tbuckley/cabot-search huggingface dataset:
Second primary lung cancers: Analysis of E5597 selenium chemoprevention study.
Authors: Rathi Narayana Pillai, Sandra J. Lee, Daniel D. Karp, Seena C. Aisner, John C. Ruckdeschel, Suresh S. Ramalingam, Fadlo Raja Khuri
Journal: Journal of Clinical Oncology (2014)

7518 Background: Non-small cell lung cancer (NSCLC) patients that undergo curative resection are at risk for development of second primary lung cancer (SPLC). The E5597 trial is the largest placebo-controlled lung cancer chemoprevention study conducted in the US. We report on the SPLC diagnosed in this cohort. Methods: E5597 randomized 1,561 (2:1) patients with resected stage I NSCLC to selenium or placebo for a total of four years with the primary objective of decreasing the incidence of SPLC. The study was stopped at first interim analysis for futility in October 2009. The participants were followed for incidence of all second primary tumors (SPT). Results: There were 290 (19%) incidences of SPT, of which 113 (7.2%) were SPLC among 112 cases (1 case with 2 incidences) as of January 2014 with median follow-up time of 5.6 years. 82 incidences in 81 cases occurred in the selenium arm (S) and 31 cases in the placebo arm (P). The median age was 67 years, and there were a higher proportion of women (52.7%). Although several patients continued smoking or had only quit within a year of SPLC (40.2%), most patients had quit smoking for at least one year (57.2%). The most common histology was adenocarcinoma (40.7%), followed by other (30.1%), squamous cell (25.6%), and large cell (1.8%). Almost all SPLC cases were detected by imaging (88.5%), but 31.9% were also clinically evident. Nearly two thirds of SPLC were stage I-II (61%). The incidence rates of SPLC were higher in the S arm compared to P arm: 1.42 versus 1.05 per 100 person years, respectively (95% CI 0.77-2.38). The median time to SPLC from randomization was 3.0 years (range 0.9-9.3 years) and from initial diagnosis of lung cancer was 4.2 years (range 0.8-28.5). Conclusions: SPLC is the most common second primary cancer in NSCLC patients. Continued surveillance even after tobacco cessation, is warranted for earlier detection of SPLC.
Durability and characteristics of objective tumor responses with the innate immune cell modulator Imprime PGG in combination with standard of care frontline treatment for patients (Pts) with metastatic non-squamous NSCLC.
Authors: Walburga Engel-Riedel, Folker Schneller, Martin Wolf, Wolfgang Schuette, Mable Ma, Paulette Mattson, Jamie R. Lowe, Ada H. Braun
Journal: Journal of Clinical Oncology (2015)

3070 Background: Recently, we reported numeric improvements in objective tumor response (OTR) and overall survival (16.1 vs 11.6 months median; HR = 0.66) with Imprime PGG (PGG) in a randomized (2:1) phase 2 study in 92 patients (pts) with stage IV non-squamous NSCLC receiving standard of care carboplatin/ paclitaxel (C/P) and bevacizumab (B) treatment first line (Engel-Riedel W et al, Ann Onc 2014, 25(5):1-41). Here, we report on the durability and characteristics of tumor regressions. Methods: The impact of treatment on the burden of malignant lesions was evaluated by modified RECIST v1.0. Imaging assessments (CT of chest and abdomen every 6 wks) were reviewed centrally in an independent, blinded facility. Pts were removed from treatment upon disease progression. Results: PGG (vs ctrl) in combination with C/P/B achieved a 60.4% (vs 43.5%) OTR rate. Time to OTR was short (12 wks vs > 18 wks) and responses were durable: median duration of response was 10.3 mos vs 5.6 mos (KM), with OTR lasting ≥ 12 mos in 7% vs 0% of pts in the PGG vs ctrl groups. Following completion of C/P chemotherapy, there was continued regression of lesions on maintenance treatment with PGG+B but not B alone: 6 pts (20%) in the PGG group vs 0 in the ctrl group had further > 1 cm reductions in target lesions’ sum of longest diameters (SLD), incl. 1 CR at 47 wks; this pt remains on treatment 2 yrs post randomization. In the PGG group, OTR were observed regardless of baseline tumor burden (up to > 30cm SLD) or lesion location (incl. lung, lymph nodes, adrenals, liver). Change from baseline in target lesions (SLD) over time will be presented for each pt. 1-yr survival was 62.8% vs 42.7% with PGG vs ctrl, and 13 (vs 1) pts remained in survival follow-up at primary analysis. Safety results have been reported previously and were favorable overall. Conclusions: Combined use of chemotherapy, B and PGG mediated rapid and durable responses of metastatic NSCLC regardless of baseline tumor burden or lesion location. There was further regression of lesions on maintenance PGG+B. Innate immune cell modulation with PGG holds promise for pts with metastatic non-squamous NSCLC. Clinical trial information: NCT00874107.
Reversible posterior leucoencephalopathy syndrome (RPLS) associated with pazopanib.
Authors: Robert Foerster, Thomas Welzel, Juergen Debus, Carsten Gruellich, Dirk Jaeger, Karin Potthoff
Journal: Journal of Clinical Oncology (2013)

