tbuckley/cabot-search huggingface dataset:
A multicenter phase II study of docosahexaenoic acid (DHA) in patients (pts) with a history of breast cancer (BC), premalignant lesions, or benign breast disease.
Authors: Ayca Gucalp, Patrick Glyn Morris, Xi Kathy Zhou, Dilip D. Giri, Neil M. Iyengar, Katherine D. Crew, Dawn L. Hershman, Judy Ellen Garber, Julie R. Nangia, Elise D. Cook, Lana Vornik, Barbara Karen Dunn, Brandy M. Heckman-Stoddard, Kathleen Foster, Powel Brown, Andrew Dannenberg, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2014)

TPS1615 Background: Obesity is a risk factor for the development of BC and is associated with poorer cancer outcomes irrespective of BC subtype. Obesity is associated with diffuse white adipose tissue (WAT) inflammation manifest histologically as crown-like structures (CLS). The presence and severity of CLS in breast WAT (CLS-B) are associated with several proinflammatory mediators known to be involved in development of BC including TNF-α/COX-2/IL-1β and aromatase. DHA, an omega-3 fatty acid, can suppress inflammation by multiple mechanisms including inhibition of TLR4-activated signaling pathways that induce TNF-α and COX-2. We hypothesize that DHA will decrease the expression of key inflammatory mediators and down-regulate aromatase in breast WAT of overweight/obese women. Methods: This is a randomized placebo-controlled, double-blinded phase II study of DHA in overweight/obese pts with a history of stage I-III BC, DCIS/LCIS, Paget’s disease, or proliferative benign breast disease (NCT01849250). We aim to determine whether oral DHA for 12 weeks at 1,000 mg twice daily as compared to placebo reduces normal breast tissue levels of TNF-α. Secondary objective: To evaluate the effect of DHA on the change from baseline in levels of COX-2/IL-1β/aromatase/CLS-B. Inclusion:1) BMI ≥ 25. 2) ≥ 6 months from all prior BC treatment. 3) No clinical evidence of disease. 4) One breast unaffected by invasive cancer, which has not been radiated or surgically augmented. Exclusion: 1) DHA supplementation (> 200 mg/day). 2) Daily aspirin/NSAID use in the week preceding the trial. 3) Regular use of steroids or immunomodulators.Percent change in TNF-α mRNA levels in normal breast tissue between DHA and placebo arm will be compared using two-sample t-test. If normality assumptions are violated, a two-sample Wilcoxon rank-sum test will be used. With 30 subjects in each arm, we will have 80% power to detect effect size as small as 0.74 at 0.05 significance level using a two-sided, two-sample, Student t-test. Assuming a 10% dropout rate and 10% non-evaluable rate, up to 76 pts will be randomized. To date, 17 pts have been consented and 9 have been randomized to participate. Clinical trial information: NCT01849250.
Phase 2 trial of PRM-151, an antifibrotic agent, in patients with myelofibrosis: Stage 1 results.
