tbuckley/cabot-search huggingface dataset:
Limited-stage, small-cell lung cancer (SCLC) treated with concurrent irinotecan-platinum.
Authors: M. E. Picton, J. Zhang, T. Parent, P. R. Walker
Journal: Journal of Clinical Oncology (2010)

e17517 Background: Irinotecan and cisplatin with concurrent radiation is an effective and tolerable regimen in limited-stage SCLC is frequently used by our Asian colleagues but infrequently by North American thoracic oncologists. (Han et al J Clin Onc 2005; 23:3488-3494 and Jeong et al Lung Cancer 2006; 53:361-366). We describe our institutional multidisciplinary thoracic oncology program experience in a group of patients with limited-stage SCLC treated with irinotecan plus platinum and concurrent thoracic irradiation. Methods: Between May 2006 and December 2009, 17 patients were identified through our database with limited-stage SCLC receiving definitive treatment with 65 mg/m2 irinotecan on days 1 and 8 and with 30 mg/m2 cisplatin on day 1 every 22 days for planned 4 cycles; three patients received carboplatin in substitution for cisplatin. Concurrent thoracic radiotherapy started with cycle 2; eight patients received 150 cGy twice-daily radiation in 30 fractions (45Gy) and five patients received once daily radiation in 30 fractions (54 Gy). Eight patients underwent prophylactic cranial irradiation. Nine patients were males (53%), and 14 patients (82%) had a performance status of 0/1. Median age 67 years and 4 patients (23%) were older than 70 years. Results: The objective response rate was 70% after concurrent chemoradiotherapy (10 CR; 2 PR). 9/17 patients are still alive at a median follow-up of 12 months. 53% are alive past the 1-year mark and 18% alive past the 2-year mark. Grade 3 neutropenia developed in 29% of patients with only one episode of febrile neutropenia, esophagitis in 18% of patients, and there were no symptomatic instances of pneumonitis. Conclusions: Irinotecan and platinum with concurrent once or twice-daily thoracic RT is a well tolerated and effective definitive treatment approach for limited-stage SCLC. Specifically, no cases of radiation pneumonitis were observed in this series of patients. No significant financial relationships to disclose.
Treatment outcomes of radiotherapy versus prostatectomy for localized prostate cancer with Gleason 8 or more on biopsy.
Authors: Christopher Baker, Andrew M. McDonald, Grant Clark, Caleb Dulaney, Eddy Shih-Hsin Yang, Rojymon Jacob, John B. Fiveash
Journal: Journal of Clinical Oncology (2015)

120 Background: There have been no prospective randomized controlled trials comparing current treatment options for patients with high-risk localized prostate cancer. This study seeks to compare the biochemical and metastatic outcomes of patients that received definitive radiotherapy (dRT) or radical prostatectomy (RP) for localized prostate cancer with Gleason score ≥ 8 on initial biopsy. Methods: A total of 106 patients met the inclusion criteria of Gleason score ≥ 8 on initial biopsy and biochemical follow-up ≥ 1 year. Seventy-one patients were initially treated with dRT (96% also receiving androgen deprivation therapy) and 35 patients were initially treated with RP (with or without postoperative RT). Our primary endpoint was biochemical failure (BF). For dRT patients, BF was recorded according to the Phoenix Consensus or if extranodal metastasis was diagnosed. For surgical patients, BF was recorded according to American Urological Association guidelines or if extranodal metastasis occurred. If adjuvant/salvage RT was given postoperatively, BF was recorded if PSA ≥ 0.5 on two consecutive measures after completion of RT. Pretreatment characteristics were compared using Pearson Chi-square method and independent samples Mann-Whitney U test. Actuarial rates of BF and metastasis were calculated using the Kaplan-Meier method. Results: Median follow-up for all patients was 5.3 years. There was no statistical difference in clinical T-stage, initial PSA, or months of follow up between patients treated initially with radiotherapy vs. prostatectomy. Patients initially treated with dRT were significantly older than those treated with RP. The dRT group had a lower rate of BF compared to the RP group, p &lt; 0.001. The Kaplan-Meier estimate of BF at 5 years was 7.6% in the dRT group compared to 34.5% in the RP group. Additionally, the Kaplan-Meier estimate of distant metastasis at 10 years was 22.7% in the dRT group compared to 55.9% of the RP group, p = 0.01. Conclusions: For our sample of patients with Gleason score ≥ 8 on initial biopsy, initial treatment with dRT was associated with lower rates of biochemical failure and extranodal metastasis when compared to initial treatment with prostatectomy.
Phase II trial of patients (pts) with extensive stage small cell lung cancer (ES-SCLC) immunized with p53-transduced dendritic cells (p53-DC): Immune sensitization to chemotherapy (CT)
Authors: A. Chiappori, M. Sereno, D. Gabrilovich, N. Mirza, M. Dunn, W. Janssen, R. Smilee, K. Menander, S. Chada, S. Antonia
Journal: Journal of Clinical Oncology (2007)

