bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of hospitalizations associated with skeletal related events in patients with breast cancer or lung cancer and bone metastases or multiple myeloma
Authors: Lage M. , Harrison D. J. , Barber B. , Jun S. 
Published: March 2020

17083 Background: Patients with bone metastases secondary to cancer often experience skeletal related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, bone surgery or radiotherapy, or initiation of opioid analgesic use. These SREs result in major morbidity and reduced quality of life. This research examines hospitalizations associated with SREs. Methods: Data for this study were obtained from i3 LabRx Database (05/01/2000 to 03/31/2005). Individuals were included in the analyses if they had at least two diagnoses of breast cancer (based upon an ICD-9 code of 174.xx), lung cancer (162.xx), or multiple myeloma (203.0x) and had at least two diagnoses of bone metastases (198.5x) after the first diagnosis of cancer. In addition, individuals were required to have at least one SRE (based upon a previously published algorithm) on or after their initial diagnosis of bone metastases (their index date). Individuals were required to be continuously insured for at least 6 months prior to, and at least one month post their index date. Data were analyzed until 03/31/2005 or until the end of their continuous coverage, whichever occurred first. Descriptive statistics for each of these cohorts are provided. Results: A total of 1,204 individuals with breast cancer, 1,094 with lung cancer, and 258 with multiple myeloma were included in the study. The vast majority of individuals with breast cancer (96.5%), lung cancer (95.9%), or multiple myeloma (96.8%) were hospitalized. All three patient groups were likely to have SRE-related hospitalizations; multiple myeloma 43.4%, breast cancer 36.2% and lung cancer 35.6%. The average number of days per patient year that patients were hospitalized related to a diagnosis or procedure for a SRE was 6.75 days for patients with lung cancer, 6.56 days for patients with multiple myeloma, and 3.75 days for patients with breast cancer. Conclusion: Hospitalizations related to SREs are common and the number of days per year is substantial. No significant financial relationships to disclose.
Analysis of antioxidant enzymes combined with the detection of MCL-1 and Bax expressions in acute childhood leukemias
Authors: Elbordiny M. , Moawia S. , Elsayed I. , Bassiuony K. , Elshahat M. 
Published: March 2020

17522 Background: Occurrence and biological characteristics of tumors are related not only to over-proliferation of carcinoma cells but also to decrease of apoptosis. Investigation of apoptosis helps to disclose the biological characteristics of tumors, and seeks new methods of diagnosis and treatment for tumors. In this study, we analyzed the level of some antioxidant enzymes in various leukemic patients including SOD. Methods: To investigate the involvement of apoptosis regulating proteins in acute leukemias, immunocytochemical examination of Mcl-1 and Bax proteins expression was investigated in two groups of patients, one with acute lymphoblastic leukemia (ALL) and the other with acute myeloid leukemia(AML). Moreover, the free radicals utilizing enzymes were sought including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT), in addition to malonaldhyde (MDH), nitric oxide (NO), and glutathione content (GSH). Results: The obtained results showed a significant difference of SOD, GSH-PX, CAT, MDH, NO, and GSH levels in the leukemia patients (AML, ALL) compared to control group (P<0.001 for each comparison). On the other hand, there was a significant difference of SOD, GSH-PX, MDH, NO, and GSH levels in the AML group compared to ALL patients (P<0.001 for each comparison). In AML patients, a significant positive correlation was existed between SOD and GSH-PX (r=0.684, P<0.001) and a negative correlation was existed between catalase and MDH (r=-0.419, P<0.019). Mcl-1 expression was found positive in ten ALL patients out of 31(32.3%) versus 17 out of 31 (54.8%) in AML patients. Concerning Bax reactivity, only seven cases (22.6%) were positive in ALL patients versus 11 cases (35.5%) in AML patients. In ALL patients, a positive correlation was found between Mcl-1 and Bax expressions (r=0.453, P=0.011). Conclusions: Our results collectively reflect remarkable differences between AML and ALL suggesting different mechanisms underlying their formation and their progression. Mcl-1 and Bax expressions relating to the programmed cell death (PCD) or apoptosis in addition to the anti-oxidant status are deregulated mechanisms that contribute in the pathobiology of ALL differently from AML. No significant financial relationships to disclose.
Elderly patients with resected stage II, IIIA non-small cell lung cancer, increased referral rate to medical oncologists, 1992-2002
Authors: Wang J. , Kuo Y. , Freeman J. L. , Goodwin J. S. 
Published: March 2020