e15574 Background: Tyrosine kinase inhibitors (TKI) are a relatively new modality for the therapy of metastatic renal cell carcinoma (MRCC). Although there are promising results, their use is often limited due to adverse reactions. We report on a case of malignant hypertension (HTN) and RPLS in a patient (PT) treated with pazopanib for MRCC. Methods: Case report. Results: A 62 year old woman with MRCC and since 8 weeks under 3 rd -line therapy with pazopanib had suddenly developed headaches, grand-mal seizures, paresis of the left arm, gait instability and nausea during her vacation. The emergency physician measured blood pressure (BP) values &gt;300 mmHG systolic and suspected a stroke. A CT without contrast agent in a local hospital only showed bone metastases. Suspecting cerebral metastases or meningeosis carcinomatosa (MC) the colleagues referred her to our radiooncologic department for diagnostics and treatment planning. At admission the PT was somnolent and unable to communicate because she had received larger quantities of diazepam as an anticonvulsive on the plane. The next day the PT was fully awake but showed significant anterograde amnesia from the onset of the headaches, psychomotoric deceleration and persistent gait instability. Brain metastases and MC were ruled out in an MRI which showed signs of RPLS in the form of band-like hyperintensities in the left parietal lob. HTN up to 220/120 mmHg persisted under 3x antihypertensive therapy and the PT reported that similar values were measured after the start of 1 st -line sunitinib 1 year ago. We discontinued pazopanib. Within 1 week the neurologic findings vanished and we discharged her. An MRI 3 weeks later showed RPLS-typical cortical infarctions in the affected area. The PT remained without any neurologic symptoms but intermittent HTN persisted. Conclusions: Vascular endothelial growth factor (VEGF) inhibitors and TKI are associated with HTN. Currently the exact mechanism remains unknown. HTN is an indicator for improved outcome under TKI therapy. BP should be closely monitored under TKI therapy. RPLS clinically mimicking cerebral metastases should always be considered as the actual reason for neurologic findings in patients with known metastatic cancers under TKI therapy.
Immediate-term chemotherapy-related cognitive impairment (CRCI) following administration of intravenous (IV) chemotherapy.
Authors: Omar Farooq Khan, Ellen R. Cusano, Soundouss Raissouni, Mica Pabia, Johanna Haeseker, Nicholas Bosma, Jenny J. Ko, Aalok Kumar, Michael M. Vickers, Patricia A. Tang
Journal: Journal of Clinical Oncology (2017)

146 Background: The acute impact of chemotherapy on cognition is unknown. This study utilized performance on the psychomotor vigilance task (PVT) and trail-making test B (TMT) to assess CRCI immediately following chemotherapy administration. Methods: Patients aged 18-80 years receiving first-line IV chemotherapy for any stage of breast or colorectal cancer were eligible. Patients with brain metastases, neurologic disorders or allergic reactions to chemotherapy were excluded. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Paired Wilcoxon Rank Sum tests were used to assess changes in median PVT reaction time, TMT completion time, TMT errors and PVT lapses. A priori, increases of 20 ms or over in median PVT reaction times (approximating reaction time changes with blood alcohol concentrations of 0.04 to 0.05 g%) were considered clinically relevant. Results: 144 patients (74 breast, 70 colorectal, median age 55.5 years) were tested. Post-chemotherapy, median PVT reaction time slowed by an average of 12.4 ms (p = 0.01). Post-chemotherapy median PVT times slowed by over 20 ms in 59 patients (40.9%). TMT completion post-chemotherapy was faster by an average of 6.1 seconds (p &lt; 0.001). No differences were seen in TMT errors (p = 0.417) or PVT lapses (p = 0.845). Change in median PVT reaction time was not associated with age, gender, number of prior chemotherapy cycles, use of paclitaxel (which contains alcohol), peripheral neuropathy grade, or self-reported anxiety, fatigue or depression. Conclusions: Median PVT reaction time was significantly slower immediately after chemotherapy compared to a pre-chemotherapy baseline, and impairment correlating to effects of alcohol was seen in 41% of patients. This effect appears independent of age, self-reported symptoms or prior chemotherapy cycles. Further studies assessing the functional implications of immediate-term CRCI are warranted.
Circulating microRNA profiling for early detection of non-small cell lung cancer.
Authors: Youping Deng, Hankui Chen, Helu Liu, Junmei Ai, Yan Li, Mehdi Pirooznia, Jeffrey Allen Borgia, Michael J. Liptay, Mary J. Fidler, Philip Bonomi
Journal: Journal of Clinical Oncology (2014)

