tbuckley/cabot-search huggingface dataset:
Outcomes of radical conformal radiotherapy and concomitant cisplatin chemotherapy for olfactory neuroblastoma—Review of a single centre experience
Authors: A. D. Nikapota, T. Sevitt, V. J. Lund, D. Howard, M. F. Spittle, T. Prior, M. I. Saunders, M. Varughese, D. M. Carnell
Journal: Journal of Clinical Oncology (2006)

5555 Background: Olfactory neuroblastoma is rare with 25 new cases annually in the UK. Cranio-facial resection and post operative radiotherapy is standard treatment. The use of concomitant chemotherapy has not been fully evaluated, although chemo-sensitivity has been demonstrated by retrospective series. This study evaluates the use of radical radiotherapy and concomitant chemotherapy. Methods: Since 1978 more than 70 patients have been seen at the Institute of Otology and Laryngology. Eighteen patients treated with radiotherapy between 1999 and 2005 were reviewed. These were all CT planned and treated with conformal radiotherapy ± cisplatin chemotherapy 100 mg/m 2 D 1, 22 and 43. The radiotherapy prescribed dose varied from 50Gy to 62 Gy in 1.8 to 2 Gy fractions, 10 (56%) received 60Gy in 30 fractions. Overall survival, disease free survival and treatment related morbidity were assessed. Results: Seventeen patients were post operative and 1 was neo-adjuvant. Mean age was 46 years (range 20–83) and the majority were Kadish stage C. Of the 17 post-operative patients, 13 (76%) had surgery as primary treatment and 4 (24%) for recurrence. Eight patients (44%) received concomitant chemotherapy. At the time of analysis follow up ranged from 4 months to 72 months (median 17.5, mean 28.2), 16 (88.9%) patients were alive and 14 (77.8%) disease free. Four (22.2%) patients developed recurrence and 2 died of disease. Of the 4 patients with recurrence, 3 did not receive concurrent cisplatin chemotherapy and the fourth patient did not undergo radical surgery. No patients reported deterioration in vision or significant morbidity following treatment. Conclusions: Post operative radiotherapy with concurrent cisplatin chemotherapy is effective and well tolerated in the management of olfactory neuroblastoma. Where concurrent chemotherapy was not given, relapse rates were high. Our results, although immature, suggest disease free survival superior to published data. A prospective multi-centre study to evaluate concomitant treatment schedules is required. No significant financial relationships to disclose.
Allografting for patients with advanced hematological malignancies: non-myeloablative conditioning followed by the reinfusion of lymphocytes engineered with hsv thymidine kinase gene
Authors: Paolo Corradini, Corrado Tarella, Marco Bregni, Paola Carrera, Magda Marcatti, Alessandra Pescarollo, Fabio Ciceri, Andres Ferreri, Alessandro M. Gianni, Claudio Bordignon
Journal: Blood (2000)
Breast cancer incidence after hormonal treatments for infertility: Systematic review update.
Authors: Matteo Puntoni, Mauro Costa, Laura Paleari, Mariapia Sormani, Nicoletta Provinciali, Andrea De Censi, Paolo Bruzzi, Alessandra Gennari
Journal: Journal of Clinical Oncology (2015)

e11552 Background: The increasing practice of hormonal infertility treatments (HITs) raised concerns about their effects on breast cancer (BC) risk. Available evidence reported conflicting results. The aim of this study was to assess the potential association between HITs and BC risk. Methods: Literature was searched through December 2014. Eligible studies included cohort studies reporting BC incidence in women undergone HITs. Data were analyzed with standard meta-analytic techniques. Subgroup analyses were performed by type of intervention (IVF versus NO IVF), follow-up duration ( < 10 versus > 10 years) and type of control (population versus infertile). Results: Twenty eligible studies (207.914 women, 2347 BC) were retrieved: no increased risk was detected (SRR = 1.05, 95%CI: 0.96-1.14), with a significant heterogeneity (I2 = 59%, p = 0.001) among studies. In the 7 studies with the In Vitro Fertilization (IVF) procedure, no increase in BC risk was observed (SRR = 0.96, 95%CI: 0.80-1.14); in the 3 NO IVF studies, an increased BC risk was identified (SRR = 1.26, 95%CI: 1.06-1.50). A borderline interaction between type of intervention (IVF versus NO IVF) and BC risk was observed (p = 0.06). An increased risk with longer follow up ( ≥ 10 versus < 10 years) was detected (SRR = 1.13, 95%CI: 1.02-1.26 versus SRR = 0.95, 95%CI 0.85-1.06). Conclusions: Overall, HITs are not associated with an increased BC risk. In particular, no increased risk was observed in women undergoing IVF. Conversely, an increased in BC risk cannot be ruled out with older treatment protocols based on clomiphene. The long-term administration of clomiphene outside the current indications should be discouraged because of a possible increase in BC risk.
Cabazitaxel plus cisplatin coadministration and drug-interaction study in patients with advanced solid tumors.
Authors: Alain C. Mita, Shankar Sundaram, John Sarantopoulos, Monica M. Mita, Alex R. Lane, Jennifer L. Moseley, Devalingam Mahalingam, Benjamin R. Tan, Jean-Francois Dedieu, Diane Stash, Xin Zhi, Florent Mazuir, Albert C. Lockhart
Journal: Journal of Clinical Oncology (2012)