Authors: Srdan Verstovsek, Ruben A. Mesa, Lynda M. Foltz, Vikas Gupta, John Mascarenhas, Ellen K. Ritchie, Ronald Hoffman, Richard T. Silver, Wan-Jen Hong, Marina Kremyanskaya, Elizabeth G. Trehu, Hagop M. Kantarjian, Jason R. Gotlib
Journal: Journal of Clinical Oncology (2014)

7114 Background: PRM-151 (PRM) is a recombinant form of Pentraxin-2, an endogenous human protein that acts at sites of tissue damage, inducing macrophage differentiation to prevent and reverse fibrosis. PRM has broad anti-fibrotic activity in multiple preclinical models of established fibrotic disease and no dose limiting toxicities in Phase 1 trials. This study investigates the potential of PRM in myelofibrosis (MF) to reduce bone marrow (BM) fibrosis and to improve key MF-related disease features including abnormal blood counts, splenomegaly, and symptoms. Methods: Patients with Intermediate-1, intermediate-2, or high risk MF with grade >2 BM fibrosis, either on no current therapy or on a stable dose of ruxolitinib (RUX) for at least 12 weeks were eligible for stage 1 of this open label adaptive trial. Assignment to one of the 4 treatment arms was per investigator and patient choice: PRM IV 1-hour infusion on days 1, 3 and 5, then weekly (QW) or every 4 weeks (Q4W), alone or with continuous oral rux. Primary endpoint is overall response rate by IWG-MRT criteria (spleen by palpation). A decrease in BM fibrosis by ≥ 1 grade with otherwise stable disease is also considered a response. BM biopsies are obtained at baseline, 3 and 6 months, read by local pathologists and a blinded central reviewer. Results: 27 subjects were enrolled in Stage 1: 7 PRM QW, 7 PRM Q4W, 7 PRM QW + RUX, 6 PRM Q4W + RUX. As of January 13, 2014, 15 and 6 subjects have completed 8 and 12 wks of treatment, respectively (none have yet completed 24 wks). There was no apparent treatment-related myelosuppression, and among all AEs, only herpes labialis and anemia occurred in >1 subject. There have been 4 serious adverse events in 3 subjects: 1 with abdominal pain, 1 with hypoxia, and an 85 year old subject who died from gastroenteritis and pneumonia. Improvement in bone marrow fibrosis (Grade 3 to 1; Grade 2 to 0; read by a local pathologist) was observed in 2 of 6 subjects at the 3-month BM mark (1 on PRM Q4W, 1 on PRM Q4W + RUX). Conclusions: In stage 1 of this phase 2 trial of MF patients, PRM has shown good tolerability both alone and in combination with RUX. Updated safety and efficacy data on all 27 subjects will be presented at the meeting, including central BM (3 and 6 month) reviews. Clinical trial information: NCT01981850.
Phase II study of neoadjuvant docetaxel (T), doxorubicin (A) and capecitabine (X) in locally advanced or inflammatory breast cancer (LABC)
Authors: G. Perez-Manga, M. Mendez, M. I. Palomero, R. Quiben, J. Belon
Journal: Journal of Clinical Oncology (2007)

11092 Background: Studies suggest that chemotherapy + surgery + radiotherapy gives a high survival rate in patients with LABC. Primary objective was to evaluate response rate. Secondary endpoints were time to progression and toxicity profile of neoadjuvant T, A and X in LABC. Methods: Eligibility: histologically confirmed LABC, ECOG PS =2, age =75 years, LVEF &gt;50%, and adequate bone marrow, renal and hepatic function. Prior systemic therapy, surgery or radiotherapy for breast cancer was not allowed. Patients with invasive bilateral breast cancer were not included. Treatment: T (30 mg/m 2 ) iv day 1, 8 and 15, A (50 mg/m 2 ) iv day 1 and X (1500 mg/m 2 o.d.) days 1–14, in a 4-week course repeated for up to 4 cycles followed by surgery. According to investigator criteria patients received a maximum of 6 cycles. Radiotherapy and hormone therapy were allowed after surgery. Expression of markers was determined by immunohistochemistry before chemotherapy. Results: 43 patients were included in this analysis, median age 48 years (25–73). ECOG PS was 0 in 37% of patients and 1 in 63%. Hormonal receptor status was ER+ 44%, PR+ 34% and C-erb2+ 59%. In total, 157 cycles (median 4, range 2–4) were given. Median relative dose intensity was 86% for T, 92% for A and 88% for X. Of 43 patients evaluable for efficacy, 13 achieved CR, 24 PR and 1 PD resulting in an ORR of 97% (CI 95%: 92–100). Surgery was performed in 40 patients: 4 (10%) achieved pathologic CR and one additional patient had non-invasive carcinoma. Grade III/IV toxicity per patient was neutropenia (74%), leukopenia (56%), febrile neutropenia (9%), mucositis (12%), diarrhea (12%), nausea/vomiting (5%), dysgeusia (2%) and asthenia (2%). Median follow-up time was 19.5 months. Conclusions: Neoadjuvant T, A and X every 28 days for 4 cycles is an active regimen in LABC with a manageable toxicity profile before surgery. No significant financial relationships to disclose.
