tbuckley/cabot-search huggingface dataset:
Clinicopathologic analysis and prognostic factors for survival in early stage patients with ampullary carcinoma.
Authors: Nuriye Özdemir, Nebi Serkan Demirci, Sinemis Yuksel, Gokmen Umut Erdem, Hatice Odabas, Melih Cem Boruban, Ilhan Hacibekiroglu, Mustafa Karaagac, Mahmut Ucar, Banu Ozturk, Yakup Bozkaya, Celaletdin Camci, Nurullah Zengin
Journal: Journal of Clinical Oncology (2016)

e15666 Background: In this study we aimed to evaluate the possible important clinicopathological features and adjuvant treatment approaches in terms of prognosis in patient with early stage ampullary carcinoma. Methods: We included 197 patients who underwent pancreaticoduodenectomy for ampullary carcinoma between 2002 and 2014. Demographics, clinical features, treatment and outcome/survival were analyzed. Results: The median age at diagnosis was 60 years. The most common presenting symptom was jaundice (60%). Lymph node involvement was observedin 46% of thepatients. Sixty-six percent of patients had stage II-III disease.Perineural and lymphovascular invasion was seen in 50 (29.4%) and 69(40%) patients, respectively. Median overall survival (OS) and disease-free survival (DFS) were 63.4 and 40.9 months, respectively. mDFS was significantly lower in the patients with lymphovascular invasion (mDFS, 27 & 108.5 p < 0.001) and lymph node involvement (28.8 & 67.8 p = 0.027). Potential predictors of decreased survival on univariate analysis included age ≥ 50(mOS, 78.8 & 53.1 p = 0.045), poor performance status(108.5 & 46 p = 0.048), weight loss (38.8 & 108.5 p = 0.045), T3-T4 tumor (108.5 & 19.3 p = 0.018), microscopic positive margin (20.1 & 78.8 p = 0.01), lymph node involvement (38.8 & 141.9 p = 0.001), lymphovascular invasion (36.9 & not reached (NR)p < 0.001), perineural invasion (39.2 & 108.8 p = 0.007), and poor histological grade (NR &36.9 p = 0.042). In the multivariate analysis, only nodal status (HR,1.98; P = 0.028) and surgical margin (HR,2.61; P = 0.03) were associated with overall survival.While 70.1% of the patients recieved chemotherapy or chemoradiotherapy, 29.9% of the patients didn’t have any adjuvant therapy. There was no survival difference between the patients without any adjuvant therapies and with an adjuvant therapy (53.1 & 108.5 P = 0.166) Conclusions: Even though ampullary carcinoma has the best prognosis among all periampullary carcinomas, its long-term survival remain slow. Nodal status and surgical margin were an independent predictor of OS for patients with ampullary carcinoma. Additional studies are necessary to specify the role of adjuvant therapy of ampullary carcinomas.
Randomized, double-blind, placebo-controlled, phase II trial of first-line platinum/docetaxel with or without erlotinib (E) in patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCCs).
Authors: William Nassib William, Lei Feng, Merrill S. Kies, Salmaan Ahmed, George R. Blumenschein, Bonnie S. Glisson, Erminia Massarelli, Faye M. Johnson, Charles Lu, Vassiliki Papadimitrakopoulou, Kathryn A. Gold, Rachel Leigh Theriault, John Heymach, Edward S. Kim
Journal: Journal of Clinical Oncology (2017)