e15116 Background: Cabazitaxel (Cbz) is a novel taxane with in vivo efficacy in taxane-sensitive and -resistant tumors. Therapeutic synergism of Cbz/cisplatin (Cis) has been shown in tumor-bearing mice. Since Cbz is primarily metabolized by CYP3A, drug interactions may occur with modulators of CYP3A. Methods: The primary objective of part 1 of this phase I study (NCT00925743) was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of Cbz/Cis. Secondary objectives included safety, pharmacokinetics (PK) and efficacy. The objective of part 2 was to assess efficacy at the MTD. The effect of the antiemetic aprepitant (a moderate CYP3A inhibitor) on the PK of Cbz was also examined. Eligible patients (pts) had ECOG PS ≤ 1 and confirmed metastatic or unresectable solid tumors for which Cis therapy was considered appropriate. A 3 + 3 dose escalation at a starting dose (level 0) of 20/75 mg/m 2 (Cbz/Cis), administered IV Q3W, was used. The MTD was the highest dose at which 0/3 or ≤ 1/6 pts experienced a DLT in Cycle 1. Results: Pts (n = 25; 10 in part 1; 15 in part 2) with a median age of 56 yrs were enrolled. The most frequent primary tumors were lung (n = 4), prostate, ovary and pancreas (each n = 2). Of 6 evaluable pts, 2 had a DLT at dose level 0 (Grade 3 acute renal failure; febrile neutropenia). The MTD was 15/75 mg/m 2 as no DLTs were observed; 18 pts were treated at the MTD and 60 cycles were administered (median = 3; range 1–8). The most frequent non-hematologic treatment-related adverse events (all grades/grade 3–4) were nausea (78%/22%), vomiting (72%/11%), fatigue (61%/17%), anorexia (67%/11%) and diarrhea (44%/0%). Incidence of grade 3–4 neutropenia was 78%; 1 pt had febrile neutropenia. The combined PK profile of Cbz/Cis did not appear to differ vs those of the single agents. The ratio of Cbz clearance with vs without aprepitant co-administration was 0.81 (90% CI 0.36–1.85). Stable disease was seen in 11 pts; 1 pt (prostate carcinoma) had an unconfirmed partial response. Conclusions: The MTD of Cbz/Cis was 15/75 mg/m 2 . The combination had a manageable safety profile consistent with a platinum/taxane combination. No PK interactions between Cis and Cbz were seen; aprepitant did not appear to alter the PK of Cbz.
A Multicenter, Open-Label Study of Posaconazole Oral Suspension in Treatment of Patients with Invasive Fungal Infection Refractory to or Intolerant of First-Line Therapy,
Authors: Xiaojun Huang, Fengrong Wang, Yuhong Chen, Ting Liu, Jianxiang Wang, Jianda Hu, Jie Jin, Fangping Chen, Shujie Wang, Zhixiang Shen, Li Yu, Kang Yu, Yingmin Liang
Journal: Blood (2011)
Hepatitis B- and C-associated hepatocellular carcinoma in a large U.S. cancer center: Do clinicopathologic features or patient outcomes differ by the potentially causative viruses?
Authors: Marc Isamu Uemura, Ahmed Omar Kaseb, Reham Abdel-Wahab, Kanwal Pratap Singh Raghav, Gehan Botrus, Ernest Hawk, Robert A. Wolff, Jeffrey Morris, Manal Hassan
Journal: Journal of Clinical Oncology (2015)