A prospective phase II trail of de-intensified chemoradiotherapy for low-risk HPV-associated oropharyngeal squamous cell carcinoma.
Authors: Bhishamjit S. Chera, Robert J Amdur, Joel E. Tepper, Rebecca L. Green, Bahjat F. Qaqish, David N. Hayes, Mark C Weissler, Jared Weiss, Trevor Hackman, Adam M Zanation, Samip Patel, Jose Zevallos, Juneko E. Grilley-Olson, William K. Funkhouser, Nathan Christopher Sheets, William M. Mendenhall
Journal: Journal of Clinical Oncology (2015)

6004 Background: This is a prospective multi-institutional phase II study of a substantial decrease in chemoradiotherapy (CRT) intensity as concurrent primary treatment for favorable risk oropharyngeal squamous cell carcinoma. Methods: The major inclusion criteria were: 1) T0-T3, N0-N2c, M0, 2) HPV or p16 positive, and 3) ≤ 10 pack-years smoking history. Treatment was limited to 60 Gy Intensity Modulated Radiotherapy with concurrent weekly intravenous cisplatin (30 mg/m2). The primary study endpoint was pathologic complete response rate (pCR) based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and N = 40 (type I error = 14.2%). Secondary endpoint measures included physician reported toxicity (CTCAE), patient reported symptoms (PRO-CTCAE), quality of life (EORTC QLQ-C30 & H&N35), and penetration aspiration scale (PAS) scores for modified barium swallow studies. Results: The study population is 43 patients. The pCR rate was 86% (37/43). Median time to biopsy/neck dissection was 9 weeks (7 - 14 weeks). All 6 non-pCR cases were limited to microscopic foci of residual cancer: 1 primary site, 5 nodal. All patients are alive with no evidence of disease (median follow-up 15 months, 4 - 31 months). Incidence of CTCAE acute Grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms were: mucositis 34%/45%, pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematological toxicities were 11%. 39% required a feeding tube, for a median of 15 weeks (5 - 22 weeks). Mean pre- and post-CRT EORTC QOL scores were: Global 80/69 (lower worse, p < 0.01), Pain 15/20 (higher worse, p = NS), Swallowing 11/18 (p = 0.04), Coughing 17/22 (p = NS), Dry Mouth 16/64 (p < 0.001), and Sticky Saliva 6/49 (p < 0.001). There were no significant differences in PAS scores before and after CRT. Conclusions: Cancer control following 60 Gy of IMRT with weekly cisplatin 30 mg/m2is likely to be very high in favorable risk oropharyngeal squamous cell carcinoma. (ClinicalTrials.gov, NCT01530997). Clinical trial information: NCT01530997.
High responses to chemotherapy in patients with metastatic urothelial cancer (MUC) after frontline immunotherapy.
Authors: Bernadett Szabados, Akhila Ganeshi Wimalasingham, Yen Zhi Tang, Anju Sahdev, Alfonso Gomez De Liano Lista, Louise Lim, Thomas Hopkins, Alison Berner, Thomas Powles
Journal: Journal of Clinical Oncology (2017)

377 Background: The effect of prior immune checkpoint inhibition therapy (CI) on the efficacy of subsequent chemotherapy is largely unknown in MUB. The identification of the optimal sequence of chemotherapy and IO is yet to be determined, but may influence outcomes. Methods: A retrospective audit and comparison of patients who progressed after first and second line CI and received subsequent standard chemotherapy was performed. Date was collected across a broad spectrum of CI. We report on patient’s characteristics and response rates of 20 sequential patients collected from one institution who received chemotherapy after CI. Patients were separated into 2 groups. Group A had not previously received chemotherapy (n=10), group B had previously received at least 1 chemotherapy regimen (n=10). Central radiology review was performed. We assessed objective response rate by RECIST v 1.1. Kaplan Meier method was used. Results: Median age for the whole cohort was 64 yrs (45-80). The commonest chemotherapy regimen in group A and B were cisplatin-gemcitabine (80%) and carboplatin paclitaxel (70%) respectively. Results are summarised in the table. The median change in target lesions in the front line immunotherapy cohort was -49% (-81 to +8%). Only two patients (20%) in group B responded to chemotherapy and both presented a long interval between first and 2 nd line chemotherapy (9-12 months); compared to 56% responding in group A. Conclusions: Chemotherapy maintains its efficacy after front line CI with deep responses. Although numbers are modest, results strongly suggest patients should be offered chemotherapy in this setting. [Table: see text]
Phase II trial of neoadjuvant bevacizumab plus pemetrexed and carboplatin in patients with unresectable stage III lung adenocarcinoma (GASTO 1001).