e22051 Background: Lung cancer is a severe health problem in Western countries and the most common cause of cancer-related death. Noninvasive methods are needed to improve current approaches to detect non-small cell lung cancer (NSCLC), and circulating microRNA (miRNA) might be applied for the early diagnosis of this disease. Methods: 108 plasma samples from 55 early stage NSCLC patients (stage I and II) and 53 high risk controls were collected at Rush University Medical Center. High risk in patients was defined to be individuals aged 55 to 75 years, having a smoking history of more than 30 pack-years, and having quit less than 15 years before randomization. All high-risk individuals were followed with annual LDCT and remained cancer-free for a minimum 2-year follow-up. Genome-wide miRNA sequencing on pooled plasma specimens from each cohort was used to identify circulating miRNA profile. Quantitative real-time PCR (qPCR) was used to confirm the expression of selected plasma miRNA targets in all individual specimens and panel performance. Results: Using miRNA sequencing we identified 29 miRNAs significantly differentially expressed among NSCLC and high risk controls. Using qPCR in all individuals, we confirmed and elevated expression of miR-21-5p and downregulated expression of another candidate miRNA in NSCLC patients when compared with high risk controls. The prediction accuracy of a combined panel of these two miRNA markers for lung cancer was seen at 62.8% sensitivity, 93.2% specificity and 85.1% AUC (Area under ROC curve). Conclusions: Our preliminary data have showed that the pooling sample strategy worked well for genome-wide circulating miRNA profiling in miRNA sequencing. We observed that NSCLC patients have a significantly different plasma miRNA profile than that of high risk controls. These miRNA patterns might be developed as novel biomarkers for lung cancer screening. Further studies are warranted to confirm these findings in more samples including benign nodules, and testing more candidate miRNA markers are still going on.
Preclinical evidence of craniofacial adverse effect of zoledronic acid in newborn mice: Potential consequences in pediatric osteosarcoma and Ewing’s sarcoma patients.
Authors: Francoise Redini, Frederic Lezot, Julie Chesneau, Severine Battaglia, Regis Brion, Jean-Christophe Farges, Geraldine Lescaille, Beatriz Castaneda, Catherine Chaussain, Perrine Marec-Berard, Laurence Brugieres, Marie-Cécile Le Deley, Sophie Piperno-Neumann, Dominique Heymann
Journal: Journal of Clinical Oncology (2014)

10047 Background: Oncologic doses of zoledronic acid (ZOL) are currently evaluated in phase III clinical trials in Europe for the treatment of malignant primary bone tumors in children and adolescents. The impact of such an intensive treatment on the craniofacial skeleton growth is a critical question in the context of patients with actively growing skeleton. Methods: Two protocols adapted from pediatric treatments were developed for newborn mice (5 or 10 injections of ZOL 50 µg/kg every two days). Their impact on skull bones and teeth growth was analyzed by micro-CT and histology up to 3 months after the last injection. In parallel, panoramic radiographs of pediatric patients from the French OS2006 trial (chemotherapy +/- zoledronic acid) were analyzed for potential orofacial consequences. Results: In mouse, ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor, first molar eruption and root elongation. Root histogenesis was severely impacted for all molars and massive odontogenic tumor-like structures were observed in lower incisors. Panoramic radiograph analysis of 23 pediatric patients treated by chemotherapy + zoledronic acid in the OS2006 protocol showed not significant increase of tooth eruption delay comparatively to 21 patients treated by chemotherapy alone. Conclusions: In mouse, oncologic doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. In human, ZOL treatment may impact the permanent teeth eruption. These observations are crucial for the follow-up of pediatric patients with bone tumors (osteosarcoma, Ewing’s sarcoma) treated with zoledronic acid in several European and American protocols. Clinical trial information: NTC00470223.
Bortezomib (BTZ) and Panobinostat (PAN) Combination Is Effective in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) or NK/T-Cell Lymphoma (NKL) and Maintenance Treatment May Be Essential for Sustained Response
Authors: Daryl Tan, William YK Hwang, Colin Phipps Diong, Wee Lee Goh, Lionel K.Y See, Yiong Huak Chan, Soon Thye Lim, Soo Chin Ng, S Fadilah, Soo-Yong Tan, Won Seog Kim, Yeow Tee Goh
Journal: Blood (2012)
Whatever happened to the polypill?
Authors: Anthony J Viera
Journal: BMJ (2017)

