tbuckley/cabot-search huggingface dataset:
Preliminary evidence of activity of pralatrexate in relapsed/refractory ovarian cancer.
Authors: Nashat Y. Gabrail, Carrie L. Smith
Journal: Journal of Clinical Oncology (2012)

e15557 Background: Pralatrexate, a novel antifolate, is approved in the US for the treatment of relapsed/refractory peripheral T-cell lymphoma at a dose of 30mg/m 2 weekly for 6 weeks of a 7-week cycle. Previous studies in solid tumors have focused on a q2w schedule at 190mg/m 2 . As pralatrexate is 30-40% renally excreted, an ongoing renal impairment study is investigating the impact of mild, moderate and severe renal impairment on pralatrexate distribution in patients with hematological malignancies and solid tumors. As folate receptor alpha is frequently overexpressed in epithelial ovarian cancers, we hypothesized that ovarian cancer may be a target for pralatrexate treatment and therefore have included a number of ovarian cancer patients in this trial. Methods: Patients with solid tumors and hematological malignancies were enrolled in a phase I clinical trial. Patients are treated in cohorts depending on renal function normal, mild renal insufficiency, moderate renal insufficiency and severe non-dialysis dependent renal failure. This analysis is limited to 6 patients with refractory ovarian cancer. The dose of pralatrexate is 30mg/m 2 weekly for 6 weeks of a 7-week cycle, with dose adjustment depending on toxicity. Results: The 6 patients, all with stage 4 refractory ovarian cancer had received 4 or more prior chemotherapy regimens and had refractory disease, defined as, nonresponsive to the last chemotherapy regimen or progression within 3 months of the last dose of chemotherapy. Of the 6 patients, 2 experienced objective responses lasting 9 months and 4 months respectively. Disease response was assessed by CA- 125 and RECIST criteria. Two patients experienced stable disease for 4 months and 5 months respectively. One patient had grade 5 mucositis after the second weekly dose and one patient had progressive disease after disease stabilization for 3 months. Conclusions: Pralatrexate given at a dose of 30mg/m 2 to patients with refractory ovarian cancer has demonstrable activity that needs to be confirmed in well-designed efficacy trials. Importantly, this is the first demonstration of clinical activity in a solid tumor at the currently approved dose.
Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy.
Authors: Orin Bloch, Jeffrey J. Raizer, Michael Lim, Michael Sughrue, Ricardo Komotar, Jonathan Abrahams, Donald O'Rourke, Anthony D'Ambrosio, Jeffrey N. Bruce, Andrew Parsa
Journal: Journal of Clinical Oncology (2015)

2011 Background: Standard therapy for glioblastoma (GBM) consists of surgical resection followed by concurrent chemo and radiotherapy with a median overall survival of 16 months. In this phase II, single arm study, addition of an autologous heat shock protein peptide vaccine was evaluated for newly diagnosed GBM. Expression of PD-L1 on peripheral monocytes has been shown to be elevated in GBM patients and was evaluated as a predictor of survival. Methods: Adult patients with GBM underwent surgical resection followed by chemoradiotherapy. Vaccine was generated from tissue obtained at surgery. Key eligibility criteria included ≥ 90% tumor resection and collection of sufficient tumor tissue to generate at least four 25 μg doses of vaccine. Within 5 weeks of completing radiotherapy, patients received weekly vaccinations, followed by adjuvant temozolomide with monthly vaccinations until depletion of vaccine or tumor progression. The primary endpoint was overall survival. Relative PD-L1 expression on circulating monocytes was measured from peripheral blood obtained at surgery. Results: A total of 46 patients from eight centers received the vaccine in addition to standard therapy. Median progression-free survival was 17.8 months (95% Confidence Interval [CI], 11.3-21.6) and median overall survival was 23.8 months (95% CI, 19.8-30.2). The vaccine was well-tolerated with no severe (grade 3 or 4) events attributed to vaccination. The median overall survival for patients with high PD-L1 expression (above the median, 54.5% of monocytes) was 18.0 months (95% CI, 10.0 – 23.3) as compared to 44.7 months (95% CI not calcuable) for low PD-L1 expressors (hazard ratio for death 3.35; 95% CI, 1.36 – 8.23; p = 0.003). A multivariate proportional hazards model revealed MGMT methylation status and PD-L1 expression as the greatest independent predictors of survival. Conclusions: Vaccination with autologous tumor-derived heat shock proteins improves survival compared to standard therapy for newly diagnosed GBM. Systemic immunosuppression driven by peripheral monocyte expression of PD-L1 is a previously unidentified factor that may mitigate vaccine efficacy. Clinical trial information: NCT00905060.
