bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second-generation inhibitors of fatty acid synthase for lung cancer treatment
Authors: Orita H. , Coulter J. , Tully E. , Pinn M. , Thupari J. , Pomper M. , Townsend C. , Ettinger D. , Kuhajda F. , Gabrielson E. 
Published: March 2020

18185 Fatty acid synthase (FAS) is highly expressed in many human cancers, including lung cancers. Previous work has shown that blocking FAS activity by cerulenin, a natural antibiotic, or C75, a first-generation synthetic small molecule, leads to apoptosis in cells that overexpress this enzyme. However, the use of C75 is limited by the dose-dependent anorexia that appears to be associated with stimulation of fatty acid oxidation. Pharmacokinetics studies show that the activity of C75 peaks within hours of administration and by 24 hours, approximately 80% of activity is lost. Thus, the effectiveness of C75 is limited by this short duration of anti-neoplastic activity and the prolonged anorexic effects.Several second-generation novel FAS-inhibitory compounds have been synthesized that show significant inhibition of FAS, without parallel stimulation of fatty acid oxidation. Among the most promising of the compounds is C93, which inhibits FAS at nearly equal potency as C75, but has significantly less stimulation of fatty acid oxidation. We treated mice with xenografts (orthotopic and subcutaneous) developed from 3 different human lung cancer cell lines (H460, A549, and LX-7) with daily intraperitoneal injections of C93 (5 days/week) at 50 mg/kg for 4 weeks and observed significant (up to 70%) inhibition of tumor growth in all xenograft models tested. Furthermore, no significant weight loss and no organ-specific toxicity were recognized in treated animals. These results suggest that it is possible to pharmacologically uncouple inhibition of FAS from stimulation of fatty acid oxidation, and thus achieve anti-neoplastic activity by inhibition of FAS without significant drug-induced anorexia. Finally, we tested an oral formulation of C93 with the intent of developing a dosing protocol suitable for clinical applications. Similar levels of drug in tumor tissue, and similar inhibition of fatty acid synthase enzyme activity, were seen after oral and intraperitoneal administrations of drug. Furthermore, repeated oral administration of C93 to animals with subcutaneous H460 lung cancer xenografts inhibited tumor growth to a similar level observed after intraperitoneal administration. Thus, fatty acid synthase appears to be a promising target for lung cancer treatment. No significant financial relationships to disclose.
Difference between skin toxicities in erlotinib (E) and gefitinib (G) in the treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Defferrari C. , Loprevite M. , Brianti A. , Catania G. , Grossi F. , Pronzato P. 
Published: March 2020

18187 Background: Cutaneous toxicities due to E or G are common and reversible adverse effects. In the two large randomized trials with E (Shepherd F et al, NEJM 2005) and G (Thatcher N et al, Lancet 2005) skin rash toxicity incidence seems different between the two drugs: all grades (gr) were observed in 76% and 37% of patients (pts), gr 3–4 in 9% and 2% respectively. The aim of this study was to assess the incidence of the most common toxicities occurred in a cohort of pts treated with E or G in the same period of time and evaluated by the same medical staff according to the Common Toxicity Criteria version 3.0. Methods: From May 2005 to July 2006, 47 pts suitable for a treatment with an EGFR inhibitor were evaluated for their eligibility in an open label phase II trial with E 150 mg/day. Pts ineligible for the latter (16) were treated with G 250 mg/day in a compassionate-use program. Fifteen pts were treated with G at progression after E. Results: Toxicities (all gr, gr 3/3–4) for E vs G consisted in: acneiform rash (64 vs 25%, 13 vs 0%), rash/desquamation (83 vs 19%, 12 vs 0%), pruritus (38 vs 16%, 6 vs 0%), dry skin (48 vs 32%, 3 vs 0%), nail changes (15 vs 6%, 3 vs 0%), diarrhea (54 vs 19%). When pts were treated with both E and G the toxicities (all gr, gr 3/3–4) observed were: acneiform rash (93 vs 20%, 27 vs 0%), rash/desquamation (100 vs 20%, 20 vs 0%), pruritus (41 vs 13%, 7 vs 0%), dry skin (54 vs 27%, 7 vs 0%), nail changes (27 vs 7%, 7 vs 0%), diarrhea (53 vs 7%). Conclusions: Our data are not conclusive being a non-randomized trial. However, these results suggest that there are less cutaneous adverse effects with G. This difference may be probably attributed either to the dose or the bioavailability of E. No significant financial relationships to disclose.
Small cell lung cancer in African Americans
Authors: Eads J. , Fu P. , Patrick L. , Levitan N. , Dowlati A. 
Published: March 2020

