bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive values of intratumoral microvascular density (MVD) in the patients (pts) with advanced NSCLC and metastatic colorectal cancer (mCRC) receiving chemotherapy plus bevacizumab
Authors: Zhang L. , Jiang W. , Zhang Y. , Xu R. , Qian C. , Resau J. H. , VandenBeldt K. 
Published: August 2020

e14618 Background: The using of bevacizumab (VEGFR inhibitor) combined with chemotherapy represents a most noticeable recent advance in clinical oncology for significantly improving pts’ survival in several tumor types. There is an unmet need for seeking biomarker(s) to predict the treatment response of bevacizumab and identify the pts sensitive to the treatment. Our study was designed to investigate the predictive value of intratumoral MVD in NSCLC and mCRC pts treated with bevacizumab. Method: Sixteen NSCLC (stage IIIB/IV) and 15 mCRC pts who underwent chemotherapy (paclitaxel+carbo for NSCLC and IFL for CRC, respectively) combined with Bevacizumab were included into this study. The paraffin-embedded tumor samples (13/16 NSCLC and all CRC samples were collected from primary tumor) were sectioned and stained immunohistochemically for blood vessel markers (CD34 and CD31) to identify the characteristics of intratumoral vasculature. A computerized image analysis program was used to quantitatively calculate the intratumoral MVD (Yao et al., Clin Cancer Res 2007). Treatment response was evaluated by computed tomography scanning. Results: Two types of blood vessel, undifferentiated (CD31+/CD34-) and differentiated (CD34+), were identified. For the 16 NSCLC pts, a positive correlation was found between the largest tumor shrinkage percentage (evaluate in the primary tumors and metastases) and the total (CD31+) MVD as well as the undifferentiated (CD31+/CD34-) MVD, with Spearman's correlation coefficients equaled to 0.567 (p=0.022) and 0.576 (p=0.019), respectively. However, no significant correlation between tumor shrinkage and MVD was found in CRC pts, in which the treatment response was evaluated in metastatic lesions while the MVD was calculated in primary tumor. Conclusion: This exploratory analysis suggests higher total vessel and undifferentiated vessel MVD appeared to be predictive of bevacizumab treatment advantage for advance NSCLC pts.Our study also indicated that the MVD of primary lesions did not correlate with the treatment response of metastatic lesions in CRC pts. Further studies are needed to verify the predictive role of MVD in the treatment of bevacizumab in NSCLC. [Table: see text]
Impact of 18F-flurodeoxyglucose positron emission tomography in the staging and treatment response assessment of extrapulmonary small cell cancer
Authors: Brennan S. M. , Gregory D. , Stillie A. , Herschtal A. , MacManus M. P. , Ball D. L. 
Published: August 2020

e14639 Background: To assess the frequency of use and impact of FDG PET in the management of extrapulmonary small cell carcinoma (EPSCC). Methods: Patients treated for EPSCC who had undergone FDG PET for staging or response assessment between 1985 and 2007 were identified from the institutional database and patient records. The PET result was compared to the conventional staging investigations and management decisions were recorded. Results: 22 patients had staging PET at diagnosis. All known disease was PET avid. Stage migration occurred in one patient. Additional disease without upstaging was noted in 3 patients. PET influenced management in 4/22 (18%) of cases, in one case changing from radical to palliative therapy, and in 3 cases altering radiation target volume. 21 patients had reassessment PET scans. There was disparity with conventional imaging in 8 cases. In 4 cases the PET was found to be correct, in 2 case the PET result was a false positive and 2 cases were not assessable. (Sensitivity 100%, specificity 80%.) PET resulted in a change in management in 25% of patients, in all cases discontinuing radical therapy in patients with persistent disease. Conclusions: PET contributes to both staging and restaging of EPSCC and may influence management in up to 25% of cases. No significant financial relationships to disclose.
Antiproliferative, antiangiogenesis, and reversal of chemoresistance by specific cathepsin L inhibitors
Authors: Rebbaa A. , Dyskin E. , Dier E. , Gallati C. , Honko C. , Simone T. , Yalcin M. , Sudha T. , Mousa S. A. 
Published: August 2020

