tbuckley/cabot-search huggingface dataset:
Management of patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) after radiological progression to first-line therapy with gefitinib.
Authors: Yukio Hosomi, Chiharu Tanai, Kiyotaka Yoh, Yasushi Goto, Yasuo Ohashi, Hideo Kunitoh
Journal: Journal of Clinical Oncology (2015)

e19124 Background: NSCLC patients harboring an activating EGFR mutation sometimes continued to receive an EGFR-tyrosine kinase inhibitor (EGFR-TKI) after radiological “progressive disease” (R-PD). We previously reported that 35% of EGFRm+ NSCLC patients (pts) continued to receive an EGFR-TKI after R-PD without clinical deterioration (C-PD), with a median time from R-PD to C-PD of 5 months. Here we analyze the outcomes of pts after R-PD without C-PD in the gefitinib (Gef) receiving cohort, relative to their characteristics. Methods: 31 institutions in Japan participated in the survey of pts with EGFRm+ advanced NSCLC who received first-line Gef between 2009 and 2011. C-PD was defined as one or more of the following: 1) symptomatic PD; 2) worsening performance status due to PD; 3) threat to major vital organ(s); or 4) multi-organ unequivocal PD. Results: 529 pts were analyzed. 247 (47%) were elderly (>70 yrs.), and 365 (69%) were female. 43 pts were still on Gef without R-PD and 68 pts, whereas Gef had been stopped without documentation of R-PD in another 68 pts. The remaining 418 pts were sub-classified into the following groups: Group A, Gef stopped at R-PD concurrently occurring with C-PD (n=161); Group B, Gef stopped at R-PD without C-PD (n=165); Group C, Gef continued beyond R-PD (n=92). Outcomes are summarized in the table. Conclusions: Clinical courses and pattern of care after radiologically documented resistance to Gef varied by age and sex. Elderly or female pts who received Gef beyond R-PD tended to have longer OS than who did not. Supported by the Public Health Research Center Foundation, with fund from AstraZeneca. Group B (N=165) Group C (N=92) N median OS (months) N median OS (months) R-PD to C-PD (months) rate of receiving Gef beyond R-PD (Group C/B+C) male (N=77) 57 21 20 22 2.6 26% female (N=180) 108 28 72 35 5.7 40% non-elderly (N=143) 94 27 49 28 3.7 34% elderly (N=114) 71 22 43 35 5.6 38%
Associations between treatment-emergent symptoms and early discontinuation of aromatase inhibitor (AI) therapy.
Authors: Kunal C. Kadakia, Claire Frances Snyder, Kelley M Kidwell, Nicholas J. Seewald, Anna Maria Storniolo, David A. Flockhart, Janet S Carpenter, Daniel F. Hayes, Vered Stearns, Norah Lynn Henry
Journal: Journal of Clinical Oncology (2015)

e20745 Background: The Exemestane and Letrozole Pharmacogenetics (ELPh) trial addressed associations between pharmacogenetics and effects of AI therapy. Here we describe changes in health-related quality-of-life (HRQOL) measures during AI therapy. We hypothesized that negative effects of AI therapy on HRQOL predict for early discontinuation. Methods: Postmenopausal women initiating AI therapy were enrolled on the ELPh trial and randomized to exemestane or letrozole for 24 months (mo). Patients completed questionnaires at baseline (BL) and serially over 24 mo, including the EuroQOL Visual analogue scale (VAS) (range 0-100), Centers for Epidemiologic Studies Depression Scale (CESD) (range 0-60), Anxiety subscale of Hospital Anxiety and Depression Scale (HADSA) (range 0-21), and a symptom assessment analyzed as 6 symptom clusters (SC): body image, vasomotor, vulvovaginal, musculoskeletal (MSK), cognitive, mood (range 0-4). A joint mixed effects and survival model was used to estimate the effect of the change in HRQOL scores over 24 mo on AI discontinuation. All HRQOL measures were treated as continuous variables. Results: 490 patients were analyzed with no significant differences between BL HRQOL measures by drug. 155 (32%) patients discontinued AI therapy within 24 mo. Each 1-point decrease in EuroQOL VAS was significantly associated with an increased risk of early discontinuation (hazard ratio (HR), 2.77; 95% confidence interval (CI) 2.72-2.81, p = 0.015). Changes in CESD and HADSA were also associated with early discontinuation (HR 1.04; 95% CI 1.01-1.06, p = 0.001 and HR 1.08; 95% CI 1.02-1.14, p = 0.006, respectively). Each 1-point increase in the MSK (HR 4.39; 95% CI 2.40-8.02, p < 0.0001), cognitive (HR 3.45; 95% CI 2.07-5.74, p < 0.0001), mood (HR 2.50; 95% CI 1.42-4.41, p = 0.002), and body image (HR 2.12; 95% CI 1.10-4.08, p = 0.025) SC were associated with early discontinuation. Conclusions: In this hypothesis-generating analysis, worsening of multiple treatment-related symptoms during AI therapy predicted early discontinuation of AI. If confirmed in independent trials, serial changes in HRQOL could be utilized to target interventions in patients at high-risk for early discontinuation. Clinical trial information: NCT00228956.