Endocrine therapy in early breast cancer: Encouraging observations in a nontrial setting.
Authors: Susan Faye Dent, Michelle M. Campbell, Freya Crawley, Mark J. Clemons, Xinni Song
Journal: Journal of Clinical Oncology (2012)

587 Background: Poor adherence to adjuvant endocrine therapy (ET) in women with hormone receptor positive (HR +) early breast cancer (EBC) is well documented. Given the availability of multiple ET strategies [aromatase inhibitor (AI) upfront, tamoxifen (TAM) to AI, AI after 5 years TAM], we evaluated the delivery of ET in a non-trial setting. Methods: Post-menopausal women with HR + EBC treated with ET (that included an AI) at The Ottawa Hospital Cancer Center between 01/99 and 12/06 were included. Data was retrospectively collected and included: demographics, choice/duration of ET, adherence and toxicities. Results: In 626 patients (pts), median age 59 years (r: 30-92) with stage I (195 pts; 31 %), stage II (339 pts; 54 %) and stage III (88 pts; 14 %) EBC. Treatment strategies included: AI (s) only (251 pts; 40 %); TAM followed by AI (s) (323 pts; 51.6 %); AI (s) followed by TAM (16 pts; 2.6 %); TAM-AI (s)-TAM (24 pts; 3.8 %) and unknown (12 pts; 1.9 %). Prescribed AI therapy (upfront or sequential) was discontinued in 39 % of cases mainly due to toxicity (62.5 %) after median of 6, 9, or 12 months (ms) on exemestane, anastrazole and letrozole respectively. Common toxicities included: arthralgias (40.6 %), hot flushes (34 %), fatigue (25 %), myalgias (24.7 %) and osteoporosis (22.5%). In cases (177) where AI therapy was discontinued due to toxicity: 98 received no further ET, 29 TAM and 50 another AI. The majority of pts received at least 5 years of ET (79 %; median duration 64 ms; r 1-156 ms) and 376 pts (60 %) completed at least 5 years of AI therapy (median duration 59 ms; r: 1-124 ms). 9.9 % of pts are still receiving ET. Conclusions: This is one of the first non-clinical trial studies to demonstrate, that despite poor adherence to initial ET, the majority of women are able to complete five years of treatment (79 %). These results are encouraging and reflect the practical use of mutilple endorcrine strategies that have been shown to be efficacious in this pt population.
Scalp cooling alopecia prevention trial (SCALP).
Authors: Julie R. Nangia, Tao Wang, Mari Rude, Frankie Ann Holmes, Joyce O'Shaughnessy, Steven W. Papish, Richard Paxman, Susan G. Hilsenbeck, C. Kent Osborne, Mothaffar F. Rimawi
Journal: Journal of Clinical Oncology (2014)

TPS9660 Background: Adjuvant chemotherapy treats micro-metastatic disease and decreases the risk of breast cancer recurrence. However, it may be associated with distressing adverse effects, including alopecia. Women with breast cancer rate chemotherapy-induced alopecia as one of the most severe, troublesome, and distressing side effects of chemotherapy. In many countries, scalp cooling has been introduced to prevent or reduce chemotherapy-induced alopecia. Scalp cooling causes cutaneous vasoconstriction, which reduces blood flow to the hair follicles during peak plasma concentrations of the chemotherapeutic agents and therefore reduces cellular uptake of these agents. It also results in reduced biochemical activity, which makes hair follicles less susceptible to the damage of the chemotherapy agents. Success rates are variable, but scalp cooling appears to be effective in preventing chemotherapy-induced alopecia especially in more recent studies. Methods: We are conducting a multi-center randomized non-blinded controlled prospective trial to demonstrate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System in reducing the incidence of chemotherapy-induced alopecia. Women with stage I-II breast cancer will receive neoadjuvant or adjuvant anthracycline- or taxane-based chemotherapy, for at least four cycles are eligible. Participants will be randomized in a 2:1 ratio to scalp-cooling and will undergo scalp-cooling using the Orbis Paxman Hair Loss Prevention System prior to, during and after each chemotherapy administration. The primary efficacy endpoints are hair preservation, defined as CTCAE v4 alopecia <2, and device safety. Two hundred and thirty five (235) patients will be enrolled which will provide 85% power to detect a 20% difference in hair preservation, 15% in control group and 35% in scalp-cooling group . Secondary endpoints include: wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Study participants will be followed for 5 years post-study for time to first recurrence, overall survival, site of first recurrence, and incidence of isolated scalp metastasis. Clinical trial information: NCT01986140.