3012 Background: Although ES-SCLC is initially, very responsive to CT, responses are not durable and relapse is characterized by chemoresistance. High incidence of p53 gene mutations, which prolong the protein’s half life, result in its frequent overexpression and enhanced detection in SCLC cells. This in turn allows for their recognition by p53-specific cytotoxic T cells. Here, we evaluated the clinical and immune response of a vaccine (vac) using p53-DC. Methods: Eligibility: Untreated, ES-SCLC pts. Age = 18 years. Performance status (PS) 0–2. Treated and controlled brain metastases. Adequate renal, hepatic and bone marrow function. Toxicity (T), survival (MST) and clinical and p53- specific immune responses were determined by CTCAE v2.0, Kaplan-Meier, RECIST and ELISPOT and tetramer staining respectively. Pts first received CT to best clinical response. Eight weeks later, those with minor progression (PD) or better, underwent leukapheresis. DC, generated from peripheral blood precursors, were infected with an adenoviral construct containing p53 (Advexin; Ad-p53) to produce the p53-DC vac. Each vaccination consisted of subcutaneous injections in 4 different nodal basins every 2 weeks x3 (2–5×10 6 p53-DC/dose). Results: Thirty-six pts received at least one vac; median age=58.8, (range=39–79), M/F=13/23, PS 0/1=16/20. All pts were evaluable for T and MST. Total vac=127 (median=3, range=2–6). Overall, vac was well tolerated (no &gt; grade 2 toxicities detected). p53-specific immune response was positive in 11/21 (52.4%) pts; pending in 15 pts. After 3 vac doses, 10 (27.7%) pts. had stable disease (SD) and 26 (72.2%) had PD. Pts with SD were re-vaccinated (x3). Upon PD, all pts were offered further CT. Clinical response to post-vac CT was evaluated in 22 pts. Ten pts (45%) responded to post-vac CT (second line=7, third line=3) and 6 pts had SD. MST=473 days (95% CI: 380,534). Conclusions: ES-SCLC pts were treated safely with p53-DC vaccine and demonstrated significant immune response. The p53-DC vaccine appears to sensitize ES-SCLC to subsequent CT resulting in improved survival. [Table: see text]
ABCF2 expression in endometrial cancer and breast cancer
Authors: H. Tsuda, Y. Ogawa, S. Nishimura, K. Kajitani, N. Kawamura, Y. Hashiguchi, R. S. Berkowitz, S. C. Mok
Journal: Journal of Clinical Oncology (2006)