The idea is slowly but surely gaining ground 

It has been nearly 15 years since Wald and Law proposed that a polypill could reduce cardiovascular events if taken by everyone from the age of 55 years (primary prevention) and all people with pre-existing cardiovascular disease (secondary prevention).1 Initial responses to the idea were mixed, with most who voiced opinions expressing opposition, some citing lack of trial data to support the “spectacular claims.”2 Others were enthusiastic about the idea’s potential, and since the 2003 publication several polypill trials have shown tolerability and benefit on intermediate and some clinical outcomes.3456 In the recent HOPE-3 trial67 a polypill reduced cardiovascular events by 29% over about 5.6 years in adults at moderate risk of cardiovascular disease (3.6% v 5.0%; P=0.005). Although overall benefit was driven by the statin, those with higher blood pressure benefited from blood pressure lowering as well.

The use of a polypill for secondary prevention, typically as a substitute for individual drugs, has …
Morvan syndrome as a paraneoplastic disorder of thymoma with anti-CASPR2 antibodies
Authors: Thiago Cardoso Vale, José Luiz Pedroso, Lívia Almeida Dutra, Lyamara Azevedo, Lucio Huebra Pimentel Filho, Lucila B F Prado, Romana Hoftberger, Gilmar F Prado, Orlando G Barsottini
Journal: The Lancet (2017)
Validation of correlation of RECIST changes with survival in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gregory Russell Pond, Arnoud J. Templeton, Daniel Peter Petrylak, Abderrahim Fandi, Bertrand F. TOMBAL, Mark Rosenthal, Guru Sonpavde
Journal: Journal of Clinical Oncology (2015)

5057 Background: In patients (pts) with mCRPC receiving chemotherapy, measurable disease response by World Health Organization criteria is prognostic for overall survival (OS). We now explored the association of changes in measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) with OS. Methods: Data from the control arm (n = 612) of the VENICE trial receiving docetaxel, prednisone and placebo (DPP) were available. Data on baseline clinical variables and outcomes were obtained. Cox proportional hazards regression was used to evaluate the prognostic ability of RECIST changes adjusting for known factors for OS using a 90-day landmark analysis. The association was validated using 388 patients in the DPP arm of the MAINSAIL trial who had RECIST measurements prior to day 90 and survival beyond day 90. Results: 363 pts in VENICE had measurable lesions, of whom 296 were evaluable for landmark analysis. 28 (9.5%) had progressive disease (PD) prior to day 90, while 58 (19.6%) had unconfirmed partial response (PR). In a multivariable analysis, the hazard ratio (HR) for OS for pts with PR was 0.64 (95% CI 0.42 – 0.99, P = 0.045) compared to those without PR, and 1.78 (95% CI 1.07 – 2.95, P = 0.026) for those with PD compared to those without PD. PD remained significant (HR = 1.85, 95% CI 1.10-3.12, P = 0.020) after adjusting for PSA changes, but PR was not (P = 0.14). The association of PR (HR 0.51, 95% CI = 0.22-1.18, p = 0.12) and PD (HR = 3.51, 95% CI 1.92-6.43, p < 0.001) with OS was externally validated in 388 pts in MAINSAIL who had measurable disease. After adjusting for PSA changes, PD was associated with poor OS (HR = 2.36, 95% CI 1.11-5.04, p = 0.026), but PR was not (p = 0.15). Conclusions: In men with mCRPC receiving first-line docetaxel-based therapy, RECIST changes within 90 days are associated with OS. Given the frequent detection of measurable disease with current imaging and the unclear association of PSA and bone scan changes with outcomes in the setting of new agents, the accrual of patients with measurable tumors in phase II trials to assess RECIST changes may provide a more objective signal of efficacy of new agents.
Staring inside of Idiopathic Hypereosinophilia: Identification of Clonality Using Targeted Exome Sequencing
Authors: Jee-Soo Lee, Heewon Seo, Kyongok Im, Si Nae Park, Jung-Ah Kim, Seon Young Kim, Joon-hee Lee, Sunghoon Kwon, Insong Koh, Seungwoo Hwang, Heung-Woo Park, Hye-Ryun Kang, Ju Han Kim, Miyoung Kim, Dong Soon Lee
Journal: Blood (2016)
Meta-analysis of upfront VEGF targeted therapy prior to nephrectomy in metastatic clear cell renal cancer.
Authors: Akhila Ganeshi Wimalasingham, Alfonso Gomez De Liano Lista, Roderick de Bruijn, John B. A. G. Haanen, Bernadett Szabados, Peter Hall, Christian U. Blank, Simon Chowdhury, Thomas Hopkins, Thomas Powles, Axel Bex
Journal: Journal of Clinical Oncology (2017)

