bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health and quality of life (QOL) issues in four groups of lung cancer patients: Low-dose computed tomography (LDCT) screened, chest x-ray detected, incidentally found, and routinely diagnosed.
Authors: Yang Ping , Yost Kathleen J. , Clark Matthew M. , de Andrade Mariza , Piderman Katherine M. , Wampfler Jason A. , Sloan Jeff A. , Midthun David E. 
Published: March 2020

1610 Background: Low dose computed tomography (LDCT) scans have reduced lung cancer deaths by 20.3% in high risk populations, although there is an unknown balance between the benefits and harms of LDCT scans as a screening tool. Our purpose was to compare health-related QOL issues among lung cancer patients who were initially detected by LDCT scans; 4 comparison groups included: lung cancer diagnosed by a screening chest X-ray, as an incidental finding from procedures taken for other medical reasons, or based on symptoms indicative for lung cancer and routinely diagnosed, and individuals who were LDCT screened but found no lung cancer (controls who participated in Mayo’s lung cancer CT screening trial). Methods: A total of 1,658 lung cancer patients (cared at Mayo Clinic) in the 4 groups (37, 151, 389, and 1081 respectively) and 488 controls were compared on following patient-reported outcomes (collected via validated tools): overall QOL, four symptoms (cough, pain, dyspnea, fatigue), mental/ physical/ emotional/ social/ spiritual QOL, and other concerns (e.g., family/ friends/ financial/ legal). A clinically significant deficit was defined as at least 10-points in difference (or <50 points) on a 0-100 scale. The rates of deficits were compared via Fisher’s exact tests and average QOL values via Kruskal-Wallis tests. Results: Overall QOL and individual symptoms were significantly worse (p<0.05) in all lung cancer groups than in controls, except for pain. LDCT-screened patients reported the greatest deficit among the 4 lung cancer groups in physical (41%), emotional (24%), social (38%), and spiritual QOL (24%); whereas chest X-ray detected patients had the least deficit in overall QOL (22%) and pain (32%). All 4 lung cancer groups experienced much worse fatigue (52-64%) than the controls (32%). Conclusions: Our preliminary results suggest that LDCT-screening detected lung cancer patients reported a different QOL profile from other lung cancer patients and non-lung cancer controls. The clinical course, smoking behavior, and QOL related health issues associated with LDCT screening for lung cancer warrant thorough investigation.
Randomized phase II 8-arm factorial study of adjuvant dose-dense (dd) temozolomide (TMZ) with permutations of thalidomide (Thal), isotretinoin (CRA), and/or celecoxib (Cel) for newly diagnosed glioblastoma (GBM).
Authors: Gilbert Mark R. , Hess Kenneth R. , Lagrone Lore , Groves Morris D. , Levin Victor A. , De Groot John Frederick , Loghin Monica Elena , Puduvalli Vinay K. , Fisch Michael , Giglio Pierre , Colman Howard , Conrad Charles A. , Aldape Kenneth D. , Yung W. K. Alfred ,   M. D. Anderson CCOP, Brain Tumor Trials Collaborative
Published: March 2020

