanisms. Further studies to typify oxaliplatin intrinsic resistance potential markers are guaranteed. No significant financial relationships to disclose.
Does severity of underlying chronic liver disease (CLD) affect treatment outcome of hepatocellular carcinoma (HCC) patients undergoing systemic chemotherapy (CT)?
Authors: Yeo W. , Mo F. K. , Hui E. P. , Lam K. C. , Ho W. M. , Koh J. , Ma B. , Mok T. , Chan A. , Chan S. L. 
Published: August 2020

e15513 Background: HCC is a common cause of morbidity and mortality. CT has been one of the treatments offered to patients (pts) who are not candidate of curative surgery. Treatment of HCC could be complicated by underlying CLD. In this study, we aimed to assess pre-CT severity of CLD on treatment outcome of HCC pts who were entered into our previously reported phase III prospective randomized CT study (J Natl Cancer Inst 2005). Methods: The severity of CLD for each pt was arbitrary assessed by adopting the Child-Pugh's classification. Patients’ characteristics were compared. Treatment outcomes in terms of responses, survival and treatment-related toxicities (NCI CTC) were compared. Results: 160 were Child's A; 28 were Child's B. Proportion of pts with cirrhosis (45% vs 71%, P=0.01) and pre-CT bilirubin level (11 vs. 15 umol/l, p=0.02) were significantly higher, while age (52 vs 45 yrs, p=0.05) and albumin level (35 vs 30 g/l, p<0.0001) were significantly lower among Child's B pts. For Child's A and B pts: the median no. of CT cycles received were 4.0 vs 2.5 (p=0.01), the response rates were 17% vs 8.3% (p=0.28), the median survival were 21 vs 10.7 months (p= 0.002). When toxicity during CT were compared, Child's B pts had significantly higher rate of grade 3/4 neutropenia (0.6% vs. 7.1%, p=0.05), hyperbilirubinaemia (11.9% vs. 28.6%, p=0.02), hyponatremia (3.1% vs. 3.6%, p=0.001) and gastrointestinal bleeding (3.1% vs. 17.9%, p=0.001). Conclusions: Child's B HCC pts experienced increased treatment-related toxicities during CT. This has probably led to a shorter duration of CT and a lower response rate to CT. Their shorter survival could also be attributed to the severity of underlying CLD. Future trials on systemic therapy in HCC patients may need to consider stratifying patients according to severity of CLD. No significant financial relationships to disclose.
Phase II capecitabine and gemcitabine fixed dose rate (FDR) in patients with advanced pancreatic cancer
Authors: Tonini G. , Vincenzi B. , Vasile E. , Catalano V. , Virzì V. , Fontana A. , Intagliata S. , Catalano G. , Falcone A. , Santini D. 
Published: August 2020

e15530 Background: The aims of this phase II trial are to determine the activity and the safety of the new combination modality with Gemcitabine fixed dose rate (FDR) infusion and Capecitabine in patients with advanced pancreatic cancer. Methods: Patients with unresectable pancreatic cancer who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS < 2 and measurable disease were enrolled. Gemcitabine (800 mg/mq IV infused in 80 minutes on days 1 and 8) and Capecitabine (650 mg/mq orally twice daily for 14 days) were administered and repeated every 21 days. Results: 47 patients were enrolled between January 2004 and October 2008. Median age was 66 (range: 37–79), 18 female and 29 male. A total of 299 cycles were administered, median cycles for patient were 6 (range: 1–17). CR was observed in one patient (2.1 %) and 10 patients achieved PR (21.3 %) giving an overall response rate of 23.4 % in intention-to-treat population. 22 pts (46.8 %) had stable disease obtaining an overall tumour control of 70.2 %. The median time to progression was 5.2 months (95 % CI, 2.4–7.6); the median overall survival was 8.4 months (95 % CI, 5.5–20). Grade 3–4 neutropenia was observed in 29.8 % of subjects, thrombocytopenia in 6.4 %. Grade 1–2 non-hematological toxicities were asthenia (61.7 %), diarrhea (29.8%), stomatitis (29.8 %) and hand foot syndrome (2.1 %). There were no treatment-related deaths. Gemcitabine was skipped at least once/reduced in 51/10.6 % of the patients, respectively. Capecitabine was skipped at least once/reduced in 16/8 % of the patients, respectively. Conclusions: The combination of FDR Gemcitabine and Capecitabine with this modality of infusion is feaseble, safe and seems to be active. No significant financial relationships to disclose.
Capecitabine (C), oxaliplatin (OXP), and radiation (RT) in resectable esophagus cancer (EC): A phase II trial with gene expression profiling (GEP)
Authors: Khushalani N. I. , Miecznikowski J. , Wang D. , Nowak N. , Nava H. , Nava M. E. , Tan W. , Iyer R. , Yang G. , Pendyala L. 
Published: August 2020