514 Background: The safety and efficacy of upfront VEGF targeted, before nephrectomy in metastatic clear cell renal cancer (mCCRC) has not been robustly evaluated. Methods: In this study we performed a meta-analysis of 3 studies (NCT) with an almost identical design and included a single institution experience (which adopted this approach as a standard). Patients with newly diagnosed mCCRC had 12-18 weeks of sunitinib or pazopanib therapy prior to planned cytoreductive nephrectomy (CN). Results: 224 patients were included in this analysis (54% had sunitinib and 46% pazopanib). Overall, 73% had MSKCC intermediate risk and 23% poor risk disease. 20% of patients had an ECOG performance status of 0.84% of patients obtained stable disease or a response to therapy (by RECIST) before surgery. The median reduction of size of the primary tumour was 14%. 60% of patients had CN. The commonest reason for not performing CN was progression of disease. Progression free survival (PFS) and overall survival (OS) was 6.2 (95% CI 5.7-6.7) and 13 (95% CI: 10.2-15.7) respectively. Patients with MSKCC poor risk disease had a poor outcome irrespective of CN (OS = 7.5 months 95% CI 5.8-9.2). A comparison of sunitinib and pazopanib showed no significant difference in median PFS 7.1 (95% CI, 6.0-9.2) and 6.0 (95% CI: 5.1-6.8) or surgical complications (p&lt;0.05). Conclusions: Outcomes with this approach are in line with expected survival for this population. Results with sunitinib and pazopanib were similar. This approach is attractive for patients with MSKCC intermediate risk disease.
Satraplatin (S) demonstrates significant clinical benefits for the treatment of patients with HRPC: Results of a randomized phase III trial
Authors: C. N. Sternberg, D. Petrylak, F. Witjes, J. Ferrero, J. Eymard, S. Falcon, K. Chatta, D. Vaughn, W. Berry, O. Sartor
Journal: Journal of Clinical Oncology (2007)

5019 Background: Chemotherapeutic options for HRPC are limited. S is a novel oral platinum compound. Methods: The SPARC trial is a multinational randomized double blind study comparing S 80 mg/m 2 /day x 5 q5weeks po + prednisone (P) vs placebo + P in HRPC patients (pts) who failed prior chemotherapy. In this analysis, progression-free survival (PFS) was the primary endpoint, defined as a composite endpoint of radiologic progression, symptomatic progression, skeletal events or death. All cases were blindly adjudicated for progression by an independent review committee (IRC). Results: 950 pts were accrued between Sept 2004 and Jan 2006. Baseline characteristics were well balanced between treatment arms. 51% of the pts had received prior docetaxel. 68% were ≥ 65 yrs old and 27% were ≥ 75 yrs old. Pts received a median of 4 courses in the S arm (range:1–28) vs 2 courses in the placebo arm (range 1–16). 802 pts had an IRC defined progression-free (PFS) event consisting in 80% of the cases of radiologic progression, pain progression or death. All analyses were conducted on an intent-to-treat basis. S was associated with a 31% reduction in the risk of PFS events (HR=0.69; 95% CI: 0.60–0.80; p&lt;0.00001) and a 33% reduction in the risk of pain progression (HR=0.67; 95% CI: 0.54 - 0.83; p=0.00028). Consistent results in favor of S were found for PFS and time to pain progression in all subsets examined, including pts treated with prior docetaxel. Superior PSA response (25% vs.12%, p=0.00007), objective tumor response (7% vs. 1%, p&lt;0.002), pain response (24% vs. 14%, p&lt;0.005), and duration of pain response (HR=0.59; 95%CI: 0.35–1.00; p=0.049) were observed for S. Final analysis of overall survival awaits the occurrence of the pre-specified number of events. S was generally well tolerated - myelosuppression was the most frequent side effect, but grade 4 neutropenia was uncommon (4%) and a single patient had grade 4 thrombocytopenia. Grade 3/4 non-hematologic side effects included infection (4%), vomiting (2%) and diarrhea (2%). Conclusions: S is well tolerated and significantly reduces the risk of disease progression for HRPC pts who have failed prior chemotherapy. Supported by GPC Biotech and Pharmion No significant financial relationships to disclose.