e14643 Background: Uncontrolled proliferation, enhanced angiogenesis and the development of resistance to therapy are hallmarks of cancer; therefore, the development of approaches to simultaneously target these three processes would be the most desirable. Previous work from our laboratory has demonstrated that NapSul-Ile-Trp-CHO (NSITC), a specific inhibitors of cathepsin L, and its analogs strongly inhibited cancer cell proliferation and suppressed the development of drug resistance in vitro (Zheng X. et al., 2004 Cancer Res. 64:1773–80). In the present study, we sought to investigate the validity of these observations in vivo, and to dissect the underlying mechanism(s). Methods: Nude mice (Strain CD1) bearing xenografts of doxorubicin resistant neuroblastoma cell line SKN-SH/R were challenged with doxorubicin (1.5 mg/Kg) alone, NSITC (20 mg/kg) alone or the combination of both. The effect of NSITC on tumor angiogenesis was also investigated using the Chick Chorioallantoic Membrane (CAM). Putative mechanisms by which NSITC inhibits cellular proliferation, drug resistance and angiogenesis were studied using cancer and endothelial cells maintained in culture. Results: The in vivo data indicated that doxorubicin alone had no effect on tumor growth, however NSITC alone exerted 40% inhibition and the combination of both drugs reduced tumor growth by about 90%. NSITC also caused a 125% inhibition of blood vessel branching in the CAM model (at 1 μg/CAM). Investigation of the underlying mechanisms of its action revealed that at low concentration, NSITC forces cancer cells into senescence, preventing them from developing resistance to classical anticancer agents, and at high concentrations, it induced autophagic cell death. NSITC also strongly inhibited the proliferation and invasion of endothelial cells in a dose dependent manner with more than 90% inhibition at 20 μM. Conclusions: Overall, these findings suggest that NSITC has multi-anticancer functions and thus, may represent a potential drug candidate for the treatment of aggressive malignancies. No significant financial relationships to disclose.
Long-term follow-up of endogenous erythropoietin, VEGF levels and red blood count in patients receiving different antiangiogenic treatment
Authors: Bloch J. , Mouawad R. , Spano J. , Vigniot S. , Magné N. , Khayat D. 
Published: August 2020

e14648 Background: Anemia, commonly defined as a hemoglobin level of <12 g/dL, occurs in over 30% of cancer patients at any time point and its incidence increases with treatment. The concept of antiangiogenic treatment for solid tumors has recently emerged and we wondered why patients under such kind of treatment did not experience anemia requiring transfusion or the use of erythropoietin. The goal of this study is to follow-up endogenous serum EPO, VEGF concentrations, hemoglobin (Hb) and hematocrit (Ht) levels in various metastatic cancers patients receiving different anti-angiogenic treatment and to try to establish the possible relation between these parameters. Patients and Methods: 30 patients (20 men and 10 women) with different cancer type (20 RCC and 10 thyroids) with a median age of 56 year were included in this study. All of theme received a angiogenic therapy. The values of hemoglobin, hematocrit and platelet were determined in all patients Endogenous serum erythropoietin,VEGF serum concentrations were quantified using Elisa test and at day 0 and each 4 weeks. Statistical analysis of the results was performed using Mann-Whitney U test and the correlation analysis was performed using Pearson test. Results: At day 0, The mean level of endogenous EPO and VEGF serum concentration was significantly higher in patients as compared to healthy donors (p=0.005 and p=0.0001 respectively). Regarding anemia, 65 % of the patients had a mild grade of anemia with 11.5 g/l of hemoglobin (Hb) and 36.4 % of Ht. Patients with normal Hb values had a lower mean EPO serum concentration and high VEGF concentration as compared to patients with anemia. A negative correlation was observed between EPO serum concentration and Hb and Ht levels. In overall patients, the follow-up of these parameters showed an increase in endogenous EPO and VEGF concentrations which was confirmed during the subsequent cycles treatment without any increase in Hb and Ht count.The study of these parameters patient by patient and the relation with the clinical response is ongoing and will be more developed. Conclusions: In overall patients we were not able to find any correlation between Hb or Ht, levels and EPO concentrations but a relation between the production of EPO and VEGF is observed. No significant financial relationships to disclose.
Comparison of l and dl forms of folinic acid in Gercor C96.1 trial (A phase III trial comparing bimonthly LV5FU2 to monthly high-dose 5FU-leucovorin in patients with Dukes’ B2 and C colon cancer)
Authors: Quinaux E. M. , Baumgaertner I. , Khalil A. , Louvet C. , Buyse M. E. , de Gramont A. , André T. 
Published: August 2020