18002 Background: Resectable non-small-cell lung cancer (NSCLC) has been once considered as a surgical disease and therefore managed by surgeons alone, as the primary therapeutic option was surgical resection. However, it is now widely accepted that the optimal care for NSCLC requires a multidisciplinary care approach between surgeons, radiation oncologists and medical oncologists. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we identified 3266 patients over 66 years with Stage II, IIIA NSCLC who underwent resection between 1992 and 2002. We examined the trend of medical oncology referral, indentified the predictors associated with medical oncology referral and subsequent use of adjuvant chemotherapy. Results: From 1992 to 2002, 1562 patients (47.8%) with resected stage II, IIIA NSCLC were referred to the medical oncologists; there was a steady rising trend in the proportion of the patients referral to medical oncology over the ten year period. The medical oncology referral rate increased from 26.9% in 1992 to 60.5% in 2002 (P<0.001). This change has paralleled to a rising trend in use of adjuvant chemotherapy in same population during same period. Among those seen by oncologists, 518 (33.2%) of patients received adjuvant chemotherapy. Female, white race, younger age, advanced tumor stage, adenocarcinoma, later year of diagnosis and being married were strong predictors to be seen by a medical oncologist. Patients older than 70 years of age, African American race and living in certain SEER geographic region were less likely to be referred to medical oncologists. Patients who had a medical oncology consultation were more likely to receive adjuvant chemotherapy (adjusted odds ratio [OR], 5.14; 95% CI, 4.11 to 6.43). Conclusions: The medical oncology referral rate doubled during last decade. Access to medical oncology consultation is linked to the use of adjuvant chemotherapy in the patients with resected Stage II, IIIA NSCLC. The steady increase in referral to medical oncologists paralleled an increase in the use of adjuvant chemotherapy. This changing pattern of medical oncology referral may mirror the changing attitude and perception towards to the benefits of adjuvant chemotherapy in the community. No significant financial relationships to disclose.
Lymphatic vessel density is not associated with lymph node metastasis or survival in non-small cell lung carcinoma (NSCLC)
Authors: Villaflor V. M. , Faoro L. , Hutto J. , Varalakshmi J. , Suzue K. , Vokes E. , Husein A. , Salgia R. 
Published: March 2020

18008 Background: Angiogenesis is accepted as being essential for tumors to grow and metastasize to distant sites. Lymphatic metastasis is also an important means of tumor spread. Vascular endothelial growth factor C (VEGF-C) plays and important role in lymphangiogenesis and activates VEGFR (VEGF receptor)-3. Numerous studies suggest that tumor expression of VEGF-C is a significant prognostic factor in NSCLC. In non-small cell lung carcinoma (NSCLC), the relationship of lymphangiogenesis with lymph node metastasis and patient prognosis is unknown. Methods: A retrospective analysis of 78 patients who were diagnosed with NSCLC from 1987 to 2004 were analyzed for lymphatic vascular density (LVD). LVD was measured by use of D2–40 monoclonal antibody staining. Survival was assessed and Mantel-Cox and Wilcoxon signed rank tests were used for statistical analysis. Results: Intratumoral and peritumoral LVD was significantly higher than in the uninvolved adjacent lung, but showed no significant association with lymph node status at the time of tumor resection. Variables which appeared to affect survival in our study were the presence of lymph node metastasis (median survival 1,425 vs absence 467 days, p=0.002). The presence of VEGF staining inversely affected median survival (present 757 vs absent 1,944 days, p= 0.014). LVD ≤ 53 events per field 895 days vs >53 median survival 1,302 days, p+0.867. Survival appeared to not be affected by LVD. Conclusions: These data suggest that although lymphangiogenesis occurs in association with NSCLC, it may not be an important factor in lymph node metastasis or in survival. In fact, there is a suggestion that the number of lymphatics that a patient inherently has appears to be more important than lymphangiogenesis when it comes to the development of lymph node metastasis. No significant financial relationships to disclose.
Phase II study of irinotecan and paclitaxel for patients with recurrent small cell lung cancer (SCLC)
Authors: Owonikoko T. K. , Ramalingam S. , Forster J. , Shuai Y. , Evans T. , Gooding W. E. , Sulecki M. , Belani C. P. 
Published: March 2020