Long-term survival in 101 metastatic gastroesophageal cancer (mGEAC) patients eventually treated with consolidative local therapy.
Authors: Dilsa Mizrak Kaya, Xuemei Wang, Kazuto Harada, Mariela A. Blum Murphy, Prajnan Das, Bruce D. Minsky, Jeannelyn Estrella, Quan Lin, Fatemeh Ghazanfari Amlashi, Jeffrey H Lee, Brian Weston, Manoop S. Bhutani, Aurelio Matamoros, Tara L. Sagebiel, Heath Devin Skinner, Carol C Wu, Wayne Lewis Hofstetter, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2017)

197 Background: Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation and/or surgery) for selected mGEAC patients. We present results in a large cohort. Methods: From our database, we identified a 101 such patients. We analyzed the association of various clinical variables (location of primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose {≥50.4 Gy vs. &lt;50.4 Gy}) with overall survival (OS). Results: There were 71 patients with proximal primary (esophageal, Siewert types I/II) and 30 patients with distal primary (Siewert type III and gastric). The median OS was 25.7 months (95% CI: 22.3-32.8 months). The OS rates at 2-years and 5-years from diagnosis were 53.8% (95% CI: 44.7%-64.8%) and 20.7% (95% CI: 13.4%-31.9%), respectively. The median OS was highly associated with the location of primary (22.8 months for proximal GEACs vs. 41.5 months for distal GEACs, p=0.03). Duration of initial chemotherapy was highly associated with OS (21.8 months for &lt;3 months vs. 32.5 months for ≥3 months, p=0.004). Association between OS and tumor/treatment characteristics. Conclusions: Selected patients with mGEAC (who have favorable clinical course) can have up to 20% 5-year survival with this strategy. Patients with distal GEAC and those who receive initial chemotherapy for longer time are the maximum beneficiaries. [Table: see text]
Outcome at first relapse after frontline RVD regimen plus lenalidomide maintenance in transplant eligible MM patients.
