bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating oncogenic pathway dysregulation in adolescents and young adults with acute myeloid leukemia.
Authors: Rao Arati , Livingston John Andy , Dave Sandeep S. 
Published: March 2020

7107 Background: Adolescent and young adults (AYAs) with Acute Myeloid Leukemia (AML) have been shown to have better outcomes with induction chemotherapy when compared to older young adults (OYAs). Multiple psychosocial, treatment, and host-related factors unique to AYAs have been identified but the contribution of disease biology to these outcomes has not yet been fully characterized. The purpose of this study was to evaluate disease biology as it relates to age-specific differences in outcomes for AYAs with AML. Methods: Clinically annotated, microarray data from 425 patients with newly diagnosed AML from two publicly available datasets: GSE1159; and GSE12417 were analyzed. Age-specific cohorts (AYAs ≤ 30 years; n = 58 and OYAs >30 but ≤ 60 years; n=276) were prospectively identified. Patients in GSE1159 were treated according to protocols of the Dutch–Belgian Hematology–Oncology Cooperative group and included 111 patients who ultimately underwent stem-cell transplantation. Patients in GSE12417 were treated per the AMLCG-1999 protocol. Gene expression analysis was conducted by applying previously defined and tested signature profiles reflecting deregulation of oncogenic signaling pathways and altered tumor environment. All statistical analysis was performed using S-plus and survival analysis by Cox proportional-hazards regression was used to assess differences in overall survival (OS) between age-specified study cohorts and a one-sided p-value ≤ 0.05 was considered statistically significant. Results: AYA patients had a significantly better OS (median survival 24.1 months vs. 13.0 months in OYAs; p=0.0285), but there was no difference in Event Free Survival (p=0.23). Analysis of oncogenic pathways revealed that AYA patients likely had better OS because of lower TNF (p=0.03) and higher myc (p=0.02) pathway activation. Conclusions: AML arising in AYAs may represent a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that contributes to OS. We hope these findings will enable clinically meaningful adjustments of treatment strategies in the AYA AML patient population.
Evidence for selective benefit of sequential treatment with azanucleosides in patients with myelodysplastic syndromes (MDS).
Authors: Komrokji Rami S. , Apuri Susmitha , Al Ali Najla , Padron Eric , Pinilla-Ibarz Javier , Ho Viet , List Alan F. , Lancet Jeffrey E. 
Published: March 2020

7113 Background: Azanucleosides (AZN) remain the mainstay of therapy in myelodysplastic syndrome (MDS). Sequential use of AZNs is common practice given the limited alternatives. The only published experience described 14 patients showing a 28% response with decitabine (DAC) after failure or lack of response to azacitidine (AZA). To investigate the potential benefit of this approach,we reviewed cases of sequential AZN treatment. Methods: Patients who received treatment with both AZNs were identified through the Moffitt Cancer Center MDS database. Two groups were identified; group one who received DAC after AZA failure and group 2, who received AZA after DAC failure. The primary objective was to estimate overall response rates according to the International Working Group (IWG) 2006 criteria. The Kaplan–Meier method was used to estimate median OS. Results: A total of 39 MDS patients were identified who received treatment with both AZNs. Complete records were available in 31 patients, including 21 patients in group 1 (DAC after AZA) and 10 patients in group 2 (AZA after DAC). The Table summarizes baseline characteristics and response rates. The median OS for Group 1 from diagnosis was 48 months and for group 2 was 100 months (p=0.7). Conclusions: Sequential use of AZNs after failure of first line may be an effective alternative outside the context of clinical trials. Response rate is higher in patients who receive AZA after DAC. Sequential use of HMA should be considered in context of randomized clinical trial of novel agent as the control arm. [Table: see text]
Cytidine deaminase status as a predictive marker in patients with hematologic malignancies treated with azacytidine or cytarabine.
Authors: Mercier Cedric , Fanciullino Raphaelle , Serdjebi Cindy , Ciccolini Joseph , Pourroy Bertrand , Milano Gerard , Costello Regis , Ouafik L'houcine 
Published: March 2020

