tbuckley/cabot-search huggingface dataset:
A phase II study of erlotinib followed by chemotherapy on progression in an unselected population of advanced non-small cell lung cancer (NSCLC) patients.
Authors: Leora Horn, Chung-I Li, William Pao, Vicki Leigh Keedy, David H. Johnson, David P Carbone
Journal: Journal of Clinical Oncology (2012)

7568 Background: Erlotinib is now accepted as first line therapy for advanced NSCLC patients with EGFR mutated tumors. However, some patients with EGFR wild-type tumors may benefit as well, and there are no accepted biomarkers to define this subset of patients or to define which patients benefit from chemotherapy. We conducted a single arm phase II trial of erlotinib followed by chemotherapy on progression (carboplatin + paclitaxel +/- bevacizumab) in treatment naïve patients with stage IV NSCLC. Methods: In this multicenter prospective phase II trial, patients with stage IV NSCLC were eligible for enrollment. Blood, frozen tissue and FFPE biopsies for molecular analysis were mandatory at the time of study entry and optional at the time of progression on erlotinib. Additional eligibility included ECOG performance status (PS) 0-2, measurable disease, and adequate marrow, renal and hepatic function. Patients with stable treated brain metastases were allowed. Patients were treated with erlotinib 150 mg daily until disease progression at which time they underwent a biopsy and were switched to carboplatin/paclitaxel +/- bevacizumab. Disease status was assessed after 4 weeks of erlotinib to detect early progression. Results: From 10/07 to 06/11, 127 patients were enrolled: 59% male, 90% Caucasian, 6% African American, 4% Asian, 30% never smokers. 7 patients failed screening. Among evaluable patients on erlotinib, 13% had PR, 48% SD, and 27% PD. Median PFS on erlotinib was 4.7 months (95% CI 3.5 to 8.3 months). In patients who went on to receive chemotherapy on protocol, 24% had PR, 27% SD, and 20% PD. In patients who went on to receive chemotherapy on protocol median progression-free survival (PFS) on chemotherapy was 8.1 months (95% CI 5.5 to 10.9 months). Among the 55 patients who did not receive chemotherapy, 23 had a decline in PS, 14 patients refused, 2 patients enrolled on another protocol, and 6 patients had other therapy. Conclusions: This is the first study to report on PFS in unselected NSCLC patients following first line therapy with erlotinib. Translational studies on this large prospectively collected cohort of tissue samples prior to initiation of erlotinib are ongoing.
Disparities in cancer treatment among HIV-infected individuals.
Authors: Gita Suneja, Chun Chieh Lin, Edgar P Simard, Xuesong Han, Eric A. Engels, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2015)

e17592 Background: HIV-infected cancer patients are less likely to receive cancer treatment compared with HIV-uninfected individuals. However, the impact of comorbidities and insurance status for this disparity is unknown. Methods: We used data from the National Cancer Database to study non-elderly adults diagnosed with diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, and head and neck, lung, upper gastrointestinal, colorectal, anal, prostate, breast, and cervical cancers from 2003-2011. We used multivariate logistic regression to examine associations between HIV status and lack of cancer treatment, adjusted for sociodemographic and clinical covariates, including insurance status and comorbidity. In a separate analysis, we examined associations for privately insured patients only. Results: A total of 10,265 HIV-infected cases and 2,219,232 HIV-uninfected cases were included in the study. In multivariate analysis, HIV-infected cancer patients were more likely to lack cancer treatment for cancers of the head and neck (adjusted odds ratio 1.48, 95%CI 1.09-2.01), upper gastrointestinal tract (2.62, 2.04-3.37), colorectum (1.70, 1.17-2.48), lung (2.46, 2.19-2.77), breast (2.14, 1.16-3.98), cervix (2.81, 1.77-4.45), and prostate (2.16, 1.69-2.76), and Hodgkin lymphoma (1.92, 1.66-2.22) and DLBCL (1.82, 1.65-2.00). Results were similar among privately insured patients. Predictors of lack of cancer treatment among HIV-infected cases varied by tumor type (solid vs. hematologic). Black race and insurance status were predictors in both groups. Conclusions: HIV-infected cancer patients are less likely to receive cancer treatment relative to HIV-uninfected individuals regardless of their insurance status and comorbidities. Further investigation is required to identify factors contributing to the observed disparity with the goal of improving survival and quality of life for HIV-infected cancer patients.
Association of HIV Status With Local Immune Response to Anal Squamous Cell Carcinoma
Authors: Elizabeth L. Yanik, Genevieve J. Kaunitz, Tricia R. Cottrell, Farah Succaria, Tracee L. McMiller, Maria L. Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J. Lipson, Suzanne L. Topalian, Eric A. Engels, Janis M. Taube
Journal: JAMA Oncology (2017)