6017 Background: In a single-arm, phase 2 study, we previously demonstrated that in pts with R/M HNSCC, cisplatin, docetaxel and E improved progression-free survival (PFS) compared to historical data (Kim et al., ASCO 2006). Herein, we evaluated this regimen in a single center, randomized, phase 2 trial. Methods: Pts with R/M HNSCC, with a performance status (PS) 0-2, were randomized (1:1) to receive up to 6 cycles of first-line chemotherapy with cisplatin 75 mg/m2 (or carboplatin AUC 6) and docetaxel 75 mg/m2 i.v. on day 1 every 21 days, plus placebo (P) vs. E 150 mg p.o. daily, followed by maintenance P or E until disease progression. The primary endpoint was PFS. With 120 pts, the study had 80% power to detect an improvement in median PFS from 3.0 to 4.9 months with a two-sided type I error rate of 0.1. Results: From 05/2010 to 07/2015, 120 pts were randomized to the P (N = 60) or E (N = 60) groups. All pts but one initiated treatment and were eligible for evaluation of the primary endpoint – 92 males; median age 62 years; 52 oropharynx, 40 oral cavity, 19 larynx, 8 hypopharynx cancer pts; 86 current/former smokers; 43 with recurrence within 6 months of completion of local treatment; 27 with prior exposure to EGFR inhibitors. Median PFS was 4.4 vs. 6.1 months for the P and E groups, respectively (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.42-0.95 months, p = 0.026). Response rates were 44% vs. 56% for P vs. E (p = 0.21). Median overall survival (OS) for P- and E-treated pts was 13.7 vs. 17.0 months (HR = 0.67, 95% CI 0.43-1.04, p = 0.07). Benefits from E on PFS and OS were more pronounced in pts with oropharyngeal tumors (p≤0.05 for interaction). In the E group, first-cycle rash grade 2-4 (34% pts) was associated with longer OS (HR = 0.40, p = 0.02). E-treated pts experienced a higher incidence of grade 3-4 adverse events (33.9 vs. 53.3%), including diarrhea (3 vs.17%), dehydration (5 vs. 15%), nausea (5 vs. 14%), rash (0 vs. 12%). Conclusions: This study met its primary endpoint. Addition of E to first-line platinum/docetaxel improved PFS and OS. This regimen may warrant further evaluation in randomized, phase 3 trials. Clinical trial information: NCT01064479.
Correction to: Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β/VEGFA signalling
Authors: Fuqing Hu, Haijie Li, Lu Liu, Feng Xu, Senyan Lai, Xuelai Luo, Junbo Hu, Xi Yang
Journal: Molecular Cancer (2018)

After the publication of this work [1] an error was noticed in Fig. 7e, in which the incorrect information is shown. The updated figure included in this correction now shows the quantification of tumor microvessel density. This correction does not affect the findings or conclusions of the article. Nevertheless, we apologize for the inconvenience.
Immunomodulation by the combination of ipilimumab and nivolumab neoadjuvant to (salvage) surgery in advanced or recurrent head and neck carcinoma, IMCISION, an investigator-initiated phase-Ib/II trial (N16IMC, NCT03003637).
Authors: Charlotte L. Zuur, Joris B. W. Elbers, Anne van der Leun, Michiel van den Brekel, Bing Tan, Bas Jasperse, Wouter Vogel, Laura Smit, Stefan M. Willems, Abrahim Al-Mamgani, Jasper Nijkamp, Ton Schumacher, Christian U. Blank, J. P. De Boer, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2018)

e18020 Background: To assess safety, toxicity and efficacy of neo-adjuvant nivolumab ± ipilimumab administration to (salvage) surgery for squamous cell carcinoma of the head and neck (HNSCC). Methods: Patients with (recurrent) T3-4N0-3M0 HNSCC, WHO 0-1, HPV+ and HPV-, treated at the Netherlands Cancer Institute. Phase IB consists of ARM A (n = 6, 3+3 design): nivolumab 240mg flat dose (week 1&3) and ARM B (n = 6, 3+3 design): nivolumab (week 1&3) + ipilimumab 1 mg/kg (week 1 only), neo-adjuvant to surgery (week 5) with/without adjuvant (C)RT. The efficacy of neo-adjuvant nivolumab w/wo ipilimumab in terms of pathological response and imaging (FDG-PET, MRI) will be studied in an expansion phase-II cohort (n = 20). Results: Report of Phase-I. Phase I, ARM A: Six patients with a T3-4N0-2b HNSCC of the oral cavity (n = 3) or oropharynx (n = 3) were included (5/6 patients underwent salvage surgery). All patients were treated as scheduled without surgical delay (surgery in week 5) or unexpected wound healing problems. Two patients experienced CTCAE grade 3 toxicity (1 pericarditis and 1 colitis) starting 38 and 70 days after immunotherapy, respectively, and were treated with prednisone ( 1mg/kg). In ARM B, so far, 4 patients with a T3-4N0-2c HNSCC of the oral cavity (n = 3) and supraglottis (n = 1) underwent surgery without delay. One of 4 patients underwent salvage surgery. One patient experienced CTCAE grade 3 colitis and thyroiditis, 18 days after immunotherapy, successfully treated with prednisone (1mg/kg) and 2x 5 mg/kg Infliximab after prednisone. Patients 5 and 6 of ARM B are scheduled for surgery within the coming weeks. Phase II will be open for accrual in March 2018. Conclusions: Nivolumab (240 mg flat dose, week 1&3) can be safely administered neoadjuvant to major (salvage) surgery in advanced (recurrent) HNSCC. Patients 5 and 6 of ARM B are scheduled for surgery within the coming weeks. Phase II will be open for accrual in March 2018. Clinical trial information: NCT03003637.
Racial disparities in palliative and hospice care beliefs of lung cancer patients.
Authors: Aditya Varnam Shreenivas, Jose Morillo, Danielle Seiden, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2018)