Authors: Murielle Roussel, Benjamin Hebraud, Denis Caillot, Xavier Leleu, Margaret Macro, Cyrille Hulin, Carine Chaleteix, Martine Escoffre Barbe, Lionel Karlin, Gerald Marit, Laurent Garderet, Brigitte Pegourie, Anne-Marie Stoppa, Pascal Lenain, Bruno Royer, Herve Avet-Loiseau, Michel Attal
Journal: Journal of Clinical Oncology (2015)

8578 Background: The IFM 2009 trial recruited 700 MM pts between 2010-2012. Pts were randomly assigned to received RVD (5-8 cycles) and 1-yr Len maintenance +/- upfront ASCT. More than 250 pts relapsed. We aimed to analyze response rates (RR) and survival outcomes after salvage therapy. Methods: Pts who relapsed during RVD cycles or first 2 months of maintenance (group 1) were considered Relapsed and Double Refractory and were likely to receive CVAD or DCEP regimen. Pts who relapsed during or early after maintenance (Group 2) were considered Relapsed and Len Refractory and were likely to receive VCD, CPAD or pomalidomide based regimen (PCD). Pts who relapsed during FU (Group 3) were standard Relapsed. Eligible pts could receive SCT (auto and/or allo). Results: 83 pts were retrospectively analyzed. Median age was 56 years (28-65), ISS 2/3=37/22. 27 pts had High Risk (HR) cytogenetics. Group 1 comprised 15 pts (10 relapsed during RVD induction/consolidation). Eight pts received CVAD, 3 DCEP and 1 PD. Three pts died before any tx. Group 2 comprised 40 pts; 14 received VCD, 8 CPAD, 4 DCEP and 11 PCD. Group 3 comprised 28 pts; 12 received VCD, 3 CPAD and 11 PCD. RR and survival outcomes are listed in table 1. ORR was 40, 67.5 and 75% in groups 1,2,3, respectively. 46 pts proceeded to SCT (allo, n = 5). Median FU is 42 months from initial therapy: 64% pts relapsed again and 29% died. Median PFS2 is 11 months and 3-year OS 74%. Pts from group 1 had the poorest prognosis with 60% death, median OS 11.7 months. Median PFS2 was 3.5 months. Conclusions: Relapsed pts within 1 year after RVD induction/consolidation have impaired prognosis after salvage therapy. Salvage Tx n ISS 2/3 PFS 1 mos BRA SCT Relapse 2 PFS 2 mos Death 3-y OS 1 Double Refractory all 15 3/6 7.2 CR2/VGPR1/PR3 8 (57%) 9* (60%) 3.5 9 (60%) 40% CVAD 8 1/4 7.2 CR 1/PR 3 6 6 2.6 3 62,5% DCEP 3 2/1 3.0 CR 1/VGPR 1 2 2 5.0 2 - 2 Len Refractory all 40 21/10 15 CR 10/VGPR 9/ PR 8 25 (62.5%) 30 (75%) 13.2 13 (32.5%) 70.5% VCD 14 8/3 13 CR 3/VGPR 3/PR 2 9 12 15.6 5 78.5% CPAD 8 4/3 16 CR 3/VGPR 3/PR 2 7 5 13.5 1 87.5% DCEP 4 2/1 9.7 CR 2/PR 1 3 3 8.3 2 50% PCD 11 6/2 19 CR 1/VGPR 3/PR 3 4 7 9 3 70% 3 Relapsed all 28 13/6 30 CR 6/VGPR 7/PR 8 13 (46.5%) 14 (50%) 14 2 (7%) 100% VCD 12 7/2 25.6 CR 2/VGPR 3/PR 3 6 7 2 90% CPAD 3 1/0 30.5 CR 2/PR 1 2 1 0 100% PCD 11 5/2 30.9 CR 2/VGPR 3/PR 4 5 4 0 100%
Promoter methylation and protein expression of the <i>Slit2</i> and <i>Robo1</i> genes in resected esophageal squamous cell carcinoma
Authors: C. Tzao, H. Hsu, S. Lee, W. Hsu, G. Sun, A. Cheng, Y. Wang
Journal: Journal of Clinical Oncology (2006)

10032 Background: Recent epigenetic studies suggest that the slit-robo pathway is involved in tumorigenesis of a number of human cancers and a role of SLIT2 as a tumor suppressor gene. In view of lack of epigenetic studies of SLIT2 and ROBO1 genes in squamous cell esophageal carcinoma (ESCC), we investigate whether promoter methylation is responsible for aberrant protien expression of SLIT2 and ROBO1 and whether promoter methylation and aberrant protein expression of these two genes are related to prognosis after resection for ESCC. Methods: We analyzed promoter methylation of SLIT2 and ROBO1 using methylation-specific polymerase chain reaction (MSP) and their protein expression using immunohistochemistry in 60 resected tumor specimens. The Pearson χ 2 test was used to compare promoter methylation and protein expression of SLIT2 and ROBO1 among patients with different clinicopathological parameters. Concordance analysis was performed between promoter methylation and protein expression of these two genes. Results: Promoter methylation of SLIT2 and ROBO1 was observed in 43 (71.6%) and 16 (26.6%) of the 60 resected specimens, respectively (P = 0.002). Aberrant protein expression of SLIT2 and ROBO1 was observed in 51 (85%) and 23 (38.3%), respectively (P &lt; 0.001). Promoter methylation of SLIT2 correlated well with smoking (P = 0.046), betel nut chewing (P = 0.032), staging (P = 0.018) and tumor (T) factor (P &lt; 0.001) of the TNM system and its aberrant protein expression correlated well with betel nut chewing (P = 0.038), staging (P = 0.025) and nodal (N) involvement (P = 0.004). Promoter methylation and protein expression of ROBO1 did not correlate with any of these clinicopathologic parameters. A concordance rate of 88.2% and 74.2% was present between expression of SLIT2 and ROBO1 protein and their promoter methylation (P &lt; 0.001) and (P = 0.004), respectively. Conclusions: Aberrant expression of SLIT2 and ROBO1 protein is frequently associated with the presence of ESCC, with SLIT2 a more predominant one. Promoter methylation is one of the major mechanisms responsible for aberrant protein expression of these two genes in resected ESCC. Promoter methylation and aberrant protein expression of SLIT2 may predict prognosis after resection for ESCC. No significant financial relationships to disclose.