The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients.To compare the local tumor immune microenvironment (TME) in anal SCCs from HIV-positive and HIV-negative patients.Anal SCC tumor specimens derived from the AIDS and Cancer Specimen Resource (National Cancer Institute) and Johns Hopkins Hospital included specimens. Tumors were subjected to immunohistochemical analysis for immune checkpoints (PD-L1, PD-1, LAG-3) and immune cell (IC) subsets (CD3, CD4, CD8, CD68). Expression profiling for immune-related genes was performed on select HIV-positive and HIV-negative cases in PD-L1+ tumor areas associated with ICs.Programmed death-ligand 1 expression on tumor cells and ICs, PD-L1 patterns (adaptive vs constitutive), degree of IC infiltration, quantified densities of IC subsets, and gene expression profiles in anal SCCs from HIV-positive vs HIV-negative patients.Approximately half of 40 tumor specimens from 23 HIV-positive and 17 HIV-negative patients (29 men and 11 women; mean [SD] age, 51 [9.9] years) demonstrated tumor cell PD-L1 expression, regardless of HIV status. Median IC densities were not significantly decreased in HIV-associated tumors for any cellular subset studied. Both adaptive (IC-associated) and constitutive PD-L1 expression patterns were observed. Immune cell PD-L1 expression correlated with increasing intensity of IC infiltration (r = 0.52; 95% CI, 0.26-0.78; P < .001) and with CD8+ T-cell density (r = 0.35; 95% CI, 0.11-0.59; P = .03). Gene expression profiling revealed comparable levels of IFNG in the TME of both HIV-positive and HIV-negative patients. A significant increase in IL18 expression levels was observed in HIV-associated anal SCCs (fold change, 12.69; P < .001).HIV status does not correlate with the degree or composition of IC infiltration or PD-L1 expression in anal SCC. These findings demonstrate an immune-reactive TME in anal SCCs from HIV-positive patients and support clinical investigations of PD-1/PD-L1 checkpoint blockade in anal SCC, irrespective of patient HIV status.
Functional SNPs in vascular endothelial growth factor (<i>VEGF-A</i>) and overall survival (OS) in bevacizumab-treated patients with metastatic colorectal cancer (mCRC).
Authors: Janet E. Murphy, Hannah M. Liebman, Qian Zhou, Josiah T. Bote, Anastassia Daskalova, Susanne M. Hooshmand, David P. Ryan, Matthew Kulke, David C. Christiani
Journal: Journal of Clinical Oncology (2012)

3594 Background: Functional SNPs in VEGF-A are prognostic for OS in several malignancies, but not described definitively in mCRC. In bevacizumab-treated patients with advanced breast cancer, VEGF -2578AA and -1154A were predictive of OS—the latter SNP reported in a recent mCRC series as well. We examined the association between five functional VEGF-A SNPs and OS in a large cohort of bevacizumab-treated patients with mCRC. Methods: 403 patients with mCRC treated from 2004-2010 were included in a retrospective analysis. DNA extraction, genotyping, and SNP evaluation were performed according to standard protocols. Survival was calculated from the time of Stage IV diagnosis until death. Data were censored as of 12/31/2010. Results: There were 279 deaths in this group of 403 patients (69%). Median age was 55.7 (24-86 y), and 54% of patients were male. Age, sex, race, tumor grade, chemotherapies, and curative surgery (metastatectomy to negative margins) were considered. Significant clinical predictors of OS in univariate Cox modeling were cetuximab treatment [HR=1.46; 95% CI 1.13-1.88; p=0.0014], irinotecan treatment [HR=2.10; 1.32-3.35; p&lt;0.001], and curative surgery [HR=0.36; 0.25-0.75; p&lt;0.001]. Significant negative interaction was found between both cetuximab and irinotecan and curative surgery, and in modeling that included this interaction, only surgery remained predictive. In multivariate analysis, no association was found between VEGF-A and OS (Table). Conclusions: There was no association between five functional VEGF-A SNPs and OS in this large bevacizumab-treated mCRC cohort. [Table: see text]
Colorectal cancer survivors' needs and preferences for survivorship information.
Authors: Talya Salz, Mary S. McCabe, Victoria Susana Blinder, Elena B. Elkin, Margaret Kemeny, Leonard Saltz, Larissa K. F. Temple, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2012)

