tbuckley/cabot-search huggingface dataset:
Phase III study of surgery (S) versus definitive concurrent chemoradiotherapy boost (def ccCRTx-BOx) in patients (pts) with operable (OP+) stage IIIA(N2)/selected IIIb (sel IIIB) non-small cell lung cancer (NSCLC) following induction (IND) chemotherapy (CTx) and concurrent CRTx (ESPATUE).
Authors: Wilfried Ernst Erich Eberhardt, Thomas Christoph Gauler, Christoph Pöttgen, Godehard Friedel, Stefanie Veit, Vanessa Heinrich, Stefan Welter, Werner Spengler, Martin Kimmich, Berthold Fischer, Heinz Schmidberger, Eleni Gkika, Sebastian Cordes, Rodrigo Hepp, Diana Luetke-Brintrup, Nils Lehmann, Martin H. Schuler, Karl-Heinz Jöckel, Georgios Stamatis, Martin Stuschke
Journal: Journal of Clinical Oncology (2014)

7510 Background: Def ccCRTx or ccCRTx + S are accepted therapies (Tx) for OP+ stage IIIA(N2) NSCLC (Albain 2009). Our multicenter phase-II showed efficacy of CTx + ccCRTx + S in IIIA(N2) / sel IIIB (CISTAXOL: Eberhardt 2013). Here we compared S with ccCRTx-BOx in OP+ stage III NSCLC following IND. With 246/500 planned pts (1/04-8/12) trial closed for slow accrual + futility. Here we report final analysis (29-Jan-2014). Methods: Pathologically proven OP+ IIIA(N2) / sel IIIB NSCLC pts, adequate organ function / functional OP+, received IND CTx (3 cycles CDDP/taxol) and ccCRTx to 45 Gy (1.5Gy bid/cc CDDP/vinorelbine). Pts were reevaluated in last week ccCRTx (PET-CT) and discussed by multidisciplinary board. OP+ pts were randomized (rand) to def ccCRTx-BOx risk adapted to 65/71 Gy (arm A) or S (arm B). Primary endpoint: overall survival (OS). Results: 246 pts (70 F 176 M; T1-3N2 75 T4N0-1 80 T4N2/anyT N3 91; age 59 (33-74); SQC 95 ADC 107, other 44) enrolled at 5 centers. 245 started IND, 161/246 OP+ pts (65.4%) were rand to arm A or B (strata: TN-group, PCI-policy, region) - post rand crossover due pts preference: 6.8%. 46 non-rand pts received def ccCRTx-BOx. Pts characteristics were well balanced. Pneumonectomy in 26%, R0-Res in 81% of arm B. Med F-UP post rand 78.2 mo. 36 are actually long-term surv with F-UP > 5 y. OS did not differ between arms ( logrank p = 0.31 ). OS at 5 y 34.1% (27.6-40.8) in 246 initially recruited (IR) and 216 (87.8%) received def local Tx. Conclusions: Long-term OS at 5 y in rand OP+ pts was excellent with both Tx. These high-volume center data confirm earlier trials: Both options are acceptable and should be discussed with individual pts. Clinical trial information: 70-3070-Eb. All IR 246 Completed IND 227 OP+ / rand 161 A: BOx 80 B: S 81 1 Y-OS% 82.5 (72.2-89.2) 77.8 (67.1-85.4) 3 Y-OS% 49.9 (38.0-60.6) 58.4 (46.4-68.6) 5 Y-OS% 40.6 (28.7-52.2) 44.2 (31.6-56.2) TRD% 2.5 6.2
Screening with whole-body MRI (WB-MRI) in pediatric patients with Li Fraumeni syndrome (LFS).
Authors: Allison Frances O'Neill, Allie Steinberger, Stephan D. Voss, Elizabeth J. Root, Judy Ellen Garber, Lisa Diller
Journal: Journal of Clinical Oncology (2013)