Authors: Si-Yu Wang, Wei Ou, Ning Li, Song-Liang Zhang, Qian-Wen Liu, Peng-Fei Xu, Cheng Yuan, Bao-Xiao Wang
Journal: Journal of Clinical Oncology (2015)

7528 Background: Unresectable stage III non-small cell lung cancer is often treated with concurrent chemoradiotherapy. Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this phase II trial is to assess the efficacy and safety of induction bevacizumab (Bev) plus chemotherapy followed by surgery in unresectable stage III lung adenocarcinoma. Methods: This phase II trial investigated induction Bev (7.5 mg/kg) plus pemetrexed (500 mg/m2) and carboplatin (AUC = 5) followed by surgery for patients with unresectable, stage III lung adenocarcinoma. Neoadjuvant therapy was administered every 3 weeks for 4 cycles. Surgery was scheduled 3-4 weeks after last neoadjuvant therapy and patients’ resectability was assessed by a medical team, including thoracic surgeons, medical oncologists, and radiologists. The primary endpoint was resectability rate. Results: From April 2012 to April 2014, 42 patients were enrolled and received Bev plus pemetrexed and carboplatin (PC). Grade 3 or 4 neoadjuvant-related adverse events included fatigue in 5 patients, neutropenia in 4, hypertension in 1, anemia in 1 and thrombocytopenia in 1. The adverse events thought to be related to bevacizumab included epistaxis in 3 patients (grade 1, 2; grade 2, 1) and hypertension in 2 patients (grade 1, 1; grade 3, 1). Complete response was achieved in 1 patient, partial response in 22, stable disease in 17, and progressive disease in 2. After neoadjuvant therapy, 31 patients underwent surgery, with pneumonectomy in 11. R0 resection was achieved in 22 patients. Postoperative complications included pneumonia (4 patients), atelectasis (2), bronchial stump insufficiency (1), empyema (1), subcutaneous emphysema (2) and arrhythmia (1). No perioperative hemorrhage events, thromboembolic events and wound-healing problems were observed. No patient died in the perioperative period. The median event-free survival (EFS) was 15.4 months, and the 1-year EFS was 56.1%. Conclusions: The treatment modality of neoadjuvant Bev-PC followed by surgery appears to be feasible and safe in patients with unresectable stage III lung adenocarcinoma. Clinical trial information: NCT01588704. Clinical trial information: NCT01588704.
Proton beam therapy for liver cancer is well tolerated: Outcomes from the Proton Collaborative Group REG001-09 trial.