e15543 Background: Novel chemotherapy regimens in combination with RT aim to improve the pathologic complete response (pCR) in EC. Following our dose-finding phase I study, the present phase II neo-adjuvant (NA) EC trial was designed to examine the pCR rate using C, OXP and RT, with secondary end-points of evaluating toxicity, quality of life, and GEP of tumor tissue for correlation to therapeutic response. Methods: EC patients (PTS) with stages II-IVa, adequate organ function and performance status (ECOG 0–1) were eligible. Treatment consisted of OXP, 85mg/m2 iv on days 1, 15 and 29, C (oral or enteral tube) 625 mg/m2 bid on days of RT, and 50.4 Gy RT (3-D conformal) in 28 fractions, followed by an esophagectomy (E) 4–6 weeks later. 2 cycles of OXP + C were administered post-operatively. GEP using Agilent microarrays was conducted on primary tumor tissue pre-treatment (Rx), day (D) 17 and at E; > 50% viable tumor cells were required. Results: 20 PTS have been enrolled (17 male, 3 female); median age 59.5 yrs; 17 adenocarcinomas & 3 squamous-cell cancers. Clinical stage: II (3), III (13) and IVa (4). 18 PTS have completed NA therapy; Grade 4 toxicity includes anemia (1), lymphopenia (2); grade 3 toxicity includes esophagitis (1), pneumonia (1), wound infection (1), anastomotic leak (2), esophageal fistula (1), bowel obstruction (1), fatigue (1), hyperbilirubinemia (1), elevated ALT, AST (1 & 2, respectively), hypoalbuminemia (3), OXP hypersensitivity (2) & leucopenia (1). One PT died > 60d post- operatively secondary to infection. 15 PTS have undergone an E with 3 pCR (20%). Analysis on pre-Rx GEP on 17 PTS revealed a distinct pattern for pCR PTS with 325 over-expressed and 79 under-expressed genes. Ongoing functional analysis will characterize GEP changes in 1) pCR PTS pre-Rx & at D17, 2) pCR & non-pCR PTS pre-Rx, and 3) by histology. Validation will be performed via RT-PCR. Accrual to the trial continues. Conclusions: C, OXP & RT appears to be a tolerable and efficacious NA regimen for EC. The exploratory GEP analysis may provide insight on predicting response to NA therapy. Acknowledgement: The study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Roche Laboratories, Inc. [Table: see text]
Assessment of prognostic factors in pancreatic ductal adenocarcinoma: Focus on the retroperitoneal margin
Authors: Bellizzi A. M. , Bloomston M. , Bellizzi S. M. , Marsh W. L. , Frankel W. L. 
Published: August 2020