10071 Background: LFS is a rare hereditary cancer syndrome characterized by a high risk of developing a wide range of malignancies. Germline mutations in the tp53 gene confer approximately a 12-fold risk of developing cancer by age 20. Given the potential for diverse malignancies, cancer surveillance in LFS patients is challenging. We piloted the use of WB-MRI for pediatric LFS patients as a cancer screening tool. Methods: Eligibility included: documented tp53 mutation, or obligate carrier status based upon family history/genetic testing, and no recent cancer diagnosis. WB-MRI was performed as a research test, in conjunction with recommended clinical screening based upon family history and clinician recommendation. Our primary aim was to determine the feasibility (defined as 87% completion rate) of obtaining two planned annual MRI scans in 15 pediatric LFS patients. Our secondary aim was to calculate the incidence and describe the characteristics of primary cancers detected. Results: Nine pediatric patients from 5 families have been enrolled and all have successfully completed one WB-MRI. Seven patients were known carriers, and 2 underwent genetic testing in order to enroll in the study. Median age was 12 years, range 6 to 15. Scan time was 60-90 minutes and 2 patients required anesthesia with propofol. There were no acute scan complications. Six of the 9 (67%) scans demonstrated incidental findings (T2 cerebral cortex abnormality, L5-S1 synovial cyst, thoracic syrinx, T12 hemangioma, 2 ovarian cysts, and degenerative disc disease). Only one patient underwent a dedicated follow-up imaging study for an abnormality on WB-MRI. None of the patients required biopsy. All patients had normal screening laboratory work. These results are being presented early to foster collaboration. Conclusions: All patients enrolled on our study tolerated WB-MRI; none were diagnosed with a new malignancy. Although preliminary, our results to date are in contrast to previous reports documenting a high incidence of cancers detected during screening of LFS patients. WB-MRI may be a promising approach to screening; a large multi-center trial will be needed to determine its efficacy in detecting incident cancers and true test characteristics.
Molecular marker analysis of SWOG S0636, a phase II trial of erlotinib and bevacizumab in never-smokers with advanced NSCLC.
Authors: Philip C. Mack, James Moon, Howard Jack West, Wilbur A. Franklin, Marileila Varella-Garcia, Murry W. Wynes, Antoinette J. Wozniak, Mary Weber Redman, Fred R. Hirsch, David R. Gandara
Journal: Journal of Clinical Oncology (2012)

7552 Background: S0636 investigated the combination of erlotinib and bevacizumab in never-smoking NSCLC patients with confirmed adenocarcinoma histology (H. West ASCO 2011). Patient eligibility was not restricted by molecular selection. Median PFS and OS were encouraging at 8 and 26 months. An analysis of molecular markers was undertaken, focusing initially on the EGFR pathway. Methods: EGFR analysis included gene copy number, mutation and protein expression. Copy number was conducted by FISH using the Colorado scoring system. An immunohistochemistry H score was developed for EGFR protein expression analysis, ranging from 0 to 400. Specimens were evaluable from 42 of the 85 eligible patients. Results: FISH positivity was identified in 17/35 pts (49%), 11 with high polysomy and 6 with true gene amplification. EGFR activating mutations were seen in 10/33 pts (30%). IHC H-score &gt;200 was observed in 17/40 pts (43%). All EGFR markers were significantly correlated with one another. In the EGFR WT subgroup, FISH-positive patients outperformed FISH-negative pts (mPFS 20 vs, 6 months, p=0.06). Conclusions: Careful analysis of EGFR markers (mutation, FISH and IHC) identified S0636 patients with favorable PFS and encouraging trends for OS. EGFR FISH and IHC provided additional predictive information beyond that of EGFR mutation status. Supported in part by DHHS: CA32102 and CA38926, and in part by Genentech. [Table: see text]
Prevalence of nonmetastatic (M0) prostate cancer (PC) patients on continuous androgen deprivation therapy (ADT) in the United States.
Authors: Karynsa Cetin, Shuling Li, Anne Hudson Blaes, Scott Stryker, Alexander Liede, Thomas J. Arneson
Journal: Journal of Clinical Oncology (2012)