e15004 In C96.1 study (André T et al; J Clin Oncol. 2007 20;25:3732–8), patients were randomized to either monthly 5FU-LV hd (dl LV 200 mg/m2 or l LV 100 mg/m2 15 min iv followed by 5FU 400 mg/m2 15 min iv, d1–5 q4 wk) or LV5FU2 (dl LV 200 mg/m2 or l LV 100 mg/m2 2-hour infusion followed by iv bolus 5FU 400 mg/m2 and 22 hours continuous infusion 600 mg/m2, d1 and d2 q 2 wk). Form l LV was administered to 60% (n=519) of patients and dl LV to 40% (n=357) of patients. It was unknown in 29 patients. No randomization was made between form l or dl (It was the choice of each center). The aim of this analysis was to compare the 2 LV forms in term of safety and efficacy. Important prognostic characteristics were well balanced between the 2 groups. The proportion of any grade III-IV toxicity was 20% in l form and 17% in dl form. There was no difference in term of toxicity between the two groups, except a trend for more diarrhea grade 3–4 in form l (8% in l form vs 4% in dl form, p=0.07). The median follow-up time was 6.2 years in l form and 6.0 years in dl form. There were no statistically significant differences between l and dl forms in term of disease free survival (33.3% vs 32.8% of patients with at least one event in l and dl forms respectively, hazard ratio=1.03, 95% CI=[0.82–1.31], p=0.78). In term of overall survival, there was a trend without statistical significance in favor of l form (21.8% vs 25.5% of patients who died, hazard ratio=1.28, 95% CI=[0.97–1.69], p=0.078). We conclude that the toxicity profile is similar between the two forms (excepted diarrhea). The difference in overall survival should not be attributed to folinic acid form as no difference was observed on DFS. No significant financial relationships to disclose.
Anti-VEGF and anti-EGFR monoclonal antibodies (Mabs) in the first-line therapy for metastatic colorectal cancer: A meta-analysis
Authors: Zhou Z. , Walsh W. V. , Bathini V. G. , Piperdi B. 
Published: August 2020

e15012 Background: Anti-VEGF (VEGFi) and anti-EGFR (EGFRi) Mabs have increased options for patients with metastatic colorectal cancers (mCRC). The optimal class of antibody to combine with chemotherapy (Ctx) in the first-line treatment for mCRC remains less well defined. Results from randomized controlled trials (RCTs) are variable. Methods: Systematic review and meta-analysis were performed on the basis of previously released RCTs results. We searched the MEDLINE, Cochrane registry, proceedings from ASCO, ECCO, ESMO until 12/ 2008 for RCTs of Mabs in first-line mCRC. Summary statistics were pooled hazard ratio (HR) of progression-free survival (PFS), overall survival (OS) and odds ratio (OR) of Response rate (RR) and 60 day mortality (60d-M). Effect of k-ras wild type and mutation were stratified in trials involving EGFRi. Results: 7 trials with complete data were identified, including 3 Ctx ± VEGFi (AVF2107g, NO16966, JCO2005.05.122), n=2422; 2 Ctx±EGFRi (CRYSTAL, OPUS), n=1554; 2 Ctx/VEGFi ± EGFRi (PACCE, CAIRO-2), n=1789. Addition of VEGFi to Ctx offered 20–30% risk reduction in disease progression and overall mortality, a 30% higher RR and nonsignificant 60d-M. Benefit of EGFRi in addition to Ctx was seen only in k-ras wild type patients with 36% reduction in disease progression and doubling in RR. However, addition of EGFRi to Ctx+VEGFi caused increased risk of progression and death with no significant increase in RR and 60d-M. Conclusions: Benefit of VEGFi in addition to Ctx in first-line mCRC is well pronounced and persistent. In k-ras wild type patients, addition of EGFRi to Ctx results in significant increase in RR and PFS. Addition of EGFRi to Ctx+VEGFi appeared harmful regardless of k- ras status. [Table: see text] [Table: see text]
Pregabalin (PGB) in treatment of oxaliplatin-induced neuropathy
Authors: Isufi I. , James E. , Keley K. , Peccerillo J. , Saif M. W. 
Published: August 2020

