tbuckley/cabot-search huggingface dataset:
Physical activity program in patients with metastatic colorectal cancer who receive palliative first-line chemotherapy: A randomized controlled phase III trial—(ACTIVE-2 SAKK 41/14).
Authors: Viviane Hess, Ralph C. Winterhalder, Karin Ribi, Barbara Handschin, Stefanie Pederiva, Jean-Marc Luthi, Marc Kueng, Daniel Helbling, Peter Moosmann, Pierre Oliver Bohanes, Bernhard C. Pestalozzi, Evelyn Rickenbacher, Christine Biaggi Rudolf, Catherine Berset, Stephanie Rondeau, Daniel Horber, Josef Thaler
Journal: Journal of Clinical Oncology (2018)

TPS3621 Background: Exercise has become a main focus of basic and clinical research worldwide during the current pandemic of physical inactivity. A clear link between inactivity and cancer incidence/relapse has been established, particularly for colon cancer, the third most common cancer. However, whether exercise has an impact on disease course and survival in advanced disease is unknown. Exercise modifies key host factors that are determinants of chemotherapy efficacy such as metabolic and immunologic tumor microenvironment, drug tolerability and treatment adherence. Thus, we aim to assess whether a supervised exercise program concomitant to first-line palliative chemotherapy for patients with metastatic colorectal cancer (mCRC) enhances chemotherapy efficacy and, therefore, increases survival and decreases symptom burden as compared to patients treated with chemotherapy alone. Methods: Patients with newly diagnosed mCRC are stratified (pre-diagnosis physical fitness, RAS-mutational status, primary tumor location, alkaline phosphatase levels) and randomly assigned to undergo standard systemic treatment and care-as-usual or standard systemic treatment combined with a 12-week structured physical activity (PA) program with twice weekly supervised, heart-rate guided interval training on a bike ergometer. Both groups undergo regular imaging with CT/MRI in order to assess the 1°endpoint of progression-free survival (PFS), i.e. the time between diagnosis and disease progression or death. Radiologists who are blinded to the group assignment will review imaging. A total of 439 events occurring in 524 patients will be needed to show a clinically meaningful HR of 0.75 for PFS with 80% power and an α of 0.03. Co-primary endpoint is self-reported symptom burden as measured by the revised Edmonton Symptom Assessment Scale (rESAS). 50 patients from 17 Swiss and Austrian Centers have been randomized. A planned feasibility analysis of the first 40 patients is ongoing. Clinical trial information: NCT02597075.
Subgroup analysis of elderly patients (pts) in ALTER0303: Anlotinib hydrochloride as 3<sup>rd</sup>-line and further line treatment in refractory advanced NSCLC pts from a randomized, double-blind, placebo-controlled phase III ALTER0303 trial.
Authors: Jianhua Shi, Baohui Han, Kai Li, Qiming Wang, Li Zhang, Zhehai Wang, Ying Cheng, Jianxing He, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin, Baolan Li
Journal: Journal of Clinical Oncology (2018)

e21181 Background: Elderly pts have limited therapy strategies compared to the younger pts. Anlotinib hydrochloride is a novel multi Tyrosine Kinase Inhibitor targeting the VEGFR, FGFR, PDGFR and c-Kit. ALTER0303 trial (NCT02388919), the phase III study has demonstrated that anlotinib significantly prolonged OS and PFS in advanced NSCLC patients as 3rd line treatment. Here, we performed a comparative analysis of survival rate for elderly pts in the placebo and anlotinib arms. Methods: 437 eligible adult IIIB/IV NSCLC pts who progressed after at least 2 lines of prior therapies were randomized 2:1 to receive anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression or intolerable toxicity. Pts harboring EGFR or ALK mutations must have received previously targeted therapies. The primary endpoint is OS. The elderly pts were stratified by age more than 70 years. Results: There