포스터전시 : B형 및 C형간염바이러스감염과 췌장암 발생의 연관성에 관한 연구
Authors: 홍승권, 윤아일린, 이현정, 이영선, 정영걸, 김정한, 정은석, 황진기, 주문경, 김지훈, 임형준, 연종은, 박종재, 김재선, 박영태, 변관수
Journal: Clinical and Molecular Hepatology (2009)
A Phase II study of the safety and efficacy of alpelisib or buparlisib plus letrozole in neoadjuvant treatment of postmenopausal women with HR+/HER2–, PIK3CA mutant or wild-type breast cancer.
Authors: Ingrid A. Mayer, Christian F. Singer, Peter A. Fasching, Frankie Ann Holmes, Michael Gnant, Laura G Estevez, Mario Campone, Michael Hubalek, Antonio C. Wolff, Jose Alejandro Perez-Fidalgo, Eric P. Winer, Gena Atalla-Vidam, Charu Kanwal, Lars Blumenstein, Nathalie Fretault, Ivan Diaz-Padilla, Carlos L. Arteaga
Journal: Journal of Clinical Oncology (2015)

TPS633 Background: The PI3K/AKT/mTOR pathway is the most frequently activated signaling pathway in breast cancer (BC). PIK3CA-activating mutations are the most common genetic alteration observed in hormone receptor-positive (HR+) BC. In preclinical studies of HR+ BC, alpelisib (PI3Kα inhibitor) and buparlisib (pan-PI3K inhibitor) demonstrated significant antitumor effects both in vitro and in vivo when combined with hormone therapy. Methods: A Phase II, randomized, double-blind, placebo-controlled trial of alpelisib/placebo (300 mg once daily [QD]) or buparlisib/placebo (100 mg QD; intermittent regimen [5 days on; 2 days off]) plus letrozole (2.5 mg QD) for the neoadjuvant treatment of postmenopausal women with HR+/HER2– BC (NCT01923168). Key inclusion criteria are stage T1c–T3, any N, M0 operable BC; measurable disease; HR+/HER2– BC; known PIK3CAstatus (mutant vs wild-type [WT]) and Ki67 level; and Eastern Cooperative Oncology Group performance status ≤ 1. Key exclusion criteria are locally recurrent/met...
Prostate cancer in 671 hypogonadal men with and without long-term testosterone treatment: Results from a controlled registry study.