18011 Background: Recurrent SCLC has a poor prognosis and is devoid of treatment options that improve overall survival. Irinotecan and paclitaxel are both active agents against SCLC, and have synergistic preclinical interactions. We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel for patients with recurrent SCLC. Methods: Patients with SCLC who relapsed following one prior chemotherapy regimen were eligible. Other pertinent inclusion criteria were: ECOG performance status 0–2, adequate bone marrow, hepatic and renal function and willingness to provide informed consent. Patients with untreated brain metastasis were excluded. Paclitaxel (75 mg/m2) and irinotecan (50 mg/m2) were administered on days 1 & 8 of every 3-week cycle. Treatment was continued until progression up to a maximum of 6 cycles or unacceptable toxicity. The primary endpoint was response rate. Toxicity was graded by CTC version 2.0. The simon two-stage design was utilized and the estimated sample size was 55 patients (stage I - 23 patients; stage 2 - 32 patients). The study has a 90% power to detect a response rate of 30%, with an alpha error rate of 10%. Results: 55 patients have been enrolled and complete data are available for 32 patients at the time of this report. Patient baseline characteristics are: male 53%, PS 0–44%; PS 1–47% and PS 2–6%. The median age is 61 years. Fifteen patients received ≥ 4 cycles. Salient grades 3–5 toxicities seen: neutropenia (13%), fatigue (13%); diarrhea (3%), hypersensitivity (3%) and hyponatremia (3%).The objective response rate is 37% (95% CI 19%-55%) with 9 PRs and 1 CR. Additional 8 patients (24%) had stable disease. The median survival is 19.6 weeks (95% CI 15.1–29.4) and the 1-year survival rate is 15%. Conclusions: The combination of irinotecan and paclitaxel is well tolerated and has promising anti-cancer activity in recurrent SCLC. Updated data on all 55 patients will be available at the time of the presentation. No significant financial relationships to disclose.
Treatment of advanced non-small cell lung cancer in the elderly: Spanish Lung Cancer Group (SLCG) experience
Authors: Provencio M. , Camps C. , Alberola V. , Dómine M. , Isla D. , De las Peñas R. , Etxaniz O. , Cobo M. , Millán I. , Massuti B. 
Published: March 2020

18012 Background: The number of elderly patients (p) with cancer continues to increase. Approximately two-thirds of p diagnosed with non-small cel lung cancer are > 65 years (y), and nearly 50% are > 70 y. The aim of our study was to discern whether clinical characteristics, toxicity, response rate, treatment and survival are different in p < 70 y vs p = 70 y. Methods: We reviewed the database of 6 SLCG clinical trials with different doublet combinations from 2000 to 2005 Results: Of 1653 p included, only 280 p (17% ) were = 70 y. No significant differences were found between the two groups with respect to gender, stage, response rate or histology. However, a higher frequency of squamous cell carcinoma was found in p = 70y. No differences were found in median number of cycles administered. The only significant difference was found in the higher frequency of grade 3–4 neutropenia among p = 70 y. (Table) Conclusions: p = 70 y were a small percentage of all p included in these clinical trials. However, outcome and toxicities were similar in p = 70y vs <70 y, and “fit” elderly p can be treated with standard doublets. Further research is warranted on genetic differences for customizing treatment in this population. [Table: see text] No significant financial relationships to disclose.
PET response following stereotactic body radiotherapy for non-small cell lung carcinoma correlates with local control
Authors: Feigenberg S. J. , Yu J. Q. , Eade T. , Buyyounouski M. , Wang L. , Langer C. , Scott W. , Movsas B. 
Published: March 2020