5035 Background: ABCF2 is a new member of the ATP-binding cassette transporter superfamily gene. We previously reported that ABCF2 protein is new biomarker in clear cell adenocarcinoma (CC) of the ovary and its expression may predict the response to chemotherapy and survival of CC patients (Proc ASCO 2005, Clin Cancer Res 2005). Both breast cancer (BC) and endometorial cancer (EC) are estrogen-dependent tumors, however, their biological behavior differ. In this study, we examined ABCF2 expression in EMCA and BC and evaluated the relationship between ABCF2 expression and clinical factor. Methods: Formalin-fixed surgical samples from 100 EMCA and 191 BC patients were included in this study. ABCF2 expression was investigated by immunohistochemistry. Positive expression of ABCF2 was &gt; 10% based on the cytoplasmic staining. Results: Histologic types and stage were as followed: EMCA: (Endometrioid (EM): 92; Adenosquamous (AS): 8), (I: 63; II: 5; III: 30; IV: 2). BC: (Papillo tu (PP): 60; Solid tub (SL): 38; Scirrhous (SC): 77; Other (OT): 15). Breast cancer was sub-classified into 3 types according to the criteria of the Japanese Breast Cancer Society. The relationship between ABCF2 expression and histologic type was shown in table. In EMCA and BC, there were no significant relationship between ABCF2 expression and clinical factor like stage, histologic type, grade and estrogen receptor (ER). In EMCA, ABCF2 expression was not related with disease free survival (DFS). However, in BC, ABCF2-positive tumors had longer DFS than ABCF2-negative tumors (p = 0.03). The ABCF2 expression were correlated with further biological variables such as tumor stage, lympho node metastasis, nuclear grade and ER status for DFS by univariate and multivariate Cox regression analysis. Multivariate analysis revealed that ABCF2 was an independent prognostic factor (HR 0.46; p = 0.018). Conclusion: The role of ABCF2 protein may differ between EMCA and BC. [Table: see text] No significant financial relationships to disclose.
ESR1 and ESR2 polymorphisms in BIG 1−98 comparing adjuvant letrozole (L) versus tamoxifen (T) or their sequence for early breast cancer.
Authors: M. Bouzyk, K. P. Gray, M. M. Regan, O. Pagani, W. Tang, R. Kammler, R. Maibach, G. Viale, P. Dell'Orto, B. J. K. Thurlimann, E. Hitre, M. Lyng, H. J. Ditzel, P. Neven, G. MacGrogan, K. N. Price, R. D. Gelber, A. S. Coates, A. Goldhirsch, B. Leyland-Jones
Journal: Journal of Clinical Oncology (2011)

1002 Background: Polymorphisms of ERα and ERβ have been associated with multiple endocrine-mediated physiological mechanisms, including lipid profile, mammographic density, VTE and cognition, and inconsistently with breast cancer risk and BMD changes. We investigated if SNPs in ESR1 and ESR2 genes predict outcome and side effects of adjuvant endocrine therapies. Methods: BIG 1−98 compared adjuvant hormonal therapies in 8010 postmenopausal pts with operable, ER-positive breast cancer: 5 yrs of T; 5 yrs of L; 2 yrs T followed by 3 yrs L (TL); and the reverse (LT). DNA was isolated from FFPE primary tumor specimens. The analytic cohort was 3303 (of 3685 with DNA) pts genotyped for 8 SNPs of ESR1 and ESR2 using SNPstream; 4 were successful {ESR1: rs9340799 (XbaI), rs2077647, rs11963577; ESR2 rs4986938} and PvuII is being rerun on Taqman. Cox models tested for association of ESR1+2 variants with breast cancer-free interval (BCFI), adverse bone events (grade 3−5 osteoporosis or bone fracture), and for genotype-by-treatment interaction. With 10% BCFI events, 40% variant prevalence there was 80% power to detect HR=1.50 (alpha=0.05). 8% of pts had bone events. Results: Rare homozygotes of XbaI, rs2077647 and ESR2 were associated with higher Ki-67 expression but not other disease features (each P≤0.05). Presence of ≥1 rare variant allele in XbaI, rs2077647 and ESR2 tended to have reduced hazard of BCFI vs wt after adjusting for disease features (HR=0.81, 95% CI (.64−1.02); 0.77 (.59−1.01); 0.83 (.63−1.09)). Treatment-by-genotype interactions were not significant. For bone events, T pts with rare Xbal homozygotes had increased hazard vs wt and het, whereas L pts had decreased hazard (P=.07 interaction). Rare rs2077647 homozygotes had increased hazard in L and T pts (HR=1.52 (1.08−2.13)) vs wt and het. Conclusions: In this large postmenopausal breast cancer population treated with endocrine therapy, we paradoxically observed that rare ESR1 homozygous polymorphisms were associated with 1) lower recurrence, but also with high Ki−67, a poor prognostic feature and 2) higher risk of bone side effects, which possibly differ by treatment. The final analysis will include longer follow-up and PvuII results.
P53, Bcl-2, PCNA expression and apoptotic rates during cervical tumorigenesis
Authors: H. Astudillo, M. Perez, J. Silva, M. Silva, S. Castillo, L. Benitez, P. Gariglio
Journal: Journal of Clinical Oncology (2004)