are 28 elder pts in ALTER0303 trail, median age was 71 years with placebo group and 72 years with anlotinib group. In anlotinib group, hypertension (81.25%), hand-foot syndrome (75%) and TSH elevation (68.75%) were the most common AEs; then, in placebo group were sinus bradycardia (50%), dyspnea (50%) and anorexia (50%). Exactly data about efficacy and grade ≥3 AEs were presented in the table. Conclusions: In elderly pts subgroup of ALTER0303 trial, significant advances in OS and PFS were found in anlotinib treated group with tolerable AE. These results indicated that anlotinib may be an appropriate option for this difficult-to-treat population as 3rd line treatment. Clinical trial information: NCT02388919. Placebo (n = 12) Anlotinib (n = 16) HR (95% CI) P value Efficacy mPFS (mos) 2.80 11.20 0.22 (0.07, 0.64) 0.0028 mOS (mos) 6.30 14.50 0.34 (0.12, 0.94) 0.0306 Grade ≥3 AEs, % Hypertension 0 12.50% Hand-foot syndrome 0 12.50% GGT elevation 0 12.50% Hyponatremia 0 12.50% Hemoptysis 8.33% 6.25% Dyspnea 8.33% 0.00%
An Open-label Randomized Phase 2 study of Durvalumab Alone or in Combination with Tremelimumab in Patients with Advanced Germ Cell Tumors (APACHE): Results from the First Planned Interim Analysis
Authors: Andrea Necchi, Patrizia Giannatempo, Daniele Raggi, Luigi Mariani, Maurizio Colecchia, Elena Farè, Francesco Monopoli, Giuseppina Calareso, Siraj M. Ali, Jeffrey S. Ross, Jon H. Chung, Roberto Salvioni
Journal: European Urology (2018)
Quantitative measurement of total erbB2 (H2T), p110 t-erbB2, and erbB2:erbB3 (H23D) heterodimer expression and p110 t-erbB2 in malignant progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).
Authors: Yu Zong, Kunwei Shen, Jeff Sperinde, Gerald Wallweber, Weidong Huang, John William Winslow, Wenchuan Liang, Mark D. Pegram
Journal: Journal of Clinical Oncology (2018)

12089 Background: We previously reported that human mammary epithelial cell lines stably expressing p110 t-erbB2, but not p95 nor erbB2 intracellular C-terminal fragment, significantly increased cell migration, invasion and xenograft formation -- more than full length p185 erbB2 [Ward, et al., Oncogene. 2013;32(19):2463-74]. Moreover, published frequency of erbB2 overexpression is higher in DCIS (41%) than IDC(~20%), suggesting erbB2 may play a role in tumor initiation, rather than progression to invasion. We hypothesized that p185 erbB2 in DCIS is insufficient to cause an invasive phenotype, and that enrichment of p110 t-erbB2 facilitates malignant progression to IDC. Methods: H2T, p110 t-erbB2, and H23D were quantified using the proximity-based HERmark and VeraTag assay technology (CLIA/CAP-certified conditions) in 67 DCIS and 70 IDC erbB2-amplified/overexpressed FFPE samples. Macrodissection ensured pure IDC or DCIS samples. Measurements were normalized to cell line standards of known H2T, p110 t-erbB2 and H23D levels, with cutoffs established as previously described [Huang W, et al., Am J Clin Pathol. 2010;134:303-311; Sperinde J, et al., Clin Cancer Res. 2010;16(16):4226-35]. Results: p110 t-erbB2 was higher in IDC than DCIS cases (p = 0.036). Level of H2T overexpression was strongly associated with high p110 t-erbB2 levels in IDC patients (R2= 0.51, p < 0.001), but not in DCIS. p110 t-erbB2 difference between IDC vs. DCIS was more pronounced in the H2T overexpressed subset (p < 0.001). H2T and p110 t-erbB2 expression were in agreement with erbB2 IHC staining (H2T p = 0.002; p110 t-erbB2 p = 0.04, respectively); and inversely correlated with estrogen receptor levels (H2T p = 0.009; p110 t-erbB2 p = 0.004, respectively). In IDC, high expression of H23D levels were not significantly different between DCIS and IDC cases (p = 0.13). Conclusions: Our study is the first quantitative assessment of H2T, p110 t-erbB2 as well as H23D expression in both DCIS and IDC. These data suggest a potential pathophysiologic role of p110 t-erbB2 in driving progression of erbB2 positive DCIS to IDC.