Breast cancer multifocality-multicentricity and locoregional recurrance.
Authors: Xiudong Lei, Siobhan P. Lynch, Limin Hsu, Funda Meric-Bernstam, Thomas A. Buchholz, Hong Zhang, Gabriel N. Hortobagyi, Vicente Valero, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2012)

1029 Background: The impact of multifocality (MF) and multicentricity (MC) on locoregional (LR) control for invasive breast cancer, and the optimal local treatment strategy for these tumors, is unknown. In particular, there is disagreement in the literature regarding the use of Breast Conservation Therapy (BCT). We evaluated a large single institution cohort of MF and MC breast cancers to determine if they had inferior LR control rate when compared to their unifocal counterparts. Methods: MF and MC were defined pathologically as more than one lesion in the same quadrant and more than one lesion in separate quadrants, respectively. Patients were categorized by presence or absence of MF or MC disease and by the LR treatment modality received – BCT (n=256), mastectomy alone (n=466), or mastectomy plus post-mastectomy radiation therapy (n=184). 10 patients who underwent BCT for MC disease against physician advice were excluded. MF and MC tumors were analyzed both as a group and as separate entities. Kaplan-Meier product limit method was used to calculate 5-year LR control rate. Cox proportional hazards models were fit to determine independent associations of MF/MC disease with LR control. Results: Median follow up was 52 months. Out of 3722 patients with stage I-III disease who did not receive neoadjuvant chemotherapy, 906 (24%) had MF (n=673) or MC (n=233) disease. 5-year rate of LR control rate was 99% in the MF group, 96% in the MC group, and 98% in the unifocal group, (P = 0.44). Subset analysis revealed no statistical difference in LR control regardless of the type of LR treatment, (P = 0.67 in the BCT group, P = 0.37 in the mastectomy alone group, and P = 0.29 in the mastectomy plus post-mastectomy radiation therapy group). There were 21 in-breast recurrences after BCT (8.2%). After controlling for other risk factors, MF and MC did not have an independent impact on LR control rate. Conclusions: MF and MC disease are not independent risk factors for LR recurrence. Patients with MF and MC breast cancer had similar rates of LR control to their unifocal counterparts, regardless of LR treatment modality. Our data suggest that BCT is a safe option for patients with MF tumors and that MF or MC disease alone is not an indication for post-mastectomy radiation therapy.
Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia
Authors: Qiao-Yang Sun, Ling-wen Ding, Kar-Tong Tan, Wenwen Chien, Anand Mayakonda, Allen Eng Juh Yeoh, Norihiko Kawamata, Yasunobu Nagata, Xiao Jin-Fen, Xin-Yi Loh, De-Chen Lin, Manoj Garg, Yan-Yi Jiang, Liang Xu, Su-Lin Lim, Li-Zhen Liu, Vikas Madan, Masashi Sanada, Lucia Torres Fernández, Hema Preethi S.S., Michael Lill, Hagop M. Kantarjian, Steven M. Kornblau, Satoru Miyano, Der-Cherng Liang, Seishi Ogawa, Lee-Yung Shih, Henry Yang, H. Phillip Koeffler
Journal: Blood (2016)
Prognostic value of absolute monocyte count in diffuse large B-cell lymphoma patient with autologous peripheral blood stem cell transplant.