4659 Background: ADT is the cornerstone treatment of metastatic PC, but the nature and extent of its use in the M0 setting is less well-described. We sought to estimate the current prevalence of M0 PC patients actively receiving continuous ADT (≥6 months) in the US. Methods: Two point-prevalent cohorts on 12/31/2008 with continuous insurance coverage in 2008 were assembled: men aged 45-64 years (yrs) enrolled in commercial health plans (MarketScan) and men aged ≥67 yrs enrolled in fee-for-service (FFS) Medicare (Medicare 5% sample). Among those with evidence of PC and no evidence of metastases, we selected men who had continuous exposure to gonadotropin-releasing hormone agonists during at least the last 6 months of 2008 or received bilateral orchiectomy prior to 7/1/2008. The number of prevalent ADT users was extrapolated to the entire national commercially insured population aged 45-64 yrs and to the entire Medicare FFS population aged ≥65 yrs using person-level weights. Applying age-specific prevalence estimates to the US Census population on 12/31/2008, we estimated the number of prevalent ADT users in the total US male population aged ≥45 yrs. Results: An estimated 11,935 (95% confidence interval [CI]: 11,310-12,561) commercially insured men aged 45-64 yrs and 115,468 (95% CI: 112,304-118,633) Medicare FFS men aged ≥65 yrs were M0 PC patients actively receiving continuous ADT for ≥6 months on 12/31/2008. Extrapolated to the total US male population aged ≥45 yrs, this estimate was 188,916 (95% CI: 184,104-193,727). Age-specific prevalence (N [95% CI]) on 12/31/2008 is presented in the table. Conclusions: We projected nearly 190,000 US men with M0 PC were actively receiving continuous ADT for ≥6 months at the end of 2008, and the vast majority (91%) of these men were aged ≥65 yrs. Additional work will address timing of initiation, duration, and other aspects of ADT use in this large population of M0 PC patients. [Table: see text]
Fever at diagnosis of pediatric acute lymphoblastic leukemia (ALL): Are antibiotics really necessary?
Authors: Monica Khurana, James Henry Feusner, Brian Lee
Journal: Journal of Clinical Oncology (2012)

9553 Background: Great variability exists in the management of suspected bacteremia in febrile, neutropenic pediatric ALL patients during chemotherapy. The National Comprehensive Cancer Network and Infectious Diseases Society of America encourage immediate, empiric antibiotics in patients with chemotherapy-induced fever and neutropenia to reduce infection-related mortality. No standard recommendation exists for patients with isolated fever at initial presentation of their ALL. This study evaluates bacteremic episodes in this subpopulation of pediatric patients. Methods: We retrospectively analyzed 245 consecutive patients with ALL at Children’s Hospital Oakland from 2000 through 2011. Using electronic medical records, we investigated each patient’s history and outcome. We surveyed bacteremic episodes up to 60 days after presentation per National Healthcare Safety Network’s guidelines. Inclusion criteria were patients with fever at presentation, which prompts a blood culture, and were started on antibiotics. We stratified bacteremic episodes into community-acquired (up to three days from admission) and nosocomial (four to 60 days). Results: Seventy-seven patients met the inclusion criteria, five of whom had positive cultures – four were contaminants (three coagulase-negative Staphylococcus and one non-anthracis Bacillus) and one was a true nosocomial bactermic episode (E coli). There were no infection-related deaths in the first 60 days of diagnosis in this cohort. Conclusions: Given our institution’s rarity of bacteremic episodes, we contemplate a more judicious use of antibiotics, including quicker narrowing of broad-spectrum antibiotics coverage and discontinuing all antibiotics sooner. These modifications may decrease bacterial resistance to antibiotics, reduce costs, and shorten patients’ hospitalization. We encourage other institutions to conduct a similar investigation.
Differences between patient and caregiver assessments and their association with caregiver burden in caregivers of older adults with cancer.
Authors: Tina Hsu, Matthew Loscalzo, Rupal Ramani, Stephen J. Forman, Leslie Popplewell, Karen L. Clark, Vani Katheria, Rex Strowbridge, Redmond Rinehart, Keith Matthews, Jeff Dillehunt, Tao Feng, David D. Smith, Arti Hurria
Journal: Journal of Clinical Oncology (2015)