10104 Background: Minority patients with lung cancer often have higher rates of morbidity and mortality. Recent data shows that early integration of palliative care with standard oncologic care for advanced lung cancer patients is associated with better quality of life and potential survival. Little is known about racial disparities in palliative and hospice care beliefs and the influence of these factors on the utilization of palliative care and hospice. Methods: We performed a prospective cohort study of patients diagnosed with advanced lung cancer (stage III and IV). At baseline (within 3 months of diagnosis), patients completed a validated survey assessing palliative and hospice beliefs as well as care preferences. Multivariate methods were used to compare differences in these beliefs among minority (Black and Hispanic) and non-minority patients. Responses to questions on beliefs were scored on a scale of 1-5, with 1 standing for strongly agree and 5 for strongly disagree. Using ANOVA, mean score differences between minorities and non-minorities were assessed. Results: We enrolled 97 of 160 eligible patients (61%). To date, baseline surveys have been completed on 61 patients. Of those, 38 (62.3%) were minorities and 23 (37.7%) were non-minorities. There were no significant differences in baseline demographics. In terms of palliative care beliefs, minorities reported feeling more hopeful (p = .008) and more secure ( p = .03) with palliative care referral. Minorities were more likely to believe that they cannot afford hospice ( p = .002 ), that hospice is not as good as the hospital for cancer care (p = .02), were less likely to believe that hospice care can be provided at home (p = .04) or that hospice can help with physical, psychological , social and spiritual needs (p = .04). Additionally, more minorities compared to non-minorities preferred palliative care to hospice (p = 0.007). Conclusions: Minority patients with advanced lung cancer are more likely to prefer palliative care than hospice and hold false beliefs about hospice. Having adequate palliative and hospice care for minorities is necessary to ensure health equity among patients with lung cancer. Future studies will be performed to see how these beliefs effect the use of these services.
Adjuvant chemotherapy for HER2-positive early breast cancer patients without perioperative radiotherapy in trastuzumab era.
Authors: Kazuki Nozawa, Keiji Sugiyama, Kazuhiro Shiraishi, Yoriko Funahashi, Yoshihito Kogure, Tomonori Kawasaki, Aya Kato, Chiyoe Kitagawa, Takako Hayashi, Takako Morita, Shu Ichihara, Hideo Saka, Yasuyuki Sato
Journal: Journal of Clinical Oncology (2018)

e12573 Background: The role of adjuvant or post-mastectomy radiation therapy (RT) for human epidermal growth factor receptor type 2 (HER2)-positive (HER2+) breast cancer patients treated with Trastuzumab (Tmab)-containing perioperative chemotherapy is unclear. This study aimed to evaluate the prognosis of HER2+ patients without perioperative RT after approval of adjuvant Tmab. Methods: Between September 2009 and December 2015, we retrospectively surveyed the charts of 1221 consecutive breast cancer patients at a single institute. Inclusion criteria were early breast cancer (invasive carcinoma, no special type) patients who underwent curative resection, and HER2+ patients who were treated with Tmab-containing perioperative chemotherapy without RT. The primary endpoint was invasive disease-free survival (IDFS). Results: Sixty-six patients were identified. Median follow-up time was 1024 days (range 351-1975). Patient characteristics were as follows: median age was 53 years (range 33-72), hormone receptor (HR) positivity/negativity (+/-) rates were 68%/32%, lymph node (LN) +/- rates were 55%/45%, and tumor size > 10/≤10 mm were 76%/24%, respectively. The chemotherapeutic regimens were anthracycline-based, taxane-based, and anthracycline + taxane-based in 19 (29%), 25 (38%), and 22 (33%) patients, respectively. Median IDFS in the entire cohort was not reached and the 3-year IDFS rate was 88% (95% CI, 75-95). The 3-year IDFS rates in LN+/- cases were 77% (95% CI, 55-99) and 100% (95% CI, 100-100), respectively (p = 0.0012), while the 3-year IDFS rates in HR +/- cases were 86% (95% CI, 62-96) and 89% (95% CI, 70-97), respectively (p = 0.711). Conclusions: Our study showed no cancer recurrence in HER2+/LN- patients. However, IDFS rates in HER2+/LN+ patients in our study were worse than those previously reported. Our results suggest that adjuvant RT is necessary for HER2+ patients with LN+.
Anthropometric factors and Breslow thickness
Authors: J.S. Stenehjem, M.B. Veierød, L.T. Nilsen, R. Ghiasvand, B. Johnsen, T.K. Grimsrud, R. Babigumira, N.C. Støer, J.R. Rees, T.E. Robsahm
Journal: British Journal of Dermatology (2018)