Authors: Michael David Chuong, Smith Apisarnthanarax, William F. Hartsell, Gary L. Larson, Henry K. Tsai, Carl Rossi, Carlos E. Vargas
Journal: Journal of Clinical Oncology (2017)

389 Background: The liver is one of the most radiosensitive organs, making radiation therapy (RT) for liver tumors extremely challenging. RT is appropriate only for a minority of liver patients with limited tumor burden; a reduction in the prescribed radiation dose may be needed to lower the probability of radiation-induced liver disease especially in the presence of cirrhosis. Proton beam therapy (PBT) delivers less dose to the liver than photon therapy and is expected to reduce toxicity while also permitting safe dose escalation for some patients with liver tumors. Methods: The Proton Collaborative Group REG001-09 trial (NCT01255748) prospectively collects data for PBT patients with a variety of cancer types. To better understand treatment details and outcomes associated with liver PBT, patients enrolled on the PCG registry trial from 5 institutions who received liver PBT for any cancer between 2012 and 2016 were analyzed. Results: A total of 43 liver cancer patients were included, most with hepatocellular carcinoma (48.8%) or cholangiocarcinoma (25.6%). The vast majority did not have surgery at any time (86%). Most were treatment naive prior to PBT; 2 previously had RT and 8 had prior chemotherapy (mostly cholangiocarcinoma patients). The median total prescribed PBT dose was 58.05 Gy(RBE) (range 21.7-67.5). The median number of prescribed fractions was 15 (range 12-37). PBT was delivered to only the liver in 90.7% of patients; inclusion of lymph nodes was rare. Uniform scanning was used in 26 (72.1%) and pencil beam scanning in 2 patients (4.7%); the delivery technique used for the remaining patients was unknown (23.2%). With median follow up of 4.4 months (range 1.3-17.9), 3 patients (7%) had an intrahepatic recurrence, 2 patients (4.6%) developed distant metastasis, and 10 patients (23.3%) died. No grade 3 or higher toxicity was reported although 17 patients (39.5%) had grade 2 toxicity predominantly fatigue, anorexia, nausea, or vomiting. Conclusions: Although longer follow up is needed to assess late toxicities as well as disease control, early outcomes from the PCG registry trial for liver cancer patients shows that predominantly hypofractionated PBT has a very favorable acute toxicity profile.
The role of lymphatic vascular invasion in the prognosis and determination of therapy in surgically resected non-small cell carcinoma of the lung.
Authors: Malcolm M. DeCamp, Adin-Cristian Andrei, Satvik Ramakrishna, Laura Nyshel Medford-Davis, Julia Shelkey, Megan McClean, Abram Recht, John M. Varlotto
Journal: Journal of Clinical Oncology (2013)

7554 Background: Lymphatic-vascular invasion (LVI) is not currently considered in staging of non-small cell lung cancer (NSCLC). We assessed the impact of LVI on overall survival (OS), local/distant recurrence (LR/DR) and patterns of recurrence. Methods: 869 consecutive patients who underwent a definitive surgical resection ± adjuvant chemotherapy for NSCLC from 2000–2008 were qualified for analysis if they did not receive any adjuvant/neo-adjuvant radiotherapy, had at least three months of follow-up, and did not have a history of other cancers within 5 years. Tumors with LVI (N = 160) were compared to tumors without LVI (N = 705). LR/DR rates at 2,3, and 5 years were calculated by the methods of Kaplan-Meier. Association between LVI and OS and LR/DR were compared in the total population and in a propensity matched population (PS) by factors affecting OS and LR/DR (n=160 matched pairs). Results: OS, LR, and DR were significantly worse in patients with LVI in the total population and in the subset of patients matched by propensity score (Table). In the PS-matched pairs, LVI was associated with a greater number of N1 nodes involved, a longer length of stay, higher histologic grade, and higher T-stage. Patterns of local failure (P&lt;.001) but not distant failure (P=.11) differed between patients with and without LVI. Tumors with LVI were 3-fold more likely to recur in ipsilateral mediastinal nodes. In a subset analysis of tumors &lt; 4cm (n=121 PS matched pairs), LVI was also associated with higher LR, DR, a lower OS and a 4-fold risk of mediastinal nodal recurrence. Conclusions: Detection of LVI in resected NSCLC predicts aggressive biologic behavior and provides important prognostic information. LVI may help identify high-risk cohorts within discreet TNM stages who could benefit from adjuvant therapies. [Table: see text]
Randomized phase Ib/II study of PF-05212384 plus 5-fluorouracil-leucovorin-irinotecan (FOLFIRI) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer (B2151007; NCT01937715).