6073 Background: We assessed colorectal cancer (CRC) survivors’ needs and preferences for information to guide development of a survivorship care plan. Methods: We conducted a survey of survivors treated for stage I-III CRC at two hospitals in New York City. Participants completed treatment 6-24 months before the interview and had not received a survivorship care plan. We evaluated whether survivors knew their basic treatment history, whether they understood ongoing risks, and their preferences for receiving survivorship information. Results: 175 CRC survivors completed the survey between June 2010 and November 2011. Survivors generally remembered basic information about their diagnosis and treatment: 88% accurately reported the location of their cancer; 95-100% accurately reported whether they had surgery, chemotherapy, or radiation; and 90-95% correctly reported the completion date (within 6 months) for each treatment. Survivors knew less about the risks of local and distant recurrences (69% and 77% correct, respectively) and of getting another CRC compared to unaffected individuals (40% correct). More than three quarters of participants received information about their cancer, their treatment history, ongoing oncology visits, and testing to be done by the oncologist (77-86% across categories). Across these categories of information, 93-99% of those who received information found it useful. Most survivors did not receive information about symptoms to report to their doctors, returning to work, financial issues, or legal issues (59-95% across categories); but those who received this information found it useful (67%-100% across categories). Conclusions: Even without receiving survivorship care plans, CRC survivors generally understood their cancer diagnosis and treatment. However, many lacked knowledge of ongoing risks, prevention, and nonmedical survivorship issues. Most survivors found the survivorship information they received useful. The greatest benefit of survivorship care plans to survivors may not be summarizing past care as much as helping survivors understand their risks and plan for the future.
Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (LV) (SCOUT) in patients with advanced colorectal cancer (ACRC): A phase I/II study
Authors: H. Sheikh, J. W. Valle, K. Palmer, G. Wilson, A. Sjursen, O. Craven, R. Swindell, M. P. Saunders
Journal: Journal of Clinical Oncology (2007)

4084 Background: The feasibility of UFT (tegafur-uracil) plus LV with alternating irinotecan and oxaliplatin was investigated in a two-stage, phase I/II, open-label, dose-finding trial in patients with ACRC. The study is now closed. Here we present results from the phase II cohort and overall results from the phase I/II study. Methods: Eligible patients aged =18 years had histologically confirmed, advanced, inoperable, measurable metastatic disease, no prior chemotherapy other than adjuvant bolus 5-FU administered =6 months previously, and adequate hematologic, hepatobiliary, and renal function. Patients in the phase I study received irinotecan 180 mg/m 2 on d1, oxaliplatin 85–100 mg/m 2 on d15 plus UFT 200–300 mg/m 2 /d with LV 90 mg/d on d1–21 of a 28-d cycle. Diarrhea, lethargy, and vomiting were dose limiting. The maximum tolerated dose (MTD) established was irinotecan 180 mg/m 2 , oxaliplatin 100 mg/m 2 , UFT 250 mg/m 2 /d, and LV 90 mg/day. Patients were treated at the MTD in the phase II study. Primary endpoints in the phase II study were objective response rate (ORR) and time to progression (TTP). Results: Forty-five patients (median age 62 [range 24–79] years, median 4 marker lesions) were entered, 16 and 29 patients in the phase I and II studies, respectively. The ORR in all 38 evaluable patients was 66% (95% CI 49–80%), with clinical benefit (CB) in 89% (95% CI 75–97%). At a median follow-up of 10.3 months, median TTP was 8.5 months (95% CI -7.6 to 10.4 months) in 40 evaluable patients and median OS (ITT population; n=45) was 16.8 months (95% CI -11.3 to 28.3 months). In the phase II study (n=29) median TTP was 8.1 months (95% CI -6.7 to 11.3 months) and median OS was 19.6 months (95% CI -7.7 to &gt;25.6 months); ORR in 25 evaluable patients was 68% (95% CI -46.5 to 85.1%) with CB in 100% (95% CI -86.3 to 100%). Of 30 patients with confirmed radiologic progression, 21 (70%) had second-line therapy. At the MTD, 3 patients (10%) had grade 3 diarrhea, 1 patient (3%) had grade 3 neurotoxicity, and 2 patients (7%) had grade 2 alopecia. No hand-foot syndrome (HFS) was seen. Conclusions: UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for patients with ACRC, with minimal alopecia and neurotoxicity and no HFS. No significant financial relationships to disclose.
Schooling and Children's Mental Health: Realigning Resources to Reduce Disparities and Advance Public Health
Authors: Marc S. Atkins, Elise Cappella, Elisa S. Shernoff, Tara G. Mehta, Erika L. Gustafson
Journal: Annual Review of Clinical Psychology (2017)