Melanoma is the most rapidly increasing cancer form in Norway, and in 2016, 2114 men and women were diagnosed with the disease. This form of cancer is often diagnosed at an early stage, and if you follow changes in your skin you will be able to detect the cancer at an early stage. Melanoma with metastasis (spreading elsewhere in the body), however, is a serious disease that is difficult to treat, and more than 300 people die in Norway from melanoma each year. The thickness of the tumour (called Breslow thickness) is an important factor for survival after melanoma; those with a thin tumour at diagnosis live longer than those with a thick tumour. In a new Norwegian study, researchers explored associations between certain factors (called anthropometric factors ‐ such as body mass index (BMI), body surface area (BSA), height, weight and weight change) and Breslow thickness, overall and by anatomical site and histological subtype (type of melanoma). Nearly 300,000 Norwegian men and women who were enrolled into a study group called the Janus population‐based cohort 1972–2003 were followed for melanoma. By 2014, 2570 cases of melanoma with information on tumour thickness were identified. This large case‐series of incident melanomas, demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and showed that Breslow thickness increased with increasing BMI, BSA and weight, before levelling off or declining at high values, suggesting that behavioural or other mechanisms apply at high values.
Clinical and prognostic significance of serum levels of angiopoietin-1 (sAng-1) and angiopoietin-2 (sAng-2) in hepatocellular carcinoma (HCC).
Authors: Roberto Carmagnani Pestana, Manal Hassan, Reham Abdel-Wahab, Yehia I. Abugabal, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2018)

e16152 Background: Ang-1 and Ang-2 have been shown to play a critical role in the process of vascular development in HCC. The aim of our study is to explore the clinical relevance of sAng-1 and sAng-2 levels as non invasive biomarkers in HCC patients (pt) and their influence on prognostic and clinicopathological features of HCC. Methods: We enrolled 767 HCC pt from MD Anderson Cancer Center from 2001 to 2014. Under IRB approval, baseline pt characteristics were retrieved from medical records. We set the cutoff value at the median levels of each angiogenic factor. Overall survival (OS) was estimated by Kaplan Meier curve and log rank test. We used univariate hazard ratio (HR) and 95% Confidence interval (CI) to determine the effect on the prognosis of HCC. Results: Univariate analysis showed that higher sAng-2 levels were significantly associated with higher Child Pugh Score (CTP), advanced stage in Barcelona clinic liver cancer stage (BCLC) and Cancer of the Liver Italian Program (CLIP), higher AFP levels, HCV positivity, presence of lymph node and distant metastasis, vascular invasion and thrombosis. Median OS was 61.8 months (CI95%, 45.1 – 78.5) for those with low sAng-2 compared to 28.5 months (CI95% 24.8 – 32.1) for those with high levels (p< .0001). sAng-1 was inversely associated with CTP, and HCV positivity. Higher sAng-1 was associated with longer OS. Median OS was 37.2 months (CI95%, 31.0 – 43.4 ) for those with high sAng-1 compared to 26.2 months (CI95% 22.2 – 30.3) for those with low levels (p= .043). Conclusions: To the best of our knowledge, we describe the largest study correlating sAng-1 and sAng-2 levels with clinical and prognostic characteristics of HCC. Higher sAng-1 levels and lower sAng-2 were associated with longer OS, These findings suggest that sAng-1 and sAng-2 levels are potential prognostic biomarkers for HCC.
Crizotinib with bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer harboring EML4-ALK fusion variant mutation: A prospective exploratory study.
Authors: Bo Yang, Zhi Cui, Xianyang Meng, Ziwei Huang, Yi Hu
Journal: Journal of Clinical Oncology (2018)