18194 Background: Several factors associated with prognosis in patients with small cell lung cancer (SCLC) have been established. The association between these known prognostic factors and race, in particular in African Americans has not been reported. This study was conducted to detect differences in presentation and prognostic factors among African Americans when compared to Caucasians. Methods: A retrospective chart review was performed identifying patients diagnosed with SCLC between July 1998 and December 2005. Data collected included demographic information (age, gender and race) as well as clinical information: stage at time of diagnosis, date of diagnosis, date of death, sites of metastases, response to chemotherapy as well as presenting symptoms and lab values including serum sodium, hemoglobin, WBC, platelets, LDH and any evidence of a neurological presentation. Results: Data was available for 198 patients. There was no significant association between race and stage (p=0.594), gender and stage (p=0.731), age and stage (p=0.505) or presence of a neurological symptom at time of diagnosis and stage (p=0.63). There was a trend that African Americans were more likely to present with a neurological symptom when compared to Caucasians (25% vs. 17% respectively) but this was not statistically significant (p=0.285). There was a significant association between race and gender (p=0.019). Of African Americans with SCLC, 71.4% were female while among Caucasians there was a more even distribution between sexes (51% female, 49% male). No significant difference was detected in overall survival when gender or race were examined (p=0.595 and p=0.953 respectively) and the difference when evaluating those with a neurological presentation was marginal (p=0.086). Other prognostic factors were similar amongst Caucasians and African Americans. Conclusions: When compared with Caucasian females, African American females are more likely to be diagnosed with SCLC than their male counterparts. Although not statistically significant, there is also a trend that African Americans with SCLC are more likely to present with neurological symptoms. No significant financial relationships to disclose.
An association between lung cancer and gastroesophageal reflux
Authors: Ghanem Z. , Sedfawy A. , Debari V. , Maroules M. 
Published: March 2020

18195 Background: Many studies have demonstrated the association between gastroesophageal reflux and a wide spectrum of extra-esophageal complications of the upper aerodigestive tract. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. In addition to that, laryngoscopy and bronchoscopy can reveal findings with a high positive predictive value for the presence of GERD. The probable role of this chronic irritative disorder as a causative agent in carcinoma of the lung has not been studied. The aim of our study is to determine the correlation between GERD and lung cancer. Methods: A hospital based retrospective age, sex, ethnicity and smoking matched case control study was performed in a tertiary care center. The medical records of 325 patients diagnosed with lung cancer and 325 matched control cases were reviewed between January 2003 and December 2005. We looked at many aspects at the presentation of the disease including right or left sided lung cancer, pathology of the tumor and the presence of other co-morbid conditions. GERD diagnosis was determined either by endoscopy, manometry or clinical diagnosis retrospectively. Results: Among the 325 lung cancer patients 75 (23%) were found to have GERD at the time of diagnosis. On the other hand, only 46 (15%) patients were found in the control group. By using the Fisher Exact Probability Test there was a statistically significant increase in the incidence of GERD among lung cancer patients compared to the control group at the time of diagnosis (p=0.0046, 95% CI = 1.21- 2.73 and Odds Ratio =1.82). Patients with lung cancer were also divided into 5 major categories: Adenocarcinoma (n=110, 34%), Squamous cell carcinoma (n=70, 22%), Small cell carcinoma (n=40, 12%), NSCLCA (n=52, 16%) and Others (e.g. large cell, neuroendocrine...etc) (n=53, 16%). Conclusion: Our analyses suggest an association between GERD and lung cancer. For this reason we may consider GERD as a possible co-promoting factor of lung cancer in some patients. No significant financial relationships to disclose.
False negative rates of PET scanning in bronchoalveolar lung (BAL) cancer and its implication for diagnosis and staging
Authors: Seidler C. W. , Buttar A. , Harrow B. 
Published: March 2020