e15045 Background: Oxaliplatin is effective in many GI cancers, especially colorectal cancer (CRC); however, severe neuropathy develops frequently. PGB is a new antiepileptic drug approved as adjunctive therapy of partial seizures in adults, pain from diabetic neuropathy and post-herpetic neuralgia. PGB is structurally related to gabapentin, but unlike gabapentin, it is well absorbed (> 90%) and its absorption is dose independent. In this study, we evaluated the role of PGB in reduction of oxaliplatin- induced neuropathy. Methods: From Nov 2006 to Dec 2008, a total of 23 pts (age range: 50–71 yrs; M:F = 14:9) with GI cancers were treated with PGB upon development of oxaliplatin-induced neuropathy > G2 (NCI-CTC 3.0). Of these pts, 15 received FOLFOX for CRC, 2 EOX for gastric ca and 6 GemOx for pancreatic ca. Neurologic symptoms were evaluated prior PGB and then q 2 wks. PGB was started at 50mg PO tid, and if tolerated, dose was escalated by 50mg increments until symptoms improved up to a maximum of 150mg PO tid. Results: 5/23 pts (22%) were escalated to 150mg PO tid. 12 pts (52%) were escalated to 100mg tid, out of which 7 (58%) continued, 4 (33%) stopped due to no benefit and 1 (8%) stopped due to weight gain. 1/23 (4%) decided to follow 100mg bid. 5/23 (22%) could not be escalated above 50mg tid; 2 continued at this dose and 3 stopped due to CNS side effects. Onset of benefit was observed in 2 - 6 wks. In 3/23 pts (13%), neuropathy improved from G3 to G2, 2/23 (9%) from G3 to G1, 5/23 (22%) from G2 to G1, 6/23 (26%) remained stable at G2 and no pts remained at G3. Most pts continued PGB even beyond disease progression on oxaliplatin (15/23). Among those who continued (15), duration of therapy was 4 -24 months. The best benefit with PGB was seen at a dose of 150mg tid, followed by 100mg tid. The most common non-hematologic toxicities were dizziness (57%), headache (26%), somnolence (22%), dry mouth (17%), ataxia (17%), tremor (13%), peripheral edema (13%), weight gain (13%), blurred vision (13%) and constipation (9%). Hematologic toxicity (G1 thrombocytopenia) was seen in 1 pt (4%) but impact of chemotherapy could not be excluded. Conclusions: PGB significantly reduces the severity of oxaliplatin-induced neuropathy. Larger, placebo-controlled trials assessing safety and efficacy of oral PGB are warranted in pts treated with oxaliplatin. [Table: see text]
Robotic radiosurgery of liver metastases of solid tumors
Authors: Stintzing S. , Hoffmann R. T. , Heinemann V. , Kufeld M. , Muacevic A. 
Published: August 2020

e15049 Background: The number of patients (pts) suffering from isolated liver metastases is growing. Although surgical excision is the treatment of choice many pts do not qualify for surgery. So local ablative techniques like radiofrequency ablation, laser induced thermal ablation therapy, brachytherapy and different external beam radiation therapies have been employed. We here report the therapeutic efficacy of a robotic radiosurgery device for local control of liver metastases of solid tumors. Methods: Patients with liver metastases not qualifying for surgery were treated with single session radiosurgery (24 Gy) using robotic image-guided real-time tumor tracking. In a prospective analysis, follow-up was done by MRI scanning at two months after the treatment, and subsequently at 3-month intervals to evaluate local control. For inclusion into the radiosurgery treatment protocol, tumor volumes had to be smaller than 80cc. Results: 27 pts (median age 62 years) with a total of 43 target lesions were evaluated. 17 pts were treated with single, 10 pts with multiple targets. Metastases (n=27) originated from: colon (12), rectum (2), pancreas (2), lung (1), bladder (2), malignant melanoma (1), stomach (1), cholangiocellular carcinoma (2), breast (1), ovary (1), appendix (1) and endometrium (1). Median tumor volume was 21cc (range 2.2–79.3). Median KPS was 100% (range 80–100). The median follow up was 12 months. 23 pts (85%) reached local control of the disease, 4 pts (15%) had local recurrence. Grade 2–4 adverse events due to cyberknife treatment were not observed. Conclusions: Robotic radiosurgery with image-guided real-time tumor tracking of liver metastases is a new and promising treatment approach for pts not eligible for surgical resection and might enhance the possibilities of multidisciplinary oncological treatment concepts. No significant financial relationships to disclose.
Chemotherapy-induced thymidine phosphorylase modulation in colorectal cancer
Authors: Aprile G. , Miscoria M. , Baldin P. , Casetta A. , Pandolfi M. , Di Loreto C. , Pizzolitto S. , Pizzolitto S. , Foltran L. , Fasola G. , Puglisi F. 
Published: August 2020