9545 Background: Caregivers are a valuable support for patients and an important source of information about patient health, particularly in older adults who are more likely to be frail or have cognitive impairment. We sought to determine whether a) differences exist between patient and caregiver assessments and b) these differences were associated with increased caregiver burden. Methods: 100 cancer patients, age ≥ 65, and their caregivers independently assessed patient function, comorbidities, nutrition, psychological status, social activity and social support. Caregiver Strain Index (CSI) was used to assess caregiver burden. Patient-caregiver assessments were compared using the Wilcoxon signed rank test. The relationship between caregiver burden and variables in which patient-caregiver assessment differed was determined using a linear regression model and adjustment for confounders was done. Results: Median patient age was 70, 70% had advanced disease, 62% were on chemotherapy. Patients reported a median of 2 comorbid conditions, no falls within 6 months, and 39% reported > 5% weight loss. Patients reported good function (median KPS 90 and Medical Outcomes Study (MOS)-physical function 67), independence with most instrumental activities of daily living (IADL) (median OARS-IADL 13), having good social support (median MOS-social support survey 92), and good mental health (median Mental Health Index 85). 75% of caregivers experienced some caregiver burden (mean CSI 3.1±3.2; 15% had high burden). Caregivers were more likely than patients themselves to rate patients as having poorer function [needing more help with IADLs (p = 0.008), lower KPS (p = 0.02), and lower MOS-physical function (p < 0.0001)], poorer mental health (p = 0.0002), but more social supports (p = 0.03). Only a difference in patient-caregiver assessment of a patient’s need for help with IADLs was associated with increased caregiver burden (p = 0.002). Conclusions: Patients and caregivers differ in their assessment of patient function, mental health, and social support. However, only differences in patient-caregiver reported need for help with IADLs were associated with increased caregiver burden.
Antitumor activity of abiraterone, enzalutamide, and docetaxel following treatment with diethystilbestrol in castration-resistant prostate cancer.
Authors: Sandra Assoun, Luca Campedel, Morgan Roupret, Christophe Vaessen, Jerome Parra, Haide Angele Boostandoost, Eva Comperat, Jean-Marc Simon, David Khayat, Marc-Olivier Bitker, Gabriel G. Malouf, Jean-PHilippe Spano
Journal: Journal of Clinical Oncology (2017)

e581 Background: Docetaxel and Next-Generation Anti-Androgens (NGAA) including abiraterone and enzalutamide represent the standard of treatment for patients with castration-resistant prostate cancer (CRPC). Treatment sequencing of these agents is a challenge. Recent studies identified cross-resistances between hormonal therapies and taxanes, as well as between different NGAA. In aiming to elucidate whether synthetic oestrogen diethylstilbestrol (DES) therapy impacts the efficacy of later-line treatments or not, we evaluated the antitumor activity of NGAA and docetaxel following DES therapy in CRPC patients. Methods: All patients with CRPC treated at Pitié-Salpêtrière hospital in first-line setting with DES from September 1995 to July 2016 were retrospectively identified. We evaluated further activities of abiraterone, enzalutamide and docetaxel in those patients after DES therapy, using Prostate Cancer Working Group 3 criteria. Clinicopathologic characteristics, including age, performans status, metastatic sites at diagnosis and treatments initiation, and data survival were also assessed. Results: Twenty-three patients with CRPC were initially treated with DES with a median time to prostate-specific antigen (PSA) progression of 9.7 months (range, 4.7-20.3). Thirteen patients(56.5%) received abiraterone or enzalutamide before docetaxel and 21 patients (91.3%) after. Median age at first NGAA initiation was 79 years) range, 55-91). Only one patient (7.7%) achieved a PSA decline before docetaxel and two out of 18 evaluable patients (11.1%) after docetaxel. Median time to PSA progression and overall survival with a NGAA treatment were respectively 2.8 (range, 2.0-4.1) and 16.5 months(range, 4.3-31.0). Fifty percent of patients showed a PSA response with docetaxel. No clinical factors were found to be significantly associated with PSA response to NGAA treatment, nor to docetaxel. Conclusions: The activity of NGAA appears markedly limited after a DES therapy, regardless of the PSA response to docetaxel. These data suggest the likelihood of a cross-resistance mechanism between DES and NGAA, without no impact on taxanes pathways.
Sequential compared to combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (ACC): A Dutch Colorectal Cancer Group (DCCG) phase III study
Authors: C. J. Punt, M. Koopman, J. Douma, J. Wals, A. H. Honkoop, F. L. Erdkamp, R. S. de Jong, C. J. Rodenburg, L. Mol, N. F. Antonini
Journal: Journal of Clinical Oncology (2007)