18196 Background: Positron Emission Tomography (PET) scanning is extensively used for the diagnosis and staging of NSCLC lung cancer. Studies have shown PET scanning has a higher sensitivity and specificity in NSCLC than conventional diagnostic studies. False negative results in bronchoaveolar (BAL) lung cancer have not been systematically studied. We conducted a retrospective review to report and evaluate the low sensitivity of PET scanning in BAL when compared to other types of NSCLC cancer. Methods: We reviewed records of all patients who were diagnosed with lung cancer at Saint Vincent Hospital from 2000 to 2005. A total of 1361 patient were identified with a pathologically confirmed diagnosed of lung cancer out of which PET scanning was done in 36. All of these 36 cases reported NSCLC cancer: 29 NSCLC (adenocarcinoma 8, squamus cell 4, undifferentiated 6, non-small cell carcinoma 10), 7 bronchoalveolar carcinoma (BAL). Results: Among the cases diagnosed with NSCLC lung cancer at our institution, PET scans were done in 36 cases. Adenocarcinoma was found in 8 cases, all of which had positive PET reports. Squamous cell carcinoma was found in 4 cases, non-small cell carcinoma (not otherwise specified) was found in 10 cases, carcinosarcoma was found in 1 case, and undifferentiated carcinoma was found in 6 cases, all of which had positive PET reports and no false negatives (n=29/29,100%). Surprisingly, in the 7 bronchoalveolar cancer cases, only one PET scan was positive with 6 false negative reports (n= 1/7, 14.2%). A bivariate analysis (chi-square with Yate’s correction for continuity) revealed that the PET scan false negatives are significantly higher (p < 0.0000007) for BAL when compared to other types of NSCLC cancers. Conclusions: PET scanning does not appear to be sensitive in the stagging and detection of BAL lung cancer with sensitivity of 14%. Routine use of PET scans for staging and diagnosis of BAL is not supported by this study. No significant financial relationships to disclose.
Pre-medications of weekly taxanes in advanced non-small cell lung cancer
Authors: Huang X. , Ye Z. , Lin Y. 
Published: March 2020

18210 Background: Taxane is a widely accepted treatment in advanced non-small cell lung cancer (NSCLC). However, a standard pre-medication for weekly taxane has not been established at present. We conducted this study to evaluate the efficacy,safety and pre-medication of weekly paclitaxel /docetaxel schedule in the treatment of advanced NSCLC and to obtain an optimal pre-medication protocol for weekly paclitaxel /docetaxel. Methods: From December 2001 to June 2006, 78 patients with advanced NSCLC (Stage III, IV) were recruited from Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute. Eleven cases were treated with paclitaxel 80–100 mg/m 2 by intravenous infusion(ivi)on days 1 and 8, 23 cases were treated with paclitaxel 50–80 mg/m2 ivi on days 1, 8 and 15, 14 cases were treated with docetaxel 25–35 mg/m2 ivi on days 1,8 and 15,30 cases were treated with docetaxel 35–45 mg/m2 ivi on days 1 and 8, all combined with a platinum(cisplatin, oxaliplatin or carboplatin), followed by 1 week rest. Four pre-medications were attempted. Results: All 78 patients received a total of 202 courses of treatment. Dose limiting toxicity was myelosuppression. Grade 3 and 4 leukopenia occurred in 19.2% (15/78) of patients. Of the 56 eligible patients who completed at least 2 courses, no patient had a complete response, 20 achieved a partial response and 5 patients showed progression. Toxicity profile of pre-medications included: hypersensitivity (1 case), hypopotassemia (8 cases), myasthenia (5 cases), hiccup (1 case), infection (2 cases). No treatment related death occurred in this study. Conclusions: Weekly administration of paclitaxel/docetaxel is a safe and active protocol for Chinese patients with advanced NSCLC. Our recommendations for weekly pre-medication of taxane are: dexamethasone 2.25 mg-7.5 mg orally 12 h and 2 h before, promethazine 25 mg intramuscularly and cimetidine 600 mg ivi 30 min before paclitaxel; oral dexamethasone 4.5 mg-7.5 mg twice daily for three consecutive days (the day before, the day of, and the day after docetaxel), promethazine 25 mg intramuscularly and cimetidine 600 mg ivi 30 min before docetaxel. No significant financial relationships to disclose.
Consolidation therapy using cyberknife radiosurgery in NSCLC patients with low-volume residual disease upon completion of systemic therapy
Authors: McLaughlin M. P. , Bordoni R. , Whitaker T. , Zolty P. , Andrews M. , Still T. , Vanapalli J. , Haile K. 
Published: March 2020