Phase II study of ex vivo expanded cord blood natural killer cells for multiple myeloma.
Authors: Nina Shah, Rohtesh Mehta, Li Li, Jessica Mccarty, Indreshpal Kaur, Robert Z. Orlowski, Laurence Cooper, Dean Anthony Lee, Kai Cao, Simrit Parmar, Chitra Hosing, Sairah Ahmed, Yago Nieto, Qaiser Bashir, Krina K. Patel, Catherine Bollard, Muzaffar H. Qazilbash, Richard E. Champlin, Katayoun Rezvani, Elizabeth J. Shpall
Journal: Journal of Clinical Oncology (2018)

8006 Background: Multiple myeloma (MM) is an incurable disease with immune dysregulation and exhaustion. Remissions in some patients (pts) after allo-stem cell transplant (SCT) suggest a graft versus myeloma effect; however toxicity limits its widespread use. Allogeneic natural killer (NK) cells are safe and potentially active against various hematologic malignancies, including MM. We previously demonstrated safety of ex vivo expanded cord blood (CB) derived NK cells in doses up to 1 e8 cells/kg in the setting of high dose melphalan and auto-SCT (ASCT) (Shah et al, Br J Haematol 2017). Here we present results of the phase II portion of our study. Methods: Pts with symptomatic MM who were appropriate candidates for ASCT were eligible. CB units with at least 4/6 match at HLA-A, B and DR were chosen for each pt. When possible, CB units with potential NK alloreactivity (KIR-HLA mismatch) were prioritized. Due to pre-clinical data demonstrating synergy between lenalidomide and NK cells, patients received lenalidomide (10 mg daily) from days (-8) to day (-2). Melphalan 200 mg/ m2 was given intravenously on day (-7). Freshly expanded CBNK cells were infused on day (-5). Autologous peripheral blood progenitor cells were infused on day (0). Results: 33 patients were enrolled. 24/33 (74%) pts had at least 1 of the following adverse features: high risk cytogenetics/FISH (del1p, amp1q, t(4;14), t(14;20), t(14;16), del (17p), cyotgenetic del (13)), history of progression/relapse or ISS III disease. Successful expansion to target dose (1 e8 cells/ kg) was achieved in all but 3 patients (who received 5 e7 cells/kg). There were no toxicities associated with the CB NK cell infusions. Responses at 3 months were CR:18/33 (55%); VGPR: 4/33 (12%); PR: 7/33 (21%). Best response was CR: 21/33 (65%); VGPR: 6/33 (18%); PR: 3/33(9%). With a median follow-up time of 22 months, 10 pts have progressed and 3 have died. Median PFS has not been reached. By DNA microsatellite chimerism analysis, donor CB-NK cells were detected 1-13 days after infusion for 25/33 (76%) pts. Conclusions: In this relatively high risk MM population, CBNK cells in the setting of auto-SCT is a promising adjunct immunotherapy. Updated data and correlative analyses will be presented at the annual meeting. Clinical trial information: NCT01729091.
Symptoms burden reported by head and neck cancer patients at their first survivorship clinic visit.