Schools have long been the primary setting for children's mental health services but have neither the resources nor the expertise to manage these services independently. The critical importance of school success for children's adjustment provides a strong rationale for schooling as an essential component of children's mental health services. In this article, we review evidence for how schooling and mental health coalesce, suggesting an alignment of school and community mental health resources that prioritizes successful schooling as a key mental health outcome. We describe collaborative principles and ecological practices that advance a public health focus on children's mental health while also reducing the burden on schools to maintain mental health services. We close with a model of mental health services illustrating these principles and practices in high-poverty urban schools and propose future directions for research and practice to promote positive mental health for all children and youth.
An investigator-initiated monocentric phase I dose escalation trial of temsirolimus and irinotecan (TEMIR) in patients with relapsing glioblastoma multiforme (reGBM).
Authors: Max E. Scheulen, Heike Richly, Halime Kalkavan, Andreas-Claudius Hoffmann, Isabel Virchow, Ralf A. Hilger, Susanne Koeppen, Ulrich Sure, Martin H. Schuler, Joerg Hense
Journal: Journal of Clinical Oncology (2012)

2086 Background: Deregulation of the PI3K/AKT pathway has been preclinically involved in the pathophysiology of GBM. The mammalian target of rapamycin (mTOR) is an important downstream mediator of PI3K/AKT signalling. The mTOR-inhibitor temsirolimus (Tem) achieves significant drug levels in brain. Thus, Tem may be effectively combined with irinotecan (Iri) which has shown promising results in combination with bevacizumab in patients (pts) with reGBM refractory to temozolomide (Tmz) in phase II. Exposure to Tem as well as Iri is substantially reduced in pts receiving CYP3A4 enzyme-inducing anticonvulsants (CYP3A4-Ind). Methods: TEMIR is a phase I trial of escalating doses of Tem in combination with Iri in pts with reGBM refractory to Tmz depending on the cotreatment with CYP3A4-Ind. In pts without CYP3A4-Ind dose escalation of Tem was performed according to the “3+3 protocol” from 15 via 20 to 25 mg iv wkly together with 85 mg/m 2 Iri iv wkly. In pts with CYP3A4-Ind the doses of Tem were 30, 40 and 50 mg iv wkly together with 170 mg/m 2 Iri iv wkly, respectively. The determination of the pharmacokinetics (PK) of Tem and its influence on the PK of Iri and its active metabolite SN38 was performed by validated RP-HPLC methods with fluorescence detection. Results: Up to now, 14 pts [4 female and 10 male, median age 47 yrs (range 41-65 yrs), 9 without and 5 with CYP3A4-Ind] have been treated. All 9 pts without CYP3A4-Ind (3 pts on 15, 20 and 25 mg Tem each) are evaluable for safety with only mild toxicity [highest CTC-grade ≥2 (gr) per pt]: diarrhea 4 (gr2) and 1 (gr3), neutropenia 1 (gr3), thrombopenia 1 (gr2), anemia 1 (gr2), pneumonia 2 (gr2), rash 1 (gr2). PK parameters of Iri and SN38 were in agreement with previously published studies and there was no significant effect of 15 to 25 mg Tem combined with 85 mg/m 2 Iri on the PK of Iri and SN38. In 7 pts evaluable for efficacy there was no remission (RECIST) and median time to symptomatic and/or MRT progression was 10 wks (7, 9+, 10, 10+, 11, 15, 20 wks). Conclusions: The combination of Tem in standard dose of 25 mg iv wkly with 85 mg/m 2 Iri wkly is safe in pts with reGBM without CYP3A4-Ind. Tem has no significant effect on the PK of Iri and SN38.
Identification and validation of an assay predictive of response and prognosis following anthracycline-based chemotherapy for early breast cancer.
Authors: Jude M. Mulligan, Laura A. Hill, Steve Deharo, Katherine E. Keating, Olaide Raji, Fionnuala A. McDyer, Jacqueline James, Gareth Irwin, David Boyle, Jennifer E. Quinn, Paul B. Mullan, Colin R. James, Manuel Salto-Tellez, Timothy S. Davison, Patrick Johnston, Fergus J. Couch, D. Paul Harkin, Richard D. Kennedy
Journal: Journal of Clinical Oncology (2013)