18213 Background: Pts with unresectable IIIB and IV NSCLC with PS 0–1 are usually treated with chemotherapy (CH) ± targeted therapy (TT) with overall survival (OS) improvement. Upon completion, standard of care is observation. Pts eventually progress within 9 to 12 months. If still in good PS, they are treated with salvage CH or TT; otherwise, they receive palliative care. We evaluated 12 patients with PR to initial therapy, found to have small volume residual disease (SVRD) defined as one or two sites to receive “consolidation” local therapy with Cyberknife Radisurgery (CRS). Methods: Since September 2006, 12 pts with NSCLC, stage IIIB unresectable (3) or IV (9), median age 64 (range 61–78), adenocarcinoma (7), squamous cell carcinoma(5), 9 males, all ECOG PS 0–1, were treated with induction CH (carboplatin/paclitaxel ± bevacizumab, cisplatin/gencitabine) with PR. CT/PET imaging showed SVRD. Eight patients had only one site; four had 2. These patients received CRS consolidative therapy to the following areas: lung-9, mediastinal node - 3, adrenal-2, liver-2. CRS dose depended on the disease site. Peripheral lung lesions - 54 Gy in 3 fractions (fx); medistinal lesions - 50 Gy in 4 fx; adrenal - 24 Gy in 3 fx and liver - 16 Gy. in 1 fx. The primary end point was efficacy (response rate, time to progression in or out of the radiosurgical fields, and OS) compared with historical matched controls. The secondary end point was safety and tolerability of CRS. Results: After a median follow up period of 65 days, all evaluable pts are still alive and without clinical or radiological (CT/PET) evidence of disease progression in or outside the sites of CRS. The treatment was well tolerated with no Grade 3–5 complications. PS remained 0–1 in all patients. Conclusions: Patients with advanced NSCLC benefit from systemic therapy with symptoms control and improved QoL and OS. Upon completion of therapy, observation is the current standard or care. Patients with good PS and SVRD tolerated CRS consolidation therapy remarkably well and may benefit with added symptoms control, improved TTP and even OS. At the June meeting efficacy and toxicity data of a projected population of 30+ patients, with a medial follow up of 8 months, will be presented. No significant financial relationships to disclose.
Absolute lymphocyte count at time of radioimmunotherapy predicted time to progression in patients with relapsed follicular lymphomas
Authors: Porrata L. F. , Ristow K. , Witzig T. E. , Wiseman G. A. , Tuinstra N. , Markovic S. N. , Markovic S. N. 
Published: March 2020

18505 Background: Besides radiation, the immunologic mechanisms of action of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) have been attributed to complement mediated lysis and antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that a stronger host immune system prior to Zevalin therapy for relapsed follicular (grade 1&2) lymphomas (FL) would result in an improved time to progression (TTP). As a surrogate marker of host immune status, we studied absolute lymphocyte count (ALC) prior to Zevalin therapy and its impact on TTP in relapsed FL patients. Methods: Between 1996 and 2006, 75 patients with relapsed FL were treated with single agent Zevalin (0.4 mCi/kg, maximum of 32 mCi) at the Mayo Clinic. ALC was obtained from the complete blood cell count prior to RIT. Results: The median age of the cohort was 60 years (range, 29–82 years). 36% (27/75) patients were rituximab refractory. The median TTP in all patients was 6.4 months (range, 1–99+ months). Univariately, ALC as a continuous (HR = 0.448, p < 0.006) or dichotomized [ALC = 1.0 x 109/l (HR = 0.684, p < 0.007)] variable was identified as a prognostic factor for TTP. Superior TTP was observed with an ALC = 1.0 x 109/l (N = 32) compared with an ALC < 1.0 x 109/l (N=43) (median: 12.4 months vs 6.5 months, respectively, p < 0.007). Both groups were balanced in regard to the Follicular Lymphoma International Prognostic Index (FLIPI). ALC, as a continuous (HR = 0.507, p < 0.02) or dichotomized [ALC = 1.0 x 109/l (HR = 0.697, p < 0.01)] variable was identified as an independent prognostic factor for TTP in the multivariate analysis when compared with FLIPI. In the ALC = 1.0 x 109/l group, 14/32 (44%) of FL patients achieved a TTP = 12 months compared to only 7/43 (16%) in the ALC < 1.0 x 109/l group, (p < 0.02). Conclusions: This study supports our hypothesis that a higher ALC, as a marker of immune status of the patient, predicts longer TTP following Zevalin therapy in relapsed FL. No significant financial relationships to disclose.
Characteristics of Hodgkin lymphoma in Hispanics compared to other ethnic groups
Authors: Ofori-Ntow S. , Ciobanu B. , Telfer M. , Jajeh A. , Kovarik P. , Nathan S. , Kouz R. , Griza D. S. , Catchatourian R. 
Published: March 2020