Authors: Guadalupe R. Palos, Kate A. Hutcheson, Kristen B Pytynia, Charles Schreiner, Katherine Ramsey Gilmore, Patricia Chapman, Weiqi Bi, Paula A. Lewis-Patterson, Ryan Goepfert, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2018)

e22090 Background: Long-term head and neck cancer survivors are at risk to high symptom burden due to the late and lasting effects of the tumor and its treatment. Herein, we report on the results of a retrospective analysis conducted to identify moderate to severe symptoms (MSS) reported by head and neck cancer (HNC) patients at their initial visit to a survivorship cancer clinic. Methods: All records of patients aged 18 and over scheduled for their first survivorship visit at our institution between from 02/14/2014 to 02/24/2017 were retrospectively analyzed. Data were collected from a) MDASI HN, b) institutional clinical and demographic databases and c) HNC survivorship clinic databases. Our primary variable was the prevalence of symptoms rated MSS, defined as symptoms rated 5 on the MDASI’s 0-10 scale. Symptom burden was identified as the 4 most severe symptoms’ ratings and their interference with physical and psychological function. Results: 490 patients (median age – 62), 74.3% males, and 84.3% white, non-Hispanic. Cancer diagnosis: 42.7% oral cavity, 30.8% oropharynx, 16.5% larynx/hypopharynx, and 10% other (nasopharynx and salivary). The X and SD of years initial diagnosis were 5.5 years (SD = 7.9 years). Table 1 summarizes the prevalence the MSS ratings of the 4 most severe symptoms and their interference with function. Conclusions: Our findings suggest there is a subset of post-treatment HNC survivors who continue to experience high symptom burden. Clinicians must screen long-term survivors for negative physical and psychological symptoms. Further research is needed to identify the characteristics of HNC survivors at-risk to high -treatment symptom burden. Table 1. Prevalence and Interference among HNC Survivors Symptom Moderate to Severe Symptoms (Percent/Number) Dry mouth 27.7% (135) Swallowing 18.3% (85) Fatigue 17.4% (84) Mucus 16.6% (80) Interference with Physical Function General activity 7.9% (37) Work 7.9% (37) Walking 6.0% (28) Interference with Psychologic Function Mood 7.1% (33) Relationships with others 4.3% (20) Enjoyment of life 5.8% (27)
Combination immunotherapy selection for non-PD-1 axis driven tumors.
Authors: Carl Morrison, Paul DePietro, Felicia L. Lenzo, Sarabjot Pabla, Mary Nesline, Sean T. Glenn, Blake Burgher, Jonathan Andreas, Vincent Giamo, Maochun Qin, Devin Dressman, Antonios Papanicolau-Sengos, Yirong Wang, Mark Gardner, Jeff Conroy
Journal: Journal of Clinical Oncology (2018)

e15058 Background: Immunotherapy for non-PD-1 axis driven tumors, defined as tumors with less than high expression of PD-1, PD-L1, or PD-L2, are generally considered less responsive to checkpoint inhibitors than non-PD-1 axis driven tumors. Understanding rational targets for potential combination immunotherapies should have value for non-PD-1 axis driven tumors. Methods: Formalin-fixed paraffin embedded (FFPE) blocks or slides from 477 patients representing 32 different tumor types who had comprehensive immune profiling completed in the context of clinical care were evaluated in order to identify actionable targets for immunotherapy. PD-1 axis driven tumors were defined as those with an expression rank < 75 (moderate or lower) as compared to the ranks for all tumor types in a reference population. Actionable immunotherapy targets beyond PD-1, PD-L1, or PD-L2, including LAG3, CTLA4, TIM3, CD137, CD27, CD40, GITR, ICOS, OX40, CCL2, CCR2, CSF1R, ADORA2A, CD39, IDO1, TNF, TGFB1, and CD38 were defined as those with an expression rank ≥ 85 (high). The percent of tumors with less than high expression of non-PD-1 axis targets was computed for all tumor types. Results: 278 (58%) of 477 tumors were classified as non-PD-1 axis driven tumors. Less than 50% of NSCLC, sarcoma, and greater than 60% of colorectal, ovarian, breast, prostate, uterine, pancreatic, H&N, gastric, and melanoma were not PD-1 axis driven tumor types. The most frequently over expressed combination immunotherapy targets across all tumor types were CSF1R (14%), GITR (11%), IDO1 (10%), TNF (10%), CD38 (8%), CD39 (7%), LAG3 (6%), ADORA2A (6%), CD40 (4%), CCL2 (4%), CD137 (4%), ICOS (3%), OX40 (3%), CCR2 (3%), CTLA4 (2%), TIM3 (2%), and CD27 (1%). Conclusions: A wide variety of combination immunotherapy targets are highly expressed in non-PD-1 axis driven tumors. The most common immunosuppressive mechanisms identified in non-PD-1 axis driven tumors are myeloid suppression (CSF1R) and immune escape (IDO1). Some markers, such as CD27, TIM3, CCR2/CCL2, OX40, ICOS, CD137, and CD40, are at a prevalence of less than 5% will require a large population if a precision immunotherapy approach is utilized.