2003 Background: Concurrent radiation and TMZ followed by 6-12 months of adjuvant TMZ (d 1-5 of a 28d cycle) is the current standard of care for patients with newly diagnosed GBM. The addition of cytostatic or signal transduction agents may enhance efficacy without a significant increase in toxicity. A phase I trial (Neuro-oncology 2009) established the safety of ddTMZ with 2 or 3 of the cytostatic agents. Methods: This randomized phase II study was conducted by the Brain Tumor Trials Collaborative (BTTC) and the MDACC CCOP. The primary objectives: determine if specific cytostatic agents added to ddTMZ alters outcomes (PFS, OS) and compare triplet with doublet therapy. Eligibility criteria: centrally confirmed newly diagnosed GBM, age ≥18, KPS≥60, stable or improved after chemoradiation (pseudoprogression allowed), adequate hematologic, renal and hepatic function. Pts were randomly assigned to 12 treatment cycles (28 d/cycle) in 8 arms: ddTMZ alone (150 mg/m2/day, 7-d on, 7-d off) or TMZ-containing doublet, triplet and quadruplet combinations with Thal, CRA, or Cel. Results: The study enrolled 155 eligible patients from 11/2005 to 9/2010 to the 8 arms of the factorial design. Median age was 53 (18-84) and median KPS, 90 (60-100). Compared with TMZ alone, the TMZ+CRA doublet had worse PFS (10.5, 6.5 mo; p=0.043) and OS (21.2, 11.7 mo; p=0.037). Trends were also seen for worse outcome (PFS, OS) for CRA-containing regimens, improved OS for Cel containing arms and no impact of Thal. A strong trend for OS improvement was seen for triplet compared with doublet regimens (20.1, 17.0 mo; p=0.15), but no difference for PFS. Treatment was well tolerated with expected high rates of grade 3/4 lymphopenia, and overall a modest toxicity rate. Conclusions: The results indicate that the addition of CRA to ddTMZ may be detrimental in patients with newly diagnosed GBM. This study demonstrated the utility of the factorial design in efficiently testing drug combinations, the impact of individual agents in these combinations as well as doublet vs. triplet regimens and supports its utility in testing combinations of targeted agents.
Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) associated with "responsive" malignancies.
Authors: Jaeckle Kurt A. , Anderson S. Keith , Willson Anna , Colon-Otero Gerardo , Patel Tejal Amar , Perez Edith A. 
Published: March 2020

2015 Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent + CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had + CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13+, 30+, 33+, and 180+ wks. 4 pts (24%) lived > 95 wks. Of 11 w/ baseline + CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear = 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.
IDH1 status and survival benefit from surgical resection of enhancing and nonenhancing tumor in malignant astrocytomas.
Authors: Cahill Daniel P. , Beiko Jason , Suki Dima , Prabhu Sujit S. , Weinberg Jeffrey , Lang Frederick F. , Gilbert Mark R. , Rao Ganesh , McCutcheon Ian E. , Aldape Kenneth D. , Sawaya Raymond 
Published: March 2020

2019 Background: The value of maximal safe resection for malignant astrocytic gliomas (AA, WHO Grade III anaplastic astrocytoma and GBM, WHO Grade IV glioblastoma) has sometimes been controversial, because of confounding between measures of surgical resection and other prognostic factors. IDH1 gene mutations are associated with improved survival in glioma patients, and are thought to identify tumors with a distinct molecular evolutionary origin. We sought to determine the prognostic impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas. Methods: Clinical parameters including preoperative and postoperative MRI-based tumor volume were recorded prospectively on 407 malignant astrocytoma patients – AA (n=157) and GBM (n=250). IDH1 status was assessed by sequencing and R132H-specific immunohistochemistry. Results: The measures of surgical resection associated with longer survival differed between IDH1 wild-type and mutant tumors. In multivariate analyses of IDH1 wild-type tumors (controlling for age, Karnofsky performance score, tumor location, and tumor grade), residual postoperative enhancement was associated with a median survival of 9.9 mo vs. 17.4 mo with no enhancement (HR=1.73, 95% CI, 1.19-2.52, p=.004). Residual non-enhancing disease, however, was not associated with survival (scored as continuous volumetric cc, 95% CI 0.99-1.01, p=.608). These results are consistent with prior studies of GBM, which are largely IDH1 wild-type lesions (Lacroix et al., J Neurosurg 95:190-8, 2001). In contrast, in IDH1 mutant tumors, both residual enhancing (HR=7.93, 95%CI 1.14-55.22, p=.037) and non-enhancing (HR=1.03, 95% CI 1.01-1.05, p=.005) postoperative tumor burden were associated with worse survival. Conclusions: These data suggest surgical resection in malignant astrocytic gliomas may be individualized based on IDH1 genotype. IDH1 mutant tumors have a better baseline overall prognosis, therefore more aggressive surgery and tolerance of temporary peri-operative neurologic deficits can be weighed in an attempt to gain the additional survival benefit that appears to be associated with reducing non-enhancing tumor burden.
Genomic characterization of meningiomas.
Authors: Brastianos Priscilla Kaliopi , Horowitz Peleg , Santagata Sandro , Jones Robert T. , McKenna Aaron , Ligon Keith , Palescandolo Emanuele , Van Hummelen Paul , Getz Gad , Hahn William C , Dunn Ian F. , Beroukhim Rameen 
Published: March 2020