18013 Background: Given the success of Stereotactic Body Radiotherapy (SBRT) for Non-Small Cell Lung Carcinoma (NSCLC), early surrogates of local failure (LF) are necessary to allow timely surgical salvage. This study tries to determine the utility of PET response as an early surrogate for LF. Methods: Eligible patients(pts) had biopsy proven NSCLC < 5 cm in size who underwent a pre- and post- SBRT PET scans. Pts treated at Fox Chase Cancer Center were either: 1. early stage (10 pts), 2. biopsy-proven local recurrences (4 patients) or 3. oligometastases (3 patients). Eleven of the 17 pts were treated on a prospective phase I dose escalation protocol and received either 40 Gy or 48 Gy in 4 fractions over 8 days. Non-protocol pts generally received 48 Gy in 4 fractions (5 of 6 pts). Treatment volumes were individualized for each pt using either 4 D or multi-phase CT simulation. As part of the prospective study design, PETs scan was obtained pre- and post-SBRT to correlate metabolic response with LF based on the work by MacManus. The post-SBRT PET scan was obtained at a median of 3 months following treatment (range, 2 to 6 months). LF was defined by my an increase in size on CT on serial imaging. Results: With a median follow up of 14 months (range 4 to 31 months), 3 LF have been documented. The median SUV max pre-SBRT was 4.7 (range 1.32 to 18.2) and 1.9 (range 0.9 to 7.0) post-SBRT. Only four pts had a post-SBRT SUV max > 2.5 (2.8, 5.1, 5.3 and 7). Overall, twelve pts had a drop in their SUV max following SBRT, while 1 pt had stabilization and 4 had an increase . Of these last 5 pts, 3 developed LF. The other two have been followed without any intervention and remain free of recurrence for > 2 years, respectively. No pt with an initial drop in post SBRT PET scan SUV has had LF. Conclusions: PET response (defined as a drop in the SUV max by 3 months) correlates with LF, and appears to be a good early surrogate of outcomes following SBRT. Larger studies are required to confirm this finding. No significant financial relationships to disclose.
Accuracy of CT-guided transthoracic needle biopsy of lung lesions: Results of 612 consecutive procedures
Authors: Ricardi U. , Priola A. M. , Priola S. M. , Novello S. , Cataldi A. , Crida B. , Scagliotti G. V. , Fava C. 
Published: March 2020

18022 Background: CT-guided transthoracic needle biopsy (TNB) is commonly used in diagnostic work-up of lung lesions. The availability of a on-site pathologist at the time of the procedure ameliorate its sensitivity, reduce the number of biopsies and false negatives. Methods: 612 procedures (608 patients with a CT-documented central or peripheral pulmonary lesion) performed at S. Luigi Hospital between November 2002 and August 2005 were prospectively analyzed; 66% males, median age was 66 years (range 29–87). Ineligibility criteria for the procedure included severe coagulopathy, previous contralateral pneumonectomy, lesions with a maximum diameter less than 5 mm or the impossibility to understand the procedure or to maintain the clinostatism for the time of the procedure. The on-site pathologist assigned to each specimen a semiquantitative score: 0 for bloody sample without other cells, 1 for aspecific benign or inflammatory cells, 2 for malignant cells without histotype characterization and 3 for well established benign or malignant histotype. Results: Most of the procedures was performed by fine needle aspiration biopsy, while in a minority of cases a tru-cut biopsy was requested. In 57.2% of the cases a single transthoracic access (range 1–4) was used and in 31% the procedure was repeated on the basis of the radiologist/pathologist judgment. In 154 patients a surgical resection was subsequently performed, while 454 were patients non-surgical. A score of 3 was obtained in 71% of cases (88% malignancies), 2 in 12.5%, 1 in 7.5% and 0 in 9%. A definitive diagnosis was made in 83.5% of procedures, while a score of 0–1 was assigned in 101 cases. Among 458 malignancies there were 411 lung cancer, 7 non-epithelial cancers and 40 metastases with only 1 false positive. The diagnostic accuracy for benign and malignant lesions was 67% and 92%, respectively (Pearson’s test p<0.005) with overall diagnostic accuracy of 83.3%. The variables affecting diagnostic accuracy were final diagnosis (benign 67%, malignant 92%, p<0.001) and lesion size (lesion 5 cm 78%, p<0.05). The presence of cavitation or necrotic areas and location of the lesion didn’t affect the diagnostic accuracy. Conclusion: In consecutive cases of CT-guided TNB final diagnosis and lesion size affect diagnostic accuracy. No significant financial relationships to disclose.
A sensitive method for detection of EGFR gene mutations in plasma
Authors: Sanders H. R. , Qu K. Z. , Sferruzza A. D. , Strom C. M. , Bender R. A. 
Published: March 2020