18510 Background: There is scant literature on the characteristics of Hodgkin’s disease in Hispanics. We studied the characteristics of this disease in Hispanics compared to other ethnic-racial groups in our large multiethnic Hodgkin’s disease caseload. Methods: A retrospective analysis of all the Hodgkin’s disease cases diagnosed between 2003 and 2006 was undertaken, using Fisher exact test. Results: Of 289 cases of lymphoma diagnosed, 65 (23%) were Hodgkin’s disease compared to SEER data of 11%; Hispanics 40%, African Americans (AA) 41%, Caucasians 19%. Median age at diagnosis: Hispanics 26, AA 27, Caucasians 38. Among the AA: 85% were men 15% women, Hispanics: 58% men 42% women, Caucasians: 33% men, 67% women (p value 0.004). Histological subtypes: Nodular sclerosis 82 % (58): AA 45%, Hispanics 34%, Caucasians 21%; Mixed cellularity 21% (8): Hispanics 75%, AA 12.5%, Caucasians12.5% (p value 0.079). Among Hispanics 62% were clinical stage 1 or 2, 38% stage 3 or 4; Caucasians 75% stage 1 or 2, 25% stage 3 or 4; AA 33% stage 1 or 2 and 66% stage 3 or 4 (p value 0.029). Among the 16 patients with limited stage disease 50% were Hispanics, 25% Caucasians and 25% AA. Of the 49 patients with advanced stage disease, 70% of the Hispanics had IPS Score 0–3, 30% had Score 4–7. Among the AA, 70% had IPS Score 0–3, 30% Score 4–7, while 33% of the Caucasians had IPS Score 0–3, 67% had Score 4–7 (p value 0.077). Conclusions: Mixed cellularity subtype is more common in the Hispanics while the nodular sclerosis subtype is relatively common in African Americans. Hispanics had early clinical and limited stage disease at diagnosis. Among the patients with advance stage disease, Caucasians had a higher IPS Score than the Hispanics. The clinical relevance of these observations remains to be determined with further studies. No significant financial relationships to disclose.
Treg phenotype in T-cell lymphomas
Authors: Morales D. , Beltran B. E. , Castañeda C. , Carrasco A. , Quiñones P. , Yabar A. 
Published: March 2020

18513 Background: Foxp3 is a key regulatory gene required for the development and function of: regulatory CD4+CD25high T cells (Treg) specialized in maintaining the balance between immunity and tolerance and activated conventional CD4+CD25low T cells without suppressive activity. Previous studies had reported the origin of Adult T-cell Leukemia/Lymphoma cells (ATLL) in Foxp3 T cells and in other lymphomas types the FOXP3 expression was only detected in the reactive T-cell background. Our objetive was to determine the presence of Treg phenotype cells by the FOXP3 expression in T-cell lymphomas. Methods: A retrospective study was performed on 48 samples collected from diverse T-cell lymphomas in our institution. A highly sensitive immunohistochemical method was used to demonstrate Treg phenotype by FOXP3 protein expression with a mouse monoclonal antibody (clone 236A/E7ABCAM) in most formalin-fixed paraffin-embedded tissue sections from lymph nodes, skin, bone marrow and extranodal sites samples as cavum and stomach. We did not co-stained with CD25 and considered a FOXP3+ tissue when positivity was > 20% of tumor cells. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Among the 48 evaluable T-cell lymphomas collected, 33 were ATLL, 8 unspecified peripheral T-cell lymphomas (U-PTCL), 6 mycosis fungoides (MF) and 1 cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma. Among the 33 ATLL: lymphomatous=17, acute=11, smoldering=1, chronic=1, cutaneous=1 and undefined=2. FOXP3 expression in tumour cells was detected in 24% (8/33) of ATLL cases and in 37% (3/8) of U-PTCL. It was negative in MF tumour cells and aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma Among the ATLL cases FOXP3 positivity were obtained in 35% (6/17) of lymphomatous type; 18% (2/11) of acute ones and none in others ATLL types studied. Interestingly 3 U-PTCL had Treg phenotype and were related to EBV (LMP1 positive); two had extranodal primary ( parotide and cavum) and one was nodal. We failed to demonstrate any correlation between FOXP3 status and survival. Conclusions: Some ATLL and U-PTCL had Treg phenotype. In our work Foxp3 expression was not found to be a prognostic factor. No significant financial relationships to disclose.