4011 Background: Hep B virus (HBV) and hep C virus (HCV) are the main viral causes of hepatocellular carcinoma (HCC) development and are responsible for ~50% of USA cases. Because HBV is a DNA virus (Hepadna family) and HCV is an RNA virus (flavivirus family), it is unclear whether such virologic differences influence clinico-pathologic features of HCC or patient outcomes. We evaluated such differences in a large-scale, single-center study. Methods: Between 1992 to 2011, 815 HCC patients (HCV = 472, HBV = 343) were referred for treatment at the Univ. of Texas MD Anderson Cancer Center. Under IRB approval, detailed patient characteristics at time of diagnosis were documented. Chi-square tests were used to assess the significance of differences in the distributions of categorical variables between HBV and HCV groups. Median survival (mos.) was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Results: 63% of patients were Texas residents with male to female ratio = 3:1. Patients with HBV were more likely to develop HCC at younger age than HCV patients, with poorly differentiated tumor (PDT), portal thrombosis (PT), larger tumor size (> 5 cm), extensive liver involvement (> 50%), high alpha-fetoprotein, and advanced CLIP stage (3-6). On the other hand, patients with HCV were more likely to exhibit underlying cirrhosis, have a history of greater alcohol and cigarette use, and had higher co-occurrence of diabetes mellitus (DM). One-year survival rates were similar between both groups (43.3%) and median survivals were 10.9 and 9.3 mos. for HCV and HBV, respectively (P = 0.9). Conclusions: Significant clinico-pathologic variations exist in HCC patients associated with HCV vs HBV, which may impact patients’ eligibility for treatment, but not prognosis. Mean +/- SD (age) and proportion (%) of HCC characteristics in HCV and HBV. Age PDT PT > 5cm > 50% Cirrhosis CLIP(3-6) Smoke Alcohol DM STT LAT AFP HCV 61.3 ± 10 18.8 30.2 35.2 26.6 86 36.9 73 70.1 23.5 27.5 27.4 17894 ± 4662 HBV 57.4 ± 14 26.5 35.7 49.4 42.9 59.5 44 56.4 49.3 18.3 36.9 17.2 55708 ± 1095 p <.001 .001 .05 .02 < .001 < .001 .03 < .001 < .001 .05 < .001 < .001 < .001
Sorafenib and metformin in pretreated patients with stage IV non-small cell lung cancer with a <i>KRAS</i> mutation: A multicenter single arm phase II study.
Authors: Wouter Willem Mellema, Sjaak A. Burgers, Harry J.M. Groen, Anne-Marie C. Dingemans, Erik Thunnissen, Danielle Heideman, Egbert F. Smit
Journal: Journal of Clinical Oncology (2014)

e19015 Background: At present, no targeted treatment is available for KRAS-mutated non-small cell lung cancer (NSCLC). In vitro, we found support for synergistic effects of sorafenib and metformin in KRAS-mutated NSCLC cell lines, which provided the rationale for this study. Methods: Patients with advanced NSCLC with a KRAS mutation, good performance score (PS; 0-1) pretreated with platinum-containing chemotherapy were included in this single arm phase II study. Treatment consisted of sorafenib 400 mg BID and metformin 1,000 mg BID until disease progression or unacceptable toxicity. Primary endpoint was disease control rate (DCR) at 6 weeks. Secondary endpoints were progression free survival (PFS), overall survival (OS) and treatment-related toxicity. A Simon's optimal design was implemented. Based on previous reported efficacy of sorafenib monotherapy [Dingemans AM et al. Clin Cancer Res. 2013 Feb 1;19(3):743-51], a DCR of at least 70% was set to declare sufficient activity of sorafenib and metformin combination therapy. Results: Fifty-five patients were included between 1st of July 2012 and 1st of June 2013. Median age 60 (34-77) years; 51% Female; PS 0: 38%. All patients had stage IV disease. 53% of the patients received >1 previous line of chemotherapy treatment. One patient never started treatment and was excluded from further analysis. After 6 weeks of treatment, 2 patients had a partial response, 30 patients stable disease and 22 patients had progressive disease; DCR: 59%. Median PFS was 2.3 months and median OS was 5.3 months. Grade III or more treatment related toxicity was reported in 17 patients (31%), mainly gastrointestinal. Two patients had a bowel perforation (grade IV) and 1 patient had grade V hemoptysis. Conclusions: Combination therapy of sorafenib and metformin showed insufficient activity compared to previously reported results of sorafenib monotherapy in pretreated stage IV NSCLC patients with a KRAS mutation to justify further clinical testing. Clinical trial information: NL38229.029.11.
In Vitro Comparison of Different TKI Activity in T-Cell Populations: Selective Sparing of Treg By Nilotinib
Authors: Elena Marinelli Busilacchi, Andrea Costantini, Nadia Viola, Benedetta Costantini, Antonella Poloni, Jacopo Olivieri, Francesco Saraceni, Giorgia Mancini, Attilio Olivieri
Journal: Blood (2016)
Post diagnosis weight gain and the role of exercise in breast cancer survivors.
Authors: Tara Beth Sanft, Marty Alvarez-Reeves, Melinda Irwin
Journal: Journal of Clinical Oncology (2012)