2020 Background: Understanding the genetic alterations in cancer has lead to groundbreaking discoveries in targeted therapies. Meningiomas are among the most common primary brain tumors, with approximately 18,000 new cases diagnosed annually. Though certain genes have been associated with the development of meningiomas, most notably the tumor suppressor gene neurofibromatosis 2 (NF2), the genetic changes that drive meningiomas remain poorly understood. Our objective was to comprehensively characterize the somatic genetic alterations of meningiomas to gain insight into the molecular pathways that drive this disease. Methods: Fresh frozen specimens and paired blood were collected from 16 consented patients. DNA was extracted from regions of high tumor purity determined by evaluation of H&E slides. Whole-genome sequencing from 10 tumor-normal pairs and whole-exome sequencing from 6 tumor-normal pairs was carried out. We performed an unbiased screen for point mutations, insertions-deletions, rearrangements and copy-number changes across the exomes and genomes. Recurrent (potential driver) events were then analyzed with additional algorithms for statistical significance. Results: Alterations in the NF2 gene were present in 9 of 16 patients. Multiple novel rearrangements and recurrent non-NF2 mutations were also identified in the cohort. Massive genomic rearrangement termed chromothripsis was observed in chromosome 1 in one sample, which has never previously been described in meningiomas, and represents a potentially new mechanism of malignant transformation in this tumor type. Conclusions: While NF2 mutations appear to drive a majority of these tumors, our analysis has uncovered additional potential driver genes in meningiomas, particularly in those tumors negative for NF2 alterations. To our knowledge, this is the first study to comprehensively characterize the totality of somatic genetic alterations in meningiomas, and brings us closer to the development of new therapeutic targets for this disease.
Pilocytic astrocytomas in adults: A retrospective study of 125 patients.
Authors: Theeler Brett James , Sadighi Zsila Sousan , Ellezam Benjamin , Puduvalli Vinay K. 
Published: March 2020

2022 Background: Pilocytic astrocytomas (PAs) are rare primary brain tumors in adults. The natural history is poorly defined with the largest published series including only 30-40 patients. To better define clinical characteristics of adult PAs, we present an analysis of adult PAs at MD Anderson Cancer Center. Methods: We conducted an IRB-approved, retrospective chart review of patients ≥18 years diagnosed with PAs from 1990-2011 at our institution. Results: We identified 125 patients with a median age of 29 (range 18-72y), female to male ratio of 1.7:1, and median follow-up of 62 months. The most common anatomic locations were brainstem 22%, cerebellum 14%, intraventricular 14%, and cortical/lobar 14% (36% other locations). 21% of cases had an initial pathologic diagnosis discordant with neuropathologic review at our institution. Comorbidities included neurofibromatosis type 1 (5 pts) and a history of asthma or autoimmune disease (14%). 38 patients had a gross total (GTR), 55 a sub-total resection (STR) and the remainder a biopsy. 62 patients were treated with radiotherapy (RT): 45 as adjuvant (adj), 17 at recurrence; 2 received RT in both adj and recurrent settings. 73 (58%) patients were stable after initial treatment (surgery +/- adj RT). Median progression free survivals (mPFS) based on upfront treatment as follows: GTR only (n=30) - not been reached, STR only (n=32) 226.6 months, GTR plus adj RT (n=8) 13.2 months, STR plus adj RT (n=23) is 52.4 months (p=0.026, logrank test for trend). At last follow-up, 77% of all patients were stable and 13% were deceased. Conclusions: This is the largest series of adult PAs reported to date. Extracerebellar location, slight female predominance, and history of allergic/autoimmune disease were associations found in this cohort. Neuropathologic review is essential to avoid misdiagnosis. A significant subset of adult PAs behave more aggressively than expected for a grade I tumor with over 40% of patients experiencing recurrence after initial treatment. Adj RT following GTR or STR did not improve PFS, and a trend towards worse PFS with adj RT was observed although these analyzed subgroups were small. These results may help provide a framework for prospective studies in this tumor type.
Impact of adjuvant anti-VEGF therapy on treatment-related pseudoprogression in patients with newly diagnosed glioblastoma receiving chemoradiation with or without anti-VEGF therapy.
Authors: Pinho Marco C , Polaskova Pavlina , Jennings Dominique , Wen Patrick Y. , Jain Rakesh K. , Sorensen A. Gregory , Gerstner Elizabeth Robins , Batchelor Tracy 
Published: March 2020