Authors: Ahmad Haider, Karim Sultan Haider
Journal: Journal of Clinical Oncology (2017)

33 Background: Despite persisting concerns, there is no evidence that TTh in men with hypogonadism increases PCa incidence or severity. Rather, a Canadian group recently found that long-term TTh decreased the risk of PCa diagnosis (Wallis et al., Lancet Diab Endocrinol 2016; 4:498). We assessed incidence and severity of PCa in hypogonadal men on long-term TTh (T-group) in comparison to an untreated hypogonadal control group (CTRL). Methods: 375 men (age range: 33-70) with testosterone ≤ 350 ng/dL and symptoms received testosterone undecanoate 1000 mg every 3 months for up to 10 years. 296 hypogonadal men (57-74) opted against TTh. Median follow-up: 7 years. Prostate volume (PV), PSA, weight and C-reactive protein (CRP) were measured and digital rectal examination/transrectal ultrasound performed before treatment initiation and then regularly every 3-6 months. Biopsies were performed when indicated according to EAU guidelines. Results: In the T-group, PV increased slightly but significantly by 2.41 mL (p &lt; 0.0001), PSA by 0.22 (NS). In CTRL, PV decreased slightly but significantly by -1.20 mL (p &lt; 0.005), PSA by -0.38 (p &lt; 0.0001). Weight dropped by 18.23% in the T-group and increased by 1.78% in CTRL, CRP decreased significantly in the T-group and remained unchanged in CTRL. In the T-group, 8 men (2.1%) were diagnosed with PCa. In CTRL, 12 (4.1%) were diagnosed with PCa. The incidence per 10,000 years was 32 in the T-group and 64 in CTRL. The mean baseline age of PCa patients was 65 years in both groups. Prostatectomy was performed in all men. In the T-group, all patients had a Gleason score ≤ 6 and a predominant Gleason score of 3. Tumor grade was G2 in all 8 (100%), tumor stage T2a in 6 (75%) and T2b in 2 (25%) patients. In CTRL, Gleason score was &gt; 6 in all 12 patients. Three men had a predominant Gleason score of 3, 8 had 4, and 1 had 5. Tumor grade was G2 in 5 (41.7%) and G3 in 7 (58.3%) patients, tumor stage T2b in 1 (8.3%), T2c in 1 (8.3%), T3b in 4 (33.3%) and T3c in 6 (50%) patients. Conclusions: TTh in hypogonadal men regularly monitored may decrease incidence of PCa compared to hypogonadal CTRL. PCa was less severe in the T-group. Weight loss and reduced inflammation by TTh may have contributed to our findings.
Trends in survival of patients with primary plasma cell leukemia: A population-based analysis from 1973 to 2010.
Authors: Wilson I. Gonsalves, Vincent Rajkumar, Ronald S. Go, Angela Dispenzieri, Martha Lacy, Vinay Gupta, Preet Paul Singh, Francis Buadi, Prashant Kapoor, David Dingli, John Anthony Lust, Suzanne R. Hayman, Steven R. Zeldenrust, Yi Lin, Robert A. Kyle, Morie A. Gertz, Shaji Kumar
Journal: Journal of Clinical Oncology (2014)

8608 Background: Primary plasma cell leukemia (pPCL) is a rare plasma cell malignancy with a very aggressive course and poor outcome compared to multiple myeloma (MM). There has been significant improvement in the survival of MM patients over the past decade as a result of the incorporation of novel agents that are now also used in pPCL. The time period after 1995 represented adoption of autologous stem cell transplantation as a standard treatment modality and 2003 marked the wide availability of the novel agents in the relapsed and refractory setting due to accelerated FDA approval. However, it was not until 2006 that these novel agents were approved to be utilized in the first-line treatment of MM. The question remains whether the survival of pPCL has improved since the advent of these novel agents. Methods: We analysed the Surveillance, Epidemiology, and End Results (SEER) database for trends in survival of patients with pPCL (ICD-O: 9733) over the time period of 1973-2010 using the SEER Stat 8.1.2software. Kaplan-Meier analysis was used to analyze the overall survival (OS) and the Cox proportional hazards model was used to assess the influence of various prognostic factors on OS. Results: A total of 318 pPCL patients were identified in the SEER database. The median age at diagnosis was 62 years (range, 19-91) and 52% were females. The median follow up was 56 months (range, 39-102) and 83% of patients had died at the time of this analysis. The median 1, 2 and 5-year OS rates were 57%, 32% and 6% respectively. The median OS based on time periods of diagnosis of 1973-1995, 1996-2002, 2003-2005 and 2006-2010 were 9, 9, 8, and 19 months, respectively (P = 0.002). OS was similar regardless of subgroups based on age, gender, and marital status at diagnosis. Among patients <70 years age, the median OS was 11 months compared to 10 months in patients >70 years age (P = 0.378). Only diagnosis in the 2006-2010 era predicted for a better OS (HR: 0.65; 95% CI: 0.45-0.94; P = 0.0018, with reference to 1973-1995 era). Conclusions: Our study identifies a recent major improvement in survival amongst patients diagnosed with pPCL within a large US population. This suggests a positive impact of incorporating novel agents in the treatment of pPCL since 2006.