e15670 Background: Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer death in the West, with a nearly superimposable incidence and mortality. Resection is the only chance for cure, and various features in resection specimens correlate with outcome. While most consider the uncinate margin (UM) to be the true retroperitoneal margin, it has been suggested that the posterior pancreatic surface (PPS) may also be important. At another site with a retroperitoneal margin (i.e. rectum), 1 mm margins are significant. We thus evaluated margin status in various ways, focusing on the retroperitoneal region and emphasizing outcome. Methods: We identified all pancreaticoduodenectomies for PDA over a 6 year period in which the PPS was histologically evaluable. Tumors were assessed for the following: size, stage, grade, lymph node (LN) status, vascular and perineural invasion, and margin status. Margin status was evaluated in 3 ways: traditional margins (tumor at pancreatic neck, bile duct, and/or uncinate margins), 1 mm margins (traditional + tumor within 1 mm of UM), and PPS margins (traditional + tumor within 1 mm of PPS or UM). Kaplan-Meier survival curves were constructed with univariate factors compared by log rank analysis; multivariate analysis was done using the Cox proportional hazard model. Results: Fifty-one tumors exhibited the following features: size (mean 3.3 cm), stage (48 T3), grade (27 low, 24 high), LN status (11 neg, 40 pos), positive margins (13 traditional, 23 1 mm, and 32 PPS). Nearly all tumors exhibited at least focal vascular and perineural invasion. Grade influenced survival (p=0.0001), while size (p=0.417) and traditional and PPS margins did not (p=0.5 and 0.95). LN status and 1 mm margins trended toward significance (p=0.17 and 0.2). Conclusions: Use of a two-tiered grading system is highly correlated with survival. Neither tumor size, LN status, nor traditional or PPS margins are significant, while 1 mm margins trend toward significance. Although lack of significance of some features (i.e. size, LN status, and traditional margin status) may be attributable to modest sample size, lack of significance of the PPS may reflect its anatomic nature (i.e. not a true surgical margin). Additional study of 1 mm margins in a larger tumor set is warranted. No significant financial relationships to disclose.
Uncommon sites for metastasis of neuroendocrine tumor in adults
Authors: Srirajaskanthan R. , Desai K. , Jayaratnam A. , Carras E. , Toumpanakis C. , Meyer T. , Caplin M. 
Published: August 2020

e15683 Background: Neuroendocrine tumours are relatively slow growing tumours. They often present with significant metastatic disease affecting liver, lymph nodes, lungs and bone. However tumour masses may be found at unusual/uncommon sites e.g. breast, orbital soft tissue and the heart raising the possibility of this being metastatic focus or presence of another primary tumour. Detection of these sites could have a significant impact on the available treatment options. Aim: to determine the most appropriate imaging modality and type of tumour metastases. Methods: We reviewed 300 consecutive clinic patients. We identified 18 patients with metastasis at uncommon sites i.e. breast, orbital and cardiac. We retrospectively evaluated clinical notes and recent radiological investigations of these patients. To characterise these lesions additional investigations included cross sectional imaging, PET imaging (68Gallium DOTA Octreotate PET and 18F- FDG PET) and histological evaluation of the metastasis where appropriate. Patients with breast metastasis underwent bilateral mammogram, patients with peri-ocular involvement underwent MRI of the brain and the orbit. Results: 18 patients had tumour masses at uncommon sites. Of these 15 masses were in the breast; 4 were in the orbital muscles and 2 patients had pericardial metastasis. Of the 15 patients with breast lesions 12 had confirmed neuroendocrine tumour metastases and 3 had breast cancer. It should be noted that breast cancer lesions were positive on the 68Gallium Octreotate PET imaging. One patient who had a defined metastasis in the pericardium showed avid uptake on the 68Gallium DOTA Octreotate PET and scan and cardiac MRI, the other patient had pericardial metastases confirmed at post mortem. Conclusions: Clear knowledge of these uncommon sites of metastasis is useful in terms of arranging further investigations and excluding other cancers. It is also important to realise that although somatostatin receptor scintigraphy especially 68Gallium DOTA Octreotate PET is very useful in detecting NET metastasis, it may also show avid uptake in patients with breast cancer and hence histological evaluation of these lesions are important. Undoubtedly within our cohort of patients and generally there is an under-diagnosis of lesions in uncommon sites. No significant financial relationships to disclose.
Patient characteristics associated with dose-limiting sunitinib adverse events
Authors: Atkinson B. , Hart J. , Lin E. , Tannir N. , Jonasch E. 
Published: August 2020