7117 Background: Cytarabine and azacytidine are mainstays for treating haematological malignancies. As most nucleosidic analogs, both azacytidine and cytarabine are metabolized in the liver by an exclusive enzymatic step driven by cytidine deaminase (CDA). CDA is highly polymorphic and dysregulations have been repeatedly associated with poor clinical outcome with gemcitabine. Methods: We have used a test to determine, on a phenotype basis, CDA status in patients. This test was used prospectively in a subset of 39 adult patients (16F, 23M, mean age 77 years), all treated for various haematological malignancies (i.e., CML, AML, lymphomas, myelodysplastic syndromes) with either aza-cytidine or a cytarabine-containing regimen. Response and treatment-related toxicities were monitored following current standards. In addition, impact of CDA status on azacytidine tolerance was evaluated in mice with or without CDA deficiency, as a proof of concept for the actual implication of metabolic deregulations in the toxicities observed in patients. Results: In patients, mean CDA activity was 3.7 +/-2.8 U/mg (min: 1, max: 14.8 U/mg). Ten out of 39 patients (i.e., 25%) showed low CDA activities and were considered as PM. Conversely, 8 patients (i.e., 20%) displayed CDA activities particurlary elevated (i.e., > 6U/mg) and were considered as UM patients. Of note, PM patients all showed severe toxicities, including two toxic-deaths. Conversely, UM patients showed little efficacy when treated with either azacytidine or cytarabine. In mice with CDA-deficiency, standard azacytidine led to profound and long-lasting neutropenia, as compared with normal mice. Drug monitoring confirmed that individuals with low CDA activity and toxicities showed higher concentrations of azacytidine as compared with normal individuals. Conclusions: Overall this pilot study strongly suggests that CDA status could be a relevant marker for predicting clinical outcome in patients treated with either azacytidine or cytarabine. CDA status could be further used as a covariate to tailor drug dosage so as to ensure an optimal efficacy/toxicity balance in patients with haematological malignancies.
Long-term follow-up of autologous hematopoietic stem cell transplantation for stage II/III breast cancer.
Authors: Meyer Andrew D. , Tolentino Angelica L. , Bitran Jacob D. , Klein Leonard M. 
Published: March 2020

7121 Background: In the 1980s and 1990s, adjuvant chemotherapy with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) was utilized for the treatment of high-risk breast cancer. Previous studies showed that ASCT significantly reduced the risk of relapse in these patients, but failed to provide evidence of improved overall survival when compared with standard therapy in randomized trials. Due to the mortality, morbidity, and cost associated with ASCT and lack of a clear overall survival benefit, the use of HDC with ASCT for high-risk breast cancer was halted. In this retrospective, observation study, we analyzed the toxicity and efficacy of ASCT in high-risk breast cancer at a large community hospital. Methods: The study population consisted of 57 women diagnosed with high-risk primary breast cancer who underwent treatment with HDC followed by ASCT from 1991-1999. Women receiving treatment for metastatic breast cancer were excluded. The medical records of the study population were retrospectively reviewed, with particular attention to long-term toxicities and efficacy. Results: Fifty seven patients were evaluated: 54 with ductal and/or lobular breast cancer and 3 with inflammatory breast cancer. Median age was 44 years (29- 61). Twenty six patients (46%) were alive at time of review. Twelve patients (21%) experienced a recurrence of their breast cancer. Four patients (7%) developed secondary malignancies. Two patients (4%) experienced cardiac toxicities. Estrogen/progesterone receptor-positive breast cancers accounted for 42% of recurrences, 100% of secondary malignancies, and 50% of cardiac toxicities. HER-2/neu status analysis revealed amplification in 17% of breast cancer recurrences, but in no cases of secondary malignancy or cardiac toxicity. Conclusions: High-dose chemotherapy and ASCT can be effective in reducing long-term recurrences in women with high-risk, Stage II/III breast cancer. This treatment, however, carries an associated risk of secondary malignancies and cardiac toxicities. Estrogen/progesterone receptor-positive breast cancer appears to have a greater association with disease recurrence and secondary malignancies.
A randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma (MPM): Clinical results of a single-center trial.
Authors: Buikhuisen Wieneke A. , Vincent Andrew D. , Scharpfenecker Marion M. , Korse Catharina M. , Griffioen Arjan W. , van Pel Renee , Baas Paul 
Published: March 2020