TPS11120 Background: Currently there is no biomarker to predict specific benefit from DNA-damaging anthracycline and cyclophosphamide-based chemotherapy in the clinic. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA-damage response pathway occurs in approximately 25% of breast cancer and results in sensitivity to DNA-damaging agents. We therefore developed an assay to detect loss of the FA/BRCA pathway, for the purpose of predicting benefit from chemotherapy. Methods: 21 FA patient samples were analyzed to identify genetic processes associated with loss of the FA/BRCA pathway. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples and a molecular subgroup was identified that was defined by the molecular processes representing loss of the FA/BRCA pathway. A 44-gene DNA Damage response deficient (DDRD) assay was developed that could identify this subgroup from formalin fixed, paraffin embedded (FFPE) samples in the clinic. Results: In a publicly available independent cohort of 204 patients, the assay predicted response to neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline and cyclophosphamide) with an odds ratio of 4.01, (95% Cl:1.69-9.54). We also analysed samples from an independent cohort of 114 node-negative breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin and cyclophosphamide treatment at the Northern Ireland Cancer Centre. The DDRD assay significantly predicted 5-year relapse free survival with a hazard ratio of 0.27 (95% Cl:0.10-0.83). The assay was not predictive of survival in patients who did not receive chemotherapy. Conclusions: An FFPE tissue-based assay that detects loss of the FA/BRCA pathway has been developed and independently validated as a predictor of response and prognosis following DNA damaging anthracycline/cyclophosphamide-based chemotherapy in the neoadjuvant and adjuvant settings.
CT perfusion as an early biomarker of treatment efficacy in advanced ovarian cancer: An ECOG-ACRIN and NRG GOG study.
Authors: Ting-Yim Lee, Chaan S. Ng, Zheng Zhang, Susanna Lee, Helga Marques, Kyle Burgers, Feng Su, Joseph Bauza, Robert S. Mannel, Joan L. Walker, Warner King Huh, Stephen C. Rubin, Paul DiSilvestro, Lainie P. Martin, John K. Chan, Michael A. Bookman, Robert L. Coleman
Journal: Journal of Clinical Oncology (2015)

5522 Background: GOG-0262 is an advanced stage ovarian cancer phase III trial comparing standard paclitaxel (q3 week)/carboplatin to dose-dense paclitaxel (weekly)/carboplatin with and without bevacizumab per physician choice. ACRIN 6695’s primary objective was to determine whether CT perfusion (CTP) parameters are prognostic of progression-free survival (PFS) at 6 months (PFS-6) in a cohort of GOG-262 patients. Methods: FIGO stage III or IV patients with suboptimal surgical cytoreduction or undergoing neoadjuvant therapy were recruited and underwent CTP studies before (T0) and at 3- (T1) and 4-weeks (T2) after chemotherapy initiation. Target lesion blood flow (BF) and blood volume were derived with CTP software (GE Healthcare). The association of BF changes from baseline to T2, dichotomized at zero (ΔBF±), and the response rate (best confirmed response by RECIST criteria) and PFS-6 rate were assessed with Fisher’s exact tests. Cox regression model was used to assess the association between ΔBF± and time-to-progression (TTP) and overall survival (OS). Results: From August 2011 to July 2013, 120 patients were screened, yielding 76 evaluable (with both T0 and T2 CTP studies analyzable) patients from 19 centers. The median age and TTP of those 76 patients were 61 (range 25-87) years and 427 (95% CI: 372-505) days. Overall response and PFS-6 rates were 74% (56/76) and 96% (73/76), respectively. 11/76(14%) patients had increase in tumor BF from baseline to T2 (positive ΔBF±). Positive ΔBF± were significantly associated with lower response rate (45% vs. 78%, p = 0.03) and shorter TTP (median TTP 335 vs. 457 days, HR 2.9, 95% CI: 1.3-6.4, p = 0.008); and a trend towards lower PFS-6 rate (82% vs. 98%, p = 0.053). The significant association between ΔBF± and TTP remained after adjusting for age, baseline tumor volume, change in tumor volume or surgery status (adjuvant vs. neo-adjuvant) individually (p < 0.02). ΔBF± was not significantly associated with OS (p = 0.28). Conclusions: CTP parameters measured within 4 weeks of initiating therapy may provide early prognostic information for treatment response and TTP, and could be used to refine treatment interventions for advanced ovarian cancer in future clinical trials. Clinical trial information: NCT01167712.