Authors: Zev A. Wainberg, Nicoletta Brega, Craig Davis, Ashwin Gollerkeri, Kristen J. Pierce, Mie Suzuki, Rachelle Perea
Journal: Journal of Clinical Oncology (2014)

TPS3657 Background: Despite recent advances in cytotoxic chemotherapies and targeted agents, metastatic colorectal cancer (mCRC) continues to be an area of great unmet medical need. Patients with mCRC are typically treated with a fluoropyrimidine plus oxaliplatin or irinotecan, with or without an anti-angiogenic agent or monoclonal antibody to epidermal growth factor receptor. Although these regimens are considered standard of care, they are only moderately effective, and more-active regimens are needed. Signaling through the phosphatidylinositol 3-kinase (PI3K) pathway is associated with resistance to chemotherapies with different mechanisms of action, including taxanes and DNA-damaging agents, in nonclinical models. In the clinic, PI3K pathway activation in tumors has been correlated with decreased response to therapy and worse clinical outcomes. The combination of PF-05212384 (intravenous PI3K/mammalian target of rapamycin inhibitor) and irinotecan was additive in preclinical mCRC models and showed preliminary antitumor activity with acceptable tolerability in a phase I study (B1271002; NCT01347866) in patients with cancer, including mCRC, warranting further exploration of irinotecan-based combination regimens. Methods: This global study includes a dose escalation, phase Ib portion to evaluate dose limiting toxicities (primary endpoint) and determine the recommended phase II dose of PF-05212384 combined with FOLFIRI. A separate lead-in cohort to confirm the safety of the PF-05212384/FOLFIRI combination will be conducted at clinical sites in Japan. Then, a randomized phase II portion will investigate whether PF-05212384 plus FOLFIRI is superior to bevacizumab plus FOLFIRI in prolonging progression-free survival (primary endpoint) in patients with mutated or wild-type KRAS mCRC and disease progression on a first-line oxaliplatin-containing regimen or with progression within six months of an oxaliplatin-containing regimen in the adjuvant setting. Secondary endpoints include safety, overall survival, and biomarker correlations associated with the PI3K pathway. This trial is now recruiting. Clinical trial information: NCT01937715.
Effect of BRCA status on overall survival of patients with both breast and ovarian cancer.
Authors: Zora Baretta, Maria Ornella Nicoletto, Giulia Tasca, Giovanni Randon, Alessandra Baldoni, Elisa Alducci, Paola Del Bianco, Haralabos Koussis, Cristina Ghiotto, Pier Franco Conte
Journal: Journal of Clinical Oncology (2015)

e12502 Background: women with a history of breast cancer (BC) have a significantly increased risk of developing primary ovarian cancer (OC) and vice versa. Aims of the study were to evaluate differences in tumor features and overall survival (OS) according to BRCA status. Methods: of 109 patients diagnosed with both BC and OC at Istituto Oncologico Veneto (1986-2013), 88 were tested for BRCA genes mutation. Chi square test and T test were used for group comparison. Kaplan-Meier method and log-rank test were used for survival analysis. Primary endpoint was OS, defined as the time interval between the diagnosis of second cancer and date of last follow up or death. Results: of 88 patients 49 (56%) were BRCA-negative (BRCA-) and 39 (44%) BRCA-positive (BRCA+). Mean age at diagnosis of BRCA+ patients was lower than BRCA- either for first cancer (49 vs 55 years, p = 0.014) and second cancer (59 vs 64 years, p = 0.032). Usually BC preceded OC, even if the diagnosis of BC after OC was more frequent in BRCA- patients than in BRCA+ (33% vs 5%, p = 0.003). Mean interval between the two diagnoses was 9 years in BRCA- cases and 10 years in BRCA+ (p = 0.534), while it was < 1 year in 12% of BRCA- patients and 8% of BRCA+. OC was more frequently stage III-IV (p = 0.012) and high grade (p = 0.001) in BRCA+ patients than in BRCA-. Hormone receptors-negative BC was more frequent in BRCA+ patients than in BRCA- (42% vs 19%, p = 0.033). OS did not differ according to BRCA status (p = 0.882). Patients who developed OC before BC had better OS than those with BC as first diagnosis even if the difference was not statistically different (p = 0.07). Conclusions: in patients with both BC and OC,BRCA-carriers were younger than BRCA- patients at diagnosis of both cancers and presented more aggressive cancers. BRCA status did not influence OS of these patients.