Potential of a novel technique for constructing tissue microarrays from core needle biopsy as seen in older women with primary breast cancer.
Authors: Mohammad A Albanghali, Emad Rakha, Andrew R. Green, Binafsha Manzoor Syed, Christopher Nolan, Maria Aranzazu Diez-Rodriguez, Ian O. Ellis, Kwok-Leung Cheung
Journal: Journal of Clinical Oncology (2016)

e23283 Background: Core needle biopsy (CNB) provides limited amount of tumour tissue which is normally sufficient for diagnostic purposes. Assessment of multiple biomarkers is often not possible. A systematic review of the literature has identified that different tissue microarray (TMA) construction techniques were developed to facilitate the use of CNB for research purpose [1]. This study aimed to assess the potential of a novel cost-effective technique for constructing TMAs using CNB from breast cancer patients. Methods: Initial work was conducted to standardise the size of obtainable tumour tissue from surgical samples in breast cancer patients. Thereafter, TMAs were constructed using the novel technique, using paired samples of 131 diagnostic CNBs and surgical excisions collected from older women with breast cancer. Final CNB TMA sections were assessed using H&E stain, and immunohistochemistry to measure ER, PgR and HER2 expression. Results: The constructed CNB TMA had a capacity of 54 cores and an estimated number of obtainable sections > 500. Microscopic examination of H&E sections indicated that morphology of tumour cells was preserved. Concordance rates of ER, PgR and HER2 between the paired samples were %89, %87 and %98 respectively. Conclusions: This work demonstrates a highly reliable technique to construct TMA using tissue collected by CNB, overcoming issues observed from previous work such as complexity of technique and the difficulty in maintaining tissue orientation during the construction process. The technique allows assessment of multiple biomarkers in women with breast cancer. This could prove pivotal in understanding the detailed biology which was previously limited by the availability of tumour tissue, notably in patients who do not undergo surgery. [1] Construction of tissue microarrays from core needle biopsies - a systematic literature review. Albanghali M, Green A, Rakha E, Aleskandarany M, Nolan C, Ellis I, Cheung KL. Histopathology. 2015 Aug 12.
Analysis of patient-reported outcomes (PROs) for GOG-258, a randomized phase III trial of cisplatin and tumor volume directed irradiation followed by carboplatin and paclitaxel (Cis-RT+CP) vs. carboplatin and paclitaxel (CP) for optimally debulked, locally advanced endometrial carcinoma: A Gynecologic Oncology Group/NRG study.