7528 Background: Since standard chemotherapy treatment does not lead to long-term survival, new treatment approaches are required. MPM is known for a high vessel count and high levels of vascular growth factors. Suppression of the neo-vasculature by adding the oral VEGF-TKI axitinib to standard chemotherapy may lead to improvement. This study had both clinical and translational objectives. We here report the secondary endpoints response, PFS, OS and toxicity. Methods: Treatment naïve patients with suspected or proven malignant mesothelioma and medically suitable for limited surgical intervention were eligible after informed consent. Patients were treated with pemetrexed (500mg/m2q3wk) and cisplatin (75mg/m2q3wk) and were randomised to daily axitinib (2x5mg tablets). Before treatment a thoracosopy was performed to confirm the diagnosis. After 3 cycles of chemotherapy a palliative pleurectomy was performed. During both interventions material was obtained for research purposes. Patients could receive an additional 2 cycles of chemotherapy. Results: From July 2009 until October 2012, 26 patients were randomised. Six consecutive patients who received chemotherapy plus axitinib to demonstrate the feasibility and safety of the study design, were also included. In total twenty patients received axitinib. There was one protocol violation in the control arm. Median age: 61 yrs (35 yrs – 75 yrs), 84% epithelial type, 94% WHO 0-1 and 6% WHO 2. Median follow up was 18 months. Toxicity: There was more grade 3, 4 toxicity in the axitinib group concerning neutropenia (40% vs. 9%; p=0.11). One patient in the axitinib group developed a CVA, one patient pulmonary emboli. No thromboembolic events occurred in the control arm. Partial response was observed in 35% of patients in the experimental arm vs. 27% in the control group (p=0.99). Median PFS was 8 months in the experimental arm vs. 8.3 months in the control arm. There was also no difference in overall survival 17 vs 18 months, respectively. Conclusions: Axitinib was well tolerated in combination with cisplatin and pemetrexed. There was no evidence of benefit in response rate, progression free or overall survival. Clinical trial information: NCT01211275.
Lymphovascular invasion as a prognostic indicator in stage I non small cell lung cancer: A systematic review and meta analysis.
Authors: Mollberg Nathan M , Bennette Carrie , Howell Eric , Backhus Leah M. , Ferguson Mark K. 
Published: March 2020

7535 Background: Identification of pathologic features able to predict outcomes in resected stage I non-small cell lung cancer (NSCLC) may help to further stratify patients into risk groups, allowing for further refinement of adjuvant treatment recommendations. We performed a systematic review and meta-analysis to evaluate whether the presence of lymphovacular invasion (LVI) is associated with disease outcome in stage I NSCLC patients. Methods: A systematic search of the literature was performed (1990 to December 2012; Medline/Embase) using search terms related to lymphovascular invasion, lung cancer and prognosis. Studies were considered eligible if they reported the outcome of lung cancer in patients with LVI compared to those without. Pooled Hazard Ratios (HR) were estimated with a random effects model. Two different endpoints were independently analyzed: recurrence-free survival (RFS) and overall survival (OS). We analyzed both unadjusted and adjusted effect estimates, for a total of four separate meta-analyses. Several studies presented multiple results (i.e. adjusted and unadjusted and/or recurrence-free and overall survival) and were therefore included in more than one pooled analysis. Results: Of 2,878 titles identified, 20 articles met the inclusion criteria. Of these, 5 studies were excluded from the analysis due to duplication of results (n=4) and lack of data to calculate HR (n=1). The unadjusted models consisted of 808 (RFS) and 1675 (OS) patients, while the adjusted models consisted of 1,545 (RFS) and 2,601 (OS). The unadjusted pooled effect of LVI was significantly associated with worse both RFS (HR: 4.71, 95% Confidence Interval (CI): 3.08-7.21), and OS (HR: 3.05, 95% CI: 2.34-3.98). Adjusting for potential confounders yielded the same results with both RFS (HR: 2.49, 95% CI: 1.6-3.89), and OS (HR: 1.80, 95% CI: 1.44-2.25) being significantly worse for patients exhibiting LVI in their pathologic specimens. Conclusions: The present study indicates that LVI is an adverse prognostic factor in patients with surgically managed stage I lung cancer. Based on these results, the use of LVI as a stratifying factor in future prospective lung cancer trials seems to be justifiable.
Effect of age on impact of adjuvant chemotherapy for resected non-small cell lung cancer.
Authors: Ganti Apar Kishor , Williams Christina D. , Gajra Ajeet , Kelley Michael J. 
Published: March 2020