4012 Background: Overall survival (OS) in phase III studies with 1 st line combination therapy in ACC may be influenced by imbalances in salvage treatments. This is the first study that prospectively investigates the sequential vs the combined use of all available effective cytotoxic drugs. Methods: Previously untreated patients (pts), WHO PS 0–2 were randomized between 1 st line capecitabine (Cap), 2 nd line irinotecan (Iri), and 3 rd line Cap + oxaliplatin (CapOx) (Arm A, sequential) vs 1 st line CapIri and 2 nd line CapOx (Arm B, combination). The dose of Cap was 1250 mg/m 2 (mono) or 1,000 mg/m 2 (combination) b.i.d. day 1–14, Iri 350 mg/m 2 (mono) or 250 mg/m 2 (combination), and Ox 130 mg/m 2 . All cycles were q 3 weeks with Iri/Ox given i.v. on day 1. Response was assessed q 3 cycles. Primary endpoint was OS. The study was designed to detect a 20% reduction in the hazard of death (HR=0.80) for an increase in median OS from 14 to 17.5 months (a=0.05, 2-tailed test). Results: 820 pts were randomized between Jan ‘03 and Dec ‘04 in 74 Dutch hospitals. Of 804 eligible pts, 796 received = 1 cycle. Median age was 63 (27–84) yrs, median WHO PS 0 (0–2), median follow-up 32 months. Pts (n) in arm A: 398 (1 st line), 248 (2 nd line), 141 (3 rd line); arm B: 398 (1 st line), 210 (2 nd line). Median OS in arm A was 16.3 months (95%CI 14.3–18.2) and in arm B 17.7 months (95%CI 15.2–19.4), logrank p=0.2. Overall gr 3–4 toxicity over all lines did not differ significantly except for gr 3 hand-foot syndrome (HFS) (13% in A and 6% in B, p=0.0009). Death was probably related to treatment in 11 pts (neutropenic sepsis and/or diarrhea, 8 arm A, 3 arm B) and involved protocol violations in some. In 1 st line significant differences in gr 3–4 toxicity in arm A vs arm B were diarrhea (10% vs 25%, p&lt;0.0001), febrile neutropenia (1% vs 6%, p=0.0001) and HFS (12% vs 5%, p=0.0004). All-cause 60-day mortality was 3.0% (n=12) in arm A and 4.5% (n=18) in arm B. Updated results will be presented at the meeting, including data on QoL (EORTC QLQ C30). Conclusions: Combination therapy does not significantly improve OS compared with sequential therapy. Both treatment strategies are valid options for pts with ACC. No significant financial relationships to disclose.
A randomised, open-label trial of a Multimodal Intervention (Exercise, Nutrition and Anti-inflammatory Medication) plus standard care versus standard care alone to prevent / attenuate cachexia in advanced cancer patients undergoing chemotherapy.
Authors: Stein Kaasa, Tora Solheim, Barry J. A. Laird, Trude Balstad, Guro Birgitte Stene, Asta Bye, Marie T Fallon, Peter Fayers, Ken Fearon
Journal: Journal of Clinical Oncology (2015)

9628 Background: The pathophysiology of cancer cachexia is multi-factorial consisting of muscle wasting, negative protein and energy balance, and systemic inflammation. There is no established treatment for cachexia, paradoxical to the importance of this condition in limiting oncology treatment. New approaches are needed to address the complexity of the syndrome and to challenge the accepted therapeutic nihilism. To treat cachexia optimally it has been argued that a multimodal intervention is necessary to enable the multi factorial pathophysiology to be targeted. Integral to this is targeting inflammation as the main driver of cachexia. Methods: An international, multicentre randomised phase II study was conducted. Eligible patients had advanced lung cancer or pancreatic cancer and were due to start palliative chemotherapy. Patients were randomised (1:1 ratio) to receive either a multimodal intervention (exercise, anti-inflammatories, energy dense nutritional supplements combined with dietary advice) or standard cancer care. Primary outcome measures were feasibility of the intervention assessed by compliance and enrolment. Secondary outcomes examined weight, physical activity (using ActivPAL) and CT based muscle mass. Means and standard deviations (SD) are reported. Results: Forty-six patients were recruited from three regional cancer center’s (Glascow (UK), Trondheim and Oslo (Norway). Overall compliance was > 54% in all components of the intervention. Patients’ in the treatment arm weight increased (0.91% (SD 2.46)), whilst those in the control arm lost weight (-2.12% (SD 2.50)), p < 0.001 (N = 41). Patients in the control arm lost 2.2% more muscle than the treatment arm, p = 0,69. There were no statistical significant differences in physical activity in the patients that had repeated measurements of physical activity with ActivPal (n = 22). Conclusions: A multimodal cachexia intervention is feasible and improves weight in patients with incurable lung or pancreatic cancer. Based on these exciting findings, a definitive phase III study is now underway. Clinical trial information: NCT01419145.