Authors: Ursula A. Matulonis, Virginia L. Filiaci, Helen Q Huang, Marcus Randall, Byoung Kim, Paul DiSilvestro, Katherine M. Moxley, David M. O'Malley, Matthew A. Powell, Nicola M. Spirtos, Krishnansu Sujata Tewari, William Richards, John Nakayama, Margaret Steinhoff, David Gardner Mutch, David S. Miller, Lari B. Wenzel, Daniela Matei
Journal: Journal of Clinical Oncology (2018)

5589 Background: Protocol GOG-258 randomized Cis-RT+CP or CP for 6 cycles to patients (pts) with stage III/IVA endometrial carcinoma (Matei et al, ASCO 2017). Recurrence-free survival was the primary endpoint and was not increased by addition of RT. PRO analyses evaluated the impact of treatment (tx) on quality of life (QOL) during tx and up to 1 year. Methods: PROs were assessed at baseline prior to tx, 6 weeks (wks) after starting tx (corresponding to 1-wk post completion of RT (Cis-RT+CP) or prior to cycle 3 (CP)), and 18 and 70 wks after tx start. The analysis used FACT-En TOI, FACT/GOG-neuropathy (Ntx) subscale, and FACT-C items C3, C5 combined with En1, O1, O3, Cx6 in TOI of FACT-En for gastrointestinal (GI) symptoms (exploratory). Results: Questionnaire compliance was 95% at baseline, 90% at 6 wks, 87% at 18 wks, and 78% at 70 wks after tx start. Pts (332 on Cis-RT+CP and 349 on CP) with valid baseline and ≥ 1 follow-up PRO assessments were evaluable for analysis. After adjusting age and baseline scores, pts receiving Cis-RT+CP reported 5.2 points (97.5% CI: 2.7~7.8; adjusted p < 0.001) lower TOI scores on average at 18 wks (end of tx) compared to CP. The tx difference remained statistically significant at 70 wks (3.4 points lower on Cis-RT+CP group; 97.5% CI: 0.7~6.2; adjusted p = 0.022); none exceeded the 6 point difference pre-set as “clinically meaningful.” Pts in both groups reported increased chemo-induced Ntx symptoms since tx start, but pts on CP reported 2.0 points lower (worse Ntx symptoms) (97.5% CI: 1.4~2.6; adjusted p-value < 0.001) in the Ntx subscale score at 6 wks (post 2 cycles of chemo) than those receiving RT. Pts on Cis-RT+CP reported significantly worse GI symptoms compared to CP arm pts at all assessments. Conclusions: The Cis-RT+CP group experienced overall worse QOL and GI toxicity; both groups reported neuropathy which did not return to baseline by 1 year. PRO differences observed with Cis-RT+CP and CP may influence choice of treatment for locally advanced endometrial cancer. Clinical trial information: NCT00942357.
Recurrence rates of cutaneous squamous cell carcinoma of the head and neck after Mohs micrographic surgery vs. standard excision: a retrospective cohort study
Authors: C.B. Lee, B.M. Roorda, M. Wakkee, Q. Voorham, A.L. Mooyaart, H.C. Vijlder, T. Nijsten, R.R. Bos
Journal: British Journal of Dermatology (2018)

BackgroundRecurrent cutaneous squamous cell carcinoma (cSCC) has been associated with an increased risk of local functional and aesthetic comorbidity, metastasis and mortality.
Comparison of Dermatologist Density Between Urban and Rural Counties in the United States
Authors: Hao Feng, Juliana Berk-Krauss, Paula W. Feng, Jennifer A. Stein
Journal: JAMA Dermatology (2018)

As the US population continues to increase and age, there is an unmet need for dermatologic care; therefore, it is important to identify and understand the characteristics and patterns of the dermatologist workforce.To analyze the longitudinal dermatologist density and urban-rural disparities using a standardized classification scheme.This study analyzed county-level data for 1995 to 2013 from the Area Health Resources File to evaluate the longitudinal trends and demographic and environmental factors associated with the geographic distribution of dermatologists.Active US dermatologist and physician density.In this study of nationwide data on dermatologists, dermatologist density increased by 21% from 3.02 per 100 000 people to 3.65 per 100 000 people from 1995 to 2013; the gap between the density of dermatologists in urban and other areas increased from 2.63 to 3.06 in nonmetropolitan areas and from 3.41 to 4.03 in rural areas. The ratio of dermatologists older than 55 years to younger than 55 years increased 75% in nonmetropolitan and rural areas (from 0.32 to 0.56) and 170% in metropolitan areas (from 0.34 to 0.93). Dermatologists tended to be located in well-resourced, urban communities.Our findings suggest that substantial disparities in the geographic distribution of dermatologists exist and have been increasing with time. Correcting the workforce disparity is important for patient care.