18027 Background: Somatic mutations in the tyrosine kinase (TK) domain of the EGFR gene are associated with clinical response to TK inhibitors in patients with non-small cell lung cancer. An assay that detects such mutations in the plasma would provide a noninvasive technique to assess suitability for TK inhibitor therapy. Here we describe: 1) the development of a sensitive assay to detect the E746-A750 deletion in the TK domain of EGFR in plasma; and 2) optimization of the method for plasma DNA extraction. Methods: Our assay uses Mse I to specifically digest wild-type (WT) genomic DNA (gDNA) to reduce non-specific amplification. After digestion, samples are PCR- amplified using 1 unlabeled primer and 1 FAM-labeled primer spanning the E746-A750 deletion region and fluorescence detected with an automated analyzer. Serial dilution studies were conducted using H1650 gDNA (del E746-A750 cell line) diluted in WT gDNA after Mse I digestion. To assess detection of the deletion in plasma, 3–4 mL whole blood was spiked with 1–37 ng H1650 gDNA; gDNA from the separated plasma was then extracted (silica column/2-propanol precipitation), digested with Mse I, and amplified as above. Several extraction methods were evaluated using pooled plasma samples and PBS spiked with 10–350 ng gDNA: silica column, magnetic bead, phenol:chloroform, and 2-propanol precipitation. Results: Digestion of the WT EGFR allele followed by deletion-specific fluorescent PCR allowed detection of caof ca. 1 copy of the del E746-A750 EGFR gene (10 pg gDNA) diluted to 0.001%. Furthermore, del E746-A750 was successfully detected in 1/5 the final DNA volume (5 μl) in all spiked blood samples. Magnetic bead-based DNA extraction yielded the highest percent recovery of gDNA from PBS (69% recovery of the 10-ng sample). Phenol:chloroform extraction gave the highest yield with pooled plasma samples. Conclusions: The combination of an optimized DNA extraction method, clearing the plasma DNA sample of amplifiable WT DNA by restriction digestion, and mutation-specific fluorescent PCR provides a highly sensitive assay for detection of somatic mutations in plasma. No significant financial relationships to disclose.
Lipoplatin plus gemcitabine versus cisplatin plus gemcitabine in NSCLC: Preliminary results of a phase III trial
Authors: Boulikas T. , Mylonakis N. , Sarikos G. , Angel J. , Athanasiou A. , Politis G. , Rapti A. , Rassidakis A. , Karabatzaki M. , Anyfantis N. 
Published: March 2020

18028 Background: Lipoplatin is a liposomal formulation of cisplatin, designed to reduce its adverse reactions without reducing efficacy. Its nanoparticles evade immune surveillance and extravasate preferentially into tumors inducing tumor cell apoptosis; lipoplatin may also act as antiangiogenesis factor. This is the initial report of a randomized, multicenter, phase III trial comparing the two drugs. Methods: Eligibility criteria included confirmed diagnosis of inoperable/metastatic NSCLC, no previous chemotherapy, WHO PS 0–1, adequate end-organ function. Patients received Lipoplatin 120 mg/m2 D1,8,15 or cisplatin 100 mg/m2 D1, combined with gemcitabine 1,000 mg/m2 D1,8, in 3-week cycles, with disease evaluation after 3 and 6 cycles. Primary endpoints are overall survival and toxicity, with Response Rates, PFS and QOL also being evaluated. Results: 59 patients have been treated, 33 with lipoplatin and 26 with cisplatin; 17 have completed treatment. 2 lipoplatin patients had a hypersensitivity reaction during the first infusion. There were no grade 4 toxicities. Grade 3 toxicities were observed in <5% of the patients and were comparable for the two groups, except neutropenia (3% for lipoplatin, 15% for cisplatin). Main grade 1–2 toxicities were anemia (93% vs 88%), leucopenia (51% vs 38%), neutropenia (45% vs 30%), thrombocytopenia (58% vs 31%), hepatotoxicity (38% vs 46%), nausea/vomiting (13% vs 35%), asthenia (31% vs 30%) and anorexia (32% vs 34%). Concerning nephrotoxicity, grade 2 was reported in only 6% of lipoplatin patients vs 19% in cisplatin, although lipoplatin was administered without pre-hydration as a 6-hour infusion. Neurotoxicity was also markedly less in lipoplatin. So far, 32 patients have been assessed for response, 16 in each group; 4 partial responses have been reported in each group. However, difference has been observed in stable disease (23% in lipoplatin vs 12% in cisplatin) as well as progressive disease (16% vs 35%). Conclusions: Preliminary results show that lipoplatin may have a better safety and therapeutic profile than cisplatin, when combined with gemcitabine, in advanced NSCLC. Particularly important might be its significantly lower neuro- and nephro-toxicity and its administration on an outpatients basis. No significant financial relationships to disclose.