5068 Background: In order to estimate the apoptotic rates during the development of cervical cancer, we investigated apoptosis by morphological criteria and by the TUNEL assay, as well as by the expression of proteins related to this process such as p53, Bcl-2 and PCNA in lesions of all phases of tumor progression in the cervical epithelium. Methods: The expression of p53, Bcl-2 and PCNA proteins were immunohistochemically examined using 31 normal cervical epithelium, 10 low grade squamous lesions (CIN I), 28 high grade squamous lesions (CIN II/III) and 36 invasive squamous cell carcinomas (ISCC). The same samples were used for TUNEL assays and HPV detection by polymerase chain reaction (PCR) and sequence. Results:Human papillomavirus (HPV) presence is necessary but not sufficient for cervical cancer development, suggesting that cellular genes participate in tumor progression. PCNA protein expression was significantly increased as the grade of cervical lesion becomes higher from normal epithelium to ISCC. Surprisingly, p53 levels also increased with lesion degree. Apoptosis as determined by TUNEL assay, and PCNA protein expression show a significant positive correlation with increasing histological abnormality. Statistical analysis showed a positive correlation between p53 and PCNA expression in CIN I (r=0.378, P=0.016). A similar correlation was found between p53 and Bcl-2 expression in CIN II/III (r=0.385, P=0.023). A total of 76 of 105 (71.4%) cervical samples were HPV positive, with HPV 16 being the most common high-risk type detected (72.4%). Conclusions:Our results suggest that p53 protein overexpression during cervical tumorigenesis could be playing a pivotal role in cervical tumor progression as a late event. Although a stronger p53 than Bcl-2 expression in CIN II/III was detected, the up-regulation of Bcl-2 in ISCC suggests that protection against apoptosis is important for maintaining cervical neoplasia. PCNA protein expression increase may be a useful marker for diagnosis of various dysplasia grades and cervical cancer. No significant financial relationships to disclose.
Influence of maternal bronchial asthma clinical phenotype on development of allergies in children
Authors: Maria Vakharlovskaya, Ludmila Jelenina, Alexander Orlov
Journal: European Respiratory Journal (2014)

Rationale: Clinical heterogeneity of bronchial asthma (BA) is undeniable. Child and adult BA phenotypes have evident differences not also in details of allergic sensitizing, but also in character and severity of its clinical course.

Purpose of the study: to analyze peculiarities of allergic pathology formation in children depending on clinical and pathogenic phenotype of maternal BA.

Materials and methods: We have examined 117 mothers with BA. Of them, 88 women (75.9%) developed BA at preschool or school age child phenotype; 29 mothers (24.8%) had onset of the disease at the age above 18 adult phenotype. Health condition of children born from mothers with BA was assessed starting from birth and up to the age of 7. The focus was made on formation of atopic dermatitis (AD), allergic rhinitis (AR), allergic laryngotracheitis (ALT), and BA.

Results: by the end of the observation period, the group of healthy subjects (who did not develop any allergic pathology during the observation period) consisted of 55 children; 23 children (19.7%) had clinical presentation of AD and/or ALT; and 39 children (33.3%) developed BA. Children born from mothers with child BA phenotype had reliably higher incidence of BA (34 patients, 38.6%), while only 5 children born from mothers with adult BA phenotype (17.2%) developed BA by the end of the observation period (p=0.034). Calculation of odds ratio showed that relative risk of BA in children under 7 years of age born from mothers with child BA phenotype was 3 times higher than that in adult BA phenotype (OR = 3,042[CI:1,013 -9,132]).