9007 Background: Obesity is linked to poor breast cancer (Br Ca) outcomes including higher risk of recurrence and death. No study has examined if post-diagnosis weight (wt) gain modifies the effect of exercise interventions on body composition. We examined wt change from diagnosis (diag) to enrollment (enroll) into a 6-mo randomized trial of exercise v. usual care to explore if post-diagnosis wt gain modified the effect of exercise on body wt, body fat, lean body mass (LBM) and bone mineral density (BMD) in breast cancer survivors. Methods: 75 inactive Br Ca survivors were recruited and randomized to exercise (n = 37) or usual care (UC) (n = 38). At baseline, women completed a questionnaire assessing self-report wt at diag and at the time of enroll into the study (~3 yr). The exercise group participated in 150 min/wk of supervised exercise. The UC group maintained their physical activity level. Body composition was assessed at enroll and 6-mo via dual-energy X-ray absorptiometry (DXA) by one radiologist blinded to intervention group. Results: Wt and DXA data were available for 68 / 75 participants. On average, women gained 3.3±8.2 kg from diag to enroll, with 53% gaining wt (mean = 8.9 ± 6.8 kg) and 47% maintaining or losing wt (mean change = -2.9 ±3.9 kg). The majority of wt gain occurred among women who were non-obese at diag (BMI &lt; 30), with 60% of non-obese women gaining wt (mean = 8.0 ± 6.8 kg) compared with 38% of obese women gaining wt (mean = 12.2 ± 6.4 kg). Those randomized to exercise lost body fat including women who gained wt since diag (mean % fat loss for exercisers (-0.92 ± 0.31) vs. UC (0.36 ±0.30), p = .0063) and women who did not gain wt since diag (mean % fat loss for exercisers (-0.65 ± 0.39) vs. UC (0.45±0.47), p = .08) even after adjusting for obesity status at diag. Similar improvements in LBM and BMD were observed with exercise in women who did or did not gain wt since diag. Conclusions: Wt gain in Br Ca survivors is common, the majority of weight gain in this study occurred among women who were not obese at diag. Exercise led to body fat loss and other favorable body composition changes among both non-obese and obese women. Exercise and other wt management programs should be offered to all Br Ca survivors regardless of BMI at diagnosis as a strategy towards prevention of wt gain.
Real-world evidence (RWE) to show improved time to progression among resected pancreatic cancer (RPC) patients receiving adjuvant chemotherapy (adjch).
Authors: Jonathan Kish, Bruce A. Feinberg, Tracy Maida, Craig Biggs, Urvi Mujumdar, Dhruv Chopra, Jalyna R. Laney, Eugene Kennedy
Journal: Journal of Clinical Oncology (2017)

242 Background: Two recent clinical trials (IMPRESS and APACT) suggest the overall survival (OS) of patients with resected pancreatic cancer (RPC) is far longer than previously believed. Improvements in patient selection, intra/post-operative surgical care adjch are suggested as explanations for the improved OS. RWE of time to progression (TTP) from surgery were calculated to assess if the results of these trials are generalizable. Methods: RPC patients (ICD-9=157.x, excluding 157.4; CPT=48140, 48146, 48150, 48152-5) diagnosed between 03/2012-06/2015 were selected from the Inovalon More 2 administrative claims database. Adjch was defined as initiating chemotherapy within 90 days of surgery. TTP was the time from surgery until the first claim for metastatic disease (ICD-9 =196.0-.3, .5-.6, 197.0-.8, 198.0-.8) using the Kaplan-Meier method. Patients without a metastatic diagnosis during their follow-up were censored at 12 months to adjust for underreporting of metastatic disease codes in claims. Results: 1,014 RPC patients selected. Mean follow-up time was 12.9 months (SD = 10.8). Mean age at diagnosis was 62.7 years (SD = 13.0) and 39.7% (n=403) had commercial insurance, 40.9% (n=415) Medicare and 18.5% (n=188) Medicaid. Of all RPC patients, 54.4% (n=552) received any chemotherapy of which 59.8% (n=330) was adjch; 37.4% (n=379) were diagnosed with metastatic disease at the time of or following resection. The rate of progression events was 40.5% (n=277) without adjch and 30.9% (n=102) with adjch (p&lt;0.01). Among all resected patients, median TTP was 15.7 months (95% CI: 13.8-26.0) with 93.7% (n=355) of progression events by 12 months. Median TTP was 20.4 months (95% CI: 15.5-NR) in patients receiving adjch vs 17.7 months (95% CI: 17.7-31.5) without adjch (p=&lt;0.0001). Conclusions: This analysis demonstrated a 2.7 month longer TTP for patients who received adjch compared to those who did not (p&lt;0.0001). The median TTP in both adjch and non-adjch groups was longer than the observed in the ESPAC-1 trial for adjch patients TTP (15.3 months) and OS (20.1 months). These data support a new baseline for efficacy in adjch trials and are in line with more recent RCT estimates.
Impact of total therapies on clinical outcome of myeloma stratified by risk and molecular subgroups.
Authors: Christoph Johann Heuck, Niels Weinhold, Sharmilan Thanendrarajan, Caleb Konrad Stein, Frits Van Rhee, Adam Rosenthal, Yogesh Jethava, Rashid Khan, Antje Hoering, Faith E Davies, Bart Barlogie, Gareth John Morgan
Journal: Journal of Clinical Oncology (2015)