Amphiregulin (AREG) SNP rs161511 to predict cetuximab efficacy independent of AREG mRNA levels: Data from FIRE3 (AIO KRK-0306).
Authors: Sebastian Stintzing, Stefan Stremitzer, Volker Heinemann, Andreas Jung, Yu Sunakawa, Satoshi Matsusaka, Shinichi Yamauchi, Wu Zhang, Dongyun Yang, Yan Ning, Ana Sebio, Diana L. Hanna, Saadat Siamak, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

3521 Background: Anti-bodies targeting the epidermal growth factor receptor (EGFR) have shown efficacy in metastatic colorectal cancer (mCRC). The extended RAS analysis has further defined EGFR dependent tumors that are more sensitive to EGFR inhibition. Beyond RAS mutations, expression of EGFR ligands (amphiregulin (AREG) and epiregulin (EREG)) have shown predictive values. The challenge to move these biomarkers into clinic are the standardization of quantitative intra-tumor measurements. If germline single nucleotide polymorphisms (SNPs) in AREG and/or EREG would be predictive this could easily used in clinical practice. We have previously shown that rs1615111 associated with time-to-recurrence in gastric cancer. Aim of this study was to test the predictive value of rs1615111 in cetuximab treated mCRC patients. Methods: Genomic DNA was isolated from tissue samples of 299 patients (median age 64 years, male 67.2%) treated in first-line with either FOLFIRI cetuximab (n=139) or FOLFIRI bevacizumab (n=160) from the FIRE-3 trial (NCT00433927). In 174 samples, tumor cells were micro-dissected for mRNA extraction. rtPCR was carried out using LightCycler technology. All patients were KRAS/NRAS wild-type. The bevacizumab arm served as negative control arm. Results: The minor allele A of rs1615111 was associated with decreased tumor response (37% vs. 78.4%, two-sided Fisher’s p=0.02) shorter progression free survival (5.9 months vs. 10.6 months, logrank p=0.001 HR 3.46) and OS (11.4 months vs. 33.1 months, logrank p=0.001, HR 3.87) in FOLFIRI plus cetuximab treated patients. Low AREG mRNA expression was associated with short OS (3.2 months vs. 33.1 months logrank p<0.001, HR 0.08) but no association with rs1615111 could be established. In FOLFIRI plus bevacizumab treated patients rs1615111 did not have any predictive value. Conclusions: AREG SNP rs1615111 is predictive for cetuximab treatment. No prognostic value could be established. Biological function of rs1615111 remains unknown as it was not associated with mRNA expression. Beyond RAS mutations and EGFR ligand expression SNPs in AREG are new promising predictive marker for EGFR inhibitors. Prospective studies to validate and confirm these data are warranted.
Characterization of Real World Treatment Patterns and Outcomes Among Older Adults with Chronic Lymphocytic Leukemia in the Pre Novel-Agents Era: An Analysis of the 2007-2013 SEER-Medicare Database
Authors: Anthony R. Mato, Jordan Jahnke, Pengxiang Li, Maneesha Mehra, Vrushabh P Ladage, Michelle Mahler, Scott F Huntington, Jalpa A Doshi
Journal: Blood (2016)
A single institutional experience of carbon-ion radiotherapy for locally advanced pancreatic cancer.