Conclusion: Therefore, we can suppose that maternal clinical BA phenotype had considerable influence on the child's BA phenotype.
Effect of complications after pancreaticoduodenectomy on adjuvant therapy utilization and survival in pancreatic cancer.
Authors: Dima Hnoosh, Hayder M. Saeed, Bin Huang, Erin Maynard, Eric B Durbin, Philip A. DeSimone, Mahesh R. Kudrimoti, Lowell Brian Anthony, Peter Joel Hosein, Patrick McGrath, Ching-Wei David Tzeng
Journal: Journal of Clinical Oncology (2015)

422 Background: While adjuvant therapy (AT) completion is a necessary component of multimodality therapy for pancreatic adenocarcinoma (PDAC), its timing and utilization can be hindered by complications after pancreaticoduodenectomy (PD). The primary aim of this study was to evaluate the impact of post-PD complications on AT utilization and overall survival (OS). Methods: Patients treated with PD for PDAC at a single institution (2000-2012) were evaluated. Data on 90-day complications were extracted from the electronic medical record with postoperative major complications (PMC) defined as Grade ≥3. Patient records were linked to the Surveillance Epidemiology End Results - Kentucky Cancer Registry for AT and OS data. Early AT required a first dose before 8 weeks, while late was 8-16 weeks. Initiation after 16 weeks was not considered adjuvant. Chi-square statistics, Kaplan-Meier plots, and log-rank tests were used to examine associations among complication status and AT timing, AT utilization, and OS. Results: Of 84 total patients, 54 (64%) received AT (34 [41%] early; 20 [24%] late). Rates of patients with 90-day complications were as follows: 44 (52%) Grade ≥1, 37 (44%) Grade ≥2, and 18 (21%) Grade ≥3. Low-grade (Grades 1-2) complications were not associated with late AT or lack of AT (both p&gt;0.082). However, PMC were associated with lower rates of AT (7/18, 39% with PMC vs. 47/66, 71% without PMC, p=0.011). Even patients who recovered from PMC were less likely to meet the early 8-week window (4/18, 22%, patients with PMC, vs. 30/66, 46%, patients with no PMC, p=0.039). PMC were associated with worse median OS (6.1 mo, 95% confidence interval, CI, 1.6-12.1, vs. 20.8 mo, 95% CI 17.3-23.8, with no PMC, p&lt;0.001), while low-grade complications were not (all p&gt;0.079). Conclusions: In this series,low-grade complications had minimal effects on AT timing, AT utilization, and OS, but PMC were associated with late and decreased AT utilization and negatively impacted OS.These data suggest that strategies to decrease PMC and/or treatment sequencing alternatives to increase multimodality completion rates in high-risk patients may improve oncologic outcomes.
Phase II study of EPOCH infusional chemotherapy in relapsed or refractory Hodgkin's lymphoma (HL). A report on toxicity, efficacy and prognostic indicators of outcome
Authors: K. M. Dunleavy, J. Butrynski, S. Steinberg, N. Grant, T. White, E. S. Jaffe, W. H. Wilson
Journal: Journal of Clinical Oncology (2004)