7539 Background: Adjuvant chemotherapy (AC) is considered standard of care in patients with resected stages 2 and 3 non-small cell lung cancer (NSCLC). However data regarding its utility in older patients are sparse. This analysis was conducted to evaluate the role of AC in older patients with early stage NSCLC. Methods: We conducted a retrospective analysis of patients with stages 1-3 NSCLC between 2001 and 2008 in the VA Central Cancer Registry. Patients were divided into two groups based on age: <70 yrs and ≥70 yrs. Descriptive statistics were used to examine patterns of AC use and to obtain survival rates associated with use of AC in the two age groups. Chi-square was used to compare distributions. Results: Of the 10,036 patients who underwent surgical resection, 3958 (39.4%) were ≥70 yrs, while 6078 were <70 yrs old. Overall, 11.2% of older patients (6.3% - stage 1, 21% - stage 2, 26.2% - stage 3) and 22.3% of younger pts (11.6% - stage 1, 41.1% - stage 2, 47.1% - stage 3) received AC. Of the patients who received AC, a greater proportion of younger patients received platinum-based AC (91.8 vs 86.4% vs; p=0.0008). Also, in each stage younger patients had a better 3 yr overall survival (OS) (Stage 1-69.2 vs 58%, stage 2 – 52.8 vs 39.1%, stage 3 – 42.5 vs 33.7%). Younger patients with stages 2 and 3 NSCLC who received AC had improved 3 yr OS (58.8 vs 48.6%; p=0.0009 and 48.8 vs 36.9%; p=0.0002 respectively). There was no difference in 3 yr OS for older patients based on AC when all stages were included. For patients with stages 2 and 3, a larger proportion of younger patients received cisplatin-based AC (11.3 vs 3.5%). Older patients with stages 2 and 3, who received cisplatin-based AC had a better 3 yr OS compared to those who received carboplatin-based AC or no AC (55.3 vs 42.2 vs 35.3% respectively; p=0.01). Similarly cisplatin-based AC had an improved 3 yr OS in younger patients with stages 2 and 3 NSCLC (61.4 vs 52 vs 43.4% respectively; p=0.0001). Conclusions: This analysis suggests that older patients do not benefit from AC after resection of stage 1-3 NSCLC to the same degree as younger patients. This differential effect may be due to less common use of cisplatin among older patients. Multivariate analyses are planned.
Outcomes of elderly stage I lung cancer patients treated with segmentectomy via video assisted thoracoscopic surgery or open resection.
Authors: Smith Cardinale B. , Mhango Grace , Wisnivesky Juan P. 
Published: March 2020

7543 Background: Video-assisted thoracic surgery (VATS) is considered an alternative to open lobectomy for the treatment of non-small cell lung cancer (NSCLC). Limited data is available however, regarding the equivalence of open vs. VATS segmental resections, particularly among elderly patients. In this study, we used population-based data to compare postoperative and oncologic outcomes following open vs. VATS segmentectomy for early NSCLC. Methods: We identified all stage I NSCLC patients >65 year treated with VATS or open segmentectomy from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims. We used propensity score methods to control for differences in the baseline characteristics of patients. Overall and lung cancer-specific survival of patients treated with VATS vs. open segmentectomy was compared after adjusting, stratifying, or matching patients based on their propensity score. We performed secondary analyses evaluating perioperative complications, need for intensive care unit (ICU) admission, extended length of stay, and perioperative mortality. These were repeated adjusting for physician characteristics (sociodemographics, specialty, and procedure volume). Results: Of the 577 study patients, 27% underwent VATS resection. VATS were mostly performed by high volume surgeons (p<0.001). Overall (hazard ratio [HR]: 0.80, 95% CI: 0.60-1.06) and lung cancer-specific (HR: 0.71, 95% CI: 0.45-1.12) survival was similar among treatment groups. VATS-treated patients had lower rates of postoperative complications (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.37-0.83), need for ICU admission (OR: 0.18, 95% CI: 0.12-0.28), and decreased length of stay (OR: 0.41, 95% CI: 0.41-0.81) after adjusting for propensity scores. The distribution of all postoperative complications, ICU admission, extended length of stay, and perioperative mortality was not significantly different across groups after adjusting for surgeon characteristics. Conclusions: VATS segmentectomy can be safely performed among elderly patients with early stage NSCLC and is associated with equivalent postoperative and long-term oncologic outcomes.
Association of miR-141 and miR-200c with time to recurrence (TTR) and overall survival (OS) in resected non-small-cell lung cancer (NSCLC) adenocarcinoma (ADC) patients (p).
Authors: Campayo Marc , Navarro Alfons , Tejero Rut , Cabanas Maria L , Molins Laureano , Marrades Ramon M , Ramirez Jose , Monzo Mariano , Vinolas Nuria 
Published: March 2020