e21186 Background: It was proved that the use of crizotinib for patients with activating EML4-ALK fusion variant mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 7.7-11.1 months. However, more combination therapies are needed to extend progression-free survival and overall survival with acceptable toxicity for this population. We aimed to discover the efficacy and safety of the combination of crizotinib and bevacizumab in patients with NSCLC with activating EML4-ALK fusion variant mutation-positive disease. Methods: In this study, patients with stage IIIB/IV NSCLC with activating EML4-ALK fusion variant mutation, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received crizotinib 500 mg/day plus bevacizumab 7.5 mg/kg every 3 weeks as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival. Results: Between June 2016 and January 2018, 16 patients were enrolled. Median progression-free survival was 13.0 months (95% CI 9.8-16.2) with crizotinib plus bevacizumab. The most common grade 3 or worse adverse event was hepatic injury(2[12.5%]). One of them dropped out of the trial. Another one patient reduced the dose of crizotinib to 250 mg/day due to nausea and vomiting. Conclusions: Crizotinib plus bevacizumab combination may be a new combined first-line regimen in activating EML4-ALK fusion variant mutation-positive NSCLC. Further investigation of the regimen is warranted.
Alliance for clinical trials in oncology trial A021501: Preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas.
Authors: Matthew H. G. Katz, Fang-Shu Ou, Joseph Herman, Syed A. Ahmad, Brian M. Wolpin, Robert de Wilton Marsh, Qian Shi, Joleen Marie Hubbard, Jeffrey A. Meyerhardt, Michael Chuong, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2017)

TPS4151 Background: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and an R0 resection was achieved in 64% of operations. However, the individual contributions of preoperative chemotherapy and radiation therapy are poorly defined.This study, Alliance for Clinical Oncology Trial A021501, will help define a standard preoperative treatment regimen for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials. Methods: In this recently activated randomized phase II trial, 134 patients with a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed radiographic criteria for borderline resectable disease are randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 and infusional 5-fluorouracil 2400 mg/m 2 for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33-40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy undergo pancreatectomy and subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 and infusional 5-fluorouracil 2400 mg/m 2 for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site. Clinical trial information: NCT02839343.
A phase 1 study of enoblituzumab in combination with pembrolizumab in patients with advanced B7-H3-expressing cancers.
Authors: Naiyer A. Rizvi, Deryk Loo, Jan E. Baughman, Soyoung Yun, Francine Chen, Paul A. Moore, Ezio Bonvini, James Robert Vasselli, Jon M. Wigginton, Roger B. Cohen, Charu Aggarwal, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2016)

TPS3104 Background: Enoblituzumab, an Fc optimized humanized IgG1 monoclonal antibody that binds to B7-H3 (CD276), a member of the B7 family, is currently in Phase 1 testing. Enoblituzumab is Fc-engineered with 5 amino acid substitutions to enhance binding to the activating FcγR and decrease binding to the inhibitory FcγR. B7-H3 has limited expression in normal tissue but high expression in many cancers including melanoma (M), squamous cell cancer of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). B7-H3 overexpression correlates with poor prognosis in a broad range of cancers suggesting a potential role in enabling tumor immune escape. The hypotheses for combining enoblituzumab with pembrolizumab are: 1) immune-modulating agent combinations may mediate additive or synergistic antitumor activity and in tumors where neither single agent alone has substantial anti-tumor effect, 2) engagement of both innate and adaptive immunity, 3) targeting both B7-H3 and PD-1 may enhance the immune response against tumors via modulation of T-cell immunosuppression, 4) limited expression of B7-H3 on normal tissues may limit the risk of auto-immune related adverse events; thus enoblituzumab may be combined more readily with immune-modulating agents. Methods: This Phase 1 trial is a dose escalation/cohort expansion study (NCT02475213) enrolling patients with advanced B7-H3 expressinors. The escalation phase uses a 3+3+3 plan to enroll successive cohorts of patients with escalating doses of weekly intravenous (IV) enoblituzumab starting at 3 mg/kg, and 2 mg/kg IV pembrolizumab administered every 3 weeks. Response is first determined at 6 weeks and followed by irRECIST; based on response, both drugs will be given up to 1 year. A 3-cohort expansion phase will open at the established maximum tolerated dose (16 patients each) with M, SCCHN, and NSCLC. Progression on previous checkpoint inhibitor is allowed. Study objectives are the characterization of safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the combination. This is the first clinical trial evaluating combined targeting of B7-H3 and PD-1 in patients with advanced cancer. Enrollment is ongoing. Clinical trial information: NCT02475213.