Authors: Makoto Shinoto, Yoshiyuki Shioyama, Hiroaki Suefuji, Shingo Toyama, Keiji Matsumoto
Journal: Journal of Clinical Oncology (2017)

461 Background: Carbon-ion radiotherapy (C-ion RT) has the potential advantages in terms of improved dose localization and enhanced biological effectiveness compared to conventional radiotherapy or proton therapy. C-ion RT is expected to contribute to the prolongation of survival in patients with pancreatic ductal adenocarcinoma (PDAC). We started C-ion RT for pancreatic cancer at SAGA HIMAT since April 2014. The aim of this study is to evaluate the clinical results of C-ion RT for locally advanced PDAC. Methods: From April 2014 to May 2016, 76 patients with pancreatic cancer were treated with definitive C-ion RT. 44 patients who were confirmed as unresectable locally advanced PDAC were included in this retrospective analysis. 32 patients were excluded because of resectable disease (n = 8), borderline disease (n = 6), without pathological confirmation (n = 20). C-ion RT was performed with 55.2 Gy (RBE) at 12 fractions in 3 weeks. The anti-tumor effect was evaluating using CT and FDG-PET according to RECIST ver. 4.0. Results: The median follow-up period was 12.8 (range 3.4-27.5) months from the initiation of C-ion RT. In all patients, planned C-ion RT was completed. Induction chemotherapy was performed in 35 (80%) and the median duration time was 3 (range 1-19) months. Forty patients (91%) underwent concurrent chemotherapy with gemcitabine or S-1. Local effect using CT criteria was CR in 2, PR in 5, and SD in 37. The evaluation adding FDG-PET criteria was CR in 25, PR in 6, and SD in 13. Five patients (11%) experienced local recurrence during follow-up period. Two patients who had SD by CT and CR by FDG-PET performed tumor resection and were revealed pathological CR. One and two-year survival rate from C-ion RT were 82% and 66%, respectively. The two-year survival rate from initial treatment was 75%. Only three patients (7%) experienced grade 3 toxicities that were leukopenia, anorexia, and gastric ulcer. There was no grade 4 or 5 toxicity. Conclusions: C-ion RT for locally advanced PDAC was effective and well tolerated. FDG-PET was useful for the evaluation of local effect after C-ion RT.
FDG PET/CT in pancreatic cancer staging and management: A retrospective study.
Authors: Ana Beatriz Kinupe Abrahao, Yee Ung, Yoo-Joung Ko, Scott R. Berry
Journal: Journal of Clinical Oncology (2017)

464 Background: FDG PET/CT scan (PET) has been approved by Cancer Care Ontario since 2011 for pancreatic cancer patients who have potentially resectable disease. A recent prospective study supported the use of PET in patients with a pancreatic mass and showed improved staging accuracy. Herein, we reviewed the outcomes of PET in the disease staging and management of patients with pancreatic mass at a single academic center. Methods: We collected demographics, CA 19-9 level, CT, MRI and PET results of patients with suspicious pancreas mass followed at Sunnybrook Health Sciences Centre from April to August 2011. We reviewed disease staging after CT/MRI and clinical management decision after PET result. We excluded patients with proven non-primary adenocarcinoma of the pancreas from the analysis. Results: In this cohort, 58 patients had PET scans. 14 patients with non-primary adenocarcinoma of the pancreas were excluded. From 44 patients analyzed, 61% of them were females, median age 70, 19 patients had biliary obstruction with biliary drain, CA 19.9 was elevated preoperatively in 27 patients (level above 1400 was seen in 37% of 44 patients), pancreatic mass median SUV = 4.8 and 7 patients had SUV &lt; 2.5 with no FDG avid at the pancreas mass (both biopsy proven). Ten patients were discovered to have metastatic disease on PET. PET results were discordant with the CT/MRI disease staging in 34% of cases. PET revealed metastatic disease in 7 patients with prior CT or MRI considered to be negative for metastasis. PET showed localized disease in 8 patients with suspicious metastasis on CT or MRI. However, none of the patients underwent pancreatic resection. Clinical management was changed after PET results in 80% of patients with discordant PET and CT/MRI results. Conclusions: In this single-centre retrospective analysis, PET results changed the metastatic disease status depicted by CT or MRI in 34% of patients and clinical management was guided by PET results for the majority of those patients. This supports the use of PET as a tool to guide staging and treatment of pancreas cancer.