e16110 Background: Sunitinib, an inhibitor of multiple tyrosine kinases, is FDA approved for metastatic renal cell cancer (mRCC). Though better tolerated than historical therapies, sunitinib is associated with adverse events (AEs) that may require dose modifications (DM). We sought to identify 1) baseline patient (pt) characteristics that predispose for DM, 2) the most common AEs requiring DM in a non-protocol setting, and 3) the impact of dose limiting AEs on treatment continuation. Methods: Single-center, retrospective chart review. Pts ≥ 18 years of age with mRCC of clear-cell histology on sunitinib therapy with active follow-up at MDACC were eligible. Univariate and multivariate logistic regression analysis of 66 pt variables (demographics, laboratory analysis, past medical and treatment history, etc) and dose-limiting AEs was completed, with a 6 month endpoint of sunitinib continuation, alternative therapy, or death. Results: From January 1, 2006 through September 30, 2007, 146 pts were identified meeting eligibility criteria. By univariate analysis, increased age (p=0.04; OR 1.04, 1.002–1.081 CI) and elevated BUN (p=0.03; OR 1.06, 1.006 –1.108 CI) were directly associated with increased incidence of dose-limiting AEs. ECOG PS of 2 (p=0.04; OR 0.3, 0.114–0.951 CI) was associated with a decreased incidence of dose limiting AEs. In a multivariate analysis, only BUN remained significant. 57% of patients (n= 83) had dose-limiting AEs. DM were often attributed to multiple AEs (55%), with fatigue, mucositis, hand-foot syndrome and nausea being the most common. At 6 months follow-up, 63% of pts with dose-limiting AEs remained on sunitinib vs. 37% (p=0.18). There was no difference in death rate at 6 months between the two groups. Conclusions: Elevated baseline BUN is associated with an increased rate of DM in patients with RCC receiving sunitinib. Despite the high-incidence of AEs, pts can be maintained on sunitinib with DM and without an adverse impact on outcome. Whether specific AEs are biologic indicators of activity should be evaluated in a larger clinical trial. [Table: see text]
Curative intended radiation therapy for young patients with invasive uterine cervical carcinoma: Clinical outcomes in 105 patients in a Japanese multi-institutional study
Authors: Niibe Y. , Ariga T. , Kazumoto T. , Kodaira T. , Etou H. , Suzuki O. , Kinoshita R. , Tsujino K. , Takemoto M. , Hayakawa K. 
Published: August 2020

e16558 Background: Recently, the number of young patients with invasive uterine cervical carcinoma is increasing in Japan because of earlier sexual activity and low rate of receiving screening test of uterine cervical carcinoma in Japan. However, no large studies have been performed so far to evaluate the clinical outcomes of curative intended radiation therapy for young patients with invasive uterine cervical carcinoma in Japan. Then, the current study was designed. Methods: One hundred and five patients under 40 years old were registered in the mulitiinstitutional study. The median age was 34.5 years old (range: 24–39 years old). According to FIGO, clinical stage was as follows. Stage Ib/IIa/IIb/IIIa/IIIb/IVa were 10/4/38/2/47/3, respectively. The median maximal tumor diameter was 5.5 cm (range: 2–9.2 cm). Curative intended radiation therapy was the combination of high-dose rate intracavitary brachytherapy (HDR-ICBT) combined with external beam radiation therapy (ERT). The total dose of ERT ranged from 44 Gy to 68 Gy. The total dose of HDR-ICBT to point A ranged from 12 Gy to 48 Gy. Eighty five patients received chemotherapy. Results: The 5-year overall survival rate and local control rate of all patients was 58.4 % and 59.3 %, respectively. The 5-year overall survival rates of stage Ib/IIa/IIb/IIIa/IIIb/IVa were 90.0 %/not available (NA)/73.8%/100%/37.4%/0%, respectively. The 5-year local control rates of Stage Ib/IIa/IIb/IIIa/IIIb/IVa were 80.0 %/50.0 %/73.8 %/100 %/54.6 %/NA, respectively. Sixteen patients experienced grade 3 or greater late radiation morbidity. Conclusions: Clinical outcomes of stage I-II in the young were equivalent to the Japanese standard treatment results of all ages. However, clinical outcomes of stage IIIb and IVa in the young were worse than those of all ages (5-year OS of all ages in Japan: IIIb: 50 %, IVa: 25 %). No significant financial relationships to disclose.
Evaluation of PET imaging in treatment decision making for early stage head and neck squamous cell cancer
Authors: Dulala R. , Campian J. L. , Dubner S. , Frank D. , Gabalski E. , Thomas A. , Akerman M. , Mehrotra B. 
Published: August 2020