7547 Background: Surgical resection remains the standard curative treatment for early-stage NSCLC, but nearly 50% of p experience recurrence, highlighting the need for novel diagnostic and therapeutic strategies. Moreover, treatments in NSCLC are often histology-dependent, underlining the need for histology-related markers. MicroRNAs (miRNAs) are promising molecular markers in cancer, with marked differences in expression according to histology. miR-200 family members have been associated in vitro with the regulation of epithelial-mesenchymal transition. We have examined their impact on outcome in resected NSCLC p. Methods: We analyzed miRNA expression using TaqMan assays in 160 tumor samples from NSCLC p who had undergone surgical resection and correlated our findings with TTR and OS. Results: p characteristics: age, 67 (51-83); 140 male; 96 (60%) stage I, 34 (21.3%) stage II, 30 (18.7%) stage III; 77(48.1%) ADC, 71(44.4%) squamous cell carcinoma (SCC); 16 (9.1%) received adjuvant treatment. With a median follow-up of 28 months (m), 64 p (40%) had relapsed. TTR for the 107 p with high miR-200c was 26.7 m vs 100.2 m for the 52 p with low miR-200c (P=0.032). OS for p with high miR-200c was 71.2 m vs. 125 m for p with low miR-200c (P=0.01). TTR for 112 p with high miR-141 was 26.7 m vs. 100.2 m for 46 p with low miR-141 (P=0.06). OS for p with high miR-141 was 72 m vs. 118 m for p with low miR-141 (P=0.02). Interestingly, neither miR-200c nor miR-141 correlated with TTR or OS in SCC p. In contrast, in ADC p, the prognostic value of both miRNAs increased: miR-200c (TTR, P=0.01; OS, P<0.0001) and miR-141 (TTR, P=0.003; OS, P<0.0001). This prognostic value was maintained in the subgroup of stage I p: miR-200c (TTR, P=0.011; OS, P<0.001) and miR-141 (TTR, P=0.018; OS, P<0.001). In the multivariate analysis, miR-200c and miR-141 emerged as an independent prognostic factor for OS (OR: 3.2, P=0.006; OR:2.5, P=0.02, respectively) together with age>65 (OR: 3.3, P=0.001) and stage I (OR: 0.3, P=0.004). Conclusions: miR-200c and miR-141 expression is associated with TTR and OS in resected ADC but not in SCC NSCLC p.
Reducing futile thoracotomy rates in PET-CT staged non small cell lung cancer: Clinical risk factors from a population-based review.
Authors: Smoragiewicz Martin , Laskin Janessa J. , Wilson Don , Ramsden Katherine , Zhai Yongliang , Ho Cheryl 
Published: March 2020

7551 Background: The use of PET-CT in staging NSCLC reduces futile thoracotomy (FT) rates to approximately 30%. We aimed to identify pre-operative clinical risk factors for FT in patients (pts) staged with PET-CT. Methods: The British Columbia Cancer Agency (BCCA) provides care to 4.5 million people. A retrospective chart review was conducted on all pts referred to the BCCA in 2009-2010 who had staging PET-CT and thoracotomy for NSCLC. Exclusion criteria: tri-modality therapy, clinical N2 disease, or cancer within 5 years. FT was defined as benign lung lesion, exploratory thoracotomy, pathologic N2 disease, stage IIIB/IV, or recurrence or death < 1 year of surgery (sx). The FT and non-FT groups were compared with the Fisher test in univariate analysis and logistic regression model multivariate analysis. Results: 108 pts met inclusion criteria. Baseline characteristics: male 42%, median age 67 (45-82), ECOG 0-1/+2: 85%/15%, never/former/current smoker 18.5/42.5/39%, weight loss >10% 9%. Disease characteristics: nonsquamous/ squamous histology 72/28%, median primary tumor size 3.2 cm, median SUVmax 10.1, PET + N1 24%. Median time from PET to sx 29 days. 29% pts received adjuvant chemotherapy. Thoracotomy was futile in 27 pts (25%); 14 recurred < 1 yr of sx, 10 pathologic N2 and 1 each incomplete resection, pleural disease at sx, death within 1 yr. On univariate analysis, PET + N1 (odds ratio [OR] 3.77, p 0.008) and primary tumor size > 3.2cm (OR 2.93, p 0.026) were associated with FT. On multivariate analysis, ECOG >1 (OR 4.57, p 0.017), PET + N1 status (OR 4.24, p 0.006) and primary tumor size > 3.2cm (OR 2.87, p 0.039) were associated with FT. Among the 26 pts wth PET + N1, 44% underwent FT; 23% due to N2 disease, 19% relapsed within 1 yr, 4% incomplete sx. 27% had mediastinoscopy or EBUS staging. Among the 82 pts with PET – N1,18% underwent FT; 5% due to N2 disease, 11% relapsed < 1 yr, 2% pleural dx or death < 1 yr. Conclusions: Pre-operative ECOG >1, primary tumor size > 3.2 cm and PET + N1 are associated with higher rates of FT in NSCLC. PET + N1 disease corresponds to higher rates of N2 disease and surgical staging may reduce FT in this population. These factors should be taken into consideration to reduce FT rates in NSCLC.