Authors: Yuankai Shi, Hongnan Mo, Xiaohong Han, Shengyu Zhou, Xiaohui He, Peng Liu, Jianliang Yang, Changgong Zhang, Sheng Yang, Yan Qin, Lin Gui, Youwu Shi, Jiarui Yao, Liya Zhao, Shuxiang Zhang, Yan Sun
Journal: Journal of Clinical Oncology (2014)

e18002 Background: High-dose therapy (HDT) and autologous peripheral blood stem cell transplant (APBSCT) improve the outcome of diffuse large B cell lymphoma (DLBCL) patients. There is a lack of prognostic indicators evaluated in the peri-transplant period for DLBCL patients. This retrospective study was designed to explore the prognostic value of absolute monocyte count (AMC) in DLBCL patients who underwent APBSCT. Methods: Patients were required to be treated with cyclophosphamide, adriamycin, vincristine and prednisone as first-line therapy, with or without Rituximab, and have undergone HDT with APBSCT. From 1997 to 2013, 86 consecutive patients with DLBCL qualified for the study. Clinical characteristics were obtained from medical records. We studied AMC at diagnosis, before APBSCT (AMC-Pre) and at day 15 after APBSCT as prognostic factor for overall survival (OS) and progression-free survival (PFS). The International Prognostic Index (IPI) score, as well as its components, were also analysis for prognostic value. Results: Median follow-up from APBSCT was 58.5 months (range: 3~167months), and for the living patients was 77.5 months (range: 4~167months). Receiver operating characteristics curve analysis established 0.285G/L as the cutoff point of AMC-Pre for survival. AMC-Pre≥0.285G/L had an AUC of 0.666 (95% CI 0.525–0.807, P=0.031) with a sensitivity 94.4% of and specificity of 32.4%. The 5-year OS was 70.3% (95%CI 57.9%-82.6%) in AMC-Pre≥0.285G/L group and 95.5% (95%CI 82.4%-100%) in AMC-Pre <0.285G/L group (P=0.013). The 5-year PFS was 56.7% (95%CI 43.8%-69.6%) in AMC-Pre≥0.285G/L group and 85.2% (95%CI 69.5%-100%) in AMC-Pre <0.285G/L group (P=0.004). In the multivariate analysis, AMC-Pre remained an independent prognostic factors for OS and PFS, with hazard ratios of 3.054 (95%CI, 1.543–6.047; P=0.001) and 2.598 (95%CI, 1.435–4.703; P=0.002). Higher IPI score at diagnosis was a significant prognostic factor associated with better overall survival unexpectedly, with hazard ratios of 0.348 (95%CI, 0.135–0.899; P=0.029). Conclusions: AMC≥0.285G/L before APBSCT could be a prognostic indicator of poor OS and PFS independent of the IPI score at diagnosis.
Prevalence of sarcopenia and predictors of body composition among women with early-stage breast cancer.