e15050 Background: Thymidine phosphorylase (TP) is an inducible enzyme responsible for nucleoside metabolism, antiapoptosis activity, and promotion of angiogenesis. In addition, conversion of the prodrug capecitabine (C) to its active form depends on TP activity. Preliminary evidence suggests that TP immunohistochemical expression may predict benefit from first-line treatment of metastatic colorectal cancer (CRC) with C plus irinotecan. Several chemotherapeutic agents have been shown to modulate TP expression. The aim of the present analysis was to verify if TP expression differs among primary and paired metastases in CRC patients, or may vary depending on patients’ exposure to chemotherapy. Methods: TP expression was evaluated by immunohistochemistry (clone p-P-GF.44C, Abcam, Cambridge, UK) in a series of 120 primary CRC and their matched distant metastases. Tsuda's scoring system was adopted, defining TP expression as negative (score 0–1) or positive (score 2–3). Results: Data on the first 57 patients are here presented. Sites of biopsied metastases were liver (n=41), lung (n=10), and peritoneum (n=6). Metastases were asynchronous in 42% of patients. Higher TP expression was observed in primary cancers than in metastases (36.8% vs. 15.8%, p=0.007). Among patients who received at least one cycle of chemotherapy before metastasis sampling (38.6%), a TP expression decrease was demonstrated in only 13% of metastatic samples. Oppositely, a significantly higher proportion of untreated patients lost TP expression in metastasis sites (36%, p=0.01). Conclusions: In advanced CRC patients, TP expression tend to decrease in metastases, particularly in those patients who did not receive chemotherapy before metastatic sampling. Although intratumoral heterogeneity and other causes of discrepancy cannot be excluded, true chemotherapy-induced modulation of TP may be hypothesized. No significant financial relationships to disclose.
The effects of Gosha-jinki-gan on oxaliplatin-related neurotoxicity: A prospective randomized study
Authors: Nishioka M. , Shimada M. , Kurita N. , Utsunomiya T. , Iwata T. , Yoshikawa K. , Higashijima J. 
Published: August 2020

e15056 Background: Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but sensory neurotoxicity is its dose-limiting toxicity. The OPTIMOX (stop and go) approach offers a reasonable strategy, but preventive agent is not established. It is reported that Gosha-jinki-gan (a blended herbal medicine) is recently considered as an effective agent for the neurotoxicity of taxanes and for vibration sensation in patients with diabetic neuropathy. Patients and Methods: From 2007, 32 patients treated with modified FOLFOX6 for advanced or unresectable colorectal cancer were randomized. Fifteen patients received oral administration of 7.5 g/day of Gosha-jinki-gan (G group) every days from first course and 17 patients (Control group) did not. Neurotoxicities were evaluated every course according to DEB-NTC (Neurotoxicity Criteria of DEBIOPHARM) and NCI-CTCAE Ver.3.0 using self-check sheet. Results: The median number of cycles of per patient of G group was 14 (range, 4–26), and that of C Group was 9 (range, 1–20). Cumulative dose of oxaliplatin of two groups was 1,190 mg/m2 (G group) and 765 mg/m2 (C Group). Peripheral neurotoxicity evaluated by DEB-NTC in Group G was grade 0 in 0 patients (0%), grade 1 in 11 (73%), grade 2 in 4 (27%) and grade 3 in 0 (0%) and, in C group, respectively, 1 (6%), 6 (35%), 7 (41%), 3 (18%). According to NCI-CTCAE, neurotoxicity was lower in G group than that of C group. Fifteen patients in G group were evaluated by RECIST criteria with a PR rate of 66.7%, SD rate of 20.0% and PD rate of 13.3%. Seventeen patients in C group were evaluated by RECIST criteria with a PR rate of 52.9%, SD rate of 35.3% and disease control rate of 11.8%. Conclusion: Gosha-jinki-gan is effective for preventing oxaliplatin-induced neuropathy in advanced or unresectable colorectal cancer patients. [Table: see text]