e17017 Background: Positron emission tomography (PET) scanning is widely used in staging of patients (pts.) with head and neck squamous cell cancers (HNSCC). However, the role of PET scan in pts. with early stage disease and clinically negative nodes remains controversial. The purpose of our study was to correlate preoperative PET scan findings in early stage disease with operative pathological findings of neck dissection. Methods: A retrospective review of medical records of all pts. treated at Long Island Jewish Medical Center with T1N0 HNSCC from 2002 to 2008 was undertaken. Institutional Review Board approval was obtained for this study. Eligibility criteria included: clinically staged T1N0, documented pre-operative PET scans and primary surgical management including a neck lymph node dissection as part of initial treatment. Data collected included age, gender, physical examination findings, PET scan results, operative pathology and modalities of treatment. Results: Sixty six pts with early stage T1N0 HNSCC were identified. Twelve of sixty six pts met eligibility criteria for this study. Median age was 61 years (range: 27 to 84 yrs), M:F ratio was 1:1. Primary sites of tumor were: tongue (n = 8) 67%; oral cavity (n = 3) 25%; larynx (n = 1) 8%. Preoperative PET scan was positive at primary sites in all pts (n = 12). Additionally, PET positivity was noted in regional lymph node sites in six of twelve pts. Operative pathology confirmed tumor presence in all primary sites. However, nodal involvement was not found in any pt. Median numbers of lymph nodes dissected were 25 (range:13–34). Based on these clinical data, the calculated statistical parameters for preoperative PET scan in detecting occult neck lymph node metastases were: negative predictive value: 100%; positive predictive value: 50%: specificity: 50%; sensitivity: 0%. Conclusions: The clinical application of PET scans in early stage (T1N0) HNSCC may be limited by its high false positive rate. A high negative predictive value suggests that a negative result can exclude metastatic lymph nodes involvement in this group of pts. with early stage disease. Correlation with SUV values of the PET scans and comparisons between the relative PET avidity of the primary tumors and the nodal uptake are ongoing. No significant financial relationships to disclose.
Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil before concurrent chemoradiotherapy or concurrent cetuximab-radiotherapy in locally advanced squamous cell carcinoma of the head and neck
Authors: Billan S. , Abdah-Bortnyak R. , Mezid F. , Bernstein Z. , Gez E. , Nasrallah H. , Kuten A. 
Published: August 2020

e17045 Background: Encouraging results have recently been reported in patients with locally advanced squamous cell carcinoma of the head and neck. The present study assessed the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) or concurrent cetuximab-radiotherapy. Methods: Induction chemotherapy consisted of TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), 5-fluorouracil 750 mg/m(2)/d continuous infusion for 96 h) every three weeks, followed by CHT-RT regimen (radiotherapy 70 Gy total dose fractionated at 2Gy per day, 5 days a week concurrently with weekly cisplatin 40 mg/m(2) or cetuximab with loading dose of 400 one week before starting radiotherapy and 250 weekly during the radiotherapy) 4–7 weeks later. Percutaneus endoscopic gastrectomy inserted before the combined treatment. The National Cancer Institute Common Toxicity Criteria (version 2) were used for classification of adverse events. Results: Between march 2007 and november 2008, 29 previously untreated patients (19 male and 4 female) with stage III-IV squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx were included to the study. The median age was 60 years (range, 56–75 years). The stage distribution was as follows: stage II, 1 patient; stage III, 14 patients; and stage IV, 14 patients. 16 patients had a performance status of 0 and 11 had a performance status of 1. The response rate (RR) after IC was: complete response (CR) for 10 pts (34%), partial response (PR) for 13 pts (57%) and no response (NR) for 3 pts (13%). Toxicity from IC included neutropenia Gr III,IV 25%,neutropenic fever 9%, mucositis and diarrhrea Gr III, IV 22% . 60% of patients completed 3 cycles, 20% received 2 cycles and 20% received only one cycle of TPF. The toxicity from the concurrent phase included mucositis Gr III-IV in 70% of patients,dermatitis Gr III-IV in 43% and no case of neutropenia Gr III-IV. The combined treatment was interrupted only in 4 patients for one week. Conclusions: TPF was well tolerated with high response rate and low rate of acute toxicity. Three cycles of TPF followed by combined treatment are feasible. No significant financial relationships to disclose.