Authors: Elizabeth (Cespedes) Feliciano, Bette Jane Caan, Carla Prado, Candyce Kroenke, Stacey Alexeeff, Patrick T Bradshaw, Erin Weltzien, Adrienne Castillo, Wendy Y. Chen
Journal: Journal of Clinical Oncology (2017)

160 Background: Body mass index (BMI) does not accurately reflect body composition, particularly among cancer survivors. Sarcopenia (low skeletal muscle mass) and low muscle radio-density (MD; suggesting fat infiltration into muscle, compromising function) increase risk of surgical complications and chemotherapy toxicity and are associated with worse survival in advanced cancer. Little is known about the prevalence or predictors of sarcopenia and low MD in early-stage breast cancer. Methods: We studied 2,914 Kaiser Permanente members diagnosed with Stage I-III breast cancer from 2005-2013. Using computed tomography (CT) scans of the third lumbar vertebra from clinical care, we determined sarcopenia (skeletal muscle index &lt; 41 muscle [cm 2 ]/height [m 2 ]) and low MD ( &lt; 25-Hounsfield Units for non-obese; &lt; 33 for obese) using published cut points. We assessed associations with characteristics including age, race, BMI, age, stage, lifestyle and co-morbidities with logistic regression. We also examined moderate/vigorous physical activity among a subset of 672 women with activity questionnaires. Results: At diagnosis, mean age was 56 years and time to CT was 1 month. Both sarcopenia and low MD were common among early-stage breast cancer survivors (40% and 38% respectively). In multivariate analyses, the odds of sarcopenia and low MD increased with age (per 5 years, Odds Ratio [OR] 95% Confidence Interval [CI] of OR = 1.33; 95%CI: 1.27, 1.39 and OR = 1.41; 95%CI: 1.35, 1.47 respectively). The odds of sarcopenia decreased with greater BMI (OR = 0.80; 95%CI: 0.78, 0.82 per kg/m 2 ), while the odds of low MD increased (OR = 1.03; 95%CI: 1.01, 1.04 per kg/m 2 ). Black race was associated with lower odds of sarcopenia and low MD, while physical activity levels were associated with lower odds of sarcopenia and more favorable MD. Conclusions: Sarcopenia and low MD are highly prevalent among breast cancer survivors. While older age is strongly associated with these conditions, they occur across ages and stages. Differences in body composition by race and age may underlie differences in the association of BMI with cancer outcomes; understanding these may help guide clinical interventions.
Double blind multicenter phase III GORTEC trial evaluating the efficacy of oral immune modulating formulae therapy during adjuvant radiochemotherapy in head and neck squamous cell carcinoma (HNSCC).
Authors: Pierre Boisselier, Pierre Graff-Cailleaud, Christian Sire, Olivier Gallocher, Sandrine Lavau-Denes, Muriel Garcia-Ramirez, Marc Alfonsi, Didier Cupissol, Marie-Christine Kaminsky, Stephanie Fiore, Nicolas Flori, Helene de Forges, Renaud Garrel, Chloe Janiszewski, Simon Thezenas, Pierre Senesse
Journal: Journal of Clinical Oncology (2015)

6066 Background: A previous phase II study showed that an oral immunomodulating formula could reduce severe toxicities and increased survival for HNSCC with concomitant cisplatin and irradiation treatment (1). We conducted a double blind prospective phase III multicenter trial. Methods: In 20 GORTEC centers after surgery with curative intent and previous standard radiochemotherapy (2, 3), 180 patients were randomly assigned to receive oral supplementation (3 bags/day, a formula enriched with L-arginine, ω-3 fatty and ribonucleic acids vs an isocaloric isonitrogenous control) for 5 days before each cycle of cisplatin. Statistical analysis was done according to an intent-to-treat (ITT) and per protocol (PP) principle. Acute mucositis (RTOG and WHO scales) and 24-months survival were analyzed. Results: ITT included 172 patients and PP, the 109 patients with a product compliance ≥ 75%. No difference was identified one month after the end of radiochemotherapy on grade 3-4 mucositis, for ITT and for PP, with both scales, RTOG (p = NS) and WHO (p = NS). In accordance with the phase II study, disease-free survival was significantly improved by the immunomodulating formula (p = 0.004) in PP patients, and a statistical trend was observed in overall survival (p = 0.07). In ITT patients, both overall and disease-free survivals were not significant (p = 0.22 and p = 0.07, respectively). Median disease-free and overall survivals were not reached. Conclusions: Oral supplementation with an immunomodulating formula did not reduce grade 3-4 mucositis but showed significant increase of disease-free survival in product compliant patients (PP). Long term follow-up of our study along with further investigations are needed to confirm these findings and perhaps could open a new avenue for standard treatment of HNSCC. Acknowledgements: We thank the Ligue Nationale contre le Cancer and the Fondation Xavier Leverve for funding and Nestlé International for the product. (1) Assenat E et al. Eur J. Clin Nut Met 2011 (2) Cooper JS et al. NEJM 2004 (3) Bernier J et al. NEJM 2004 Clinical trial information: 2009-A00384-53.