6598 Background: In relapsed/refractory HL, an effective and well tolerated salvage regimen has important roles both prior to autologous stem cell transplant (SCT) and as palliative therapy in patients (pts) who are ineligible for or have failed SCT. Methods: Eligible pts had relapsed/refractory HL and adequate organ function unless due to HL. Pts received fixed dose EPOCH chemotherapy (etoposide 200 mg/m2, vincristine 1.6 mg/m2 (no cap) and doxorubicin 40 mg/m2 CIVI x 96-hrs D1–4; cyclophosphamide 750 mg/m2 IV D5 and prednisone 60 mg/m2 qd D1–6 ) with G-CSF q21 days until disease progression or stabilization over ≥ 2 cycles. Results: Of 54 pts, median (range) age was 31 yrs (19–64), 35 (66%) were male, stage was III in 11(21%) and IV in 30(56%), and 29 (55%) had B symptoms. Histology included nodular sclerosis 34 (64%), mixed cellularity 3 (25%), and lymphocyte depleted 5 (9%) classical HL, and nodular lymphocyte predominant HL 1 (2%). 24 (45%) pts had had ≥ 2 prior regimens, 27 (51%) pts received chemotherapy within the previous 10 mos, and 40 (75%) pts had responded to their last treatment. Over 202 cycles, toxicities included fever and neutropenia on 9 (4%), grade (gr) 4 neutropenia on 31 (15%), gr 4 thrombocytopenia on 20 (10%), and ≥ gr 2 gastrointestinal toxicity on 20 (10%) cycles; ≥ gr 2 cardiotoxicity occurred in 2 (4%) and ≥ gr 2 neurotoxicity in 11 (20%) pts. There was one treatment related death. 45 (84%) pts responded with 23 (44%) CR and 21 (40%) PR. With a median follow-up of 68 mos, the median progression-free (PFS) and overall survivals (OS) are 10 and 40 mos, and at 68 mos median follow-up, PFS and OS are 21% and 41%. Among 33 pts who underwent SCT, median PFS is 15 mos and OS has not been reached. Multivariate analysis revealed that the no. of prior drugs and response to the preceding regimen significantly influenced OS and PFS; in addition PFS was significantly influenced by performance status and mos since previous chemotherapy. Conclusions: EPOCH is well tolerated and has a high response rate in relapsed/refractory HL. It should be considered as salvage therapy prior to SCT or for palliation in incurable HL. No significant financial relationships to disclose.
Severe neutropenia in cycle one of CHOP is a marker of early death among intermediate and high grade lymphoma (IHL) patients
Authors: A. P. Rabinowitz, N. J. Weiner, D. Steinberg, J. T. Sparks, M. Fridman, R. Liberman, D. J. Delgado
Journal: Journal of Clinical Oncology (2004)

6717 Background: Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy is effective therapy for IHL. However, it may produce severe neutropenia in cycle 1 (C1SN), which can lead to dose modifications and early termination of therapy. We recently developed a predictive model for C1SN, using clinical information routinely obtained before chemotherapy initiation (ASH 2003). In the current study, we assessed the relationship between C1SN and 6-month survival. Methods: Medical records of IHL (Working Formulation D-H) patients (pts) treated at a single institution between 1981 and 2002 were retrospectively reviewed. 187 pts treated with CHOP who did not receive preemptive growth factor in cycle 1 were selected. SN was defined as absolute neutrophil count ≤250/mm3 or febrile neutropenia. Early death was defined as death within 6 months of chemotherapy initiation. Stepwise logistic regression analysis was used to select risk factors significantly associated with early death. Results: 55 pts (29.4%) experienced C1SN. 15 pts (8.0%) had early death, of which 11 (73.3%) had C1SN. Causes of death were lymphoma (7), sepsis (4), chemotherapy toxicity (3), and other (1). C1SN increased the observed risk of early death in pts with good and poor performance status (PS) 8.9-fold and 7.5-fold, respectively (p=0.89). Risk factors associated with early death in univariate analysis included C1SN, poor PS, decreased serum albumin and elevated LDH. In multivariate analysis, C1SN (OR 8.3; 95% CI 2.4–28.5) and poor PS (OR 5.3; 95% CI 1.6–17.4) showed significant association with early death (c-statistic 0.81). For pts with C1SN the predicted probability of early death was 0.46 and 0.14 in pts with poor and good PS, respectively. For pts without C1SN the predicted probability of early death was 0.09 and 0.02 in pts with poor and good PS, respectively. Conclusions: SN in cycle 1 of CHOP chemotherapy may serve as an early warning sign for increased risk of premature death. Pts with C1SN appear to have significantly greater risk of early death regardless of baseline PS. The biological significance of this observation needs to be explored. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc. Amegn, Inc. Amgen, Inc.