2025 Background: Chemoradiation (CRT) can significantly modify the appearance of glioblastoma (GBM) on MRI, especially within the 3-month window after CRT. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this scenario, and is thought to be secondary to increased permeability of the tumor vessels from irradiation, possibly enhanced by temozolomide (TMZ). We sought to determine if the addition of a VEGF signaling inhibitor (cediranib) during and after CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed GBMs. Methods: Two groups of patients enrolled in IRB-approved trials underwent serial MRIs at baseline, weekly during CRT and monthly thereafter. The control group received radiation plus TMZ, while the other group (CED) also received cediranib until progression (which was defined by RANO criteria) or toxicity. Patients that progressed up to 3 months after CRT were considered to have apparent progression (AP) and kept on treatment. Lesions that subsequently stabilized/regressed were classified as PsP, while those that maintained growth despite treatment were classified as true early progression (EP). Results: Forty patients were enrolled in CED and 11 as controls. Ten patients from CED and three controls were excluded due to treatment discontinuation before 3 months (drug-related toxicity and enrollment in post-CRT trials respectively). Three patients in CED (6%) had AP (all confirmed as EP) and no patients fulfilled criteria for PsP. Six patients from control (54%) had AP; 3 (27%) were eventually classified as EP and 3 (27%) as PsP. The frequency of PsP was significantly higher in the control group (p=0.0086). Conclusions: The addition of a VEGF inhibitor as part of adjuvant treatment in this cohort of glioblastoma patients prevented the development of early treatment-related effects (PsP). Suppressing the edema and mass effect that accompanies PsP may improve the tolerability of treatment. Additionally, this effect may be exploited as a strategy to make chemoradiation feasible in patients with large, unresectable tumors and/or poor baseline performance status.
A single-institution phase II trial of radiation (RT), temozolomide (TMZ), erlotinib, and bevacizumab for initial treatment of glioblastoma (GBM).
Authors: Clarke Jennifer Leigh , Molinaro Annette M , Butowski Nicholas A. , Chang Susan Marina , Phillips Joanna J , Costa Bruno M , Costello Joseph F , Rabbitt Jane E , Kivett Valerie A , DeSilva Ashley A , Prados Michael 
Published: March 2020