8586 Background: Despite the introduction of new agents multiple myeloma (MM) is a disease with unpredictable clinical course consistent with it being composed of a variety of subtypes with distinct molecular features. In order to shed light on the impact of this molecular heterogeneity on treatment response we examined clinical outcomes in our series of Total Therapy (TT) trials, stratified by risk status and molecular subgroup. Methods: We included 1318 patients with available baseline gene expression profiling (GEP) data enrolled on Total Therapy 2–5, stratified by GEP70-defined risk and molecular subgroup. We analyzed their effect on outcomes and timing of treatment failure in relation to protocol phase. Results: For GEP70-defined low risk (LR) MM, PFS and OS has incrementally improved with addition of thalidomide in TT2 and bortezomib (Bz) in TT3a and 3b. While Bz improved outcomes for LRMM within the MS molecular subgroup, it had no significant impact on MF cases. Outcomes for patients treated on TT4 designed for LRMM were similar to TT3a/b. The lower intensity treatment arm TT4-L had inferior outcomes compared to the standard arm. However patients with adverse cytogenetics had improved outcomes on TT4-L. Treatment failures in LRMM were rare and not correlated to treatment phase. CR rates in high-risk (HR) MM are similar to LRMM. Yet a more dose-dense chemotherapy in Total Therapy (TT) 5 failed to improve survival in HRMM. For HRMM treated on TT2 and 3, treatment failures occurred early in the inter-transplant or consolidation phases. Interestingly with dose dense therapy in TT5 treatment failure was not seen until the maintenance phase. Conclusions: HRMM has a distinct clinical course with high rates of primary refractory disease and early relapse. Changing therapy for HRMM from dose intense to dose dense has shifted treatment failure from the inter-transplant to the maintenance phase, which is now a setting where novel approaches can be used. For LRMM we can define distinct clinical response and outcome patterns dependent upon GEP-defined molecular subgroups. This differential response dependent upon treatment used at induction opens the potential for adjusting maintenance to take account of the disease subtype. Clinical trial information: NCT00869232.
Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control
Authors: C Pawlyn, M D Bright, A F Buros, C K Stein, Z Walters, L I Aronson, F Mirabella, J R Jones, M F Kaiser, B A Walker, G H Jackson, P A Clarke, P L Bergsagel, P Workman, M Chesi, G J Morgan, F E Davies
Journal: Blood Cancer Journal (2017)

Abstract Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly defined high-risk patients who continue to do badly. Novel therapeutic approaches are, therefore, required. A growing number of epigenetic inhibitors are now available including EZH2 inhibitors that are in early-stage clinical trials for treatment of haematological and other cancers with EZH2 mutations or in which overexpression has been correlated with poor outcomes. For the first time, we have identified and validated a robust and independent deleterious effect of high EZH2 expression on outcomes in myeloma patients. Using two chemically distinct small-molecule inhibitors, we demonstrate a reduction in myeloma cell proliferation with EZH2 inhibition, which leads to cell cycle arrest followed by apoptosis. This is mediated via upregulation of cyclin-dependent kinase inhibitors associated with removal of the inhibitory H3K27me3 mark at their gene loci. Our results suggest that EZH2 inhibition may be a potential therapeutic strategy for the treatment of myeloma and should be investigated in clinical studies.