2026 Background: Standard treatment for GBM includes surgery followed by RT and TMZ, rarely a curative treatment. Both the EGFR and VEGF pathways are frequently overactive in GBM; we previously added erlotinib, an EGFR inhibitor, to RT and TMZ, with modest improvement in survival. The present study combined bevacizumab, a VEGF inhibitor, and erlotinib with RT and TMZ, with the goal of improving overall survival (OS). Methods: Treatment consisted of fractionated RT to 60 Gy with daily TMZ at 75 mg/m2/d and erlotinib 150-200 mg/d (or 500-600 mg/d for patients on enzyme-inducing antiepileptic drugs [EIAEDs]). Bevacizumab was given at 10 mg/kg every 2 wks, starting ≥ 4 wks after surgery. After RT, adjuvant TMZ was given at 200 mg/m2/d x 5d per 28d cycle, with unchanged erlotinib and bevacizumab doses. Treatment was continued until progression or for 12 mo, with an option to continue for up to 24 mo. OS and progression-free survival (PFS) from initial diagnosis were compared against institutional historical controls (recent prior up-front clinical trials including RT and TMZ). Results: 59 pts were enrolled; 12 were receiving EIAEDs. Median age was 54 yrs; median KPS was 90. 33% underwent gross total resection and 53% subtotal resection. 16 pts had tumors with methylated MGMT (mMGMT), 26 with unmethylated MGMT (umMGMT), and 17 with unknown status. The most frequent related grade 3/4 AEs were lymphopenia (68%) thrombocytopenia (24%), neutropenia (10%), diarrhea (14%), weight loss (14%), and fatigue (12%). 1 pt died of aspergillosis. Median OS and PFS were 19.8 mo and 13.5 mo, respectively, vs. 18 mo and 8.6 mo for the historical control. The hazard ratio (adj for age, KPS, and extent of surgery) for PFS was 0.7 (95% CI 0.49-0.99, p=0.04). Median OS in pts with mMGMT was 20.9 mo, vs. 17.5 mo in pts with umMGMT; median PFS was 14 mo vs. 12.4 mo, respectively. Conclusions: The combination of bevacizumab, erlotinib, TMZ, and RT showed improved PFS but not OS vs. historical controls. Though the numbers were small, PFS and OS for pts with umMGMT were not significantly different from pts with mMGMT, suggesting that this combination may be more effective than standard therapy alone for pts with unMGMT tumors.
NCCTG N057K phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: A North Central Cancer Treatment Group trial.
Authors: Ma Daniel , Galanis Evanthia , Schiff David , Wu Wenting , Peller Patrick J. , Giannini Caterina , Brown Paul D. , Uhm Joon H. , McGraw Steven , Jaeckle Kurt A. , Flynn Patrick J. , Buckner Jan C. , Sarkaria Jann Nagina 
Published: March 2020

2031 Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt pathway as a critical modulator of cell survival. Preclinical studies in GBM indicate that the combination of mTOR inhibitors, such as everolimus (RAD001), with either radiation therapy (RT) or temozolomide (TMZ) provide increased tumor cell killing. Methods: Newly diagnosed GBM pts were eligible for the study. RAD001 was dosed orally at 70 mg/week weekly, starting 1 week prior to RT/TMZ, and continued throughout RT/TMZ, adjuvant TMZ and then until progression. This was a single arm phase II design powered to detect a true overall survival at 12 months (OS12) of 73% (vs 58% in historical controls). Secondary endpoints were toxicity, response rate, and time to progression (TTP). A subgroup of patients with measurable residual disease were eligible for the PET imaging component of the study, consisting of an 18FLT-PET/CT scan performed before and after the initial two doses of RAD001 but before the first dose of RT or TMZ. Results: 103 patients were accrued to phase II of which 100 were evaluable. The median age was 60.5 years (23-81), median ECOG PS was 1, 46 patients had GTR, 33 STR, and the remainder had biopsy at diagnosis. Treatment tolerance was acceptable: 17% patient had at least one grade 3 hematologic toxicity; 14% had at least one grade 4 hematologic toxicity, 42% had at least one grade 3 non-heme toxicity, while 12% had at least one grade 4 non-heme toxicity. No increased incidence of infectious complications was observed and there were no treatment related deaths. Median PFS was 5.3 months (1.3-21.4), with 22 patients progression free. Mature OS data will be available at the meeting. MGMT methylation status analysis is ongoing. Of the pts who had evaluable FLT-PET data, three of eight (37.5%) had a drop in SUVmax >25% after two treatments of RAD001. Conclusions: RAD001 with standard of care chemoradiation had moderate toxicity. Serial 18FLT-PET was feasible for evaluating drug-induced changes in tumor proliferation following RAD001. Final outcome data and association of MGMT status with outcome will be reported at the meeting.